Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment.
Placebo controlled double-blinded, prospectively randomized clinical trial with 17 patients (11 verum, 5 placebo) for evaluation of cellulite treatment with Acoustic Wave Therapy, (AWT(®)) was performed. The patients were treated once a week for 7 weeks, a total of 8 treatments with the D-ACTOR(®) 200 by Storz Medical AG. Data were collected at baseline, before 8th treatment, at 1 month (follow-up 1) and at 3 months (follow-up 2) after the last treatment with a patients' questionnaire, weight control, measurement of circumference and standardized photography. Treatment progress was further documented using a specially designed 3D imaging system (SkinSCAN(3D), 3D-Shape GmbH) providing an objective measure of cellulite (primary efficacy criteria). Patient's questionnaire in the verum group revealed an improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference. The overall result (of skin waviness, Sq and Sz, surface and volume of depressions and elevations, Vvv and Vmp) at two follow-up visits indicates a more than medium sized superiority (MW = 0.6706) and is statistically significant (pWei-Lachin = 0.0106). The placebo group revealed no statistical significance. No side effects were seen. This indicates the efficacy and safety of AWT(®) for patients with cellulite.


Morphology controls the thermoelectric power factor of a doped semiconducting polymer.
The electrical performance of doped semiconducting polymers is strongly governed by processing methods and underlying thin-film microstructure. We report on the influence of different doping methods (solution versus vapor) on the thermoelectric power factor (PF) of PBTTT molecularly p-doped with F n TCNQ (n = 2 or 4). The vapor-doped films have more than two orders of magnitude higher electronic conductivity (σ) relative to solution-doped films. On the basis of resonant soft x-ray scattering, vapor-doped samples are shown to have a large orientational correlation length (OCL) (that is, length scale of aligned backbones) that correlates to a high apparent charge carrier mobility (μ). The Seebeck coefficient (α) is largely independent of OCL. This reveals that, unlike σ, leveraging strategies to improve μ have a smaller impact on α. Our best-performing sample with the largest OCL, vapor-doped PBTTT:F4TCNQ thin film, has a σ of 670 S/cm and an α of 42 μV/K, which translates to a large PF of 120 μW m-1 K-2. In addition, despite the unfavorable offset for charge transfer, doping by F2TCNQ also leads to a large PF of 70 μW m-1 K-2, which reveals the potential utility of weak molecular dopants. Overall, our work introduces important general processing guidelines for the continued development of doped semiconducting polymers for thermoelectrics.


Endoglin (CD 105) expression in human lymphoid organs and placenta.
Endoglin (CD 105) is a cell surface antigen widely expressed on vascular endothelium, syncytiotrophoblast, some tissue macrophages, certain culture cells (including early leukemic B-lineage) and some endothelial cell lines. Though its relation to the transforming growth factor-beta (TGF-beta) receptor system is well documented, its function and detailed pattern of expression still remain to be clarified. We examined the differential tissue distribution of endoglin in human lymphoid organs and placenta with several anti-CD 105 monoclonal antibodies (mAbs) using an indirect immunoperoxidase technique, and performed semi-quantitative measurements using an image-analyzing system for comparison. Arterial, venous and capillary endothelia in these organs were reactive with anti-CD 105 mAbs at varying intensities. Interestingly, a distinctly stronger staining pattern was observed in the high endothelial venules (HEVs) which may indicate a special role for endoglin in lymphocyte trafficking. Syncytiotrophoblast expressed endoglin strongly on their apical cell membrane. Extravillous trophoblasts at certain locations selectively expressed endoglin on their cell membranes, suggesting a special role for this surface antigen during trophoblast differentiation.


Genetic stability of Borrelia burgdorferi recovered from chronically infected immunocompetent mice.
Persistent infection with Borrelia burgdorferi in the presence of a vigorous host immune response has been demonstrated in humans and in animal models of Lyme disease. Long-term persistence of B. burgdorferi was documented recently in our studies of BALB/c and C3H mice infected with cloned and uncloned strains of B. burgdorferi. From mice inoculated with the cloned strain, 11 isolates were recovered from the skin, bladder, and blood after 1 year of infection. Analysis of the genes encoding the major outer surface proteins (OspA and OspB) by restriction digestion and DNA sequencing showed no evidence of point mutations or other small genetic alterations after 1 year. Genomic macrorestriction analysis of whole B. burgdorferi showed no loss or gross alterations of the plasmids encoding OspA, OspB, or OspC. However, in two isolates, loss of a 38-kb plasmid encoding outer surface protein D was noted. Our studies suggest that loss or alteration of the genes encoding OspA and OspB is not a common occurrence during persistent spirochetal infection and that other possible mechanisms, including invasion of immunologically privileged sites, should be actively explored.


Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer.
The immune suppressive molecule programmed death-1 (PD-1) is upregulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1, CD274) and B7-DC (PD-L2, CD273). Substantial experimental data from in vitro cell culture systems and animal models, and more recently from clinical trials, indicate that PD-1/PD-1-ligand interactions are a major mechanism of immune suppression within the tumor microenvironment. Initial clinical studies of antibodies directed against PD-1 and B7-H1 showed both an encouraging safety profile and remarkable antitumor activity in subsets of patients with metastatic disease, including malignancies--such as lung cancer--which were previously thought to be unresponsive to immunotherapy. Preliminary data have suggested a correlation between tumor membrane B7-H1 expression and clinical response to anti-PD-1 antibodies. Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biologic significance of all potential ligand-receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy that address key mechanisms involved in positive and negative regulation of antitumor immune responses.


A digitalized program to improve antenatal health care in a rural setting in North-Western Burundi: Early evidence-based lessons.
In Burundi, the north-western region continues to grapple with the lowest level of antenatal care (ANC) attendance rate which is constantly about half the national average of 49% ANC4 coverage. Despite a dearth of empirical evidence to understand the determinants of this suboptimal attendance of ANC, widespread evidence informs that women forget scheduled ANC appointments. We designed and tested a digital intervention that uses a reminder model aimed at increasing the number of women who attend at least 4 ANC visits in this region. We enrolled a cohort of 132 pregnant women who were followed until childbirth using a single arm pre- and post-test design. The digital model builds on the collaboration between midwives or nurses, community health workers (CHWs), and pregnant women who are centrally connected through regular automated communications generated by the cPanel of the digital intervention. In addition to ANC attendances, we nested a cross-sectional survey to understand mothers' perceptions and acceptability of the digital intervention using the acceptability framework by Sekhon et al. (2017). Descriptive analyses were performed to observe the trend in ANC attendance and logistic regressions fitted to seize determinants affecting mothers' acceptability of the intervention. Of 132 enrolled pregnant women, 1 (0.76%) dropped out. From a baseline of 23%, nearly 73.7% of mothers attended their subsequent ANC visits after the start of the intervention. From the third month of intervention, about 80% of mothers constantly attended ANC appointments; which corresponds to greater than 200% increase from the baseline. Findings showed that 96.2% of mothers expressed satisfaction, 77.1% positively reacted to automated reminders (attitudes), 70.2% expressed willingness to participate, and 86.3% had the ability to actively participate to the intervention. Conversely, half of mothers confirmed that participation to this programme somewhat affected their time management. A key learning is that digital interventions have a lot of promise to improve pregnancy monitoring in rural settings. However, the overall user acceptability was low especially among mothers lacking personal mobile phone.


Developing RT-LAMP assays for rapid diagnosis of SARS-CoV-2 in saliva.
The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has killed millions of people worldwide. The current crisis has created an unprecedented demand for rapid test of SARS-CoV-2 infection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a fast and convenient method to amplify and identify the transcripts of a targeted pathogen. However, the sensitivity and specificity of RT-LAMP were generally regarded as inferior when compared with the gold standard RT-qPCR. To address this issue, we combined bioinformatic and experimental analyses to improve the assay performance for COVID-19 diagnosis. First, by experimental screening as well as high-throughput sequencing studies, we discovered new primer features that impacted LAMP sensitivity and specificity. These features were then used to build an improved bioinformatics algorithm to design LAMP primers targeting SARS-CoV-2. We further rigorously validated these new assays for their efficacy and specificity. We demonstrated that multiplexed RT-LAMP assay could directly detect as low as 1.5 copies/µL of SARS-CoV-2 particles in saliva, without the need of RNA isolation. We further tested this ultra-sensitive and specific RT-LAMP assay using saliva samples from COVID-19 patients. Clinical validation results indicated that the new RT-LAMP assay was comparable to standard RT-qPCR in overall assay sensitivity and specificity. In summary, our new LAMP primer design algorithm along with the validated assays provide a fast and reliable method for the diagnosis of COVID-19 cases. National Institutes of Health.


Histone H3 phosphorylation is required for the initiation, but not maintenance, of mammalian chromosome condensation.
The temporal and spatial patterns of histone H3 phosphorylation implicate a specific role for this modification in mammalian chromosome condensation. Cells arrest in late G2 when H3 phosphorylation is competitively inhibited by microinjecting excess substrate at mid-S-phase, suggesting a requirement for activity of the kinase that phosphorylates H3 during the initiation of chromosome condensation and entry into mitosis. Basal levels of phosphorylated H3 increase primarily in late-replicating/early-condensing heterochromatin both during G2 and when premature chromosome condensation is induced. The prematurely condensed state induced by okadaic acid treatment during S-phase culminates with H3 phosphorylation throughout the chromatin, but in an absence of mitotic chromosome morphology, indicating that the phosphorylation of H3 is not sufficient for complete condensation. Mild hypotonic treatment of cells arrested in mitosis results in the dephosphorylation of H3 without a cytological loss of chromosome compaction. Hypotonic-treated cells, however, complete mitosis only when H3 is phosphorylated. These observations suggest that H3 phosphorylation is required for cell cycle progression and specifically for the changes in chromatin structure incurred during chromosome condensation.


Interpretability of Input Representations for Gait Classification in Patients after Total Hip Arthroplasty.
Many machine learning models show black box characteristics and, therefore, a lack of transparency, interpretability, and trustworthiness. This strongly limits their practical application in clinical contexts. For overcoming these limitations, Explainable Artificial Intelligence (XAI) has shown promising results. The current study examined the influence of different input representations on a trained model's accuracy, interpretability, as well as clinical relevancy using XAI methods. The gait of 27 healthy subjects and 20 subjects after total hip arthroplasty (THA) was recorded with an inertial measurement unit (IMU)-based system. Three different input representations were used for classification. Local Interpretable Model-Agnostic Explanations (LIME) was used for model interpretation. The best accuracy was achieved with automatically extracted features (mean accuracy Macc = 100%), followed by features based on simple descriptive statistics (Macc = 97.38%) and waveform data (Macc = 95.88%). Globally seen, sagittal movement of the hip, knee, and pelvis as well as transversal movement of the ankle were especially important for this specific classification task. The current work shows that the type of input representation crucially determines interpretability as well as clinical relevance. A combined approach using different forms of representations seems advantageous. The results might assist physicians and therapists finding and addressing individual pathologic gait patterns.


A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.
Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.


Continuous renal replacement therapy for management of overhydration in heart failure.
An estimated 4.8 million Americans are diagnosed with heart failure. Of those, 5% to 10% meet criteria for the refractory state of the disease. While therapeutic interventions continue to evolve with the changing conceptualization of heart failure pathophysiology, overhydration and its deleterious sequelae remain a problem for those in the refractory state. The incidence of heart failure continues to rise in older individuals. As baby-boomers age across America, greater focus on new, more effective therapies must be considered for treatment of this disease. Continuous renal replacement therapy (CRRT) is one such treatment. The gentle removal of fluid and metabolites while maintaining electrolyte balance helps reduce the effects of overhydration in patients with heart failure. Increasing use of the therapy in the refractory state of heart failure is generating support for early initiation as it continues to demonstrate positive effects. Reduction in edema, attenuation of the sympathoadrenal cascade, and improved respiratory status have all been documented using the therapy. The intent of this article is to provide information for advanced practice nurses and direct care providers regarding CRRT for the treatment of heart failure refractory to typical therapy.


Effect of serotonin modulating pharmacotherapies on body mass index and dysglycaemia among children and adolescents: a systematic review and network meta-analysis protocol.
Serotonin-modulating medications are commonly prescribed for mental health issues. Currently, there is limited consensus on weight gain and dysglycaemia development among children using these medications. The objective of this study is to review and synthesise all the available evidence on serotonin-modulating medications and their effects on body mass index (BMI), weight and glycaemic control. We will conduct a systematic review of all randomised controlled trials evaluating the use of serotonin-modulating medications in the treatment of children 2-17 years with mental health conditions. The outcome measures are BMI, weight and dysglycaemia. We will perform literature searches through Ovid Medline, Ovid Embase, PsycINFO and grey literature resources. Two reviewers from the team will independently screen titles and abstracts, assess the eligibility of full-text trials, extract information from eligible trials and assess the risk of bias and quality of the evidence. Results of this review will be summarised narratively and quantitatively as appropriate. We will perform a multiple treatment comparison using network meta-analysis to estimate the pooled direct, indirect and network estimate for all serotonin-modulating medications on outcomes if adequate data are available. Serotonin-modulating medications are widely prescribed for children with mental health diseases and are also used off-label. This network meta-analysis will be the first to assess serotonin modulating antidepressants and their effects on weight and glycaemic control. We anticipate that our results will help physicians and patients make more informed choices while considering the side effect profile. We will disseminate the results of the systematic review and network meta-analysis through peer-reviewed journals. CRD42015024367.


The conundrum of current anti-SARS-CoV-2 vaccines.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has given rise to the urgent need for vaccines and therapeutic interventions to address the spread of the SARS-CoV-2 virus. SARS-CoV-2 vaccines in development, and those being distributed currently, have been designed to induce neutralizing antibodies using the spike protein of the virus as an immunogen. However, the immunological correlates of protection against the virus remain unknown. This raises questions about the efficacy of current vaccination strategies. In addition, safety profiles of several vaccines seem inadequate or have not yet been evaluated under controlled experimentation. Here, evidence from the literature regarding the efforts already made to identify the immunological correlates of protection against SARS-CoV-2 infection are summarized. Furthermore, key biological features of most of the advanced vaccines and considerations regarding their safety and expected efficacy are highlighted.


Water-Soluble Fullerenol C60(OH)36 toward Effective Anti-Air Pollution Induced by Urban Particulate Matter in HaCaT Cell.
Particulate matter (PM), a widespread air pollutant, consists of a complex mixture of solid and liquid particles suspended in air. Many diseases have been linked to PM exposure, which induces an imbalance in reactive oxygen species (ROS) generated in cells, and might result in skin diseases (such as aging and atopic dermatitis). New techniques involving nanomedicine and nano-delivery systems are being rapidly developed in the medicinal field. Fullerene, a kind of nanomaterial, acts as a super radical scavenger. Lower water solubility levels limit the bio-applications of fullerene. Hence, to improve the water solubility of fullerene, while retaining its radical scavenger functions, a fullerene derivative, fullerenol C60(OH)36, was synthesized, to examine its biofunctions in PM-exposed human keratinocyte (HaCaT) cells. The PM-induced increase in ROS levels and expression of phosphorylated mitogen-activated protein kinase and Akt could be inhibited via fullerenol pre-treatment. Furthermore, the expression of inflammation-related proteins, cyclooxygenase-2, heme oxygenase-1, and prostaglandin E2 was also suppressed. Fullerenol could preserve the impaired state of skin barrier proteins (filaggrin, involucrin, repetin, and loricrin), which was attributable to PM exposure. These results suggest that fullerenol could act against PM-induced cytotoxicity via ROS scavenging and anti-inflammatory mechanisms, and the maintenance of expression of barrier proteins, and is a potential candidate compound for the treatment of skin diseases.


Clinical evaluation of a resin composite and bonding agent in Class I and II restorations: 2-year results.
The purpose of this study was to evaluate the clinical performance and longevity of Tetric Ceram and Syntac Sprint restorations in stress-bearing areas performed in general practice. The light-curing resin composite Tetric Ceram in combination with the bonding material Syntac Sprint were used as restorative materials in three public dental health clinics. All the restorations were done by general practitioners in an ordinary patient pool attending a public health clinic. Before starting, the general practitioners were instructed and trained in performing the restorations according to a standardized clinical procedure, and the evaluations were done according to United States Public Health Service criteria. One hundred forty-eight restorations (27 Class I, 121 Class II) were done in 123 patients. After 2 years, 140 restorations (95%) could be assessed. Color slides and bitewings were taken to supplement the clinical evaluations of color match, marginal discoloration, secondary caries, and marginal adaptation. Wear of the restorations was evaluated according to the Leinfelder method. After 2 years, 7 out of 148 restorations had failed, giving a failure rate of 5% of the tested materials. Five restorations failed due to hypersensitivity, one to secondary caries, and one to fracture. The wear rate was low (mean 37 microm) and did not result in any replacement. This 2-year study showed that clinically satisfactory results could be obtained using resin composite Class I and II restorations in stress-bearing areas done in general practice on an ordinary clientele when the clinical procedure is standardized.


A comprehensive study of the association between hepatitis C virus and glomerulopathy.
Hepatitis C virus (HCV)-related infection is commonly associated with a wide range of glomerulonephritides (GN) including membranoproliferative glomerulonephritis (MPGN). The causal link between HCV infection and renal disease has been postulated through the induction of cryoglobulinaemia and secondary GN. However, the detection of viral particles or genomes within the kidneys of HCV-infected patients has proved to be difficult. With that in mind, we have studied a population of Egyptian HCV-positive patients with associated GN in an attempt to detect viral particles, antigens or RNA within their kidneys. Fifty patients were found to be HCV positive out of 303 who presented with a glomerulopathy between 1998 and 1999 at the Mansoura Urology and Nephrology Center, Egypt. Comprehensive investigations of these 50 patients were undertaken including an evaluation of their clinical, biochemical, histological, virological and immunological parameters. In addition, their kidney biopsy material was analysed by electron microscopy (EM) to detect viral particles, by immunohistochemistry to detect a viral core antigen and by RT-PCR to detect RNA. This was compared with 50 HCV-negative controls. Positivity for HCV antibodies was higher among patients with GN (38%) compared with healthy blood donors (16%). Genotype 4 was sequenced in 70% of the HCV-positive samples examined. MPGN was the most common type of GN accounting for 54% of patients. Extrarenal manifestations were absent in the majority (80%) of patients even though 54% had cryoglobulinaemia. EM revealed virus-like particles in 50% of biopsies. Immunohistochemistry failed to reveal HCV-related antigens in kidney sections. HCV RNA was detected in the cryoprecipitates in 66% of patients and 22% of frozen renal sections. Control sections were negative. Our findings suggest a causal link between HCV and GN based on the observation of virus-like particles as well as viral RNA within the kidney sections of patients with HCV-associated glomerulopathies.


Comorbidity of diabetes and eating disorders. Does diabetes control reflect disturbed eating behavior?
This multicenter study was designed to explore the prevalence of clinical and subclinical eating disorders (EDs), the extent of intentional omission of insulin and oral antidiabetic agents, and its relationship to glycemic control in an inpatient and outpatient population of men and women with type 1 and type 2 diabetes. Data have been collected from 12 diabetes medical centers in two German cities. In a questionnaire and interview-based study, a sample of male and female patients (n = 341 type 1, n = 322 type 2) was assessed for the following eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified. For lack of interview data of several patients meeting the screening criteria, prevalence ranges were calculated. The overall prevalence range of current EDs was 5.9-8.0% (lifetime prevalence 10.3-14.0%). When patients were stratified according to type 1 and type 2 diabetes, there was no difference in prevalence of EDs. However, the distribution of the EDs was different in both types of diabetes, with a predominance of binge eating disorder in the type 2 diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to lose weight. Compared with control subjects, neither the presence of EDs nor insulin omission influenced diabetic control. There seems to be no difference in prevalence rates of EDs in both types of diabetes; however, distribution of EDs is different. The findings suggest that neither EDs nor insulin omission are necessarily associated with poor control of glycemia. Binge eating disorder seems to precede type 2 diabetes in most patients and could be one of the causes of obesity that often precedes type 2 diabetes.


High-resolution genome-wide analysis of irradiated (UV and γ-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (LOH) events.
In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either γ-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and γ-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by γ-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote.


Physician and patient factors associated with the prescribing of medications for sleep difficulties that are associated with high abuse potential or are expensive: an analysis of data from the National Ambulatory Medical Care Survey for 1996-2001.
This study evaluated the association between various socioeconomic and clinical factors relating to patients and physicians and the prescribing of medications that have a high abuse potential or are expensive for the treatment of sleep difficulties in a nationally representative sample of outpatient physician visits in the United States. This cross-sectional study used data from the National Ambulatory Medical Care Survey from 1996-2001. Patients aged > or =18 years who received treatment for sleep difficulties in US outpatient settings over this period were included in the study sample. Office visits were considered related to insomnia/sleep difficulties if relevant International Classification of Diseases, Ninth Revision, diagnosis codes were recorded and if insomnia was reported as the reason for the visit or any medication with a primary indication for insomnia was prescribed. Medications associated with dependence and withdrawal symptoms were categorized as having a high abuse potential. Medications were considered expensive if the average wholesale price of 100 tablets was > or =$150 (ie, the 75th percentile of the total cost of all medications prescribed for sleep disorders only). The data were subjected to multivariate logistic regression analysis. From 1996 through 2001, 2966 unweighted patient visits for insomnia/sleep difficulty were identified, representing approximately 94.6 million weighted observations in the overall US population; pharmacotherapy only was prescribed at 48% (45 million) of these visits. Medications with abuse potential were prescribed at 53% (24 million) of visits. Among visits at which pharmacotherapy was prescribed, visits by male patients were 39% less likely than visits by female patients to result in a prescription for a medication with abuse potential (odds ratio [OR] = 0.61; 95% CI, 0.45-0.81). Visits by patients with psychiatric comorbidities were 80% more likely to be associated with receipt of a prescription for a medication with abuse potential than were visits by patients with no such comorbidities (OR = 1.80; 95% CI, 1.31-2.47). Expensive medications were prescribed at 25% (15 million) of visits involving some pharmacotherapy. Patients aged > or =65 years were 44% less likely to receive a prescription for an expensive medication than was the reference group, patients aged 18 to 34 years (OR = 0.56; 95% CI, 0.35-0.90). Hispanic patients were 56% less likely to receive a prescription for an expensive medication than were non-Hispanic patients (OR = 0.44; 95% CI, 0.22-0.88). This study found an increased probability of female patients with sleep difficulties receiving a medication with high abuse potential in outpatient settings in the United States from 1996 through 2001. In addition, there was a possible association between the age and ethnicity of patients with insomnia/sleep difficulties and the prescribing of expensive medications for sleep difficulties.


Building a hair: tip growth in Arabidopsis thaliana root hairs.
The Arabidopsis thaliana root hair is used as a model for studying tip growth in plants. We review recent advances, made using physiological and genetic approaches, which give rise to different, yet compatible, current views of the establishment and maintenance of tip growth in epidermal cells. For example, an active calcium influx channel localized at the tip of Arabidopsis root hairs has been identified by patch-clamp measurements. Actin has been visualized in vivo in Arabidopsis root hairs by using a green-fluorescent-protein-talin reporter and shown to form a dense mesh in the apex of the growing tip. The kojak gene, which encodes a protein similar to the catalytic subunit of cellulose synthase, is needed in the first stages of hair growth. A role for LRX1, a leucine-rich repeat extensin, in determining the morphology of the cell wall of root hairs has been established using reverse genetics. The new information can be integrated into a general and more advanced view of how these specialized plant cells grow.


Vitamin D deficiency in children with a chronic illness-seasonal and age-related variations in serum 25-hydroxy Vitamin D concentrations.
Children and adolescents with a chronic illness have potential risk factors for vitamin D deficiency. An optimal vitamin D status might have multiple health effects. This study evaluated vitamin D status and its association with age, gender, and season in a large cohort of chronically ill Finnish patients at a tertiary pediatric outpatient clinic. A cross-sectional register-based study was carried out, involving altogether 1351 children (51% boys, age range 0.2-18 years), who visited the outpatient clinic during 2007-2010 and had their vitamin D status (S-25-OHD) determined. A post-doc analysis was conducted to identify predisposing and preventing factors for vitamin D deficiency. Almost half (47%) of the S-25-OHD values were consistent with subnormal vitamin D status (S-25-OHD <50 nmol/L) while only 12% were >80 nmol/L. Age and season were the most important determinants for S-25-OHD concentration. Mean S-25-OHD concentration differed between age groups (Kruskal-Wallis; p<0.001), adolescents being at highest risk for vitamin D insufficiency. Young age and vitamin D supplementation were preventive factors for deficiency, while non-Finnish ethnic background was a predisposing factor. S-25-OHD showed significant seasonal variation in children older than 6 years. In the whole cohort, S-25-OHD was on average 13 nmol/L higher in summer than in winter, and the prevalence of vitamin D deficiency ( = S-25-OHD <37.5 nmol/l) varied from 11% in summer to 29% in winter. The finding that almost half of the studied Finnish children with a chronic illness had suboptimal vitamin D status is alarming. Inferior vitamin D status was noted in adolescents compared with younger children, suggesting that imbalance between intake and requirement evolves with age. Although less common during summer, subnormal vitamin D status was still observed in 28% of those evaluated in summer. Clinicians should identify individuals at risk and actively recommend vitamin D supplementation.


Angiotensin regulates release and synthesis of serotonin in brain.
Angiotensin II released serotonin from neuron terminals and accelerated synthesis of the serotonin. This increase in synthesis depended on the activation of tryptophan hydroxylase. A biphasic effect was observed: at high doses the stimulatory effect depended on conversion of angiotensin II to angiotensin III. At low doses an inhibitory effect was found, possible dependent on an angiotensin II metabolite. These actions represent a subtle regulation of the open-loop serotonin system.


[Toxoplasmosis, rubella, syphilis, hepatitis B and HIV infection in women being followed for pregnancy in a population on the east coast of New Caledonia ].
In view of the sparse available data concerning the main infectious illnesses screened for during pregnancy (toxoplasmosis, rubella, syphilis, hepatitis B virus and HIV) in the Northern Province and generally throughout New Caledonia, we decided to undertake a retrospective study based on the files of pregnant women having consulted between September 1996 and September 1999 in the East-Coast provincial hospital (New-Caledonia). First, we wished to estimate the prevalence of toxoplasmosis, rubella, syphilis, hepatitis B virus and HIV Second, we wished to specify the main characteristics of these pregnant women, to trace the evolution of seroprevalence over the study time period and consider the influence of various factors such as age, place of residence and professional occupation. The biological study of these pregnancies was hindered by the fact that approximately half of women consult only from the second trimester of their pregnancy. This result underlines the importance of emphasising efforts aiming to bring women to consult earlier and of improving the regularity and also the interpretation of serological tests (especially for toxoplasmosis serology). Within this population, we found the following percentages of seroprevalence: for toxoplasmosis between 83.6% and 89.6% (zone of hyperendemla), for rubella between 91.6% and 95.8%, for syphilis between 7% and 12.4%, for hepatitis B virus between 61.8% and 76% (for women immune to hepatitis B, the frequency of acquisition of immunity by viral infection was understood between 64.3% and 80.3%) and for HIV 0%. The hepatitis B surface antigen (HbsAg) carrier rate was estimated between 1.7% and 4.9%. Following and informing pregnant women of the risk of toxoplasmosis appears to be of key importance as well as screening HbsAg carriers in order to limit viral transmission to the foetus.


Herpes simplex virus glycoprotein D interferes with binding of herpesvirus entry mediator to its ligands through downregulation and direct competition.
To initiate membrane fusion and virus entry, herpes simplex virus (HSV) gD binds to a cellular receptor such as herpesvirus entry mediator (HVEM). HVEM is a tumor necrosis factor (TNF) receptor family member with four natural ligands that either stimulate (LIGHT and LTα) or inhibit (BTLA and CD160) T cell function. We hypothesized that the interaction of gD with HVEM affects the binding of natural ligands, thereby modulating the immune response during infection. Here, we investigated the effect that gD has on the interaction of HVEM with its natural ligands. First, HSV gD on virions or cells downregulates HVEM from the cell surface. Similarly, trans-interaction with BTLA or LIGHT also downregulates HVEM from the cell surface, suggesting that HSV may subvert a natural mechanism for regulating HVEM activity. Second, we showed that wild-type gD had the lowest affinity for HVEM compared with the four natural ligands. Moreover, gD directly competed for binding to HVEM with BTLA but not LTα or LIGHT, indicating the possibility that gD selectively controls HVEM signals. On the other hand, natural ligands influence the use of HVEM by HSV. For instance, soluble BTLA, LTα, and LIGHT inhibited the binding of wild-type gD to HVEM, and soluble BTLA and LTα blocked HSV infection of HVEM-expressing cells. Thus, gD is at the center of the interplay between HVEM and its ligands. It can interfere with HVEM function in two ways, by competing with the natural ligands and by downregulating HVEM from the cell surface.


Brain-compatible learning: principles and applications in athletic training.
To discuss the principles of brain-compatible learning research and provide insights into how this research may be applied in athletic training education to benefit the profession. In the past decade, new brain-imaging techniques have allowed us to observe the brain while it is learning. The field of neuroscience has produced a body of empirical data that provides a new understanding of how we learn. This body of data has implications in education, although the direct study of these implications is in its infancy. An overview of how the brain learns at a cellular level is provided, followed by a discussion of the principles of brain-compatible learning. Applications of these principles and implications for the field of athletic training education are also offered. Many educational-reform fads have garnered attention in the past. Brain-compatible learning will not likely be one of those, as its origin is in neuroscience, not education. Brain-compatible learning is not an educational-reform movement. It does not prescribe how to run your classroom or offer specific techniques to use. Rather, it provides empirical data about how the brain learns and suggests guidelines to be considered while preparing lessons for your students. These guidelines may be incorporated into every educational setting, with every type of curriculum and every age group. The field of athletic training lends itself well to many of the basic principles of brain-compatible learning.


Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated gelatin hydrogels.
Cell-laden methacrylated gelatin (GelMA) hydrogels with high (approximately 90%) transparency were prepared to mimic the natural form and function of corneal stroma. They were synthesized from GelMA with a methacrylation degree of 70% as determined by nuclear magnetic resonance. Hydrogels were strong enough to withstand handling. Stability studies showed that 87% of the GelMA hydrogels remained after 21 days in phosphate buffered saline (PBS). Cell viability in the first 2 days was over 90% for the human keratocytes loaded in the gels as determined with the live-dead analysis. Cells in the hydrogel elongated and connected to each other as observed by confocal laser scanning microscopy (CLSM) images and scanning electron microscope analysis after 3 weeks in the culture medium and cells were seen to be distributed throughout the hydrogel bulk. Cells were found to synthesize collagen Types I and V, decorin, and biglycan (representative collagens and proteoglycans of human corneal stroma, respectively) showing that keratocytes maintained their functions and preserved their phenotypes in the hydrogels. Transparency of cell-loaded and cell-free hydrogels after 21 days was found to be over 90% at all time points in the visible light range and was comparable to the transparency of the native cornea. The corneal stroma equivalent produced in this study that has cells entrapped in it leads to a product with homogenous distribution of cells. It was transparent at the very beginning and is expected to allow better vision than nontransparent substrates. It, therefore, has a significant potential to be used as an alternative to the current products used to treat corneal blindness.


Continuing medical education for flexible sigmoidoscopy--toward a conceptual model for procedural skills training.
Participants in two one-day continuing medical education courses on flexible sigmoidoscopy were surveyed before, immediately after and ten months after the courses. 52 (29.5% of 176) participants completed all three survey forms. Before the course 32 (61.5%) expected to immediately use the flexible sigmoidoscope without further training. Ten months after the course 33 (63.4%) were using the flexible sigmoidoscope; four additional respondents were expecting to begin using the instrument. Twenty three of these (69.7%) had only attended the course without additional training. Those who found the instrument more difficult to use, or decided immediately after the course that more education was necessary, were less likely to use the instrument. Those not using the instrument also were older, more likely to be in solo practice and more likely to be surgeons. The course altered the educational plans of 23.1% of the respondents. This one-day format combining didactic and laboratory work with the instrument proved to be an efficient and effective means of education for using the instrument.


Computational and biophysical determination of pathogenicity of variants of unknown significance in cardiac thin filament.
Point mutations within sarcomeric proteins have been associated with altered function and cardiomyopathy development. Difficulties remain, however, in establishing the pathogenic potential of individual mutations, often limiting the use of genotype in management of affected families. To directly address this challenge, we utilized our all-atom computational model of the human full cardiac thin filament (CTF) to predict how sequence substitutions in CTF proteins might affect structure and dynamics on an atomistic level. Utilizing molecular dynamics calculations, we simulated 21 well-defined genetic pathogenic cardiac troponin T and tropomyosin variants to establish a baseline of pathogenic changes induced in computational observables. Computational results were verified via differential scanning calorimetry on a subset of variants to develop an experimental correlation. Calculations were performed on 9 independent variants of unknown significance (VUS), and results were compared with pathogenic variants to identify high-resolution pathogenic signatures. Results for VUS were compared with the baseline set to determine induced structural and dynamic changes, and potential variant reclassifications were proposed. This unbiased, high-resolution computational methodology can provide unique structural and dynamic information that can be incorporated into existing analyses to facilitate classification both for de novo variants and those where established approaches have provided conflicting information.


Proper technical procedures improved outcomes in a retrospective analysis of EVAS FORWARD IDE trial 3-year results.
Adverse outcomes observed late in the Nellix EndoVascular Aneurysm Sealing (EVAS) System (Endologix, Inc, Irvine, Calif) investigational device exemption trial prompted refinement of the anatomic instructions for use (IFU). This study aimed to investigate the association of procedural factors during Nellix endograft deployment and patient outcomes. We retrospectively reviewed 1-month imaging of 333 patients enrolled in the prospective, multicenter EVAS investigational device exemption trial between January 2014 and September 2016. Initial observations of those patients who met revised anatomic IFU yet still experienced late adverse events suggested that inadequate seal and low graft placement were common among these patients. Key procedural variables identified from a univariate analysis were applied to construct four cohorts stratified by procedural technical performance (technically adequate [P+] or technically inadequate [P-]) and the revised anatomic indications for use (anatomically within IFU [A+] or anatomically outside of IFU [A-]) and to compare them for aneurysm-related outcomes. A logistic regression analysis was performed to identify significant predictors of sac expansion or migration. Proximal and distal seal zones and low graft placement were identified by logistic regression analysis as significant predictors of sac expansion or migration. Accordingly, acquisition of ≥10-mm proximal and distal seal zones and the position of the lowest stent within 10 mm of the lowest renal artery were clinically justified as thresholds for a technically adequate procedure. Patients who did not achieve these parameters were deemed to have a technically inadequate procedure. By use of the proposed procedural adequacy criteria and established anatomic criteria, patients were stratified into four cohorts: A+/P+ (n = 77), A+/P- (n = 54), A-/P+ (n = 71), and A-/P- (n = 131). Three-year estimates of freedom from migration of 10 mm were 98.6% in A+/P+, 95.9% in A+/P-, 85.8% in A-/P+, and 80.1% in A-/P-; freedom from type IA endoleak estimates were 98.6% in A+/P+, 100% in A+/P-, 96.4% in A-/ P+, and 90.3% in A-/P- cohorts. Freedom from sac expansion and secondary intervention were 96.9% and 90.6% in A+/P+, 86.0% and 93.6% in A+/P-, 87.1% and 83.1% in A-/P+, and 80.5% and 79.8% in A-/P- groups, respectively. Two early deaths (aneurysm-related mortality) on days 4 and 12 postoperatively were reported within the A+/P- group. Kaplan-Meier estimates of freedom from all-cause mortality and aneurysm-related mortality at 3 years were similar between cohorts. This post hoc analysis suggests that achieving a 10-mm proximal and distal seal with adequate positioning of the endograft with respect to the renal arteries is associated with improved patient outcomes.


Stimulation of cartilage resorption by extracellular ATP acting at P2-purinoceptors.
Net loss of the cartilage extracellular matrix occurs in all forms of arthritis, and it is important to identify the factors that initiate and maintain this process. Extracellular ATP can elicit biological responses via P2-purinoceptors, and we have obtained evidence for the presence of these receptors at the surface of cultured human articular chondrocytes. We have extended this work by examining whether exogenous ATP also promotes cartilage resorption. Cultured explants of bovine nasal cartilage were used, and breakdown of proteoglycans was monitored by measuring the release of glycosaminoglycans. ATP, GTP, CTP, UTP, ITP, 2-methylthioadenosine 5'-triphosphate, and adenosine 5'-O-(3-thiotriphosphate) all promoted release of glycosaminoglycans, whereas ADP, AMP, adenosine, and adenosine 5'-(alpha,beta-methylene)triphosphate were inactive. On lowering the concentration of foetal calf serum in the tissue culture medium from 10% (v/v) to 2.5% (v/v), the response to ATP was enhanced and the minimum effective concentration was reduced. The ATP-elicited release of glycosaminoglycans was also enhanced by interleukin 1 beta, tumour necrosis factor alpha, and transforming growth factor-beta, although only high concentrations of the latter were effective. These data provide further evidence for the presence of P2-purinoceptors in cartilage, and indicate that if ATP arises extracellularly, it could have potentially deleterious effects. The enhancement of the response to ATP by interleukin 1 beta and tumour necrosis factor alpha suggests an additional mechanism whereby these cytokines can promote cartilage resorption.


The Impacts of Oil Palm on Recent Deforestation and Biodiversity Loss.
Palm oil is the most widely traded vegetable oil globally, with demand projected to increase substantially in the future. Almost all oil palm grows in areas that were once tropical moist forests, some of them quite recently. The conversion to date, and future expansion, threatens biodiversity and increases greenhouse gas emissions. Today, consumer pressure is pushing companies toward deforestation-free sources of palm oil. To guide interventions aimed at reducing tropical deforestation due to oil palm, we analysed recent expansions and modelled likely future ones. We assessed sample areas to find where oil palm plantations have recently replaced forests in 20 countries, using a combination of high-resolution imagery from Google Earth and Landsat. We then compared these trends to countrywide trends in FAO data for oil palm planted area. Finally, we assessed which forests have high agricultural suitability for future oil palm development, which we refer to as vulnerable forests, and identified critical areas for biodiversity that oil palm expansion threatens. Our analysis reveals regional trends in deforestation associated with oil palm agriculture. In Southeast Asia, 45% of sampled oil palm plantations came from areas that were forests in 1989. For South America, the percentage was 31%. By contrast, in Mesoamerica and Africa, we observed only 2% and 7% of oil palm plantations coming from areas that were forest in 1989. The largest areas of vulnerable forest are in Africa and South America. Vulnerable forests in all four regions of production contain globally high concentrations of mammal and bird species at risk of extinction. However, priority areas for biodiversity conservation differ based on taxa and criteria used. Government regulation and voluntary market interventions can help incentivize the expansion of oil palm plantations in ways that protect biodiversity-rich ecosystems.


Phylogenetic analysis of Cronobacter isolates based on the rpoA and 16S rRNA genes.
The reclassification of the genus Cronobacter (previously known as Enterobacter sakazakii) was based on a polyphasic analysis that led to the description of five species. These bacteria are opportunistic pathogens that can cause neonatal meningitis and other infections in immuno-compromised individuals. Cronobacter species have been reported to show differences in sensitivity to antibiotics, heat and chemicals, as well as differences in virulence. The objective of this study was to classify Cronobacter isolates from infant formula milk, the food processing environment and fresh produce in South Africa and to evaluate the phylogenetic placement of these isolates based on the rpoA and 16S ribosomal RNA (rRNA) gene sequences. All the South African strains were identified as Cronobacter sakazakii despite the wide variety of isolation sources. No relation between the phylogenetic placement and strain origin could be determined. Strains of C. sakazakii, Cronobacter dublinensis, Cronobacter turicensis and Cronobacter muytjensii could be differentiated from each other, but it was not possible to differentiate between C. sakazakii and Cronobacter malonaticus based on the rpoA and 16S rRNA gene sequences alone. However, sequence data of these two genes can be used to differentiate between C. sakazakii and C. malonaticus when used in combination with biochemical analysis based on the utilisation of malonate.


Protein kinase C isoform expression and regulation in the developing rat heart.
To determine whether age-dependent differences in cardiac responses to autonomic agonists could result from developmental changes in protein kinase C (PKC) isoform expression, we probed extracts from the fetal, neonatal, and adult heart as well as cultured neonatal and isolated adult ventricular myocytes with specific antisera to calcium-dependent (alpha and beta) and calcium-independent (delta, epsilon and zeta) isoforms of the enzyme. Although PKC-beta immunoreactivity could not be detected in cultured neonatal or isolated adult ventricular myocytes, adult and neonatal myocytes expressed multiple other isoforms of PKC. Our studies revealed an age-dependent decline in the immunoreactivity for three PKC isoforms. PKC-alpha was detected in extracts from the fetal and 2-day-old neonatal heart as well as cultured neonatal rat ventricular myocytes. Only faint PKC-alpha immunoreactivity was detected in extracts from the adult heart, and PKC-alpha was not detected in extracts from isolated adult ventricular myocytes, suggesting that PKC-alpha resides in nonmyocyte elements in the adult heart. PKC-delta also was detected in greater abundance in fetal and neonatal than in adult myocardial extracts. The decline in PKC-alpha and PKC-delta expression occurred during the first 2 postnatal weeks. PKC-zeta was detected in greatest abundance in extracts from the fetal heart. PKC-zeta expression declined markedly by the second postnatal day, and only faint PKC-zeta immunoreactivity was detected in extracts from adult myocardium. Failure to detect PKC-zeta in extracts from isolated adult ventricular myocytes suggests that PKC-zeta resides primarily in nonmyocyte elements in the adult heart. PKC-epsilon was detected in all preparations, but it was detected in greatest abundance in extracts from neonatal hearts. In vitro sympathetic innervation of previously noninnervated neonatal ventricular myocytes or in vivo chemical sympathectomy of the neonatal heart did not modulate PKC isoform expression, suggesting that sympathetic innervation does not significantly regulate PKC isoform expression. PKC-alpha partitioned to the soluble fraction of unstimulated myocytes and was selectively translocated to the particulate fraction by Ca2+. In contrast, a major portion of the novel PKC isoforms partitioned to the particulate fraction of unstimulated myocytes. The subcellular distribution of novel PKC isoforms was not influenced by Ca2+. 12-O-Tetradecanoylphorbol 13-acetate (TPA, 300 nmol/L) induced translocation of soluble PKC-alpha, PKC-delta, and PKC-epsilon to the particulate fraction at 30 minutes and complete (PKC-alpha and PKC-delta) or 80% (PKC-epsilon) downregulation at 24 hours. PKC-zeta was not affected by TPA.(ABSTRACT TRUNCATED AT 400 WORDS)


Strategies for the hyperpolarization of acetonitrile and related ligands by SABRE.
We report on a strategy for using SABRE (signal amplification by reversible exchange) for polarizing (1)H and (13)C nuclei of weakly interacting ligands which possess biologically relevant and nonaromatic motifs. We first demonstrate this via the polarization of acetonitrile, using Ir(IMes)(COD)Cl as the catalyst precursor, and confirm that the route to hyperpolarization transfer is via the J-coupling network. We extend this work to the polarization of propionitrile, benzylnitrile, benzonitrile, and trans-3-hexenedinitrile in order to assess its generality. In the (1)H NMR spectrum, the signal for acetonitrile is enhanced 8-fold over its thermal counterpart when [Ir(H)2(IMes)(MeCN)3](+) is the catalyst. Upon addition of pyridine or pyridine-d5, the active catalyst changes to [Ir(H)2(IMes)(py)2(MeCN)](+) and the resulting acetonitrile (1)H signal enhancement increases to 20- and 60-fold, respectively. In (13)C NMR studies, polarization transfers optimally to the quaternary (13)C nucleus of MeCN while the methyl (13)C is hardly polarized. Transfer to (13)C is shown to occur first via the (1)H-(1)H coupling between the hydrides and the methyl protons and then via either the (2)J or (1)J couplings to the respective (13)Cs, of which the (2)J route is more efficient. These experimental results are rationalized through a theoretical treatment which shows excellent agreement with experiment. In the case of MeCN, longitudinal two-spin orders between pairs of (1)H nuclei in the three-spin methyl group are created. Two-spin order states, between the (1)H and (13)C nuclei, are also created, and their existence is confirmed for Me(13)CN in both the (1)H and (13)C NMR spectra using the Only Parahydrogen Spectroscopy protocol.


Neural control of the circulation during exercise: insights from the 1970-1971 Oxford studies.
During exercise the magnitude of the cardiovascular response is closely matched to the intensity of the exercise. In achieving this appropriate matching, an important role is played by the autonomic nervous system. Two mechanisms have been postulated to regulate this response. In one mechanism the changes in autonomic nerve activity to the heart and blood vessels are caused by signals arising in a central area of the brain and in the other mechanism the changes are caused by signals arising in the contracting skeletal muscle. In 1970-71 two studies were performed in Oxford which furthered our understanding of these two mechanisms. In one of these studies it was shown in cats that a reflex arising in the contracting skeletal muscle reflexly increased blood pressure and heart rate and that the thinly myelinated (Group III or A ) and the unmyelinated (Group IV or C) afferent nerve fibers were responsible. In the second of these studies it was shown in humans that a central mechanism could also increase the blood pressure and heart rate during static contraction at a fixed force. Tendon vibration of a skeletal muscle induces an involuntary reflex contraction. Utilizing this effect the central command needed to produce the same tension development was reduced or increased. When the same force was achieved with less central command the cardiovascular response was reduced and with more central command was increased. This demonstrated that descending motor commands from higher brain centers have an effect on the cardiovascular response to exercise.


Fluctuating multicomponent lattice Boltzmann model.
Current implementations of fluctuating lattice Boltzmann equations (FLBEs) describe single component fluids. In this paper, a model based on the continuum kinetic Boltzmann equation for describing multicomponent fluids is extended to incorporate the effects of thermal fluctuations. The thus obtained fluctuating Boltzmann equation is first linearized to apply the theory of linear fluctuations, and expressions for the noise covariances are determined by invoking the fluctuation-dissipation theorem directly at the kinetic level. Crucial for our analysis is the projection of the Boltzmann equation onto the orthonormal Hermite basis. By integrating in space and time the fluctuating Boltzmann equation with a discrete number of velocities, the FLBE is obtained for both ideal and nonideal multicomponent fluids. Numerical simulations are specialized to the case where mean-field interactions are introduced on the lattice, indicating a proper thermalization of the system.


Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance.
Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact. The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils. Tonsil allergen-specific FOXP3(+) regulatory T (Treg) cells, plasmacytoid dendritic cells (pDCs), and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining, [(3)H]-thymidine incorporation, and carboxy-fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy. CD4(+)FOXP3(+) Treg cells and pDCs constitute important T- and dendritic cell-compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4(+)CD25(+)CD127(-)FOXP3(+) Treg cells with suppressive property from naive T cells. CD4(+)FOXP3(+) Treg cells proliferate and colocalize with pDCs in vivo in T-cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3(+) Treg cells enables the allergen-induced proliferation of tonsil T cells, indicating an active role of Treg cells in allergen-specific T-cell unresponsiveness. High numbers of major birch pollen allergen, Bet v 1-specific CD4(+)FOXP3(+) Treg cells, are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3(+) Treg cells and pDCs is observed in tonsils from nonatopic individuals. Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.


Medium-finesse optical cavity for the stabilization of Rydberg lasers.
We describe the design, construction, and characterization of a medium-finesse Fabry-Perot cavity for simultaneous frequency stabilization of two lasers operating at 960 and 780 nm wavelengths, respectively. The lasers are applied in experiments with ultracold rubidium Rydberg atoms, for which a combined laser linewidth similar to the natural Rydberg linewidth (≈10 kHz) is desired. The cavity, with a finesse of ≈1500, is used to reduce the linewidth of the lasers to below this level. By using a spacer made of ultra low expansion (ULE) glass with active temperature stabilization, the residual frequency drift is limited to ≲1 MHz/day. The design optimizes for ease of construction, robustness, and affordability.


Alcohol consumption and blood pressure in a group of young Australian males.
Several studies have suggested that regular consumption of alcoholic beverages is associated with hypertension. Recent studies, however, have implied tht whilst moderate or high ingestion of alcohol may be detrimental, a threshold exists for alcohol consumption below which alcohol may even exert a beneficial effect. As part of a larger study of a male, service population (average age 23 years) undergoing an initial training course of ten weeks duration, we measured both blood pressure and alcohol consumption in 350 men at entry and/or exit from the course. Alcohol intake was assessed using a supervised, self-administered dietary questionnaire which included two pre-tested measures of alcohol consumption. High alcohol consumption in these young men was not related to elevated systolic or diastolic blood pressure; neither was the recently reported lowering of blood pressure in low alcohol consumers compared to non-drinkers, apparent in this young population. The lack of relationship between alcohol consumption and blood pressure in this predominantly young group suggests that the relationship, if there is one, between these two factors only becomes clinically obvious either with longer exposure to alcohol, or in an older age group in whom the mechanism of control of blood pressure may already be somewhat compromised by other age-related physiological changes which are not readily measurable.


Circular polymerase extension cloning of complex gene libraries and pathways.
High-throughput genomics and the emerging field of synthetic biology demand ever more convenient, economical, and efficient technologies to assemble and clone genes, gene libraries and synthetic pathways. Here, we describe the development of a novel and extremely simple cloning method, circular polymerase extension cloning (CPEC). This method uses a single polymerase to assemble and clone multiple inserts with any vector in a one-step reaction in vitro. No restriction digestion, ligation, or single-stranded homologous recombination is required. In this study, we elucidate the CPEC reaction mechanism and demonstrate its usage in demanding synthetic biology applications such as one-step assembly and cloning of complex combinatorial libraries and multi-component pathways.


Human Second Window Pre-Conditioning and Post-Conditioning by Nitrite Is Influenced by a Common Polymorphism in Mitochondrial Aldehyde Dehydrogenase.
Pre-conditioning is an exciting physiological phenomenon that, despite great efforts, has so far resisted translation to mainstream clinical medicine. Many potential triggers (e.g., ischemia of the organ in question or a remote organ, many different drugs) have been investigated, but recent work has implicated activation of mitochondrial aldehyde dehydrogenase (ALDH2) as central to the process. A genetic polymorphism, known as ALDH2*2, is common worldwide (present in up to 40% of Han Chinese people) and produces a functionally different enzyme. The authors used a variety of protocols in the human ischemic forearm model, in participants with both enzyme types, to assess cytoprotection with low-dose sodium nitrite and attempt to further elucidate the role of ALDH2.


Exploring uncertainty in geodemographics with interactive graphics.
Geodemographic classifiers characterise populations by categorising geographical areas according to the demographic and lifestyle characteristics of those who live within them. The dimension-reducing quality of such classifiers provides a simple and effective means of characterising population through a manageable set of categories, but inevitably hides heterogeneity, which varies within and between the demographic categories and geographical areas, sometimes systematically. This may have implications for their use, which is widespread in government and commerce for planning, marketing and related activities. We use novel interactive graphics to delve into OAC--a free and open geodemographic classifier that classifies the UK population in over 200,000 small geographical areas into 7 super-groups, 21 groups and 52 sub-groups. Our graphics provide access to the original 41 demographic variables used in the classification and the uncertainty associated with the classification of each geographical area on-demand. It also supports comparison geographically and by category. This serves the dual purpose of helping understand the classifier itself leading to its more informed use and providing a more comprehensive view of population in a comprehensible manner. We assess the impact of these interactive graphics on experienced OAC users who explored the details of the classification, its uncertainty and the nature of between--and within--class variation and then reflect on their experiences. Visualization of the complexities and subtleties of the classification proved to be a thought-provoking exercise both confirming and challenging users' understanding of population, the OAC classifier and the way it is used in their organisations. Users identified three contexts for which the techniques were deemed useful in the context of local government, confirming the validity of the proposed methods.


A structure-activity analysis of antagonism of the growth factor and angiogenic activity of basic fibroblast growth factor by suramin and related polyanions.
The ability of a series of polysulphonated naphthylureas structurally related to suramin to inhibit basic fibroblast growth factor (bFGF) or serum-stimulated growth of endothelial cells [either large vessel, human umbilical vein endothelial cells (HUVEC) or microvascular, bovine adrenal capillary endothelial (BACE) cells] and angiogenesis in vivo has been examined. The polyanions encompassed two main structural variations, namely the number of aromatic amide groups intervening between two terminal naphthyl rings and/or variation in the substitution pattern of the naphthyl rings. The polyanions were either inactive (group I) or inhibited (group II) bFGF-stimulated uptake of [3H]methylthymidine by BACE cells. Group I compounds shared a common structural feature in that they were simple binaphthyl-substituted ureas. In contrast, group II compounds all had an extended multiple ring structure with at least two aromatic groups intervening between the two terminal naphthyl rings. Compounds with either two or four intervening groups were equipotent in blocking bFGF in vitro. However, compounds with two bridging aromatic groups were 5- to 10-fold less toxic than suramin in mice, suggesting a potential for an improved therapeutic ratio. The ability of the polyanions to block bFGF-driven endothelial cell proliferation in vitro correlated with antiangiogenic activity in vivo as shown by use of the rat sponge angiogenesis model. These observations could substantially widen the anti-tumour therapeutic opportunities for this class of compound.


Investigating the generators of the scalp recorded visuo-verbal P300 using cortically constrained source localization.
Considerable ambiguity exists about the generators of the scalp recorded P300, despite a vast body of research employing a diverse range of methodologies. Previous investigations employing source localization techniques have been limited largely to equivalent current dipole models, with most studies identifying medial temporal and/or hippocampal sources, but providing little information about the contribution of other cortical regions to the generation of the scalp recorded P3. Event-related potentials (ERPs) were recorded from 5 subjects using a 124-channel sensor array during the performance of a visuo-verbal Oddball task. Cortically constrained, MRI-guided boundary element modeling was used to identify the cortical generators of this target P3 in individual subjects. Cortical generators of the P3 were localized principally to the intraparietal sulcus (IPS) and surrounding superior parietal lobes (SPL) bilaterally in all subjects, though with some variability across subjects. Two subjects also showed activity in the lingual/inferior occipital gyrus and mid-fusiform gyrus. A group cortical surface was calculated by non-linear warping of each subject's segmented cortex followed by averaging and creation of a group mesh. Source activity identified across the group reflected the individual subject activations in the IPS and SPL bilaterally and in the lingual/inferior occipital gyrus primarily on the left. Activation of IPS and SPL is interpreted to reflect the role of this region in working memory and related attention processes and visuo-motor integration. The activity in left lingual/inferior occipital gyrus is taken to reflect activation of regions associated with modality-specific analysis of visual word forms.


Dynamics of mutated GFAP aggregates revealed by real-time imaging of an astrocyte model of Alexander disease.
Alexander disease (AxD) is a rare neurodegenerative disorder characterized by large cytoplasmic aggregates in astrocytes and myelin abnormalities and caused by dominant mutations in the gene encoding glial fibrillary acidic protein (GFAP), the main intermediate filament protein in astrocytes. We tested the effects of three mutations (R236H, R76H and L232P) associated with AxD in cells transiently expressing mutated GFAP fused to green fluorescent protein (GFP). Mutated GFAP-GFP expressed in astrocytes formed networks or aggregates similar to those found in the brains of patients with the disease. Time-lapse recordings of living astrocytes showed that aggregates of mutated GFAP-GFP may either disappear, associated with cell survival, or coalesce in a huge juxtanuclear structure associated with cell death. Immunolabeling of fixed cells suggested that this gathering of aggregates forms an aggresome-like structure. Proteasome inhibition and immunoprecipitation assays revealed mutated GFAP-GFP ubiquitination, suggesting a role of the ubiquitin-proteasome system in the disaggregation process. In astrocytes from wild-type-, GFAP-, and vimentin-deficient mice, mutated GFAP-GFP aggregated or formed a network, depending on qualitative and quantitative interactions with normal intermediate filament partners. Particularly, vimentin displayed an anti-aggregation effect on mutated GFAP. Our data indicate a dynamic and reversible aggregation of mutated GFAP, suggesting that therapeutic approaches may be possible.


GABAergic anxiolytic drug in water increases migration behaviour in salmon.
Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.


Differences in questing tick species distribution between Atlantic and continental climate regions in Spain.
Climate and vegetation in Spain vary from north to south, affecting tick distribution and consequently the presence of tick-borne diseases. The aim of this study was to investigate throughout a 2-yr study the distribution of the different exophilic questing tick species present in 18 areas: eight located in central and 10 in northern Spain. The same methodology was used in both areas, sampling vegetation on a monthly basis by blanket dragging for 20- to 30-min intervals. A total of 12 species belonging to the genera Ixodes, Haemaphysalis, Rhipicephalus, Dermacentor, and Hyalomma was identified. Differences in species distribution and prevalence were dramatically different. The most frequent and abundant species in northern Spain were Ixodes ricinus (67% of adult ticks) and Haemaphysalis punctata (8%), whereas Hyalomma lusitanicum (86%) and Dermacentor marginatus (12%) were the most abundant in central Spain. There were important differences in the monthly seasonal patterns for the different tick species. These results highlight important differences in tick distribution in neighboring areas and underline the need for ongoing surveillance programs to monitor tick population dynamics and the prevalence of tick-borne pathogens.


Signal transduction mechanism of the seabream growth hormone secretagogue receptor.
We have recently cloned the full-length cDNAs of the two growth hormone secretagogue receptor (GHSR) subtypes from a teleost species, the black seabream (Acanthopagrus schlegeli) [Mol. Cell. Endocrinol. 214 (2004) 81], namely sbGHSR-1a and sbGHSR-1b. Functional expression of these two receptor constructs in human embryonic kidney 293 (HEK293) cells indicated that stimulation of sbGHSR-1a by growth hormone secretagogues (GHS) could evoke increases in intracellular Ca2+ concentration ([Ca2+]i), whereas sbGHSR-1b appeared to play an inhibitory role on the signal transduction activity of sbGHSR-1a. In the present study, we have further investigated the signal transduction mechanism of sbGHSR-1a. The peptide GHS GHRP-6 and the non-peptide GHS L163,540 were able to trigger a receptor specific and phospholipase C (PLC)-dependent elevation of [Ca2+]i in HEK293 cells stably expressing sbGHSR-1a. This GHS-induced calcium mobilization was also dependent on protein kinase C activated L-type calcium channel opening. It was found that sbGHSR-1a could function in an agonist-independent manner as it exhibited a high basal activity of inositol phosphate production in the absence of GHS, indicating that the fish receptor is constitutively active. In addition, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) were found to be activated upon stimulation of sbGHSR-1a by GHRP-6. This observation provides direct evidence in the coupling of sbGHSR-1a to ERK1/2 activation. Neither Gs nor Gi proteins are coupled to the receptor, as GHS did not induce cAMP production nor inhibit forskolin-stimulated cAMP accumulation in the sbGHSR-1a bearing cells. Furthermore, the ability of the GHSR antagonist D-Lys3-GHRP-6 to inhibit basal PLC and basal ERK1/2 activity suggests that this compound is an inverse agonist. In summary, the sbGHSR-1a appears to couple through the G(q/11)-mediated pathway to activate PLC, resulting in increased IP3 production and Ca2+ mobilization from both intracellular and extracellular stores. Moreover, sbGHSR-1a may trigger multiple signal transduction cascades to exert its physiological functions.


Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis.
To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment. Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited. This review included overweight or obese (BMI ≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events. A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses. Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156). Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review.


On the correct interpretation of measured force and calculation of material stress in biaxial tests.
Biaxial tests are commonly used to investigate the mechanical behaviour of soft biological tissues and polymers. In the current paper we uncover a fundamental problem associated with the calculation of material stress from measured force in standard biaxial tests. In addition to measured forces, localised unmeasured shear forces also occur at the clamps and the inability to quantify such forces has significant implications for the calculation of material stress from simplified force-equilibrium relationships. Unmeasured shear forces are shown to arise due to two distinct competing contributions: (1) negative shear force due to stretching of the orthogonal clamp, and (2) positive shear force as a result of material Poisson-effect. The clamp shear force is highly dependent on the specimen geometry and the clamp displacement ratio, as consequently, is the measured force-stress relationship. Additionally in this study we demonstrate that commonly accepted formulae for the estimation of material stress in the central region of a cruciform specimen are highly inaccurate. A reliable empirical correction factor for the general case of isotropic materials must be a function of specimen geometry and the biaxial clamp displacement ratio. Finally we demonstrate that a correction factor for the general case of non-linear anisotropic materials is not feasible and we suggest the use of inverse finite element analysis as a practical means of interpreting experimental data for such complex materials.


An Introductory Overview of Image-Based Computational Modeling in Personalized Cardiovascular Medicine.
Cardiovascular diseases account for the number one cause of deaths in the world. Part of the reason for such grim statistics is our limited understanding of the underlying mechanisms causing these devastating pathologies, which is made difficult by the invasiveness of the procedures associated with their diagnosis (e.g., inserting catheters into the coronal artery to measure blood flow to the heart). Likewise, it is also difficult to design and test assistive devices without implanting them in vivo. However, with the recent advancements made in biomedical scanning technologies and computer simulations, image-based modeling (IBM) has arisen as the next logical step in the evolution of non-invasive patient-specific cardiovascular medicine. Yet, due to its novelty, it is still relatively unknown outside of the niche field. Therefore, the goal of this manuscript is to review the current state-of-the-art and the limitations of the methods used in this area of research, as well as their applications to personalized cardiovascular investigations and treatments. Specifically, the modeling of three different physics - electrophysiology, biomechanics and hemodynamics - used in the cardiovascular IBM is discussed in the context of the physiology that each one of them describes and the mechanisms of the underlying cardiac diseases that they can provide insight into. Only the "bare-bones" of the modeling approaches are discussed in order to make this introductory material more accessible to an outside observer. Additionally, the imaging methods, the aspects of the unique cardiac anatomy derived from them, and their relation to the modeling algorithms are reviewed. Finally, conclusions are drawn about the future evolution of these methods and their potential toward revolutionizing the non-invasive diagnosis, virtual design of treatments/assistive devices, and increasing our understanding of these lethal cardiovascular diseases.


Mach-zehnder interferometer as a spectral analyzer for molecular Doppler wind lidar.
The theoretical performance of a Mach-Zehnder interferometer used as a spectral analyzer for wind-speed measurement by direct-detection Doppler lidar is presented. The interferometer is optimized for measurement of wind velocity from the signal backscattered by the molecules. Two arrangements are proposed, involving two detection channels (DMZ) or four detection channels (QMZ). Using the assumption of a pure molecular signal with a Gaussian spectral profile, we derive an analytic expression for the standard deviation of the measurement error for each arrangement. They are then compared with the ideal spectral analyzer (ISA) and with the double-edge Fabry-Perot (DFP) in the case of a shot-noise-limited signal. The DMZ measurement error is shown to be only 1.65 times that of the ISA and is 1.4 times lower than that given by the DFP. The QMZ arrangement provides a measurement that is insensitive to the aerosol scattering contribution but gives a measurement error that is 1.4 times higher than that of the DMZ.


Prognostic and immune implications of a novel ferroptosis-related ten-gene signature in lung adenocarcinoma.
Lung cancer has been the focus of attention for many researchers in recent years due to its leading contribution to cancer-related death worldwide, with lung adenocarcinoma (LUAD) being the most common histological type. Ferroptosis, a novel iron-dependent form of regulated cell death, can be induced by sorafenib. Emerging evidence shows that triggering ferroptosis has potential as a cancer therapy. This work aimed to build a ferroptosis-related gene signature for predicting the outcome of LUAD. The TCGA-LUAD dataset was set as the training cohort, and the GSE72094 and GSE68465 datasets were set as the validation cohorts. Sixty-two ferroptosis-related genes were retrieved from the literature. A univariate Cox regression model was constructed for the training cohort to preliminarily screen for potential prognostic ferroptosis-related genes. A gene signature was generated from a LASSO Cox regression model and assessed with the training and validation cohorts through Kaplan-Meier, Cox, and ROC analyses. In addition, the correlation between the risk score and autophagy-related genes was determined by the Pearson test. Finally, GSEA and immune infiltrating analyses were performed to better study the functional annotation of the signature and the role of each kind of immune cell. A ten-gene signature was constructed from the training cohort and validated in three cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognostic value in LUAD. Moreover, a ROC analysis conducted with all cohort data confirmed the predictive ability of the ten-gene signature for LUAD prognosis. A total of 62.85% (308/490) of autophagy-related genes were found to be significantly correlated with risk scores. GSEA detailed the exact pathways related to the gene signature, and immune-infiltrating analyses identified crucial roles for resting mast cells and resting dendritic cells in the prognosis of LUAD. We identified a novel ferroptosis-related ten-gene signature (PHKG2, PGD, PEBP1, NCOA4, GLS2, CISD1, ATP5G3, ALOX15, ALOX12B, and ACSL3) that can accurately predict LUAD prognosis and is closely linked to resting mast cells and resting dendritic cells.


Towards microbiome-informed dietary recommendations for promoting metabolic and mental health: Opinion papers of the MyNewGut project.
The gut microbiota coexists in partnership with the human host through adaptations to environmental and physiological changes that help maintain dynamic homeostatic healthy states. Break-down of this delicate balance under sustained exposure to stressors (e.g. unhealthy diets) can, however, contribute to the onset of disease. Diet is a key modifiable environmental factor that modulates the gut microbiota and its metabolic capacities that, in turn, could impact human physiology. On this basis, the diet and the gut microbiota could act as synergistic forces that provide resilience against disease or that speed the progress from health to disease states. Associations between unhealthy dietary patterns, non-communicable diseases and intestinal dysbiosis can be explained by this hypothesis. Translational studies showing that dietary-induced alterations in microbial communities recapitulate some of the pathological features of the original host further support this notion. In this introductory paper by the European project MyNewGut, we briefly summarize the investigations conducted to better understand the role of dietary patterns and food components in metabolic and mental health and the specificities of the microbiome-mediating mechanisms. We also discuss how advances in the understanding of the microbiome's role in dietary health effects can help to provide acceptable scientific grounds on which to base dietary advice for promoting healthy living.


Latin America intensive care unit disaster preparedness: Results from a web-based attitudes and perceptions survey.
Disasters burden on hospital emergency intensive care units (ICUs). This burden is increased in Latin America (LATAM) where hospital resources, intrahospital disaster simulations, and perceived level of preparedness vary greatly among different communities. The objective of the study was to assess LATAM ICU leaders' knowledge and attitudes regarding disaster preparedness. We developed a ten-item, web-based knowledge and attitude survey administered via LATAM ICU leaders online forums. Descriptive statistics were used. Epi Info™ software was used for analysis. Chi-square and Fisher's exact test with P < 0.05 were implemented for statistical significance, and odds ratio was used to measure the strength of association among variables. There were 68 respondents in the survey. 13/68 respondents felt prepared for disasters. 16/68 worked at hospitals with 250+ beds and 52/68 represented hospitals with <250 beds. 23/68 participated in hospital committees for disaster, 24/68 participated in simulations or drills, and 22/68 participated in trainings or courses for disasters. Feeling prepared for disasters did not correlate with hospital size (odds ratio [OR] = 2.87 [95% confidence interval (CI): 0.83-9.92], P = 0.91), participation in hospital committees for disaster (OR = 3.10 [95% CI: 1.02-9.26], P = 0.08), and participation in simulations or drills (OR = 2.78 [95% CI: 0.93-8.29], P = 0.11), but participation in disaster trainings and courses appeared to directly correlate with the perception of being prepared (OR = 3.43 [95% CI: 1.13-10.41], P = 0.03). Among the 68 centers represented, the majority did not feel their institution to be adequately prepared for disasters, but training appeared to change that perception. A small sample size represents the major limitation of this study.


Genomewide patterns of variation in genetic diversity are shared among populations, species and higher-order taxa.
Genomewide screens of genetic variation within and between populations can reveal signatures of selection implicated in adaptation and speciation. Genomic regions with low genetic diversity and elevated differentiation reflective of locally reduced effective population sizes (Ne ) are candidates for barrier loci contributing to population divergence. Yet, such candidate genomic regions need not arise as a result of selection promoting adaptation or advancing reproductive isolation. Linked selection unrelated to lineage-specific adaptation or population divergence can generate comparable signatures. It is challenging to distinguish between these processes, particularly when diverging populations share ancestral genetic variation. In this study, we took a comparative approach using population assemblages from distant clades assessing genomic parallelism of variation in Ne . Utilizing population-level polymorphism data from 444 resequenced genomes of three avian clades spanning 50 million years of evolution, we tested whether population genetic summary statistics reflecting genomewide variation in Ne would covary among populations within clades, and importantly, also among clades where lineage sorting has been completed. All statistics including population-scaled recombination rate (ρ), nucleotide diversity (π) and measures of genetic differentiation between populations (FST , PBS, dxy ) were significantly correlated across all phylogenetic distances. Moreover, genomic regions with elevated levels of genetic differentiation were associated with inferred pericentromeric and subtelomeric regions. The phylogenetic stability of diversity landscapes and stable association with genomic features support a role of linked selection not necessarily associated with adaptation and speciation in shaping patterns of genomewide heterogeneity in genetic diversity.


In-house polymerase chain reaction for affordable and sustainable Chlamydia trachomatis detection in Trinidad and Tobago.
To provide a preliminary assessment of in-house polymerase chain reaction (PCR) as an alternative to the more costly commercial test for detection of asymptomatic infection by Chlamydia trachomatis and to provide much needed demographic data on infection indicators within the Trinidad and Tobago public health care system. An inexpensive in-house nested-PCR with an Internal Amplification Control was used to detect C. trachomatis and Neisseria gonorrhoeae in urine samples collected from 273 apparently healthy, pregnant women from March-September 2004 in Trinidad, West Indies. Demographic information on participants was collected and subjected to statistical analyses. C. trachomatis was detected in 57/273 (21%) samples, of which 5 (2%) were also positive for N. gonorrhoeae. Infection correlated well with certain demographic parameters, with the highest incidence of C. trachomatis infection found among pregnant women that were single or of African descent. Given the lack of commercial tests in Trinidad, in-house PCR is an inexpensive alternative that can be used to detect asymptomatic infections of C. trachomatis and to provide demographic information needed for interventions by the public health care system.


A Novel Statistical Model for Predicting the Efficacy of Vagal Nerve Stimulation in Patients With Epilepsy (Pre-X-Stim) Is Applicable to Different EEG Systems.
Background: Identifying patients with intractable epilepsy who would benefit from therapeutic chronic vagal nerve stimulation (VNS) preoperatively remains a major clinical challenge. We have developed a statistical model for predicting VNS efficacy using only routine preimplantation electroencephalogram (EEG) recorded with the TruScan EEG device (Brazdil et al., 2019). It remains to be seen, however, if this model can be applied in different clinical settings. Objective: To validate our model using EEG data acquired with a different recording system. Methods: We identified a validation cohort of eight patients implanted with VNS, whose preimplantation EEG was recorded on the BrainScope device and who underwent the EEG recording according to the protocol. The classifier developed in our earlier work, named Pre-X-Stim, was then employed to classify these patients as predicted responders or non-responders based on the dynamics in EEG power spectra. Predicted and real-world outcomes were compared to establish the applicability of this classifier. In total, two validation experiments were performed using two different validation approaches (single classifier or classifier voting). Results: The classifier achieved 75% accuracy, 67% sensitivity, and 100% specificity. Only two patients, both real-life responders, were classified incorrectly in both validation experiments. Conclusion: We have validated the Pre-X-Stim model on EEGs from a different recording system, which indicates its application under different technical conditions. Our approach, based on preoperative EEG, is easily applied and financially undemanding and presents great potential for real-world clinical use.