Life after COVID-19 outbreak: Expectations and thoughts

The occurrence of the novel coronavirus (COVID-19) pandemic presents an unparalleled health enlightenment challenge. It’s extremely contagious and erratically lethal, and the pervasiveness of asymptomatic prevalence makes it difficult to contain. All infectious disease epidemics rear ethical concerns, from the restraint of individual independence to triaging and resource provision. It seems that we did not take lessons from the preceding epidemics and were poorly prepared to pledge with the threat that COVID-19 epidemic has put forward. The COVID-19 epidemic highlighted the significance of this query to both pandemic preparation strategies and healthcare policies. As the outbreak turned out to be a global pandemic, there is an improved emphasis on finding answers for vaccine preparation, focusing on neglected diseases, more virome study, and research collaboration across the globe in the future, being key tools to resist infection spread in future. Decelerating the COVID-19 spread necessitates people to enthusiastically transform their lives and monitor the finest practices for social isolation and sanitation. This review provides an overview of future research perceptions and offers suggestions on how we can help people to believe in normal life and how this pandemic will strengthen the trade, affect the individual habits and values, revolution in primary health care after these uncertain situations.Keywords: COVID-19; Pandemic; Neglected diseases; Primary health; Virom

M. leprae inhibits apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 gene expression

BACKGROUND: Virulent Mycobacterium leprae interfere with host defense mechanisms such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and apoptotic proteins is found in leprosy lesions and M. leprae has been shown to activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which M. leprae modulates apoptosis is as yet unclear. We investigated expression of apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non-pathogenic M. bovis BCG. RESULTS: M. leprae did not induce apoptosis in THP-1 cells, while BCG induced a significant loss of cell viability by 18 h post-infection at both (multiplicity of infection) MOI-10 and 20, with an increase by 48 h. BCG-induced cell death was accompanied by characteristic apoptotic DNA laddering in cells. Non-viable BCG had a limited effect on host cell death suggesting that BCG-induced apoptosis was a function of mycobacterial viability. M. leprae also activated lower levels of TNF-alpha secretion and TNF-alpha mRNA expression than BCG. Mycobacterium-induced activation of apoptotic gene expression was determined over a time course of infection. M. leprae reduced Bad and Bak mRNA expression by 18 h post-stimulation, with a further decrease at 48 h. Outcome of cell viability is determined by the ratio between pro- and anti-apoptotic proteins present in the cell. M. leprae infection resulted in downregulation of gene expression ratios, Bad/Bcl-2 mRNA by 39% and Bak/Bcl-2 mRNA by 23%. In contrast, live BCG increased Bad/Bcl-2 mRNA (29 %) but had a negligible effect on Bak/Bcl-2 mRNA. Heat killed BCG induced only a negligible (1–4 %) change in mRNA expression of either Bak/Bcl-2 or Bad/Bcl-2. Additionally, M. leprae upregulated the expression of anti-apoptotic gene Mcl-1 while, BCG downregulated Mcl-1 mRNA. CONCLUSION: This study proposes an association between mycobacterium-induced apoptosis in THP-1 cells and the regulation of Bcl-2 family of proteins. M. leprae restricts apoptosis in THP-1 cells by downregulation of Bad and Bak and upregulation of Mcl-1 mRNA expression

Differential combination of cytokine and interferon- gamma +874 T/A polymorphisms determines disease severity in pulmonary tuberculosis.

Background:Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-gamma is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-gamma gene (+874 T/A) which determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder phenotypes have shown variable associations with tuberculosis disease outcome in different ethnic populations. The objective of the current study was to analyze IFN-gamma gene combinations with other IFN-gamma regulating cytokine genes (IL-10, TNF -alpha, IL-6) to see the effect of gene- combinations on disease severity outcome in pulmonary tuberculosis. Methods andFindings:Study groups comprised of pulmonary TB Patients stratified according to lung tissue involvement into mild (Pmd = 74) or advance (Pad = 23) lung disease and compared with healthy controls (TBNA = 166). Genotype analysis was carried out using amplification refractory mutation system-PCR (ARMS-PCR). IFN-gamma gene (+874 T/A) functional SNP combinations in TNFalpha (-308 G/A), IL-10 (-1082 A/G) and IL-6 (-174 G/C) were analyzed. Single gene analysis (Pearson chi) showed a dominant association of IFN-gamma TT (hi) genotype (p = 0.001) and T allele (p = 0.001) with mild disease. IFN-gamma(lo) -IL-10(lo) genotype combination was associated with advanced disease (p = 0.002). IFN-gamma(hi) -IL-6(hi) combination was associated with mild disease (p = 0.0005) while IFN-gamma(lo) -IL-6(int) was associated with protection against both forms of pulmonary disease (p = 0.002).Conclusion:Our results show that a limited number of IFN-gamma gene combinations with other cytokine functional SNPs determine the outcome of disease severity in tuberculosis

Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis

BACKGROUND: Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-γ is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-γ gene (+874 T/A) which determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder phenotypes have shown variable associations with tuberculosis disease outcome in different ethnic populations. The objective of the current study was to analyze IFN-γ gene combinations with other IFN-γ regulating cytokine genes (IL-10, TNF -α, IL-6) to see the effect of gene- combinations on disease severity outcome in pulmonary tuberculosis. METHODS AND FINDINGS: Study groups comprised of pulmonary TB patients stratified according to lung tissue involvement into mild (Pmd = 74) or advance (Pad = 23) lung disease and compared with healthy controls (TBNA = 166). Genotype analysis was carried out using amplification refractory mutation system-PCR (ARMS-PCR). IFN-γ gene (+874 T/A) functional SNP combinations in TNFα (-308 G/A), IL-10 (-1082 A/G) and IL-6 (-174 G/C) were analyzed. Single gene analysis (Pearson χ²) showed a dominant association of IFN-γ TT (hi) genotype (p = 0.001) and T allele (p = 0.001) with mild disease. IFN-γ(lo) -IL-10(lo) genotype combination was associated with advanced disease (p = 0.002). IFN-γ(hi) -IL-6(hi) combination was associated with mild disease (p = 0.0005) while IFN-γ(lo) -IL-6(int) was associated with protection against both forms of pulmonary disease (p = 0.002). CONCLUSION: Our results show that a limited number of IFN-γ gene combinations with other cytokine functional SNPs determine the outcome of disease severity in tuberculosis

Clinical characteristics and outcomes of patients with H1N1 influenza pneumonia admitted at a tertiary care hospital in Karachi, Pakistan

Introduction: Influenza viruses specifically, A and B mainly contribute to seasonal outbreaks that occur globally. However, due to limited diagnostics for influenza there is little data regarding clinical outcomes of patients with H1N1 pneumonia in our region. Our objective was to determine the clinical characteristics and outcomes of patients hospitalized with H1N1 pneumonia at a tertiary care facility in Karachi, Pakistan.Methods: A retrospective study of adult patients admitted with influenza pneumonia from November 2017 to February 2018 at a tertiary care hospital in Karachi, Pakistan. Patient characteristics were compared between influenza A H1N1 and other types of influenza using multivariable logistic regression analysis and subgroup analysis for factors associated with mortality in H1N1 Pneumonia was performed.Results: Out of 497 adult patients with community acquired pneumonia (CAP), 172 fulfilled the criteria for Influenza like illness (ILI). 88 patients had PCR confirmed Influenza pneumonia of whom n = 57 (65%) had Influenza A H1N1. The mean age of patients 53.5 years (SD: 17.3) and 60% were male. The overall mortality from Influenza in this study was 15.9% (n = 14); out of these 11 (78.5%) had Influenza A H1N1. Multivariable analysis showed that the increase in length of hospital admission was significantly associated with H1N1 Influenza A infection (OR: 1.47 CI: 1.2-1.8). Factors associated with mortality showed that presence of ARDS, Septic shock and multi-organ failure was highly significantly associated with death (p-value \u3c 0.001) along with deranged liver function tests (p-value 0.01) and presence of nosocomial infection (p-value 0.027).Conclusion: Influenza A H1N1 is associated with greater length of stay compared with infection due to other types of Influenza and mortality in H1N1 Pneumonia was found to be associated with presence of nosocomial infection among several other factors which may have implications given higher rates in a low-middle income country

Impact of Bank Profitability on Default Risk: Empirical Evidence from Pakistan

This empirical study investigates the effect of the bank-specific determinants of bank profitability on the default risk of the banks listed on the Stock Exchange of Pakistan. For this purpose, the study considers balanced panel data covering the period 2009-2018 for the 20 selected commercial banks of Pakistan, and the probability of default is used to measure the default risk of these banks. The bank profitability is measured using bank-specific determinants such as the net interest margin, non-interest income to total assets, return on assets, return on equity, and spread ratios. The empirical findings of the fixed effects model reported that net interest margin, non-interest income, and spread ratio are the significant determinants of default risk. The findings highlight that the bank profitability determinants can act as early warning signs of a bank’s deteriorating stability level. The study recommended that the central bank of Pakistan should guide the commercial banks to disclose the probability of default values in their financial reports. The study also suggested that the risk management department of a bank should consider these bank-specific determinants of profitability to manage default risk

Measuring Water Poverty Index in Urban Areas of Punjab

The urban population of Punjab is growing rapidly. It is projected that there will be a 25 to 30 percent increase in urban population by 2020. This rapid population increase is causing major problems in the efficient provision of urban services in these cities. To evaluate the effect of this population increase, this paper tries to produce an integrated assessment of water stress and scarcity, linking physical estimates of water availability with socioeconomic variables that reflect poverty, i.e., a Water Poverty Index. It is understood that poor households face the problem of the accessibility of potable water, and this results in a significant loss of time and effort, especially for women. On the basis of multiple data sources, this paper evaluates water poverty in three panels of large, intermediate, and small cities of Punjab. The results show the same water poverty level within the panels but a higher poverty level in large cities than small and intermediate cities

The rapid emergence of stimulus specific perceptual learning

Is stimulus specific perceptual learning the result of extended practice or does it emerge early in the time course of learning? We examined this issue by manipulating the amount of practice given on a face identification task on Day 1, and altering the familiarity of stimuli on Day 2. We found that a small number of trials was sufficient to produce stimulus specific perceptual learning of faces: on Day 2, response accuracy decreased by the same amount for novel stimuli regardless of whether observers practiced 105 or 840 trials on Day 1. Current models of learning assume early procedural improvements followed by late stimulus specific gains. Our results show that stimulus specific and procedural improvements are distributed throughout the time course of learning

Perceptual learning reduces crowding in amblyopia and in the normal periphery

Amblyopia is a developmental visual disorder of cortical origin, characterized by crowding and poor acuity in central vision of the affected eye. Crowding refers to the adverse effects of surrounding items on object identification, common only in normal peripheral but not central vision. We trained a group of adult human amblyopes on a crowded letter identification task to assess whether the crowding problem can be ameliorated. Letter size was fixed well above the acuity limit, and letter spacing was varied to obtain spacing thresholds for central target identification. Normally sighted observers practiced the same task in their lower peripheral visual field. Independent measures of acuity were taken in flanked and unflanked conditions before and after training to measure crowding ratios at three fixed letter separations. Practice improved the letter spacing thresholds of both groups on the training task, and crowding ratios were reduced after posttest. The reductions in crowding in amblyopes were associated with improvements in standard measures of visual acuity. Thus, perceptual learning reduced the deleterious effects of crowding in amblyopia and in the normal periphery. The results support the effectiveness of plasticity-based approaches for improving vision in adult amblyopes and suggest experience-dependent effects on the cortical substrates of crowding