Effect of Nutritional Rehabilitation on Neurodevelopmental Status of Children With Severe Acute Malnutrition.

Objective: To evaluate the change in the neurodevelopmental status of children (1-30-months-old) with severe acute malnutrition (SAM) following nutritional rehabilitation.

Methods: A prospective study was conducted in the Severe Malnutrition Therapeutic Unit (SMTU) of a tertiary hospital in Central India, between April 2021 and October 2022. Children with primary neurological conditions like cerebral palsy and epilepsy were excluded.

Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens.

The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance. We investigated the activity of RBx 10080758 against Gram-positive bacteria and . RBx 10080758 showed a potent 50% inhibitory concentration of 0.

Novel FtsZ inhibitor with potent activity against Staphylococcus aureus.

Objectives: FtsZ is an essential bacterial protein and an unexplored target for the development of antibacterial drugs. The development of a novel inhibitor targeting FtsZ offers a potential opportunity to combat drug resistance. DS01750413, a new derivative of PC190723, is a novel FtsZ inhibitor with improved in vitro and in vivo activity.

Novel azoles with potent antileishmanial activity.

To investigate the antileishmanial activity of novel azole compounds against , which causes deadly visceral leishmaniasis disease. A focused azole-based library was screened against both promastigotes and amastigotes forms of strains in flat-bottomed 96-well tissue culture plates and J774A.1 macrophage cell-line infected with .

Azithromycin Exhibits Activity Against in Chronic Rat Lung Infection Model.

forms biofilms in the lungs of chronically infected cystic fibrosis patients, which are tolerant to both the treatment of antibiotics and the host immune system. Normally, antibiotics are less effective against bacteria growing in biofilms; azithromycin has shown a potent efficacy in cystic fibrosis patients chronically infected with and improved their lung function. The present study was conducted to evaluate the effect of azithromycin on biofilm.

Next-Generation Molecular Diagnostics Development by CRISPR/Cas Tool: Rapid Detection and Surveillance of Viral Disease Outbreaks.

Virus disease spreads effortlessly mechanically or through minute insect vectors that are extremely challenging to avoid. Emergence and reemergence of new viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), H1N1 influenza virus, avian influenza virus, dengue virus, Citrus tristeza virus, and Tomato yellow leaf curl virus have paralyzed the economy of many countries. The cure for major viral diseases is not feasible; however, early detection and surveillance of the disease can obstruct their spread.

Host sphingolipids: Perspective immune adjuvant for controlling SARS-CoV-2 infection for managing COVID-19 disease.

Sphingolipids are potent bioactive agents involved in the pathogenesis of various respiratory bacterial infections. To date, several sphingolipid derivatives are known, but S1P (Sphingosine-1-phosphate) and Ceramide are the best-studied sphingolipid derivatives in the context of human diseases. These are membrane-bound lipids that influence host-pathogen interactions.

Inhibition ELISA as a putative tool for the identification and quantification of meningococcal A and X polysaccharides at various stages of vaccine development.

The multivalent glycoconjugate vaccines against Neisseria meningitidis are extremely high-priced for the developing world. The high cost is due to the manufacturing set-up required to produce an effective vaccine and other inflators like complex production steps including the production and purification of the polysaccharide and consequently its conjugation with a protein and finally formulating the finished multivalent product. There is an urgent need for assays which are simple, precise, can be applicable at multiple steps and contribute in reducing the overall manufacturing cost, thereby making the vaccines more equitable to the developing world.

Potential of the fluoroketolide RBx 14255 against Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in an experimental murine meningitis model.

Background: RBx 14255 is a fluoroketolide in pre-clinical evaluation with potent activity against MDR Gram-positive pathogens.

Objectives: To investigate the efficacy of RBx 14255 against bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis or Haemophilus influenzae in an experimental murine meningitis model.

Methods: In vitro activity of RBx 14255 was evaluated against clinical isolates of S.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor with Activity against Pseudomonas aeruginosa.

DS86760016 is a new leucyl-tRNA-synthetase inhibitor at the preclinical development stage. DS86760016 showed potent activity against extended-spectrum multidrug-resistant isolated from clinical samples and biofilms. In a murine catheter-associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of from the kidney, bladder, and catheter without developing drug resistance.

Evaluation of impact of temperature and pH alterations on the size and antigenicity of meningococcal serogroup A and X polysaccharides and conjugates.

The changes in the recommended storage conditions of the glycoconjugate vaccines against Neisseria meningitidis (Men) serogroup A and serogroup X can affect its activity or potency. Elevated temperature and the change in pH may result in the physical instability leading to the size degradation of the polysaccharide (PS) and subsequent loss of PS epitopes. Moreover, high temperature may also result in protein aggregation and altered tertiary structure of the protein in the conjugate.

Synthesis and evaluation of thiomannosides, potent and orally active FimH inhibitors.

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coli (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally.

Effect of DS-2969b, a novel GyrB inhibitor, on rat and monkey intestinal microbiota.

DS-2969b, a novel GyrB inhibitor, transiently and reversibly altered the counts of limited intestinal microbiota at around 10 μg/g of faecal levels in rats and monkeys. Considering the high activity of DS-2969b against Clostridium difficile, 10 μg/g of faecal levels would be sufficient for clearing C. difficile from the intestine.

and Activities of DS-2969b, a Novel GyrB Inhibitor, and Its Water-Soluble Prodrug, DS11960558, against Methicillin-Resistant Staphylococcus aureus.

DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the activity of DS-2969b and the activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant (MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of DNA gyrase and the decatenation activity of its topoisomerase IV.

In vivo efficacy and pharmacokinetics of bi-aryl oxazolidinone RBx 11760 loaded polylactic acid-polyethylene glycol nanoparticles in mouse hematogenous bronchopneumonia and rat groin abscess caused by Staphylococcus aureus.

RBx 11760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11760 in PLA-PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11760 loaded NPs were found to be 106.

and Activities of DS-2969b, a Novel GyrB Inhibitor, against Clostridium difficile.

DS-2969b is a novel GyrB inhibitor that is currently under clinical development for the treatment of infection (CDI). In this study, the and activities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity of DNA gyrase.

and Activities of DS86760016, a Novel Leucyl-tRNA Synthetase Inhibitor for Gram-Negative Pathogens.

The emergence of multidrug-resistant (MDR) Gram-negative bacilli is a major concern in the treatment of nosocomial infections. Antibacterial agents with novel modes of action can be useful, as these pathogens have become resistant to almost all existing standard-of-care agents. GSK2251052, a leucyl-tRNA synthetase inhibitor, has a novel mode of action against Gram-negative bacteria.

In Vitro and In Vivo Activities of a Bi-Aryl Oxazolidinone, RBx 11760, against Gram-Positive Bacteria.

RBx 11760, a bi-aryl oxazolidinone, was investigated for antibacterial activity against Gram-positive bacteria. The MICs of RBx 11760 and linezolid against Staphylococcus aureus were 2 and 4 mg/liter, against Staphylococcus epidermidis were 0.5 and 2 mg/liter, and against Enterococcus were 1 and 4 mg/liter, respectively.

Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes.

Background: Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs) and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.

Methodology/principal Findings: Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity.

Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure.

Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon.

A novel ketolide, RBx 14255, with activity against multidrug-resistant Streptococcus pneumoniae.

We present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for its in vitro and in vivo activities against sensitive and macrolide-resistant Streptococcus pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae, including an in-house-generated telithromycin-resistant strain (S.

Anti-anaerobic potential of ranbezolid: insight into its mechanism of action against Bacteroides fragilis.

This study reports the anti-anaerobic properties of ranbezolid, a new investigational oxazolidinone. A time-kill kinetics study against anaerobes showed that ranbezolid was superior to linezolid and killed the anaerobic pathogens at 4-8h, except for Bacteroides fragilis where killing was observed at 24h. In addition, the time-kill kinetics study showed a concentration-dependent bactericidal potential of ranbezolid against anaerobes.

In vitro and in vivo activities of the novel Ketolide RBx 14255 against Clostridium difficile.

The MIC(90) of RBx 14255, a novel ketolide, against Clostridium difficile was 4 μg/ml (MIC range, 0.125 to 8 μg/ml), and this drug was found to be more potent than comparator drugs. An in vitro time-kill kinetics study of RBx 14255 showed time-dependent bacterial killing for C.

Non invasive real-time monitoring of bacterial infection & therapeutic effect of anti-microbials in five mouse models.

Background & Objectives: In vivo imaging system has contributed significantly to the understanding of bacterial infection and efficacy of drugs in animal model. We report five rapid, reproducible, and non invasive murine pulmonary infection, skin and soft tissue infection, sepsis, and meningitis models using Xenogen bioluminescent strains and specialized in vivo imaging system (IVIS).

Methods: The progression of bacterial infection in different target organs was evaluated by the photon intensity and target organ bacterial counts.

Activity of RBx 11760, a novel biaryl oxazolidinone, against Clostridium difficile.

Objectives: RBx 11760, a novel oxazolidinone, was investigated for in vitro and in vivo activity against Clostridium difficile.

Methods: The in vitro activity of RBx 11760 and three other agents against 50 diverse C. difficile clinical isolates and other obligate anaerobic bacteria was determined.