Transcription factor loading on the MMTV promoter: a bimodal mechanism for promoter activation.
The mouse mammary tumor virus (MMTV) promoter attains a phased array of six nucleosomes when introduced into rodent cells. This architecture excludes nuclear factor 1/CCAAT transcription factor (NF1/CTF) from the promoter before glucocorticoid treatment and hormone-dependent access of nucleolytic agents to promoter DNA. In contrast, when the promoter was transiently introduced into cells, NF1/CTF was bound constitutively and nucleolytic attack was hormone-independent. Thus, induction at this promoter was a bimodal process involving receptor-dependent remodeling of chromatin that allows NF1/CTF loading and direct receptor-mediated recruitment of additional transcription factors.


Teaching Father-Infant Massage during Postpartum Hospitalization: A Randomized Crossover Trial.
The purpose of this study was to evaluate acceptability and impact of infant massage video instruction on fathers' behaviors in early postpartum. A randomized crossover design was used. Participants were fathers of healthy term infants born at a Magnet hospital in Southern California. Measures included a demographic survey, Father-to-Infant Bonding Scale, Father-Infant Observation Scale, and postdischarge phone interview. Study nurses observed father-infant interactions for 5 minutes. Fathers were randomized to one of two groups: fathers in group 1 saw the massage video before they were observed with their infants and fathers in group 2 saw the video after. Fathers completed the Bonding Scale at baseline in person and again within a week of discharge by phone. Statistics were descriptive and comparative. Responses to interview questions were categorized and described. Ninety-eight fathers aged 18 to 44 years participated. Over half of fathers identified as Hispanic and the majority spoke English at home. Most fathers had positive responses to infants on individual Bonding Scale items. Fathers differed significantly in observed interactions with infants depending upon timing of massage instruction; fathers observed immediately after the video had more total interactions, specifically fingertip touching. Poststudy evaluations were predominantly positive. We found a brief infant massage instruction offered by video was well accepted by fathers and increased observed father-infant interactions.


Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40.
Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca2+ oscillations originated from intracellular Ca2+ stores and were followed by store-operated Ca2+ entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management.


Effect of Loop Defects on the High Strain Rate Behavior of PEGDA Hydrogels: A Molecular Dynamics Study.
The high strain rate behavior of nonideal poly(ethylene glycol) diacrylate hydrogels under uniaxial tension and transient-state shear deformations is investigated using molecular dynamics (MD) simulations. This work specifically focuses on the influence of first-order loop defects, including their effect on topological evolutions. Two approaches are proposed to systematically introduce first-order loops, allowing separate and controllable investigations of effective cross-link functionality and cross-link density. MD simulations confirm that first-order loop defects are elastically inactive, but the topological disruptions caused by the presence of loop defects influence mechanical behavior. For decreasing effective cross-link functionality but constant cross-link density, a weaker tensile stress-strain response and decreasing shear-thickening behavior are observed. This is due to nonaffine translation of cross-link junction positions during deformation. Hydrogels with lower cross-link density but constant effective functionality show a stronger stress-strain response and an earlier transition between entropic and enthalpic deformation regimes. This behavior is correlated to changes in mesh size caused by the introduction of loops within an elastically active network. However, the resulting range of cross-link densities is not sufficient to cause measurable changes in shear-thickening behavior. To conclude, reductions in effective cross-link functionality are more important to high strain rate behavior than reductions in cross-link density.


Resection of spinal column tumors utilizing image-guided navigation: a multicenter analysis.
OBJECTIVE The use of intraoperative stereotactic navigation has become more available in spine surgery. The authors undertook this study to assess the utility of intraoperative CT navigation in the localization of spinal lesions and as an intraoperative tool to guide resection in patients with spinal lesions. METHODS This was a retrospective multicenter study including 50 patients from 2 different institutions who underwent biopsy and/or resection of spinal column tumors using image-guided navigation. Of the 50 cases reviewed, 4 illustrative cases are presented. In addition, the authors provide a description of surgical technique with image guidance. RESULTS The patient group included 27 male patients and 23 female patients. Their average age was 61 ± 17 years (range 14-87 years). The average operative time (incision to closure) was 311 ± 188 minutes (range 62-865 minutes). The average intraoperative blood loss was 882 ± 1194 ml (range 5-7000 ml). The average length of hospitalization was 10 ± 8.9 days (range 1-36 days). The postoperative complications included 2 deaths (4.0%) and 4 radiculopathies (8%) secondary to tumor burden. CONCLUSIONS O-arm 3D imaging with stereotactic navigation may be used to localize lesions intraoperatively with real-time dynamic feedback of tumor resection. Stereotactic guidance may augment resection or biopsy of primary and metastatic spinal tumors. It offers reduced radiation exposure to operating room personnel and the ability to use minimally invasive approaches that limit tissue injury. In addition, acquisition of intraoperative CT scans with real-time tracking allows for precise targeting of spinal lesions with minimal dissection.


The Goitrous Salting Madonnas: Iconography of Goiter in Religious Portraits.
George Salting was an art collector, who bequeathed his collection of paintings to the National Gallery of London. The present investigation has revealed five portraits of five different artists belonging to this collection in which the Holy Mother holding the child has been portrayed with a variable grade of thyroid gland enlargement. The name Salting, applied to the Madonnas with child by Antonello da Messina, Robert Campin, Dirk Bouts, Cima da Conegliano, and Andrea del Verrocchio, denotes George Salting, the collector who donated the masterworks to the gallery in 1910. The five paintings were analyzed to determine the accuracy of the diagnosis of neck swelling and the underlying iconographical significance of this depiction, which is relatively uncommon in religious artworks. The present investigation highlighted an abnormal profile of the neck of the Virgin Mary, which is suggestive of a presumptive medico-artistic diagnosis of goiter. The inclusion of thyroid swelling in a holy sitter is relatively uncommon and is related to specific meanings that the painter wanted to illustrate in the work, the reasons for which are herein discussed. It seems likely that the integration of the goiter in the paintings is a stylistic hallmark. Indeed, the depiction of a slight neck enlargement is most probably a rhetorical tendency of representing an idealized female beauty, especially in holy sitters, imbued by a balanced neck and graceful body. At the same time, it probably also reflects better anatomic accuracy and knowledge of Renaissance artists applied toward a more realistic and precise representation of subjects.


Trajectories of maternal depressive symptoms in the early childhood period and family-wide clustering of risk.
Previous research on individual differences in the course of maternal depressive symptoms has yielded inconsistent findings, with significant variation in the number and pattern of trajectories identified. In addition, missing from the literature is a comprehensive examination of predictors and longitudinal consequences of particular depression trajectories. Participants in this study included a community cohort of 501 women assessed for depression using the Center for Epidemiologic Depression Scale at infant age 2, 18, 36, and 54 months. A multi-informant approach was used to examine predictors and outcomes of trajectory membership. Using growth mixture modeling, three distinct trajectories emerged: 84% of the sample demonstrated low-stable levels of depressive symptoms, 9.5% had high-decreasing scores, and 6.5% had moderate-increasing scores. While socioeconomic status and marital conflict differentiated the low-stable group from the high-decreasing and moderate-increasing group, neighborhood collective efficacy differentiated the latter two groups. At 54 months, a clustering of family risks was prevalent for the moderate-increasing depression group, including higher marital conflict and household chaos, lower parental positivity, and heightened levels of child psychopathology. Limitations include reliance on self-reports to assess maternal depression and the relatively small sample size of certain trajectory classes. The onset and course of maternal depression in the early childrearing period is heterogeneous, with distinct subgroups in the population. Comprehensive assessment of individual, family, and neighborhood stressors augments our understanding of the predictors and consequences of trajectory membership over this critical period of child and family adaptation.


Mucinous tubular and spindle cell carcinoma of the kidney with neuroendocrine differentiation: report of two cases.
We encountered 2 cases of mucinous tubular and spindle cell carcinoma (MTSCC) during a short time. In a 61-year-old man who had macroscopic hematuria for 1 month, the 14.5 x 14.0 x 12.0-cm resected tumor involved the right middle aspect of the renal parenchyma and compressed the renal pelvis. In an asymptomatic 47-year-old man, a renal tumor was found during an annual physical examination. The 3.5 x 3.0 x 2.0-cm tumor was located at the upper pole of the right kidney. The histologic findings in both cases were similar Tumors consisted of tightly packed, small, elongated tubules separated by pale mucinous stroma. The tumor cells were cuboidal to spindled with eosinophilic cytoplasm and low nuclear grade. Mitoses were few or nonexistent and without abnormal figures. Both tumors were immunoreactive for cytokeratin (CK) cocktail (AE1/AE3), high-molecular-weight CK (34betaE12), low-molecular-weight CK (35betaH11), CK7, epithelial membrane antigen, E-cadherin, and vimentin. The tumor cells also were reactive for neuron-specific enolase, chromogranin, and synaptophysin. The ultrastructure of the tumor cells contained abundant mitochondria, junctional complex, and dense-core neurosecretory granules. We present 2 additional cases of MTSCC showing typical morphologic features with neuroendocrine differentiation.


Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy.
The contribution of the decline in thymic activity for the emergence of autoimmunity is still debatable. Immune-competent adults submitted to complete thymectomy early in life provide a unique model to address this question. We applied here strict criteria to identify adults lacking thymic activity based on sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement, they featured severe naïve CD4 T-cell depletion and contraction of T-cell receptor diversity. Notwithstanding this, there was neither increased incidence of autoimmune disease in comparison with age-matched controls nor significant changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through extensive arrays. We reasoned that the observed relative preservation of the regulatory T-cell compartment, including maintenance of naïve regulatory CD4 T-cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our findings have implications in other clinical settings with impaired thymic activity, and are particularly relevant to studies of autoimmunity in ageing.


Intracameral air injection during Ahmed glaucoma valve implantation in neovascular glaucoma for the prevention of tube obstruction with blood clot: Case Report.
Glaucoma drainage implant surgery is a treatment option for the management of neovascular glaucoma. However, tube obstruction by blood clot after Ahmed glaucoma valve (AGV) implantation is an unpredictable clinically challenging situation. We report 4 cases using intracameral air injection for the prevention of the tube obstruction of AGV by blood clot. The first case was a 57-year-old female suffering from ocular pain because of a tube obstruction with blood clot after AGV implantation in neovascular glaucoma. Surgical blood clot removal was performed. However, intractable bleeding was noted during the removal of the blood clot, and so intracameral air injection was performed to prevent a recurrent tube obstruction. After the procedure, although blood clots formed around the tube, the tube opening where air could touch remained patent. In 3 cases of neovascular glaucoma with preoperative severe intraocular hemorrhages, intracameral air injection and AGV implantation were performed simultaneously. In all 3 cases, tube openings were patent. It appears that air impeded the blood clots formation in front of the tube opening. Intracameral air injection could be a feasible option to prevent tube obstruction of AGV implant with a blood clot in neovascular glaucoma with high risk of tube obstruction.


Prediction of genomic breeding values for dairy traits in Italian Brown and Simmental bulls using a principal component approach.
The large number of markers available compared with phenotypes represents one of the main issues in genomic selection. In this work, principal component analysis was used to reduce the number of predictors for calculating genomic breeding values (GEBV). Bulls of 2 cattle breeds farmed in Italy (634 Brown and 469 Simmental) were genotyped with the 54K Illumina beadchip (Illumina Inc., San Diego, CA). After data editing, 37,254 and 40,179 single nucleotide polymorphisms (SNP) were retained for Brown and Simmental, respectively. Principal component analysis carried out on the SNP genotype matrix extracted 2,257 and 3,596 new variables in the 2 breeds, respectively. Bulls were sorted by birth year to create reference and prediction populations. The effect of principal components on deregressed proofs in reference animals was estimated with a BLUP model. Results were compared with those obtained by using SNP genotypes as predictors with either the BLUP or Bayes_A method. Traits considered were milk, fat, and protein yields, fat and protein percentages, and somatic cell score. The GEBV were obtained for prediction population by blending direct genomic prediction and pedigree indexes. No substantial differences were observed in squared correlations between GEBV and EBV in prediction animals between the 3 methods in the 2 breeds. The principal component analysis method allowed for a reduction of about 90% in the number of independent variables when predicting direct genomic values, with a substantial decrease in calculation time and without loss of accuracy.


A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses.
To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two heterologous viral vectors expressing L3SEPTL induced a strong cellular response directed against an LSA1 peptide located in the C-terminal region of the polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN-gamma-secreting T cells specific for each of the six antigens were induced after vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce multispecific T cells against P. falciparum. The use of polyprotein constructs in nonreplicating poxviruses should broaden the target antigen range of vaccine-induced immunity and increase the number of potential epitopes available for immunogenetically diverse human populations.


Mindfulness Improves Brain-Computer Interface Performance by Increasing Control Over Neural Activity in the Alpha Band.
Brain-computer interfaces (BCIs) are promising tools for assisting patients with paralysis, but suffer from long training times and variable user proficiency. Mind-body awareness training (MBAT) can improve BCI learning, but how it does so remains unknown. Here, we show that MBAT allows participants to learn to volitionally increase alpha band neural activity during BCI tasks that incorporate intentional rest. We trained individuals in mindfulness-based stress reduction (MBSR; a standardized MBAT intervention) and compared performance and brain activity before and after training between randomly assigned trained and untrained control groups. The MBAT group showed reliably faster learning of BCI than the control group throughout training. Alpha-band activity in electroencephalogram signals, recorded in the volitional resting state during task performance, showed a parallel increase over sessions, and predicted final BCI performance. The level of alpha-band activity during the intentional resting state correlated reliably with individuals' mindfulness practice as well as performance on a breath counting task. Collectively, these results show that MBAT modifies a specific neural signal used by BCI. MBAT, by increasing patients' control over their brain activity during rest, may increase the effectiveness of BCI in the large population who could benefit from alternatives to direct motor control.


Volunteer geographic information in the Global South: barriers to local implementation of mapping projects across Africa.
The world is awash in data-by 2020 it is expected that there will be approximately 40 trillion gigabytes of data in existence, with that number doubling every 2 to 3 years. However, data production is not equal in all places-the global data landscape remains heavily concentrated on English-speaking, urban, and relatively affluent locations within the Global North. This inequality can contribute to new forms of digital and data colonialism. One partial solution to these issues may come in the form of crowdsourcing and volunteer geographic information (VGI), which allow Global South populations to produce their own data. Despite initial optimism about these approaches, many challenges and research gaps remain in understanding the opportunities and barriers that organizations endemic to the Global South face in carrying out their own sustainable crowdsourcing projects. What opportunities and barriers do these endemic organizations face when trying to carry out mapping projects driven by their own goals and desires? This paper contributes answers to this question by examining a VGI project that is currently mapping public libraries across the African continent. Our findings highlight how dramatically digital divides can bias crowdsourcing results; the importance of local cultural views in influencing participation in crowdsourcing; and the continued importance of traditional, authoritative organizations for crowdsourcing. These findings offer important lessons for researchers and organizations attempting to develop their own VGI projects in the Global South.


Changes in the distribution of tenascin during tooth development.
Tenascin is an extracellular matrix molecule that was earlier shown to be enriched in embryonic mesenchyme surrounding the budding epithelium in various organs including the tooth. In the present study tenascin was localized by immunohistology throughout the course of tooth development in the mouse and rat using polyclonal antibodies against chick tenascin. The results indicate that tenascin is expressed by the lineage of dental mesenchymal cells throughout tooth ontogeny. The intensity of staining with tenascin antibodies in the dental papilla mesenchyme was temporarily reduced at cap stage when the tooth grows rapidly and undergoes extensive morphogenetic changes. During the bell stage of morphogenesis, the staining intensity increased and tenascin was accumulated in the dental pulp even after completion of crown development and eruption. Tenascin was present in the dental basement membrane at the time of odontoblast differentiation. The dental papilla cells ceased to express tenascin upon differentiation into odontoblasts and tenascin was completely absent from dentin. It can be speculated that the remarkable expression of tenascin in the dental mesenchymal cells as compared to other connective tissues is associated with their capacity to differentiate into hard-tissue-forming cells.


Increased efficacy and reduced cardiotoxicity of metronomic treatment with cyclophosphamide in rat breast cancer.
It has been reported that continuous low-dose (metronomic) administration of cytotoxic drugs may be better tolerated and may have greater antitumor effects than a single high-dose chemotherapy. The aim of this study was to examine the efficacy and cardiotoxicity of metronomic administration of two of the most commonly used anticancer agents, cyclophosphamide (CPA) and doxorubicin (DOX), on an experimental breast cancer of rats. Breast tumors were induced in Fisher 344 female rats by implanting Mat B III cells. Rats with tumors were randomized into three groups and were treated with a total dose of 160 mg/kg CPA and a total dose of 12 mg/kg DOX, administered twice per week for four weeks. Control rats were injected with saline according to the same schedule. Echocardiography was performed before the start of treatment and before sacrifice, which took place two weeks after the last injection, when plasma troponin was also measured. The metronomic CPA eradicated the tumors and preserved body weight and echocardiographic parameters. The metronomic DOX slowed tumor growth, but was not able to prevent DOX-induced cardiotoxicity. These results suggest that the success of a metronomic chemotherapy in terms of both efficacy and toxicity depends on the target, the class and the route of administration of the anticancer agent.


Aerosol deposition and dispersion characterize lung injury in a canine model of emphysema.
The deposition and dispersion of inhaled aerosol boluses were investigated as markers of lung injury in three dogs before and after emphysema was induced by papain exposure. After the experiments, lung damage was assessed histologically. Four unexposed dogs were used as controls. Effective air space diameter (EAD) was determined from aerosol deposition during a 5-s breath hold. Nonuniform ventilation was assessed from the spreading of the expired bolus, quantified as a coefficient of dispersion (CD), and from expired bolus skewness (SK). Experiments were done with a range of bolus penetrations and ventilatory flow rates. After papain exposure, EAD measured with the most penetrating boluses increased an average of 89% (P < 0.0001); CD and SK measured with boluses of medium penetration and a flow rate of 0.5 l/s increased an average of 24% (P < 0.02) and 98% (P < 0.002), respectively. The effects of lung injury on CD and SK increased with flow rate. Lung injury was confirmed by changes in lung mechanics and by histology. EAD measured with deeply penetrating boluses correlated significantly with the mean chord length measured morphometrically (P < 0.05). No correlation was found with more shallow boluses. The results indicate that EAD, CD, and SK are sensitive markers of lung injury in experimental emphysema and that EAD is a specific marker of increased air space size.


Podoplanin in Inflammation and Cancer.
Podoplanin is a small cell-surface mucin-like glycoprotein that plays a crucial role in the development of the alveoli, heart, and lymphatic vascular system. Emerging evidence indicates that it is also involved in the control of mammary stem-cell activity and biogenesis of platelets in the bone marrow, and exerts an important function in the immune response. Podoplanin expression is upregulated in different cell types, including fibroblasts, macrophages, T helper cells, and epithelial cells, during inflammation and cancer, where it plays important roles. Podoplanin is implicated in chronic inflammatory diseases, such as psoriasis, multiple sclerosis, and rheumatoid arthritis, promotes inflammation-driven and cancer-associated thrombosis, and stimulates cancer cell invasion and metastasis through a variety of strategies. To accomplish its biological functions, podoplanin must interact with other proteins located in the same cell or in neighbor cells. The binding of podoplanin to its ligands leads to modulation of signaling pathways that regulate proliferation, contractility, migration, epithelial⁻mesenchymal transition, and remodeling of the extracellular matrix. In this review, we describe the diverse roles of podoplanin in inflammation and cancer, depict the protein ligands of podoplanin identified so far, and discuss the mechanistic basis for the involvement of podoplanin in all these processes.


Increased survival associated with surgery and radiation therapy in metastatic gastric cancer: a Surveillance, Epidemiology, and End Results database analysis.
Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients stratified by surgery and radiation therapy. The Surveillance, Epidemiology, and End Results (SEER) database was accessed to identify patients with AJCC M1 stage IV gastric cancer (based on the American Joint Committee on Cancer Cancer Staging Manual, 6th edition) between 2004 thru 2008. Patients were divided into 4 groups: group 1, no surgery or radiation; group 2, radiation alone; group 3, surgery alone; group 4, surgery and radiation. Survival analysis was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard ratio model. A total of 5072 patients were identified. Surgery and/or radiation were associated with a survival benefit. Median and 2-year survival for groups 1, 2, 3, and 4 was 7 months and 8.2%, 8 months and 8.9%, 10 months and 18.2%, and 16 months and 31.7%, respectively (P < .00001). MVA for all patients revealed that surgery and radiation were associated with decreased mortality whereas T-stage, N-stage, age, signet ring histology, and peritoneal metastases were associated with increased mortality. In patients treated with surgery, MVA showed that radiation was associated with decreased mortality, whereas T-stage, N-stage, age, removal of < 15 lymph nodes, signet ring histology, and peritoneal metastases was associated with increased mortality. Age was the only prognostic factor in patients who did not undergo surgery. Surgery and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer.


Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions.
Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury, but this approach is limited by their poor viability after transplantation. To reduce cell loss after transplantation, we introduced the fibroblast growth factor-2 (FGF-2) gene ex vivo before transplantation. The isolated MSCs produced colonies with a fibroblast-like morphology in 2 weeks; over 95% expressed CD71, and 28% expressed the cardiomyocyte-specific transcription factor, Nkx2.5, as well as a-skeletal actin, Nkx2.5, and GATA4. In hypoxic culture, the FGF-2-transfected MSCs (FGF-2-MSCs) secreted increased levels of FGF-2 and displayed a threefold increase in viability, as well as increased expression of the anti-apoptotic gene, Bcl2, and reduced DNA laddering. They had functional adrenergic receptors, like cardiomyocytes, and exposure to norepinephrine led to phosphorylation of ERK1/2. Viable cells persisted 4 weeks after implantation of 5.0 yen 105 FGF-2-MSCs into infarcted myocardia. Expression of cardiac troponin T (CTn T) and a voltage-gated Ca2+ channel (CaV2.1) increased, and new blood vessels formed. These data suggest that genetic modification of MSCs before transplantation could be useful for treating myocardial infarction and end-stage cardiac failure.


ICR142 Benchmarker: evaluating, optimising and benchmarking variant calling performance using the ICR142 NGS validation series.
Evaluating, optimising and benchmarking of next generation sequencing (NGS) variant calling performance are essential requirements for clinical, commercial and academic NGS pipelines. Such assessments should be performed in a consistent, transparent and reproducible fashion, using independently, orthogonally generated data. Here we present ICR142 Benchmarker, a tool to generate outputs for assessing germline base substitution and indel calling performance using the ICR142 NGS validation series, a dataset of Illumina platform-based exome sequence data from 142 samples together with Sanger sequence data at 704 sites. ICR142 Benchmarker provides summary and detailed information on the sensitivity, specificity and false detection rates of variant callers. ICR142 Benchmarker also automatically generates a single page report highlighting key performance metrics and how performance compares to widely-used open-source tools. We used ICR142 Benchmarker with VCF files outputted by GATK, OpEx and DeepVariant to create a benchmark for variant calling performance. This evaluation revealed pipeline-specific differences and shared challenges in variant calling, for example in detecting indels in short repeating sequence motifs. We next used ICR142 Benchmarker to perform regression testing with DeepVariant versions 0.5.2 and 0.6.1. This showed that v0.6.1 improves variant calling performance, but there was evidence of minor changes in indel calling behaviour that may benefit from attention. The data also allowed us to evaluate filters to optimise DeepVariant calling, and we recommend using 30 as the QUAL threshold for base substitution calls when using DeepVariant v0.6.1. Finally, we used ICR142 Benchmarker with VCF files from two commercial variant calling providers to facilitate optimisation of their in-house pipelines and to provide transparent benchmarking of their performance. ICR142 Benchmarker consistently and transparently analyses variant calling performance based on the ICR142 NGS validation series, using the standard VCF input and outputting informative metrics to enable user understanding of pipeline performance. ICR142 Benchmarker is freely available at https://github.com/RahmanTeamDevelopment/ICR142_Benchmarker/releases.


The plant extracts of Momordica charantia and Trigonella foenum-graecum have anti-oxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus.
Oxidative stress is currently suggested to play a major role in the development of diabetes mellitus. There is an increasing demand of natural anti-diabetic agents, as continuous administration of existing drugs and insulin are associated with many side effects and toxicity. The present study was aimed to investigate the effect of Momordica charantia (MC) and Trigonella foenum graecum (TFG) extracts (aqueous) on antioxidant status and lipid peroxidation in heart tissue of normal and alloxan induced diabetic rats. In a 30 days treatment, rats were divided into six groups (I-VI) of five animals in each,experiments were repeated thrice. Administration of MC (13.33 g pulp/kg body weight/day) and TFG (9 g seeds powder/kg body weight/day) extracts in diabetic rats has remarkably improved the elevated levels of fasting blood glucose. A significant decrease in lipid peroxidation (p<0.001) and significant increase in the activities of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and reduced glutathione (GSH ) contents in heart tissue of diabetic rats were observed (group V and VI) upon MC and TFG treatment. Our studies demonstrate the anti-hyperglycemic and anti-oxidative potential of Momordica charantia and Trigonella foenum graecum, which could exert beneficial effects against the diabetes and associated free radicals complications in heart tissue.


Persistent Organochlorine Pesticide Exposure Related to a Formerly Used Defense Site on St. Lawrence Island, Alaska: Data from Sentinel Fish and Human Sera.
St. Lawrence Island, Alaska, is the largest island in the Bering Sea, located 60 km from Siberia. The island is home to approximately 1600 St. Lawrence Island Yupik residents who live a subsistence way of life. Two formerly used defense sites (FUDS) exist on the island, one of which, Northeast Cape, has been the subject of a $123 million cleanup effort. Environmental monitoring demonstrates localized soil and watershed contamination with polychlorinated biphenyls (PCB), organochlorine (OC) pesticides, mercury, and arsenic. This study examined whether the Northeast Cape FUDS is a source of exposure to OC pesticides. In total, 71 serum samples were collected during site remediation from volunteers who represented three geographic regions of the island. In addition, ninespine stickleback (Pungitius pungitius) and Alaska blackfish (Dallia pectoralis) were collected from Northeast Cape after remediation to assess continuing presence of OC pesticides. Chlordane compounds, DDT compounds, mirex, and hexachlorobenzene (HCB) were the most prevalent and present at the highest concentrations in both fish tissues and human serum samples. After controlling for age and gender, activities near the Northeast Cape FUDS were associated with an increase in serum HCB as compared to residents of the farthest village from the site. Positive but nonsignificant relationships for sum-chlordane and sum-DDT were also found. Organochlorine concentrations in fish samples did not show clear geographic trends, but appear elevated compared to other sites in Alaska. Taken together, data suggest that contamination of the local environment at the Northeast Cape FUDS may increase exposure to select persistent OC pesticides.


Differential backscatter from the atmospheric aerosol: the implications for IR differential absorption lidar.
To avoid systematic errors in differential absorption lidar experiments, which use the atmospheric aerosol as a distributed reflector, the assumption has to be made that the volume backscattering coefficient is approximately the same at the two wavelengths. A model of the aerosol has been used to show that in the 9-11-microm region this assumption may be invalid since absorption by the aerosol makes the backscattering term a sensitive function of frequency and relative humidity. To illustrate the problem we examine five pairs of laser frequencies recommended in the literature for monitoring ammonia, ozone, ethylene, and Freon-11 and show that peak-to-peak differential backscatter of >10% is common across the whole humidity range. We also show that the sensitivity of backscattering to humidity changes is such that the volume backscattering coefficient at the on-line wavelength can become larger than the off-line value as the relative humidity increases, an effect that may nullify any rise in trace gas concentration that happens to take place.


Heterodyne moiré surface profilometry.
In this study, a novel moiré fringe analysis technique is proposed for measuring the surface profile of an object. After applying a relative displacement between two gratings at a constant velocity, every pixel of CMOS camera can capture a heterodyne moiré signal. The precise phase distribution of the moiré fringes can be extracted using a one-dimensional fast Fourier transform (FFT) analysis on every pixel, simultaneously filtering the harmonic noise of the moiré fringes. Finally, the surface profile of the tested objected can be generated by substituting the phase distribution into the relevant equation. The findings demonstrate the feasibility of this measuring method, and the measurement error was approximately 4.3 μm. The proposed method exhibits the merits of the Talbot effect, projection moiré method, FFT analysis, and heterodyne interferometry.


Implementation and Operational Research: Impact of a Systems Engineering Intervention on PMTCT Service Delivery in Côte d'Ivoire, Kenya, Mozambique: A Cluster Randomized Trial.
Efficacious interventions to prevent mother-to-child HIV transmission (PMTCT) have not translated well into effective programs. Previous studies of systems engineering applications to PMTCT lacked comparison groups or randomization. Thirty-six health facilities in Côte d'Ivoire, Kenya, and Mozambique were randomized to usual care or a systems engineering intervention, stratified by country and volume. The intervention guided facility staff to iteratively identify and then rectify barriers to PMTCT implementation. Registry data quantified coverage of HIV testing during first antenatal care visit, antiretrovirals (ARVs) for HIV-positive pregnant women, and screening HIV-exposed infants (HEI) for HIV by 6-8 weeks. We compared the change between baseline (January 2013-January 2014) and postintervention (January 2015-March 2015) periods using t-tests. All analyses were intent-to-treat. ARV coverage increased 3-fold [+13.3% points (95% CI: 0.5 to 26.0) in intervention vs. +4.1 (-12.6 to 20.7) in control facilities] and HEI screening increased 17-fold [+11.6 (-2.6 to 25.7) in intervention vs. +0.7 (-12.9 to 14.4) in control facilities]. In prespecified subgroup analyses, ARV coverage increased significantly in Kenya [+20.9 (-3.1 to 44.9) in intervention vs. -21.2 (-52.7 to 10.4) in controls; P = 0.02]. HEI screening increased significantly in Mozambique [+23.1 (10.3 to 35.8) in intervention vs. +3.7 (-13.1 to 20.6) in controls; P = 0.04]. HIV testing did not differ significantly between arms. In this first randomized trial of systems engineering to improve PMTCT, we saw substantially larger improvements in ARV coverage and HEI screening in intervention facilities compared with controls, which were significant in prespecified subgroups. Systems engineering could strengthen PMTCT service delivery and protect infants from HIV.


Self referral to accident and emergency department: patients' perceptions.
A study was conducted (a) to assess the number of patients registered with a south London general practice who over 11 weeks referred themselves to an accident and emergency department, (b) to identify the characteristics of those patients, and (c) to determine their perceptions of the services and resources available within their general practices and of the role of accident and emergency departments. Two hundred and thirty four patients referred themselves to a casualty department during the study period, of whom 217 (93%) were interviewed by means of a semistructured questionnaire. Of the 217 patients interviewed, only 15 had tried to contact their general practitioner before attending the casualty department. Eighty nine patients considered that their problem was urgent and required immediate attention and many that they would need an x ray examination. A substantial minority of patients thought that their doctor would not be available. It is concluded that patients' perceptions of their problems and of access to their doctors are the main determinants of self referral to a casualty department. These findings have important implications for patient education.


CT recognition of optic nerve sheath meningioma: abnormal sheath visualization.
Optic nerve sheath meningiomas and optic nerve gliomas can be difficult to differentiate by computed tomography (CT). Three patients with optic nerve sheath meningiomas were studied with a CT/T 8800 scanner with 1.5-mm-thick axial sections and intravenous contrast material. In each case, an abnormal optic nerve sheath was identified by CT. A soft-tissue mass arose from one side of the sheath in one patient, and the entire sheath was enlarged in two patients. This provides a basis for distinguishing optic nerve sheath meningioma from optic nerve glioma.


Evidence supporting dissimilatory and assimilatory lignin degradation in Enterobacter lignolyticus SCF1.
Lignocellulosic biofuels are promising as sustainable alternative fuels, but lignin inhibits access of enzymes to cellulose, and by-products of lignin degradation can be toxic to cells. The fast growth, high efficiency and specificity of enzymes employed in the anaerobic litter deconstruction carried out by tropical soil bacteria make these organisms useful templates for improving biofuel production. The facultative anaerobe Enterobacter lignolyticus SCF1 was initially cultivated from Cloud Forest soils in the Luquillo Experimental Forest in Puerto Rico, based on anaerobic growth on lignin as sole carbon source. The source of the isolate was tropical forest soils that decompose litter rapidly with low and fluctuating redox potentials, where bacteria using oxygen-independent enzymes likely play an important role in decomposition. We have used transcriptomics and proteomics to examine the observed increased growth of SCF1 grown on media amended with lignin compared to unamended growth. Proteomics suggested accelerated xylose uptake and metabolism under lignin-amended growth, with up-regulation of proteins involved in lignin degradation via the 4-hydroxyphenylacetate degradation pathway, catalase/peroxidase enzymes, and the glutathione biosynthesis and glutathione S-transferase (GST) proteins. We also observed increased production of NADH-quinone oxidoreductase, other electron transport chain proteins, and ATP synthase and ATP-binding cassette (ABC) transporters. This suggested the use of lignin as terminal electron acceptor. We detected significant lignin degradation over time by absorbance, and also used metabolomics to demonstrate moderately significant decreased xylose concentrations as well as increased metabolic products acetate and formate in stationary phase in lignin-amended compared to unamended growth conditions. Our data show the advantages of a multi-omics approach toward providing insights as to how lignin may be used in nature by microorganisms coping with poor carbon availability.


Relative contribution of various airway protective mechanisms to prevention of aspiration during swallowing.
Deglutitive airway protective mechanisms include glottal closure, epiglottal descent, and anterosuperior displacement of the larynx. Aspiration of swallowed material may occur during the pre-, intra-, or postpharyngeal phase of swallowing. Our objectives were to determine the relative contribution of the airway protective mechanisms during each phase of swallow in 14 decerebrated cats before and after suprahyoid myotomy, epiglottectomy, and unilateral cordectomy. After myotomy, superior excursions of the hyoid, thyroid, and cricoid cartilages and anteroposterior diameter of maximum upper esophageal spincter (UES) opening were significantly diminished, but the incidence of pharyngeal residue significantly increased (P < 0.05). No aspiration was observed in the predeglutitive period. After myotomy, the incidence of aspiration significantly increased in both intra- and postdeglutitive periods. Epiglottectomy did not alter aspiration incidence, but unilateral cordectomy resulted in a 100% incidence of intra- and postdeglutitive aspiration. In conclusion, glottal closure constitutes the primary mechanism for prevention of intra- and postdeglutitive aspiration, but laryngeal elevation may assist this function. Bolus pulsion without laryngeal distraction can open the UES, but at risk of aspiration due to decreased pharyngeal clearance. The epiglottis provides no apparent airway protection during any phase of swallowing.


[Nutritional status and aerobic capacity among children attending public elementary schools in Chile].
The Chilean Ministry of Health has developed a health promotion program called "Vida Chile", whose aim is to target risk factors for chronic diseases. To achieve this, school-based initiatives in nutrition and physical activity have been implemented. The evaluation of these initiatives includes a baseline assessment of these two variables. Baseline assessment of the nutritional status and aerobic capacity of elementary school children (1st to 8th grade). Children from seven public schools were studied. Weight, height, triceps skinfold thickness and waist circumference were measured. To test the aerobic capacity, the 20-m Shuttle Run Test (Navette) was utilized. The assessment included 4,271 children, mean age was 10.2 years. The percentile of body mass index, as compared to the CDC 2000 Reference was 67.8 +/- 26.7 and 68 +/- 26.7 for boys and girls, respectively. The prevalence of obesity among children from 6 to 8 years, was 20.3 and 17.7% for boys and girls, respectively. Approximately 30% of males and 15% of females with normal weight had a good aerobic resistance, compared to 15 and 4% of their overweight counterparts. Aerobic capacity decreased with increasing age. There is a high prevalence of obesity and a deficient level of aerobic capacity among children attending public schools in Chile.


Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2.
A major Grb2-associated binder-1 (Gab1) binding partner in epidermal growth factor (EGF)-stimulated cells is protein-tyrosine phosphatase (PTPase) SHP2, which contains tandem SH2 domains. The SHP2 PTPase activity is required for activation of the extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein (MAP) kinase by EGF. To investigate the mechanism by which Gab1 and SHP2 mediate ERK activation, we characterized the Gab1-SHP2 interaction. We found that both Tyr-627 and Tyr-659 of Gab1 were required for SHP2 binding to Gab1 and for ERK2 activation by EGF. Far Western blot analysis suggested that the tandem SH2 domains of SHP2 bind to Gab1 in a specific orientation, in which the N-SH2 domain binds to phosphotyrosine (Tyr(P))-627 and the C-SH2 domain binds to Tyr(P)-659. When assayed with peptide substrates, SHP2 PTPase was activated by a bisphosphopeptide containing both Tyr(P)-627 and Tyr(P)-659, but not by monophosphopeptides containing Tyr(P)-627 or Tyr(P)-659 or a mixture of these monophosphopeptides. These results suggest that Tyr(P)-627 and Tyr(P)-659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) that binds and activates SHP2. Remarkably, while a constitutively active SHP2 (SHP2DeltaN) could not rescue the defect of a SHP2-binding defective Gab1 (Gab1FF) in ERK2 activation, expression of a Gab1FF-SHP2DeltaN chimera resulted in constitutive activation of ERK2 in transfected cells. Thus, physical association of activated SHP2 with Gab1 is necessary and sufficient to mediate the ERK mitogen-activated protein kinase activation. Phosphopeptides derived from Gab1 were dephosphorylated by active SHP2 in vitro. Consistently, substrate-trapping experiments with a SHP2 catalytic inactive mutant suggested that Gab1 was a SHP2 PTPase substrate in the cells. Therefore, Gab1 not only is a SHP2 activator but also is a target of its PTPase.


Meconium-stained amniotic fluid is associated with puerperal infections.
The purpose of this study was to determine whether meconium-stained amniotic fluid is associated with puerperal infection and whether the quality of the meconium is further associated with this risk. We designed a retrospective cohort study of all deliveries beyond 37 weeks gestational age from 1992 to 2002 at a single community hospital. Data were collected on rates of chorioamnionitis, endomyometritis, quality of amniotic fluid, and length of labor and analyzed with bivariate and multivariate analyses. We found that, among the 43,200 women who were delivered at term, 18.9% of the women had meconium staining (8.8% thin, 5.5% moderate, 4.6% thick). Compared with deliveries with clear amniotic fluid, those with meconium-stained amniotic fluid had higher rates of chorioamnionitis (2.3% vs 4.1%, P<.001) and endomyometritis (1.0% vs 1.7%, P<.001). Further, the severity of meconium staining was associated with increased rates of infection. We found that the presence and severity of meconium-stained amniotic fluid is associated with puerperal infection even when being controlled for confounders.


Electromyography of swallowing with fine wire intramuscular electrodes in healthy human: activation sequence of selected hyoid muscles.
Few studies have reported the activation sequence of the swallowing muscles in healthy human participants. We examined temporal characteristics of selected hyoid muscles using fine wire intramuscular electromyography (EMG). Thirteen healthy adults were studied using EMG of the anterior belly of digastric (ABD), geniohyoid (GH), sternohyoid (SH), and masseter (MA, with surface electrodes) while ingesting thin liquid, banana, tofu, and cookie (3 trials each). Onset timing was measured from rectified and integrated EMG. Data were analyzed using repeated-measures ANOVA with Bonferroni correction. When drinking thin liquid, MA, GH, and ABD were activated almost simultaneously, but SH was activated later (using GH onset as 0 s, MA -0.07 (-0.20 to 0.17) second [median (interquartile range)]; ABD 0.00 (-0.10 to 0.07) second; SH 0.17 (0.02 to 0.37) second; P < 0.01). With solid foods, MA contraction preceded GH and ABD; SH was last and delayed relative to liquid swallows (GH 0 s; MA -0.17 (-0.27 to 0.07) second; ABD 0.00 (-0.03 to 0.03) second; SH 0.37 (0.23 to 0.50) second; P < 0.01). The role of the MA differs between solids and liquids so the variation in its timing is expected. The synchronous contraction of GH and ABD was consistent with their role in hyolaryngeal elevation. The SH contracted later with solids, perhaps because if the longer duration of the swallow. The consistent pattern among foods supports the concept of a central pattern generator for pharyngeal swallowing.


Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis.
The mitochondrial permeability transition pore is a recognized drug target for neurodegenerative conditions such as multiple sclerosis and for ischemia-reperfusion injury in the brain and heart. The peptidylprolyl isomerase, cyclophilin D (CypD, PPIF), is a positive regulator of the pore, and genetic down-regulation or knock-out improves outcomes in disease models. Current inhibitors of peptidylprolyl isomerases show no selectivity between the tightly conserved cyclophilin paralogs and exhibit significant off-target effects, immunosuppression, and toxicity. We therefore designed and synthesized a new mitochondrially targeted CypD inhibitor, JW47, using a quinolinium cation tethered to cyclosporine. X-ray analysis was used to validate the design concept, and biological evaluation revealed selective cellular inhibition of CypD and the permeability transition pore with reduced cellular toxicity compared with cyclosporine. In an experimental autoimmune encephalomyelitis disease model of neurodegeneration in multiple sclerosis, JW47 demonstrated significant protection of axons and improved motor assessments with minimal immunosuppression. These findings suggest that selective CypD inhibition may represent a viable therapeutic strategy for MS and identify quinolinium as a mitochondrial targeting group for in vivo use.


Perinatal methanol exposure in the rat. I. Blood methanol concentration and neural cell adhesion molecules.
Although the acute toxicity of methanol is well documented, few studies have addressed the consequences of perinatal exposures to the low concentrations that are expected to arise from its proposed use as a component of automobile fuel. This report describes the general research design of a series of studies, the effects of methanol exposures on blood concentrations in dams and neonates, and indices of brain development. Four cohorts of Long-Evans pregnant rats, each cohort consisting of an exposure (n = 12) and a control (n = 12) group, were exposed whole-body to 4500 ppm methanol vapor or air for 6 hr daily beginning on Gestation Day 6. Both dams and pups were then exposed through Postnatal Day 21 (PND 21). Blood methanol concentrations determined by gas chromatography from samples obtained immediately following a 6-hr exposure reached approximately 500-800 micrograms/ml in the dams during gestation and lactation. Average concentrations for pups attained levels about twice those of the dams. Selected offspring from Cohort 4 were exposed for one additional 6-hr session at ages that extended out to PND 52. Regression analyses showed that the blood methanol concentrations of the pups declined until about PND 48, at which time their levels approximated those of their dams. Such pharmacokinetic differences might increase the risks posed to developing organisms. Light-microscopic analysis showed no significant abnormalities in the brains of the methanol-treated animals. However, assays of neural cell adhesion molecules (NCAMs) in brains of pups sacrificed on PND 4 showed staining for both the 140 and the 180 kDa isoforms to be less intense in the cerebellum of exposed animals. NCAM differences were not apparent in animals sacrificed 15 months after their final exposure.


A designed experiments approach to optimization of automated data acquisition during characterization of bacteria with MALDI-TOF mass spectrometry.
MALDI-TOF MS has been shown capable of rapidly and accurately characterizing bacteria. Highly reproducible spectra are required to ensure reliable characterization. Prior work has shown that spectra acquired manually can have higher reproducibility than those acquired automatically. For this reason, the objective of this study was to optimize automated data acquisition to yield spectra with reproducibility comparable to those acquired manually. Fractional factorial design was used to design experiments for robust optimization of settings, in which values of five parameters (peak selection mass range, signal to noise ratio (S:N), base peak intensity, minimum resolution and number of shots summed) commonly used to facilitate automated data acquisition were varied. Pseudomonas aeruginosa was used as a model bacterium in the designed experiments, and spectra were acquired using an intact cell sample preparation method. Optimum automated data acquisition settings (i.e., those settings yielding the highest reproducibility of replicate mass spectra) were obtained based on statistical analysis of spectra of P. aeruginosa. Finally, spectrum quality and reproducibility obtained from non-optimized and optimized automated data acquisition settings were compared for P. aeruginosa, as well as for two other bacteria, Klebsiella pneumoniae and Serratia marcescens. Results indicated that reproducibility increased from 90% to 97% (p-value[Formula: see text]0.002) for P. aeruginosa when more shots were summed and, interestingly, decreased from 95% to 92% (p-value [Formula: see text] 0.013) with increased threshold minimum resolution. With regard to spectrum quality, highly reproducible spectra were more likely to have high spectrum quality as measured by several quality metrics, except for base peak resolution. Interaction plots suggest that, in cases of low threshold minimum resolution, high reproducibility can be achieved with fewer shots. Optimization yielded more reproducible spectra than non-optimized settings for all three bacteria.


Does Short-Term Dietary Omega-3 Fatty Acid Supplementation Influence Brain Hippocampus Gene Expression of Zinc Transporter-3?
Dietary omega-3 fatty acids have been recognized to improve brain cognitive function. Deficiency leads to dysfunctional zinc metabolism associated with learning and memory impairment. The objective of this study is to explore the effect of short-term dietary omega-3 fatty acids on hippocampus gene expression at the molecular level in relation to spatial recognition memory in mice. A total of 24 male BALB/c mice were randomly divided into four groups and fed a standard pellet as a control group (CTL, n = 6), standard pellet added with 10% (w/w) fish oil (FO, n = 6), 10% (w/w) soybean oil (SO, n = 6) and 10% (w/w) butter (BT, n = 6). After 3 weeks on the treatment diets, spatial-recognition memory was tested on a Y-maze. The hippocampus gene expression was determined using a real-time PCR. The results showed that 3 weeks of dietary omega-3 fatty acid supplementation improved cognitive performance along with the up-regulation of α-synuclein, calmodulin and transthyretin genes expression. In addition, dietary omega-3 fatty acid deficiency increased the level of ZnT3 gene and subsequently reduced cognitive performance in mice. These results indicate that the increased the ZnT3 levels caused by the deficiency of omega-3 fatty acids produced an abnormal zinc metabolism that in turn impaired the brain cognitive performance in mice.


Prevalence of genital warts in reproductive-aged Turkish women presenting at gynecology outpatient clinics for any reason.
The objective of this multicenter descriptive study was to calculate the frequency of genital warts among Turkish women aged 15-49 years, who visited outpatient gynecology clinics for a variety of reasons. The study was conducted in February 2011 to collect data for a minimum of 154 patients at each center, and the total sample size reached 2,967 women (95.1% completion rate). Oral informed consents were obtained. A questionnaire including data on socio-demographic characteristics and reasons for admission was administered, and a pelvic examination was performed. The overall point prevalence was 35% (95% CI = 3.1%-4.0%), correcting for sampling design, with the highest rates observed in the 15 to 19-year-old group. The odds of having a genital wart was 1.82 times (95% CI = 0.99-3.33) higher among non-pregnant participants than in pregnant women (p = 0.051). The overall point prevalence of genital warts among reproductive-aged women attending gynecology outpatient clinics for any reason in Turkey was 35%.


Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology.
This paper aims to provide information and explanations regarding the clinically relevant options, strengths, and limitations of cardiovascular magnetic resonance (CMR) in relation to adults with congenital heart disease (CHD). Cardiovascular magnetic resonance can provide assessments of anatomical connections, biventricular function, myocardial viability, measurements of flow, angiography, and more, without ionizing radiation. It should be regarded as a necessary facility in a centre specializing in the care of adults with CHD. Also, those using CMR to investigate acquired heart disease should be able to recognize and evaluate previously unsuspected CHD such as septal defects, anomalously connected pulmonary veins, or double-chambered right ventricle. To realize its full potential and to avoid pitfalls, however, CMR of CHD requires training and experience. Appropriate pathophysiological understanding is needed to evaluate cardiovascular function after surgery for tetralogy of Fallot, transposition of the great arteries, and after Fontan operations. For these and other complex CHD, CMR should be undertaken by specialists committed to long-term collaboration with the clinicians and surgeons managing the patients. We provide a table of CMR acquisition protocols in relation to CHD categories as a guide towards appropriate use of this uniquely versatile imaging modality.


Self-administration of the endogenous trace amines beta-phenylethylamine, N-methyl phenylethylamine and phenylethanolamine in dogs.
beta-Phenylethylamine and phenylethanolamine are biogenic amines structurally related to amphetamine which are known to occur endogenously in trace amounts in mammalian brain. The purpose of the present experiments was to determine whether these endogenous biogenic amines, like amphetamine, have reinforcing properties. Dogs surgically prepared with i.v. catheters were permitted 4-hr daily access to i.v. infusions of beta-phenylethylamine, phenylethanolamine, N-methylphenylethylamine, cocaine or d-amphetamine under a fixed-ratio one-response schedule of reinforcement. In dogs which had not previously self-administered drugs, the number of infusions self-administered per session of beta-phenylethylamine, N-methyl phenylethylamine and cocaine increased above that for saline typically within 5 to 10 sessions. Increases in the number of injections per session were observed in only two of five dogs with phenylethanolamine, and in only three of five dogs with d-amphetamine within as many as 20 to 40 sessions. Does-effect curves were determined in dogs which had been trained previously to self-administer drug and whose daily drug intake was stable. The relative potencies of these compounds in maintaining self-administration behavior during the 4-hr session were d-amphetamine greater than cocaine greater than phenylethanolamine greater than or equal to N-methyl phenylethylamine greater than or equal to beta-phenylethylamine. These data indicate that the endogenous trace amines beta-phenylethylamine, phenylethanolamine and the N-methyl homolog of beta-phenylethylamine can function as reinforcers and are compatible with hypotheses that they may play a physiological role in the reinforcement process or in neuropsychiatric disorders.


Who reports sexual function problems? Empirical evidence from Britain's 2000 National Survey of Sexual Attitudes and Lifestyles.
To identify sociodemographic, sexual, and health behavioural and attitudinal factors associated with reporting sexual function problems. A probability sample survey of 11 161 men and women aged 16-44 years resident in Britain in 2000. Data collected by a combination of computer assisted face to face and self interviewing. Outcomes were self report of a range of sexual function problems, considered as "any problems" (1+ lasting 1+ months in the past year) and "persistent problems" (1+ lasting 6+ months in the past year), and associations with sociodemographic, behavioural, and attitudinal variables. Both "any" and "persistent" sexual function problems were more commonly reported by women than men. A variety of sociodemographic factors were associated with both measures but differed by gender. For example, the adjusted odds ratio (AOR) for reporting any problems for married v single respondents was 0.70 (95% confidence interval (CI) 0.57 to 0.87) v 1.31 (95% CI 1.10 to 1.56) for men and women, respectively. Sexual behaviours significantly associated with reporting sexual function problems included competence at first sex, paying for sex in the past 5 years, number of occasions of sex and masturbation, both in the past 4 weeks. For men (only), reporting STI diagnosis(es) was significantly associated with reporting "any" problems (AOR 2.1, 95% CI 1.4 to 3.2) and "persistent" problems (AOR 2.1, 95% CI 1.1 to 3.9). Both measures were significantly more likely among men and women who reported communication difficulties with their partners, with AORs in excess of 1.9. Sexual fulfilment is an important part of sexual health. Understanding factors associated with reporting sexual problems, and recognising that such factors maybe partnership specific, is an important step towards improving our understanding of sexual function and thus improving the provision of care and support available.


Low thyroid-stimulating hormone as an independent risk factor for Alzheimer disease.
To assess a possible relationship between thyroid-stimulating hormone (TSH) levels, vascular risk factors, and Alzheimer disease (AD). TSH levels were measured in 178 AD patients (35 confirmed post mortem) and 291 cognitively screened control subjects who were all euthyroid (TSH: 0.5 to 6 mU/L). The risk of AD was determined in participants with lower levels of TSH, several cerebrovascular risk factors, and other potential confounds. AD patients had significantly lower levels of TSH than control subjects. Lowered TSH was associated with a more than twofold increased risk of AD (odds ratio = 2.36, 95% CI = 1.19 to 4.67), independent of other risk factors. Lowered TSH within the normal range is a risk factor for AD, independent of several cerebrovascular risk factors and confounding variables.


The actin nucleator WASp is required for myoblast fusion during adult Drosophila myogenesis.
Myoblast fusion provides a fundamental, conserved mechanism for muscle fiber growth. We demonstrate here that the functional contribution of Wsp, the Drosophila homolog of the conserved actin nucleation-promoting factor (NPF) WASp, is essential for myoblast fusion during the formation of muscles of the adult fly. Disruption of Wsp function results in complete arrest of myoblast fusion in all muscles examined. Wsp activity during adult Drosophila myogenesis is specifically required for muscle cell fusion and is crucial both for the formation of new muscle fibers and for the growth of muscles derived from persistent larval templates. Although Wsp is expressed both in fibers and individual myoblasts, its activity in either one of these cell types is sufficient. SCAR, a second major Arp2/3 NPF, is also required during adult myoblast fusion. Formation of fusion-associated actin 'foci' is dependent on Arp2/3 complex function, but appears to rely on a distinct, unknown nucleator. The comprehensive nature of these requirements identifies Arp2/3-based branched actin polymerization as a universal mechanism underlying myoblast fusion.


Free and total plasma levels of lopinavir during pregnancy, at delivery and postpartum: implications for dosage adjustments in pregnant women.
Physiological changes associated with pregnancy may alter antiretroviral plasma concentrations and might jeopardize prevention of mother-to-child HIV transmission. Lopinavir is one of the protease inhibitors more frequently prescribed during pregnancy in Europe. We described the free and total pharmacokinetics of lopinavir in HIV-infected pregnant and non-pregnant women, and evaluated whether significant alterations in its disposition and protein binding warrant systematic dosage adjustment. Plasma samples were collected at first, second and third trimester of pregnancy, at delivery, in umbilical cord and postpartum. Lopinavir free and total plasma concentrations were measured by HPLC-MS/MS. Bayesian calculations were used to extrapolate total concentrations to trough (Cmin). A total of 42 HIV-positive pregnant women and 37 non-pregnant women on lopinavir/ritonavir were included in the study. Compared to postpartum and control values, total lopinavir Cmin was decreased moderately (31-39%) during pregnancy, and free Cmin minimally, showing significant alteration only at delivery (-35%). However, total and free Cmin remained in all patients above the target concentrations for wild-type virus of 1,000 ng/ml, and above the unbound IC50(WT) of 0.64-0.77 ng/ml of lopinavir, respectively. Lopinavir free fractions remained higher during pregnancy compared to postpartum and controls, and were influenced by α-1-acid-glycoprotein and albumin decrease. Free cord-to-mother ratio (0.43) was 2.7-fold higher than total cord-to-mother ratio (0.16), suggesting higher fetal exposure. The moderate decrease of total lopinavir concentrations during pregnancy is not associated with proportional decrease in free concentrations. Both reach a nadir at delivery, albeit not to an extent that would put treatment-naive women at risk of insufficient exposure to the free, pharmacologically active concentrations of lopinavir. No dosage adjustment is therefore needed during pregnancy as it is unlikely to further enhance treatment efficacy but could potentially increase the risk of maternal and fetal toxicity. Nonetheless, in case of viral resistance in treatment-experienced pregnant women, loss of virological control or questionable adherence, it is justified to consider lopinavir dosage adjustment based on total plasma concentration measurement.


Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.
Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.


Nanoskiving core-shell nanowires: a new fabrication method for nano-optics.
This paper describes the fabrication of functional optical devices by sectioning quantum-dot-in-nanowires systems with predefined lengths and orientations. This fabrication process requires only two steps, embedding the nanowires in epoxy and using an ultramicrotome to section them across their axis ("nanoskiving"). This work demonstrates the combination of the following four capabilities: (i) the control of the length of the nanowire sections at the nanometer scale; (ii) the ability to process the nanowires after cutting using wet etching; (iii) the possibility of modifying the geometry of the wire by varying the sectioning angle; and (iv) the generation of as many as 120 consecutive slabs bearing nanowires that have uniform size and approximately reproducible lateral patterns and that can subsequently be transferred to different substrates. The quantum dots inside the nanowires are functional and of a high optical quality after the sectioning process and exhibit photoluminescent emission with wavelengths in the range of 650-710 nm.


Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure.
Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose-response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59-2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure.


Paralimbic gray matter reductions in incarcerated adolescent females with psychopathic traits.
Psychopathy-related paralimbic and limbic structural brain abnormalities have been implicated in incarcerated adult and adolescent male samples. However, there have been few neuroimaging studies of psychopathic traits in females in general and no studies from incarcerated female youth in particular. Here we present the first study to examine the relationship between brain gray matter volumes and psychopathic traits (assessed using the Psychopathy Checklist-Youth Version [PCL-YV]) in a sample of maximum-security incarcerated female adolescents (N = 39; mean age = 17.6 years). Consistent with male samples, regional gray matter volumes were negatively related to psychopathic traits in female youth offenders in limbic and paralimbic areas, including orbitofrontal cortex, parahippocampal cortex, temporal poles, and left hippocampus. These results provide evidence that psychopathic traits manifest similar neural abnormalities across sex and age.


Association of Vegetable Nitrate Intake With Carotid Atherosclerosis and Ischemic Cerebrovascular Disease in Older Women.
A short-term increase in dietary nitrate (NO3-) improves markers of vascular health via formation of nitric oxide and other bioactive nitrogen oxides. Whether this translates into long-term vascular disease risk reduction has yet to be examined. We investigated the association of vegetable-derived nitrate intake with common carotid artery intima-media thickness (CCA-IMT), plaque severity, and ischemic cerebrovascular disease events in elderly women (n=1226). Vegetable nitrate intake, lifestyle factors, and cardiovascular disease risk factors were determined at baseline (1998). CCA-IMT and plaque severity were measured using B-mode carotid ultrasound (2001). Complete ischemic cerebrovascular disease hospitalizations or deaths (events) over 14.5 years (15 032 person-years of follow-up) were obtained from the West Australian Data Linkage System. Higher vegetable nitrate intake was associated with a lower maximum CCA-IMT (B=-0.015, P=0.002) and lower mean CCA-IMT (B=-0.012, P=0.006). This relationship remained significant after adjustment for lifestyle and cardiovascular risk factors (P≤0.01). Vegetable nitrate intake was not a predictor of plaque severity. In total 186 (15%) women experienced an ischemic cerebrovascular disease event. For every 1 SD (29 mg/d) higher intake of vegetable nitrate, there was an associated 17% lower risk of 14.5-year ischemic cerebrovascular disease events in both unadjusted and fully adjusted models (P=0.02). Independent of other risk factors, higher vegetable nitrate was associated with a lower CCA-IMT and a lower risk of an ischemic cerebrovascular disease event.


The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.
Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS. The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression. Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects. FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.


Generalized, switch-like competitive heterodimerization networks.
High-dimensional switches have been proposed as a way to model cellular differentiation, particularly in the context of basic Helix-Loop-Helix (bHLH) competitive heterodimerization networks. A previous study derived a simple rule showing how many elements can be co-expressed, depending on the rate of competition within the network. A limitation to that rule, however, is that many biochemical parameters were considered to be identical. Here, we derive a generalized rule. This in turns allows one to study more ways in which these networks could be regulated, linking intrinsic cellular differentiation determinants to extracellular cues.


CeO2-based catalysts with engineered morphologies for soot oxidation to enhance soot-catalyst contact.
AS MORPHOLOGY PLAYS A RELEVANT ROLE IN SOLID/SOLID CATALYSIS, WHERE THE NUMBER OF CONTACT POINTS IS A CRITICAL FEATURE IN THIS KIND OF REACTION, THREE DIFFERENT CERIA MORPHOLOGIES HAVE BEEN INVESTIGATED IN THIS WORK AS SOOT OXIDATION CATALYSTS: ceria nanofibers, which can become organized as a catalytic network inside diesel particulate filter channels and thus trap soot particles at several contact points but have a very low specific surface area (4 m(2)/g); solution combustion synthesis ceria, which has an uncontrolled morphology but a specific surface area of 31 m(2)/g; and three-dimensional self-assembled (SA) ceria stars, which have both high specific surface area (105 m(2)/g) and a high availability of contact points. A high microporous volume of 0.03 cm(3)/g and a finer crystallite size compared to the other morphologies suggested that self-assembled stars could improve their redox cycling capability and their soot oxidation properties. In this comparison, self-assembled stars have shown the best tendency towards soot oxidation, and the temperature of non-catalytic soot oxidation has dropped from 614°C to 403°C in tight and to 552°C in loose contact conditions, respectively. As far as the loose contact results are concerned, this condition being the most realistic and hence the most significant, self-assembled stars have exhibited the lowest T 10% onset temperature of this trio (even after ageing), thus proving their higher intrinsic activity. Furthermore, the three-dimensional shape of self-assembled stars may involve more of the soot cake layer than the solution combustion synthesis or nanofibers of ceria and thus enhance the total number of contact points. The results obtained through this work have encouraged our efforts to understand soot oxidation and to transpose these results to real diesel particulate filters.


Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets.
The strength and breadth of an individual's antibody repertoire is an important predictor of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but have not previously been included in mathematical models of antibody landscapes, including: titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting a role for a mechanism describing diminishing antibody boosting with repeated exposures. Although there was considerable uncertainty in our estimates of antibody waning parameters, our results suggest that both short and long term waning were present and would be identifiable with a larger set of experiments. These results highlight the potential use of repeat exposure animal models in revealing short-term, strain-specific immune dynamics of influenza.


Ultrastructural observation on cells meeting the histological criteria for preosteoblasts--a study in the mouse tibial metaphysis.
Preosteoblasts are currently defined as the precursors of mature osteoblasts. These cells are morphologically diverse and may represent a continuum during osteoblast differentiation. We have attempted to categorize the different preosteoblastic phenotypes in vivo by examining bone cells expressing the runt-related transcription factor 2, alkaline phosphatase and BrdU incorporation - histological traits of a preosteoblast - under transmission electron microscopy (TEM). TEM observations demonstrated, at least, in part two preosteoblastic subtypes: (i) a cell rich in cisterns of rough endoplasmic reticulum (rER) with vesicles and vacuoles and (ii) a subtype featuring extended cytoplasmic processes that connect with distant cells, with a small amount of scattered cisterns of rER and with many vesicles and vacuoles. ER-rich cells, whose cellular machinery is similar to that of an osteoblast, were often seen adjacent to mature osteoblasts, and therefore, may be ready for terminal differentiation. In contrast, ER-poor and vesicle-rich cells extended their cytoplasmic processes to mature osteoblasts and, frequently, to bone-resorbing osteoclasts. The abundant vesicles and vacuoles identified in this cell type indicate that this cell is involved in vesicular transport rather than matrix synthesis activity. In summary, our study verified the morphological diversity and the ultrastructural properties of osteoblastic cells in vivo.


Microstructure Imaging of Crossing (MIX) White Matter Fibers from diffusion MRI.
Diffusion MRI (dMRI) reveals microstructural features of the brain white matter by quantifying the anisotropic diffusion of water molecules within axonal bundles. Yet, identifying features such as axonal orientation dispersion, density, diameter, etc., in complex white matter fiber configurations (e.g. crossings) has proved challenging. Besides optimized data acquisition and advanced biophysical models, computational procedures to fit such models to the data are critical. However, these procedures have been largely overlooked by the dMRI microstructure community and new, more versatile, approaches are needed to solve complex biophysical model fitting problems. Existing methods are limited to models assuming single fiber orientation, relevant to limited brain areas like the corpus callosum, or multiple orientations but without the ability to extract detailed microstructural features. Here, we introduce a new and versatile optimization technique (MIX), which enables microstructure imaging of crossing white matter fibers. We provide a MATLAB implementation of MIX, and demonstrate its applicability to general microstructure models in fiber crossings using synthetic as well as ex-vivo and in-vivo brain data.


T cell response and persistence of the microsporidia.
The microsporidia are a diverse phylum of obligate intracellular parasites related to the fungi that cause significant and sometimes life-threatening disease in immune-compromised hosts, such as AIDS and organ transplant patients. More recently, their role in causing pathology in immune-competent populations has also been appreciated. Interestingly, in several instances, the microsporidia have been shown to persist in their hosts long term, causing at opposite ends of the spectrum either an intractable chronic diarrhea and wasting in patients with advanced-stage AIDS or asymptomatic shedding of spores in healthy populations. Much remains to be studied regarding the immune response to these pathogens, but it seems clear that CD8+ T cells are essential in clearing infection. However, in the infection models examined thus far, the role for CD4+ T cells is unclear at best. Here, we discuss the possible reasons and ramifications of what may be a weak primary CD4+ T cell response against Encephalitozoon cuniculi. Given the central role of the CD4+ T cell in other models of adaptive immunity, a better appreciation of its role in responding to microsporidia may provide insight into the survival strategies of these pathogens, which allow them to persist in hosts of varied immune status.


Characteristics and Extent of Mental Health Issues in Contemporary Dance Students.
This study investigated the extent and characteristics of mental health issues in contemporary dance students, as clear insight into these health problems is lacking. During one academic year, 134 dance and dance-teacher students were monitored on a monthly basis using the Performing artist and Athlete Health Monitor (PAHM). In total, 130 students were included in the analyses, comprising 81 dance students and 49 dance-teacher students. The response rate of the monthly questionnaires was 79.7%. Overall, 96.9% of the students reported at least one physical/mental health problem. The incidence proportion (IP) of all reported mental health issues for one academic year was 44.6% (n=58). Furthermore, 29.2% of the students reported a mental health issue as their most severe health problem, of whom 39.4% indicated a substantial mental health issue (i.e., problems leading to moderate, severe, or complete reductions in training volume or performance). The monthly IP of mental health issues ranged from 2.9 to 8.9% and 0 to 5.3% for substantial mental health issues. The most reported types of mental health issues were general anxiety (20.0%), stress due to external factors (18.3%), and constant tiredness (16.7%). Dance-teacher students of all study years and second-year students from both educational programs indicated significantly more mental health issues, while sex showed no significant differences. Contemporary dance students are at risk of mental health issues. Dance schools should pay special attention to stress, anxiety, and (constant) tiredness of their students. More research is needed to gain insight into specific characteristics and risk factors of mental health issues in dance students.


Analysis of N-terminal pro-B-type natriuretic peptide and cardiac index in multiple injured patients: a prospective cohort study.
Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS. Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP(R) assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution. Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 +/- 21 pg/mL in group A versus 209 +/- 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001). Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.


[The efficacy of mexidol for transient ischemic attacks in the vertebrobasilar system in elderly patients with chronic cerebral ischemia].
To evaluate the clinical efficacy, metabolic and membrane protective effects of mexidol for transient ischemic attacks (TIA) in the vertebrobasilar system in elderly patients with chronic cerebral ischemia (CCI). Fifty-three patients, aged from 60 to 74 years, with the first episode of TIA in the vertebrobasilar system and CCI were examined. Patients of the main group (n=33) received mexidol in the dose of 500 mg for 10 days along with standard therapy, patients of the comparison group (n=20) received only standard therapy. The clinical implications of TIA, laboratory indices of the state of oxidant and antioxidant systems and percentage absorption of lipid-phospholipid complexes in the infrared spectrum of blood serum were studied. The control group consisted of 20 healthy people. The use of mexidol was associated with more rapid regression of the focal neurological deficit. Mexidol significantly reduced the intensity of lipid peroxidation and had a positive impact on the level of neuronal membrane phospholipids. Metabolic and membrane protective effects of mexidol and it's positive impact on the regression of focal neurological deficit justify its inclusion into complex therapy of TIA in the vertebrobasilar system developed in patients with CCI, especially in elderly patients.


Evolution and comparative genomics of odorant- and pheromone-associated genes in rodents.
Chemical cues influence a range of behavioral responses in rodents. The involvement of protein odorants and odorant receptors in mediating reproductive behavior, foraging, and predator avoidance suggests that their genes may have been subject to adaptive evolution. We have estimated the consequences of selection on rodent pheromones, their receptors, and olfactory receptors. These families were chosen on the basis of multiple gene duplications since the common ancestor of rat and mouse. For each family, codons were identified that are likely to have been subject to adaptive evolution. The majority of such sites are situated on the solvent-accessible surfaces of putative pheromones and the lumenal portions of their likely receptors. We predict that these contribute to physicochemical and functional diversity within pheromone-receptor interaction sites.


Evaluation of the effect of site substitution of Pr doping in the lithium garnet system Li5La3Nb2O12.
Li ion conducting garnets have been attracting considerable interest for use as the electrolyte in all solid-state batteries, due to their high ionic conductivity and wide electrochemical stability window. Consequently, there have been a number of doping studies aimed at optimising the conductivity, focusing on both doping in Li7La3Zr2O12 and Li5La3(Nb/Ta)2O12 systems. In this paper, we report a detailed study of Pr doping in Li5La3Nb2O12, and show that this is a rare example of an ambi-site dopant, being able to be doped onto either the La or Nb site. Interestingly the resultant Pr oxidation state is determined by the site substitution, with oxidation states of 3+ for the La site, and 4+ for the Nb site. While the conductivity is essentially unchanged for the La site substitution, Pr4+ substitution on the Nb site leads to a large increase in the conductivity associated with the increase in Li content (Li5+xLa3Nb2-xPrxO12) up to 0.56 mS cm-1 (at 50 °C) for x = 0.8. Overall, this work highlights the flexibility of these garnet materials to doping, and suggests that further consideration of site substitution be considered for other dopants.


Preparation and characterisation of silicone-based coatings filled with carbon nanotubes and natural sepiolite and their application as marine fouling-release coatings.
This article reports on the preparation and partial characterisation of silicone-based coatings filled with low levels of either synthetic multiwall carbon nanotubes (MWCNTs) or natural sepiolite (NS). The antifouling and fouling-release properties of these coatings were explored through laboratory assays involving representative soft-fouling (Ulva) and hard-fouling (Balanus) organisms. The bulk mechanical properties of the coatings appeared unchanged by the addition of low amounts of filler, in contrast to the surface properties, which were modified on exposure to water. The release of Ulva sporelings (young plants) was improved by the addition of low amounts of both NS and MWCNTs. The most profound effect recorded was the significant reduction of adhesion strength of adult barnacles growing on a silicone elastomer containing a small amount (0.05%) of MWCNTs. All the data indicate that independent of the bulk properties, the surface properties affect settlement, and more particularly, the fouling-release behaviour, of the filled materials.