A protein biomarker discovery workflow was applied to plasma samples from patients at different stages of diabetic kidney disease. The proteomics platform produced a panel of significant plasma biomarkers that were statistically scrutinised against the current gold standard tests on an analysis of 572 patients. Five proteins were significantly associated with diabetic kidney disease defined by albuminuria, renal impairment (eGFR) and chronic kidney disease staging (CKD Stage ≥1, ROC curve of 0.77). The results prove the suitability and efficacy of the process used, and introduce a biomarker panel with the potential to improve diagnosis of diabetic kidney disease.

The sea surface microlayer (SML) is the uppermost layer of the water column that links the ocean and atmosphere. It accumulates a variety of biogenic surface-active and buoyant substances, including gelatinous material, such as transparent exopolymer particles (TEP) and Coomassie stainable particles (CSP), potentially affecting air-sea exchange processes. Here, we studied the influence of the annual cycle of phytoplankton production on organic matter (OM) accumulation in the SML relative to the subsurface water (SSW). Sampling was performed monthly from April 2012 to November 2013 at the Boknis Eck Time Series Station (Baltic Sea). For SML sampling, we used the Garrett screen, while SSW samples were collected by Niskin bottles at 1 m depth. Samples were analyzed for carbohydrates, amino acids, TEP, CSP, chlorophyll a (SSW only) and bacterial abundance. Our data showed that the SML reflected the SSW during most parts of the year, with changes mainly responding to bloom formation and decay. OM composition during phytoplankton blooms clearly differed from periods of higher bacterial abundance. Of all components investigated, only the enrichment of total carbohydrates in the SML was inversely related to the wind speed indicating that wind-driven mixing also affected the accumulation of OM in the SML during our study.

Background: The most common entrapment mononeuropathy of the upper extremity is carpal tunnel syndrome (CTS). It consists 90% of entrapment neuropathies. The purpose of this study was to compare cross-sectional area (CSA) of the median nerve at the wrist in CTS patients and healthy controls and define the best cut-off point of CSA to differentiate patients and controls in Iranian population. Methods: In this study, 45 patients with confirmed idiopathic CTS and 62 healthy controls were evaluated. Based on electrophysiological findings, patients were divided based on CTS severity into three groups of mild, moderate and severe. The largest CSA was measured at the level of distal wrist crease which is consistent with carpal tunnel inlet. Results: Mean CSA was 0.124 ± 0.031 mm2, 0.146 ± 0.028 mm2 and 0.194 ± 0.062 mm2 in mild, moderate and severe CTS patients respectively, and 0.077 ± 0.011 mm2 in controls. Our results showed that participants with CSA > 0.010 had CTS with 100% specificity and 83.12% sensitivity. Conclusion: It is possible to diagnose CTS by measuring CSA and using above-mentioned cut-off point.

Background: As there was no evidence of long-term studies on stroke trend, stroke subtypes and its relationships to stroke risk factors and demographic characteristics in Iran, we aimed to evaluate the 10-year trend of stroke incidence and stroke subtypes in Isfahan, Iran. Methods: In a hospital-based retrospective study, 24186 cases with the first-ever stroke were analyzed. We assessed the incidence trend of annual stroke and its subtypes [ischemic stroke (IS) subarachnoid hemorrhage (SAH), and intracranial hemorrhage (ICH)] during the years 2003 to 2013 by sex, and studied the association of demographic and major stroke risk factors with incidence and mortality rate of stroke. Results: The mean age was 69.46 ± 14.87 years, and 49.29% of patients were women. IS was the most frequent type among all the types of strokes (76.18%). Stroke and its subtypes had decreasing incidence trend during the study period, except for SAH that increased. In addition, stroke and its subtypes had decreasing mortality trend during the study period, except for SAH that did not change anymore. Stroke mortality and incidence rates were lower in urban inhabitants compared to residents of rural areas [odds ratio (OR) = 0.763, P < 0.001]. Conclusion: Despite the relatively high incidence of stroke over the study period, the incidence rate of stroke, especially ICH subtype, had a decreasing trend over the last decade in Isfahan. However, given the current young population in Iran, we can expect that the incidence of stroke would have an escalating trend in future.

No abstract available

Type 2 diabetes (T2D) is a significant public health problem, with U.S. Pacific Islander communities-such as the Marshallese-bearing a disproportionate burden. Using a community-based participatory approach (CBPR) that engages the strong family-based social infrastructure characteristic of Marshallese communities is a promising way to manage T2D.

The burden of communicable and non-communicable diseases in Sub-Saharan Africa poses a challenge in achieving quality healthcare. Although therapeutic drugs have generally improved health, their efficacy differs from individual to individual. Variability in treatment response is mainly because of genetic variants that affect the pharmacokinetics and pharmacodynamics of drugs.

Rupture of lens cataract (RLC) is a hereditary mouse model that shows spontaneous rupture of the lens at the posterior pole at 45-100 days of age. The responsible gene for this phenotype was identified as Dock5, a guanine nucleotide exchange factor for small GTPase Rac1. This study was performed to elucidate the pathway initiating this phenotype.

Chromosomal rearrangements are common in cancer. More than 50% occur in common fragile sites and disrupt tumor suppressors. However, such rearrangements are not known in gastric cancer. Here we report recurrent 18q2 breakpoints in 6 of 17 gastric cancer cell lines. The rearranged chromosome 18, t(9;18), in MKN7 cells was flow sorted and identified by reverse chromosome painting. High-resolution tiling array hybridization mapped breakpoints to DOK6 (docking protein 6) intron 4 in FRA18C (18q22.2) and an intergenic region in 9q22.2. The same rearrangement was detected by FISH in 22% of 99 primary gastric cancers. Intron 4 truncation was associated with reduced DOK6 transcription. Analysis of The Cancer Genome Atlas stomach adenocarcinoma cohort showed significant correlation of DOK6 expression with histological and molecular phenotypes. Multiple oncogenic signaling pathways (gastrin-CREB, NGF-neurotrophin, PDGF, EGFR, ERK, ERBB4, FGFR1, RAS, VEGFR2 and RAF/MAP kinase) known to be active in aggressive gastric cancers were strikingly diminished in gastric cancers with low DOK6 expression. Median survival of patients with low DOK6-expressing tumors was 2100 days compared with 533 days in patients with high DOK6-expressing tumors (log-rank P = 0.0027). The level of DOK6 expression in tumors predicted patient survival independent of TNM stage. These findings point to new functions of human DOK6 as an adaptor that interacts with diverse molecular components of signaling pathways. Our data suggest that DOK6 expression is an integrated biomarker of multiple oncogenic signals in gastric cancer and identify FRA18C as a new cancer-associated fragile site.

Pathogenic Escherichia coli, one of the primary causes of urinary tract infections, has shown significant resistance to the most popular antibiotic, trimethoprim (TMP), which inhibits dihydrofolate reductase (DHFR). The resistance is modulated by single point mutations of DHFR. The impact of two clinically relevant mutations, P21L and W30R, on the activity of DHFR was evaluated via measurement of Michaelis-Menten and inhibitory kinetics, and structural characterization was undertaken by native mass spectrometry with ultraviolet photodissociation (UVPD). Compared to WT-DHFR, both P21L and W30R mutants produced less stable complexes with TMP in the presence of co-factor NADPH as evidenced by the relative abundances of complexes observed in ESI mass spectra. Moreover, based on variations in the fragmentation patterns obtained by UVPD mass spectrometry of binary and ternary DHFR complexes, notable structural changes were localized to the substrate binding pocket for W30R and to the M20 loop region as well as the C-terminal portion containing the essential G-H functional loop for the P21L mutant. The results suggest that the mutations confer resistance through distinctive mechanisms. A novel propargyl-linked antifolate compound 1038 was shown to be a reasonably effective inhibitor of the P21L mutant.

Simulation training offers an opportunity to educate anaesthesia and intensive care (AIC) residents safely. At present, it is not yet a mandatory part of residency curriculum.The aim of the study was to evaluate the residents' perception of the inclusion of simulation-based training in the Romanian AIC residency program.

The current study sought to examine the impact of strengthening cigarette pack warnings on attention, message processing, and perceived effectiveness, through a systematic review of longitudinal observational studies. The review included 22 studies (N = 81,824 participants). Strengthened warnings increased attention to warnings, recall of warnings, and thinking about the health risks of smoking. Strengthened warnings also increased several perceived effectiveness outcomes, including perceptions that warnings reduce smoking and motivate quitting. Strengthened cigarette pack warnings achieve their goal of attracting attention and enhancing motivation to act. Strengthening warning policies should be a priority for tobacco control globally.

The use of spinal fusion surgery as a treatment for degenerative spinal conditions and chronic back pain is increasing. However, this technique requires use of a bone grafting material to fuse the vertebrae, traditionally autologous bone, which consists of an optimal combination of osteogenic cell precursors, extracellular matrix proteins and mineral components. To date, this remains the 'gold standard' material but its supply is limited and is associated with a number of clinical and ethical difficulties; consequently, various combinations of cells with biological scaffold materials have been tested but have failed to achieve fusion rates even comparable to autologous bone. We successfully fabricated a novel collagen-based scaffold using self-organising atelocollagen combined with nano-hydroxyapatite and chondroitin sulphate, cross-linked by microbial transglutaminase. The scaffold was characterised using a range of imaging, chemical composition and thermal analysis techniques. It was found to exhibit appropriate stiffness and suitable pore size for the adhesion, growth and differentiation of MSCs. The low toxicity makes it suitable for clinical application, and its slow degradation profile would enable the scaffold to promote bone growth over an extended period. This material therefore shows promise for clinical use in spinal fusion and other procedures requiring the use of bone grafts.

There is an increasing need to develop indicators of vulnerability and adaptive capacity to determine the robustness of response strategies over time and better understand the underlying processes. This study aimed to determine levels of risk of food insecurity using defined vulnerability indicators. For the purpose of this study, factors influencing food insecurity and different vulnerable indicators were examined using quantitative and qualitative research methods. Observations made on the physical environment (using tools for spatial analysis) and socio-economic surveys conducted with local populations have quantified vulnerability indicators in the Niayes agricultural region. Application of the Classification and Regression Tree (CART) model has enabled us to quantify the level of vulnerability of the zone. The results show that the decrease in agricultural surface areas is the most discriminant one in this study. The speed of reduction of the agricultural areas has specially increased between 2009 and 2014, with a loss of 65% of these areas. Therefore, a decision-making system, centred on the need for reinforcing the resilience of local populations, by preserving the agricultural vocation of the Niayes region and even in the Sahelian regions requires support and extension services for the farmers in order to promote sustainable agricultural practices.

Pimavanserin (Nuplazid™) is an atypical antipsychotic currently indicated for the treatment of hallucinations and delusions associated with Parkinson disease psychosis. The antipsychotic effects of this new agent are believed to occur via selective inverse agonist activity at serotonin 5-HT2a receptors.

Background: Motivated by concern over lack of access to nutritious food in low-income neighborhoods, healthy food financing initiatives have encouraged the introduction of new supermarkets. Extensive research on the association between the food retail environment and nutrition outcomes has shown mixed results. There has been less research specifically on food security outcomes. Objective: We assessed the association between multiple food environment measures and food security for low-income US households. Methods: By using the USDA's nationally representative 2012-2013 Food Acquisition and Purchase Survey (FoodAPS; n = 4826 households), which provides unique information about neighborhood- and household-level food retailer access, we quantified cross-sectional associations between food environment characteristics and household-level outcomes, with and without regression controls. Logistic regression analysis was used for binary household food security outcomes. Results: Most households bypassed the nearest retailer to select a primary retailer farther from home. For low-income households, distance to the nearest supermarket and to the primary retailer was not associated with food security. In comparison to shopping with households' own automobile, the odds of being food secure were lower for households that used another automobile (OR: 0.59; 95% CI: 0.38, 0.90) or other transportation (OR: 0.32; 95% CI: 0.17, 0.61) to reach the primary retailer. Conclusions: Having a closest supermarket ≤1 mile from home was not associated with household food security. In contrast, the mode of transportation used to access the primary retailer was associated with household food security. In future research, it may be valuable to not only focus on the distance to the nearest supermarket but to investigate the qualities of the food retail environment at distances >1 mile that are most strongly associated with food security outcomes.

Background: High intakes of total and animal protein are associated with the risk of type 2 diabetes (T2D). The influence of protein type on insulin resistance, a key precursor of T2D, has not been extensively studied. Objective: The aim of this study was to determine the associations between dietary total, animal, and plant protein intakes as well as the animal-to-plant protein (AP) intake ratio with insulin resistance in middle-aged and older adults. Methods: This was a cross-sectional analysis in 548 participants (mean ± SD age: 66.2 ± 13.7 y) from the calibration substudy of the AHS-2 (Adventist Health Study 2) cohort. Participants consumed diets with a low AP intake ratio. Dietary intakes of total and particular types of protein were calculated from six 24-h dietary recalls. Participants completed a self-administered questionnaire on demographic, lifestyle, health, diet intake, and physical activity characteristics. Anthropometric variables including weight, height, and waist circumference were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by using fasting serum glucose and insulin. Multiple linear regression models were used to test the relations between total and specific protein intakes with insulin resistance. Results: The ranges of dietary intakes of animal and plant protein and the AP intake ratio were 0.4-87.4 and 14.0-79.2 g/d and 0.02-4.43, respectively. Dietary intakes per 10-g/d increments of total protein (β: 0.11; 95% CI: 0.02, 0.21) and animal protein (β: 0.11; 95% CI: 0.01, 0.20) and the AP intake ratio (β: 1.82; 95% CI: 0.80, 2.84) were positively related to HOMA-IR. Plant protein was not significantly related to insulin resistance. Conclusion: Total and animal protein intakes and the AP intake ratio were positively associated with HOMA-IR in adults with relatively a low intake of animal protein and a high consumption of plant protein.

The Malawian health sector has a strong tradition of systematic data collection for monitoring and evaluation of large-scale services. A highly successful adapted Directly Observed Treatment, Short course "DOTS" framework, based on patient registers and paper-based mastercards was introduced to facilitate the management and monitoring of the scale up of antiretroviral therapy. Subsequently, a simple, touch-screen based electronic medical record system (EMRs) was effectively introduced at high burden ART sites. Based on this model, in 2010, a diabetes specific EMRs was introduced in the diabetes clinic at Queen Elizabeth Central Hospital. In this paper we report on the first 3 years experience with the diabetes EMRs. We highlight the strengths and weaknesses of the diabetes EMRs and present data on glycaemic control recorded in the system.

Within the spectrum of kinase inhibitors, covalent-reversible inhibitors (CRIs) provide a valuable alternative approach to classical covalent inhibitors. This special class of inhibitors can be optimized for an extended drug-target residence time. For CRIs, it was shown that the fast addition of thiols to electron-deficient olefins leads to a covalent bond that can break reversibly under proteolytic conditions. Research groups are just beginning to include CRIs in their arsenal of compound classes, and, with that, the understanding of this interesting set of chemical warheads is growing. However, systems to assess both characteristics of the covalent-reversible bond in a simple experimental setting are sparse. Here, we have developed an efficient methodology to characterize the covalent and reversible properties of CRIs and to investigate their potential in targeting clinically relevant variants of the receptor tyrosine kinase EGFR.

A novel to Europe Schmallenberg virus (SBV) causes clinical disease manifested by reproduction disorders in farm ruminants. In free-living ruminants, SBV antibodies as well as the virus were detected. Recent studies also revealed SBV antibodies in wild boars. The study investigates SBV antibodies occurring in wild boars in Poland at the peak of recent virus epidemics in the country.