Potential for Sulfate Reduction in Mangrove Forest Soils: Comparison between Two Dominant Species of the Americas.
Avicennia and Rhizophora are globally occurring mangrove genera with different traits that place them in different parts of the intertidal zone. It is generally accepted that the oxidizing capacity of Avicennia roots is larger than that of Rhizophora roots, which initiates more reduced conditions in the soil below the latter genus. We hypothesize that the more reduced conditions beneath Rhizophora stands lead to more active sulfate-reducing microbial communities compared to Avicennia stands. To test this hypothesis, we measured sulfate reduction traits in soil samples collected from neighboring Avicennia germinans and Rhizophora mangle stands at three different locations in southern Florida. The traits measured were sulfate reduction rates (SRR) in flow-through reactors containing undisturbed soil layers in the absence and presence of easily degradable carbon compounds, copy numbers of the dsrB gene, which is specific for sulfate-reducing microorganisms, and numbers of sulfate-reducing cells that are able to grow in liquid medium on a mixture of acetate, propionate and lactate as electron donors. At the tidal locations Port of the Islands and South Hutchinson Islands, steady state SRR, dsrB gene copy numbers and numbers of culturable cells were higher at the A. germinans than at the R. mangle stands, although not significantly for the numbers at Port of the Islands. At the non-tidal location North Hutchinson Island, results are mixed with respect to these sulfate reduction traits. At all locations, the fraction of culturable cells were significantly higher at the R. mangle than at the A. germinans stands. The dynamics of the initial SRR implied a more in situ active sulfate-reducing community at the intertidal R. mangle stands. It was concluded that in agreement with our hypothesis R. mangle stands accommodate a more active sulfate-reducing community than A. germinans stands, but only at the tidal locations. The differences between R. mangle and A. germinans stands were absent at the non-tidal, impounded location.


Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.
The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.


RNA sequencing and transcriptome arrays analyses show opposing results for alternative splicing in patient derived samples.
RNA sequencing (RNA-seq) and microarrays are two transcriptomics techniques aimed at the quantification of transcribed genes and their isoforms. Here we compare the latest Affymetrix HTA 2.0 microarray with Illumina 2000 RNA-seq for the analysis of patient samples - normal lung epithelium tissue and squamous cell carcinoma lung tumours. Protein coding mRNAs and long non-coding RNAs (lncRNAs) were included in the study. Both platforms performed equally well for protein-coding RNAs, however the stochastic variability was higher for the sequencing data than for microarrays. This reduced the number of differentially expressed genes and genes with predictive potential for RNA-seq compared to microarray data. Analysis of this variability revealed a lack of reads for short and low abundant genes; lncRNAs, being shorter and less abundant RNAs, were found especially susceptible to this issue. A major difference between the two platforms was uncovered by analysis of alternatively spliced genes. Investigation of differential exon abundance showed insufficient reads for many exons and exon junctions in RNA-seq while the detection on the array platform was more stable. Nevertheless, we identified 207 genes which undergo alternative splicing and were consistently detected by both techniques. Despite the fact that the results of gene expression analysis were highly consistent between Human Transcriptome Arrays and RNA-seq platforms, the analysis of alternative splicing produced discordant results. We concluded that modern microarrays can still outperform sequencing for standard analysis of gene expression in terms of reproducibility and cost.


Bile duct changes in different etiologic types of end-stage chronic liver disease: a study on native explant livers.
Bile duct changes in the form of intraepithelial neoplasia or dysplasia have been well studied in chronic biliary tract diseases. It is important to analyse the morphologic spectrum of bile duct changes in non-biliary diseases as a link has been reported between intrahepatic cholangiocarcinoma and chronic liver disease associated with viral hepatitis, metabolic syndromes and with alcohol abuse. The authors retrospectively reviewed liver explants of alcoholic liver disease (ALD)-, hepatitis C virus- and non-alcoholic fatty liver disease-related end-stage liver diseases to analyse morphologic changes in large intrahepatic bile ducts. Diagnostic criteria of biliary intraepithelial lesions at end-stage disease are discussed. Majority of explants exhibited reactive changes. Normal cuboidal epithelium of septal bile ducts was observed in minority of cases. Low-grade biliary intraepithelial neoplastic lesions were identified in all cases with variable frequency. None of the cases were associated with cholangiocarcinoma. Nuclear hyperchromasia, cellular polarity and presence o inflammation were considered as differentiating points between reactive and neoplastic lesions. At end stage of liver disease, large septal bile ducts rarely show normal morphology. Presence of low-grade biliary dysplasia at end stage signifies its frequent occurrence probably in response to alcohol/viral/metabolic syndrome-related injury. ADDITION TO LITERATURE: Observational analysis of large bile ducts in non-biliary diseases of varied aetiology has not been discussed from this part of world where incidence of cholangiocarcinoma is low. Identifying these lesions correctly is important. The frequency of these lesions is not uncommon especially at the end-stage liver disease.


LGBT in the Military: Policy Development in Sweden 1944-2014.
This article contributes to the growing field of research on military LGBT policy development by exploring the case of Sweden, a non-NATO-member nation regarded as one of the most progressive in terms of the inclusion of LGBT personnel. Drawing on extensive archival work, the article shows that the story of LGBT policy development in the Swedish Armed Forces from 1944 to 2014 is one of long periods of status quo and relative silence, interrupted by leaps of rapid change, occasionally followed by the re-appearance of discriminatory policy. The analysis brings out two periods of significant change, 1971-1979 and 2000-2009, here described as turns in LGBT policy. During the first turn, the military medical regulation protocol's recommendation to exempt gay men from military service was the key issue. During these years, homosexuality was classified as mental illness, but in the military context it was largely framed in terms of security threats, both on a national level (due to the risk of blackmail) and for the individual homosexual (due to the homophobic military environment). In the second turn, the focus was increasingly shifted from the LGBT individual to the structures, targeting the military organization itself. Furthermore, the analysis shows that there was no ban against LGBT people serving in the Swedish Armed Forces, but that ways of understanding and regulating sexual orientation and gender identity have nonetheless shaped the military organization in fundamental ways, and continue to do so.


Double level osteotomy of the knee: a method to retain joint-line obliquity. Clinical results.
Although general guidelines have been proposed for proximal tibial and supracondylar osteotomies, double level osteotomy provides the advantage of maintaining neutral joint-line obliquity in addition to correcting limb malalignment around the knee. The goal of this prospective study was to determine the outcome of double level osteotomy of the knee performed after analysis with computer-aided preoperative planning software in patients with varus malalignment. Twenty-nine double level osteotomies of the knee were performed in twenty-four patients. The patients were followed for an average duration of 82.7 months (range, twenty-seven to 137 months). All knees had moderate-to-severe varus deformity and arthritis. The mean preoperative mechanical tibiofemoral angle was 193.9 degrees (that is, 13.9 degrees of varus). Preoperative and postoperative evaluations included clinical (scores according to the Knee Society system), radiographic, and computer-aided analysis of the mechanical status of the knee joint. Failure was defined as conversion of an osteotomy to a total knee arthroplasty or the presence of severe pain in a patient who declined arthroplasty. The mean clinical and functional scores according to the Knee Society system improved from 34 and 64 points, respectively, before the osteotomy to 90 (p < 0.0001) and 81 points (p = 0.079) at the time of the final follow-up examination. One patient was lost to follow-up. One of the twenty-nine knees was subsequently converted to total knee arthroplasty forty-nine months postoperatively. The cumulative rate of survival at 100 months was 96% (95% confidence interval, +4.5 to -8.7), with eight patients remaining at risk. Double osteotomy is a valuable procedure for patients with such a large varus deformity that appropriate realignment and load transfer to the unaffected compartment, together with an acceptable joint-line obliquity, cannot be achieved by a single osteotomy.


Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register.
Italy was an important producer of raw asbestos until 1992 (when it was banned) and it is now experiencing severe public health consequences due to large-scale industrial use of asbestos in shipbuilding and repair, asbestos-cement production, railways, buildings, chemicals and many other industrial sectors. Latency of malignant mesothelioma generally shows a large variability and the relationship with the modality of asbestos exposure is still not fully clarified. We present an analysis of latency period among the case list collected by the Italian mesothelioma register (ReNaM) in the period of diagnosis 1993-2001 (2544 malignant mesothelioma (MM) cases with asbestos exposure history). Exposure is assessed retrospectively by interview. Statistical univariate analyses were performed to estimate median and variability measures of latency time by anatomical site, gender and diagnosis period. The role of diagnostic confidence level, the morphology of the tumour and the modalities of asbestos exposure were verified in a regression multivariate model. We found a median latency period of 44.6 years increasing in recent years with a linear trend. Anatomical site, gender and morphology were not relevant for MM latency time whereas a shorter latency period was documented among occupationally exposed subjects (43 years) with respect to environmentally and household exposed ones (48 years).


Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism.
Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Volatile compounds were examined using solid phase microextraction--gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary metabolites with catabolism of branched chain amino acids, alcohol biosynthesis, and β-oxidation of fatty acids. 3) Intracellular chemical development in A. parasiticus is linked to morphological development. 4) Understanding carbon flow through secondary metabolic pathways and catabolism of branched chain amino acids is essential for controlling and customizing production of natural products.


Weight-based dosing of enoxaparin in obese patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE initiative.
To evaluate how enoxaparin is dosed in contemporary clinical practice as a function of patients' total body weight (TBW) and body mass index (BMI), and to determine any association between dose and major bleeding. Retrospective cohort study. The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology-American Heart Association Guidelines (CRUSADE) national quality improvement initiative database. A total of 19,061 patients enrolled in the CRUSADE initiative between January 1, 2004, and March 31, 2006, who received enoxaparin for the initial treatment of non-ST-segment elevation acute coronary syndromes. Demographic and clinical data, enoxaparin doses, and frequency of major bleeding unrelated to coronary artery bypass graft (CABG) surgery were compared among patient groups stratified by TBW(< or = 100, 101-120, 121-150, and > 150 kg). Adjusted odds ratios (OR) of major bleeding unrelated to CABG surgery were calculated with each dose increase of 0.25 mg/kg stratified by BMI (< 18.5, 18.5-24.9, 25.0-29.9, and > or = 30 kg/m(2)), as well as for patients receiving a reduced dose (< 0.95 mg/kg) compared with those receiving a recommended dose (0.95-1.05 mg/kg), stratified by TBW. An inverse association was noted between enoxaparin dose and patient weight. Median initial doses were 1 mg/kg in those weighing 100 kg or less, 0.96 mg/kg in those 101-120 kg, 0.92 mg/kg in those 121-150 kg, and 0.65 mg/kg in those weighing more than 150 kg (p<0.0001 for < or = 100 kg vs > 150 kg). Up to 80% of patients weighing more than 150 kg received an initial enoxaparin dose below the recommended dose. In contrast to patients with normal body weight, those weighing more than 150 kg who received a recommended dose of enoxaparin had a higher bleeding risk relative to those who received a lower dose (adjusted OR 2.42, 95% confidence interval 0.70-8.37). Clinicians tend to use reduced weight-based doses of enoxaparin in overweight and obese patients. Although data are limited, use of the recommended enoxaparin dose of 1 mg/kg is associated with a higher bleeding risk in those weighing more than 150 kg. Thus, further study of enoxaparin dosing in very obese patients with non-ST-segment elevation acute coronary syndromes is warranted.


Modulation of H+ transport mechanisms by interleukin-1 in isolated bovine articular chondrocytes.
The proinflammatory cytokine interleukin-1 (IL-1) promotes the degradation of articular cartilage by inhibiting matrix synthesis and stimulating degradative enzyme activity. Generation of nitric oxide (NO) in response to IL-1 is implicated in these actions. The catabolic actions of IL-1 can be inhibited by manoeuvres which are predicted to dissipate H+ gradients across the chondrocyte plasma membrane. In the present study, the effects of IL-1 on H+ extrusion from bovine articular chondrocytes were investigated. pH was measured using the H+-sensitive fluorescent dye BCECF. Cells were acidified by ammonium rebound and the contribution of the Na+-H+ exchanger (NHE) and of the vacuolar H+-ATPase to acid extrusion was characterised by ion substitution and inhibitor studies. Overnight (18 h) exposure to IL-1 stimulated acid extrusion in a dose-dependent fashion. This effect represented stimulation of both NHE and the ATPase. Characterisation of the timecourse of this response indicated that, while stimulation of acid extrusion was rapid, effects on the ATPase were only apparent after greater than 8h incubation with the cytokine. In keeping with this observation, the protein synthesis inhibitor cycloheximide abolished the stimulatory effect of IL-1 on ATPase-mediated extrusion. The upregulation of ATPase activity by IL-1 was inhibited by the NOS inhibitor L-NAME and by the NO scavenger PTIO. In cells which had not been exposed to IL-1, treatment with the NO donor SNAP also stimulated acid extrusion by the ATPase. In contrast, NHE activity was not altered by any of these compounds. Taken together, these results imply that IL-1 can stimulate acid extrusion in chondrocytes and that this reflects rapid upregulation of NHE with slower induction of H+-ATPase activity which requires elevated levels of NO. While ATPase induction involves protein synthesis, this process may not constitute synthesis of ATPase proteins per se, but rather of some associated regulatory process.


Basic rescue and resuscitation. Trauma system concept in the United States.
Trauma has become the most expensive health care problem in the United States. It is the leading cause of death in persons younger than 44 years old. In 1990, there were approximately 92,000 deaths from trauma, 50% of which were caused by automobile accidents. Before 1976, there was no systemized approach for care of the traumatized patient. The American College of Surgeons Committee on Trauma has developed guidelines covering the spectrum of care of the trauma patient from access and prehospital care to hospital treatment and rehabilitation. The effectiveness of trauma systems has been proven in many studies that show a significant decrease in the preventable death rate in traumatized patients receiving care at a trauma center. The implementation of a national trauma system has proven difficult because of expense, commitment, and effective legislation. Small strides continue to be made, but many hurdles remain.


A well supported multi gene phylogeny of 52 dictyostelia.
The Dictyostelid social amoebas are a popular model system for cell- and developmental biology and for evolution of sociality. Small subunit (SSU) ribosomal DNA-based phylogenies subdivide the known 150 species into four major and some minor groups, but lack resolution within groups, particularly group 4, and, as shown by genome-based phylogenies of 11 species, showed errors in the position of the root and nodes separating major clades. We are interested in the evolution of cell-type specialization, which particularly expanded in group 4. To construct a more robust phylogeny, we first included 7 recently sequenced genomes in the genome-based phylogeny of 47 functionally divergent proteins and next selected 6 proteins (Agl, AmdA, PurD, PurL, RpaA, SmdA) that independently or in sets of two fully reproduced the core-phylogeny. We amplified their coding regions from 34 Dictyostelium species and combined their concatenated sequences with those identified in the 18 genomes to generate a fully resolved phylogeny. The new AAPPRS based phylogeny (after the acronym of the 6 proteins) subdivides group 4 into 2 branches. These branches further resolve into 5 clades, rather than the progressively nested group 4 topology of the SSU rDNA tree, and also re-orders taxa in the other major groups. Ancestral state reconstruction of 25 phenotypic traits returned higher "goodness of fit" metrics for evolution of 19 of those traits over the AAPPRS tree, than over the SSU rDNA tree. The novel tree provides a solid framework for studying the evolution of cell-type specialization, signalling and other cellular processes in particularly group 4, which contains the model Dictyostelid D. discoideum.


Photoplethysmography Enabled Wearable Devices and Stress Detection: A Scoping Review.
Mental and physical health are both important for overall health. Mental health includes emotional, psychological, and social well-being; however, it is often difficult to monitor remotely. The objective of this scoping review is to investigate studies that focus on mental health and stress detection and monitoring using PPG-based wearable sensors. A literature review for this scoping review was conducted using the PRISMA (Preferred Reporting Items for the Systematic Reviews and Meta-analyses) framework. A total of 290 studies were found in five medical databases (PubMed, Medline, Embase, CINAHL, and Web of Science). Studies were deemed eligible if non-invasive PPG-based wearables were worn on the wrist or ear to measure vital signs of the heart (heart rate, pulse transit time, pulse waves, blood pressure, and blood volume pressure) and analyzed the data qualitatively. Twenty-three studies met the inclusion criteria, with four real-life studies, eighteen clinical studies, and one joint clinical and real-life study. Out of the twenty-three studies, seventeen were published as journal-based articles, and six were conference papers with full texts. Because most of the articles were concerned with physiological and psychological stress, we decided to only include those that focused on stress. In twelve of the twenty articles, a PPG-based sensor alone was used to monitor stress, while in the remaining eight papers, a PPG sensor was used in combination with other sensors. The growing demand for wearable devices for mental health monitoring is evident. However, there is still a significant amount of research required before wearable devices can be used easily and effectively for such monitoring. Although the results of this review indicate that mental health monitoring and stress detection using PPG is possible, there are still many limitations within the current literature, such as a lack of large and diverse studies and ground-truth methods, that need to be addressed before wearable devices can be globally useful to patients.


Structure of the Complex of F-Actin and DNGR-1, a C-Type Lectin Receptor Involved in Dendritic Cell Cross-Presentation of Dead Cell-Associated Antigens.
DNGR-1 is a C-type lectin receptor that binds F-actin exposed by dying cells and facilitates cross-presentation of dead cell-associated antigens by dendritic cells. Here we present the structure of DNGR-1 bound to F-actin at 7.7 Å resolution. Unusually for F-actin binding proteins, the DNGR-1 ligand binding domain contacts three actin subunits helically arranged in the actin filament, bridging over two protofilaments, as well as two neighboring actin subunits along one protofilament. Mutation of residues predicted to mediate ligand binding led to loss of DNGR-1-dependent cross-presentation of dead cell-associated antigens, formally demonstrating that the latter depends on F-actin recognition. Notably, DNGR-1 has relatively modest affinity for F-actin but multivalent interactions allow a marked increase in binding strength. Our findings shed light on modes of actin binding by cellular proteins and reveal how extracellular detection of cytoskeletal components by dedicated receptors allows immune monitoring of loss of cellular integrity.


Effects of Ramadan on physical capacities of North African boys fasting for the first time.
Most of the literature related to the effects of Ramadan fasting on physical performance has focused on adults, and only three studies have examined its impact on children's physical performance. To examine the effects of Ramadan fasting on first-time fasting boys' performance in short-term explosive exercises [vertical and horizontal jump tests (VJT and HJT), 20-m and 30-m sprints and medicine-ball throw (MBT)], as well as in sub-maximal endurance [6-min walking distance (6MWD) measured during the 6-min walk test (6MWT)]. Eighteen Tunisian boys [mean±standard deviation (SD) of age and body mass (BM): 11.9±0.8 y and 55.4±18.2 kg, respectively] were included. The experimental design comprised four testing phases: 2-weeks before Ramadan (BR), the end of the second week (R2) and the fourth week (R4) of Ramadan, and 10-12 days after the end of Ramadan (AR). At each phase, boys performed two test sessions in the afternoon (15:00-17:00 h) interrupted by 48 h of recovery (first test session: BM, VJT, HJT, and 20-m and 30-m sprint tests; second session: MBT and 6MWT). The study was conducted during the summer of 2012 from July 5 to August 29. 6MWDs (m) were significantly shorter during R2 (652±101) and R4 (595±123) compared to BR (697±86) and came back to baseline values AR. BM (kg) mean±SD did not significantly change during R2 (52±15) and during R4 (53±15) compared to BR (55±17), and short-term explosive performances were unchanged throughout the study. In non-athletic children, first-ever Ramadan fasting impairs sub-maximal aerobic capacity but has no effect on BM or short-term explosive performance.


Determination of mitochondrial genetic diversity in mammals.
Mitochondrial DNA (mtDNA) is one of the most popular population genetic markers. Its relevance as an indicator of population size and history has recently been questioned by several large-scale studies in animals reporting evidence for recurrent adaptive evolution, at least in invertebrates. Here we focus on mammals, a more restricted taxonomic group for which the issue of mtDNA near neutrality is crucial. By analyzing the distribution of mtDNA diversity across species and relating it to allozyme diversity, life-history traits, and taxonomy, we show that (i) mtDNA in mammals does not reject the nearly neutral model; (ii) mtDNA diversity, however, is unrelated to any of the 14 life-history and ecological variables that we analyzed, including body mass, geographic range, and The World Conservation Union (IUCN) categorization; (iii) mtDNA diversity is highly variable between mammalian orders and families; (iv) this taxonomic effect is most likely explained by variations of mutation rate between lineages. These results are indicative of a strong stochasticity of effective population size in mammalian species. They suggest that, even in the absence of selection, mtDNA genetic diversity is essentially unpredictable, knowing species biology, and probably uncorrelated to species abundance.


Microwave diathermy induces mitogen-activated protein kinases and tumor necrosis factor-α in cultured human monocytes.
Although rehabilitation practice for most patients consists of a combined use of thermotherapy that is produced from diathermy devices resulting faster and deeper heating to the patient, major concerns about occupational exposure to electromagnetic radiation for the operators must be considered. In most occasions, physiotherapists have involved multi-hour treatment sessions to different patients, resulting overuse of the diathermy device. Recently, our team along with other groups have raised serious concerns about the occupational safety aspects related to microwave diathermy (MWD) use. Driven by these recent reports, in this work, we tried to investigate the in vitro effects of a physiotherapist routine MWD device regarding its potential inflammatory biological effects that could be evoked in human cultured monocytes. Our results show that MWD does not alter the integrity of the cell membrane and, consequently, the viability of monocytes as assessed by Trypan blue and MTT measurements. Then again, members of the MAPK family (p38 and ERK1/2) were activated upon MWD exposure at 5-30 min, eventually leading to a time-dependent considerable increase in TNF-α production, a key pro-inflammatory mediator. Our results are indicative of a stress-activated phenomenon of monocytes upon MWD radiation, which could trigger potential hazardous cellular outcomes due to thermal and/or non-thermal bystander effects. Our results deserve further investigation, planned by our team in due course, to delineate the clinical correlations of these findings.


Effect of day-to-day variations in adrenal cortex hormone levels on abdominal symptoms.
The hypothalamic-pituitary-adrenal axis is known to be related to abdominal symptoms, and the relationship between abdominal pain and cortisol secretory patterns has been previously investigated using a cross-sectional approach. Here, we investigated the effect of day-to-day variations in salivary cortisol and dehydroepiandrosterone-sulfate levels on abdominal symptoms in healthy individuals. Eleven college students (4 males and 7 females) participated in this study. The participants were asked to collect their saliva immediately after awakening and before bedtime for eight consecutive days. They also completed a questionnaire about abdominal symptoms before bedtime. The linear mixed model was applied to analyze the effects of the day-by-day variability or the 8-day average adrenal hormone level (at awakening, before bedtime, slope from awakening to bedtime) on abdominal symptoms. The day-to-day variability of cortisol levels before bedtime was negatively related with loose stool, while the day-to-day variability of the cortisol slope was positively correlated with loose stool. A low 8-day average dehydroepiandrosterone-sulfate level at awakening was positively related with frequent bowel movements, loose stool, and long bouts of severe abdominal pain. Likewise, a low 8-day average dehydroepiandrosterone-sulfate slope was positively related with long bouts of abdominal pain. Low cortisol levels before bedtime and a steeper diurnal cortisol slope during the day may be related to bouts of diarrhea during the day.


Initial Host Response to Bacteria in the Murine Lung Differs Between Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae.
Phagocytosis of bacteria is an important process during early host defence. It has been directly observed only ex vivo or in vitro. Here, we report on the observation of phagocytosis under in vivo conditions by using intravital microscopy in the murine lung. Suspensions of fluorescently labelled Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa cells were each instilled intratracheally to anaesthetized mice. After thoracotomy, the alveolar surface was observed for 30 min. Alveolar phagocytes exhibiting ingested bacteria could be detected and counted. The highest numbers were found after the infection with P. aeruginosa. By using intravital microscopy, cellular host defence could be observed in living mice lungs. The initial phagocytic reaction crucially depends on the species of applied bacteria invading the lung.


Methodological guidelines and publications of benefit-risk assessment for health technology assessment: a scoping review protocol.
Benefit-risk assessment (BRA) is used in multiple phases along the health technology's life-cycle to evaluate the balance between the benefits and risks, as it is fundamental to all stakeholders. BRA and its methodological approaches have been applied primarily in the context of regulatory agencies. However, BRA's application and extent in the context of health technology assessment (HTA) bodies remain less clear. Our goal is to perform a scoping review to identify and map methodological guidelines and publications on methods of BRA. This will be done considering the different phases of the life-cycle of health technologies to underline both the depth and extent of research concerning BRA, especially in the context of HTA. This scoping review protocol was developed following the framework proposed by Arksey and O'Malley, and the updated guidelines by the Joanna Briggs Institute. We will include methodological publications that provide recommendations or guidelines on methods for BRA. We will conduct electronic searches on Medline (PubMed) and EMBASE (Ovid) databases; manual searches on the main websites of HTA bodies and drug regulatory organisations; and contact experts in the field. Systematic extraction forms will be used to screen and assess the identified publications by independent assessors. We will provide a qualitative synthesis using descriptive statistics and visual tools. Results will be summarised in systematic evidence tables and comparative evidence scoping charts. This review will use data publicly available and does not require ethics approval. The results of this scoping review will contribute to scientific knowledge and act as a basis for methodologists, guideline developers and researchers for the development of BRA to inform regulatory decisions, reimbursement and coverage decision making. The results will be disseminated through peer-reviewed articles, conferences, policy briefs and workshops. Open Science Framework (https://doi.org/10.17605/OSF.IO/69T3V).


Crystal structures of two complexes of the rare-earth-DOTA-binding antibody 2D12.5: ligand generality from a chiral system.
We report the crystal structures of antibody 2D12.5 Fab bound to an yttrium-DOTA analogue and separately to a gadolinium-DOTA analogue. The rare earth elements have many useful properties as probes, and 2D12.5 binds the DOTA (1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid) complexes of all of them (Corneillie et al. J. Am. Chem. Soc. 2003, 125, 3436-3437). The structures show that there are no direct protein-metal interactions: a bridging water acts as a link between the protein and metal, with the chelate present as the M isomer in each case. DOTA forms an amphipathic cylinder with the charged carboxylate groups toward the face of the chelate near the metal ion, while nonpolar methylene groups from the macrocycle and the carboxymethyl groups occupy the rear and sides of the molecule. The orientation of the metal-DOTA in the 2D12.5 complex places most of the methylene carbon atoms of DOTA in hydrophobic contact with aromatic protein side chains. Other binding interactions between the metal complex and the antibody include a bidentate salt bridge, four direct H-bonds, and four to five water-mediated H-bonds. We find that 2D12.5 exhibits enantiomeric binding generality, binding yttrium chelates in both Lambda(deltadeltadeltadelta) and Delta(lambdalambdalambdalambda) configurations with modestly different affinities. This develops from the symmetrical nature of the DOTA chelate, which places heteroatoms and hydrophobic atoms in approximately the same relative positions regardless of the helicity of DOTA.


Regional cerebral blood flow study with 123I-IMP in patients with degenerative dementia.
Regional cerebral blood flow was evaluated by single-photon emission CT (SPECT) with 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) in 11 patients with dementia of the Alzheimer type, three patients with progressive dementia and motor neuron disease, and eight healthy control subjects. Regional blood flow measurements in the bilateral frontal, parietal association, and temporal cortices were lower in the Alzheimer dementia patients than in controls. Flow deficits in the parietal association cortex were demonstrated in all patients with Alzheimer-type dementia; these deficits were correlated with the severity of disease. Lateral hemispheric asymmetry was seen in nine of 11 patients with Alzheimer-type dementia. In all three patients with progressive dementia and motor neuron disease, flow deficits were demonstrated in the bilateral frontal and temporal cortices, but no flow deficits were seen in the parietal association cortex. Brain SPECT with 123I-IMP may be useful in the differential diagnosis and evaluation of the severity of degenerative dementia.


Informal Caregivers' Learning Experiences With Self-Management Support of Individuals Living With Bipolar Disorder: A Phenomenological Study.
The degree of informal caregiver involvement influences the self-management of individuals living with bipolar disorder (BD). This article aims to provide a description of informal caregivers' learning experiences in self-management support of BD in order to guide professionals in tailoring future psychosocial and psychoeducational interventions. In-depth open interviews with 10 informal caregivers of patients with BD who followed treatment in the context of specialized outpatient bipolar care were conducted. Four learning phases emerged from the phenomenological analysis describing the informal caregivers learning process: (1) understanding BD, (2) overcoming the dilemmas in self-management support for individuals living with BD, (3) dividing tasks and responsibilities, and (4) acquiring a personal definition of self-management support for individuals living with BD. By grasping the concept of BD, informal caregivers gradually learn how to overcome dilemmas resulting from living with someone with BD, and how to control the expression of emotions. They learn to reflect on the nature of conflicts and how to share the responsibilities of illness management with individuals living with BD and professionals. Mastering these skills eventually allows them to define and delimit their supporting informal caregiver role in the self-management of BD. Our findings provide information regarding the educational needs of informal caregivers to tailor counseling, and psychosocial and psychoeducational interventions in specialized outpatient care for individuals living with BD.


Managing uncertainty, ambiguity and ignorance in impact assessment by embedding evolutionary resilience, participatory modelling and adaptive management.
In the context of continuing uncertainty, ambiguity and ignorance in impact assessment (IA) prediction, the case is made that existing IA processes are based on false 'normal' assumptions that science can solve problems and transfer knowledge into policy. Instead, a 'post-normal science' approach is needed that acknowledges the limits of current levels of scientific understanding. We argue that this can be achieved through embedding evolutionary resilience into IA; using participatory workshops; and emphasising adaptive management. The goal is an IA process capable of informing policy choices in the face of uncertain influences acting on socio-ecological systems. We propose a specific set of process steps to operationalise this post-normal science approach which draws on work undertaken by the Resilience Alliance. This process differs significantly from current models of IA, as it has a far greater focus on avoidance of, or adaptation to (through incorporating adaptive management subsequent to decisions), unwanted future scenarios rather than a focus on the identification of the implications of a single preferred vision. Implementing such a process would represent a culture change in IA practice as a lack of knowledge is assumed and explicit, and forms the basis of future planning activity, rather than being ignored.


Technology and Occupation: Past, Present, and the Next 100 Years of Theory and Practice.
During the first 100 years of occupational therapy, the profession developed a remarkable practice and theory base. All along, technology was an active and core component of practice, but often technology was mentioned only as an adjunct component of therapy and as if it was a specialty. This lecture proposes a new foundational theory that places technology at the heart of occupational therapy as a fundamental part of human occupation and the human experience. Moreover, this new Metaphysical Physical-Emotive Theory of Occupation pushes the occupational therapy profession and the occupational science discipline to overtly consider occupation on the level of a metaphysical-level reality. The presentation of this theory at the Centennial of the profession charges the field to test and further define the theory over the next 100 years and to leverage technology and its role in optimizing occupational performance into the future.


Predicting complications in pre-eclampsia: external validation of the fullPIERS model using the PETRA trial dataset.
The internally validated fullPIERS model predicts adverse maternal outcomes in women with pre-eclampsia within 48h after eligibility. Our objective was to assess generalizability of this prediction model. External validation study using prospectively collected data from two tertiary care obstetric centers. The existing PETRA dataset, a cohort of women (n=216) with severe early-onset pre-eclampsia, eclampsia, HELLP syndrome or hypertension-associated fetal growth restriction was used. The fullPIERS model equation was applied to all women in the dataset using values collected within 48h after inclusion. The performance (ROC area and R-squared) of the model, risk stratification and calibration were assessed from 48h up to a week after inclusion. Of 216 women in the PETRA trial, 73 (34%) experienced an adverse maternal outcome(s) at any time after inclusion. Adverse maternal outcome was observed in 32 (15%) cases within 48h and 62 (29%) within 7 days after inclusion. The fullPIERS model predicted adverse maternal outcomes within 48h (AUC ROC 0.97, 95% CI: 0.87-0.99) and up to 7 days after inclusion (AUC ROC 0.80, 95% CI: 0.70-0.87). The fullPIERS model performed well when applied to the PETRA dataset. These results confirm the usability of the fullPIERS prediction model as a 'rule-in' test for women admitted with severe pre-eclampsia, eclampsia, HELLP syndrome or hypertension-associated fetal growth restriction. Future research should focus on intervention studies that assess the clinical impact of strategies using the fullPIERS model.


First carrot, then stick: how the adaptive hybridization of incentives promotes cooperation.
Social institutions often use rewards and penalties to promote cooperation. Providing incentives tends to be costly, so it is important to find effective and efficient policies for the combined use of rewards and penalties. Most studies of cooperation, however, have addressed rewarding and punishing in isolation and have focused on peer-to-peer sanctioning as opposed to institutional sanctioning. Here, we demonstrate that an institutional sanctioning policy we call 'first carrot, then stick' is unexpectedly successful in promoting cooperation. The policy switches the incentive from rewarding to punishing when the frequency of cooperators exceeds a threshold. We find that this policy establishes and recovers full cooperation at lower cost and under a wider range of conditions than either rewards or penalties alone, in both well-mixed and spatial populations. In particular, the spatial dynamics of cooperation make it evident how punishment acts as a 'booster stage' that capitalizes on and amplifies the pro-social effects of rewarding. Together, our results show that the adaptive hybridization of incentives offers the 'best of both worlds' by combining the effectiveness of rewarding in establishing cooperation with the effectiveness of punishing in recovering it, thereby providing a surprisingly inexpensive and widely applicable method of promoting cooperation.


Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation--a randomized controlled trial.
Evidence from in vitro studies suggests that antioxidant olive oil phenolic compounds can prevent LDL oxidation. However, in vivo evidence in support of this hypothesis is sparse. to establish the antioxidant effect of olive oils with differences in their phenolic compounds content in humans A controlled, double blind, cross-over, randomized, clinical trial using three similar olive oils with increasing phenolic concentration (from 0 to 150 mg/Kg) was conducted in 30 healthy volunteers. Olive oils were administered over three periods of 3 weeks preceded by two-week washout periods. Urinary tyrosol and hydroxytyrosol increased (p < 0.020), in vivo plasma oxidized LDL decreased (p = 0.006), and ex vivo resistance of LDL to oxidation increased (p = 0.012) with the phenolic content of the olive oil administered. After virgin olive oil administration, an increase (p = 0.029) was observed in HDL cholesterol levels. Sustained consumption of virgin olive oil with the high phenolic content was more effective in protecting LDL from oxidation and in rising HDL cholesterol levels than that of other type of olive oils. Dose-dependent changes in oxidative stress markers, and phenolic compounds in urine, were observed with the phenolic content of the olive oil administered. Our results support the hypothesis that virgin olive oil consumption could provide benefits in the prevention of oxidative processes.


Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity.
Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F-containing homo- and heterodimers displaying impaired, but not abolished, activity. These experiments of nature indicate that human IL-17A and IL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.


MS1-based label-free proteomics using a quadrupole orbitrap mass spectrometer.
Presented is a data set for benchmarking MS1-based label-free quantitative proteomics using a quadrupole orbitrap mass spectrometer. Escherichia coli digest was spiked into a HeLa digest in four different concentrations, simulating protein expression differences in a background of an unchanged complex proteome. The data set provides a unique opportunity to evaluate the proteomic platform (instrumentation and software) in its ability to perform MS1-intensity-based label-free quantification. We show that the presented combination of informatics and instrumentation produces high precision and quantification accuracy. The data were also used to compare different quantitative protein inference methods such as iBAQ and Hi-N. The data can also be used as a resource for development and optimization of proteomics informatics tools, thus the raw data have been deposited to ProteomeXchange with identifier PXD001385.


A counterintuitive Mg2+-dependent and modification-assisted functional folding of mitochondrial tRNAs.
Mitochondrial tRNAs (mtRNAs) often lack domains and posttranscriptional modifications that are found in cytoplasmic tRNAs. These structural and chemical elements normally stabilize the folding of cytoplasmic tRNAs into canonical structures that are competent for aminoacylation and translation. For example, the dihydrouridine (D) stem and loop domain is involved in the tertiary structure of cytoplasmic tRNAs through hydrogen bonds and a Mg2+ bridge to the ribothymidine (T) stem and loop domain. These interactions are often absent in mtRNA because the D-domain is truncated or missing. Using gel mobility shift analyses, UV, circular dichroism and NMR spectroscopies and aminoacylation assays, we have investigated the functional folding interactions of chemically synthesized and site-specifically modified mitochondrial and cytoplasmic tRNAs. We found that Mg2+ is critical for folding of the truncated D-domain of bovine mtRNAMet with the tRNA's T-domain. Contrary to the expectation that Mg2+ stabilizes RNA folding, the mtRNAMet D-domain structure was unfolded and relaxed, rather than stabilized in the presence of Mg2+. Because the D-domain is transcribed prior to the T-domain, we conclude that Mg2+ prevents misfolding of the 5'-half of bovine mtRNAMet facilitating its correct interaction with the T-domain. The interaction of the mtRNAMet D-domain with the T-domain was enhanced by a pseudouridine located in either the D or T-domains compared to that of the unmodified RNAs (Kd=25.3, 24.6 and 44.4 microM, respectively). Mg2+ also affected the folding interaction of a yeast mtRNALeu1, but had minimal effect on the folding of an Escherichia coli cytoplasmic tRNALeu. The D-domain modification, dihydrouridine, facilitated mtRNALeu folding. These data indicate that conserved modifications assist and stabilize the formation of the functional mtRNA tertiary structure.


Parental presence at anaesthesia induction: A systematic review.
This systematic review assessed the effectiveness of parental presence for children undergoing surgical or diagnostic procedures under general anaesthesia (such as bronchoscopy, laryngoscopy and laparoscopy). Randomized and quasi randomized trials with healthy children scheduled for elective diagnostic and surgical procedures under general anaesthesia (age range 0-16 years) where the intervention was parental presence at anaesthesia induction were included. A comprehensive literature search was conducted using electronic databases and the reference lists of included studies. The Cochrane collaboration's tool for assessing risk of bias was used for assessment of risk of bias. The Review Manager software was used to analyse and synthesize data. A random-effect meta-analysis was used when there was evidence of clinical and/or statistical heterogeneity. Of the 102 citations identified, nine trials involving 1021 children were eligible for inclusion. Only four were sufficient to be included in the meta-analysis. There was no statistically significant difference on average in the level of anxiety in children and their parents either at separation or at induction between children allocated to parental presence and those allocated to no presence, premedication or parental presence plus premedication groups. Significant debate still surrounds this issue, and future trials should focus on the use of reliable and validated tools in assessing outcome measures.


High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.
We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4+ T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4+ T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4+ T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence.


Pre-procedural dual antiplatelet therapy in patients undergoing transcatheter aortic valve implantation increases risk of bleeding.
To evaluate the clinical benefit of pre-procedural antiplatelet therapy in patients undergoing transfemoral (TF) transcatheter aortic valve implantation (TAVI). OCEAN (Optimized transCathEter vAlvular interveNtion)-TAVI is a prospective, multicentre, observational cohort registry, enrolling 749 patients who underwent TAVI from October 2013 to August 2015 in Japan. We identified 540 patients (median age 85 years, 68.1% female) undergoing TF-TAVI; of these, 80 had no pre-procedural antiplatelet therapy and 460 had antiplatelet therapy. The endpoints were any bleeding (life-threatening, major, and minor bleeding) and thrombotic events (stroke, myocardial infarction, and valve thrombosis) during hospitalisation. Patients with dual antiplatelet therapy (DAPT) had a significantly higher incidence of any bleeding than those with single antiplatelet therapy (SAPT) (36.5% vs 27.5%, p=0.049) and no antiplatelet therapy (36.5% vs 21.3%, p=0.010). Patients without pre-procedural antiplatelet therapy did not experience an increased risk of thrombotic events. In multivariable logistic regression analysis, DAPT before TF-TAVI significantly increased any bleeding compared with SAPT (OR 2.05, 95% CI 1.16 to 3.65) and no antiplatelet therapy (OR 2.30, 95% CI 1.08 to 4.90). The current study demonstrated that DAPT before TF-TAVI increased the risk of bleeding compared with single or no antiplatelet therapy. Lower intensity antiplatelet therapy was not associated with thrombotic events. In modern practice, it might be reasonable to perform TAVI using single or no pre-procedural antiplatelet therapy with an expectation of no increase of adverse events. UMIN-ID; 000020423; Results.


Repression of p53 activity by Smyd2-mediated methylation.
Specific sites of lysine methylation on histones correlate with either activation or repression of transcription. The tumour suppressor p53 (refs 4-7) is one of only a few non-histone proteins known to be regulated by lysine methylation. Here we report a lysine methyltransferase, Smyd2, that methylates a previously unidentified site, Lys 370, in p53. This methylation site, in contrast to the known site Lys 372, is repressing to p53-mediated transcriptional regulation. Smyd2 helps to maintain low concentrations of promoter-associated p53. We show that reducing Smyd2 concentrations by short interfering RNA enhances p53-mediated apoptosis. We find that Set9-mediated methylation of Lys 372 inhibits Smyd2-mediated methylation of Lys 370, providing regulatory cross-talk between post-translational modifications. In addition, we show that the inhibitory effect of Lys 372 methylation on Lys 370 methylation is caused, in part, by blocking the interaction between p53 and Smyd2. Thus, similar to histones, p53 is subject to both activating and repressing lysine methylation. Our results also predict that Smyd2 may function as a putative oncogene by methylating p53 and repressing its tumour suppressive function.


Purification and characterization of Streptococcus sobrinus dextranase produced in recombinant Escherichia coli and sequence analysis of the dextranase gene.
The plasmid (pYA902) with the dextranase (dex) gene of Streptococcus sobrinus UAB66 (serotype g) produces a C-terminal truncated dextranase enzyme (Dex) with a multicomplex mass form which ranges from 80 to 130 kDa. The Escherichia coli-produced enzyme was purified and characterized, and antibodies were raised in rabbits. Purified dextranase has a native-form molecular mass of 160 to 260 kDa and specific activity of 4,000 U/mg of protein. Potential immunological cross-reactivity between dextranase and the SpaA protein specified by various recombinant clones was studied by using various antisera and Western blot (immunoblot) analysis. No cross-reactivity was observed. Optimal pH (5.3) and temperature (39 degrees C) and the isoelectric points (3.56, 3.6, and 3.7) were determined and found to be similar to those for dextranase purified from S. sobrinus. The dex DNA restriction map was determined, and several subclones were obtained. The nucleotide sequence of the dex gene was determined by using subclones pYA993 and pYA3009 and UAB66 chromosomal DNA. The open reading frame for dex was 4,011 bp, ending with a stop codon TAA. A ribosome-binding site and putative promoter preceding the start codon were identified. The deduced amino acid sequence of Dex revealed the presence of a signal peptide of 30 amino acids. The cleavage site for the signal sequence was determined by N-terminal amino acid sequence analysis for Dex produced in E. coli chi 2831(pYA902). The C terminus consists of a serine- and threonine-rich region followed by the peptide LPKTGD, 3 charged amino acids, 19 amino acids with a strongly hydrophobic character, and a charged pentapeptide tail, which are proposed to correspond to the cell wall-spanning region, the LPXTGX consensus sequence, and the membrane-anchoring domains of surface-associated proteins of gram-positive cocci.


Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease.
Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.


A comparison of La Crosse virus isolated obtained from different ecological niches and an analysis of the structural components of California encephalitis serogroup viruses and other bunyaviruses.
Analyses of the oligonucleotide fingerprints of the three genome ribonucleic acid (RNA) species of 11 isolates of La Crosse (LAC) virus, obtained from various ecological niches in the northern United States and compared to those of prototype LAC virus, showed that in each place from which these isolates were obtained LAC variants and varieties were present with related, but distinguishable, nucleotide sequences for their large, medium, or small RNA species. The RNA genomes of prototypes trivittatus (TVT), snowshoe hare (SSH), Tahyna (TAH), and Lumbo (a variety of TAH) viruses of the California encephalitis (CE) serogroup, and Guaroa of the Bunyamwera serogroup also consist of three RNA species, each with unique and distinguishable nucleotide sequences which bear little resemblance to those of the LAC virus isolates. The virions of CE group viruses (CE, Jamestown Canyon, Keystone, LAC, Melao, SSH, TVT, TAH viruses and South River, an unregistered virus) have three major viral polypeptides, designated G1, G2, and N.


Biofeedback training for lower urinary tract symptoms: factors affecting efficacy.
Biofeedback therapy is a valuable modality in children with dysfunctional voiding. However, it is unclear what factors contribute to the outcome. To define who may or may not benefit from biofeedback therapy we reviewed our experience with this treatment. We retrospectively reviewed the charts of 77 children referred between July 2005 and September 2008 for biofeedback therapy. An MR 20 Synergy trainer (Prometheus Group, Dover, New Hampshire) provided nonanimated and animated biofeedback. Uroflowmetry was performed at the start and end of each session. A total of 67 females and 10 males with a mean age of 9.0 years (range 4.8 to 18.2) comprised the cohort group. The primary referral diagnosis was nonfebrile urinary tract infection in 52 patients (67.5%), daytime and nighttime wetting in 47 (61%), voiding postponement in 14 (18.2%) and daytime incontinence in 10 (13%). Children were categorized by an outcome of success, improvement or failure. Results were analyzed using the chi-square, Fisher exact probability and Student t tests. Success, improvement and failure were achieved in 22 (26.8%), 29 (37.7%) and 26 cases (33.7%), respectively. Age and gender were not statistically significant predictors of outcome. A median of 3.0 sessions (range 1 to 8) was administered. Children with 3 or greater sessions were more likely to succeed (p <0.005). The improvement in urinary tract infections was statistically significant (p <0.001). Of 37 children 20 (54%) transformed a staccato voiding pattern to a normal one on uroflowmetry. Biofeedback therapy can be effective in children with dysfunctional voiding and urinary tract infection. Children with a staccato voiding pattern may require a minimum of 3 visits to improve the voiding pattern. Children who complete 3 sessions are more likely to succeed.


Revisiting the use of sPLA2-sensitive liposomes in cancer therapy.
The first developed secretory phospholipase A2 (sPLA2) sensitive liposomal cisplatin formulation (LiPlaCis®) is currently undergoing clinical evaluation. In the present study we revisit and evaluate critical preclinical parameters important for the therapeutic potential and safety of platinum drugs, here oxaliplatin (L-OHP), formulated in sPLA2 sensitive liposomes. We show the mole percentage of negatively charged phospholipid needed to obtain enzyme-sensitivity for saturated systems is ≥25% for 16-carbon chain lipid membranes, and >40% for 18-chain lipid membranes, which was surprising as 25% is used clinically in LiPlaCis®. Efficient sPLA2-dependent growth inhibition of colorectal cancer cells was demonstrated in vitro, where cell membrane degradation and cytolysis depends on the sensitivity of the formulation towards the enzyme and is governed by the amount of lysolipids generated and the presence of serum proteins. We found that serum proteins did not affect the lipase activity of the enzyme towards the membranes but instead sequester the lysolipid byproducts consequently inhibiting their detergent-like cytotoxic properties. In vivo therapeutic potential and safety of the liposomes was investigated in nude mice bearing sPLA2-deficient FaDu squamous carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. After intravenous injections, the tumor growth was suppressed for liposomal L-OHP relative to free drug, but only a weak response was observed for both slow- and fast-releasing sPLA2-sensitive formulations compared to non-sensitive liposomes. Also, the mice did not show longer survival. In turn, for the highly sPLA2-sensitive liposomes, multiple high doses caused petechial cutaneous hemorrhages, along with multifocal hepatonecrotic lesions, suggestive of premature activation in skin and liver irrespective of sPLA2-status of the tumor engraft. These results indicate that although liposomal carriers can improve the antitumor efficacy of platinum drugs, sPLA2-triggered release suffers from a narrow therapeutic index and has safety concerns.


Evolutionary Consequences of Sex-Specific Selection in Variable Environments: Four Simple Models Reveal Diverse Evolutionary Outcomes.
The evolutionary trajectories of species with separate sexes depend on the effects of genetic variation on female and male traits as well as the direction and alignment of selection between the sexes. Classical theory has shown that evolution is equally responsive to selection on females and males, with natural selection increasing the product of the average relative fitness of each sex over time. This simple rule underlies several important predictions regarding the maintenance of genetic variation, the genetic basis of adaptation, and the dynamics of "sexually antagonistic" alleles. Nevertheless, theories of sex-specific selection overwhelmingly focus on evolution in constant environments, and it remains unclear whether they apply under changing conditions. We derived four simple models of sex-specific selection in variable environments and explored how conditions of population subdivision, the timing of dispersal, sex differences in dispersal, and the nature of environmental change mediate the evolutionary dynamics of sex-specific adaptation. We find that these dynamics are acutely sensitive to ecological, demographic, and life-history attributes that vary widely among species, with classical predictions breaking down in contexts of environmental heterogeneity. The evolutionary rules governing sex-specific adaptation may therefore differ between species, suggesting new avenues for research on the evolution of sexual dimorphism.


Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease.
The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune cells alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design and synthesize a selective near-infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of metastases in mice reveals predominant probe accumulation in Mer-expressing tumor-associated macrophages.


Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia.
Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values.


Non-rheumatic streptococcal myocarditis - warm hands, warm heart.
Acute myopericarditis in the developed world is ascribed predominantly to viral infections. Enteroviruses and adenoviruses are commonly implicated but are not routinely tested for, as the condition is self-limiting and has a good prognosis. However, we recently encountered two cases of acute myopericarditis associated with concomitant Streptococcus pyogenes [group A Streptococcus (GAS)] pharyngotonsillitis. A microbiological aetiology was pursued because of the severity of the upper respiratory tract infection and associated systemic illness rather than to explain the myopericarditis per se. We report these two cases and review the literature of this potentially under-recognized condition. In the absence of features of rheumatic fever, we hypothesize a toxin-mediated process as opposed to an immune-mediated one. We suggest that perhaps all patients with myopericarditis be assessed for GAS pharyngitis.


Enhanced mobility-lifetime products in PbS colloidal quantum dot photovoltaics.
Colloidal quantum dot (CQD) photovoltaics offer a promising approach to harvest the near-IR region of the solar spectrum, where half of the sun's power reaching the earth resides. High external quantum efficiencies have been obtained in the visible region in lead chalcogenide CQD photovoltaics. However, the corresponding efficiencies for band gap radiation in the near-infrared lag behind because the thickness of CQD photovoltaic layers from which charge carriers can be extracted is limited by short carrier diffusion lengths. Here, we investigate, using a combination of electrical and optical characterization techniques, ligand passivation strategies aimed at tuning the density and energetic distribution of charge trap states at PbS nanocrystal surfaces. Electrical and optical measurements reveal a more than 7-fold enhancement of the mobility-lifetime product of PbS CQD films treated with 3-mercaptopropionic acid (MPA) in comparison to traditional organic passivation strategies that have been examined in the literature. We show by direct head-to-head comparison that the greater mobility-lifetime products of MPA-treated devices enable markedly greater short-circuit current and higher power conversion efficiency under AM1.5 illumination. Our findings highlight the importance of selecting ligand treatment strategies capable of passivating a diversity of surface states to enable shallower and lower density trap distributions for better transport and more efficient CQD solar cells.


Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index.
Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries. To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA). This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline. Biologic therapy for psoriasis. Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status. Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI -71.22 HU [interquartile range (IQR), -75.85 to -68.11 HU] at baseline vs -76.09 HU [IQR, -80.08 to -70.37 HU] at 1 year; P < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, -71.98 [IQR, -77.36 to -65.64] at baseline vs -72.66 [IQR, -78.21 to -67.44] at 1 year; P = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti-tumor necrosis factor α (median FAI, -71.25 [IQR, -75.86 to -66.89] at baseline vs -75.49 [IQR, -79.12 to -68.58] at 1 year; P < .001) and anti-IL-12/23 or anti-IL-17 therapy (median FAI, -71.18 [IQR, -75.85 to -68.80] at baseline vs -76.92 [IQR, -81.16 to -71.67] at 1 year; P < .001). In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.


The effects of McKenzie exercises for patients with low back pain, our experience.
To investigate influence of McKenzie exercises on decreasing the pain in patients with low back pain, to show occurrence of Centralization sign, as a predictor of good treatment outcomes and to evaluate use of McKenzie exercises, as a routine method for lower back pain in Physical Medicine and Rehabilitation Centres. Clinical, prospective, manipulative study. Physiotherapy and Rehabilitation Clinic in Community Based Rehabilitation Centers and Institute for Physical Medicine and Rehabilitation affiliated with a Medical College Sarajevo. Thirty-four patients with symptoms of low back pain. McKenzie exercise program for low back pain were performed individually to the need and possibility of each patient. Patients attended exercise program daily, under supervision of physiatrist and physiotherapist and do it also at home, five times a day in series of 5 to 10 repetition each time, depending of stage of disease and pain intensity. The average training period was 15,5 days. All patients were assessed before and after the treatment. Visual Analog Scale (VAS) measured intensity of pain, localization of pain was noted on special forms and Shober test was used to show differences in spinal movement before and after the treatment. Measurements of spinal movements and flexibility of spine showed significant improvement in all patients. Average difference in values of Shober test before and after treatment was 1,1 cm with SD 0,98. Difference test was t=6,263 with significant difference p<0,01. Mean pain intensity was reduced significantly as a result of treatment. Pain was reduced on VAS for X=2,8 with S.D. 1,56. Difference Test was t=10,332, with significant difference p<0.01. 61,5% of total number of participants had signs of centralisation (6% were in acute stage of pain, 32% in subacute and 23,5% in chronic pain). Centralisation sign was noted in 40% of acute patients, 57.5% subacute and 80% of chronic patients with a low back pain who exercised McKenzie program. McKenzie exercises for low back pain are beneficial treatment for increasing flexibility of spine and improving the pain with better results in pain relief. Although done by minimally trained physiotherapists in McKenzie approach, McKenzie exercises are successful method for decreasing and centralising the pain and increasing spinal movements in patients with low back pain.


Effect of acute intraocular pressure changes on short posterior ciliary artery haemodynamics.
Vascular insufficiency due to abnormal autoregulation has been proposed as a major factor in the development of glaucoma. The anterior optic nerve is primarily perfused by the short posterior ciliary arteries. The autoregulatory capacity of these vessels in response to acutely elevated intraocular pressure (IOP) was examined in normal human subjects. Colour Doppler imaging was performed on the short posterior ciliary arteries of 10 normal subjects at baseline and during four incremental IOP elevations. Using a scleral suction cup placed temporally, IOP was elevated to approximately 25, 30, 40, and 50 mm Hg. Additional measurements were performed immediately after pressure release. Systolic and diastolic flow velocities were measured and Pourcelot's resistivity index was calculated. Systolic and diastolic flow velocities decreased linearly with each incremental increase in IOP (p < 0.001). Pourcelot's resistivity index increased linearly with each incremental increase in IOP (p < 0.001). Changes in end diastolic velocity, peak systolic velocity, and Pourcelot's resistivity index were linearly related to changes in IOP. The normal healthy eye is not able to autoregulate to maintain PCA blood flow velocities in response to acute large elevations in IOP.


Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.
Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.


Defining the phylogenomics of Shigella species: a pathway to diagnostics.
Shigellae cause significant diarrheal disease and mortality in humans, as there are approximately 163 million episodes of shigellosis and 1.1 million deaths annually. While significant strides have been made in the understanding of the pathogenesis, few studies on the genomic content of the Shigella species have been completed. The goal of this study was to characterize the genomic diversity of Shigella species through sequencing of 55 isolates representing members of each of the four Shigella species: S. flexneri, S. sonnei, S. boydii, and S. dysenteriae. Phylogeny inferred from 336 available Shigella and Escherichia coli genomes defined exclusive clades of Shigella; conserved genomic markers that can identify each clade were then identified. PCR assays were developed for each clade-specific marker, which was combined with an amplicon for the conserved Shigella invasion antigen, IpaH3, into a multiplex PCR assay. This assay demonstrated high specificity, correctly identifying 218 of 221 presumptive Shigella isolates, and sensitivity, by not identifying any of 151 diverse E. coli isolates incorrectly as Shigella. This new phylogenomics-based PCR assay represents a valuable tool for rapid typing of uncharacterized Shigella isolates and provides a framework that can be utilized for the identification of novel genomic markers from genomic data.


Fatty acid esters of monochloropropanediol (MCPD) and glycidol in refined edible oils.
Recently, fatty acid esters of monochloropropanediol (MCPD) and that of glycidol have been reported in refined edible oils. Since then a wealth of research has been published on the factors influencing the formation of these contaminants in foods. It can be noted that the predominant precursors in a given matrix will not necessarily be the same as in other matrices. Further, proven relationships in the past between precursors responsible for free MCPD or free glycidol formation will not necessarily be valid for their fatty acid-esterified counterparts. This review attempts to summarise the current status of the literature as it pertains to the reasons surrounding the manifestation of MCPD esters and glycidyl esters in oils and fats. Recent efforts to mitigate the levels of these contaminants were highlighted and put into the context of their respective reaction matrices. As more accurate occurrence data for MCPD esters and glycidyl esters in other foods are collected, more targeted mitigation experiments can be formulated with respect to the reaction matrices under investigation.


The inter-relationship between mood, self-esteem and response styles in adolescent offspring of bipolar parents: an experience sampling study.
The response styles theory of depression (Nolen-Hoeksema, 1991) proposes three main strategies individuals employ in response to low mood: rumination, active coping (distraction and problem-solving) and risk taking. Although recent research has suggested this theory has utility in understanding the symptoms of bipolar disorder (BD), the role of these processes in conferring vulnerability to the condition is poorly understood. Twenty-three adolescent children of patients with BD and 25 offspring of well parents completed the Experience Sampling Method (ESM; Csikszentmihalyi and Larson, 1987) diary for six days. Longitudinal analyses were carried out to examine inter-relationships between mood, self-esteem and response styles. Increased negative as well as positive mood resulted in greater rumination in both groups. Low self-esteem triggered greater risk-taking at the subsequent time point in the at-risk group, while negative affect instigated increased active coping in the control group. In both groups, engagement in risk-taking improved mood at the subsequent time point, whilst rumination dampened self-esteem. Differential longitudinal associations between mood, self-esteem and response styles between at-risk and control children suggest early psychological vulnerability in the offspring of BD parents, with important indications for early intervention.


Human area 5 modulates corticospinal output during movement preparation.
Neuroimaging evidence suggests that human Brodmann area 5 (BA5) within the superior parietal lobule contributes to movement planning. However, a causal role for the contribution of BA5 to preparatory processes has yet to be reported. We used paired-pulse transcranial magnetic stimulation to investigate the influence of human BA5 on corticospinal excitability during movement preparation in the context of a GO/NO-GO task. Functional connectivity between BA5 and the ipsilateral primary motor cortex (M1) was investigated by probing corticospinal output to the first dorsal interosseous muscle of the right hand. Results indicate that BA5 influences M1 during movement preparation in a task-specific manner: motor-evoked potentials are suppressed in the context of a NO-GO versus GO task. These findings provide evidence that human BA5 participates in movement preparation and differentiates between whether a movement is withheld or executed.


Presentation approaches for enhancing interpretability of patient-reported outcomes (PROs) in meta-analysis: a protocol for a systematic survey of Cochrane reviews.
Meta-analyses of clinical trials often provide sufficient information for decision-makers to evaluate whether chance can explain apparent differences between interventions. Interpretation of the magnitude and importance of treatment effects beyond statistical significance can, however, be challenging, particularly for patient-reported outcomes (PROs) measured using questionnaires with which clinicians have limited familiarity. The objectives of our study are to systematically evaluate Cochrane systematic review authors' approaches to calculation, reporting and interpretation of pooled estimates of patient-reported outcome measures (PROMs) in meta-analyses. We will conduct a methodological survey of a random sample of Cochrane systematic reviews published from 1 January 2015 to 1 April 2017 that report at least one statistically significant pooled result for at least one PRO in the abstract. Author pairs will independently review all titles, abstracts and full texts identified by the literature search, and they will extract data using a standardised data extraction form. We will extract the following: year of publication, number of included trials, number of included participants, clinical area, type of intervention(s) and control(s), type of meta-analysis and use of the Grading of Recommendations, Assessment, Development and Evaluation approach to rate the quality of evidence, as well as information regarding the characteristics of PROMs, calculation and presentation of PROM effect estimates and interpretation of PROM effect estimates. We will document and summarise the methods used for the analysis, reporting and interpretation of each summary effect measure. We will summarise categorical variables with frequencies and percentages and continuous outcomes as means and/or medians and associated measures of dispersion. Ethics approval for this study is not required. We will disseminate the results of this review in peer-reviewed publications and conference presentations.


Clostridium botulinum type-C intoxication associated with consumption of processed alfalfa hay cubes in horses.
An episode of nervous system dysfunction was observed in horses on 17 premises in 4 counties of southern California. Thirty-eight horses were affected, and 31 of those died. The common clinical signs of disease in the affected horses were: increased appetite; anxious attitude; rythmic, intermittent muscle tremors in the area of the tricep muscles; decreased palpebral tone; mydriasis; small hard fecal balls; and tendency to become sternally recumbent with the neck extended. The temporal distribution of cases on all 17 premises suggested a relationship between exposure to a common batch of alfalfa hay cubes and manifestations of similar clinical signs of disease in affected horses. Fifteen horses were submitted for necropsy. Diagnosis of botulism was established on the basis of detection of type-C1 toxin in the feed, in intestinal contents of 1 horse, and in the liver of the aforementioned horse and another horse. Toxigenic strains of Clostridium botulinum type-C were isolated from intestinal contents of 5 affected horses, one of which also contained type-C1 and type-C2 toxins. Seven of 10 horses treated with type-C antitoxin and plasma obtained from horses hyperimmunized with C botulinum type-C toxoids survived.


Invasive candidiasis in non neutropenic critically ill - need for region-specific management guidelines.
Use of antifungal agents has increased over past few decades. A number of risk factors such as immunosuppression, broad spectrum antibiotics, dialysis, pancreatitis, surgery, etc., have been linked with the increased risk of invasive candidiasis. Though there are various guidelines available for the use of antifungal therapy, local/regional epidemiology plays an important role in determining the appropriate choice of agent in situations where the offending organism is not known (i.e. empirical, prophylactic or preemptive therapy). Developing countries like India need to generate their own epidemiological data to facilitate appropriate use of antifungal therapy. In this article, the authors have highlighted the need for region-specific policies/guidelines for treatment of invasive candidiasis. Currently available Indian literature on candidemia epidemiology has also been summarized here.


Effects of a home based exercise intervention on cardiac biomarkers, liver enzymes, and cardiometabolic outcomes in CABG and PCI patients.
We investigated the impact of a home-based exercise intervention (HBEI) on cardiac biomarkers, liver enzymes, cardiometabolic outcomes, and health-related quality of life (HRQL) in clinically stable patients after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). The study was a nonrandomized clinical trial conducted in Tehran, Iran, from July 2019 to January 2020. Forty cardiac patients (after the cardiac intervention, CABG, n = 32; PCI, n = 8) were recruited based on the study inclusion criteria and were allocated consecutively to one of two groups: (1) HBEI (n = 18) and (2) conventional center-based exercise program (CBEP, n = 22). The CBEP group performed the routine exercise program of Sadr Heart Clinic, and the HBEI group performed a home-based remotely monitored exercise protocol, both three times per week, for 8 weeks. The following variables were assessed before and after the intervention: anthropometric measures; blood pressure; lipid profile; cardiac biomarkers including cardiac troponin I, creatine kinase, and total and Mb isozyme; liver enzymes including aspartate aminotransferase and alanine aminotransferase; creatinine; urea; exercise capacity; and HRQL. In comparison with pretest in both CBEP and HBEI groups, a significant improvement in all of the measured variables (P < 0.05), but not in ejection fraction was observed (P > 0.05). Moreover, in the CBEP group, a more significant decline in troponin I levels (P = 0.03), and in the HBEI group, a greater reduction in weight (P = 0.01) and body mass index (P = 0.04) occurred. The findings suggest that a properly designed and monitored HBEI may be as effective as conventional center-based cardiac rehabilitation (CR) exercise programs and should be encouraged in those cardiac patients who are unable or uninterested in conventional center-based CR exercise programs.


Positive effect of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) on homogeneous photocatalytic reduction of CO2.
A significant decrease in the amount of the sacrificial electron donor triethanolamine (TEOA) required for the homogeneous photocatalytic reduction of CO2 using rhenium-based catalytic systems can be achieved by adding small quantities of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to the reaction mixture. The turnover numbers (TONs) and frequencies (TOFs) measured for the reactions described herein are even higher than those observed in reaction mixtures containing high concentrations of TEOA. Furthermore, replacing TEOA with DBU in the solutions of Re(i)/Ru(ii) mixed catalytic systems leads to a doubling of the values of TON and TOF.


Tuberculosis in tropical areas and immigrants.
About 95% of cases and 98% of deaths due to tuberculosis (TB) occur in tropical countries while, in temperate low incidence countries, a disproportionate portion of TB cases is diagnosed in immigrants. Urbanization, poverty, poor housing conditions and ventilation, poor nutritional status, low education level, the HIV co-epidemic, the growing impact of chronic conditions such as diabetes are the main determinants of the current TB epidemiology in tropical areas. TB care in these contests is complicated by several barriers such as geographical accessibility, educational, cultural, sociopsychological and gender issues. High quality microbiological and radiological facilities are not widely available, and erratic supply of anti-TB drugs may affect tropical areas from time to time. Nevertheless in recent years, TB control programs reached major achievements in tropical countries as demonstrated by several indicators. Migrants have a high risk of acquire TB before migration. Moreover, after migration, they are exposed to additional risk factors for acquiring or reactivating TB infection, such as poverty, stressful living conditions, social inequalities, overcrowded housing, malnutrition, substance abuse, and limited access to health care. TB mass screening programs for migrants have been implemented in low endemic countries but present several limitations. Screening programs should not represent a stand-alone intervention, but a component of a wider approach integrated with other healthcare activities to ensure the health of migrants.


Profile of presentation of human immunodeficiency virus infection in north India, 2003-2007.
Clinico-epidemiological profile of the Human immunodeficiency virus (HIV) epidemic in India is varied and depends on multitude of factors including geographic location. We analyzed the characteristics of HIV-infected patients attending our Immunodeficiency Clinic to determine any changes in their profile over five years. A retrospective observational study. The study sample included all patients with HIV infection from January 1, 2003 to December 31, 2007. Diagnosis of HIV was made according to National AIDS Control Organization guidelines. Of 3 067 HIV-infected patients, 1 887 (61.5%) were male and 1 180 (38.5%) were female patients. Mean age of patients was 35.1 ± 9.0 years. Majority (91.8%) of patients were in the age group of 15 to 49 years. Progressively increasing proportion of female patients was noted from year 2004 onward. Median CD4 count at presentation in year 2003 was 197/μl (Interquartile range [IQR] = 82.5-373) while in year 2007 it was 186.5/μl (IQR = 86.3-336.8). Mean CD4 count of male patients was 203.7 ± 169.4/μl, significantly lower as compared with female patients, which was 284.8 ± 223.3/μl (P value ≤0.05). Every year, substantial proportions of patients presenting to clinic had CD4 count<200/μl indicating advanced disease. Predominant route of transmission was heterosexual in 2 507 (81.7%) patients. Tuberculosis and oropharyngeal candidiasis were the most common opportunistic infections (OIs). Cryptococcal meningitis was the most common central nervous infection. Our patients had comparatively lower median CD4 counts at the time of presentation with various OIs. Patients had advanced stage of HIV infection at the time of presentation throughout five years. Females presented earlier during the course of HIV infection. There is need for early screening and increasing awareness in healthcare providers to make a diagnosis of HIV much sooner.


Northern Rivers Ecosystem Initiative: distribution and effects of contaminants.
In response to a number of recommendations following the Northern Rivers Basin Studies (NRBS) contaminant program, the Northern Rivers Ecosystem Initiative (NREI) focused considerable attention on assessing contaminants from specific sources including pulp mill effluents, atmospheric transport of mercury and the Alberta oil sands operations. NRBS identified a number of major contaminants of concern including polychlorinated biphenyls, dioxins and furans, mercury and various hydrocarbons. Together, the NRBS and the NREI studies have demonstrated major declines in the levels of dioxins and furans over the last decade as pulp and paper mills have changed their process and treatment strategies in response to new Federal regulations. Polychlorinated biphenyls however, continue to be a concern for the region as their levels have not declined in fish and sediments over the course of these studies. Higher levels in sediments downstream of Grande Prairie and Hinton were identified, but the source of these contaminants remains unknown. Chlorinated pesticides were also investigated, and although toxaphene, DDT and other chlorinated organic pesticides were detected in fish tissue, they were present at very low levels. Studies on the oil sands industry in northern Alberta demonstrated limited impacts on the Athabasca River to date, although studies did identify slight to moderate impacts of natural oil seeps on fish and benthic communities in tributary streams. NREI studies also identified endocrine active compounds in the three pulp and paper mill effluents tested, but endocrine disruptive effects in wild fish were minimal. Municipal sewage effluents also contain endocrine active compounds and it is recommended that monitoring continue around these point sources.