HIV risk among female sex workers in Miami: the impact of violent victimization and untreated mental illness.
Street-based female sex workers constitute a vulnerable population for HIV, as they are often enmeshed in chronic patterns of substance use, sexual risk, homelessness, and violent victimization. This study examined the specific contributions of victimization history and abuse-related traumagenic factors to mental health functioning and sexual risk behaviors, while considering the impact of environmental risk factors as well. Using targeted sampling strategies, we enrolled 562 Miami-based female sex workers into an intervention trial testing the relative effectiveness of two alternative case management conditions in establishing linkages with health services and reducing risk for HIV. Lifetime prevalence of abuse was extremely elevated at 88%. Nearly half reported abuse before the age of 18, while 34% reported violent encounters with "dates" or clients in the past 90 days. Serious mental illness (SMI) was quite common, with 74% reporting severe symptoms of depression, anxiety, or traumatic stress. For those with histories of abuse, SMI appeared to mediate the association between abuse-related trauma and unprotected sex behaviors. Mental health treatment would appear to be an important component of effective HIV prevention among this vulnerable group, and should form part of a compendium of services offered to female sex workers.


Region-Based Prediction for Image Compression in the Cloud.
Thanks to the increasing number of images stored in the cloud, external image similarities can be leveraged to efficiently compress images by exploiting inter-images correlations. In this paper, we propose a novel image prediction scheme for cloud storage. Unlike current state-of-the-art methods, we use a semi-local approach to exploit inter-image correlation. The reference image is first segmented into multiple planar regions determined from matched local features and super-pixels. The geometric and photometric disparities between the matched regions of the reference image and the current image are then compensated. Finally, multiple references are generated from the estimated compensation models and organized in a pseudo-sequence to differentially encode the input image using classical video coding tools. Experimental results demonstrate that the proposed approach yields significant rate-distortion performance improvements compared with the current image inter-coding solutions such as high efficiency video coding.


Emergence of a new type of porcine circovirus in swine (PCV): a type 1 and type 2 PCV recombinant.
In late September 2008, tissue samples from piglets experiencing an acute outbreak of porcine reproductive and respiratory syndrome (PRRS) were submitted to the Veterinary diagnostic service of the University of Montreal. Several diagnostic assays were performed including a multiplex real-time quantitative PCR assay (mrtqPCR) for the detection and differentiation of porcine circovirus (PCV) type 2a and 2b genotypes in the lung and lymph nodes. The pig samples were found to be positive for PCV2a using the mrtqPCR but odd results were obtained. The Ct values obtained with mrtqPCR probes targeting the ORF1 and ORF2 of PCV2 were not as expected which suggested the presence of genomic variations in the PCV2 viral genome. Ultimately, a total of three diagnostic cases with mrtqPCR unusual results were investigated. After virus isolation and sequence analyses, a new type of PCV was identified in those three cases. Based on sequence analyses, this new PCV genome contains the ORF1 of PCV1 and the ORF2 of PCV2a and its entire viral genome nucleotide identity compared to PCV1, PCV2a and 2b are 86.4%, 88.7% and 86.5%, respectively. It is proposed to name this new PCV by taking into account the nomenclature of Segales et al. (2008) and by indicating the origin of the ORF1 at first and the origin of the ORF2 in second. Consequently, the name proposed for this new PCV is PCV1/2a. The prevalence of PCV1/2a seems to be very low in Quebec, Canada (2.5% of PCV positive cases), and its origin is now in debate.


The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.
Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and functional pathway level. Here, we describe one path forward-an initiative aimed at mapping the physical and genetic interaction networks of these conditions and then using these maps to connect the genomic data to neurobiology and, ultimately, the clinic. These efforts will include a team of geneticists, structural biologists, neurobiologists, systems biologists, and clinicians, leveraging a wide array of experimental approaches and creating a collaborative infrastructure necessary for long-term investigation. This initiative will ultimately intersect with parallel studies that focus on other diseases, as there is a significant overlap with genes implicated in cancer, infectious disease, and congenital heart defects.


Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.
An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.


Social support and self-care behaviors in individuals with heart failure: an integrative review.
The purpose of this review is to examine and synthesize recent literature regarding the relationship between social support and self-care behaviors in individuals with heart failure (HF). Self-care is an important factor in maintaining health and well-being for individuals with heart failure. Self-care behaviors are an integral component of self-care, and may be impacted by the disease process of heart failure. However, social support may positively influence an individual's self-care behaviors by assisting with activities associated with symptom management and evaluation, as well as activities associated with maintaining heart failure-related treatment regimens. This review will synthesize the current knowledge related to the influence of social support on heart failure self-care behaviors. Using an integrative review method, a review of current empirical literature was conducted utilizing CINAHL, PsycARTICLES, and PubMed computerized databases for a period of January 2000 to December 2012. Thirteen studies were identified that met the inclusion criteria for review and investigated aspects of social support and heart failure self-care behaviors. Social support appears to have a positive relationship on heart failure self-care behaviors, with an individual's family playing an important role in assisting individuals to maintain positive self-care behaviors. Social support appears to influence both heart failure self-care maintenance and management related behaviors by assisting with maintaining treatment regimens and by participating in the decision-making process related to the management of symptoms, as well as seeking treatment for symptoms of heart failure. All four types of social support (i.e., emotional support, instrumental/tangible support, informational support, and appraisal support) are involved in the interactive process between an individual's social network (i.e., family and peers) and the individual with heart failure to maintain self-care behaviors that enhance health and well-being. However, more research is needed, specifically longitudinal and experimental designs, to determine the effectiveness of social support on self-care behaviors in individuals with heart failure, since this review revealed mostly cross-sectional, correlational studies which limits the ability to infer causality.


Lectins discriminate between pathogenic and nonpathogenic South American trypanosomes.
Cell surface carbohydrates of Trypanosoma cruzi, Trypanosoma rangeli, and Trypanosoma conorhini were analyzed by a micro-agglutination assay employing 27 highly purified lectins and by binding assays using various 125I-labeled lectins. The following seven lectins discriminated between the trypanosomes: 1) tomato lectin (an N-acetyl-D-glucosamine-binding protein), both in purified form and as crude tomato juice; 2) Bauhinea purpurea and Sophora japonica lectins (both N-acetyl-D-galactosamine-binding proteins), which selectively agglutinated T. cruzi; 3) Vicia villosa (an N-acetyl-D-galactosamine-binding protein) which was specific for T. rangeli; 4) peanut lectin (a D-galactose-binding protein) both in purified form and as crude saline extract; and 5) Ulex europaeus and Lotus tetragonolobus (both L-fucose-binding proteins) lectins which reacted only with T. conorhini. Binding studies with 125I-labeled lectins were performed to find whether unagglutinated cells of the three different species of trypanosomes might have receptors for these lectins, in which case absence of agglutination could be due to a peculiar arrangement of the receptors. These assays essentially confirmed the agglutination experiments.


Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells.
Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell-cell and cell-matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.


Investigating the possible causal association of coffee consumption with osteoarthritis risk using a Mendelian randomization analysis.
This study examined whether coffee consumption is causally associated with osteoarthritis. A two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW) and weighted median estimates, and the MR-Egger regression method were performed. The publicly available summary statistical datasets of coffee consumption genome-wide association studies (GWASs) meta-analyses on coffee intake from eight Caucasian cohorts (n = 18,176), GWAS meta-analyses of predominately regular-type coffee consumers of European ancestry (n = up to 91,462), and a GWAS in 7410 patients with osteoarthritis in the arcOGEN study with 11,009 controls of European ancestry were evaluated. Four single-nucleotide polymorphisms (SNPs) from GWASs of coffee consumption as instrumental variables (IVs) to improve inference were selected. These SNPs were located at neurocalcin delta (NCALD) (rs16868941), cytochrome p450 oxidoreductase (POR) (rs17685), cytochrome p450 family 1 subfamily A member 1 (CYP1A1) (rs2470893), and neuronal cell adhesion molecule (NRCAM) (rs382140). The IVW method (beta = 0.381, SE = 0.170, p = 0.025) and the weighted median approach (beta = 0.419, SE = 0.206, p = 0.047) showed evidence to support a causal association between coffee consumption and osteoarthritis. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = 0.064; p = 0.549), but showed no causal association between coffee consumption and osteoarthritis (beta = - 0.518, SE = 1.270, p = 0.723). Cochran's Q test and the funnel plot indicated no evidence of heterogeneity between IV estimates based on the individual variants. The results of MR analysis support the observation that coffee consumption is causally associated with an increased risk of osteoarthritis.


Geospatial epidemiology of Staphylococcus aureus in a tropical setting: an enabling digital surveillance platform.
Delivery of information to clinicians on evolving antimicrobial susceptibility needs to be accurate for the local needs, up-to-date and readily available at point of care. In northern Australia, bacterial infection rates are high but resistance to first- and second-line antibiotics is poorly described and currently-available datasets exclude primary healthcare data. We aimed to develop an online geospatial and interactive platform for aggregating, analysing and disseminating data on regional bacterial pathogen susceptibility. We report the epidemiology of Staphylococcus aureus as an example of the power of digital platforms to tackle the growing spread of antimicrobial resistance in a high-burden, geographically-sparse region and beyond. We developed an online geospatial platform called HOTspots that visualises antimicrobial susceptibility patterns and temporal trends. Data on clinically-important bacteria and their antibiotic susceptibility profiles were sought from retrospectively identified clinical specimens submitted to three participating pathology providers (96 unique tertiary and primary healthcare centres, n = 1,006,238 tests) between January 2008 and December 2017. Here we present data on S. aureus only. Data were available on specimen type, date and location of collection. Regions from the Australian Bureau of Statistics were used to provide spatial localisation. The online platform provides an engaging visual representation of spatial heterogeneity, demonstrating striking geographical variation in S. aureus susceptibility across northern Australia. Methicillin resistance rates vary from 46% in the west to 26% in the east. Plots generated by the platform show temporal trends in proportions of S. aureus resistant to methicillin and other antimicrobials across the three jurisdictions of northern Australia. A quarter of all, and up to 35% of methicillin-resistant S. aureus (MRSA) blood isolates in parts of the northern Australia were resistant to inducible-clindamycin. Clindamycin resistance rates in MRSA are worryingly high in regions of northern Australia and are a local impediment to empirical use of this agent for community MRSA. Visualising routinely collected laboratory data with digital platforms, allows clinicians, public health physicians and guideline developers to monitor and respond to antimicrobial resistance in a timely manner. Deployment of this platform into clinical practice supports national and global efforts to innovate traditional disease surveillance systems with the use of digital technology and to provide practical solutions to reducing the threat of antimicrobial resistance.


Brain responses reveal hardwired detection of native-language rule violations.
Mismatch negativity (MMN) is a neural correlate of the preattentive detection of any change in the acoustic characteristics of sounds. Here we provide evidence that violations of a purely phonological constraint in a listener's native language can also elicit the brain's automatic change-detection response. The MMN differed between Finnish and Estonian listeners, conditions being equal except for the native language of the listeners. We used two experimental conditions: synthetic vowels in isolation and the same vowels embedded in a pseudo-word context. MMN responses to isolated vowels were similar for Finns and Estonians, while the same vowels in a pseudoword context elicited different MMN patterns depending on the listener's mother tongue.


Enhanced anticancer potential of encapsulated solid lipid nanoparticles of TPD: a novel triterpenediol from Boswellia serrata.
A pentacyclic triterpenediol (TPD) from Boswellia serrata has significant cytotoxic and apoptotic potential in a large number of human cancer cell lines. To enhance its anticancer potential, it was successfully formulated into solid lipid nanoparticles (SLNs) by the microemulsion method with 75% drug entrapment efficiency. SEM and TEM studies indicated that TPD-SLNs were regular, solid, and spherical particles in the range of 100-200 nm, and the system indicated that they were more or less stable upon storing up to six months. TPD loaded SLNs showed significantly higher cytotoxic/antitumor potential than the parent drug. TPD-SLNs have 40-60% higher cytotoxic and apoptotic potential than the parent drug in terms of IC(50), extent of apoptosis, DNA damage, and expression of pro-apoptotic proteins like TNF-R1, cytochrome-c, and PARP cleavage in HL-60 cells. Moreover, blank SLNs did not have any cytotoxic effect on the cancer as well as in normal mouse peritoneal macrophages. The in vivo antitumor potential of TPD-SLNs was significantly higher than that of TPD alone in Sarcoma-180 solid tumor bearing mice. Therefore, SLNs of TPD successfully increased the apoptotic and anticancer potential of TPD at comparable doses (both in vitro and in vivo). This work provides new insight into improvising the therapeutic efficacy of TPD by adopting novel delivery strategies such as solid lipid nanoparticles.


Complete objective response of oesophageal squamocellular carcinoma to biological treatment.
The synergetic use of Somatostatin, Melatonin, Retinoids, Vitamins C, D3, and E, Calcium, sulphated Aminoglucosides, and minimum doses of cyclophosphamide in a 70-year old male patient with inoperable scarcely differentiated oesophageal carcinoma, has provided, from the beginning of treatment in 1995 to the present date, an excellent quality of life, as well as a cure with functional recovery. This paper discusses the rationale and molecular action mechanisms of the treatment which has a differentiating, apoptotic anti-proliferation effect, preserving and enhancing, unlike chemo- and/or radiotherapy, both the trophic and functional capacity of organs and tissues, and immunity and antiblastic homeostasis. This result confirms the efficacy of this biological multiple treatment (MDB); it is also in line with the positive results already published on the use of MDB in low-grade NHL (66) and in stage 3 or 4 lung carcinomas (53). The MDB, with no need for hospitalisation, no toxicity and without in the least reducing working activity, gradually and slowly reduced, and then eliminated the tumour formation. According to the author, reporting this case is useful in order to call for greater interest in the possibilities offered to oncology by the MDB biological and receptor treatment.


Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder.
Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naïve first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naïve first-episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP.


"Gone are the days of mass-media marketing plans and short term customer relationships": tobacco industry direct mail and database marketing strategies.
As limitations on traditional marketing tactics and scrutiny by tobacco control have increased, the tobacco industry has benefited from direct mail marketing which transmits marketing messages directly to carefully targeted consumers utilising extensive custom consumer databases. However, research in these areas has been limited. This is the first study to examine the development, purposes and extent of direct mail and customer databases. We examined direct mail and database marketing by RJ Reynolds and Philip Morris utilising internal tobacco industry documents from the Legacy Tobacco Document Library employing standard document research techniques. Direct mail marketing utilising industry databases began in the 1970s and grew from the need for a promotional strategy to deal with declining smoking rates, growing numbers of products and a cluttered media landscape. Both RJ Reynolds and Philip Morris started with existing commercial consumer mailing lists, but subsequently decided to build their own databases of smokers' names, addresses, brand preferences, purchase patterns, interests and activities. By the mid-1990s both RJ Reynolds and Philip Morris databases contained at least 30 million smokers' names each. These companies valued direct mail/database marketing's flexibility, efficiency and unique ability to deliver specific messages to particular groups as well as direct mail's limited visibility to tobacco control, public health and regulators. Database marketing is an important and increasingly sophisticated tobacco marketing strategy. Additional research is needed on the prevalence of receipt and exposure to direct mail items and their influence on receivers' perceptions and smoking behaviours.


Evolution and the Growth Process: Natural Selection of Entrepreneurial Traits.
This research suggests that a Darwinian evolution of entrepreneurial spirit played a significant role in the process of economic development and the dynamics of inequality within and across societies. The study argues that entrepreneurial spirit evolved non-monotonically in the course of human history. In early stages of development, risk-tolerant, growth promoting traits generated an evolutionary advantage and their increased representation accelerated the pace of technological progress and the process of economic development. In mature stages of development, however, risk-averse traits gained an evolutionary advantage, diminishing the growth potential of advanced economies and contributing to convergence in economic growth across countries.


Non-linear modelling of breast tissue.
Previous approaches to modelling the large deformation of breast tissue, as occurs, e.g. in imaging using magnetic resonance imaging or mammography, include using linear elasticity and pseudo-non-linear elasticity, in which case the non-linear deformation is approximated by a series of small linear isotropic deformations, with the (constant) Young's modulus of each linear deformation an exponential function of the total non-linear strain. In this paper, these two approaches are compared to the solution of the full non-linear elastic problem for tissue with an exponential relationship between stress and strain. Having formulated each model and related the coefficients between the models, numerical simulations are performed on a block of incompressible material. These demonstrate that the simpler models may not be appropriate even in the case of modelling deformations of the human breast under gravity.


Satisfaction among ambulatory surgery patients in two hospitals in Iceland.
This study aims to investigate the level of satisfaction of care received among patients undergoing ambulatory surgery in two hospitals in Iceland, using the Patient Satisfaction Instrument (PSI). The PSI consists of 25 items, broken down into three sub-scales which measure the patients' attitude towards nursing care. The sample consisted of ambulatory patients undergoing orthopaedic, urological, hernia or varicose veins operations. The patients were 16 years or older and we enlisted 70 individuals from each hospital. Overall, the results show that patients are generally satisfied with the level of care they have received. The patients in group I are more satisfied than the patients in group II; however, only four out of the 25 items which were scored attracted a significance level of < 0.05. The patients perceived the clinical skills of the nurses as satisfactory but felt they did not receive enough information about their operation from the nurses. Although the patients were generally satisfied with the level of care received, they also identified instances where they felt that the level of care was inadequate; however, as results from other studies show, patients often experience difficulties articulating something negative about their nurses and the care they have received.


Keeping newborns warm: beliefs, practices and potential for behaviour change in rural Ghana.
This study aimed to collect data on thermal care practices in rural Ghana to inform the design of a community newborn intervention. All 635 women who delivered in six districts in Ghana in the first 2 weeks of December 2006 were interviewed about immediate newborn care. Qualitative data on thermal care practices and barriers and facilitators to behaviour change were collected from recently delivered/pregnant women, birth attendants/grandmothers, and husband through birth narratives, in-depth interviews and focus group discussion. Respondents knew that keeping the baby warm was essential for health but 71% of babies born at home had delayed drying, 79% delayed wrapping, 93% early bathing and 10% were placed skin-to-skin. Birth attendants were usually in charge of mother and baby immediately after birth. Delays in drying/wrapping were linked to leaving the baby unattended until the placenta was delivered. Early bathing was linked to reducing body odour in later life, shaping the baby's head, and helping the baby sleep and feel clean. Respondents thought that changing bathing behaviours would be difficult, especially as babies are bathed early in facilities. The concept of skin-to-skin care was easily understood and most women said they would try it if it was good for the baby. Thermal care is a key component of community newborn interventions, the design of which should be based on an understanding of current behaviours and beliefs. Formative research can help select focus behaviours, decide who to include in interventions, ensure consistent messages and determine what messages and approaches are needed to overcome behaviour change barriers.


Relationship of age and blood pressure to baroreflex sensitivity and arterial compliance in man.
1. The relationship between baroreflex sensitivity (BRS) and arterial compliance index (ACI) has been investigated (a) in paired subjects matched in one instance for systolic blood pressure with differing ages, and (b) in another instance matched for age with differing systolic blood pressures. 2. There was a significant negative correlation between BRS and age and between ACI and age in the twelve systolic blood pressure-matched subjects. 3. A significant negative correlation of systolic blood pressure with both BRS and ACI was observed in the fourteen age-matched subjects. 4. Both BRS and ACI appear to decrease with increasing age and systolic blood pressure. This decrease in BRS is probably due at least in part to the observed reduction in arterial distensibility.


Thermographic Analysis of Tooth Vascularization Using Thermal Stimulation.
The current pulp diagnostic techniques based on subjective patient response to electrical or thermal stimuli are unable to assess tooth vascularization, which is a true indicator of pulp vitality. The present study evaluates thermography as a pulp vitality test, assessing tooth recovery following thermal stimulation. A model simulating intrapulpal circulation was developed. Superficial thermographic measurements were obtained from teeth with and without elevation of the intracoronal temperature before and after applying thermal stress with cold. The data were analyzed using analysis of variance (ANOVA), and the level of significance was set at P<0.05. The model obtained could help differentiate between teeth with and without simulated pulp circulation. Recovery following application of thermal stress showed significant differences between the two types of teeth. Thermography has the potential to be used as a diagnostic tool for the vascularity status of the dental pulp.


Mechanisms of tethering and cargo transfer during epididymosome-sperm interactions.
The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored in preparation for ejaculation. Making important contributions to both processes are epididymosomes, small extracellular vesicles released from the epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining the cargo transferred between epididymosomes and spermatozoa, comparatively less is known about the mechanistic basis of these interactions. To investigate this phenomenon, we have utilized an in vitro co-culture system to track the transfer of biotinylated protein cargo between mouse epididymosomes and recipient spermatozoa isolated from the caput epididymis; an epididymal segment that is of critical importance for promoting sperm maturation. Our data indicate that epididymosome-sperm interactions are initiated via tethering of the epididymosome to receptors restricted to the post-acrosomal domain of the sperm head. Thereafter, epididymosomes mediate the transfer of protein cargo to spermatozoa via a process that is dependent on dynamin, a family of mechanoenzymes that direct intercellular vesicle trafficking. Notably, upon co-culture of sperm with epididymosomes, dynamin 1 undergoes a pronounced relocation between the peri- and post-acrosomal domains of the sperm head. This repositioning of dynamin 1 is potentially mediated via its association with membrane rafts and ideally locates the enzyme to facilitate the uptake of epididymosome-borne proteins. Accordingly, disruption of membrane raft integrity or pharmacological inhibition of dynamin both potently suppress the transfer of biotinylated epididymosome proteins to spermatozoa. Together, these data provide new mechanistic insight into epididymosome-sperm interactions with potential implications extending to the manipulation of sperm maturation for the purpose of fertility regulation.


Both mTORC1 and mTORC2 are involved in the regulation of cell adhesion.
mTOR is a central controller for cell growth/proliferation and survival. Recent studies have shown that mTOR also regulates cell adhesion, yet the underlying mechanism is not known. Here we found that inhibition of mTOR by rapamycin reduced the basal or type I insulin-like growth factor (IGF-1)-stimulated adhesion of cancer cells. Further research revealed that both mTORC1 and mTORC2 were involved in the regulation of cell adhesion, as silencing expression of raptor or rictor inhibited cell adhesion. Also, PP242, an mTORC1/2 kinase inhibitor, inhibited cell adhesion more potently than rapamycin (mTORC1 inhibitor). Of interest, ectopic expression of constitutively active and rapamycin-resistant mutant of p70 kinase 1 (S6K1) or downregulation of eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) conferred resistance to rapamycin inhibition of cell adhesion, whereas expression of constitutively hypophosphorylated 4E-BP1 (4EBP1-5A) or downregulation of S6K1 suppressed cell adhesion. In contrast, neither genetic manipulation of Akt activity nor pharmacological inhibition of Akt affected cell adhesion. The results suggest that both mTORC1 and mTORC2 are involved in the regulation of cell adhesion; and mTORC1 regulates cell adhesion through S6K1 and 4E-BP1 pathways, but mTORC2 regulates cell adhesion via Akt-independent mechanism.


Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis.
The effect of intravenous bicarbonate on the changes in intermediary metabolites during the initial treatment of diabetic ketoacidosis was examined in 16 patients. The results were compared with the changes seen in 16 patients receiving intravenous saline. Infusion of 150 mmol (mEq) bicarbonate significantly delayed the fall in blood lactate, lactate:pyruvate ratio, and total ketone bodies observed in the saline treated group. No difference in the rate of fall of blood glucose concentration was found. There is no metabolic indication for the use of intravenous bicarbonate in the treatment of diabetic ketoacidosis.


Untreated hypertension in the UK household population - Who are missed by the general health checks?
Hypertension is an age-related, long-term condition and a leading risk factor for premature death and disability worldwide. Due to its asymptomatic nature it can often be left undiagnosed. Long-term treatment is available, but blood pressure can also be reduced through health behaviour changes in weight control, smoking cessation, higher physical activity levels, reduced salt and alcohol intake, and healthful diets if discovered early. This paper investigates the prevalence and characteristics of those with untreated (compared to treated) hypertension who did not have a history of cardiovascular disease (CVD); a group who is in effect missed by general health checks. Untreated hypertension was studied in 8933 individuals aged 40-74 years representative of the UK household population, who were interviewed and underwent a physical health examination in their home, 2010-2012. The prevalence of untreated hypertension without a history of CVD was 7% for men, 2% for women, and 5% overall. Untreated hypertension was particularly high among the 55-64 year age group. Age and sex-adjusted analyses found strong positive associations with male gender, smoking, self-reported good-excellent health, full fat dairy preference, white bread preference, higher alcohol consumption, and living alone. Strong negative associations were found for possessing 5 + prescription drugs, statins or antiplatelets, being diagnosed with diabetes or possessing antidiabetics, and long-term limiting illness status. Notably, many reported their health as good to excellent. A fact which emphasises the importance of motivating individuals to take part in the general health checks for an asymptomatic condition such as hypertension.


A multicenter experience of the management of collapsed thoracic endografts.
Thoracic endograft collapse after thoracic endovascular aortic repair (TEVAR) is a potentially devastating complication. This study evaluates the management of thoracic stent graft collapse. A multicenter review of thoracic stent graft collapse was performed from 2005 to 2009. Diagnosis and preoperative planning was performed by computed tomography angiography (CTA). Outcome measures included success of endovascular salvage, postoperative complications, and conversion to open repair. Eleven patients (10 men) with thoracic endograft collapse were identified. Mean age was 41.2 years old (range, 21-66 years). Indications for the index TEVAR were traumatic aortic transections in 8 patients and acute type B dissections in 3 patients. All were initially treated with the TAG endoprosthesis (Gore and Associates, Flagstaff, Ariz). The median duration from initial repair to diagnosis of collapse was 9 days (range, 1 day-38 months). All collapses were initially treated by endovascular means using another TAG device in 7 patients, a Talent (Medtronic, Santa Rosa, Calif) thoracic stent graft in 3 patients, and a Palmaz (Cordis Endovascular, Warren, NJ) stent in 1 patient. In 1 patient, the secondary TAG did not resolve the collapse and required a Palmaz stent placement. Technical success rate was 91%, while re-expansion of the collapsed endograft was achieved in all patients. Early and late complications were observed in 3 patients. Delayed (>30 days) open conversion with device explantation was performed for an aortoesophageal fistula, physiological aortic coarctation, and prevention of a recurrent collapse in 1 patient each. There were no perioperative deaths or recurrent collapses. Endograft collapse can be successfully managed by endovascular techniques in most cases. Redo-TEVAR using high radial force devices should be considered the initial treatment of choice. Late endograft-related complications after treatment of collapsed endografts are not uncommon and can be safely managed by open conversion.


The Impact of the Progressive Efficiency Test on a Rowing Ergometer on White Blood Cells Distribution and Clinical Chemistry Changes in Paralympic Rowers During the Preparatory Stage Before the Paralympic Games in Rio, 2016 - A Case Report.
There is a large gap in knowledge regarding research on post-exercise blood changes in disabled athletes. There are relatively few data on adaptive mechanisms to exercise in disabled athletes, including disabled rowers. Two rowers from a Polish adaptive rowing settle TAMix2x that qualified for the Paralympic Games in Rio, 2016 took part in this study. They performed a progressive test on a rowing ergometer until exhaustion. The cardiorespiratory fitness measures, complete blood count, white blood cells' distribution and 30 clinical chemistry variables describing laboratory diagnostic profiles and general health were determined. The extreme effort induced changes in all studied metabolites (glucose, creatinine, urea, uric acid, total and direct bilirubin), albumin, total protein levels in both participants. Furthermore, a post-exercise increase in aspartate transaminase activity, yet a 2-fold decrease during the recovery time in both rowers were found. White blood cell count increased 2-fold after the test. The percentages of natural killer cells were higher and total T lymphocytes were lower after the exercise protocol. There were higher percentages of suppressor/cytotoxic and lower percentages of helper/inducer T lymphocyte subsets in both studied rowers. No changes in B lymphocytes distribution were observed. Lack of inflammatory symptoms during the experiment suggests a high level of rowers' biological adaptation to the physical effort. The different changes in physiological, biochemical and immunological variables are related to the adaptive mechanism to physical exercise allowing for improvement of performance.


Multiple benefits drive helping behavior in a cooperatively breeding bird: an integrated analysis.
Several hypotheses exist to explain the seemingly altruistic helping behavior of cooperative breeders, although the general utility of these hypotheses remains unclear. While the potential importance of inclusive fitness benefits (kin selection) is traditionally widely appreciated, it is increasingly recognized that direct benefits may be more important than assumed. We use an integrative two-step framework to assess support for current hypotheses in purple-crowned fairy wrens, a species where subordinates vary in relatedness to breeders and helping increases productivity. After establishing that assumptions of pay-to-stay and social prestige hypotheses (predicting that helping functions as "paying rent" to stay on the territory or as a signal of individual quality, respectively) were not met and that parentage by subordinates is extremely rare, we tested whether subordinates adjusted nestling feeding rates following the predictions of the kin selection and group augmentation hypotheses. Benefits of kin selection result from investment in relatives, and group augmentation benefits accrue when subordinates invest more in their own future helpers, for example, when they have a better chance of inheriting the breeding position. We found that subordinates fed siblings more than unrelated nestlings, indicating that kin selection could facilitate cooperation. Moreover, the effect of relatedness on feeding effort varied depending on the probability of inheriting a breeding position, suggesting that active group augmentation can explain investment by unrelated subordinates. This statistical interaction would have gone undetected had we not considered both factors simultaneously, illustrating that a focus on single hypotheses could lead to underestimation of their importance in explaining cooperative breeding.


Contraceptive, estrogenic and anti-estrogenic potentials of methanolic root extract of Carpolobia lutea in rodents.
Several plants are used in herbal medicine for family planning. Carpolobia lutea is a medicinal plant in South Eastern Nigeria used for family planning. The study was designed to investigate the contraceptive, estrogenic and antiestrogenic potentials of the methanolic root extract of Carpolobia lutea in both rats and mice. The contraceptive effect of extract (7 - 21mg/kg) administered by intraperitoneal route for four days in divided doses was tested in mice and rats. Sexually-active males were introduced on day 5 at the ratio of 3F:1M and kept with these females till the end of the experiment. Investigations on the estrogenic and antiestrogenic property of the extract (7-21mg/kg) were done in immature rats that had undergone surgical removal of both ovaries. The effects of the extract (vaginal opening, vaginal cornification, uterine wet weight) were compared with 17-beta-estradiol (0.1µg/rat/day) as standard drug. Twenty-four hours later, the animals were sacrificed following the last dose and the weights of uterus, kidney, liver and small intestine were recorded. The extract prevented conception in both mice and rats for two gestational periods. Significant changes (p<0.05-0.001) were observed in the length and weight of pups relative to control. There were no abnormalities observed in the pups over thirty days. In ovariectomized immature young rats, the extract showed estrogenic effect (vaginal opening, vaginal cornification and increased uterine wet weight) in low doses while in high doses, it showed anti-estrogenic effect. These findings agree with the traditional use of Carpolobia lutea in the control of fertility. The contraceptive property of the extract may be associated with the direct effects of its chemical constituents.


mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.


Microdeletion of chromosome 1q21.3 in fraternal twins is associated with mental retardation, microcephaly, and epilepsy.
Reported here are twins, both of whom have a 1q21.3 microdeletion and who exhibit key features common to previously reported cases such as microcephaly and developmental delay. However, some clinical findings and deleted genes differed from those in previously reported cases. The karyotype was normal 46, XX for both of the twins. Array comparative genomic hybridization (CGH) identified a 2.6 Mb deletion on chromosome 1q21.3 (chr1: 153,514,121-156,171,335 bp) in case 1 and a 1.6 Mb deletion on chromosome 1q21.3 (chr1: 154,748,365-156,358,923 bp) in case 2. The deleted region includes DPM3, MUC1, GBA, PKLR, RIT1, and LAMTOR2 in both siblings. To the extent known, this is the second report of a 1q21.3 microdeletion in a family with mental retardation, developmental delay, seizures, and some dysmorphic features, thus expanding the phenotypic spectrum.


Tissue-specific actions of glucocorticoids on apoptosis: a double-edged sword.
First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.


The role of anillin in meiotic cytokinesis of Drosophila males.
Anillin is a 190 kDa actin-binding protein that concentrates in the leading edges of furrow canals during Drosophila cellularization and in the cleavage furrow of both somatic and meiotic cells. We analyzed anillin behavior during D. melanogaster spermatogenesis, and focused on the relationships between this protein and the F-actin enriched structures. In meiotic anaphases anillin concentrates in a narrow band around the cell equator. Cytological analysis of wild-type meiosis and examination of mutants defective in contractile ring assembly (chickadee and KLP3A), revealed that the formation of the anillin cortical band occurs before, and does not require the assembly of the F-actin based contractile ring. However, once the acto-myosin ring is assembled, the anillin band precisely colocalizes with this cytokinetic structure, accompanying its contraction throughout anaphase and telophase. In chickadee and KLP3A mutant ana-telophases the cortical anillin band fails to constrict, indicating that its contraction is normally driven by the cytokinetic ring. These findings, coupled with the analysis of anillin behavior in twinstar mutants, suggested a model on the role of anillin during cytokinesis. During anaphase anillin would concentrate in the cleavage furrow before the assembly of the contractile ring, binding the equatorial cortex, perhaps through its carboxy-terminal pleckstrin homology (PH) domain. Anillin would then interact with the actin filaments of the acto-myosin ring through its actin-binding domain, anchoring the contractile ring to the plasma membrane throughout cytokinesis.


Time-lapse mapping of cortical changes in schizophrenia with different treatments.
Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 +/- 5.1 SD years) randomized to haloperidol (HAL) (n = 15) or olanzapine (OLZ) treatment (n = 21), imaged at baseline, 3, 6, and 12 months (144 scans). Based on surface-based cortical models and point-by-point measures of gray matter volume, we generated time-lapse maps for each treatment. Disease trajectories differed for atypical versus typical neuroleptic drugs. A rapidly advancing parietal-to-frontal deficit trajectory, in HAL-treated patients, mirrored normal cortical maturation but greatly intensified. The disease trajectory advanced even after symptom normalization, involving the frontal cortex within 12 months with typical drug treatment. Areas with fastest tissue loss shifted anteriorly in the first year of psychosis. This trajectory was not seen with OLZ. Whether this association reflects either reduced neurotoxicity or neuroprotection cannot be addressed with neuroimaging; changes may relate to glial rather than neural components. These maps revise current models of schizophrenia progression; due to power limitations, the findings require confirmation in a sample large enough to model group x time interactions.


Eleventh International Foamy Virus Conference-Meeting Report.
The Eleventh International Foamy Virus Conference took place on 9-10 June 2016 at the Institut Pasteur, Paris, France. The meeting reviewed progress on foamy virus (FV) research, as well as related current topics in retrovirology. FVs are complex retroviruses that are widespread in several animal species. Several research topics on these viruses are relevant to human health: cross-species transmission and viral emergence, vectors for gene therapy, development of antiretroviral drugs, retroviral evolution and its influence on the human genome. In this article, we review the conference presentations on these viruses and highlight the major questions to be answered.


The effects of Con A on cell surface shedding in cell cultures.
A cell surface immobilizing concentration of Con A inhibits the shedding of [3H]fucose-containing glycoproteins from the surface of chick embryonic leg and breast muscle cell cultures and cultures of the rat skeletal muscle cell line L6. The Con A-induced inhibition of shedding is much less in the mouse fibroblast cell line 3T3. In all 4 cell types the lectin inhibits the shedding of some fucosyl-glycoproteins more than others, especially those of a lipid-containing fraction which is excluded in Biogel A-5m chromatography. This differential nature of the Con A effect is not changed by the cytoskeletal disruptors cytochalasin B or colchicine. Con A causes an increase in the amount of trypsin-sensitive surface fucosylglycoprotein in the cell surface and appears to decrease the overall amount of cell surface degradation suggesting the inhibition of shedding caused by Con A is not due to an increase in internalization and degradation. The data suggest that some shedding may occur at specific cell surface sites to which surface materials must laterally migrate.


Limit-cycle oscillations and tubuloglomerular feedback regulation of distal sodium delivery.
A mathematical model was used to evaluate the potential effects of limit-cycle oscillations (LCO) on tubuloglomerular feedback (TGF) regulation of fluid and sodium delivery to the distal tubule. In accordance with linear systems theory, simulations of steady-state responses to infinitesimal perturbations in single-nephron glomerular filtration rate (SNGFR) show that TGF regulatory ability (assessed as TGF compensation) increases with TGF gain magnitude gamma when gamma is less than the critical value gamma(c), the value at which LCO emerge in tubular fluid flow and NaCl concentration at the macula densa. When gamma > gamma(c) and LCO are present, TGF compensation is reduced for both infinitesimal and finite perturbations in SNGFR, relative to the compensation that could be achieved in the absence of LCO. Maximal TGF compensation occurs when gamma approximately gamma(c). Even in the absence of perturbations, LCO increase time-averaged sodium delivery to the distal tubule, while fluid delivery is little changed. These effects of LCO are consequences of nonlinear elements in the TGF system. Because increased distal sodium delivery may increase the rate of sodium excretion, these simulations suggest that LCO enhance sodium excretion.


Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.
Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.


Identifying the miRNA Signature Association with Aging-Related Senescence in Glioblastoma.
Glioblastoma (GBM) is the most common malignant brain tumor and its malignant phenotypic characteristics are classified as grade IV tumors. Molecular interactions, such as protein-protein, protein-ncRNA, and protein-peptide interactions are crucial to transfer the signaling communications in cellular signaling pathways. Evidences suggest that signaling pathways of stem cells are also activated, which helps the propagation of GBM. Hence, it is important to identify a common signaling pathway that could be visible from multiple GBM gene expression data. microRNA signaling is considered important in GBM signaling, which needs further validation. We performed a high-throughput analysis using micro array expression profiles from 574 samples to explore the role of non-coding RNAs in the disease progression and unique signaling communication in GBM. A series of computational methods involving miRNA expression, gene ontology (GO) based gene enrichment, pathway mapping, and annotation from metabolic pathways databases, and network analysis were used for the analysis. Our study revealed the physiological roles of many known and novel miRNAs in cancer signaling, especially concerning signaling in cancer progression and proliferation. Overall, the results revealed a strong connection with stress induced senescence, significant miRNA targets for cell cycle arrest, and many common signaling pathways to GBM in the network.


Is research working for you? Validating a tool to examine the capacity of health organizations to use research.
'Is research working for you? A self-assessment tool and discussion guide for health services management and policy organizations', developed by the Canadian Health Services Research Foundation, is a tool that can help organizations understand their capacity to acquire, assess, adapt, and apply research. Objectives were to: determine whether the tool demonstrated response variability; describe how the tool differentiated between organizations that were known to be lower-end or higher-end research users; and describe the potential usability of the tool. Thirty-two focus groups were conducted among four sectors of Canadian health organizations. In the first hour of the focus group, participants individually completed the tool and then derived a group consensus ranking on items. In the second hour, the facilitator asked about overall impressions of the tool, to identify insights that emerged during the review of items on the tool and to elicit comments on research utilization. Discussion data were analyzed qualitatively, and individual and consensus item scores were analyzed using descriptive and non-parametric statistics. The tool demonstrated good usability and strong response variability. Differences between higher-end and lower-end research use organizations on scores suggested that this tool has adequate discriminant validity. The group discussion based on the tool was the more useful aspect of the exercise, rather than the actual score assigned. The tool can serve as a catalyst for an important discussion about research use at the organizational level; such a discussion, in and of itself, demonstrates potential as an intervention to encourage processes and supports for research translation.


An improved approach for the segmentation of starch granules in microscopic images.
Starches are the main storage polysaccharides in plants and are distributed widely throughout plants including seeds, roots, tubers, leaves, stems and so on. Currently, microscopic observation is one of the most important ways to investigate and analyze the structure of starches. The position, shape, and size of the starch granules are the main measurements for quantitative analysis. In order to obtain these measurements, segmentation of starch granules from the background is very important. However, automatic segmentation of starch granules is still a challenging task because of the limitation of imaging condition and the complex scenarios of overlapping granules. We propose a novel method to segment starch granules in microscopic images. In the proposed method, we first separate starch granules from background using automatic thresholding and then roughly segment the image using watershed algorithm. In order to reduce the oversegmentation in watershed algorithm, we use the roundness of each segment, and analyze the gradient vector field to find the critical points so as to identify oversegments. After oversegments are found, we extract the features, such as the position and intensity of the oversegments, and use fuzzy c-means clustering to merge the oversegments to the objects with similar features. Experimental results demonstrate that the proposed method can alleviate oversegmentation of watershed segmentation algorithm successfully. We present a new scheme for starch granules segmentation. The proposed scheme aims to alleviate the oversegmentation in watershed algorithm. We use the shape information and critical points of gradient vector flow (GVF) of starch granules to identify oversegments, and use fuzzy c-mean clustering based on prior knowledge to merge these oversegments to the objects. Experimental results on twenty microscopic starch images demonstrate the effectiveness of the proposed scheme.


Comprehensive multimodality characterization of hemodynamically significant and non-significant coronary lesions using invasive and noninvasive measures.
There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions. The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures. This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively. Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR <0.8 (n = 9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a lesions without significant stenosis (lesion-QFR>0.8; n = 19) (5.32 (4.47-7.02) vs. 2.42 (1.04-5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68-6.75) vs. 2.09 (0.91-6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions. The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesions.


Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells.
The mechanism of alloantigen-activated spleen cell suppression of mixed lymphocyte reaction (MLR) is explored in this report. Activated murine suppressor spleen cells elaborated a soluble noncytotoxic factor which suppressed MLR responses by 55-95%. Generation of suppressor factor required both in vivo alloantigen sensitization and specific in vitro restimulation. Suppressor factor was not produced by activated spleen cells which had been treated with anti-Thy-1.2 serum and complement. Antigenic specificity toward alloantigens of the stimulator cells was not demonstrable. In contrast, suppressor factor effectively inhibited MLR response only of responder cells of those strains that shared the D-end and the I-C subregion of the H-2 complex with the cells producing suppressor factor. Therefore, active suppression appears to require an MHC-directed homology relationship between regulating and responder cells in MLR.


Tracembler--software for in-silico chromosome walking in unassembled genomes.
Whole genome shotgun sequencing produces increasingly higher coverage of a genome with random sequence reads. Progressive whole genome assembly and eventual finishing sequencing is a process that typically takes several years for large eukaryotic genomes. In the interim, all sequence reads of public sequencing projects are made available in repositories such as the NCBI Trace Archive. For a particular locus, sequencing coverage may be high enough early on to produce a reliable local genome assembly. We have developed software, Tracembler, that facilitates in silico chromosome walking by recursively assembling reads of a selected species from the NCBI Trace Archive starting with reads that significantly match sequence seeds supplied by the user. Tracembler takes one or multiple DNA or protein sequence(s) as input to the NCBI Trace Archive BLAST engine to identify matching sequence reads from a species of interest. The BLAST searches are carried out recursively such that BLAST matching sequences identified in previous rounds of searches are used as new queries in subsequent rounds of BLAST searches. The recursive BLAST search stops when either no more new matching sequences are found, a given maximal number of queries is exhausted, or a specified maximum number of rounds of recursion is reached. All the BLAST matching sequences are then assembled into contigs based on significant sequence overlaps using the CAP3 program. We demonstrate the validity of the concept and software implementation with an example of successfully recovering a full-length Chrm2 gene as well as its upstream and downstream genomic regions from Rattus norvegicus reads. In a second example, a query with two adjacent Medicago truncatula genes as seeds resulted in a contig that likely identifies the microsyntenic homologous soybean locus. Tracembler streamlines the process of recursive database searches, sequence assembly, and gene identification in resulting contigs in attempts to identify homologous loci of genes of interest in species with emerging whole genome shotgun reads. A web server hosting Tracembler is provided at http://www.plantgdb.org/tool/tracembler/, and the software is also freely available from the authors for local installations.


3D-FE analysis of functionally graded structured dental posts.
This study aimed to compare the biomechanical behaviour of functionally graded structured posts (FGSPs) and homogenous-type posts in simulated models of a maxillary central incisor. Two models of FGSPs consisting of a multilayer xTi-yHA composite design, where zirconia and alumina was added as the first layer for models A and B respectively were compared to homogenous zirconia post (model C) and a titanium post (model D). The amount of Ti and HA in the FGSP models was varied in gradations. 3D-FEA was performed on all models and stress distributions were investigated along the dental post. In addition, interface stresses between the posts and their surrounding structures were investigated under vertical, oblique, and horizontal loadings. Strain distribution along the post-dentine interface was also investigated. The results showed that FGSPs models, A and B demonstrated better stress distribution than models C and D, indicating that dental posts with multilayered structure dissipate localized and interfacial stress and strain more efficiently than homogenous-type posts.


Patient perceptions about illness self-management in ANCA-associated small vessel vasculitis.
To characterize patient perceptions, related to eight self-management behaviours relevant for adults with ANCA-associated small vessel vasculitis (ANCA-SVV), and to determine if these perceptions were associated with performance of each behaviour. Adults with ANCA-SVV (n = 202) completed a self-administered questionnaire that assessed eight self-management behaviours (adherence to recommendations for medication, health service use, diet, exercise, infection avoidance and symptom monitoring; prompt reporting of symptoms and side effects; and adjusting activities in response to symptoms), perceptions about these behaviours, socio-demographics, clinical factors and social desirability bias. Descriptive statistics were generated to characterize patients' perceptions about difficulty of, importance of, and specific barriers to performing each behaviour. Regression analyses explored whether these variables were associated with performing each behaviour, controlling for potential confounders. With few exceptions, higher perceived importance and lower perceived difficulty of each behaviour were associated with more frequent performance of the behaviour. For each behaviour, several specific barriers were frequently endorsed by patients and a number of these were associated with lower levels of self-management. This study reveals that patient perceptions about the illness and its treatment influence ANCA-SVV self-management. Perceived barriers to medication, health services, diet and exercise adherence were similar to those in other illnesses. This study also provides insight into barriers experienced by patients in performing behaviours (infection avoidance, symptom monitoring, reporting symptoms and side-effects and adjusting activities) not often previously studied. How the identification of these barriers can help inform future interventions for ANCA-SVV patients is to be discussed.


Attachment to primary care and team-based primary care: Retrospective cohort study of people who experienced imprisonment in Ontario.
To examine attachment to primary care and team-based primary care in the community for people who experienced imprisonment in Ontario, and to compare these attachment data with data for the general population. Population-based retrospective cohort study. Ontario. All persons released from provincial prison in Ontario to the community in 2010 who were linked with provincial health administrative data, and an age- and sex-matched general population group. Primary care attachment and team-based primary care attachment in the 2 years before admission to provincial prison (baseline) and in the 2 years after release in 2010 (follow-up) for the prison release group, and for the corresponding periods for the general population group. People in the prison release group (n = 48 861) were less likely to be attached to primary care compared with the age- and sex-matched general population group (n = 195 444), at 58.9% versus 84.1% at baseline (P < .001) and 63.0% versus 84.4% during follow-up (P < .001), respectively. The difference in attachment to team-based primary care was small in magnitude but statistically significant, at 14.4% versus 16.1% at baseline (P < .001) and 19.9% versus 21.6% during follow-up (P < .001), respectively. People who experience imprisonment have lower primary care attachment compared with the general population. Efforts should be made to understand barriers and to facilitate access to high-quality primary care for this population, including through initiatives to link people while in prison with primary care in the community.


Femtosecond fluorescence dynamics of porphyrin in solution and solid films: the effects of aggregation and interfacial electron transfer between porphyrin and TiO2.
The excited-state relaxation dynamics of a synthetic porphyrin, ZnCAPEBPP, in solution, coated on a glass substrate as solid films, mixed with PMMA and coated on a glass substrate as solid films, and sensitized on nanocrystalline TiO2 films were investigated by using femtosecond fluorescence up-conversion spectroscopy with excitation in the Soret band, S2. We found that the S2--> S1 electronic relaxation of ZnCAPEBPP in solution and on PMMA films occurs in 910 and 690 fs, respectively, but it becomes extremely rapid, <100 fs, in solid films and TiO2 films due to formation of porphyrin aggregates. When probed in the S1 state of porphyrin, the fluorescence transients of the solid films show a biphasic kinetic feature with the rapid and slow components decaying in 1.9-2.4 and 19-26 ps, respectively. The transients in ZnCAPEBPP/TiO2 films also feature two relaxation processes but they occur on different time scales, 100-300 fs and 0.8-4.1 ps, and contain a small offset. According to the variation of relaxation period as a function of molecular density on a TiO2 surface, we assigned the femtosecond component of the TiO2 films as due to indirect interfacial electron transfer through a phenylethynyl bridge attached to one of four meso positions of the porphyrin ring, and the picosecond component arising from intermolecular energy transfer among porphyrins. The observed variation of aggregate-induced relaxation periods between solid and TiO2 films is due mainly to aggregation of two types: J-type aggregation is dominant in the former case whereas H-type aggregation prevails in the latter case.


Covariates and Spatial Interpolation of HIV Screening in Mozambique: Insight from the 2015 AIDS Indicator Survey.
We examined the factors associated with human immunodeficiency virus (HIV) screening and developed a HIV screening prevalence surface map using spatial interpolation techniques to identify the geographical areas with the highest and lowest rates of HIV screening in Mozambique. We analyzed the cross-sectional 2015 Mozambique AIDS Indicator Surveys with an analytic sample of 12,995 participants. Analyses were conducted on SPSS-21, STATA-14, and R freeware 3.5.3. We adjusted for the sample design and population weights. Results indicated that 52.5% of Mozambicans had undergone HIV screening. Mozambicans with these characteristics have a higher probability of undergoing HIV screening: females, those with a primary education or higher, urban dwellers, residents of wealthy households, having at least one lifetime sexual partner, and dwelling in these provinces-Niassa, Tete, Manica, Sofala, Inhambane, Gaza, Maputo Provincia, and Maputo Cidade. The spatial map revealed that the national and regional estimates mask sub-regional level estimates. Generally, zones with the highest HIV screening prevalence are found in southern provinces while the lowest prevalence was found in the northern provinces. The map further revealed intraregional differences in HIV screening estimates. We recommend that HIV screening be expanded, with equitable screening resource allocations that target more nuanced areas within provinces which have a low HIV screening prevalence.


The more the merrier: comparative analysis of microarray studies on cell cycle-regulated genes in fission yeast.
The last two years have seen the publication of three genome-wide gene expression studies of the fission yeast cell cycle. While these microarray papers largely agree on the main patterns of cell cycle-regulated transcription and its control, there are discrepancies with regard to the identity and numbers of periodically expressed genes. We present benchmark and reproducibility analyses showing that the main discrepancies do not reflect differences in the data themselves (microarray or synchronization methods seem to lead only to minor biases) but rather in the interpretation of the data. Our reanalysis of the three datasets reveals that combining all independent information leads to an improved identification of periodically expressed genes. These evaluations suggest that the available microarray data do not allow reliable identification of more than about 500 cell cycle-regulated genes. The temporal expression pattern of the top 500 periodically expressed genes is generally consistent across experiments and the three studies, together with our integrated analysis, provide a coherent and rich source of information on cell cycle-regulated gene expression in Schizosaccharomyces pombe. The reanalysed datasets and other supplementary information are available from an accompanying website: http://www.cbs.dtu.dk/cellcycle/. We hope that this paper will resolve the apparent discrepancies between the previous studies and be useful both for wet-lab biologists and for theoretical scientists who wish to take advantage of the data for follow-up work.


Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition.
The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles ("components") whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech.


Patient perspectives on type 2 diabetes and medicine use during Ramadan among Pakistanis in Denmark.
Type 2 diabetes is highly prevalent among people of Pakistani background. Studies show that adherence to medicines is complicated for people with type 2 diabetes in general. Also, studies indicate that many people with type 2 diabetes and Muslim background fast during the month of Ramadan without adequate counselling on how to adjust their medicines. To explore patient perspectives on medicine use during Ramadan, reasons for fasting and experiences with counselling on medicine use during Ramadan among people of Pakistani background with type 2 diabetes and at least one other chronic condition. Greater Copenhagen, Denmark. The analysis is based on a study exploring lived experiences with counselling on medicines using semi-structured interviews and medication reviews. The analysis presented here builds on the subset of patients with Pakistani background (six interviewers). All interviewees pointed out that Islam allows ill people to refrain from fasting during Ramadan. However, all had fasted during Ramadan despite being diagnosed with type 2 diabetes. While fasting, they adapted their use of medicines in different ways, e.g. by changing the time of intake or by skipping morning medicines. Fasting during Ramadan meant a feeling of improvement in well-being for all interviewees. Reasons for this improvement included physiological, social and religious aspects. Healthcare professionals were rarely included in the decision-making process on whether or not to fast. Instead, friends and relatives, especially those with type 2 diabetes, were considered important to the decision-making process. For people with Muslim background and a chronic condition, fasting during Ramadan may mean changes in medicine use that are not always discussed with healthcare professionals. Healthcare professionals should acknowledge that Muslim patients may find fasting during Ramadan beneficial to their well-being and therefore choose to fast despite the Islamic rule of exemption. This patient-centred approach to counselling on medicines may facilitate better medicine use and thus better clinical health outcomes among patients that choose to fast.


Observations of limited secondary effects to benthic invertebrates and macrophytes with activated carbon amendment in river sediments.
Amendment of activated carbon to sediments has been shown to effectively reduce the bioavailability of hydrophobic organic contaminants, but concerns have been raised about the potential toxicological impacts of administering a strong sorbent into sediments. The present study provides a summary of several investigations carried out as part of a pilot-scale study in a river to understand the secondary effects of activated carbon added to reduce the bioavailability of sediment-associated polychlorinated biphenyls. While some previous laboratory amendment studies have found reduced lipid content in freshwater worms exposed to activated carbon-treated sediments, the authors did not observe an impact with fine-granular activated carbon-amended sediments aged in the field. Benthic community studies did not find differences between control and activated carbon-treated field sites over 3 yr of postapplication monitoring. Laboratory studies with submerged aquatic plants indicated reduced growth in sediments amended with ≥5% activated carbon, which was attributed to volume dilution of nutritional sediment or bulk density changes and was also observed when the sediment was amended with biochar and inert perlite. Since in situ sorbent amendment is likely to be implemented in depositional sediment environments, potential negative impacts will likely be short-term if the treated site is slowly covered with new sediment over time. Overall suitability of activated carbon amendment for a site will depend on balancing ecosystem and human health benefits from contaminant bioavailability reduction with any potential negative impacts expected under field conditions.


Role of dietary modification in alleviating chronic fatigue syndrome symptoms: a systematic review.
To review the evidence for the role of dietary modifications in alleviating chronic fatigue syndrome symptoms. A systematic literature review was guided by PRISMA and conducted using Scopus, CINAHL Plus, Web of Science and PsycINFO scientific databases (1994-2016) to identify relevant studies. Twenty-two studies met the inclusion criteria, the quality of each paper was assessed and data extracted into a standardised tabular format. Positive outcomes were highlighted in some included studies for polyphenol intakes in animal studies, D-ribose supplementation in humans and aspects of symptom alleviation for one of three polynutrient supplement studies. Omega three fatty acid blood levels and supplementation with an omega three fatty acid supplement also displayed positive outcomes in relation to chronic fatigue syndrome symptom alleviation. Limited dietary modifications were found useful in alleviating chronic fatigue syndrome symptoms, with overall evidence narrow and inconsistent across studies. Implications for public health: Due to the individual and community impairment chronic fatigue syndrome causes the population, it is vital that awareness and further focused research on this topic is undertaken to clarify and consolidate recommendations and ensure accurate, useful distribution of information at a population level.


Use of digital retinal imaging in screening for retinopathy of prematurity.
The frequency of premature births is increasing world-wide. This factor, combined with improved survival and revised screening criteria, is resulting in an increased workload in screening for retinopathy of prematurity. Digital retinal imaging is emerging as an important alternative tool for diagnosing retinopathy of prematurity, and its use has even been extended to developing countries. Neonatal nurses and technicians can be trained to use digital imaging devices effectively. This is important in areas that do not have ready access to paediatric ophthalmologists. The ability to transfer images electronically makes it a valuable tool in telemedicine, while the ability to store and retrieve images is also advantageous from a medico-legal perspective. Image analysis software can further improve the accuracy of diagnosis. The main limitation of this technology is its high capital cost.


Epigenetics and cardiovascular disease.
Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only explain a small part of the variability in CVD risk, which is a major obstacle for its prevention and treatment. A more thorough understanding of the factors that contribute to CVD is, therefore, needed to develop more efficacious and cost-effective therapy. Application of the 'omics' technologies will hopefully make these advances a reality. Epigenomics has emerged as one of the most promising areas that will address some of the gaps in our current knowledge of the interaction between nature and nurture in the development of CVD. Epigenetic mechanisms include DNA methylation, histone modification, and microRNA alterations, which collectively enable the cell to respond quickly to environmental changes. A number of CVD risk factors, such as nutrition, smoking, pollution, stress, and the circadian rhythm, have been associated with modification of epigenetic marks. Further examination of these mechanisms may lead to earlier prevention and novel therapy for CVD.


Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME.
Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases. 10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry. IgG levels dropped to median 0.73 g/l (normal 7-16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pretreatment. Frequency of memory B cells significantly decreased and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6-12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening. IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development. Data from our pilot trial warrants further studies in CFS/ME.


Cytoplasmic domains of the reduced folate carrier are essential for trafficking, but not function.
The reduced folate carrier (RFC) protein has a secondary structure consistent with the predicted 12 transmembrane (TM) domains, intracellular N- and C-termini and a large cytoplasmic loop between TM6 and TM7. In the present study, the role of the cytoplasmic domains in substrate transport and protein biogenesis were examined using an array of hamster RFC deletion mutants fused to enhanced green fluorescent protein and expressed in Chinese hamster ovary cells. The N- and C-terminal tails were removed both individually and together, or the large cytoplasmic loop was modified such that the domain size and role of conserved sequences could be examined. The loss of the N- or C-terminal tails did not appear to significantly disrupt protein function, although both termini appeared to have a role in the efficiency with which molecules exited the endoplasmic reticulum to localize at the plasma membrane. There appeared to be both size and sequence requirements for the intracellular loop, which are able to drastically affect protein stability and function unless met. Furthermore, there might be an indirect role for the loop in substrate translocation, since even moderate changes significantly reduced the V(max) for methotrexate transport. Although these cytoplasmic domains do not appear to be absolutely essential for substrate transport, each one is important for biogenesis and localization.


Steroid resistance in Diamond Blackfan anemia associates with p57Kip2 dysregulation in erythroid progenitors.
Despite the effective clinical use of steroids for the treatment of Diamond Blackfan anemia (DBA), the mechanisms through which glucocorticoids regulate human erythropoiesis remain poorly understood. We report that the sensitivity of erythroid differentiation to dexamethasone is dependent on the developmental origin of human CD34+ progenitor cells, specifically increasing the expansion of CD34+ progenitors from peripheral blood (PB) but not cord blood (CB). Dexamethasone treatment of erythroid-differentiated PB, but not CB, CD34+ progenitors resulted in the expansion of a newly defined CD34+CD36+CD71hiCD105med immature colony-forming unit-erythroid (CFU-E) population. Furthermore, proteomics analyses revealed the induction of distinct proteins in dexamethasone-treated PB and CB erythroid progenitors. Dexamethasone treatment of PB progenitors resulted in the specific upregulation of p57Kip2, a Cip/Kip cyclin-dependent kinase inhibitor, and we identified this induction as critical; shRNA-mediated downregulation of p57Kip2, but not the related p27Kip1, significantly attenuated the impact of dexamethasone on erythroid differentiation and inhibited the expansion of the immature CFU-E subset. Notably, in the context of DBA, we found that steroid resistance was associated with dysregulated p57Kip2 expression. Altogether, these data identify a unique glucocorticoid-responsive human erythroid progenitor and provide new insights into glucocorticoid-based therapeutic strategies for the treatment of patients with DBA.


Simulating Groundcover Community Assembly in a Frequently Burned Ecosystem Using a Simple Neutral Model.
Fire is a keystone process that drives patterns of biodiversity globally. In frequently burned fire-dependent ecosystems, surface fire regimes allow for the coexistence of high plant diversity at fine scales even where soils are uniform. The mechanisms on how fire impacts groundcover community dynamics are, however, poorly understood. Because fire can act as a stochastic agent of mortality, we hypothesized that a neutral mechanism might be responsible for maintaining plant diversity. We used the demographic parameters of the unified neutral theory of biodiversity (UNTB) as a foundation to model groundcover species richness, using a southeastern US pine woodland as an example. We followed the fate of over 7,000 individuals of 123 plant species for 4 years and two prescribed burns in frequently burned Pinus palustris sites in northwest FL, USA. Using these empirical data and UNTB-based assumptions, we developed two parsimonious autonomous agent models, which were distinct by spatially explicit and implicit local recruitment processes. Using a parameter sensitivity test, we examined how empirical estimates, input species frequency distributions, and community size affected output species richness. We found that dispersal limitation was the most influential parameter, followed by mortality and birth, and that these parameters varied based on scale of the frequency distributions. Overall, these nominal parameters were useful for simulating fine-scale groundcover communities, although further empirical analysis of richness patterns, particularly related to fine-scale burn severity, is needed. This modeling framework can be utilized to examine our premise that localized groundcover assemblages are neutral communities at high fire frequencies, as well as to examine the extent to which niche-based dynamics determine community dynamics when fire frequency is altered.


Screening of ectoparasites from domesticated dogs for bacterial pathogens in Vientiane, Lao PDR.
Arthropod-borne diseases are widespread worldwide and are a complex interaction between animals, humans and ectoparasites. The understanding of the diversity and epidemiology of organisms transmitted by arthropod vectors, and the role of hosts and vectors in transmission of infections remain limited in Lao PDR. What knowledge does exist is primarily focused on more rural regions of the country. This study screened ectoparasites from domestic dogs in Vientiane city for the presence of bacterial pathogens of zoonotic importance. A total of 3,511 arthropod vectors were collected from 112 dogs. Vectors collected were Rhipicephalus sanguineus ticks, Ctenocephalides felis felis and Ctenocephalides felis orientis fleas and Heterodoxus spiniger lice. A sub-sample of vectors from each dog was analysed by PCR to identify the potential bacteria. From 129 vector pools, Rickettsia spp. was detected in 6.7% (7/105) pools of ticks, 86.4% (19/22) pools of fleas and both pools of lice. Sequencing analysis confirmed Rickettsia felis in 13 flea pools and one louse pool and Rickettsia asembonensis in six flea pools. Anaplasmataceae was identified in 14.3% (15/105) tick pools and 100% (22/22) flea pools. Sequencing revealed the presence of Anaplasma platys in ticks and Wolbachia pipientis in fleas. Leptospira spp. was detected in one tick and one louse pool, and Brucella spp. was detected in 12.4% (13/105) tick pools. All samples were negative for Bartonella spp., Coxiella burnetii and Borrelia burgdorferi. This is the first study providing evidence of R. asembonensis in fleas in Laos. Results from this study show arthropods are potential vectors to transmit zoonotic infection in Vientiane city, suggesting humans are at risk of zoonotic infections in the city.


Calmodulin kinase II is required for fight or flight sinoatrial node physiology.
The best understood "fight or flight" mechanism for increasing heart rate (HR) involves activation of a cyclic nucleotide-gated ion channel (HCN4) by beta-adrenergic receptor (betaAR) agonist stimulation. HCN4 conducts an inward "pacemaker" current (I(f)) that increases the sinoatrial nodal (SAN) cell membrane diastolic depolarization rate (DDR), leading to faster SAN action potential generation. Surprisingly, HCN4 knockout mice were recently shown to retain physiological HR increases with isoproterenol (ISO), suggesting that other I(f)-independent pathways are critical to SAN fight or flight responses. The multifunctional Ca(2+) and calmodulin-dependent protein kinase II (CaMKII) is a downstream signal in the betaAR pathway that activates Ca(2+) homeostatic proteins in ventricular myocardium. Mice with genetic, myocardial and SAN cell CaMKII inhibition have significantly slower HRs than controls during stress, leading us to hypothesize that CaMKII actions on SAN Ca(2+) homeostasis are critical for betaAR agonist responses in SAN. Here we show that CaMKII mediates ISO HR increases by targeting SAN cell Ca(2+) homeostasis. CaMKII inhibition prevents ISO effects on SAN Ca(2+) uptake and release from intracellular sarcoplasmic reticulum (SR) stores that are necessary for increasing DDR. CaMKII inhibition has no effect on the ISO response in SAN cells when SR Ca(2+) release is disabled and CaMKII inhibition is only effective at slowing HRs during betaAR stimulation. These studies show the tightly coupled, but previously unanticipated, relationship of CaMKII to the betaAR pathway in fight or flight physiology and establish CaMKII as a critical signaling molecule for physiological HR responses to catecholamines.


Health Competency Standards in Physical Therapist Practice.
Although the physical therapist profession is the leading established, largely nonpharmacological health profession in the world and is committed to health promotion and noncommunicable disease (NCD) prevention, these have yet to be designated as core physical therapist competencies. Based on findings of 3 Physical Therapy Summits on Global Health, addressing NCDs (heart disease, cancer, hypertension, stroke, diabetes, obesity, and chronic lung disease) has been declared an urgent professional priority. The Third Summit established the status of health competencies in physical therapist practice across the 5 World Confederation for Physical Therapy (WCPT) regions with a view to establish health competency standards, this article's focus. Three general principles related to health-focused practice emerged, along with 3 recommendations for its inclusion. Participants acknowledged that specific competencies are needed to ensure that health promotion and NCD prevention are practiced consistently by physical therapists within and across WCPT regions (ie, effective counseling for smoking cessation, basic nutrition, weight control, and reduced sitting and increased activity/exercise in patients and clients, irrespective of their presenting complaints/diagnoses). Minimum accreditable health competency standards within the profession, including use of the WCPT-supported Health Improvement Card, were recommended for inclusion into practice, entry-to-practice education, and research. Such standards are highly consistent with the mission of the WCPT and the World Health Organization. The physical therapist profession needs to assume a leadership role vis-à-vis eliminating the gap between what we know unequivocally about the causes of and contributors to NCDs and the long-term benefits of effective, sustained, nonpharmacological lifestyle behavior change, which no drug nor many surgical procedures have been reported to match.