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Background Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population are limited. Aim To delineate the adverse factors associated with outcomes of COVID-19 patients ≥75 years of age. Design Retrospective cohort study. Methods Patients were classified into mild/moderate, severe/very severe and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. Results A total of 355 patients aged ≥75 years hospitalized with COVID-19 between 19 March and 25 April 2020 were included.Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease: 17.4%, severe/very severe disease: 71.3%, critical disease: 94.9%, P  < 0.001).Increased age, dementia, and severe/very severe and critical disease groups were independently associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR: 0.12, 95% CI: 0.02–0.60, P  < 0.05). None of the cardiovascular comorbidities were significantly associated with mortality. Conclusion Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality. [ABSTRACT FROM AUTHOR]

The present study explores the suitability of groundwater for drinking purpose and evaluates non-carcinogenic health risks for children, women, and men. For this purpose, 47 groundwater samples were collected and analyzed for physicochemical parameters, including nitrate concentration. The results revealed that nitrate concentration varied from 15 to 85 mg/L and that 48.93% of the groundwater samples exceeded the Bureau of Indian Standards' limits of 45 mg/L. The spatial map of the pollution index of groundwater specifies that most of the study area lies in moderate to high pollution zones. Principal component analysis was also applied, and five principal components achieving eigenvalues more than 1 with a cumulative variance of 77.36% were found to be sufficient. The findings of non-carcinogenic risk rates range from 0.628 to 3.559 (average of 2.069) for children, 0.427 to 2.421 (average of 1.408) for women, and 0.362 to 2.049 (average of 1.191) for men, and approximately 80% of the population in the study region is exposed to high health risks. The health risk assessment specified that children in the study area are more susceptible than women and men. The findings of this study suggest that groundwater quality in the region has deteriorated, emphasizing the need for treatment before drinking.

Host protein HuR translocation from nucleus to cytoplasm following infection is crucial for the life cycle of several RNA viruses including hepatitis C virus (HCV), a major causative agent of hepatocellular carcinoma. HuR assists the assembly of replication-complex on the viral-3'UTR, and its depletion hampers viral replication. Although cytoplasmic HuR is crucial for HCV replication, little is known about how the virus orchestrates the mobilization of HuR into the cytoplasm from the nucleus. We show that two viral proteins, NS3 and NS5A, act co-ordinately to alter the equilibrium of the nucleo-cytoplasmic movement of HuR. NS3 activates protein kinase C (PKC)-δ, which in-turn phosphorylates HuR on S318 residue, triggering its export to the cytoplasm. NS5A inactivates AMP-activated kinase (AMPK) resulting in diminished nuclear import of HuR through blockade of AMPK-mediated phosphorylation and acetylation of importin-α1. Cytoplasmic retention or entry of HuR can be reversed by an AMPK activator or a PKC-δ inhibitor. Our findings suggest that efforts should be made to develop inhibitors of PKC-δ and activators of AMPK, either separately or in combination, to inhibit HCV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Raheja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The emergence and evolution of SARS-CoV-2 is characterized by the occurrence of diverse sets of mutations that affect virus characteristics, including transmissibility and antigenicity. Recent studies have focused mostly on spike protein mutations; however, SARS-CoV-2 variants of interest (VoI) or concern (VoC) contain significant mutations in the nucleocapsid protein as well. To study the relevance of mutations at the virion level, recombinant baculovirus expression system-based virus-like particles (VLPs) were generated for the prototype Wuhan sequence along with spike protein mutants like D614G and G1124V and the significant RG203KR mutation in nucleocapsid. All four structural proteins were assembled in a particle for which the morphology and size, confirmed by transmission electron microscopy, closely resembled that of the native virion. The VLP harboring RG203KR mutations in nucleocapsid exhibited augmentation of humoral immune responses and enhanced neutralization by immunized mouse sera. Results demonstrate a noninfectious platform to quickly assess the implication of mutations in structural proteins of the emerging variant. IMPORTANCE Since its origin in late 2019, the SARS-CoV-2 virus has been constantly mutating and evolving. Current studies mostly employ spike protein (S) pseudovirus systems to determine the effects of mutations on the infectivity and immunogenicity of variants. Despite its functional importance and emergence as a mutational hot spot, the nucleocapsid (N) protein has not been widely studied. The generation of SARS-CoV-2 VLPs in a baculoviral system in this study, with mutations in the S and N proteins, allowed examination of the involvement of all the structural proteins involved in viral entry and eliciting an immune response. This approach provides a platform to study the effect of mutations in structural proteins of SARS-CoV-2 that potentially contribute to cell infectivity, immune response, and immune evasion, bypassing the use of infectious virus for the same analyses.

Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S 2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S D domain) and G1124V (in S 2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.

During enteroviral infections, the canonical translation factor eukaryotic translation initiation factor 4 γ I (eIF4GI) is cleaved by viral protease 2A. The resulting C-terminal fragment is recruited by the viral internal ribosome entry site (IRES) for efficient translation of the viral RNA. However, the 2A protease is not present in the viral capsid and is synthesized only after the initial round of translation. This presents the conundrum of how the initial round of translation occurs in the absence of the C-terminal eIF4GI fragment. Interestingly, the host protein DAP5 (also known as p97, eIF4GIII, and eIF4G2), an isoform of eIF4GI, closely resembles the eIF4GI C-terminal fragment produced after 2A protease-mediated cleavage. Using the Coxsackievirus B3 (CVB3) IRES as a model system, here we demonstrate that DAP5, but not the full-length eIF4GI, is required for CVB3 IRES activity for translation of input viral RNA. Additionally, we show that DAP5 is specifically required by type I IRES but not by type II or type III IRES, in which cleavage of eIF4GI has not been observed. We observed that both DAP5 and C-terminal eIF4GI interact with CVB3 IRES in the same region, but DAP5 exhibits a lower affinity for CVB3 IRES compared with the C-terminal eIF4GI fragment. It appears that DAP5 is required for the initial round of viral RNA translation by sustaining a basal level of CVB3 IRES activity. This activity leads to expression of 2A protease and consequent robust CVB3 IRES-mediated translation by the C-terminal eIF4GI fragment., (© 2019 Dave et al.)

Coxsackievirus B3 is an enterovirus, with positive-sense single-stranded RNA genome containing 'Internal Ribosome Entry Site' (IRES) in the 5'UTR. Once sufficient viral proteins are synthesized in the cell from the input RNA, viral template switches from translation to replication to synthesize negative-strand RNA. Inhibition of translation is a key step in regulating this switch as the positive-strand RNA template should be free of ribosomes to enable polymerase movement. In this study, we show how a host protein hnRNP C1/C2 inhibits viral RNA translation. hnRNP C1/C2 interacts with stem-loop V in the IRES and displaces poly-pyrimidine tract binding protein, a positive regulator of translation. We further demonstrate that hnRNP C1/C2 induces translation to replication switch, independently from the already known role of the ternary complex (PCBP2-3CD-cloverleaf RNA). These results suggest a novel function of hnRNP C1/C2 in template switching of positive-strand from translation to replication by a new mechanism. Using mathematical modelling, we show that the differential affinity of hnRNP C1/C2 for positive and negative-strand RNAs guides the final ± RNA ratio, providing first insight in the regulation of the positive to negative-strand RNA ratio in enteroviruses.

Human metapneumo virus is an emerging cause of upper and lower respiratory tract illness with increasing reports of a varied spectrum of disease over all age groups. We report an outbreak of 6 cases of human metapneumo virus infection in the intensive care unit of a metropolitan tertiary care center over 6 weeks, leading to severe acute respiratory distress syndrome. We report the subsequent favorable outcomes due to the institution of extracorporeal membrane oxygenation.

Objective: To evaluate outcomes of routine invasive strategy (RIS) compared with selective invasive strategy (SIS) in elderly patients older than 75 years with non-ST-segment elevation acute coronary syndrome (NSTE-ACS)., Methods: We systematically searched databases for randomized controlled trials (RCTs) between January 1, 1990, and October 1, 2016, comparing RIS with SIS for elderly patients (age>75 years) with NSTE-ACS. Random effects meta-analysis was conducted to estimate odds ratio (OR) with 95% CIs for composite of death or myocardial infarction (MI), and individual end points of all-cause death, cardiovascular (CV) death, MI, revascularization, and major bleeding., Results: A total of 6 RCTs with 1887 patients were included in the final analysis. Compared with an SIS, RIS was associated with significantly decreased risk of the composite end point of death or MI (OR, 0.65; 95% CI, 0.51-0.83). Similarly, RIS led to a significant reduction in the risk of MI (OR, 0.51; 95% CI, 0.40-0.66) and need for revascularization (OR, 0.31; 95% CI, 0.11-0.91) compared with SIS. There were no significant differences between RIS and SIS in terms of all-cause death (OR, 0.85; 95% CI, 0.63-1.20), CV death (OR, 0.84; 95% CI, 0.61-1.15), and major bleeding (OR, 1.96; 95% CI, 0.97-3.97)., Conclusion: In elderly patients older than 75 years with NSTE-ACS, RIS is superior to SIS for the composite end point (death or MI), primarily driven by reduced risk of MI., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature., Objective: Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes., Methods: A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review., Results: Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions., Conclusion: The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.

Background: Invasive aspergillosis (IA) is an increasingly common and fatal opportunistic fungal infection in patients with haematological diseases. Early diagnosis is difficult as mycological culture techniques have low sensitivity and the radiological tools have low specificity. Galactomannan enzyme immunoassay (GEI) detects galactomannan in the human serum with a reported sensitivity and specificity between 30% and 100%., Aims: The aim of this study was to analyse the role of GEI in diagnosis of IA in patients with febrile neutropenia and to evaluate the role of GEI in the diagnosis of IA as per the revised (2008) European Organization for Research and Treatment of Cancer-Mycoses Study Group (EORTC-MSG) criteria at two different optical density (OD) cut-offs of 0.5 and 1.0., Setting: This prospective study was conducted in Safdarjung Hospital, New Delhi, India., Methods: GEI testing was performed in adult patients of febrile neutropenia with evidence of IA. Results at two different OD indices (ODIs) of 0.5 and 1.0 were analysed. The evaluation of the diagnostic parameter, that is, GEI was measured in terms of sensitivity, specificity and positive and negative predictive value and was validated with the revised (2008) EORTC-MSG diagnostic criteria of IA., Results: One hundred and eleven patients had evidence of IA, of which 79 patients were GEI positive when cut-off ODI was 0.5, whereas with cut-off ODI 1.0, 55 patients were GEI positive., Conclusion: ODI of 1.0 should be considered as positive while in patients with OD between 0.5 and 1.0, repeat sampling from the patient is recommended.

Background: Invasive fungal infection (IFI) is a fatal infection in haematology patients. There is an urgent need for reliable screening methods facilitating timely diagnosis and treatment. A real-time panfungal polymerase chain reaction (PCR) assay based on TaqMan technology targeting 18S ribosomal RNA gene was used to screen whole blood specimen obtained from series of Haematology malignancy patients for IFIs., Materials and Methods: The panfungal (Pan-ACF) assay was employed to investigate specimen from 133 patients in duplicate with suspected IFI. In addition twenty healthy subjects and twenty patients with bacterial infections were taken as control. The patients with suspected IFI were also diagnosed by conventional methods including direct microscopy, culture techniques and antigen detection (galactomannan antigen ELISA and latex agglutination for cryptococcal antigen). The results of molecular testing were evaluated in relation to the criteria proposed by the European Organization for Research and Treatment of Cancer and patients were classified as having proven and probable IFD., Results: Of 133 patients, 89 had proven, 18 had probable and 26 had possible IFI. One hundred four samples were reverse transcription-PCR positive. Of 89 proven cases, 84 were panfungal PCR positive. These 84 cases included 82 cases which revealed growth on fungal blood culture and two cases were negative on fungal blood culture. Of the 82 cases which revealed growth on culture: 74 grew Candida in culture, 3 grew Fusarium solani, 5 grew Aspergillus species on blood culture. The later five were also galactomannan antigen positive. The five specimen which were negative on panfungal PCR, two grew Trichosporon asahii, one grew Candida rugosa and two grew as Cryptococcus neoformans var. neoformans. Of the 18 probable cases, 18 were panfungal PCR positive. These were also galactomannan antigen positive. The sensitivity and specificity of panfungal PCR in proven cases were 94.3% and 95.2%, respectively. The positive and negative predictive values proven cases were 97.6% and 88.9%, respectively., Conclusions: The panfungal (Pan-ACF) real-time PCR assay can detect common fungal genera and it may be used as an adjunct to conventional methods for screening of IFI.

Background: The purpose of the present study is to investigate the prevalence of dental anomalies according to gender among children., Materials & Methods: This cross-sectional study was conducted a group of 600 children, of them 293 (48.8%) were males and 275 (45.8%) females which were taken with proper sampling technique. Type III clinical examination was done to know the prevalence of dental anomalies. The Statistical software namely SPSS version 16.0 was used for data analysis. Chi-square test was used at p value of 0.05 or less., Results: Impactions (39.2%) were the most common anomaly in this study and most of the impacted teeth were related to maxilla. A significant difference was seen in case of hypodontia, microdontia and talons cusp according to gender in which first two anomalies were more among females and last one among males. Children with one dental anomaly were 25.8%, and 13.4% were having more than one., Conclusion: The percentage of dental anomalies were high specially impaction and rotated teeth. So these anomalies should be treated earlier to avoid further complications. How to cite this article: Kathariya MD, Nikam AP, Chopra K, Patil NN, Raheja H, Kathariya R. Prevalence of Dental Anomalies among School Going Children in India. J Int Oral Health 2013; 5(5):10-4.