Ciprofloxacin-Resistant Neisseria meningitidis, Delhi, India

Decreased susceptibility of Neisseria meningitidis isolates to ciprofloxacin emerged from an outbreak in Delhi, India. Results of antimicrobial susceptibility testing of the meningococcal isolates to ciprofloxacin and further sequencing of DNA gyrase A quinolone-resistance–determining region confirmed the emergence of ciprofloxacin resistance in the outbreak

Efficacy of maternal B-12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial

INTRODUCTION: Vitamin B12 deficiency is widely prevalent across many low- and middle-income countries, especially where the diet is low in animal sources. While many observational studies show associations between B12 deficiency in pregnancy and infant cognitive function (including memory, language and motor skills), evidence from clinical trials is sparse and inconclusive. METHODS AND ANALYSIS: This double-blind, multicentre, randomised controlled trial will enrol 720 vegetarian pregnant women in their first trimester from antenatal clinics at two hospitals (one in India and one in Nepal). Eligible mothers who give written consent will be randomised to receive either 250 mcg methylcobalamin or 50 mcg (quasi control), from enrolment to 6 months post-partum, given as an oral daily capsule. All mothers and their infants will continue to receive standard clinical care. The primary trial outcome is the offspring's neurodevelopment status at 9 months of age, assessed using the Development Assessment Scale of Indian Infants. Secondary outcomes include the infant's biochemical B12 status at age 9 months and maternal biochemical B12 status in the first and third trimesters. Maternal biochemical B12 status will also be assessed in the first trimester. Modification of association by a priori identified factors will also be explored. ETHICAL CONSIDERATIONS AND DISSEMINATION: The study protocol has been approved by ethical committees at each study site (India and Nepal) and at University College London, UK. The study results will be disseminated to healthcare professionals and academics globally via conferences, presentations and publications. Researchers at each study site will share results with participants during their follow-up visits.Trial registration numberCTRI/2018/07/015048 (Clinical Trial Registry of India); NCT04083560 (ClinicalTrials.gov)

Network Inference Algorithms Elucidate Nrf2 Regulation of Mouse Lung Oxidative Stress

A variety of cardiovascular, neurological, and neoplastic conditions have been associated with oxidative stress, i.e., conditions under which levels of reactive oxygen species (ROS) are elevated over significant periods. Nuclear factor erythroid 2-related factor (Nrf2) regulates the transcription of several gene products involved in the protective response to oxidative stress. The transcriptional regulatory and signaling relationships linking gene products involved in the response to oxidative stress are, currently, only partially resolved. Microarray data constitute RNA abundance measures representing gene expression patterns. In some cases, these patterns can identify the molecular interactions of gene products. They can be, in effect, proxies for protein–protein and protein–DNA interactions. Traditional techniques used for clustering coregulated genes on high-throughput gene arrays are rarely capable of distinguishing between direct transcriptional regulatory interactions and indirect ones. In this study, newly developed information-theoretic algorithms that employ the concept of mutual information were used: the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE), and Context Likelihood of Relatedness (CLR). These algorithms captured dependencies in the gene expression profiles of the mouse lung, allowing the regulatory effect of Nrf2 in response to oxidative stress to be determined more precisely. In addition, a characterization of promoter sequences of Nrf2 regulatory targets was conducted using a Support Vector Machine classification algorithm to corroborate ARACNE and CLR predictions. Inferred networks were analyzed, compared, and integrated using the Collective Analysis of Biological Interaction Networks (CABIN) plug-in of Cytoscape. Using the two network inference algorithms and one machine learning algorithm, a number of both previously known and novel targets of Nrf2 transcriptional activation were identified. Genes predicted as novel Nrf2 targets include Atf1, Srxn1, Prnp, Sod2, Als2, Nfkbib, and Ppp1r15b. Furthermore, microarray and quantitative RT-PCR experiments following cigarette-smoke-induced oxidative stress in Nrf2+/+ and Nrf2−/− mouse lung affirmed many of the predictions made. Several new potential feed-forward regulatory loops involving Nrf2, Nqo1, Srxn1, Prdx1, Als2, Atf1, Sod1, and Park7 were predicted. This work shows the promise of network inference algorithms operating on high-throughput gene expression data in identifying transcriptional regulatory and other signaling relationships implicated in mammalian disease

Bacterial & fungal biofilms in chronic rhinosinusitis.

Chronic Rhinosinusitis (CRS) is a recalcitrant disease, characterized by headache, nasal discharge / blockage, which substantially impairs daily functioning and negatively affect quality of life. Endoscopic Sinus Surgery (ESS) is an important treatment option for CRS, but has variable success rates. Biofilms are well organised heterogeneous communities of microbes embedded in a mosaic of extracellular matrix, adherent to biotic / abiotic surfaces. As they are resistant to host defences and medical treatments, they have been touted as possible pathogenic factors in CRS, which may perpetuate the recurrent and recalcitrant character of the disease and negatively affect treatment outcomes. This thesis encompasses research undertaken to enhance our understanding about the effect that presence and types of biofilms have on the clinical profile and treatment outcomes of patients suffering with chronic rhinosinusitis. An in-vitro model of fungal biofilms and a potential tool to assay in-vivo mucosal biofilms on sinonasal tissues has also been described. Chapter 1 of the thesis comprehensively reviews the scientific literature pertaining to biofilms and CRS, and exhaustively evaluates the evidence present in relation to bacterial and fungal biofilms in CRS. Chapter 2 describes a study to investigate the effect of biofilms on outcomes following ESS in CRS patients using internationally accepted standardised symptom scores, quality of life measures and endoscopy scores to assess the disease. It showed that patients with biofilms presented with more severe disease before surgery, and after surgery had persistent symptoms, ongoing mucosal inflammation and infections necessitating extra post-operative visits and multiple antibiotic treatments. This study thus strengthened the evidence for the role that biofilms may play in recalcitrant CRS. Chapter 3 describes a further subgroup analysis of the above patients in whom the specific organisms forming the biofilms were identified and how patients with specific biofilm types progressed after surgery was studied. Patients with polymicrobial biofilms suffered more severe disease and had worse post-surgery mucosal outcomes requiring more post–operative visits. S.aureus biofilms played a dominant role in negatively affecting outcomes of ESS with persisting post-operative symptoms, ongoing mucosal inflammation and infections. Chapter 4 describes an in-vitro model characterizing A. fumigatus biofilm formation on primary human sinonasal epithelium cultures under different growth conditions. 3-dimensional biofilm structures with parallel-packed and cross-linked hyphae, channels/passages, extracellular matrix (ECM) encasing the hyphae, were formed. Biofilms formed under flow conditions displayed more robust and faster growth kinetics as compared to those under static conditions, with extensive ECM production. Chapter 5 investigates application of an analysis program ‘COMSTAT 2’ for assaying & quantitatively describing the 3-dimensional in-vivo biofilm structures observed via confocal scanning microscopy on sino-nasal mucosal samples. This can be used for temporal analysis of biofilm development, comparison of different types of biofilms formed under controlled conditions, analysis of influence of varying environmental factors on biofilms and the efficacy of different antibiofilm treatments. Chapter 6 summarises and discusses the salient features of the studies included in this thesis which has attempted to characterize fungal and bacterial biofilms and the impact they may have in CRS patients.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201

Clinicopathological study of cerebellar astrocytoma in children

Introduction: The first successful treatment of a pediatric brain tumor was in 1879 when Sir William Macewen successfully removed a meningioma from a 14-year-old girl. Brain tumors are the most common form of solid tumors and the leading cause of death from solid tumors in children (SEER program 1975–1999). Materials and Methods: Study area: This study was conducted at Bangur Institute of Neuroscience (BIN) and S.S.K.M Hospital. Study Population: Patients attending BIN OPD and admitting in BIN and S.S.K.M Hospital wards were selected. Inclusion Criteria: The following criteria were included in the study: (a) Patients with the diagnosis of cerebellar astrocytomas after magnetic resonance imaging investigation, (b) patients giving consent to be included in the study, and (c) patient willing to come for follow up. Study Period: The study period was 2 years (from September 1, 2010, to December 31, 2012). Sample Size: All diagnosed cases of cerebellar astrocytoma during the stated period. Exclusion Criteria: Patients not willing for the study were excluded from the study. Study Design: This was a non-randomized prospective clinical study. Pilocytic astrocytomas are the most common pediatric brain tumors in our population and are most commonly located in the cerebellum. Results: Most of the patients, 20 (90.9%), had neurological improvement on discharge. 1 patient (4.5%) died during the hospital course. The follow-up time period ranged from 3 months to 2 years, with a mean follow-up period of 1.5 years. Recurrence was observed in 5 patients (22.72%), but reoperation was done in 3 patients (13.63%). Of them, 1 patient (4.5%) received radiotherapy in spite of that recurrence was developed in 1.5 years. 2 patients (9.09%) have been kept under observation because these are asymptomatic. The solid consistency of tumors led to a poor prognosis, as it was associated with a greater number of ICU admissions, recurrence of tumors, and repeat surgeries (13.63%). The follow-up time period ranged from 3 months to 2 years, with a mean follow-up period of 1.5 years. Conclusion: A “wait and see” strategy is justified in patients with non-progressive recurrent or residual cerebellar LGG after primary tumor resection (23.30) radiotherapy can be considered

Combined spinal epidural for labor analgesia comparison of two different doses of intrathecal bupivacaine 1.25 mg and fentanyl 25 µg with bupivacaine 2.5 mg and fentanyl 25 µg

Background and Objective: The responsibility of the anesthetist in obstetrics is very high. This study compares two different low doses of intrathecal bupivacaine 1.25 mg and 2.5 mg along with 25 µg fentanyl as the spinal component of combined spinal epidural (CSE) analgesia in the early part of labor, followed by epidural top-up. Methodology: Approval was obtained from the institutional review board and written informed consent was obtained from 60 healthy term primigravida or the second gravid parturients, with cephalic singleton pregnancy between 36 and 42 weeks, ASA Grade I/II patients. The study was conducted using low-dose intrathecal bupivacaine 1.25 mg and fentanyl 25 µg (GroupI) with bupivacaine 2.5 mg and fentanyl 25 µg (Group II) as the spinal component of CSE analgesia in the early part of labor. We compared the two with respect to their onset, duration of sensory and motor block, quality of analgesia during early part of labor and the side effects of the drugs. Results: The onset of analgesia was equally rapid with both groups within 5 min, lower incidence of motor block with Group I compared to Group II. Duration of analgesia was longer in Group II, associated with higher dermatome levels of sensory block with longer time for regression of the block. Coclusion: We found that bupivacaine 1.25 mg was as effective as bupivacaine 2.5 mg when added to fentanyl 25 µg for CSE.&nbsp