BICKERSTAFF BRAINSTEM ENCEPHALITIS AND MILLER FISHER SYNDROME – VARIANT OF GUILLAIN-BARRÉ SYNDROME A SPECTRUM OF CLINICAL MANIFESTATION OF SAME DISEASE

Guillain-Barré syndrome (GBS) and its variants are parainfectious (2/3 cases) neurological illness involving the lower motor neuron but they can also involve central nervous system (CNS). Bickerstaff brainstem encephalitis (BBE) and Miller Fisher syndrome (MFS) are the two variants of GBS with CNS involvement. The present case series highlights the variable presentation and laboratory findings in BBE and MFS, which may help clinicians in early recognition and timely management of the condition

Development of a Methodology to Determine Antibiotic Concentrations in Water Samples Using High-Pressure Liquid Chromatography

Antibiotic concentrations are typically measured using solid-phase extraction along with liquid chromatography, but this process is not practical due to a large number of man hours involved. The use of a lyophilizer with high-pressure liquid chromatography (HPLC) is an accurate and cost-effective method of analyzing antibiotics in water samples. An initial antibiotic analysis methodology was developed with the goal of concentrating antibiotics in water samples for greater detection; however, it was observed that the methodology required additional refinement to improve accuracy, particularly when manure was present in the water samples. Based on prior tetracycline antibiotic research, we hypothesized that sample preparation techniques and HLPC characteristics would influence our ability to detect these antibiotics in water samples. We anticipated that analysis of larger sample volumes would improve antibiotic detection while higher manure concentrations would decrease detection capabilities. The objective of this study was to examine the effects of a secondary sample preparation step (filtration), mobile phase solution, HPLC column, sample volumes, wavelengths, and manure concentrations on the recovery rates of three common antibiotics, specifically chlortetracycline (CTC), tetracycline (TC), and oxytetracycline (OTC). The study examined three filtration methods, two mobile phase solutions, two HPLC columns, five sample volumes, three wavelengths, and four manure concentrations. Best results were obtained with a mobile phase solution of acetonitrile with 0.05% formic acid, the Acclaim® RSLC C18 PA2 column, smaller sample volumes, and a wavelength of 356nm. This study highlighted some of the challenges associated with detecting antibiotics in water samples. The accurate detection of antibiotics in water samples is an important step in developing and testing methods to reduce antibiotic transport in the environment

Crystal and Molecular Structure of Secoisolariciresinol

The R,R-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butandiol lignan secoisolariciresinol (1) is a constituent of Gymnosperms used in the treatment of benign prostatic hyperplasya. The results of crystallographic and ab initio theoretical studies are reported and discussed. In the crystal, the molecule of (1) assumes a clustered conformation, characterized by the facing of the two phenyl rings. This geometry is stabilized by the formation of a network of hydrogen bonds. Theoretical calculations indicate that: i) the intramolecular hydrogen bond O1−H1⋅⋅⋅O1\u27 is the major factor dictating the facing of the two phenyl groups, while intermolecular hydrogen bonds and crystal packing have smaller effects; ii) the 1−4O⋅⋅⋅O non-bonded interactions in the vanillyl groups are important in determining the most stable conformation; iii) calculations with two explicit water molecules in the model give a good simulation of the local effects of a water solvent and indicate that (1) probably assumes a clustered conformation also in polar solvents

Pre-exposure hydroxychloroquine prophylaxis for COVID-19 in healthcare workers: a retrospective cohort

Background: While several trials are ongoing for treatment of Corona virus 2019 (COVID-19), scientific research on chemoprophylaxis is still lacking even though it has potential to flatten the curve allowing us time to complete research on vaccines.Methods: This retrospective cohort study explores the potential of hydroxychloroquine (HCQ) as a pre- exposure prophylaxis for COVID-19 among 106 health care workers (HCW) exposed to COVID-19 patients, at a tertiary care hospital in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken HCQ prior to exposure were considered one cohort while those who had not were considered to be the Control group. All participants with a verifiable high-risk contact history were tested for COVID-19 by RT- PCR.Results: The two cohorts were comparable in terms of age, gender, co-morbidity and exposure. The primary outcome was incidence rates of RT-PCR positive COVID-19 infection among HCQ users and Controls.106 HCW were examined of whom 54 were HCQ users. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (4 out of 54 HCW), compared to those who were not on it (20 out of 52 HCW), χ2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.Conclusions: The study demonstrated that voluntary pre- exposure HCQ prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2.

Crystal and Molecular Structure of Secoisolariciresinol

The R,R-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]-1,4-butandiol lignan secoisolariciresinol (1) is a constituent of Gymnosperms used in the treatment of benign prostatic hyperplasya. The results of crystallographic and ab initio theoretical studies are reported and discussed. In the crystal, the molecule of (1) assumes a clustered conformation, characterized by the facing of the two phenyl rings. This geometry is stabilized by the formation of a network of hydrogen bonds. Theoretical calculations indicate that: i) the intramolecular hydrogen bond O1−H1⋅⋅⋅O1\u27 is the major factor dictating the facing of the two phenyl groups, while intermolecular hydrogen bonds and crystal packing have smaller effects; ii) the 1−4O⋅⋅⋅O non-bonded interactions in the vanillyl groups are important in determining the most stable conformation; iii) calculations with two explicit water molecules in the model give a good simulation of the local effects of a water solvent and indicate that (1) probably assumes a clustered conformation also in polar solvents

The Transcription Factor CrWRKY1 Positively Regulates the Terpenoid Indole Alkaloid Biosynthesis in Catharanthus roseus1[W][OA]

Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are an important source of natural or semisynthetic anticancer drugs. The biosynthesis of TIAs is tissue specific and induced by certain phytohormones and fungal elicitors, indicating the involvement of a complex transcriptional control network. However, the transcriptional regulation of the TIA pathway is poorly understood. Here, we describe a C. roseus WRKY transcription factor, CrWRKY1, that is preferentially expressed in roots and induced by the phytohormones jasmonate, gibberellic acid, and ethylene. The overexpression of CrWRKY1 in C. roseus hairy roots up-regulated several key TIA pathway genes, especially Tryptophan Decarboxylase (TDC), as well as the transcriptional repressors ZCT1 (for zinc-finger C. roseus transcription factor 1), ZCT2, and ZCT3. However, CrWRKY1 overexpression repressed the transcriptional activators ORCA2, ORCA3, and CrMYC2. Overexpression of a dominant-repressive form of CrWRKY1, created by fusing the SRDX repressor domain to CrWRKY1, resulted in the down-regulation of TDC and ZCTs but the up-regulation of ORCA3 and CrMYC2. CrWRKY1 bound to the W box elements of the TDC promoter in electrophoretic mobility shift, yeast one-hybrid, and C. roseus protoplast assays. Up-regulation of TDC increased TDC activity, tryptamine concentration, and resistance to 4-methyl tryptophan inhibition of CrWRKY1 hairy roots. Compared with control roots, CrWRKY1 hairy roots accumulated up to 3-fold higher levels of serpentine. The preferential expression of CrWRKY1 in roots and its interaction with transcription factors including ORCA3, CrMYC2, and ZCTs may play a key role in determining the root-specific accumulation of serpentine in C. roseus plants

Compassionate use of a novel β-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing Pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report

Abstract Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based β-lactam/ β-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo β-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens

Herbal informatics approach for the selection of natural compounds targeting diabetes mellitus

270-275Diabetes mellitus is a chronic metabolic disorder where the Beta-cells present on the islets of Langerhans of pancreas fail to produce enough insulin resulting in unstable blood glucose level that pave the way for insulin resistance by tissues. According to recent WHO (2016) report, 422 million populations were suffering from this metabolic disorder worldwide. Inflammatory mediators such as Alpha-glucosidase, Glucose Transporter Type-4, Sodium Glucose Transporter Type-2, Glucagon like peptide-1, 11 beta-Hydroxysteroid dehydrogenases, etc., are known to play an important role in pathogenesis of this disease and have been considered as potential therapeutic targets.  However, despite the great progress achieved in synthesis of drugs designed to act on targeted molecules, treatment to diabetes is still a challenge because of the common side effects associate with these medicines. Medicinal plants and their biomolecules may be feasible alternative for treatment of diabetes. In the present study, we have utilized in silico herbal informatics model to develop a natural remedies with minimal or no side effects which can inhibit the mediators of disease. In this study bio-prospection model were used where random search is included, followed by the index and rationale based selection of plant products targeting the diabetic factors. These models provide Nigella sativa L., Momordica charantia L. and Camellia sinensis (L.) Kuntze as identified plants that can be used to target the disease at both in vitro and in vivo level