Paternal Alcohol Consumption and Childhood Malnutrition: A Community-based Participatory Case-control Study among Adivasis in Rural South India.

BACKGROUND: Childhood malnutrition in India remains among the highest in the world. Adult alcohol consumption and severe malnutrition have increased among indigenous people in South India. However, the association between them is poorly understood. OBJECTIVES: We aimed to evaluate this association, which could help design better intervention strategies. METHODS: This case-control observational study was conducted in the Nilgiri district in South India. Cases included children aged 1-5 years with moderate malnutrition. Controls were defined as children in the same age group with normal weight-for-age. A questionnaire was used to collect data on demographics, socioeconomic status (SES), and parental education. The WHO Alcohol Use Disorders Identification Test (AUDIT) questionnaire was used to estimate parental alcohol use. Health-care workers collected data from within the community. RESULTS: The baseline demographics of the children in the control (n = 250) and case groups (n = 177) were similar. Paternal age and AUDIT scores were not different in the two groups. SES was lower in the malnourished group, while maternal education among cases was significantly lower. Maternal and paternal education were associated with childhood malnutrition (odds ratio [OR]: 0.728 [95% confidence interval (CI): 0.583-0.903] and OR: 0.753 [95% CI: 0.589-0.957], respectively). After adjustment for covariates, paternal alcohol use was associated with a higher risk of malnutrition (OR: 1.56 [95% CI: 1.00-2.47]), which SES partly mediated. CONCLUSION: Paternal alcohol consumption is associated with childhood malnutrition, partially mediated by lower SES. Furthermore, lower SES appeared to be strongly associated with paternal alcohol consumption.

COVID-19: Does the infectious inoculum dose-response relationship contribute to understanding heterogeneity in disease severity and transmission dynamics?

The variation in the speed and intensity of SARS-CoV-2 transmission and severity of the resulting COVID-19 disease are still imperfectly understood. We postulate a dose-response relationship in COVID-19, and that "the dose of virus in the initial inoculum" is an important missing link in understanding several incompletely explained observations in COVID-19 as a factor in transmission dynamics and severity of disease. We hypothesize that: (1) Viral dose in inoculum is related to severity of disease, (2) Severity of disease is related to transmission potential, and (3) In certain contexts, chains of severe cases can build up to severe local outbreaks, and large-scale intensive epidemics. Considerable evidence from other infectious diseases substantiates this hypothesis and recent evidence from COVID-19 points in the same direction. We suggest research avenues to validate the hypothesis. If proven, our hypothesis could strengthen the scientific basis for deciding priority containment measures in various contexts in particular the importance of avoiding super-spreading events and the benefits of mass masking.

The COVID-19 pandemic: diverse contexts; different epidemics-how and why?

It is very exceptional that a new disease becomes a true pandemic. Since its emergence in Wuhan, China, in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has spread to nearly all countries of the world in only a few months. However, in different countries, the COVID-19 epidemic takes variable shapes and forms in how it affects communities. Until now, the insights gained on COVID-19 have been largely dominated by the COVID-19 epidemics and the lockdowns in China, Europe and the USA. But this variety of global trajectories is little described, analysed or understood. In only a few months, an enormous amount of scientific evidence on SARS-CoV-2 and COVID-19 has been uncovered (knowns). But important knowledge gaps remain (unknowns). Learning from the variety of ways the COVID-19 epidemic is unfolding across the globe can potentially contribute to solving the COVID-19 puzzle. This paper tries to make sense of this variability-by exploring the important role that context plays in these different COVID-19 epidemics; by comparing COVID-19 epidemics with other respiratory diseases, including other coronaviruses that circulate continuously; and by highlighting the critical unknowns and uncertainties that remain. These unknowns and uncertainties require a deeper understanding of the variable trajectories of COVID-19. Unravelling them will be important for discerning potential future scenarios, such as the first wave in virgin territories still untouched by COVID-19 and for future waves elsewhere.

HIV-1 inhibits haematopoiesis via microRNA secreted by virus-infected CD4+ T cells.

INTRODUCTION: HIV-1-infected patients develop haematological disorders such as cytopenias. One possible explanation is the inhibition of haematopoiesis at the level of differentiation of CD34+ haematopoietic progenitor stem cells. Based on our previous studies, we hypothesised that there may be viral encoded, or host cellular factors which participate in the process of inhibition of haematopoiesis. MATERIALS AND METHODS: Virus-depleted media from infected CD4+ T cells was prepared by filtration and added to CD34+ cell differentiation semisolid medium. We have also used the virus-depleted media to isolate host/viral factors including miRNA. Isolated miRNAs were screened for their haematopoietic inhibitory function using the miRNA mining approach. RESULTS: Addition of virus-depleted media caused a 40% inhibition of differentiation of CD34+ cells into myeloid and erythroid colony formation. Real-time RT-PCR showed miR-15a and miR-24 from both pIndie-C1 and pNL4.3 HIV-1-infected cells showed a significant differential expression when compared to control media. CONCLUSION: In this study, we have identified two miRNAs, miR-15a and miR-24 secreted from purified HIV-1-infected CD4+ T cells that inhibited CD34+ haematopoietic progenitor stem cell differentiation into myeloid and erythroid colonies in vitro.

Optimization of Ex Vivo Murine Bone Marrow Derived Immature Dendritic Cells: A Comparative Analysis of Flask Culture Method and Mouse CD11c Positive Selection Kit Method.

12-14 days of culturing of bone marrow (BM) cells containing various growth factors is widely used method for generating dendritic cells (DCs) from suspended cell population. Here we compared flask culture method and commercially available CD11c Positive Selection kit method. Immature BMDCs' purity of adherent as well as suspended cell population was generated in the decreasing concentration of recombinant-murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) in nontreated tissue culture flasks. The expression of CD11c, MHCII, CD40, and CD86 was measured by flow cytometry. We found significant difference (P < 0.05) between the two methods in the adherent cells population but no significant difference was observed between the suspended cell populations with respect to CD11c+ count. However, CD11c+ was significantly higher in both adhered and suspended cell population by culture method but kit method gave more CD11c+ from suspended cells population only. On the other hand, using both methods, immature DC expressed moderate level of MHC class II molecules as well as low levels of CD40 and CD86. Our findings suggest that widely used culture method gives the best results in terms of yield, viability, and purity of BMDCs from both adherent and suspended cell population whereas kit method works well for suspended cell population.

Differential proteomic analysis of respiratory samples from patients suffering from influenza.

The exact molecular pathways involved in the pathogenesis of influenza are yet unclear. In the present study we investigated the upper respiratory proteome in influenza patients. 200 nasal and throat swab samples were collected from patients suffering from acute respiratory illness. These samples were confirmed for influenza pandemic A/H1N1/2009 and influenza type B using qRT-PCR. 10 similar swabs were collected from healthy individuals and were used as controls. Proteins were extracted from the cell pellets and were subjected to 2-D gel electrophoresis. The differentially expressed proteins were identified using MALDI-TOF. Identified proteins were classified into different functional groups based on functions reported in the databases. 25 % of these proteins were involved in cytoskeletal formation, whereas 14 % were involved in signal transduction. Proteins involved in anti-viral responses, Ca-signaling, transport, and tumor suppression constituted 10 % each, where as 5 % of proteins each belong to Nicotinic acetylcholine receptor, Protein Synthesis and anti-bacterial proteins. 10 % of the proteins have not been described previously. This is the first report on respiratory proteome profile in Influenza patients. The study emphasizes the role of such profiling studies using multiple platforms for bio-marker discoveries, especially non-invasive diagnostic marker in Influenza and other infectious diseases.

Bacillus Calmette-Guérin Confers Neuroprotection in a Murine Model of Japanese Encephalitis.

OBJECTIVE: Japanese encephalitis (JE) is a debilitating disease caused by infection with the JE virus (JEV; family: Flaviviridae), which leaves neurological sequelae in survivors but more often leads to mortality. Neurodegeneration caused by inflammation is the primary pathology behind the clinical manifestation of encephalitis caused by JEV. Bacillus Calmette-Guérin (BCG) has been used in immunoprophylaxis for tuberculosis and in the adjuvant therapy of many malignancies, and has exhibited neuroprotective activities in experimental models of Parkinson and Alzheimer disease. This study aimed at assessing the neuroprotective role of BCG in a murine model of JE. METHODS: Suckling mice were inoculated with 106 CFU of BCG and at 18 days postinoculation were challenged with 100 LD50 of JEV. PBS-inoculated mice were used as controls. Mice were sacrificed on days 2, 4, 6, and 8. Brain tissue was homogenized for RNA extraction. One-step real-time RT-PCR was performed to assess the relative gene expressions of TNF-α, IL-6, and iNOS. RESULTS: The BCG-inoculated (BCG+JEV) group exhibited a significant delay in the presentation of neuropathological symptoms, longer survival, and a downregulation in the expression of TNF-α, IL-6, and iNOS on days 2, 4, and 6 post-JEV challenge compared to the JEV group. CONCLUSION: These findings indicate that the administration of BCG offers neuroprotection in the murine model of JE. BCG should therefore be further investigated as an adjuvant in the management of JE. BCG is an accepted vaccine for tuberculosis in many countries that are endemic for JEV. This approach may have a significant impact on the public health burden in these countries.

Characterization of influenza virus among influenza like illness cases in Mumbai, India.

The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007-2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was further confirmed and typed by hemagglutination assay and hemagglutination inhibition assay. Out of 193 samples 24 (12.4 3%) samples tested positive for influenza virus, of which 13 (6.73 %) were influenza type A virus and 10 (5.18 %) were influenza type B virus, while 1 sample (0.51 %) was positive for both. By culture methods, 3 (1.55 %) viral isolates were obtained. All the three isolates were found to be Influenza type B/Malaysia (Victoria lineage) by Hemagglutination Inhibition Assay. The data generated from the present study reveals that both Influenza type A and B are prevalent in Mumbai with considerable activity. The peak activity was observed during monsoon season.

Evaluation of Jatropha curcas Linn. leaf extracts for its cytotoxicity and potential to inhibit hemagglutinin protein of influenza virus.

Influenza is a serious respiratory illness which can be debilitating and cause complications that lead to hospitalization and death. Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. Given temporal and geographic changes and the shifts in antiviral drug resistance among influenza viruses, it is time to consider natural antiviral agents against influenza virus. Jatropha curcas is known for various medicinal uses. Its antimicrobial, anti-cancer and anti-HIV activity has been well recognized. Because of its broad-spectrum activity, we investigated aqueous and methanol leaf extracts for cytotoxicity and its potential to inhibit hemagglutinin protein of influenza virus. The bioactive compounds from leaf extracts were characterized by high-performance thinlayer chromatography which revealed the presence of major phytochemicals including flavonoids, saponins and tannins. The cytotoxic concentration 50 for aqueous and methanol extracts were determined using trypan blue dye exclusion assay. Inhibition of hemagglutinin protein was assessed using minimal cytotoxic concentrations of the extracts and 10(2.5) TCID50 (64 HA titre) of the Influenza A (H1N1) virus with different exposure studies using hemagglutination assay. Aqueous and methanol extracts were found to be non toxic to Madin darby canine kidney cells below concentration of 15.57 and 33.62 mg/mL for respectively. Inhibition of hemagglutinin was studied using reducing hemagglutination titre which confirmed that the J. curcas extracts have direct effect on the process of virus adsorption leading to its inhibition. Our results provide the information which shows the potential of Jatropha extracts in the treatment of influenza A (H1N1) virus infection. With an established reduced toxicity and prevention of infection by inhibiting hemagglutinin protein, these extracts and its derivatives may be further developed as broad spectrum anti-influenza drugs for prevention and treatment of infections by different types of influenza viruses with further mechanistic studies on anti-influenza.