MetalWalls: Simulating electrochemical interfaces between polarizable electrolytes and metallic electrodes.
Electrochemistry is central to many applications, ranging from biology to energy science. Studies now involve a wide range of techniques, both experimental and theoretical. Modeling and simulations methods, such as density functional theory or molecular dynamics, provide key information on the structural and dynamic properties of the systems. Of particular importance are polarization effects of the electrode/electrolyte interface, which are difficult to simulate accurately. Here, we show how these electrostatic interactions are taken into account in the framework of the Ewald summation method. We discuss, in particular, the formal setup for calculations that enforce periodic boundary conditions in two directions, a geometry that more closely reflects the characteristics of typical electrolyte/electrode systems and presents some differences with respect to the more common case of periodic boundary conditions in three dimensions. These formal developments are implemented and tested in MetalWalls, a molecular dynamics software that captures the polarization of the electrolyte and allows the simulation of electrodes maintained at a constant potential. We also discuss the technical aspects involved in the calculation of two sets of coupled degrees of freedom, namely the induced dipoles and the electrode charges. We validate the implementation, first on simple systems, then on the well-known interface between graphite electrodes and a room-temperature ionic liquid. We finally illustrate the capabilities of MetalWalls by studying the adsorption of a complex functionalized electrolyte on a graphite electrode.


Estimated amount of 24-hour urine sodium excretion is positively correlated with stomach and breast cancer prevalence in Korea.
Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.


Data assimilation as a nonlinear dynamical systems problem: stability and convergence of the prediction-assimilation system.
We study prediction-assimilation systems, which have become routine in meteorology and oceanography and are rapidly spreading to other areas of the geosciences and of continuum physics. The long-term, nonlinear stability of such a system leads to the uniqueness of its sequentially estimated solutions and is required for the convergence of these solutions to the system's true, chaotic evolution. The key ideas of our approach are illustrated for a linearized Lorenz system. Stability of two nonlinear prediction-assimilation systems from dynamic meteorology is studied next via the complete spectrum of their Lyapunov exponents; these two systems are governed by a large set of ordinary and of partial differential equations, respectively. The degree of data-induced stabilization is crucial for the performance of such a system. This degree, in turn, depends on two key ingredients: (i) the observational network, either fixed or data-adaptive, and (ii) the assimilation method.


Patient Discharge Instructions in the Emergency Department and Their Effects on Comprehension and Recall of Discharge Instructions: A Systematic Review and Meta-analysis.
We conduct a systematic review with meta-analysis to provide an overview of the different manners of providing discharge instructions in the emergency department (ED) and to assess their effects on comprehension and recall of the 4 domains of discharge instructions: diagnosis, treatment, follow-up, and return instructions. We performed a systematic search in the PubMed, EMBASE, Web of Science Google Scholar, and Cochrane databases for studies published before March 15, 2018. A quality assessment of included articles was performed. Pooled proportions of correct recall by manner of providing discharge instructions were calculated. A total of 1,842 articles were screened, and after selection, 51 articles were included. Of the 51 included studies, 12 used verbal discharge instructions only, 30 used written discharge instructions, and 7 used video. Correct recall of verbal, written, and video discharge instructions ranged from 8% to 94%, 23% to 92%, and 54% to 89%, respectively. Meta-analysis was performed on data of 1,460 patients who received verbal information only, 3,395 patients who received written information, and 459 patients who received video information. Pooled data showed differences in correct recall, with, on average, 47% for patients who received verbal information (95% confidence interval 32.2% to 61.7%), 58% for patients who received written information (95% confidence interval 44.2% to 71.2%), and 67% for patients who received video information (95% confidence interval 57.9% to 75.7%). Communicating discharge instructions verbally to patients in the ED may not be sufficient. Although overall correct recall was not significantly higher, adding video or written information to discharge instructions showed promising results for ED patients.


Dyspareunia in women.
Dyspareunia is recurrent or persistent pain with sexual activity that causes marked distress or interpersonal conflict. It affects approximately 10% to 20% of U.S. women. Dyspareunia can have a significant impact on a woman's mental and physical health, body image, relationships with partners, and efforts to conceive. The patient history should be taken in a nonjudgmental way and progress from a general medical history to a focused sexual history. An educational pelvic examination allows the patient to participate by holding a mirror while the physician explains normal and abnormal findings. This examination can increase the patient's perception of control, improve self-image, and clarify findings and how they relate to discomfort. The history and physical examination are usually sufficient to make a specific diagnosis. Common diagnoses include provoked vulvodynia, inadequate lubrication, postpartum dyspareunia, and vaginal atrophy. Vaginismus may be identified as a contributing factor. Treatment is directed at the underlying cause of dyspareunia. Depending on the diagnosis, pelvic floor physical therapy, lubricants, or surgical intervention may be included in the treatment plan.


Surveillance for Foodborne Disease Outbreaks - United States, 2009-2015.
Known foodborne disease agents are estimated to cause approximately 9.4 million illnesses each year in the United States. Although only a small subset of illnesses are associated with recognized outbreaks, data from outbreak investigations provide insight into the foods and pathogens that cause illnesses and the settings and conditions in which they occur. 2009-2015 DESCRIPTION OF SYSTEM: The Foodborne Disease Outbreak Surveillance System (FDOSS) collects data on foodborne disease outbreaks, which are defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. Since the early 1960s, foodborne outbreaks have been reported voluntarily to CDC by state, local, and territorial health departments using a standard form. Beginning in 2009, FDOSS reporting was made through the National Outbreak Reporting System, a web-based platform launched that year. During 2009-2015, FDOSS received reports of 5,760 outbreaks that resulted in 100,939 illnesses, 5,699 hospitalizations, and 145 deaths. All 50 states, the District of Columbia, Puerto Rico, and CDC reported outbreaks. Among 2,953 outbreaks with a single confirmed etiology, norovirus was the most common cause of outbreaks (1,130 outbreaks [38%]) and outbreak-associated illnesses (27,623 illnesses [41%]), followed by Salmonella with 896 outbreaks (30%) and 23,662 illnesses (35%). Outbreaks caused by Listeria, Salmonella, and Shiga toxin-producing Escherichia coli (STEC) were responsible for 82% of all hospitalizations and 82% of deaths reported. Among 1,281 outbreaks in which the food reported could be classified into a single food category, fish were the most commonly implicated category (222 outbreaks [17%]), followed by dairy (136 [11%]) and chicken (123 [10%]). The food categories responsible for the most outbreak-associated illnesses were chicken (3,114 illnesses [12%]), pork (2,670 [10%]), and seeded vegetables (2,572 [10%]). Multistate outbreaks comprised only 3% of all outbreaks reported but accounted for 11% of illnesses, 34% of hospitalizations, and 54% of deaths. Foodborne disease outbreaks provide information about the pathogens and foods responsible for illness. Norovirus remains the leading cause of foodborne disease outbreaks, highlighting the continued need for food safety improvements targeting worker health and hygiene in food service settings. Outbreaks caused by Listeria, Salmonella, and STEC are important targets for public health intervention efforts, and improving the safety of chicken, pork, and seeded vegetables should be a priority. The causes of foodborne illness should continue to be tracked and analyzed to inform disease prevention policies and initiatives. Strengthening the capacity of state and local health departments to investigate and report outbreaks will assist with these efforts through identification of the foods, etiologies, and settings linked to these outbreaks.


The structure and growth of valve-pocket thrombi in femoral veins.
The structure of 50 small thrombi in femoral valve pockets and the microscopic contents of 35 apparently empty pockets were studied in an attempt to ascertain the nature of the microscopic nidi from which thrombi form and their manner of growth to visible thrombi. Sixteen thrombi had little or no cellular invasion. Most of these recent structures had two main regions, red areas restricted distally in the pocket by the vein wall, and larger white regions comprising most of the thrombus length and often covering the red areas. Red areas are the early sites of cellular adhesion and invasion and the likely sites of origin of most thrombi. They were usually dominated by red cells and fibrin. White zones, which represent propagation growth, are characterized by many foci of platelets with fibrin borders (platelet-fibrin units). Some red areas also contained platelet-fibrin units but they were few and tiny; platelets were not seen in others and one small wholly red thrombus was devoid of platelets. Degenerative changes in platelet-fibrin units were observed, and it is postulated that many become purely fibrin structures. There was no significant evidence of preceding intimal damage in the vein wall. Therefore nidi are laid down on normal endothelium probably on the vein wall near the apex of the pocket. Some pockets, empty of thrombi, contained condensed foci of red cells or tiny fibrin fragments surfaced by endothelial cells and considered to be the remnants of aborted thrombi; a few contained clumps of platelets or leucocytes. It is postulated that any of these may represent the nidi from which thrombi grow. Several thrombi also incorporated large fat droplets, numerous in two. Fat embolic globules derived from fractures are their likely source.


Evaluation of Chimpanzee Adenovirus and MVA Expressing TRAP and CSP from Plasmodium cynomolgi to Prevent Malaria Relapse in Nonhuman Primates.
Plasmodium vivax is the world's most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80-90% new P. vivax malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of P. vivax infections. Here, we describe the development of new recombinant ChAdOx1 and MVA vectors expressing P. cynomolgi Thrombospondin Related Adhesive Protein (PcTRAP) and the circumsporozoite protein (PcCSP). Both were shown to be immunogenic in mice prior to their assessment in rhesus macaques. We confirmed good vaccine-induced humoral and cellular responses after prime-boost vaccination in rhesus macaques prior to sporozoite challenge. Results indicate that there were no significant differences between mock-control and vaccinated animals after challenge, in terms of protective efficacy measured as the time taken to 1st patency, or as number of relapses. This suggests that under the conditions tested, the vaccination with PcTRAP and PcCSP using ChAdOx1 or MVA vaccine platforms do not protect against pre-erythrocytic malaria or relapses despite good immunogenicity induced by the viral-vectored vaccines.


Clinical characteristics of acute aortic syndrome in korean patients: from the korean multi-center registry of acute aortic syndrome.
Acute aortic syndrome (AAS) is a heterogeneous group of disorders that often present with severe chest or back pain. It includes acute aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis have not been studied in a large number of Korean patients. Therefore, we organized a multi-center registry to identify the clinical characteristics and treatment patterns, as well as long-term outcomes in Korean patients with AAS. Five-hundred twenty-eight patients, who had been diagnosed with AAS, were enrolled into this registry from 10 centers. On a retrospective basis, we collected demographic, laboratory, imaging data, as well as follow-up clinical outcomes by reviewing medical records from individual centers. All the data were collected in core lab and analyzed in detail. The mean patient age was 60.1±14.5 years; the male-to-female ratio was M : F=297 : 231. The prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes (52, 11.1%). The components of AAS that are included in this study are acute AD (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with Stanford B were 54.4% of enrolled patients. Among nearly half of the patients were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and 4.3% underwent endovascular treatment. Overall, the in-hospital event rate was 21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was 42.8 months and there showed 22.9% of total event and 10.1% of death during this period. By organizing a multi-center registry of AAS, we could identify the characteristics of AAS in real-world Korean patients. Further, prospective study is warranted with a larger number of patients.


Kinetics of serum 25-hydroxyvitamin D in haemodialysis patients treated with monthly oral cholecalciferol.
We previously reported that oral cholecalciferol (CCF) (100 000 IU) taken monthly by haemodialysis patients is effective in accomplishing serum 25-hydroxyvitamin D (25-D) levels >75 nmol/L in >80% of cases. We aimed to study the weekly kinetecs of serum 25-D in HD patients receiving oral CCF during the first 6 months of HD. All new HD patients at our dialysis centre during the autumn months of 2011-2014 were offered entry into the study if their baseline serum 25-D level was <75 nmol/L. Oral CCF (100 000 IU) was administrated monthly during an HD session. The kinetic study included weekly serum sampling for 16 weeks, and every other week thereafter. Biological and treatment data were compared between baseline and 6 months after starting HD and CCF. Patients who required calcimimetics, calcitriol and analogues were excluded from the study. The data from 21 patients were available for analysis. These patients had a mean age of 72.2 ± 12 years, 33% were women, 28.5% had diabetes, and 33% had a central venous catheter. Serum 25-D levels increased from 26.8 ± 13 nmol/L at baseline to 102.3 ± 24 nmol/L after 6 months (P < 0.001). Serum calcium and albumin levels both increased during the study period. Serum phosphate level did not change significantly, and serum parathyroid hormone (PTH) level decreased. Serum 25-D level reached a plateau after 11 weeks of oral CCF. Two patients (9.5%) with low baseline 25-D values, had a stable 25-D level <75 nmol/L after 6 months. No peak effect was observed 48 h after the first dose of CCF. The oral administration of 100 000 IU CCF once a month maintains a normal serum level in 90% of HD patients. Serum 25-D level reaches a plateau level after 12 weeks of therapy.


User survey of Nanny Angel Network, a free childcare service for mothers with cancer.
The purpose of the present study was to determine user satisfaction with Nanny Angel Network (nan), a free childcare service for mothers undergoing cancer treatment. All 243 living mothers who had used the nan service were invited by telephone to participate in an online research survey; 197 mothers (81%) consented to participate. The survey, sent by e-mail, consisted of 39 items divided into these categories: demographics, supports, use, satisfaction, and general comments. Of the 197 mothers who consented to receive the e-mailed survey, 104 (53%) completed it. More than 90% of the mothers were very satisfied with the help and support from their Nanny Angel. Many mothers mentioned that the Nanny Angel was most helpful during treatment and medical appointments, with 75% also mentioning that their Nanny Angel helped them to adhere to their scheduled medical appointments. However, 64% felt that they had not received enough visits from their Nanny Angel. Satisfaction with the nan childcare provider was high, but mothers wished the service had been available to them more often. Our study highlights the importance of providing childcare to mothers with inadequate support systems, so as to allow for greater adherence to treatment and medical appointments, and for more time to recover.


Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.
Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698-4151 g) and gestational ages (35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.


Assessing phytotoxicity of trace element-contaminated soils phytomanaged with gentle remediation options at ten European field trials.
Gentle remediation options (GRO), i.e. in situ stabilisation, (aided) phytoextraction and (aided) phytostabilisation, were implemented at ten European sites contaminated with trace elements (TE) from various anthropogenic sources: mining, atmospheric fallout, landfill leachates, wood preservatives, dredged-sediments, and dumped wastes. To assess the performance of the GRO options, topsoil was collected from each field trial, potted, and cultivated with lettuce (Lactuca sativa L.) for 48days. Shoot dry weight (DW) yield, photosynthesis efficiency and major element and TE concentrations in the soil pore water and lettuce shoots were measured. GRO implementation had a limited effect on TE concentrations in the soil pore water, although use of multivariate Co-inertia Analysis revealed a clear amelioration effect in phytomanaged soils. Phytomanagement increased shoot DW yield at all industrial and mine sites, whereas in agricultural soils improvements were produced in one out of five sites. Photosynthesis efficiency was less sensitive than changes in shoot biomass and did not discriminate changes in soil conditions. Based on lettuce shoot DW yield, compost amendment followed by phytoextraction yielded better results than phytostabilisation; moreover shoot ionome data proved that, depending on initial soil conditions, recurrent compost application may be required to maintain crop production with common shoot nutrient concentrations.


Associations between legal performance-enhancing substance use and future cardiovascular disease risk factors in young adults: A prospective cohort study.
Legal performance-enhancing substances (PES), such as creatine, are commonly used by adolescents and young adults. As PES are mostly unregulated by the US Food and Drug Administration, there has been limited empirical attention devoted to examining their long-term safety and health outcomes. Preliminary studies have demonstrated associations between PES use and severe medical events, including hospitalizations and death. PES could be linked to cardiovascular disease (CVD), the most common cause of mortality in the US, by altering the myocardium, vasculature, or metabolism. The objective of this study was to examine prospective associations between the use of legal PES in young adulthood and CVD risk factors at seven-year follow-up. Nationally representative longitudinal cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves III (2001-2002) and IV (2008), were analyzed. Regression models determined the prospective association between the use of legal PES (e.g. creatine monohydrate) and CVD risk factors (e.g. body mass index, diabetes, hypertension, hyperlipidemia), adjusting for relevant covariates. Among the diverse sample of 11,996 male and female participants, no significant differences by PES use in body mass index, diabetes, hypertension, or hyperlipidemia were noted at Wave III. In unadjusted comparisons, legal PES users (versus non-users) were more likely to be White, be male, be college educated, drink alcohol, and engage in weightlifting, exercise, individual sports, team sports, and other strength training. There were no significant prospective associations between legal PES use at Wave III and body mass index, hemoglobin A1c, systolic and diastolic blood pressure, and cholesterol (total, HDL, LDL, triglycerides) deciles at seven-year follow-up (Wave IV), adjusting for demographics, health behaviors, and Wave III CVD risk factors. Similarly, there were no significant prospective associations between legal PES use and diabetes, hypertension, or hyperlipidemia based on objective measures or self-reported medications and diagnoses, adjusting for demographics, health behaviors, and Wave III CVD risk. We do not find evidence for a prospective association between legal PES use and CVD risk factors in young adults over seven years of follow-up, including BMI, diabetes, hypertension, or hyperlipidemia. It should be noted that legal PES use was operationalized dichotomously and as one broad category, which did not account for frequency, amount, or duration of use. Given the lack of regulation and clinical trials data, observational studies can provide much needed data to inform the safety and long-term health associations of legal PES use and, in turn, inform clinical guidance and policy.


Self-Organization of Vocabularies under Different Interaction Orders.
Traditionally, the formation of vocabularies has been studied by agent-based models (primarily, the naming game) in which random pairs of agents negotiate word-meaning associations at each discrete time step. This article proposes a first approximation to a novel question: To what extent is the negotiation of word-meaning associations influenced by the order in which agents interact? Automata networks provide the adequate mathematical framework to explore this question. Computer simulations suggest that on two-dimensional lattices the typical features of the formation of word-meaning associations are recovered under random schemes that update small fractions of the population at the same time; by contrast, if larger subsets of the population are updated, a periodic behavior may appear.


Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging.
The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood. To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months. The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, Aβ positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit. Concentration of plasma total tau. Risk of MCI and dementia; global and domain-specific cognitive decline. Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain Aβ, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient [b] = -0.50 [0.15], P < .001) and global cognition (b = -0.27 [0.10], P = .009) at 15 months. Adjusting for elevated brain Aβ did not attenuate any association. There was no interaction between plasma total tau level and brain Aβ for prognosis with any outcome. These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain Aβ.


A Scalable Strand-Specific Protocol Enabling Full-Length Total RNA Sequencing From Single Cells.
RNA sequencing (RNAseq) has been widely used to generate bulk gene expression measurements collected from pools of cells. Only relatively recently have single-cell RNAseq (scRNAseq) methods provided opportunities for gene expression analyses at the single-cell level, allowing researchers to study heterogeneous mixtures of cells at unprecedented resolution. Tumors tend to be composed of heterogeneous cellular mixtures and are frequently the subjects of such analyses. Extensive method developments have led to several protocols for scRNAseq but, owing to the small amounts of RNA in single cells, technical constraints have required compromises. For example, the majority of scRNAseq methods are limited to sequencing only the 3' or 5' termini of transcripts. Other protocols that facilitate full-length transcript profiling tend to capture only polyadenylated mRNAs and are generally limited to processing only 96 cells at a time. Here, we address these limitations and present a novel protocol that allows for the high-throughput sequencing of full-length, total RNA at single-cell resolution. We demonstrate that our method produced strand-specific sequencing data for both polyadenylated and non-polyadenylated transcripts, enabled the profiling of transcript regions beyond only transcript termini, and yielded data rich enough to allow identification of cell types from heterogeneous biological samples.


Relationship of household salt intake level with long-term all-cause and cardiovascular disease mortality in Japan: NIPPON DATA80.
In Asian countries, a major source of salt intake is from seasoning or table salt added at home. However, little is known about the adverse effects of salt intake evaluated according to household unit. We investigated the relationship between household salt intake level and mortality from all-cause and cardiovascular diseases (CVDs). Participants included 8702 individuals (56% women) who were living with someone else and who were aged 30-79 years and enrolled in the National Nutritional Survey of Japan in 1980 with a 24-year follow-up. Household nutrient intake was evaluated using a 3-day weighing record method in which all foods and beverages consumed by any of the household members were recorded. The household salt intake level was defined as the amount of salt consumed (g) per 1000 kcal of total energy intake in each household, and its average was 6.25 (2.02) g/1000 kcal. During the follow-up, there were 2360 deaths (787 CVD, 168 coronary heart disease [CHD], and 361 stroke). Cox proportional hazard ratios (HRs) for an increment of 2 g/1000 kcal in household salt intake were calculated and adjusting for sex, age, body mass index, smoking status, alcohol consumption status, self-reported work exertion level, household potassium intake, household saturated fatty acid intake, and household long-chain n-3 polyunsaturated fatty acid intake. The HRs (95% confidence intervals) were 1.07 (1.02, 1.12) for all-cause mortality, 1.11 (1.03, 1.19) for CVD, 1.25 (1.08, 1.44) for CHD, and 1.12 (1.00, 1.25) for stroke. The household salt intake level was significantly associated with long-term risk of all-cause, CVD, CHD, and stroke mortality in a representative Japanese population.


What do we know about child abuse and neglect patterns of co-occurrence? A systematic review of profiling studies and recommendations for future research.
Latent class (LCA) and latent profile (LPA) analysis represent methodological approaches to identify subgroups of maltreated individuals. Although research examining child abuse and neglect (CAN) profiles is still rare, the application of person-centered techniques to clarify CAN types co-occurrence has substantially increased in recent years. Therefore, the aim of the present study was to provide a summary and critical evaluation of the findings of LCA/LPA child maltreatment research to: (a) systemize the current understanding of patterns of maltreatment across populations and (b) elucidate interactive effects of CAN types on psychosocial functioning. A search in PsychInfo, Eric, PubMed, Scopus, and Science Direct, and Google Scholar was performed. Sixteen studies examining the co-occurrence between child physical abuse, emotional abuse, sexual abuse, neglect, and/or exposure to domestic violence were identified. A critical review of the studies revealed inconsistent findings as to the number of CAN classes, but most research uncovered a poly-victimized and a low abuse group. Further, multiple victimization was associated with most adverse internalizing and externalizing outcomes, especially when sexual abuse was present. Exposure to physical and emotional abuse was frequently reported to lead to behavioural problems. Based on the present study results, we provide a set of recommendations for surpassing the current methodological and conceptual limitations in future research.


Steady optical spectra and light propagation dynamics in cold atomic samples with homogeneous or inhomogeneous densities.
We study both steady and dynamic optical responses of three samples with the same amounts of cold atoms but very different density functions. These samples are driven into the regime of electromagnetically induced transparency by a probe and a coupling in the Lambda configuration. When the coupling is in the traveling-wave pattern, all samples have the same transmission spectra and therefore identical transmitted pulses at the sample exits. In the case of a standing-wave coupling, however, very different reflection and transmission spectra are found for the three samples. Accordingly, reflected pulses at the sample entrances and transmitted pulses at the sample exits are quite sensitive to the spatial inhomogeneity of cold atoms. These interesting phenomena are qualitatively analyzed in terms of constructive and destructive interference between forward and backward probe photons scattered by a standing-wave atomic grating.


A dual response organogel system based on an iridium complex and a Eu(iii) hybrid for volatile acid and organic amine vapors.
A thiophene-based hybrid organogel system consisting of complex iridium (Ir) and EuCl3·6H2O was designed and synthesized to realize dual responses to volatile acids and organic amine vapors. The photophysical properties and self-assembly of compound 1 and the hybrid organogel were also studied. Compound 1 could gelate some organic solvents and self-assemble into 3D nanofibers in the gels. The stable hybrid organogel 1-Ir-Eu could be obtained after addition of complex Ir and EuCl3·6H2O. FTIR spectral results showed that the hydrogen bond still remained even upon addition of complex Ir, EuCl3·6H2O, NaOH and CF3COOH to organogel 1. Interestingly, the emission properties of the hybrid organogel 1-Ir-Eu could undergo interconversion between cyan light and red light via addition of NaOH and CF3COOH. The emission properties of xerogel film 1-Ir-Eu obtained in the presence of NaOH could also undergo fast and reversible transition in response to volatile acids such as CF3COOH, formic acid, acetic acid, propionic acid and organic amine vapors such as ammonium hydroxide, Et3N, tripropylamine, and ethylenediamine. The emission spectral change of Ir-Eu in the organogel or xerogel in the presence of base and acid demonstrated the formation of a new complex between complex Ir and EuCl3·6H2O. This dual-response process could be repeated many times. Contact angle experiment results further showed the morphology and internal components of the xerogel film surface in the process of response to gaseous CF3COOH and Et3N. This work provides a method for producing multifunctional supramolecular materials for sensing volatile acids and organic amine vapors.


New insights into the ideal adsorbed solution theory.
The GCMC technique is used for simulation of adsorption of CO2-CH4, CO2-N2 and CH4-N2 mixtures (at 298 K) on six porous carbon models. Next we formulate a new condition of the IAS concept application, showing that our simulated data obey this condition. Calculated deviations between IAS predictions and simulation results increase with the rise in pressure as in the real experiment. For the weakly adsorbed mixture component the deviation from IAS predictions is higher, especially when its content in the gas mixture is low, and this is in agreement with the experimental data. Calculated activity coefficients have similar plots to deviations between IAS and simulations, moreover obtained from simulated data activity coefficients are similar qualitatively as well as quantitatively to experimental data. Since the physical interpretation of activity coefficients is completely lacking we show for the first time that they can be described by the formulas derived from the expression for G(ex) for the ternary mixture. Finally we also for the first time show the linear relationship between the chemical potentials of nonideal and ideal solutions and the reduced temperature of interacting mixture components, and it is proved that the deviation from ideality is larger if adsorption occurs in a more microporous system.


Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.
Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159-62. ©2016 AACR.


Assessment of single risk indicators in relation to caries increment in adolescents.
Base-line data on a series of risk indicators were related to 11-month caries increment in 181 subjects with a mean age of 13 years and 3 months. A caries increment equalling or exceeding one tooth surface was recorded in 21% of the subjects. The risk indicators consisted of past caries experience, white spot lesions, visible plaque and gingivitis, and six salivary tests: secretion rate, buffer effect, sucrase, mutans streptococci, lactobacilli, and Candida. Significant associations between caries increment and past caries experience (p = 0.002), white spot lesions (p = 0.01), lactobacilli (p = 0.02), Candida (p = 0.006), and sucrase (p = 0.02) were observed. The ensuing odds ratios were thus recorded: past caries experience, 3.6; white spot lesions, 2.9; salivary sucrase activity, 2.9; lactobacilli, 2.5; and Candida, 2.8.


Reducing antibiotics for respiratory tract symptoms in primary care: consolidating 'why' and considering 'how'.
We summarize recently published evidence showing that antibiotic treatment offers little or no benefit to most patients presenting with sore throats, acute otitis media, maxillary sinusitis, and acute bronchitis. Despite this research, the prescription of antibiotics for respiratory tract conditions is rising in Britain. This wastes money, encourages people to consult for self-limiting conditions, and causes bacteria to become resistant to antimicrobials. Ways of changing present practice are underresearched. Enhanced consulting skills, guidelines and monitoring strategies, patient education, and anti-inflammatory drugs for recurrent and chronic sufferers all hold promise.


Influence of stance width on frontal plane postural dynamics and coordination in human balance control.
The influence of stance width on frontal plane postural dynamics and coordination in human bipedal stance was studied. We tested the hypothesis that when subjects adopt a narrow stance width, they will rely heavily on nonlinear control strategies and coordinated counter-phase upper and lower body motion to limit center-of-mass (CoM) deviations from upright; as stance increases, the use of these strategies will diminish. Freestanding frontal plane body sway was evoked through continuous pseudorandom rotations of the support surface on which subjects stood with various stimulus amplitudes. Subjects were either eyes open (EO) or closed (EC) and adopted various stance widths. Upper body, lower body, and CoM kinematics were summarized using root-mean-square and peak-to-peak measures, and dynamic behavior was characterized using frequency-response and impulse-response functions. In narrow stance, CoM frequency-response function gains were reduced with increasing stimulus amplitude and in EO compared with EC; in wide stance, gain reductions were much less pronounced. Results show that the narrow stance postural system is nonlinear across stimulus amplitude in both EO and EC conditions, whereas the wide stance postural system is more linear. The nonlinearity in narrow stance is likely caused by an amplitude-dependent sensory reweighting mechanism. Finally, lower body and upper body sway were approximately in-phase at low frequencies (<1 Hz) and out-of-phase at high frequencies (>1 Hz) across all stance widths, and results were therefore inconsistent with the hypothesis that subjects made greater use of coordinated counter-phase upper and lower body motion in narrow compared with wide stance conditions.


Structure-related frustrated magnetism of nanosized polyoxometalates: aesthetics and properties in harmony.
The structural versatility characterizing polyoxometalate chemistry, in combination with the option to deliberately use well-defined building blocks, serves as the foundation for the generation of a large family of magnetic clusters, frequently comprising highly symmetric spin arrays. If the spin centers are coupled by antiferromagnetic exchange, some of these systems exhibit spin frustration, which can result in novel magnetic properties of purely molecular origins. We discuss here the magnetic properties of selected nanosized polyoxometalate clusters featuring spin triangles as their magnetic 'building blocks' or fragments. This includes unique porous Keplerate clusters of the type {(Mo)Mo(5)}(12)M(30) (M = Fe(III), Cr(III), V(IV)) with the spin centers defining a regular icosidodecahedron and the {V(15)As(6)}-type cluster sphere containing a single equilateral spin triangle; these species are widely discussed and studied in the literature for their role in materials science as molecular representations of Kagomé lattices and in relation to quantum computing, respectively. Exhibiting fascinating and unique structural features, these magnetic molecules allow the study of the implications of frustrated spin ordering. Furthermore, this perspective covers the impact of spin frustration on the degeneracy of the ground state and related problems, namely strong magnetic anisotropy and the interplay of antisymmetric exchange and structural Jahn-Teller effects.


ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale.
The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system-that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it-together with the grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required. In this paper, we explain the key challenges and the approaches adopted to overcome them. We also consider wider implications for the present ambitious plans to develop natural-scale, integrated models of the human body that can make contributions to personalized health care, such as the European Virtual Physiological Human initiative. Finally, we ask a key question: How long will it take us to resolve these challenges and when can we expect to have fully functional models that will deliver health-care benefits in the form of personalized care solutions and improved disease prevention?


Nonclassical intensity correlation from a type I phase-matched optical parametric oscillator.
Signal and idler beams from a type I phase-matched nondegenerate optical parametric oscillator are separated by a Mach-Zehnder interferometer. Broadband nonclassical intensity correlation is observed, in agreement with a theory that includes pump noise. The maximum observed correlation, which occurs at 1.1 MHz, yields a noise level 2.8 dB below the shot noise.


Calcium and delayed potassium currents in mouse pancreatic beta-cells under voltage-clamp conditions.
Pancreatic islets of NMRI mice were dissociated into single cells which were kept in tissue culture for 1-3 days. The whole-cell configuration of the patch-clamp technique was used to study inward and delayed outward currents of beta-cells under voltage-clamp conditions at 20-22 degrees C. Outward currents were suppressed by substituting the impermeant cation N-methyl-D-glucamine for intracellular K+. The remaining inward current had a V-shaped current-voltage relation reaching a peak value of 39 +/- 4 pA (mean +/- S.E. of mean) around -15 mV. It was identified as a Ca2+ current, because the peak amplitude was increased 1.6 times by increasing external [Ca2+] ([Ca2+]o) from 2.6 mM to 10 mM and it was blocked by Co2+ (5 mM) or nifedipine (5 microM) but not by TTX (20 microM). The activation time constant of the inward current at -10 mV was 1.28 +/- 0.08 ms. The relation between the degree of activation (estimated from the size of the tail currents) and membrane potential V followed the sigmoidal function f = 1/(1 + exp [(Vh-V)/k]) with half-maximal activation potential, Vh = 4 +/- 1 mV and slope factor, k = 14 +/- 1 mV (for [Ca2+]o 10 mM). The inward current inactivated only weakly during depolarizing pulses of 0.1-1 s duration. The delayed outward current (in experiments with 155 mM-internal [K+] ([K+]i)) had a linear voltage dependence at potentials above -20 mV; its amplitude at -10 mV was 210 +/- 30 pA. Tail currents related to the activation of the outward current had K+-dependent reversal potentials. The current was blocked by extracellularly applied tetraethylammonium (20 mM) and 4-aminopyridine (2 mM). It was not affected by glibenclamide (3 microM), tolbutamide (0.2 mM) and alterations of intracellular [Ca2+] (1 nM-1 microM). The activation time constant of the outward current at -10 mV was 21 +/- 3 ms. The voltage dependence of activation could be described by the sigmoidal function (see above) with Vh = 19 +/- 1 mV and k = 5.6 +/- 0.4 mV. The outward current inactivated during long (15 s) depolarizing pre-pulses (time constant at -10 mV: 2.6 +/- 0.6 s). 50% inactivation occurred at Vh = -36 +/- 2 mV, k was -4.1 +/- 0.2 mV. Inward and outward currents during depolarizing voltage pulses in beta-cells are similar to Ca2+ and delayed K+ currents in other cell types. These currents seem sufficient to generate the action potentials of the beta-cell.


Impact of erythropoietic activity on red cell parameters in chronic renal failure patients.
We measured red cell parameters during recombinant human erythropoietin (rHuEPO) therapy associated with appropriate iron supplementation in chronic hemodialysis patients. Increased erythropoietic activity led to a bias in red cell parameter determination. The percentage of hypochromic red blood cells, usually used as the most effective predictor of response to iron supplementation, increased following the appearance of a younger red cell population since the same Hb content in these younger, larger cells gives a lower Hb concentration.


Caffeic acid phenethyl ester attenuates lipopolysaccharide-stimulated proinflammatory responses in human gingival fibroblasts via NF-κB and PI3K/Akt signaling pathway.
Periodontal diseases often begin with chronic gingival inflammation, which causes the destruction of periodontal tissues. Inflammatory immune responses from host cells to bacteria, such as Porphyromonas gingivalis (P. gingivalis), cause periodontal degradation. Human gingival fibroblasts (HGFs) are the major cells in periodontal soft tissues. When stimulated by lipopolysaccharide (LPS), HGFs could secrete several pro-inflammatory cytokines and chemokines, such as interleukins (ILs) IL-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Caffeic acid phenethyl ester (CAPE) is the main active component of propolis, which is collected by honeybees from different plants and known for its anti-inflammatory effects. The anti-inflammatory effects of CAPE on the LPS-induced HGFs were demonstrated in this study. HGFs were pretreated with CAPE (10, 20, and 30µm) for 1h, followed by LPS stimulation (1μg/ml) for 24h. Enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence staining were used to evaluate the production of IL-6, IL-8, iNOS, and COX-2, as well as the activation of TLR4-mediated NF-κB, PI3K/AKT, and MAPK signaling pathways. The results indicated that CAPE inhibits LPS-induced IL-6, IL-8, iNOS, and COX-2 production in a dose-dependent manner. Moreover, CAPE suppresses LPS-induced TLR4/MyD88 and nuclear factor kappa B (NF-κB) activation. In addition, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) phosphorylation was inhibited by CAPE. These results demonstrated that CAPE could be effective for treating of periodontal diseases.


Number of prior episodes and the presence of depressive symptoms are associated with longer length of stay for patients with acute manic episodes.
Few studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management. This was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS. A total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05). Patients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.


Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study.
The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions.


Time-resolved characterization of the formation of a collisionless shock.
We report on the temporally and spatially resolved detection of the precursory stages that lead to the formation of an unmagnetized, supercritical collisionless shock in a laser-driven laboratory experiment. The measured evolution of the electrostatic potential associated with the shock unveils the transition from a current free double layer into a symmetric shock structure, stabilized by ion reflection at the shock front. Supported by a matching particle-in-cell simulation and theoretical considerations, we suggest that this process is analogous to ion reflection at supercritical collisionless shocks in supernova remnants.


The evolutionary consequences of oxygenic photosynthesis: a body size perspective.
The high concentration of molecular oxygen in Earth's atmosphere is arguably the most conspicuous and geologically important signature of life. Earth's early atmosphere lacked oxygen; accumulation began after the evolution of oxygenic photosynthesis in cyanobacteria around 3.0-2.5 billion years ago (Gya). Concentrations of oxygen have since varied, first reaching near-modern values ~600 million years ago (Mya). These fluctuations have been hypothesized to constrain many biological patterns, among them the evolution of body size. Here, we review the state of knowledge relating oxygen availability to body size. Laboratory studies increasingly illuminate the mechanisms by which organisms can adapt physiologically to the variation in oxygen availability, but the extent to which these findings can be extrapolated to evolutionary timescales remains poorly understood. Experiments confirm that animal size is limited by experimental hypoxia, but show that plant vegetative growth is enhanced due to reduced photorespiration at lower O(2):CO(2). Field studies of size distributions across extant higher taxa and individual species in the modern provide qualitative support for a correlation between animal and protist size and oxygen availability, but few allow prediction of maximum or mean size from oxygen concentrations in unstudied regions. There is qualitative support for a link between oxygen availability and body size from the fossil record of protists and animals, but there have been few quantitative analyses confirming or refuting this impression. As oxygen transport limits the thickness or volume-to-surface area ratio-rather than mass or volume-predictions of maximum possible size cannot be constructed simply from metabolic rate and oxygen availability. Thus, it remains difficult to confirm that the largest representatives of fossil or living taxa are limited by oxygen transport rather than other factors. Despite the challenges of integrating findings from experiments on model organisms, comparative observations across living species, and fossil specimens spanning millions to billions of years, numerous tractable avenues of research could greatly improve quantitative constraints on the role of oxygen in the macroevolutionary history of organismal size.


Phonological Processing in Primary Progressive Aphasia.
Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.


Trefoil factor 3 predicts incident chronic kidney disease: a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) study.
Early detection of individuals at high risk for chronic kidney disease (CKD) may aid prevention. Urinary levels of trefoil factor 3 (TFF3) are associated with acute kidney injury in animal models, but the association of TFF3 levels with incident CKD in humans is unknown. We conducted a case-control study nested within the Atherosclerosis Risk in Communities (ARIC) Study and the ARIC Carotid MRI Study to determine whether urinary TFF3 levels predict incident CKD over 8.6 years of follow-up. A total of 143 participants with incident CKD (eGFR decreasing by ≥25% to <60 ml/min/1.73 m(2)) were matched on age, sex and race to 143 non-cases. Higher TFF3 levels at baseline were strongly associated with Black race, diabetes (both p = 0.002), and antihypertensive medication use (p = 0.02). Compared to participants with TFF3 levels in the lowest quartile, the odds ratio (OR) of incident CKD was 1.84 (95% confidence interval (CI): 0.80, 4.22) for individuals with TFF3 levels in the second quartile, 2.43 (95% CI: 1.06, 5.53) for the third quartile, and 2.77 (95% CI: 1.22, 6.28) for the fourth quartile (p trend = 0.02). Adjustment for covariates, including urinary albumin: creatinine ratio, did not markedly change the associations. Twofold higher TFF3 levels were strongly associated with incident CKD after adjustment for CKD risk factors (adjusted OR = 1.35; 95% CI: 1.11, 1.64). Higher urinary TFF3 levels may indicate ongoing repair of damage in the kidney. Additional studies are needed to confirm whether TFF3 can be useful as a marker of increased risk for CKD.


Th2 cell hyporesponsiveness during chronic murine schistosomiasis is cell intrinsic and linked to GRAIL expression.
Chronic infections are associated with progressively declining T cell function. Infections with helminth parasites, such as Schistosoma mansoni, are often chronic and characterized by the development of strong Th2 responses that peak during the acute stage of infection and then decline despite ongoing infection; this minimizes Th2-dependent immunopathology during the chronic stage of infection. We sought to understand the basis for the decline in Th2 responses in chronic schistosomiasis. Using IL-4 reporter mice (mice that express EGFP as a reporter for Il4 gene expression) to identify Th2 cells, we found that Th2 cell numbers plateaued during acute infection and remained constant thereafter. However, the percentages of Th2 cells proliferating during late infection were strikingly lower than those during acute infection. Th2 cell hyporesponsiveness was evident within 10 d of initiation of the Th2 response and became progressively ingrained thereafter, in response to repeated Ag stimulation. Gene expression analyses implicated the E3-ubiquitin ligase gene related to anergy in lymphocytes (GRAIL) in the hyporesponsive state. Consistent with this, suppression of GRAIL expression using retrovirally delivered siRNA prevented the development of hyporesponsiveness induced by repeated Ag stimulation in vitro or in vivo. Together, these data indicate that the decline in Th2 cell responsiveness during chronic schistosomiasis is the net result of the upregulation of GRAIL expression in response to repeated Ag stimulation.


Extensive Turnover of Compatible Solutes in Cyanobacteria Revealed by Deuterium Oxide (D2O) Stable Isotope Probing.
Cyanobacteria are important primary producers of organic matter in diverse environments on a global scale. While mechanisms of CO2 fixation are well understood, the distribution of the flow of fixed organic carbon within individual cells and complex microbial communities is less well characterized. To obtain a general overview of metabolism, we describe the use of deuterium oxide (D2O) to measure deuterium incorporation into the intracellular metabolites of two physiologically diverse cyanobacteria: a terrestrial filamentous strain (Microcoleus vaginatus PCC 9802) and a euryhaline unicellular strain (Synechococcus sp. PCC 7002). D2O was added to the growth medium during different phases of the diel cycle. Incorporation of deuterium into metabolites at nonlabile positions, an indicator of metabolite turnover, was assessed using liquid chromatography mass spectrometry. Expectedly, large differences in turnover among metabolites were observed. Some metabolites, such as fatty acids, did not show significant turnover over 12-24 h time periods but did turn over during longer time periods. Unexpectedly, metabolites commonly regarded to act as compatible solutes, including glutamate, glucosylglycerol, and a dihexose, showed extensive turnover compared to most other metabolites already after 12 h, but only during the light phase in the cycle. The observed extensive turnover is surprising considering the conventional view on compatible solutes as biosynthetic end points given the relatively slow growth and constant osmotic conditions. This suggests the possibility of a metabolic sink for some compatible solutes (e.g., into glycogen) that allows for rapid modulation of intracellular osmolarity. To investigate this, uniformly 13C-labeled Synechococcus sp. PCC 7002 were exposed to 12C glucosylglycerol. Following metabolite extraction, amylase treatment of methanol-insoluble polymers revealed 12C labeling of glycogen. Overall, our work shows that D2O probing is a powerful method for analysis of cyanobacterial metabolism including discovery of novel metabolic processes.


Pick up and release of micro-objects: a motion-free method to change the conformity of a capillary contact.
We propose a new 3D-printed capillary gripper equipped with a textured surface for motion-free release. The gripper classically picks up micro-objects thanks to the capillary forces induced by a liquid bridge. Micro-objects are released by decreasing the volume of this bridge through evaporation. The latter can be either natural or speeded up by a heating source (an IR laser or the Joule effect). The volume reduction changes the conformity of the contact between the gripper and the object. We analyze the gripper performance and the capillary force generated, and then we rationalize the release mechanism by defining the concept of contact conformity in the context of capillary forces.


Precarious employment, working hours, work-life conflict and health in hotel work.
Precarious or temporary work is associated with adverse outcomes including low control over working hours, work-life conflict and stress. The rise in precarious employment is most marked in the service sector but little research has been done on its health effects in this sector. This study compares permanent and temporary workers in the hotel industry, where working hours are highly variable. Survey data from 150 workers from eight 3-Star hotels in urban and regional areas around Sydney were analyzed. Forty-five per cent were male and 52 per cent were female. Fifty four per cent were permanent full-time and 46 per cent were temporary workers. The effects of employment status on perceived job security, control over working hours, and work-life conflict are investigated using PLS-Graph 3.0. The effects of control over working hours, on work-life conflict and subsequent health outcomes are also explored. Temporary workers perceived themselves as less in control of their working hours, than permanent workers (β = .27). However, they also reported lower levels of work intensity (β = .25) and working hours (β = .38). The effects of low hours control (β = .20), work intensity (β = .29), and excessive hours (β = .39) on work-life conflict (r² = .50), and subsequent health effects (r² = .30), are illustrated in the final structural equation model.


Spatial presentation of biological molecules to cells by localized diffusive transfer.
Cellular decisions in human development, homeostasis, regeneration, and disease are coordinated in large part by signals that are spatially localized in tissues. These signals are often soluble, such that biomolecules produced by one cell diffuse to receiving cells. To recapitulate soluble factor patterning in vitro, several microscale strategies have been developed. However, these techniques often introduce new variables into cell culture experiments (e.g., fluid flow) or are limited in their ability to pattern diverse solutes in a user-defined manner. To address these challenges, we developed an adaptable method that facilitates spatial presentation of biomolecules across cells in traditional open cultures in vitro. This technique employs device inserts that are placed in standard culture wells, which support localized diffusive pattern transmission through microscale spaces between device features and adherent cells. Devices can be removed and cultures can be returned to standard media following patterning. We use this method to spatially control cell labeling with pattern features ranging in scale from several hundred microns to millimeters and with sequential application of multiple patterns. To better understand the method we investigate relationships between pattern fidelity, device geometry, and consumption and diffusion kinetics using finite element modeling. We then apply the method to spatially defining reporter cell heterogeneity by patterning a small molecule modulator of genetic recombination with the requisite sustained exposure. Finally, we demonstrate use of this method for patterning larger and more slowly diffusing particles by creating focal sites of gene delivery and infection with adenoviral, lentiviral, and Zika virus particles. Thus, our method leverages devices that interface with standard culture vessels to pattern diverse diffusible factors, geometries, exposure dynamics, and recipient cell types, making it well poised for adoption by researchers across various fields of biological research.


Perceived stigma and barriers to care in UK Armed Forces personnel and veterans with and without probable mental disorders.
Previous studies have found that perceptions of mental health related stigma can negatively impact help-seeking, particularly in military samples. Moreover, perceptions of stigma and barriers to care can vary between individuals with different psychiatric disorders. The aim of this study was to examine whether perceptions of stigma and barriers to care differed in a UK military sample between those with and without a current likely mental health diagnosis. Structured telephone interviews were carried out with 1432 service personnel and veterans who reported recent subjective mental ill health in the last 3 years. Participants completed self-reported measures relating to perceived stigma, barriers to care and psychological wellbeing. Those meeting criteria for probable common mental disorders (CMD) and PTSD were significantly more likely to report concerns relating to perceived and internalised stigma and barriers to care compared to participants without a likely mental disorder. Compared to individuals with likely CMD and alcohol misuse, those with probable PTSD reported higher levels of stigma-related concerns and barriers to care - although this difference was not significantly different. These results indicate that perceptions of stigma continue to exist in UK serving personnel and military veterans with current probable mental disorders. Efforts to address particular concerns (e.g. being seen as weak; difficulty accessing appointments) may be worthwhile and, ultimately, lead to improvements in military personnel and veteran wellbeing.


The demography of free-roaming dog populations and applications to disease and population control.
1. Understanding the demography of domestic dog populations is essential for effective disease control, particularly of canine-mediated rabies. Demographic data are also needed to plan effective population management. However, no study has comprehensively evaluated the contribution of demographic processes (i.e. births, deaths and movement) to variations in dog population size or density, or determined the factors that regulate these processes, including human factors. 2. We report the results of a 3-year cohort study of domestic dogs, which is the first to generate detailed data on the temporal variation of these demographic characteristics. The study was undertaken in two communities in each of Bali, Indonesia and Johannesburg, South Africa, in rabies-endemic areas and where the majority of dogs were free-roaming. None of the four communities had been engaged in any dog population management interventions by local authorities or animal welfare organizations. All identified dogs in the four communities were monitored individually throughout the study. 3. We observed either no population growth or a progressive decline in population size during the study period. There was no clear evidence that population size was regulated through environmental resource constraints. Rather, almost all of the identified dogs were owned and fed regularly by their owners, consistent with population size regulated by human demand. Finally, a substantial fraction of the dogs originated from outside the population, entirely through the translocation of dogs by people, rather than from local births. These findings demonstrate that previously reported growth of dog populations is not a general phenomenon and challenge the widely held view that free-roaming dogs are unowned and form closed populations. 4.Synthesis and applications. These observations have broad implications for disease and population control. The accessibility of dogs for vaccination and evaluation through owners and the movement of dogs (some of them infected) by people will determine the viable options for disease control strategies. The impact of human factors on population dynamics will also influence the feasibility of annual vaccination campaigns to control rabies and population control through culling or sterilization. The complex relationship between dogs and people is critically important in the transmission and control of canine-mediated rabies. For effective management, human factors must be considered in the development of disease and population control programmes.


Expanded CODIS STR allele frequencies - Evidence for the irrelevance of race-based DNA databases.
The US Federal Bureau of Investigation's (FBI) core Combined DNA Index System (CODIS) short tandem repeat (STR) panel is required for the calculations of random match probabilities (RMPs) in forensic DNA analysis. Current practice dictates that RMPs should be generated across appropriate reference STR allele frequency databases, including African American, Asian, Caucasian, Hispanic, and Native American, when the suspect's race is unknown. Should the suspect declare their race, a specific reference database that pertains to that designation is used. This practice is based on the presumption that racial population group is relevant for calculating conservative RMPs that favor the defendant. The core CODIS panel has been expanded to 20 STRs, however, the relationship between RMP and race has not been re-evaluated. Genetic structure analyses and Bayesian-based population assignment of expanded CODIS profiles from one race-neutral and five race-specific reference databases revealed that STR data could not distinguish races as distinct biological clusters. For instance, while the average race-specific RMPs for Hispanic or Caucasian profiles were almost equally-conservative when calculated from either population's reference database, the Hispanic profiles closely affined with the Native American population. Race-neutral RMPs computed with a correction factor (θ) of 0.03 favor the defendant as much as race-specific RMPs based on a θ of 0.01. Insufficient genetic differentiation observed among the US racial populations as well as inconsequential differences between race-specific and race-neutral RMPs undermine the value of using "race" in the context of forensic DNA analysis and support the argument that forensic databases should be race-neutral.


Changes in human EEG caused by low level modulated microwave stimulation.
This study focuses on the effect of low level microwave radiation on human EEG alpha and theta rhythms. During the experiment, 20 healthy volunteers were exposed to a 450 MHz microwaves with 7 Hz on-off modulation. The field power density at the scalp was 0.16 mW/cm2. Signals from the following EEG channels were used: FP1, FP2, P3, P4, T3, T4, O1, and O2. The experimental protocol consisted of one cycle of short term photic and ten cycles of the repetitive microwave stimulation. The changes caused by photic as well as microwave stimulation were more regular on the alpha rhythm. In the majority of cases, photic stimulation caused changes in the EEG energy level in the occipital and microwave stimulation in the frontal region. Our experimental results demonstrated that microwave stimulation effects became apparent, starting from the third stimulation cycle. Changes varied strongly from subject to subject. Therefore, photic and microwave exposure did not cause statistically significant changes in the EEG activity level for the whole group. For some subjects, clear tendencies of changes in microwave on-off cycles were noticeable.


Giant pH-responsive microgel colloidosomes: preparation, interaction dynamics and stability.
The interactions of two oil droplets grown in the presence of swollen, lightly cross-linked cationic poly(tert-butylamino)ethyl methacrylate (PTBAEMA) microgels was monitored using a high-speed video camera. Three oils (n-dodecane, isopropyl myristate and sunflower oil) were investigated, each in the absence and presence of an oil-soluble cross-linker [tolylene 2,4-diisocyanate-terminated poly(propylene glycol), PPG-TDI]. Adsorption of the swollen microgel particles was confirmed by interfacial tension, interfacial elasticity and dilational viscosity measurements on single pendant oil droplets, and assessment of the oscillatory dynamics for coalescing droplet pairs. Like the analogous bulk emulsions, particle adsorption alone did not prevent coalescence of pairs of giant Pickering emulsion droplets. However, prior addition of surface-active PPG-TDI cross-linker to the oil phase results in the formation of highly stable microgel colloidosomes via reaction with the secondary amine groups on the PTBAEMA chains. Colloidosome stability depended on the age of the oil-water interface. This reflects a balance between the adsorption kinetics of the PPG-TDI cross-linker and the microgel particles, each of which must be present at the interface to form a stable colloidosome. Colloidosome formation was virtually instantaneous in n-dodecane, but took up to 120 s in the case of isopropyl myristate. The impact of an acid-induced latex-to-microgel transition on the interaction of giant colloidosomes (originally prepared at pH 10 using isopropyl myristate) was also studied. This acid challenge did not result in coalescence, which is consistent with a closely-related study (A. J. Morse et al., Langmuir, 2014, 30(42), 12509-12519). No evidence was observed for inter-colloidosome cross-linking, which was attributed to retention of an aqueous film between the adjacent pair of colloidosomes.


Failure of NIV in acute asthma: case report and a word of caution.
Noninvasive ventilation (NIV) is the provision of ventilatory support without the need for an invasive airway, and has revolutionized the management of patients with diverse forms of respiratory failure. The advantages of NIV include improved patient comfort and reduced need for sedation, while avoiding the complications of endotracheal intubation, including upper airway trauma, sinusitis, otitis, and nosocomial pneumonia. In selected patients, NIV has also been shown to improve survival. The role of NIV in acute severe asthma is at best controversial. In this case report, we describe a patient with acute severe asthma who was initially managed and failed with NIV, and was successfully managed with invasive ventilation. We also review the pathophysiological mechanisms of benefit of NIV in acute severe asthma, and the current literature on the use of NIV in acute asthma. In conclusion, a trial of NIV in acute asthma may be justified in carefully selected and monitored patients who do not respond to initial medical therapy. However, as its role is not clear and as the condition of an asthmatic patient may deteriorate abruptly, extreme caution is advisable to recognize failure of NIV as in the case presented here. Facilities for immediate endotracheal intubation and next level of treatment should be readily available.


Angiotensin type 2 receptor (AT2R): a challenging twin.
Angiotensin II (AngII) regulates such physiological responses as salt and water balance, blood pressure, and vascular tone, and thus plays a critical role in the pathogenesis of diabetes, hypertension, myocardial infarction, congestive heart failure, and stroke. These effects are mediated through at least three receptors: AT1R, AT2R, and AT4R, which are expressed under different developmental, tissue-specific, and disease-specific conditions and which couple to distinct effector pathways. Signaling through the AT1R, a classical G protein-coupled receptor, has been extensively studied and is well understood. Less is known about signaling through the AT2R, which often antagonizes the effects of signaling through the AT1R, but intriguing data are beginning to emerge concerning the signaling strategies and pathways that the AT2R employs.


Bilateral limb phase relationship and its potential to alter muscle activity phasing during locomotion.
It is well established that the sensorimotor state of one limb can influence another limb and therefore bilateral somatosensory inputs make an important contribution to interlimb coordination patterns. However, the relative contribution of interlimb pathways for modifying muscle activation patterns in terms of phasing is less clear. Here we studied adaptation of muscle activity phasing to the relative angular positions of limbs using a split-crank ergometer, where the cranks could be decoupled to allow different spatial angular position relationships. Twenty neurologically healthy individuals performed the specified pedaling tasks at different relative angular positions while surface electromyographic (EMG) signals were recorded bilaterally from eight lower extremity muscles. During each experiment, the relative angular crank positions were altered by increasing or decreasing their difference by randomly ordered increments of 30 degrees over the complete cycle [0 degrees (in phase pedaling); 30, 60, 90, 120, 150, and 180 degrees (standard pedaling); and 210, 240, 270, 300, and 330 degrees out of phase pedaling]. We found that manipulating the relative angular positions of limbs in a pedaling task caused muscle activity phasing changes that were either delayed or advanced, dependent on the relative spatial position of the two cranks and this relationship is well-explained by a sine curve. Further, we observed that the magnitude of phasing changes in biarticular muscles (like rectus femoris) was significantly greater than those of uniarticular muscles (like vastus medialis). These results are important because they provide new evidence that muscle phasing can be systematically influenced by interlimb pathways.


Downregulation of HuR as a new mechanism of doxorubicin resistance in breast cancer cells.
HuR, an RNA binding protein involved in the post-transcriptional regulation of a wide spectrum of mRNAs, has been demonstrated to be a determinant of carcinogenesis and tumor aggressiveness in several cancer types. In this study, we investigated the role of HuR in the apoptosis and in the chemoresistance induced by the widely used anticancer drug doxorubicin in human breast cancer cells (MCF-7). We showed that HuR acts in the early phase of cell response to doxorubicin, being induced to translocate into the cytoplasm upon phosphorylation. Reducing HuR levels diminished the apoptotic response to doxorubicin. Doxorubicin-induced apoptosis was also correlated with the presence of HuR in the cytoplasm. Rottlerin, which was able to block HuR nuclear export, had correspondingly antagonistic effects with doxorubicin on cell toxicity. The proapoptotic activity of HuR was not due to cleavage to an active form, as was previously reported. In in vitro selected doxorubicin resistant MCF-7 cells (MCF-7/doxoR) overexpressing the multidrug resistance (MDR) related ABCG2 transporter, we observed a significant HuR downregulation that was paralleled by a corresponding downregulation of HuR targets and by loss of rottlerin toxicity. Restoration of HuR expression in these cells resensitized MCF-7/doxoR cells to doxorubicin, reactivating the apoptotic response. The present study shows that HuR is necessary to elicit the apoptotic cell response to doxorubicin and that restoration of HuR expression in resistant cells resensitizes them to the action of this drug, thereby identifying HuR as a key protein in doxorubicin pharmacology.


Perceptions of electronic cigarettes among ethno-culturally diverse Latino adults in four US urban centers.
The aim of this study was to examine perceptions including knowledge, attitudes, and beliefs about e-cigarettes among ethno-culturally diverse Latino adults living in the US, a rapidly growing minority group for which we know little about their e-cigarette perceptions. A total of 25 focus groups with Latinos (n = 180; ages 18-64 years) were conducted in 2014. E-cigarettes users and non-users were recruited via purposive sampling techniques. Participants completed brief questionnaires on sociodemographic factors and tobacco use. Focus group discussions were conducted in English and Spanish, audio-recorded, and transcribed. Data were analyzed using thematic analysis procedures. Participants were of diverse Latino backgrounds. Over one-third (35%) reported current cigarette smoking and 8% reported current e-cigarette or hookah use. Nonsmokers reported experimenting with e-cigarettes and hookah during social occasions. Participants' perceptions towards e-cigarettes were generally formed in comparison to conventional cigarettes. Perceived benefits of using e-cigarettes included their utility as a smoking cessation aid, higher social acceptability, and lower harm compared to conventional cigarettes. Negative perceptions of e-cigarettes included lower overall satisfaction compared to conventional cigarettes and high content of toxins. Socio-cultural factors (e.g. gender roles, familismo, and simpatía) also influenced perceptions of e-cigarette of study participants. Overall, Latino adults knew relatively little about the potential health risks associated with e-cigarette use. The limited knowledge about and misinformation of e-cigarettes among this rapidly growing minority group have important public health implications. Findings may inform culturally tailored health communication campaigns, which are much needed among underserved US Latino populations in light of low effectiveness of tobacco control and regulatory efforts.


Engineering blood vessels and vascularized tissues: technology trends and potential clinical applications.
Vascular tissue engineering has the potential to make a significant impact on the treatment of a wide variety of medical conditions, including providing in vitro generated vascularized tissue and organ constructs for transplantation. Since the first report on the construction of a biological blood vessel, significant research and technological advances have led to the generation of clinically relevant large and small diameter tissue engineered vascular grafts (TEVGs). However, developing a biocompatible blood-contacting surface is still a major challenge. Researchers are using biomimicry to generate functional vascular grafts and vascular networks. A multi-disciplinary approach is being used that includes biomaterials, cells, pro-angiogenic factors and microfabrication technologies. Techniques to achieve spatiotemporal control of vascularization include use of topographical engineering and controlled-release of growth/pro-angiogenic factors. Use of decellularized natural scaffolds has gained popularity for engineering complex vascularized organs for potential clinical use. Pre-vascularization of constructs prior to implantation has also been shown to enhance its anastomosis after implantation. Host-implant anastomosis is a phenomenon that is still not fully understood. However, it will be a critical factor in determining the in vivo success of a TEVGs or bioengineered organ. Many clinical studies have been conducted using TEVGs, but vascularized tissue/organ constructs are still in the research & development stage. In addition to technical challenges, there are commercialization and regulatory challenges that need to be addressed. In this review we examine recent advances in the field of vascular tissue engineering, with a focus on technology trends, challenges and potential clinical applications.


Error analysis in inverse scatterometry. I. Modeling.
Scatterometry is an optical technique that has been studied and tested in recent years in semiconductor fabrication metrology for critical dimensions. Previous work presented an iterative linearized method to retrieve surface-relief profile parameters from reflectance measurements upon diffraction. With the iterative linear solution model in this work, rigorous models are developed to represent the random and deterministic or offset errors in scatterometric measurements. The propagation of different types of error from the measurement data to the profile parameter estimates is then presented. The improvement in solution accuracies is then demonstrated with theoretical and experimental data by adjusting for the offset errors. In a companion paper (in process) an improved optimization method is presented to account for unknown offset errors in the measurements based on the offset error model.


Exploring Community Mobilization in Northern Quebec: Motivators, Challenges, and Resilience in Action.
Nunavimmiut (people of the land) are the Indigenous peoples of the northern peninsula of the province of Quebec. Communities of Nunavik and its regional organizations have been making concerted efforts in implementing community-based strategies to support family wellbeing. These community strategies are grounded in many of the values underpinning community psychology: favoring empowerment-oriented approaches, fostering community capacity, and transforming organizational cultures to allow for new modes of interaction, as well as new policies and practices that are grounded in community and culture. Despite the growing support and expectation for community mobilization, there is still very little research on the processes and challenges to such mobilization. In this study, we explored the unique challenges and facilitators to community endeavors in northern Quebec in order to better understand the complex dynamics and the strengths that Inuit build upon. We first used a focused ethnographic approach in the context of a 5-year community mobilization project in Nunavik. We then conducted 12 individual interviews and two small group interviews with Inuit working on community-based wellbeing-oriented mobilization projects in four additional communities. Results expose how sociogeographical realities and colonialism influence the process of community mobilization. They also highlight the values and motivational factors that lead community members to move beyond these influences.


[Seroprevalence of Measles Antibodies in Healthcare Professionals in a Central Hospital in Portugal].
Immunity against measles may result from previous contact with the virus or vaccination. In this study we aimed to evaluate the prevalence of immunity to measles in healthcare professionals of a central hospital. Retrospective study, with description of the results of measles-specific IgG assay in healthcare professionals, between May 2010 and March 2018. The results of 1339 healthcare professionals were analyzed. The average age was 39.3 ± 10.11 years, 71.1% female. The prevalence of positive IgG was 81.5%, higher among professionals in the age groups 40 - 49 and over 50 years (91.9% and 94.6% respectively). Healthcare professionals who presented negative or equivocal IgG were mostly under 40 years old (83.1%) (p < 0.05). The prevalence of serological immunity to measles in healthcare professionals was found to be lower than in other studies. That may be due to differences between the characteristics of the studied samples. Susceptibility to measles was higher in lower age groups. These results may reflect low vaccination coverage in this age group, an incomplete vaccination schedule, or the possibility of older healthcare professionals having the disease, which may confer an immune response with higher IgG levels. Knowing the prevalence of susceptibility to measles in healthcare professionals enabled the establishment of prevention strategies for outbreaks that may occur. Vaccination remains the best preventative measure, but a third dose of vaccine may be considered in certain epidemiological contexts, particularly in the youngest exposed healthcare professionals.


Enzyme Tunnels and Gates As Relevant Targets in Drug Design.
Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme's structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features. In addition, we highlight the potential of enzyme tunnels and gates as targets for the binding of small molecules. The different types of binding that are possible and the potential pharmacological benefits of such targeting are discussed. Twelve examples of ligands bound to the tunnels and/or gates of clinically relevant enzymes are used to illustrate the different binding modes and to explain some new strategies for drug design. Such strategies could potentially help to overcome some of the problems facing medicinal chemists and lead to the discovery of more effective drugs.


Behaviour of topological marker proteins targeted to the Tat protein transport pathway.
The Escherichia coli Tat system mediates Sec-independent export of protein precursors bearing twin arginine signal peptides. Formate dehydrogenase-N is a three-subunit membrane-bound enzyme, in which localization of the FdnG subunit to the membrane is Tat dependent. FdnG was found in the periplasmic fraction of a mutant lacking the membrane anchor subunit FdnI, confirming that FdnG is located at the periplasmic face of the cytoplasmic membrane. However, the phenotypes of gene fusions between fdnG and the subcellular reporter genes phoA (encoding alkaline phosphatase) or lacZ (encoding beta-galactosidase) were the opposite of those expected for analogous fusions targeted to the Sec translocase. PhoA fusion experiments have previously been used to argue that the peripheral membrane DmsAB subunits of the Tat-dependent enzyme dimethyl sulphoxide reductase are located at the cytoplasmic face of the inner membrane. Biochemical data are presented that instead show DmsAB to be at the periplasmic side of the membrane. The behaviour of reporter proteins targeted to the Tat system was analysed in more detail. These data suggest that the Tat and Sec pathways differ in their ability to transport heterologous passenger proteins. They also suggest that caution should be observed when using subcellular reporter fusions to determine the topological organization of Tat-dependent membrane protein complexes.


The incidence, prevalence, nature, severity and mechanisms of injury in elite female cricketers: A prospective cohort study.
Incidence, prevalence, nature, severity and mechanisms of injury in elite female cricketers over two seasons from March 2014 to March 2016, inclusive. Prospective cohort study. Injury data collected via Cricket Australia's Athlete Management System on all elite female players over two seasons were analysed. Profiles of the nature, anatomical location and mechanism of injuries were presented according to dominant player position. Injury incidence rates were calculated based on match playing hours. There were 600 medical-attention injuries; with 77.7% players reporting ≥1 injury. There were 79.5% acute injuries compared to gradual onset injuries. Of the all medical-attention injuries, 20.2% led to time-loss; 34.7% were match-time-loss injuries. Match injury incidence was 424.7 injuries/10,000h for all injuries and 79.3 injuries/10,000h for time-loss injuries. Of all the injuries, 31.8% were muscle injuries and 16.0% joint sprains. Wrist and hand (19.8%), lumbar spine (16.5%) and knee (14.9%) injuries were the most common time-loss injuries. Six players sustained lumber spine bone stress injury that resulted in the most days missed due to injury (average 110.5days/injury). There is a need to focus on specific injuries in female cricket, including thigh, wrist/hand and knee injuries because of their frequency, and lumbar spine injuries because of their severity.


Reading and writing assessment scales: preliminary reliability evidences.
Reliability of Reading and Writing Assessment Instruments. To investigate the reliability of two scales created to evaluate both reading and writing of children with ages between 8:0 and 11:11 years. Two scales were created: a reading scale, composed of 12 testing items organized into four competency fields (letter knowledge and phonographemic relation, decoding of isolated items, reading fluency, reading comprehension), and a writing scale, with five items organized into three fields (letter writing and graphophonemic relation, codification of isolated items, writing construction). One hundred students (64 girls) from Public Schools, with ages raging between 8:0 and 11:11 years, were selected. Twenty students (12 girls) participated in the applicability study, resulting in the study version of the Scales. These scales were later applied to the remaining 80 students (52 girls). The obtained responses were assessed and computed for score assignment: item scores, competence field score (CFS) and raw scale score (RSS). Data were submitted to statistical analysis: the Cronbach's alpha coefficient was calculated and correlations between items (Pearson's correlation coefficient) were verified. A significance level of 0.05 was used. a = 0.866 and a = 0.461 were obtained for the Reading and Writing Scales, respectively. Correlations between the items were observed, ranging from weak to strong, and confirmed the alpha values. The Reading Scale was proven reliable, achieving acceptable levels for diagnostic instruments; the Writing Scale did not present an acceptable reliability level to measure the performance of the tested children.