65 research outputs found

    Perception of SME Growth Constraints in Bangladesh: An Empirical Examination from Institutional Perspective

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    This article wrestles with the perception of concern institutions[1]/organisations for developing small and medium enterprise (SMEs) development of Bangladesh. The findings include the need for perceptual as well as conceptual development in the present practice of enterprise/entrepreneurship development of Bangladesh. The summary and conclusion emphasised the importance of comprehensive training for the concerned organisation for successful SME sector. Recommendations that could help sustain emerging as well as existing small enterprises and other concerned organisations.   Keywords: Small Enterprise, Perception, Growth Determinants, and Frame of Reference [1] Institution refers in this study as “it is mechanism that sets humanly devised rules in a society that shape human interaction. In consequence they structure incentives and reward in human exchange, whether political, social or economic. Institutional change shapes the way societies evolve through time and hence is the key to understanding historical change” (see more in North 1990:p.3).

    Prevalence and factors associated with mental health impact of COVID-19 pandemic in Bangladesh : a survey-based cross-sectional study

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    Background: Feelings of isolation, insecurity, and instability triggered by COVID-19 could have a long-term impact on the mental health status of individuals. Objectives: The aim of this study was to examine the prevalence of mental health symptoms (anxiety, depression, and stress) in Bangladesh and the factors associated with these symptoms during the COVID-19 pandemic. Methods: From 1 to 30 April 2020, we used a validated self-administered questionnaire to conduct a cross-sectional study on 10,609 participants through an online survey platform. We assessed mental health status using the Depression, Anxiety, and Stress Scale (DASS-21). The total depression, anxiety, and stress subscale scores were divided into normal, mild, moderate, severe, and multinomial logistic regression was used to examine associated factors. Findings: The prevalence of depressive symptoms was 15%, 34%, and 15% for mild, moderate, and severe depressive symptoms, respectively. The prevalence of anxiety symptoms was 59% for severe anxiety symptoms, 14% for moderate anxiety symptoms, and 14% for mild anxiety symptoms, while the prevalence for stress levels were 16% for severe stress level, 22% for moderate stress level, and 13% for mild stress level. Multivariate analyses revealed that the most consistent factors associated with mild, moderate, and severe of the three mental health subscales (depression, anxiety, and stress) were respondents who lived in Dhaka and Rangpur division, females, those who self-quarantined in the previous seven days before the survey, and those respondents who experienced chills, breathing difficulty, dizziness, and sore throat. Conclusion: Our results showed that about 64%, 87%, and 61% of the respondents in Bangladesh reported high levels of depression, anxiety, and stress, respectively. There is a need for mental health support targeting women and those who self-quarantined or lived in Dhaka and Rangpur during the pandemic

    Maturation of the functional mouse CRES amyloid from globular form

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    The epididymal lumen contains a complex cystatin-rich nonpathological amyloid matrix with putative roles in sperm maturation and sperm protection. Given our growing understanding for the biological function of this and other functional amyloids, the problem still remains: how functional amyloids assemble including their initial transition to early oligomeric forms. To examine this, we developed a protocol for the purification of nondenatured mouse CRES, a component of the epididymal amyloid matrix, allowing us to examine its assembly to amyloid under conditions that may mimic those in vivo. Herein we use X-ray crystallography, solution-state NMR, and solid-state NMR to follow at the atomic level the assembly of the CRES amyloidogenic precursor as it progressed from monomeric folded protein to an advanced amyloid. We show the CRES monomer has a typical cystatin fold that assembles into highly branched amyloid matrices, comparable to those in vivo, by forming β-sheet assemblies that our data suggest occur via two distinct mechanisms: a unique conformational switch of a highly flexible disulfide-anchored loop to a rigid β-strand and by traditional cystatin domain swapping. Our results provide key insight into our understanding of functional amyloid assembly by revealing the earliest structural transitions from monomer to oligomer and by showing that some functional amyloid structures may be built by multiple and distinctive assembly mechanisms

    Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

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    Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

    Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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    BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

    An epigenetic vaccine model active in the prevention and treatment of melanoma

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    Abstract Background Numerous immune genes are epigenetically silenced in tumor cells and agents such as histone deacetylase inhibitors (HDACi), which reverse these effects, could potentially be used to develop therapeutic vaccines. The conversion of cancer cells to antigen presenting cells (APCs) by HDACi treatment could potentially provide an additional pathway, together with cross-presentation of tumor antigens by host APCs, to establish tumor immunity. Methods HDACi-treated B16 melanoma cells were used in a murine vaccine model, lymphocyte subset depletion, ELISpot and Cytotoxicity assays were employed to evaluate immunity. Antigen presentation assays, vaccination with isolated apoptotic preparations and tumorigenesis in MHC-deficient mice and radiation chimeras were performed to elucidate the mechanisms of vaccine-induced immunity. Results HDACi treatment enhanced the expression of MHC class II, CD40 and B7-1/2 on B16 cells and vaccination with HDACi-treated melanoma cells elicited tumor specific immunity in both prevention and treatment models. Cytotoxic and IFN-γ-producing cells were identified in splenocytes and CD4+, CD8+ T cells and NK cells were all involved in the induction of immunity. Apoptotic cells derived from HDACi treatments, but not H2O2, significantly enhanced the effectiveness of the vaccine. HDACi-treated B16 cells become APCs in vitro and studies in chimeras defective in cross presentation demonstrate direct presentation in vivo and short-term but not memory responses and long-term immunity. Conclusion The efficacy of this vaccine derives mainly from cross-presentation which is enhanced by HDACi-induced apoptosis. Additionally, epigenetic activation of immune genes may contribute to direct antigen presentation by tumor cells. Epigenetically altered cancer cells should be further explored as a vaccine strategy.</p

    Interferon regulatory factor-8 is important for histone deacetylase inhibitor-mediated antitumor activity.

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    The notion that epigenetic alterations in neoplasia are reversible has provided the rationale to identify epigenetic modifiers for their ability to induce or enhance tumor cell death. Histone deacetylase inhibitors (HDACi) represent one such class of anti-neoplastic agents. Despite great interest for clinical use, little is known regarding the molecular targets important for response to HDACi-based cancer therapy. We had previously shown that interferon regulatory factor (IRF)-8, originally discovered as a leukemia suppressor gene by regulating apoptosis, also regulates Fas-mediated killing in non-hematologic tumor models. Furthermore, we and others have shown that epigenetic mechanisms are involved in repression of IRF-8 in tumors. Therefore, in our preclinical tumor model, we tested the hypothesis that IRF-8 expression is important for response to HDACi-based antitumor activity. In the majority of experiments, we selected the pan-HDACi, Trichostatin A (TSA), because it was previously shown to restore Fas sensitivity to tumor cells. Overall, we found that: 1) TSA alone and more so in combination with IFN-γ enhanced both IRF-8 expression and Fas-mediated death of tumor cells in vitro; 2) TSA treatment enhanced IRF-8 promoter activity via a STAT1-dependent pathway; and 3) IRF-8 was required for this death response, as tumor cells rendered IRF-8 incompetent were significantly less susceptible to Fas-mediated killing in vitro and to HDACi-mediated antitumor activity in vivo. Thus, IRF-8 status may underlie a novel molecular basis for response to HDACi-based antitumor treatment

    TSA treatment enhances apoptosis and immune gene expression on melanoma cells and TSA-treated vaccines generate immunity

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    <p><b>Copyright information:</b></p><p>Taken from "An epigenetic vaccine model active in the prevention and treatment of melanoma"</p><p>http://www.translational-medicine.com/content/5/1/64</p><p>Journal of Translational Medicine 2007;5():64-64.</p><p>Published online 10 Dec 2007</p><p>PMCID:PMC2231344.</p><p></p> ) B16 cells were stained with mAb, isotype controls and annexinV after treatment with TSA and analyzed by flow cytometry for the expression of MHC class I, class II, CD80, CD86 and CD40. Isotype controls are shown as shaded peaks and heavy lines represent expression determined by specific mAb staining. Values indicated in the histograms are the percent of cells positive for the respective mAb relative to the isotype staining. The data presented here are representative of more than three independent experiments. ) Kaplan-Meier plot of B6 mice (10 in each group) inoculated with TSA-treated (500 nM for 48 h) or untreated B16 cells in the trunk. ) Durable immunity in 100% of the immune animals. Tumor-free mice, 40 days after vaccination with TSA-treated B16, were re-challenged with untreated B16 cells and observed for another 60 days. The number of tumor-free mice compared to total numbers used in each treatment group is shown in parentheses
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