Implementation of a patient safety training program in radiation oncology residency: A pilot study.

PURPOSE: An educational program using Radiation Oncology-Incident Learning System (RO-ILS) was developed to improve safety culture and training for radiation oncology (RO) residents. METHODS: The program included a pre-training assessment, interactive training, integration of residents into quality assurance meetings, and a post-training assessment over a 3 month rotation. RESULTS: Twelve residents completed the safety training program. Pre-training assessment mean scores (five-point scale) of experience with Incident Learning Systems (ILS), root-cause analysis (RCA), failure-mode and effect analysis (FMEA), safety training, and culture were 2.3, 2.8, 2.0, 4.0, and 4.4, respectively. Post-training assessment showed a significant increase in ILS 4.0 (p < 0.001), RCA 3.8 (p = 0.008), and FMEA 3.3 (p = 0.006) and safety culture (4.8, p = 0.043). Additionally, residents were anonymously surveyed ≥ 10 months after graduation to determine the long-term value of the program. The overall assessment from the graduated residents indicates that this education is valued by RO in many institutions. The majority of the residents are either currently utilizing or plan to utilize the information gained in this program in their new institutions. CONCLUSIONS: We report a successful implementation of a safety training program in a RO residency with significant improvements in self-reported confidence with the concepts of ILS, RCA, and FMEA and an improved perception of safety culture. This program can be implemented across all residency programs.

Implementation barriers and facilitators to a COVID-19 intervention in Bangladesh: The benefits of engaging the community for the delivery of the programme.

BACKGROUND: BRAC (Bangladesh Rural Advancement Committee), the largest NGO globally, implemented a community-based comprehensive social behavior communication intervention to increase community resilience through prevention, protection, and care for COVID-19. We conducted implementation research to assess fidelity and explore the barriers and facilitators of this intervention implementation. METHODS: We adopted a concurrent mixed-method triangulation design. We interviewed 666 members of 60 Community Corona Protection Committees (CCPCs) and 80 members of 60 Community Support Teams (CSTs) through multi-stage cluster sampling using a structured questionnaire. The qualitative components relied on 54 key informant interviews with BRAC implementers and government providers. RESULTS: The knowledge about wearing mask, keeping social distance, washing hands and COVID-19 symptoms were high (on average more than 70%) among CCPC and CST members. While 422 (63.4%) CCPC members reported they 'always' wear a mask while going out, 69 (86.3%) CST members reported the same practice. Only 247 (37.1%) CCPC members distributed masks, and 229 (34.4%) donated soap to the underprivileged population during the last two weeks preceding the survey. The key facilitators included influential community members in the CCPC, greater acceptability of the front-line health workers, free-of-cost materials, and telemedicine services. The important barriers identified were insufficient training, irregular participation of the CCPC members, favouritism of CCPC members in distributing essential COVID-19 preventive materials, disruption in supply and shortage of the COVID-19 preventative materials, improper use of handwashing station, the non-compliant attitude of the community people, challenges to ensure home quarantine, challenges regarding telemedicine with network interruptions, lack of coordination among stakeholders, the short duration of the project. CONCLUSIONS: Engaging the community in combination with health services through a Government-NGO partnership is a sustainable strategy for implementing the COVID-19 prevention program. Engaging the community should be promoted as an integral component of any public health intervention for sustainability. Engagement structures should incorporate a systems perspective to facilitate the relationships, ensure the quality of the delivery program, and be mindful of the heterogeneity of different community members concerning capacity building. Finally, reaching out to the underprivileged through community engagement is also an effective mechanism to progress through universal health coverage.

Acute monocyte pro inflammatory response predicts higher positive to negative acute phase reactants ratio and severe hemostatic derangement in dengue fever.

PURPOSE: The present study was intended to investigate whether monocyte immune activation shapes plasma positive to negative acute phase reactants (APRs) ratio and predicts disease severity in dengue infection. METHODS: Serum level of ferritin, ceruloplasmin and transferrin was measured by means of electrochemiluminescence and immunoturbidimetry, respectively. Gene expression and plasma level for TNF-α, IL-6 and IL1-ß was measured by means of RT-qPCR and ELISA. RESULTS: A significant increased serum ferritin to transferrin [6.6 (3-11.7) vs 3.4 (1.9-6.1)] and ceruloplasmin to transferrin ratio [0.48 (0.21-0.87) vs 0.22 (0.13-0.43)] has been detected among the subjects with secondary dengue infection (SDENI) compared to primarily infected (PDENI) subjects (P < 0.001). Significant increased expression for CD14+ monocyte TNF-α, IL-6 and IL-1ß has been detected in SDENI patients (vs PDENI and control, P < 0.001). Plasma ferritin to transferrin ratio was found in a significant association with high level of plasma TNF-α [ρ = 0.6522, 95% CI (0.4714-0.7805)], IL-6 [ρ = 0.6181, 95% CI (0.4257-0.7571)] and IL- 1ß [ρ = 0.4119, 95% CI (0.1689-0.6077)] level among SDENI patients at 5th day time point after progression of the disease, with significantly low platelet [P < 0.001] and prolonging prothrombin time [P < 0.001] compared to control and PDENI subjects, respectively. CONCLUSION: Acute proinflammatory cytokine response is significantly associated with increased positive to negative APRs ratio in SDENI patients, which predicts intense immune activation, and renders SDENI patients extremely susceptible to hemostatic derangement.

Evolution, purification, and characterization of RC0497: a peptidoglycan amidase from the prototypical spotted fever species Rickettsia conorii.

Rickettsial species have independently lost several genes owing to reductive evolution while retaining those predominantly implicated in virulence, survival, and biosynthetic pathways. In this study, we have identified a previously uncharacterized Rickettsia conorii gene RC0497 as an N-acetylmuramoyl-L-alanine amidase constitutively expressed during infection of cultured human microvascular endothelial cells at the levels of both mRNA transcript and encoded protein. A homology-based search of rickettsial genomes reveals that RC0497 homologs, containing amidase_2 family and peptidoglycan binding domains, are highly conserved among the spotted fever group (SFG) rickettsiae. The recombinant RC0497 protein exhibits α-helix secondary structure, undergoes a conformational change in the presence of zinc, and exists as a dimer at higher concentrations. We have further ascertained the enzymatic activity of RC0497 via demonstration of its ability to hydrolyze Escherichia coli peptidoglycan. Confocal microscopy on E. coli expressing RC0497 and transmission immunoelectron microscopy of R. conorii revealed its localization predominantly to the cell wall, septal regions of replicating bacteria, and the membrane of vesicles pinching off the cell wall. In summary, we have identified and functionally characterized RC0497 as a peptidoglycan hydrolase unique to spotted fever rickettsiae, which may potentially serve as a novel moonlighting protein capable of performing multiple functions during host-pathogen interactions.

Study protocol to assess the impact of an integrated nutrition intervention on the growth and development of children under two in rural Bangladesh.

BACKGROUND: The period from birth to two years is the "critical window" for achieving optimal growth and development. An inadequate quality and quantities of complementary foods, poor child-feeding practices and infection negatively impact the growth of under-twos. Approximately one-third of under-fives in developing countries are stunted; many are also micronutrient deficient. An estimated 6% of mortalities among under-fives can be prevented by ensuring optimal complementary feeding. The objective of the study was to assess the ability of a 12-month integrated nutrition intervention to improve the nutritional status (length-for-age Z-score) of 6 to 12-month-old children in rural Bangladesh. METHODS: In this community-based randomized controlled trial, the intervention group received a package of interventions that includes, food vouchers; to prepare egg-based nutritious snacks (suji firni for < 1-year-olds, suji halwa for > 1-year-olds), micronutrient powder to fortify children's food at home, child feeding counselling and water, sanitation and hygiene (WASH), behaviour change communication. The control group received routine health messages provided by the government. Baseline and endline surveys were conducted; Data collection was performed monthly on children's growth, food voucher utilization, child feeding and morbidity. In addition, we assessed the cognitive development of the children after 12 months of intervention. CONCLUSION: This trial aims to explore whether an integrated nutrition intervention can mitigate childhood stunting during the critical window of opportunity in rural Bangladesh. The results may provide robust evidence to improve the linear growth of children in developing countries. TRIAL REGISTRATION: The study was retrospectively registered on August 17, 2018 and is available online at ClinicalTrials.gov (ID: NCT02768181).

Integrated Functional Analysis of the Nuclear Proteome of Classically and Alternatively Activated Macrophages.

Macrophages (Mφ) play a central role in coordinating host response to pathogens, cellular injury, and environmental stimuli. Herein, we report multidimensional, nuclear proteomic analyses of protein expression and posttranslational modifications (PTMs) that control biological processes during Mφ activation. For this, Mφ were incubated with IFN-γ/LPS and IL-4, and their differentiation to proinflammatory (M1) and anti-inflammatory (M2a, referred as M2 for simplicity throughtout the manuscript) phenotypes was confirmed by detection of CD64 and CD206 surface markers and TNF-α, arginase I, and iNOS-dependent nitrite levels. We used a sequential method of organellar enrichment and labeling of nuclear fractions with BODIPY FL-maleimide fluorescence dye followed by two-dimensional electrophoresis (2DE) to capture quantitative changes in abundance and S-nitrosylated (SNO) proteome signatures. Exact same gels were then labeled with Pro-Q Diamond to detect protein phosphorylation. MALDI-TOF/TOF MS analysis of the protein spots with fold change of ≥|1.5| in any of the groups yielded 229 identifications. We found that 145, 78, and 173 protein spots in M1 Mφ and 105, 81, and 164 protein spots in M2 Mφ were changed in abundance, S-nitrosylation, and phosphorylation, respectively, with respect to M0 controls (fold change: ≥|1.5|, p ≤ 0.05). Targeted analysis by immunoprecipitation and Western blotting was performed to verify the differential abundance and phosphorylation levels of two of the proteins in M1 and M2 (vs. M0) Mφ. Ingenuity Pathway Analysis of the nuclear proteome datasets showed that the abundance and posttranslational (SNO and Phosphor) modifications of the proteins predicted to be involved in cytoskeletal organization/cell movement, phagocytosis/endocytosis, and cell proliferation/cell death were differentially regulated with proinflammatory and anti-inflammatory activation of Mφ.

Autism Spectrum disorders (ASD) in South Asia: a systematic review.

BACKGROUND: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders. The prevalence of ASD in many South Asian countries is still unknown. The aim of this study was to systematically review available epidemiological studies of ASD in this region to identify gaps in our current knowledge. METHODS: We searched, collected and evaluated articles published between January 1962 and July 2016 which reported the prevalence of ASD in eight South Asian countries. The search was conducted in line with the PRISMA guidelines. RESULTS: We identified six articles from Bangladesh, India, and Sri Lanka which met our predefined inclusion criteria. The reported prevalence of ASD in South Asia ranged from 0.09% in India to 1.07% in Sri Lanka that indicates up to one in 93 children have ASD in this region. Alarmingly high prevalence (3%) was reported in Dhaka city. Study sample sizes ranged from 374 in Sri Lanka to 18,480 in India. The age range varied between 1 and 30 years. No studies were found which reported the prevalence of ASD in Pakistan, Nepal, Bhutan, Maldives and Afghanistan. This review identifies methodological differences in case definition, screening instruments and diagnostic criteria among reported three countries which make it very difficult to compare the studies. CONCLUSIONS: Our study is an attempt at understanding the scale of the problem and scarcity of information regarding ASD in the South Asia. This study will contribute to the evidence base needed to design further research and make policy decisions on addressing this issue in this region. Knowing the prevalence of ASD in South Asia is vital to ensure the effective allocation of resources and services.

Expression Profiling of Long Noncoding RNA Splice Variants in Human Microvascular Endothelial Cells: Lipopolysaccharide Effects In Vitro.

Endothelial cell interactions with lipopolysaccharide (LPS) involve both activating and repressing signals resulting in pronounced alterations in their transcriptome and proteome. Noncoding RNAs are now appreciated as posttranscriptional and translational regulators of cellular signaling and responses, but their expression status and roles during endothelial interactions with LPS are not well understood. We report on the expression profile of long noncoding (lnc) RNAs of human microvascular endothelial cells in response to LPS. We have identified a total of 10,781 and 8310 lncRNA transcripts displaying either positive or negative regulation of expression, respectively, at 3 and 24 h posttreatment. A majority of LPS-induced lncRNAs are multiexonic and distributed across the genome as evidenced by their presence on all chromosomes. Present among these are a total of 44 lncRNAs with known regulatory functions, of which 41 multiexonic lncRNAs have multiple splice variants. We have further validated splice variant-specific expression of EGO (NONHSAT087634) and HOTAIRM1 (NONHSAT119666) at 3 h and significant upregulation of lnc-IL7R at 24 h. This study illustrates the genome-wide regulation of endothelial lncRNA splice variants in response to LPS and provides a foundation for further investigations of differentially expressed lncRNA transcripts in endothelial responses to LPS and pathophysiology of sepsis/septic shock.

Macrophages Promote Oxidative Metabolism To Drive Nitric Oxide Generation in Response to Trypanosoma cruzi.

Trypanosoma cruzi is the causative agent of chronic chagasic cardiomyopathy. Why macrophages (mφs), the early responders to infection, fail to achieve parasite clearance is not known. Mouse (RAW 264.7) and human (THP-1 and primary) mφs were infected for 3 h and 18 h with T. cruzi TcI isolates, SylvioX10/4 (SYL, virulent) and TCC (nonpathogenic), which represent mφ stimulation and infection states, respectively. Mφs incubated with lipopolysaccharide and gamma interferon (LPS/IFN-γ) and with interleukin-4 (IL-4) were used as controls. We monitored the cytokine profile (using enzyme-linked immunosorbent assay [ELISA]), reactive oxygen species (ROS; fluorescent probes), nitric oxide (·NO; Griess assay), and metabolic state using a custom-designed mitoxosome array and Seahorse XF24 Analyzer. LPS/IFN-γ treatment of mφs elicited a potent increase in production of tumor necrosis alpha (TNF-α) at 3 h and of ROS and ·NO by 18 h. Upon SYL infection, murine mφs elicited an inflammatory cytokine profile (TNF-α ≫ TGF-ß + IL-10) and low levels of ·NO and ROS production. LPS/IFN-γ treatment resulted in the inhibition of oxidative metabolism at the gene expression and functional levels and a switch to the glycolytic pathway in mφs, while IL-4-treated mφs utilized oxidative metabolism to meet energy demands. SYL infection resulted in an intermediate functional metabolic state with increased mitoxosome gene expression and glycolysis, and IFN-γ addition shut down the oxidative metabolism in SYL-infected mφs. Further, TCC- and SYL-stimulated mφs exhibited similar levels of cell proliferation and production of TNF-α and ROS, while TCC-stimulated mφs exhibited up to 2-fold-higher levels of oxidative metabolism and ·NO production than SYL-infected mφs. Inhibiting ATP-coupled O2 consumption suppressed the ·NO generation in SYL-infected mφs. Mitochondrial oxygen consumption constitutes a mechanism for stimulating ·NO production in mφs during T. cruzi infection. Enhancing the oxidative metabolism provides an opportunity for increased ·NO production and pathogen clearance by mφs to limit disease progression.

Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy.

The present study was aimed to investigate the relation between nuclear factor kappa beta (NFκB) activation and downstream up-regulation of vascular endothelial growth factor (VEGF) in diabetic retinopathy (DR). Moreover the study was intended to evaluate the role of VEGF gene single nucleotide polymorphisms (SNPs) in DR occurrence and to investigate the functional relevance of VEGF gene SNPs in terms of VEGF expression in DR. Serum level of VEGF, VEGF R1 (receptor 1), VEGF R 2 (receptor 2) and NFκB (p50/65) activity was measured by enzyme linked immune sorbent assay. Genotyping and allelic composition of different SNPs i.e., rs2010963, rs3025039, rs1570360 and rs 2071559 were investigated by Taqman SNP genotyping assay. VEGF, NFκB p50/p65, and VEGF R1 & R2 gene expressions were quantified by real time quantitative polymerase chain reaction. Increased NFκB p50/p65 activity and expressions were observed in non proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subjects compared to type 2 diabetes mellitus without retinopathy (DNR) group. Significantly elevated levels of serum VEGF and highest VEGF expression were found among PDR subjects compared to DNR or NPDR subjects. CC genotype and C allele of rs2010963 and TT genotype and T allele of rs3025039 were significantly over represented among PDR subjects compared to DNR group. Increased activation of NFκß in NPDR and PDR subjects might involve increased up regulation of VEGF. VEGF SNPs i.e., rs2010963 C allele and rs3025039 T allele might be associated with PDR occurrence and in turn regulates VEGF expression among PDR subjects.

Role of N-ε- carboxy methyl lysine, advanced glycation end products and reactive oxygen species for the development of nonproliferative and proliferative retinopathy in type 2 diabetes mellitus.

PURPOSE: The aim of the present study was to evaluate the collective role of N-epsilon-carboxy methyl lysine (N(ε)-CML), advanced glycation end-products (AGEs), and reactive oxygen species (ROS) for the development of retinopathy among type 2 diabetic subjects. METHODS: Seventy type 2 diabetic subjects with nonproliferative diabetic retinopathy (NPDR), 105 subjects with proliferative diabetic retinopathy (PDR), and 102 patients with diabetes but without retinopathy (DNR) were enrolled in this study. In addition, 95 normal individuals without diabetes were enrolled as healthy controls in this study. Serum and vitreous N(ε)-CML and AGEs were measured by enzyme-linked immunosorbent assay. The peripheral blood mononuclear cell (PBMC) ROS level was measured by flow cytometric analysis. Serum and PBMC total thiols were measured by spectrophotometry. RESULTS: Serum AGEs and N(ε)-CML levels were significantly elevated in subjects with PDR (p<0.0001) and NPDR (p=0.0297 and p<0.0001, respectively) compared to DNR subjects. Further vitreous AGEs and N(ε)-CML levels were found to be significantly high among PDR subjects compared to the control group (p<0.0001). PBMC ROS production was found to be strikingly high among NPDR (p<0.0001) and PDR (p<0.0001) subjects as compared to the DNR group. Serum and PBMC total thiol levels were remarkably decreased in NPDR (p<0.0001 and p=0.0043, respectively) and PDR (p=0.0108 and p=0.0332 respectively) subjects than those were considered as DNR. CONCLUSIONS: Our findings suggest that N(ε)-CML and ROS are the key modulators for the development of nonproliferative retinopathy among poorly controlled type 2 diabetic subjects. Furthermore, AGEs under persistent oxidative stress and the deprived antioxidant state might instigate the pathogenic process of retinopathy from the nonproliferative to the proliferative state.

Role of hyperglycemia-mediated erythrocyte redox state alteration in the development of diabetic retinopathy.

PURPOSE: To evaluate erythrocyte redox state and its surrogates in patients with different stages of diabetic retinopathy and their association with cellular metabolic derangement developed in retinal microvascular cells. METHODS: Sixty type 2 diabetic patients with nonproliferative diabetic retinopathy (NPDR), 85 patients with proliferative diabetic retinopathy (PDR), and 70 patients with diabetes but without retinopathy were considered as diabetic control (DC) for the study. In addition, 65 normal individuals without diabetes were enrolled as healthy control in this study. Erythrocyte oxidized nicotinamide adenine dinucleotide phosphate / reduced nicotinamide adenine dinucleotide phosphate (NADP / NADPH), oxidized nicotinamide adenine dinucleotide / reduced nicotinamide adenine dinucleotide (NAD / NADH) glutathione, plasma and vitreous lactate, and pyruvate levels were determined by enzymatic reaction-based spectrophotometric assay for the patients and individuals. RESULT: Erythrocyte NADP+ to NADPH ratio to NADPH ratio was found to be significantly higher among NPDR and PDR patients compared with DC subjects (P < 0.0001). Erythrocyte-reduced glutathione was significantly decreased in patients of NPDR (P = 0.0004) and patients of PDR (P = 0.0157) compared to DC. Erythrocyte NAD to NADH ratio was also significantly decreased in patients of NPDR (P < 0.0001) and PDR (P < 0.0001) compared to DC subjects. Lactate to pyruvate ratio of plasma was elevated significantly in patients with NPDR compared with DC (P < 0.0001) and those having PDR (P = 0.0046). In the vitreous fluid, the lactate to pyruvate ratios were found to be significantly lower in normal individuals without diabetes compared with patients having PDR (P < 0.0001). CONCLUSION: Hyperglycemia-mediated erythrocyte redox state alterations might be a potential risk factor for the development of NPDR in poorly controlled diabetic subjects.

Subunit nanovaccine elicited T cell functional activation controls Trypanosoma cruzi mediated maternal and placental tissue damage and improves pregnancy outcomes in mice.

This study investigated a candidate vaccine effect against maternal Trypanosoma cruzi (Tc) infection and improved pregnancy outcomes. For this, TcG2 and TcG4 were cloned in a nanoplasmid optimized for delivery, antigen expression, and regulatory compliance (nano2/4 vaccine). Female C57BL/6 mice were immunized with nano2/4, infected (Tc SylvioX10), and mated 7-days post-infection to enable fetal development during the maternal acute parasitemia phase. Females were euthanized at E12-E17 (gestation) days. Splenic and placental T-cell responses were monitored by flow cytometry. Maternal and placental/fetal tissues were examined for parasites by qPCR and inflammatory infiltrate by histology. Controls included age/immunization-matched non-pregnant females. Nano2/4 exhibited no toxicity and elicited protective IgG2a/IgG1 response in mice. Nano2/4 signaled a splenic expansion of functionally active CD4+ effector/effector memory (Tem) and central memory (Tcm) cells in pregnant mice. Upon challenge infection, nano2/4 increased the splenic CD4+ and CD8+T cells in all mice and increased the proliferation of CD4+Tem, CD4+Tcm, and CD8+Tcm subsets producing IFNγ and cytolytic molecules (PRF1, GZB) in pregnant mice. A balanced serum cytokines/chemokines response and placental immune characteristics indicated that pregnancy prevented the overwhelming damaging immune response in mice. Importantly, pregnancy itself resulted in a significant reduction of parasites in maternal and fetal tissues. Nano2/4 was effective in arresting the Tc-induced tissue inflammatory infiltrate, necrosis, and fibrosis in maternal and placental tissues and improving maternal fertility, placental efficiency, and fetal survival. In conclusion, we show that maternal nano2/4 vaccination is beneficial in controlling the adverse effects of Tc infection on maternal health, fetal survival, and pregnancy outcomes.

Acute muscle mass loss was alleviated with HMGB1 neutralizing antibody treatment in severe burned rats.

Burn injury is associated with muscle wasting, though the involved signaling mechanisms are not well understood. In this study, we aimed to examine the role of high mobility group box 1 (HMGB1) in signaling hyper-inflammation and consequent skeletal muscle impairment after burn. Sprague Dawley rats were randomly assigned into three groups: (1) sham burn, (2) burn, (3) burn/treatment. Animals in group 2 and group 3 received scald burn on 30% of total body surface area (TBSA) and immediately treated with chicken IgY and anti-HMGB1 antibody, respectively. Muscle tissues and other samples were collected at 3-days after burn. Body mass and wet/dry weights of the hind limb muscles (total and individually) were substantially decreased in burn rats. Acute burn provoked the mitochondrial stress and cell death and enhanced the protein ubiquitination and LC3A/B levels that are involved in protein degradation in muscle tissues. Further, an increase in muscle inflammatory infiltrate associated with increased differentiation, maturation and proinflammatory activation of bone marrow myeloid cells and αß CD4+ T and γδ T lymphocytes was noted in in circulation and spleen of burn rats. Treatment with one dose of HMGB1 neutralizing antibody reduced the burn wound size and preserved the wet/dry weights of the hind limb muscles associated with a control in the markers of cell death and autophagy pathways in burn rats. Further, anti-HMGB1 antibody inhibited the myeloid and T cells inflammatory activation and subsequent dysregulated inflammatory infiltrate in the muscle tissues of burn rats. We conclude that neutralization of HMGB1-dependent proteolytic and inflammatory responses has potential beneficial effects in preventing the muscle loss after severe burn injury.

Clinical capability of modern brain tumor segmentation models.

PURPOSE: State-of-the-art automated segmentation methods achieve exceptionally high performance on the Brain Tumor Segmentation (BraTS) challenge, a dataset of uniformly processed and standardized magnetic resonance generated images (MRIs) of gliomas. However, a reasonable concern is that these models may not fare well on clinical MRIs that do not belong to the specially curated BraTS dataset. Research using the previous generation of deep learning models indicates significant performance loss on cross-institutional predictions. Here, we evaluate the cross-institutional applicability and generalzsability of state-of-the-art deep learning models on new clinical data. METHODS: We train a state-of-the-art 3D U-Net model on the conventional BraTS dataset comprising low- and high-grade gliomas. We then evaluate the performance of this model for automatic tumor segmentation of brain tumors on in-house clinical data. This dataset contains MRIs of different tumor types, resolutions, and standardization than those found in the BraTS dataset. Ground truth segmentations to validate the automated segmentation for in-house clinical data were obtained from expert radiation oncologists. RESULTS: We report average Dice scores of 0.764, 0.648, and 0.61 for the whole tumor, tumor core, and enhancing tumor, respectively, in the clinical MRIs. These means are higher than numbers reported previously on same institution and cross-institution datasets of different origin using different methods. There is no statistically significant difference when comparing the dice scores to the inter-annotation variability between two expert clinical radiation oncologists. Although performance on the clinical data is lower than on the BraTS data, these numbers indicate that models trained on the BraTS dataset have impressive segmentation performance on previously unseen images obtained at a separate clinical institution. These images differ in the imaging resolutions, standardization pipelines, and tumor types from the BraTS data. CONCLUSIONS: State-of-the-art deep learning models demonstrate promising performance on cross-institutional predictions. They considerably improve on previous models and can transfer knowledge to new types of brain tumors without additional modeling.

Prevalence and correlates of knowledge and practices regarding infection prevention and control, and triage in primary healthcare settings: A cross-sectional study in Bangladesh.

Background: Despite the high prevalence of healthcare-acquired infection in resource-limited settings, healthcare workers' (HCWs') knowledge and practices of infection prevention and control (IPC) and triage are not well-researched. We examined thisin Bangladesh's primary healthcare facilities (HCFs) during the COVID-19 pandemic. Methods: We surveyed 312 HCWs in 94 community clinics (CCs) and 90 family welfare centres (FWCs) in six districts from February to April 2021. We assessed HCWs' self-reported knowledge and observed practices in four domains: personal hygiene, medical instrument processing, waste management, and triage. We constructed a weighted composite knowledge score and estimated the association between knowledge and background characteristics using a generalised linear mixed effects model. Practices were described through univariate analysis. Findings: On a scale of 100, the mean composite knowledge score was 38.3 (SD: 13.3) overall and 44.0 (SD: 13.1) and 33.8 (SD: 11.6) for FWCs and CCs, respectively. The HCWs of FWCs were more aged, experienced, and educated than those of CCs. Knowledge score was the highest in personal hygiene and the lowest in medical waste segregation. Knowledge was significantly associated with HCWs' designation and education. Concerning practices, not more than one-third of the HCWs or HCFs, on average, followed the recommended protocols, except for wearing face masks while on duty (87.1%) and referring potential COVID-19 patients to higher-level facilities (68.3%). Conclusions: HCWs' capacity in instrument processing, waste management, and triage needs to be improved through formal education and training initiatives. Our study can contribute to the under-researched IPC and triage domains in resource-limited settings.

A molecular approach to identification and profiling of first-line-drug-resistant mycobacteria from sputum of pulmonary tuberculosis patients.

Conventional and molecular techniques were applied to detect and characterize drug resistance of mycobacteria in the sputum samples of clinically confirmed tuberculosis. The sensitivities of mycobacterium detection by ZN staining, culture, multiplex PCR, and restriction fragment length polymorphism (RFLP) were 27.7%, 19.9%, 92.9%, and 95.7%, respectively, but all were 100% specific. The conventional and multiple-allele-specific PCR (MAS-PCR) methods enabled establishment of the drug resistance in 19.3% and 86.9% cases, respectively. We demonstrated that molecular techniques have potential in the accurate diagnosis of tuberculosis.

Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes.

PURPOSE: Chronic hyperglycemia and hypoxemia are believed to be causal factors in the development of proliferative diabetic retinopathy (PDR) among individuals with type 2 diabetes. It is hypothesized that formation of new blood vessels in the retina due to prolonged hypoxia is associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we investigated the association of genetic polymorphisms in vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-ß), and interferon γ (IFN-γ) genes, which may be responsible for the hypoxia-induced VEGF-mediated neovascularization pathway for the pathogenesis of PDR. METHODS: Our case-control association study composed of 493 ethnically matched volunteers (253 with PDR [cases] and 240 diabetic controls [DC]). Gene polymorphisms were determined with Taqman-based real-time PCR and amplification refractory mutation analysis system PCR. RESULTS: The VEGF-460C (rs833061C; p=0.0043) and IFN-γ +874T (rs2430561T; p=0.0011) alleles were significantly associated with PDR. CONCLUSIONS: Genetic variations at VEGF-460C and IFN-γ +874T might accelerate the pathogenesis of retinal neovascularization in PDR.

Association of tumor necrosis factor α, interleukin 6, and interleukin 10 promoter polymorphism with proliferative diabetic retinopathy in type 2 diabetic subjects.

PURPOSE: New blood vessel formation in the retina because of prolonged hypoxia is believed to be directly associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we made an attempt to investigate the possible association of the promoter polymorphisms of interleukin 6, tumor necrosis factor α, and interleukin 10 for the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: This case-control study comprised 493 volunteers (253 PDR cases and 240 diabetic controls). Cases and controls were ascertained such that age, sex, nutrition, and glycemic status were matched. Genotypes were determined by polymerase chain reaction-based methods. RESULTS: Interleukin 10-1082GG (P = 0.0037; odds ratio [OR] = 2.232), tumor necrosis factor α-238AA (P = 0.0001; OR = 5.791), and GA (P = 0.0015; OR = 1.909) genotypes were significantly associated with PDR occurrence. The interleukin 10-1082G allele (P = 0.0048, OR = 1.4442) and the tumor necrosis factor α-238A allele (P = 0.0001; OR = 2.2897) were significantly increased among PDR cases. CONCLUSION: From our study, it may be concluded that the genetic variation, that is, tumor necrosis factor α-238A and interleukin 10-1082G alleles are the potent risk factors for the pathogenesis of PDR.