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Percutaneous coronary intervention, a common treatment for atherosclerotic coronary artery lesions, occasionally results in perforations associated with increased mortality rates. Stents coated with a bioresorbable polymer membrane may offer an effective solution for sealing coronary artery perforations. Additionally, such coatings could be effective in mitigating neointimal hyperplasia within the vascular lumen and correcting symptomatic aneurysms. This study examines polymer membranes fabricated by electrospinning of polycaprolactone, polydioxanone, polylactide-co-caprolactone, and polylactide-co-glycolide. In uniaxial tensile tests, all the materials appear to surpass theoretically derived elongation thresholds necessary for stent deployment, albeit polydioxanone membranes are found to disintegrate during the experimental balloon expansion. As revealed by in vitro hemocompatibility testing, polylactide-co-caprolactone membranes exhibit higher thrombogenicity compared to other evaluated polymers, while polylactide-co-glycolide samples fail within the first day post-implantation into the abdominal aorta in rats. The PCL membrane exhibited significant water leakage in the permeability test. Comprehensive evaluation of mechanical testing, bio- and hemocompatibility, as well as biodegradation dynamics shows the advantage of membranes based on and the mixture of polylactide-co-caprolactone and polydioxanone over other polymer groups. These findings lay a foundational framework for conducting preclinical studies on stent configurations in large laboratory animals, emphasizing that further investigations under conditions closely mimicking clinical use are imperative for making definitive conclusions.

Measurements of water vapor are important for understanding the hydrological cycle, the thermodynamic structure of the lower troposphere, and broader atmospheric circulation. Subsequently, many scientific communities have emphasized a need for high-accuracy and spatial resolution profiles of water vapor within and above the planetary boundary layer (PBL). Advancements in lidar technologies at the NASA Langley Research Center are ongoing to enable the first space-based water vapor differential absorption lidar (DIAL) that can provide high-accuracy and vertical resolution retrievals of moisture in the PBL and through the mid-troposphere. The performance of this space-based DIAL is assessed here for sensitivity throughout the troposphere and globally with representative canonical cases of water vapor and aerosol loading. The specific humidity retrieval sensitivity to systematic and random errors is assessed, and measurement resolutions and capabilities are provided. We show that tunable operation along the side of the 823-nm absorption line allows for the optimization of the lower-tropospheric water vapor retrievals across different meteorological regimes and latitudes and provides the operational flexibility needed to dynamically optimize random errors for different scientific applications. The analysis presented here suggests that baseline and threshold systematic error requirements of

Consumption of fish containing elevated levels of radionuclides can lead to undesirable health effects for consumers. People in the Singida Municipality harvest fish from lakes and ponds of granite rocks which are linked with hazardous radioisotopes that may be bio-concentrated by fishes they consume. Currently, no study has ascertained the levels of radioisotopes in fish from these environments. This study was carried out to analyse the radioactivity levels of 226Ra, 228Ra and 40K isotopes in order to assess the radiological risk associated with Tilapia fish consumption and its environment in Singida Municipality. Some 51 samples, which included water (20), sediment (20), Nile tilapia (8) and Manyara tilapia (3), were randomly sampled and composited; then, they were analysed using a high-purity germanium (HPGe) detector, between May and June 2022. The results revealed that (i) the activity levels of 228Ra were below the detection limit for fish and water samples, while in sediment, the combined activity of 228Ra was within the acceptable international levels; (ii) the mean activity concentrations of 226Ra and 40K in all other samples were within the recommended levels; (iii) the activities of radionuclides in the samples analysed were high in sediments, followed by fish, and lastly water; (iv) the bioaccumulation results show that only 40K was bio-accumulated (with 1.26 in Nile tilapia), while other radionuclides (226Ra, 228Ra) were not bio-accumulated; (vi) the radionuclide transfer from water to fish was higher compared to the radionuclide transfer from sediment to fish; (vii) the human effective doses due to consumption of Nile tilapia and Manyara tilapia were 0.00973 and 0.005 mSv/y, respectively, which is below the 1 mSv/y international limit. These findings therefore show that the current levels of radioactivity in fish in the study area do not pose a significant radiological risk to fish consumers. However, more studies on other types of fish are recommended.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10–9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

Abstract Background Despite sexual development being ubiquitous to vertebrates, the molecular mechanisms underpinning this fundamental transition remain largely undocumented in many organisms. We designed a time course experiment that successfully sampled the period when Atlantic salmon commence their trajectory towards sexual maturation. Results Through deep RNA sequencing, we discovered key genes and pathways associated with maturation in the pituitary-ovarian axis. Analyzing DNA methylomes revealed a bias towards hypermethylation in ovary that implicated maturation-related genes. Co-analysis of DNA methylome and gene expression changes revealed chromatin remodeling genes and key transcription factors were both significantly hypermethylated and upregulated in the ovary during the onset of maturation. We also observed changes in chromatin state landscapes that were strongly correlated with fundamental remodeling of gene expression in liver. Finally, a multiomic integrated analysis revealed regulatory networks and identified hub genes including TRIM25 gene (encoding the estrogen-responsive finger protein) as a putative key regulator in the pituitary that underwent a 60-fold change in connectivity during the transition to maturation. Conclusion The study successfully documented transcriptome and epigenome changes that involved key genes and pathways acting in the pituitary – ovarian axis. Using a Systems Biology approach, we identified hub genes and their associated networks deemed crucial for onset of maturation. The results provide a comprehensive view of the spatiotemporal changes involved in a complex trait and opens the door to future efforts aiming to manipulate puberty in an economically important aquaculture species.

Gulnur Com,1 Raid Amin,2 Mohini Gunnett,3 Callah Antonetti4 1Department of Pediatric Pulmonology, University of Florida, Ascension Sacred Heart, Pensacola, FL, USA; 2Department of Mathematics & Statistics, University of West Florida, Pensacola, FL, USA; 3Department of Pediatric Pulmonology, University of Alabama, Birmingham, AL, USA; 4Department of Pediatrics, University of Florida, Ascension Sacred Heart, Pensacola, FL, USACorrespondence: Callah Antonetti, Department of Pediatrics, University of Florida and Ascension Sacred Heart, Pensacola, FL, USA, Tel +1 850 416-4071, Fax +1 850 416-4246, Email callahantonetti@ufl.eduPurpose: To describe the socio-demographics and clinical characteristics of children in a pulmonology clinic or admitted to a children’s hospital with well-controlled and poorly controlled asthma, and to assess caregiver knowledge of asthma pathogenesis, treatment, and self-management.Patients and Methods: A cohort of 132 children aged 2– 18 years and their caregivers seen in a pediatric pulmonology clinic with a diagnosis of asthma (n=112) or admitted to the hospital with a diagnosis of asthma exacerbation (n=20) were invited to participate in a cross-sectional study. Caregivers completed a survey, which healthcare providers then used to tailor asthma education to the patient and caregiver. Two-tail t-tests and Chi-square tests were used to compare demographics and clinical characteristics of children with well-controlled vs poorly controlled asthma.Results: Of 132 children, 111 children in this cohort had poorly controlled asthma (84%). Medicaid insurance was associated with poorly controlled asthma versus well-controlled asthma (63% vs 35% p=0.01). Asthma action plans (AAP) had previously been given to 113 caregivers (86%), but caregivers of children with both well-controlled and poorly controlled asthma still reported misconceptions about asthma pathology and management, such as stopping daily medications when asthma is controlled.Conclusion: This study contributes to the existing evidence that socio-demographics have a significant impact on asthma prevalence and proper management. Our study suggests that caregivers of children with asthma need comprehensive asthma education beyond the AAP focusing on asthma-related misconceptions.Keywords: asthma, asthma education

Acute tubular necrosis (ATN) is the most important and frequent cause of acute kidney injury (AKI). Controversy exists concerning the role of renal biopsy in the evaluation of ATN prognosis. We aim in our study to evaluate the role of renal biopsy for the detection of recovery and progression and rate of recovery of ATN. The study was designed to include all biopsies with the diagnosis in ATN in adults >21-year-old, from January 2016 to December 2018. Biopsies were recruited retrospectively and were reviewed by three pathologists and quantitated. Four histological ATN features were evaluated. Flattening cells, distension or dilatation, debris, and vacuolation and for each a score were attributed as follows: 0 = less than 5% of section, 1 = 6%–25%, 2 = 26%–50%, 3 = >50%. Thirty-five patients with 35 renal biopsies were analyzed. Flattening was seen 50% in five patients. Dilatation was seen 50% in eight patients. The presence of debris was seen in 50% seen in five patient. Vacuolation was seen in 5% in eight patients, 6%–25% in 14 patients, 26%–50% in seven patients, and >50% in six patients. It was found that flattening 50% in renal biopsy are the good indicators for recovery and good prognosis of cases of ATN, in addition debris 50% and vacuolation 50% are also indicators for delayed recovery and poor prognosis of cases of ATN. Renal biopsy in AKI with the diagnosis of ATN with scoring system of flattening, dilatation, debris, and vacuolation can point to indication of recovery or progression of these cases.

Background: There are two main causes of exudative effusion including malignancy-induced effusion and tuberculosis. Considering that in reactive ejections, such as tuberculosis-induced effusion, the role of B lymphocytes and in the malignant effusion, the role of T lymphocytes are more important, in this study we analyzed the frequency of CD4, CD8, CD19, CD56-16, CD64, QuantiFERON in the pleural and serum samples of patients with exudative lymphocytic-dominant effusion. Methods: In total, 73 patients were enrolled in the study by exudative lymphocyte effusion, and finally, 63 patients had definite diagnoses. The patients were sorted into three groups including malignant, tuberculosis, and none. The sample of blood plasma and pleural effusion were collected and CD markers were analyzed using flow cytometry. Results: The mean age in the malignancy and tuberculous (TB) groups was 63.16 ± 12 and 52.15 ± 22.62, respectively. There was no significant difference in the frequency of CD8, CD4, and CD16-56 cells in blood samples of patients with tuberculosis and malignancy. Compared to those with tuberculosis, the percentage of CD64 cells was significantly higher in patients with tuberculosis than in malignant subjects. Moreover, a comparison of the frequency of cells with CD8, CD4, CD19, CD64, CD16-56, and CD14 markers in pleural samples showed no significant difference between groups. Other inflammatory factors were also investigated. The erythrocyte sedimentation rate (ESR) value for tuberculosis patients was significantly higher than malignancy. Also, QuantiFERON was positive in 14.3% of malignant patients, and 62.5% of patients with TB, which had a significant difference.Conclusion: Considering that there are many confounding variables in the study, such as previous medications, subtypes of Mycobacterium, and race of patients conducting studies in different groups and performing data mining for using a set of parameters can be used to detect the exact diagnosis.

Background Coronavirus disease-19 (COVID-19) is an ongoing pandemic causing considerable fatalities worldwide. Vitamin D modulates the immune response through effects on various cells, such as: macrophages, B and T lymphocytes, neutrophils, and dendritic cells. Aim To explore whether supplementation of vitamin D, in the form of a single intramuscular cholecalciferol injection, to patients with diabetes, COVID-19, and low vitamin D levels could improve the prognosis of those patients. Methods This was a placebo-controlled randomized prospective study. The study has two arms as follows: the intervention arm (40 vitamin D deficient diabetes elderly patients that acquired SARS-CoV-2), compared to the control arm (16 elderly diabetes patients, with deficient vitamin D with SARS-CoV-2). Patients in the intervention arm were given vitamin D as a single intramuscular injection (200,000 IU); patients in the control arm were given placebo. The primary outcome was mortality within 6 weeks of the diagnosis of COVID-19. Clinical, laboratory, treatment, and outcome data were recorded after 6 weeks of follow-up. Results No significant difference in 6 weeks mortality was observed between patients who received vitamin D and patients who received placebo (17.5% vs 18.8%, p = 0.838). Age, presence of hypertension, and chronic obstructive pulmonary disease were independent predictors of mortality at 6 weeks. Conclusion Vitamin D supplementation did not reduce the severity or mortality of COVID-19 at 6 weeks. Further large scale studies are required to explore the effect of vitamin D therapy on survival in patients with diabetes mellitus who acquire COVID-19.

Abstract Background Dinoflagellates in the family Symbiodiniaceae are important photosynthetic symbionts in cnidarians (such as corals) and other coral reef organisms. Breakdown of the coral-dinoflagellate symbiosis due to environmental stress (i.e. coral bleaching) can lead to coral death and the potential collapse of reef ecosystems. However, evolution of Symbiodiniaceae genomes, and its implications for the coral, is little understood. Genome sequences of Symbiodiniaceae remain scarce due in part to their large genome sizes (1–5 Gbp) and idiosyncratic genome features. Results Here, we present de novo genome assemblies of seven members of the genus Symbiodinium, of which two are free-living, one is an opportunistic symbiont, and the remainder are mutualistic symbionts. Integrating other available data, we compare 15 dinoflagellate genomes revealing high sequence and structural divergence. Divergence among some Symbiodinium isolates is comparable to that among distinct genera of Symbiodiniaceae. We also recovered hundreds of gene families specific to each lineage, many of which encode unknown functions. An in-depth comparison between the genomes of the symbiotic Symbiodinium tridacnidorum (isolated from a coral) and the free-living Symbiodinium natans reveals a greater prevalence of transposable elements, genetic duplication, structural rearrangements, and pseudogenisation in the symbiotic species. Conclusions Our results underscore the potential impact of lifestyle on lineage-specific gene-function innovation, genome divergence, and the diversification of Symbiodinium and Symbiodiniaceae. The divergent features we report, and their putative causes, may also apply to other microbial eukaryotes that have undergone symbiotic phases in their evolutionary history.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.

Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.

Abstract Background Dinoflagellates are taxonomically diverse and ecologically important phytoplankton that are ubiquitously present in marine and freshwater environments. Mostly photosynthetic, dinoflagellates provide the basis of aquatic primary production; most taxa are free-living, while some can form symbiotic and parasitic associations with other organisms. However, knowledge of the molecular mechanisms that underpin the adaptation of these organisms to diverse ecological niches is limited by the scarce availability of genomic data, partly due to their large genome sizes estimated up to 250 Gbp. Currently available dinoflagellate genome data are restricted to Symbiodiniaceae (particularly symbionts of reef-building corals) and parasitic lineages, from taxa that have smaller genome size ranges, while genomic information from more diverse free-living species is still lacking. Results Here, we present two draft diploid genome assemblies of the free-living dinoflagellate Polarella glacialis, isolated from the Arctic and Antarctica. We found that about 68% of the genomes are composed of repetitive sequence, with long terminal repeats likely contributing to intra-species structural divergence and distinct genome sizes (3.0 and 2.7 Gbp). For each genome, guided using full-length transcriptome data, we predicted > 50,000 high-quality protein-coding genes, of which ~40% are in unidirectional gene clusters and ~25% comprise single exons. Multi-genome comparison unveiled genes specific to P. glacialis and a common, putatively bacterial origin of ice-binding domains in cold-adapted dinoflagellates. Conclusions Our results elucidate how selection acts within the context of a complex genome structure to facilitate local adaptation. Because most dinoflagellate genes are constitutively expressed, Polarella glacialis has enhanced transcriptional responses via unidirectional, tandem duplication of single-exon genes that encode functions critical to survival in cold, low-light polar environments. These genomes provide a foundational reference for future research on dinoflagellate evolution.

MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence in order to reach the molecular mechanism and clinical significance of miR-877 in different types of cancer. Dysregulation of miR-877 level in various types of malignancies as bladder cancer, cervical cancer, cholangiocarcinoma, colorectal cancer (CRC), gastric cancer, glioblastoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma, laryngeal squamous cell carcinoma, melanoma, non-small cell lung cancer (NSCLC), oral squamous cell carcinoma, ovarian cancer (OC), pancreatic ductal adenocarcinoma, and renal cell carcinoma (RCC) have reported, significantly increase or decrease in its level, which can be indicated to its function as oncogene or tumor suppressor. MiR-877 is involved in cell proliferation, migration, and invasion through cell cycle pathways in cancer. MiR-877 could be potential a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-877 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis.

Currently, an ultrastructural analysis of cardiovascular tissues is significantly complicated. Routine histopathological examinations and immunohistochemical staining suffer from a relatively low resolution of light microscopy, whereas the fluorescence imaging of plaques and bioprosthetic heart valves yields considerable background noise from the convoluted extracellular matrix that often results in a low signal-to-noise ratio. Besides, the sectioning of calcified or stent-expanded blood vessels or mineralised heart valves leads to a critical loss of their integrity, demanding other methods to be developed. Here, we designed a conceptually novel approach that combines conventional formalin fixation, sequential incubation in heavy metal solutions (osmium tetroxide, uranyl acetate or lanthanides, and lead citrate), and the embedding of the whole specimen into epoxy resin to retain its integrity while accessing the region of interest by grinding and polishing. Upon carbon sputtering, the sample is visualised by means of backscattered scanning electron microscopy. The technique fully preserves calcified and stent-expanded tissues, permits a detailed analysis of vascular and valvular composition and architecture, enables discrimination between multiple cell types (including endothelial cells, vascular smooth muscle cells, fibroblasts, adipocytes, mast cells, foam cells, foreign-body giant cells, canonical macrophages, neutrophils, and lymphocytes) and microvascular identities (arterioles, venules, and capillaries), and gives a technical possibility for quantitating the number, area, and density of the blood vessels. Hence, we suggest that our approach is capable of providing a pathophysiological insight into cardiovascular disease development. The protocol does not require specific expertise and can be employed in virtually any laboratory that has a scanning electron microscope.

Abstract Background A key developmental transformation in the life of all vertebrates is the transition to sexual maturity, whereby individuals are capable of reproducing for the first time. In the farming of Atlantic salmon, early maturation prior to harvest size has serious negative production impacts. Results We report genome wide association studies (GWAS) using fish measured for sexual maturation in freshwater or the marine environment. Genotypic data from a custom 50 K single nucleotide polymorphism (SNP) array was used to identify 13 significantly associated SNP for freshwater maturation with the most strongly associated on chromosomes 10 and 11. A higher number of associations (48) were detected for marine maturation, and the two peak loci were found to be the same for both traits. The number and broad distribution of GWAS hits confirmed a highly polygenetic nature, and GWAS performed separately within males and females revealed sex specific genetic behaviour for loci co-located with positional candidate genes phosphatidylinositol-binding clathrin assembly protein-like (picalm) and membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (magi2). Conclusions The results extend earlier work and have implications for future applied breeding strategies to delay maturation in this important aquaculture species.

Insulin growth factor-1 (IGF-1) and growth hormone (GH) have cardiac protective effects through many mechanisms; they can directly oppose endothelial dysfunction in a number of ways. Many studies assessed the effect of GH or IGF-like growth factor 1 in patients with cardiac dysfunction, but no previous study assessed the GH and insulin-like growth factor-1 in renal transplant recipients with and without cardiac dysfunction, especially elderly. Eighty patients with renal transplantation and age limit above 75 years. They were subdivided into two groups according to the presence or absence of cardiac dysfunction based on medical history, clinical findings, electrocardiogram, and echocardiography. Serum GH and insulin-like growth factor-1 were studied by immunoradiometric assay. The echocardiography study was performed. M-mode two-dimensional and Doppler measurements were taken to obtain the four- and five-chamber views, chambers' dimensions, left ventricular end-diastolic dimensions, left ventricular end-systolic dimensions, septal wall thickness (SWT), distance between leading edges of the endocardial and pericardial echoes of left ventricular posterior wall (posterior wall thickness), aortic root and left atrial dimensions (LAD), fractional shortening and ejection fraction. IGF-1 is lower in patients with cardiac dysfunction with renal transplantation with mean value of 61 ± 30.05 than those control group with mean value 145.52 ± 70.5. Level of human growth factor is higher in patients with dysfunction with renal transplantation with mean value 2.62 ± 3.05 than those control group after renal transplantation with mean value 0.85 ± 0.9. No correlations were found between IGF-1 and various echocardiographic parameters. Only SWT and LAD were negatively correlated with GH, r = −0.08, P

Matrix metalloproteinase-2 (MMP2) has been implicated in chronic disease and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with diabetic nephropathy (DN). We investigated whether serum MMP-2 levels were associated with proteinuria, intima-media thickness (IMT) in DN patients. Diabetic patients not on hemodialysis (n = 50) were enrolled for the study. MMP-2 levels were measured using an ELISA system. IMT was evaluated by highresolution ultrasonography. Univariate analyses revealed that MMP-2 (P = 0.013) were independent correlates of proteinuria. Further, multivariate analyses revealed that MMP-2 levels (P = 0.001) were independent correlates of IMT. MMP-2 levels were significantly (P = 0.001) higher in patients with atherosclerosis than those without it. The present study demonstrates that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with DN. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in DN patients.

Introduction and aims Pretransplant administration of cyclosporine (CsA) may reduce post-transplant maintenance dose and consequently CsA inhibitor nephrotoxicity and helps in achieving the desired target C2 levels earlier. The optimum dose or timing of administration of CsA induction dose is still debatable. Patients and methods We compared three different protocols for pretransplant administration of CsA aiming to reach a target C2 therapeutic level of greater than 800 ng/ml on the third day post-transplant. Sixty kidney transplant recipients from Cairo University hospitals were divided into: group 1 (n=20) who received a single CsA induction dose of 2 mg/kg 12 h pretransplant; group 2 (n=20) who received four CsA consecutive doses of 4 mg/kg 48 h pre-transplant; and group 3 (n=20) who received four CsA consecutive doses of 2 mg/kg 48 h pretransplant. Results The desired therapeutic level in the earlier post-transplantation period was achieved in 65% in group 1, 100% in groups 2 and 3). In group 2 a lower dose was needed to maintain C2 within the therapeutic range during the first year post-transplantation (P

Objectives: Despite many publications describing sheep models for functional endoscopic sinus surgery (FESS) procedures, accurate endoscopic anatomical studies are lacking. There are no publications correlating computed tomography (CT) and 3D models with endoscopic anatomical descriptions. This study evaluates and describes the endoscopic anatomy of a sheep model. Methods: Ten live sheep (20-sides) were included. Two cadaveric specimens, imaged using thin slice CT for 3D reconstruction correlation were also included. Using endoscopy, anatomical structures were measured and described. Measurement of the same structures was carried out using the 3D imaging model. Results: Three sets of turbinates were identified at 2.3, 5.1 and 8.5 cm from the anterior nasal sill. Frontal recess and uncinate process were identified at 12.7 cm. The septum has a bony and cartilaginous component and measures 10.5 cm. The sphenopalatine foramen was measured at 12.1 cm. All anatomical measurements were correlated with the measurements on the CT scan 3D volume-rendering model, thereby allowing for an accurate description of the sheep sinonasal anatomy. Conclusion: This study describes the endoscopic sinonasal anatomical measurements of the adult sheep. It is the first study to evaluate the sheep CT and endoscopic anatomy in order to determine its feasibility as an animal model for research in FESS. Keywords: Sinus anatomy, Animal model, Sinus endoscopy, Sinus research, Sinus surgery

Marine farmed Atlantic salmon (Salmo salar) are susceptible to recurrent amoebic gill disease (AGD) caused by the ectoparasite Neoparamoeba perurans over the growout production cycle. The parasite elicits a highly localized response within the gill epithelium resulting in multifocal mucoid patches at the site of parasite attachment. This host-parasite response drives a complex immune reaction, which remains poorly understood. To generate a model for host-parasite interaction during pathogenesis of AGD in Atlantic salmon the local (gill) and systemic transcriptomic response in the host, and the parasite during AGD pathogenesis was explored. A dual RNA-seq approach together with differential gene expression and system-wide statistical analyses of gene and transcription factor networks was employed. A multi-tissue transcriptomic data set was generated from the gill (including both lesioned and non-lesioned tissue), head kidney and spleen tissues naïve and AGD-affected Atlantic salmon sourced from an in vivo AGD challenge trial. Differential gene expression of the salmon host indicates local and systemic upregulation of defense and immune responses. Two transcription factors, znfOZF-like and znf70-like, and their associated gene networks significantly altered with disease state. The majority of genes in these networks are candidates for mediators of the immune response, cellular proliferation and invasion. These include Aurora kinase B-like, rho guanine nucleotide exchange factor 25-like and protein NDNF-like inhibited. Analysis of the N. perurans transcriptome during AGD pathology compared to in vitro cultured N. perurans trophozoites, as a proxy for wild type trophozoites, identified multiple gene candidates for virulence and indicates a potential master regulatory gene system analogous to the two-component PhoP/Q system. Candidate genes identified are associated with invasion of host tissue, evasion of host defense mechanisms and formation of the mucoid lesion. We generated a novel model for host-parasite interaction during AGD pathogenesis through integration of host and parasite functional profiles. Collectively, this dual transcriptomic study provides novel molecular insights into the pathology of AGD and provides alternative theories for future research in a step towards improved management of AGD.

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory “dimensions” coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module.

Introduction and aim of the work Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) are at increased risk of renal disease. This study compares factors associated with proteinuria and doubling of serum creatinine level in patients who were infected with HCV or HBV alone with those who were coinfected with HCV and HBV. Materials and methods The study was performed on 1243 patients who were diagnosed with HBV and/or HCV at the Cairo University Hospitals. All the included subjects underwent urine analysis for proteinuria and serum creatinine level. Clinical characteristics were recorded at baseline and at last follow-up. Results Of 1243 patients, 293 (23.6%) patients had proteinuria. Subset analysis of the patients with proteinuria showed that 10.6% were HBV infected, 63.8% were HCV infected, and the remaining 25.6% were coinfected with both HBV and HCV. Overall, coinfection with both viruses (P=0.01), lower serum albumin (P=0.001), hypertension (P=0.01), and diabetes (P=0.001) were associated with an increase in risk of proteinuria. Coinfection (P=0.001), presence of HBV (P=0.001), and increasing HCV RNA level in patients with HCV and in coinfected patients (P=0.05) was associated with doubling of serum creatinine level. Conclusion The patients coinfected with HBV and HCV are at greater risk of clinically significant proteinuria and loss of renal function owing to complex virological profile. Progressive loss of renal function in that population is associated with markers of viral activity such as proteinuria and increasing HCV RNA levels among HCV-infected patients.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Tissue-engineered vascular graft for the reconstruction of small arteries is still an unmet clinical need, despite the fact that a number of promising prototypes have entered preclinical development. Here we test Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)Poly(ε-caprolactone) 4-mm-diameter vascular grafts equipped with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and stromal cell-derived factor 1α (SDF-1α) and surface coated with heparin and iloprost (PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo, n = 8) in a sheep carotid artery interposition model, using biostable vascular prostheses of expanded poly(tetrafluoroethylene) (ePTFE, n = 5) as a control. Primary patency of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts was 62.5% (5/8) at 24 h postimplantation and 50% (4/8) at 18 months postimplantation, while all (5/5) ePTFE conduits were occluded within the 24 h after the surgery. At 18 months postimplantation, PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts were completely resorbed and replaced by the vascular tissue. Regenerated arteries displayed a hierarchical three-layer structure similar to the native blood vessels, being fully endothelialised, highly vascularised and populated by vascular smooth muscle cells and macrophages. The most (4/5, 80%) of the regenerated arteries were free of calcifications but suffered from the aneurysmatic dilation. Therefore, biodegradable PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts showed better short- and long-term results than bio-stable ePTFE analogues, although these scaffolds must be reinforced for the efficient prevention of aneurysms.

Respiratory tract infections are prevalent among Hajj pilgrims with pneumonia being a leading cause of hospitalization. Streptococcus pneumoniae is a common pathogen isolated from patients with pneumonia and respiratory tract infections during Hajj. There is a significant burden of pneumococcal disease in India, which can be prevented. Guidelines for preventive measures and adult immunization have been published in India, but the implementation of the guidelines is low. Data from Bangladesh are available about significant mortality due to respiratory infections; however, literature regarding guidelines for adult immunization is limited. There is a need for extensive awareness programs across India and Bangladesh. Hence, there was a general consensus about the necessity for a rapid and urgent implementation of measures to prevent respiratory infections in pilgrims traveling to Hajj. About ten countries have developed recommendations for pneumococcal vaccination in Hajj pilgrims: France, the USA, Kuwait, Qatar, Bahrain, the UAE (Dubai Health Authority), Singapore, Malaysia, Egypt, and Indonesia. At any given point whether it is Hajj or Umrah, more than a million people are present in the holy places of Mecca and Madina. Therefore, the preventive measures taken for Hajj apply for Umrah as well. This document puts forward the consensus recommendations by a group of twenty doctors following a closed-door discussion based on the scientific evidence available for India and Bangladesh regarding the prevention of respiratory tract infections in Hajj pilgrims.

The development of novel biodegradable vascular grafts of a small diameter (Hep/Ilo). Animals with carotid artery autograft implantation and those implanted with clinically used GORE-TEX® grafts were used as control groups. We observed that 24 h following surgery, animals with carotid artery autograft implantation showed 87.5% patency, while all the PHBV/PCL-GFmix and GORE-TEX® grafts displayed thrombosis. PHBV/PCL-GFmixHep/Ilo grafts demonstrated 62.5% patency 24 h following surgery and it had remained at 50% 1 year post-operation. All the PHBV/PCL grafts completely degraded less than 1 year following surgery and were replaced by de novo vasculature without evidence of calcification. On the other hand, GORE-TEX® grafts displayed substantial amounts of calcium deposits throughout graft tissues. Thus, here we report a potential clinical usefulness of PHBV/PCL grafts upon their additional modification by growth factors and drugs to promote endothelialization and reduce thrombogenicity.

The availability of a reference genome assembly for Atlantic salmon, Salmo salar, SNP genotyping platforms and low cost sequencing are enhancing the understanding of both life history and production-related traits in this important commercial species. We collected and analyzed transcriptomes from selected tissues of Atlantic salmon to inform future functional and comparative genomics studies. Messenger RNA (mRNA) was isolated from pituitary gland, brain, ovary, and liver before Illumina sequencing produced a total of 640 million 150-bp paired-end reads. Following read mapping, feature counting, and normalization, cluster analysis identified genes highly expressed in a tissue-specific manner. We identified a cluster of 508 tissue specific genes for pituitary gland, 3395 for brain, 2939 for ovary, and 539 for liver. Functional profiling identified gene clusters describing the unique functions of each tissue. Moreover, highly-expressed transcription factors (TFs) present in each tissue-specific gene cluster were identified. TFs belonging to homeobox and bhlh families were identified for pituitary gland, pou and zf-c2h2 families for brain, arid, and zf-c2h2 for ovary and rxr-like family for liver. The data and analysis presented are relevant to the emerging Functional Annotation of All Salmonid Genomes (FAASG) initiative that is seeking to develop a detailed understanding of both salmonid evolution and the genomic elements that drive gene expression and regulation.

A laser transmitter has been developed and incorporated into a micro-pulse differential absorption lidar (DIAL) for water vapor profiling in the lower troposphere as an important step towards long-term autonomous field operation. The laser transmitter utilizes two distributed Bragg reflector (DBR) diode lasers to injection seed a pulsed tapered semiconductor optical amplifier (TSOA), and is capable of producing up to 10 mJ of pulse energy with a 1 ms pulse duration and a 10 kHz pulse repetition frequency. The on-line wavelength of the laser transmitter can operate anywhere along the water vapor absorption feature centered at 828.187 nm (in vacuum) depending on the prevailing atmospheric conditions, while the off-line wavelength operates at 828.287 nm. This laser transmitter has been incorporated into a DIAL instrument utilizing a 35.6 cm Schmidt-Cassegrain telescope and fiber coupled avalanche photodiode (APD) operating in the photon counting mode. The performance of the DIAL instrument was demonstrated over a ten-day observation period. During this observation period, data from radiosondes were used to retrieve water vapor number density profiles for comparisons with the number density profiles retrieved from the DIAL data.

SM Sabbir Alam,1 Ruhul Amin,1 Mohammed Ziaur Rahman,2 M Anwar Hossain,1 Munawar Sultana11Department of Microbiology, University of Dhaka, Dhaka, Bangladesh; 2International Centre for Diarrhoeal Disease Research, Dhaka, BangladeshAbstract: Foot and mouth disease virus (FMDV), with its seven serotypes, is a highly contagious virus infecting mainly cloven-hoofed animals. The serotype Asia1 occurs mainly in Asian regions. An in-silico approach was taken to reveal the antigenic heterogeneities within the capsid protein VP1 of Asia1. A total of 47 VP1 sequences of Asia1 isolates from different countries of South Asian regions were selected, retrieved from database, and were aligned. The structure of VP1 protein was modeled using a homology modeling approach. Several antigenic sites were identified and mapped onto the three-dimensional protein structure. Variations at these antigenic sites were analyzed by calculating the protein variability index and finding mutation combinations. The data suggested that vaccine escape mutants have derived from only few mutations at several antigenic sites. Five antigenic peptides have been identified as the least variable epitopes, with just fewer amino acid substitutions. Only a limited number of serotype Asia1 antigenic variants were found to be circulated within the South Asian region. This emphasizes a possibility of formulating synthetic vaccines for controlling foot-and-mouth disease by Asia1 serotypes.Keywords: protein modeling, antigenic sites, sequence variation

Background It is recognized that patients who undergo endoscopic sinus surgery (ESS) do not always achieve control of their disease. The causes are multifactorial; variations in surgical practice have been identified as possible factors in refractory disease. Objective To reflect on the frequent anatomic findings of patients with chronic rhinosinusitis (CRS) who require revision ESS. Methods A retrospective review of patients who required revision ESS at a tertiary institution over a 3-year period. Patients for whom maximal medical therapy failed for CRS underwent computed tomography of the paranasal sinuses and image-guided surgery. Surgical records of anatomic findings were reviewed and analyzed. Results Over 3 years, a total of 75 patients underwent revision procedures, 28% of all ESS performed in the unit. The most frequent finding was a residual uncinate process in 64% of the patients (n = 48); other findings included a maxillary antrostomy not based on the natural ostium of the maxillary sinus in 47% (n = 35), an oversized antrostomy in 29% (n = 22), resected middle turbinates in 35% (n = 26), middle meatal stenosis in 15% (n = 11), synechiae in 29% (n = 22), and osteitic bone that required drilling in 13% (n = 10). Conclusion Surgical technique can give rise to anatomic variations that may prevent adequate mucociliary clearance and medication delivery, which leads to failure in ESS in patients with CRS. This study demonstrated the surgical findings encountered in revision ESS that should be highlighted in the training of Ear, Nose and Throat surgeons to help prevent primary failure and reduce health care costs.

The combination of a natural hydrophilic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(ε-caprolactone) (PCL) is promising for the preparation of biodegradable and biocompatible small-diameter vascular grafts for bypass surgery. However, physico-mechanical properties and endothelialization rate of PHBV/PCL grafts are poor. We suggested that incorporation of vascular endothelial growth factor (VEGF) into PHBV/PCL grafts may improve their physico-mechanical properties and enhance endothelialization. Here we compared morphology, physico-mechanical properties, and in vivo performance of electrospun small-diameter vascular grafts prepared from PHBV/PCL with and without VEGF. Structure of the graft surface and physico-mechanical properties were examined by scanning electron microscopy and universal testing machine, respectively. Grafts were implanted into rat abdominal aorta for 1, 3, and 6 months with the further histological, immunohistochemical, and immunofluorescence examination. PHBV/PCL grafts with and without VEGF were highly porous and consisted mostly of nanoscale and microscale fibers, respectively. Mean pore diameter and mean pore area were significantly lower in PHBV/PCL/VEGF compared to PHBV/PCL grafts (1.47 µm and 10.05 µm2; 2.63 µm and 47.13 µm2, respectively). Durability, elasticity, and stiffness of PHBV/PCL grafts with VEGF were more similar to internal mammary artery compared to those without, particularly 6 months postimplantation. Both qualitative examination and quantitative image analysis showed that three-fourths of PHBV/PCL grafts with VEGF were patent and had many CD31-, CD34-, and vWF-positive cells at their inner surface. However, all PHBV/PCL grafts without VEGF were occluded and had no or a few CD31-positive cells at the inner surface. Therefore, VEGF enhanced endothelialization and improved graft patency at all the time points in a rat abdominal aorta replacement model. In conclusion, PHBV/PCL grafts with VEGF have better biocompatibility and physico-mechanical properties compared to those without. Incorporation of VEGF improves graft patency and accelerates formation of endothelial cell monolayer.

Background During the past decade, the number of Egyptians showing overweight and obesity as measured in terms of BMI (kg/m2) has been documented through different surveys. This increase in adiposity has been associated with metabolic syndromes in Egyptians and with higher fasting insulin concentrations. The purpose of this study was to assess the relationship between BMI and percentage body fat (PBF) in Egyptians and to determine whether this relationship differs between men and women. MethodsWe conducted a cohort study including 152 healthy participants; body fat composition was calculated using the BMI equation and bioelectrical impedance (BEI). Results The predicted PBF values based on BMI values between 15 and 50 for women and 18 and 50 for men were analysed, which showed that the trend of predicted PBF values differs in accordance with BMI:at BMI at least 30, men tended to have higher PBF compared with women;at BMI at least 35, women tended to have higher PBF compared with men. Conclusion The present study has investigated the relationship between PBF and BMI in Egyptians. The Results show a significant difference in PBF on the basis of BMI and sex. There are some potential explanations for this difference, including sedentary lifestyles and possible genetic makeup. Similar observations with regard to the mediation of BMI on PBF according to sex have been reported previously. It is important to emphasize that the PBF values obtained in this study using BMI are estimates determined on the basis of the samples and that significant differences were found only among women.

OBJECTIVE: As the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT. STUDY DESIGN: The study includes plasma samples collected from patients with high-risk pregnancies in our CLIA-licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting. RESULTS: NIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥ 35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5%) with 2.61% yielding a positive NIPT result. CONCLUSION: NIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the current standard of care.

Circulating cell-free (ccf) fetal DNA comprises 3-20% of all the cell-free DNA present in maternal plasma. Numerous research and clinical studies have described the analysis of ccf DNA using next generation sequencing for the detection of fetal aneuploidies with high sensitivity and specificity. We sought to extend the utility of this approach by assessing semi-automated library preparation, higher sample multiplexing during sequencing, and improved bioinformatic tools to enable a higher throughput, more efficient assay while maintaining or improving clinical performance.Whole blood (10mL) was collected from pregnant female donors and plasma separated using centrifugation. Ccf DNA was extracted using column-based methods. Libraries were prepared using an optimized semi-automated library preparation method and sequenced on an Illumina HiSeq2000 sequencer in a 12-plex format. Z-scores were calculated for affected chromosomes using a robust method after normalization and genomic segment filtering. Classification was based upon a standard normal transformed cutoff value of z = 3 for chromosome 21 and z = 3.95 for chromosomes 18 and 13.Two parallel assay development studies using a total of more than 1900 ccf DNA samples were performed to evaluate the technical feasibility of automating library preparation and increasing the sample multiplexing level. These processes were subsequently combined and a study of 1587 samples was completed to verify the stability of the process-optimized assay. Finally, an unblinded clinical evaluation of 1269 euploid and aneuploid samples utilizing this high-throughput assay coupled to improved bioinformatic procedures was performed. We were able to correctly detect all aneuploid cases with extremely low false positive rates of 0.09%,

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine–glycine–aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31+/CD34+/vWF+ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31+CD34−vWF+ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31+/CD34+ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

Objective: To assess if the pharmacy department should be more involved in the medication reconciliation process to assist in the reduction of medication errors that occur during transition of care points in the hospital setting. Methods: This was an observational prospective cohort study at a 531-bed hospital in Pensacola, FL from June 1, 2014 to August 31, 2014. Patients were included in the study if they had health insurance and were taking five or more medications. Patients with congestive heart failure were excluded from the study. Student pharmacists collected and evaluated medication histories obtained from patients’ community pharmacies, and directed patient interviews. Primary care providers were only contacted on an as needed basis. The information collected was presented to the clinical pharmacist, where interventions were made utilizing clinical judgment. Results: During the three month study, 1045 home medications were reviewed by student pharmacist. Of these, 290 discrepancies were discovered (27.8%; p=0.02). The most common medication discrepancy found was dose optimization (45.5%). The remaining discrepancies included: added therapy (27.6%), other (15.2%), and discontinued therapy (11.7%). Pharmacists made 143 interventions based on clinical judgment (49.3%; p=0.04). Conclusion: Involvement of pharmacy personnel during the medication reconciliation process can be an essential component in reducing medical errors. With the addition of the pharmacy department during the admission process, accuracy, cost savings, and patient safety across all phases and transition points of care were achieved.

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/.

People's subjective response to any thermal environment is commonly investigated by using rating scales describing the degree of thermal sensation, comfort, and acceptability. Subsequent analyses of results collected in this way rely on the assumption that specific distances between verbal anchors placed on the scale exist and that relationships between verbal anchors from different dimensions that are assessed (e.g. thermal sensation and comfort) do not change. Another inherent assumption is that such scales are independent of the context in which they are used (climate zone, season, etc.). Despite their use worldwide, there is indication that contextual differences influence the way the scales are perceived and therefore question the reliability of the scales’ interpretation. To address this issue, a large international collaborative questionnaire study was conducted in 26 countries, using 21 different languages, which led to a dataset of 8225 questionnaires. Results, analysed by means of robust statistical techniques, revealed that only a subset of the responses are in accordance with the mentioned assumptions. Significant differences appeared between groups of participants in their perception of the scales, both in relation to distances of the anchors and relationships between scales. It was also found that respondents’ interpretations of scales changed with contextual factors, such as climate, season, and language. These findings highlight the need to carefully consider context-dependent factors in interpreting and reporting results from thermal comfort studies or post-occupancy evaluations, as well as to revisit the use of rating scales and the analysis methods used in thermal comfort studies to improve their reliability.