Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death.

Death is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.

Leuconostoc, a masquerading pathogen in oral cancer patient: A rare case report.

Osteoradionecrosis is the most common cause of mandibular osteomyelitis. Here we are reporting a case of osteomyelitis of the mandible caused by Leuconostoc mesenteroides spp cremoris. The frequency of Leuconostoc infections are under reported mainly due to its difficult identification. Non pathogenic organism like leuconostoc can cause infection in the immunocompromised and should warrant proper microbial identification and adequate targeted treatment to manage the patients.

Structural Differences In 3C-like protease (Mpro) From SARS-CoV and SARS-CoV-2: Molecular Insights For Drug Repurposing Against COVID-19 Revealed by Molecular Dynamics Simulations.

A recent fatal outbreak of novel coronavirus SARS-CoV-2, identified preliminary as a causative agent for series of unusual pneumonia cases in Wuhan city, China has infected more than 20 million individuals with more than 4 million mortalities. Since, the infection crossed geographical barriers, the WHO permanently named the causing disease as COVID-2019 by declaring it a pandemic situation. SARS-CoV-2 is an enveloped single-stranded RNA virus causing a wide range of pathological conditions from common cold symptoms to pneumonia and fatal severe respiratory syndrome. Genome sequencing of SARS-CoV-2 has revealed 96% identity to the bat coronavirus and 79.6% sequence identity to the previous SARS-CoV. The main protease (known as 3C-like proteinase/ Mpro) plays a vital role during the infection with the processing of replicase polyprotein thus offering an attractive target for therapeutic interventions. SARS-CoV and SARS-CoV-2 Mpro shares 97% sequence identity, with 12 variable residues but none of them present in the catalytic and substrate binding site. With the high level of sequence and structural similarity and absence of any drug/vaccine against SARS-CoV-2, drug repurposing against Mpro is an effective strategy to combat COVID-19. Here, we report a detailed comparison of SARS-CoV-2 Mpro with SARS-CoV Mpro using molecular dynamics simulations to assess the impact of 12 divergent residues on the molecular microenvironment of Mpro. A structural comparison and analysis is made on how these variable residues affects the intra-molecular interactions between key residues in the monomer and biologically active dimer form of Mpro. The present MD simulations study concluded the change in microenvironment of active-site residues at the entrance (T25, T26, M49 and Q189), near the catalytic region (F140, H163, H164, M165 and H172) and other residues in substrate binding site (V35T, N65S, K88R and N180K) due to 12 mutation incorporated in the SARS-CoV-2 Mpro. It is also evident that SARS-CoV-2 dimer is more stable and less flexible state compared to monomer which may be due to these variable residues, mainly F140, E166 and H172 which are involved in dimerization. This also warrants a need for inhibitor design considering the more stable dimer form. The mutation accumulated in SARS-CoV-2 Mpro indirectly reconfigures the key molecular networks around the active site conferring a potential change in SARS-CoV-2, thus posing a challenge in drug repurposing SARS drugs for COVID-19. The new networks and changes in microenvironment identified by our work might guide attempts needed for repurposing and identification of new Mpro inhibitors.

Patient satisfaction with services of the outpatient department.

BACKGROUND: Patients' satisfaction is a useful measure to provide an indicator of quality in healthcare and thus needs to be measured frequently. The aim of the study was to analyse and compare the level of satisfaction of patients attending the Outpatient Department of a Hospital. METHODS: Study was conducted by using a pre-structured questionnaire with 120 samples. Samples were further stratified into sub-populations of Officers, Junior Commissioned Officers (JCOs) and Other Ranks (ORs) including dependents as study population. RESULTS: JCOs predominantly expressed lower satisfaction judgement with several attributes. Overall satisfaction judgement with Outpatient Department services were rated lower by JCOs (2.56) when compared with Officers and ORs (3.10), the difference being statistically significant. CONCLUSION: Statistically significant differences have been identified by this study against various study attributes as well as overall impression towards OPD services among the study groups, which need to be addressed by the hospital leadership to achieve consumer delight.

Leprosy: down but not out.

Leprosy is a chronic disabling disease and there are areas of high endemicity in India. Case findings and management strategies suffer a setback when disease manifestations are not picked up in time by health-care providers. This article attempts to estimate the annual incidents of leprosy and to study the confounding factors which may potentially cause delays in diagnosis in an office-based, tertiary health-care setting.

Poor perinatal care practices in urban slums: possible role of social mobilization networks.

BACKGROUND: Making perinatal care accessible to women in marginalized periurban areas poses a public health problem. Many women do not utilize institutional care in spite of physical accessibility. Home-based care by traditional birth attendants (TBA) is hazardous. Inappropriate early neonatal feeding practices are common. Many barriers to perinatal care can be overcome by social mobilization and capacity building at the community level. OBJECTIVES: To determine the existing perinatal practices in an urban slum and to identify barriers to utilization of health services by mothers. STUDY DESIGN: This is a cross-sectional descriptive study. SETTING AND PARTICIPANTS: The high-risk periurban areas of Nabi Nagar, Aligarh has a population of 40,000 living in 5,480 households. Mothers delivering babies in September 2007 were identified from records of social mobilization workers (Community Mobilization Coordinators or CMCs) already working in an NGO in the area. A total of 92 mothers were interviewed at home. Current perinatal practices and reasons for utilizing or not utilizing health services were the topics of inquiry. STATISTICAL ANALYSIS: Data was tabulated and analyzed using SPSS 12. RESULTS: Analyses revealed that 80.4% of mothers had received antenatal care. However, this did not translate into safe delivery practices as more than 60% of the women had home deliveries conducted by traditional untrained or trained birth attendants. Reasons for preferring home deliveries were mostly tradition (41.9%) or related to economics (30.7%). A total of 56% of the deliveries were conducted in the squatting position and in 25% of the cases, the umbilical cord was cut using the edge of a broken cup. Although breast-feeding was universal, inappropriate early neonatal feeding practices were common. Prelacteal feeds were given to nearly 50% of the babies and feeding was delayed beyond 24 hours in 8% of the cases. Several mothers had breastfeeding problems. CONCLUSION: Barriers to utilization of available services leads to hazardous perinatal practices in urban slums.