A clinical trial of treatment of uncomplicated typhoid fever: efficacy of ceftriaxone-azithromycin combination

Background: Typhoid fever is a systemic infection caused by Gram-negative bacterium Salmonella enterica serovar typhi (S. typhi). It is a major health problem in India. It carries significant morbidity and mortality. Antimicrobial therapy is critical for the management of typhoid fever. Emergence of multidrug-resistant (MDR) and nalidixic acid-resistant (NAR) strains of S. typhi has complicated therapy by limiting treatment options. Hence, this study was conducted to evaluate the efficacy and safety profile of ceftriaxone and azithromycin combination therapy in uncomplicated typhoid fever.Methods: Adults patients of blood culture proven uncomplicated typhoid fever admitted in the medicine ward of Teerthanker Mahaveer Medical College and Research Centre were treated with ceftriaxone intravenously (2 g daily for 14 days) and azithromycin orally (500 mg daily for 7 days). Patients were clinically and bacteriologically evaluated during the study period and follow-up.Results: 96% cure rate was observed. No relapse was recorded.Conclusion: Ceftriaxone-azithromycin combination may be considered as an empirical therapy for treatment of uncomplicated typhoid fever in view of the emergence of MDR and NAR strains of S. typhi

Recommendations for detection, validation, and evaluation of RNA editing events in cardiovascular and neurological/neurodegenerative diseases.

peer reviewedRNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding. With advancing RNA sequencing technology, more RNA editing events are being discovered, studied, and reported. However, RNA editing events are still often overlooked or discarded as sequence read quality defects. With this position paper, we aim to provide guidelines and recommendations for the detection, validation, and follow-up experiments to study RNA editing, taking examples from the fields of cardiovascular and brain disease. We discuss all steps, from sample collection, storage, and preparation, to different strategies for RNA sequencing and editing-sensitive data analysis strategies, to validation and follow-up experiments, as well as potential pitfalls and gaps in the available technologies. This paper may be used as an experimental guideline for RNA editing studies in any disease context

Structural insights into putative molybdenum cofactor biosynthesis protein C (MoaC2) from Mycobacterium tuberculosis H37Rv.

The Molybdenum cofactor (Moco) biosynthesis pathway is an evolutionary conserved pathway seen in almost all eukaryotes including the pathogenic species Mycobacterium tuberculosis. This pathway comprises of several novel reactions which include the initial formation of precursor Z from guanosine triphosphate (GTP), catalysed by two enzymes MoaA and MoaC. Although Moco biosynthesis is well understood, the first step is still not clear. In M. tuberculosis H37Rv, three orthologous genes of MoaC have been annotated: moaC1 (Rv3111), moaC2 (Rv0864) and moaC3 (Rv3324c). Rv0864 (MoaC2) is a 17.5 kDa protein and is reported to be down-regulated by ∼3 times in the nutrient starvation model for Mycobacterium tuberculosis. The crystal structure of Moco-biosynthesis protein MoaC2 from Mycobacterium tuberculosis (2.20 Å resolution, space group P213) has been determined. Based on a comparative analysis of structures of homologous proteins, conserved residues were identified and are implicated in structural and functional roles. Molecular docking studies with probable ligands carried out in order to identify its ligand, suggests that pteridinebenzomonophosphate as the most likely ligand. Sequence based interaction study identified MoaA1 to interact with MoaC2. A homology model of MoaA1 was then complexed with MoaC2 and protein-protein interactions are also discussed

Evidence for serpentine as a novel antioxidant by a redox sensitive HABP1 over expressing cell line by inhibiting its nuclear translocation of NF-κB

Herbal antioxidants are gradually gaining importance as dietary supplements considering the growing implications of oxidative stress in most degenerative diseases and aging. Thus, continuous attempts are made to search for novel herbal molecules with antioxidative properties, using chemical methods predominantly with the need arising for cell based assays. We have generated a stable cell line F-HABP07, by constitutively overexpressing human Hyaluronan Binding Protein1 (HABP1) in murine fibroblasts which accumulates in the mitochondria leading to excess ROS generation without any external stimuli. In the present study, we demonstrated the nuclear translocation of p65 subunit of NF-κB in F-HABP07 cells, an important signature of ROS induced signalling cascade providing us an opportunity to use it as a screening system for ROS scavengers. Using known antioxidants on our designer cell line, we have demonstrated a dose dependant reduction in ROS generation and observed inhibition of p65 subunit of NF-KB nuclear translocation, increase in glutathione content and down-regulation of apoptotic marker Bax establishing its antioxidant biosensing capacity. With the help of this cell line, we for the first time demonstrated serpentine, one of the active components from the roots of Rauwolfia serpentina (a traditional medicinal plant), to be a novel non-cytotoxic antioxidant. The authenticity of this cell line screening system based discovery was validated using standard chemical assays thus, opening up new therapeutic avenues for this herbal compound and the use of this designer cell line

Antral follicle count in normal (fertility-proven) and infertile Indian women

Background: Antral follicle count (AFC) has been labeled as the most accurate biomarker to assess female fecundity. Unfortunately, no baseline Indian data exists, and we continue using surrogate values from the Western literature (inferred from studies on women, grossly different than Indian women in morphology and genetic makeup). Aims: (1) To establish the role of AFC as a function of ovarian reserve in fertility-proven and in subfertile Indian women. (2) To establish baseline cut-off AFC values for Indian women. Settings and Design: Prospective observational case-control study. Materials and Methods: Thirty patients undergoing workup for infertility were included and compared to equal number of controls (women with proven fertility). The basal ovarian volume and AFC were measured by endovaginal. USG the relevant clinical data and hormonal assays were charted for every patient. Statistical Analysis Used: SPSS platform was used to perform the Student′s t-test and Mann-Whitney U-test for intergroup comparisons. Correlations were determined by Pearson′s ranked correlation coefficient. Results: Regression analysis revealed the highest correlation of AFC and age in fertile and infertile patients with difference in mean AFC of both the groups. Comparison of the data recorded for cases and controls showed no significant difference in the mean ovarian volume. Conclusions: AFC has the closest association with chronological age in normal and infertile Indian women. The same is lower in infertile women than in matched controls. Baseline and cut-off values in Indian women are lower than that mentioned in the Western literature

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate–severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate–severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration

Identification of 1‑[4-Benzyloxyphenyl)-but-3-enyl]‑1<i>H</i>‑azoles as New Class of Antitubercular and Antimicrobial Agents

A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1<i>H-</i>azoles has been identified as potent antitubercular agents against <i>Mycobacterium tuberculosis</i>. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds <b>26</b>, <b>34</b>, and <b>36</b> exhibited significant antitubercular activities with MIC value as low as 1.56, 1.56, and 0.61 μg/mL, respectively, comparable to many standard drugs. These compounds were also screened against other strains of bacteria and fungi, and few of them showed good antifungal activity against <i>A. fumigatus</i>, responsible for lung infection