Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast.

Yeast and humans share thousands of genes despite a billion years of evolutionary divergence. While many human genes can functionally replace their yeast counterparts, nearly half of the tested shared genes cannot. For example, most yeast proteasome subunits are "humanizable," except subunits comprising the ß-ring core, including ß2c (HsPSMB7, a constitutive proteasome subunit). We developed a high-throughput pipeline to humanize yeast proteasomes by generating a large library of Hsß2c mutants and screening them for complementation of a yeast ß2 (ScPup1) knockout. Variants capable of replacing ScPup1 included (1) those impacting local protein-protein interactions (PPIs), with most affecting interactions between the ß2c C-terminal tail and the adjacent ß3 subunit, and (2) those affecting ß2c proteolytic activity. Exchanging the full-length tail of human ß2c with that of ScPup1 enabled complementation. Moreover, wild-type human ß2c could replace yeast ß2 if human ß3 was also provided. Unexpectedly, yeast proteasomes bearing a catalytically inactive HsPSMB7-T44A variant that blocked precursor autoprocessing were viable, suggesting an intact propeptide stabilizes late assembly intermediates. In contrast, similar modifications in human ß2i (HsPSMB10), an immunoproteasome subunit and the co-ortholog of yeast ß2, do not enable complementation in yeast, suggesting distinct interactions are involved in human immunoproteasome core assembly. Broadly, our data reveal roles for specific PPIs governing functional replaceability across vast evolutionary distances.

Compliance of healthcare workers with the infection prevention and control guidance in tertiary care hospitals: quantitative findings from an explanatory sequential mixed-methods study in Bangladesh.

OBJECTIVES: To assess healthcare workers' (HCWs) compliance with the infection prevention and control (IPC) practices and identify the factors influencing this compliance using the Health Belief Model as the theoretical framework. DESIGN: Quantitative data from an explanatory sequential mixed-methods study were employed in this research. PARTICIPANTS AND SETTINGS: From 17 May to 30 August 2020, 604 physicians and nurses working at six randomly selected tertiary care facilities in Dhaka City in Bangladesh took part in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Compliance with the WHO's guidance on IPC measures, as well as the associated factors, was the primary outcome. RESULTS: A mean compliance score of 0.49 (±0.25) was observed on a 0-1 scale. HCWs were most compliant with the medical mask wearing guidelines (81%) and were least compliant with the high-touch surface decontamination regulations (23%). Compliance with the IPC guidance was significantly associated with increasing age, female sex, working as a nurse, having non-communicable diseases and history of exposure to patients with COVID-19. Perceived benefits (B=0.039, 95% CI 0.001 to 0.076), self-efficacy (B=0.101, 95% CI 0.060 to 0.142) and cues to action (B=0.045, 95% CI 0.002 to 0.088) were positively associated with compliance. Compliance with IPC guidance was 0.061 times greater among participants who reported low perceived barriers compared with those with high perceived barriers. CONCLUSION: Overall, compliance with IPC guidance among HCWs was unsatisfactory. As self-efficacy exerted the greatest contribution to compliance, it should be emphasised in any endeavour to improve HCWs' IPC adherence. Such interventions should also focus on perceived barriers, including unreliability of the information sources, unsafe working places and unavailability of protective equipment and cues to action, including trust in the administration and availability of adequate IPC guidance.

Challenges for tuberculosis control at selected primary healthcare centers in Bangladesh: A mixed-method study.

BACKGROUND: The national tuberculosis control program in Bangladesh is progressing to end tuberculosis (TB) epidemic by 2035. Despite improved diagnostic and treatment facilities, the disease burden remains high. This mixed-method study aimed to identify existing challenges for successfully implementing the tuberculosis control program in primary healthcare centers (PHCs) of Bangladesh. METHODS: Qualitative data were collected by observing six PHCs and interviewing TB patients (n = 12) and healthcare providers (n = 12). Quantitative data were collected by interviewing 94 TB patients. Data were integrated through a narrative approach. RESULTS: Mean patient and health system delay were 99.0 (SD = 98.7) and 42.9 (SD = 79.9) days respectively. Patient delay was related to poor care-seeking behavior, unfamiliarity with tuberculosis symptoms, and unavailability of healthcare facilities. About 74 percent of patients sought initial treatment from village doctors or drug vendors. Health system delay was related to inadequate manpower, unskilled staff, and limited diagnostic facilities. Every second patient reported non-adherence to the directly observed treatment short-course (DOTS) guideline. DOTS provider's inaccessibility, inadequate incentive, and unreasonable patient demand lead to non-adherence. Insufficient administrative and structural facilities for infection control were observed at the selected facilities. CONCLUSIONS: This study provides an insight into the recent challenges in TB control at PHCs in Bangladesh.

Prevalence of chronic obstructive pulmonary disease (COPD) among rural population: A national survey in Bangladesh.

Background: In Bangladesh, there is a scarcity of nationally representative data on the burden of chronic obstructive pulmonary disease (COPD). Methods: To estimate the COPD prevalence in rural settings, this cross-sectional, population-based study was conducted in all eight administrative divisions of Bangladesh, and involved adults aged 40 years and above. By using multi-stage random sampling, 2,458 individuals were enrolled. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines were used to diagnose COPD based on post-bronchodilator lung function, while additional participant data was gathered through computer-assisted personal interviews. Results: A 2% COPD prevalence (95% CI: 1.45, 2.55) was found in the study sample with a statistically significant difference between males (2.7%; 95% CI: 1.8, 3.6) and females (1.2%; 95% CI: 0.59, 1.81). Increasing age significantly inflated the odds of having COPD irrespective of sex (OR: 1.03; 95% CI: 1.00, 1.05; P value < 0.05). Furthermore, prevalence of COPD was higher among manual workers, cigarette smokers, and those that used the indoor kitchen and did not have a primary education. Sex-based analysis showed that smokeless tobacco consumption was significantly associated with COPD occurrence among males (OR: 2.14; 95% CI: 1.05, 4.37; P value < 0.05), but not females. Further, using an indoor kitchen increased the odds of developing COPD by 400% among female participants (OR: 4.39; 95% CI: 1.37, 14.10; P value < 0.05). Conclusion: This study provides a comprehensive sex-based estimation of COPD prevalence among rural population and imparts significant contribution to the growing database on COPD prevalence in Bangladesh.

Duration and Risk Factors of Post-COVID Symptoms Following Recovery Among the Medical Doctors in Bangladesh.

A large number of coronavirus disease 2019 (COVID-19) recovered patients are suffering from related symptoms. We conducted telephone interviews with 186 COVID-19 recovered medical doctors to determine the post-COVID symptoms, duration, and associated risk factors. About 70% of participants had at least one acute post-COVID symptom, including fatigue (43.0%), sleep disturbance (13.4%), lack of concentration (11.8%), breathing difficulty (10.2%), headache (6.5%), and muscle pain (6.5%). However, about 24% of participants reported having long post-COVID symptoms. Logistic regression analysis showed that female sex (odds ratio {OR}, 2.79; 95% CI, 1.28-6.06; p-value: 0.010) and comorbid conditions (OR, 2.28; 95% CI, 1.08-4.79; p: value, 0.030) are risk factors for the long post-COVID symptoms.

Parenting stress among caregivers of children with neurodevelopmental disorders: A cross-sectional study in Bangladesh.

This cross-sectional study explored stressful situations of caregivers related to life events of their children suffering from neurodevelopmental disorders along with potential contributing factors. A total of 906 caregivers of children with diagnosed neurodevelopmental disorder, from eight administrative districts and two city corporation areas in Bangladesh were interviewed. The Family Stress and Coping Interview scale was used to evaluate parenting stress. The diagnosis of neurodevelopmental disorder at the outset, feelings about the cause of the disorder, future planning for employment and accommodation for the child and dealing with child sexuality were some important stressful situations for parents. Parenting stress is found to be higher among female [regression coefficient (B) = 5.09, p < 0.001] and less educated caregivers [B = 2.69, p < 0.01]. Increasing age of child [B = 0.82, p < 0.001] and diagnosis of neurodevelopmental disorder before child's second birthday [B = 4.22, p < 0.001] are also associated with higher parenting stress.

An unique case report: Unusual presentation of mediastinal lymph node tuberculosis in an adult.

Tuberculosis (TB) is a serious public health problem in Bangladesh. National tuberculosis control program recognizes that almost half of the TB cases remain undiagnosed in the country. To increase case detection rate, it is very important to familiarize the physicians with unusual presentation of TB. We describe a 51 years old woman with a past medical history of Hypertension (HTN), Type 2 Diabetes Mellitus (DM), and Nonalcoholic steatohepatitis-chronic liver disease (NASH-CLD) who presented to us with low grade fever, anorexia, nausea, and recurrent vomiting for one month. Physical examination and laboratory tests revealed no significant abnormalities and symptoms were treated symptomatically. After about two months, the condition did not improve. All routine blood biochemistry and imaging reports were not suggestive of any disease except for high ESR and abnormal LFT (mild increase in ALP, ALT and moderate increase in GGTP). To exclude the differential diagnoses (such as abdominal TB), we advised computed tomography (CT) scan of chest and abdomen but the results came out normal. Her PPD came out positive but it was not confirmatory of TB as the patient was previously vaccinated with BCG vaccine. As the patient was immune-compromised we suggested starting Anti-TB drugs based on clinical judgment and in the context of Bangladesh being a TB endemic area. But the patient was not convinced to take anti-Tb drugs without definite diagnosis. After another month of persistent symptoms a repeat CT of the chest was advised that revealed multiple enlarged mediastinal lymph-nodes. As the patient had a history of CLD and high PT, Fine Needle Aspiration Cytology (FNAC) was deferred. Patient was started on Anti tubercular treatment and symptoms subsided within three weeks. Treatment was continued for one year. This case summarizes the unusual presentation of mediastinal lymph node Tuberculosis in an adult.

Role of serum uric acid in ischemic stroke: A case-control study in Bangladesh.

INTRODUCTION: Increased level of serum uric acid (SUA) is often considered a risk factor for ischemic stroke. This study was conducted to examine the association of SUA level with ischemic stroke and assessed gender-based differences, if any. METHODS: In this case-control study, neuroimaging-confirmed ischemic stroke patients were recruited as cases within three days of an incident from neurology in-patient department, and as controls, patients without stroke history were recruited from neurology out-patient department. Blood was collected from the respondents of both groups to assess SUA level, lipid profile and oral glucose tolerance test. Binary logistic regression was done for estimating the risks of ischemic stroke. RESULTS: A total of 338 participants were recruited, where 169 were cases and 169 were controls. Around 60 percent respondents of both case and control groups were male. Mean SUA levels for cases and controls were 6.03 (SD 1.84) mg/dl and 4.04 (SD 1.46) mg/dl, respectively. After adjustment for age, tobacco consumption status, diabetes, hypertension, coronary heart disease and dyslipidemia, elevated SUA level was found to be significantly associated with ischemic stroke only in females (OR = 1.49; 95% CI = 1.01-2.19; p<0.05). Overall, each unit increase in SUA level exhibits 25 percent increment in odds of having ischemic stroke (OR = 1.25; 95% CI = 1.02-1.5372; p<0.05). CONCLUSION: This study concluded that elevated SUA level is significantly associated with the acute phase of an ischemic stroke and gender-specific analysis demonstrates this association only in females.

Assessment of risk perception and risk communication regarding COVID-19 among healthcare providers: An explanatory sequential mixed-method study in Bangladesh.

Background: Any public health emergency demands adequate risk communication with the vulnerable population along with their optimized perception about the impending risk to ensure proper risk management and crisis control. Hence, this study will be conducted to explore healthcare providers' perceptions regarding risks of coronavirus disease 2019 (COVID-19), as well as how they are being communicated to about the risk, and how they practice risk reduction measures. Methods: A two-phased explanatory sequential mixed-method study will be conducted among physicians and nurses from randomly selected tertiary healthcare facilities in Dhaka, the capital of Bangladesh. In the first phase, the general pattern and quantifiable measures of risk perception, risk communication, and infection prevention practices will be assessed quantitatively. Multiple linear regression analyses will be performed to explore how much variability of risk perception is predicted by risk communication methods and contents. In the second phase, qualitative data will be collected for in-depth understanding and exploration of participants' experiences and insights regarding COVID-19 risk through interviews and document reviews. Thematic content analysis of the qualitative data will be done manually. Findings from both quantitative and qualitative phases will then be triangulated to illustrate the research objectives. Discussion: Based on the psychometric dimensions of risk perception and psycho-social theory of the health belief model, perception of COVID-19 risk among healthcare providers will be evaluated in this study. The relationship between risk perception and infection prevention and control practices among healthcare providers will also be investigated. The explanatory sequential design of this study is expected to generate hypotheses on how risk perception is being shaped in a time of uncertainty and thus, will help to build a proper risk communication strategy to minimize risk perception among healthcare providers.