Microbial Biofilms

Biofilms are the aggregation of microbial cells, which are associated with the surface in almost an irreversible manner. It exists in variety of forms like dental plaque, pond scum, or the slimy build up in sink. Biofilm formation involves sequence of steps like conditioning, attachment, metabolism, and detachment. Biofilm consists of water channels, EPS (Exopolysaccharide), and eDNA (Environmental DNA), which plays an important role in nutrient circulation, its development, and structure stabilization. Resistance of planktonic bacteria against antimicrobial agents gets increased on the formation of biofilm, which may be the presence of diffusive barrier EPS or neutralizing enzyme, cells undergoing starvation, or due to spore formation. There are numerous factors, which affects biofilm formation such as substratum effects, conditioning film on substratum, hydrodynamics, characteristics of the aqueous medium, cell characteristics, and environmental factors. Biofilm can cause industrial, medical, and household damage and is a reason for loss of billions of dollars every year. Development of biofilm on catheters, medical implants, and devices is a major cause of infections and diseases in humans. Examples include Plaque, Native Valve Endocarditis, Otitis media, Prostatitis, Cystic fibrosis, Periodontitis, Osteomyelitis, and many more

Clinicolaboratory profile of children with celiac disease in North India

Background: Prevalence of celiac disease (CD) has increased worldwide, but there are only few studies reporting clinicolaboratory profile of children with CD. Aim: To study the current clinicolaboratory profile of celiac disease in North Indian children. Methods: This retrospective study was done in pediatric gastroenterology clinic of a tertiary care center of North India. The primary objective was to study clinical and laboratory profile in children with CD. Secondary objective was to find correlation between duodenal biopsy Marsh stage and IgA tissue with tissue transglutaminase antibody (tTG) titers and also with serum hemoglobin, serum iron levels, and severity of anemia. A total of the 54 children fulfilling the diagnostic criteria of CD were included, and details were reviewed and analyzed. Results: Average age of onset of symptoms was 4.7±2.5 years, 80% had onset of symptoms after 2 years of age. Chronic diarrhea (70.3%), pain abdomen (62.9%), and abdomen distention (53.7%) were the most common manifestations. Wasting (38.4% - <5 years, 41.4% in >5 years), stunting (46.3%), rickets (22%), and anemia (90.7%) were common. Serum hemoglobin levels and serum iron levels were inversely correlated to the serum tTG levels and Marsh biopsy staging; though, not significant. Correlation of hemoglobin levels between Marsh stage 3A and 3C was statistically significant (p=0.036). There was no correlation between serum tTG levels and Marsh biopsy staging with anemia and its severity. Conclusion: Gastrointestinal symptoms still remain the most common presentation in children with celiac disease. Malnourishment, anemia, and rickets require special attention in these children

The India brain infections guidelines project: Global evidence for local application.

Background Brain infections are a major cause of morbidity and mortality globally. India lacks systematically evidence-informed guidelines for brain infections. Methods We had set up a group of experts in brain infections, evidence synthesis and guideline development to produce guidelines for hospital clinicians diagnosing and treating patients with suspected and confirmed brain infections in India. Questions are being drafted and prioritised, and a plan for GRADE-informed evidence synthesis and guideline development is in place, using methods to increase efficiency of the process where possible. Dissemination and outputs The guidelines will be disseminated through publication as well as on a dedicated website. Training of clinicians in evidence synthesis and guideline development, and setting up a network of institutions and professional societies, will provide lasting impact in terms of national capacity strengthening

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Antimicrobial Peptides: Mechanism of Action

Antimicrobial peptides (AMPs) are a diverse class of small peptides that are found in most life forms ranging from microorganisms to humans. They can provoke innate immunity response and show activity against a wide range of microbial cells which includes bacteria, fungi, viruses, parasites, and even cancer cells. In recent years AMPs have gained considerable attention as a therapeutic agent since bacterial resistance towards conventional antibiotics is accelerating rapidly. Thus, it is essential to analyze the mechanism of action (MOA) of AMPs to enhance their use as therapeutics. The MOA of AMPs is classified into two broad categories: direct killing and immunological regulation. The direct killing action mechanism is categorized into membrane targeting and non-membrane targeting mechanisms. There are several models and biophysical techniques which determine the action mechanism of antimicrobial peptides

Needle-Free Immunization with Chitosan-Based Systems

Despite successful use, needle-based immunizations have several issues such as the risk of injuries and infections from the reuse of needles and syringes and the low patient compliance due to pain and fear of needles during immunization. In contrast, needle-free immunizations have several advantages including ease of administration, high level of patient compliance and the possibility of mass vaccination. Thus, there is an increasing interest on developing effective needle-free immunizations via cutaneous and mucosal approaches. Here, we discuss several methods of needle-free immunizations and provide insights into promising use of chitosan systems for successful immunization

Hematological Profile of HIV-Infected Patients on First-Line Highly Active Antiretroviral Therapy and Its Correlation With CD4 Count

Introduction Human immunodeficiency virus (HIV) infection is a state of profound immunodeficiency. Disorders of hematopoietic system are a common but often overlooked complication of HIV infection. This can manifest at any stage of the disease but more commonly in the advanced stage with low CD4 count. Anemia is the most common hematological abnormality in HIV patients and prevalence ranges from 1.3 to 95%. As HIV disease progresses, the prevalence and severity of anemia also increase. Hence, this study was undertaken to assess the hematological parameters of HIV-infected patients on highly active antiretroviral therapy (HAART) at different treatment durations with the hope to improve the HAART outcome in HIV patients and its correlation with CD4 count. Methods This prospective longitudinal study enrolled 134 HIV-infected patients admitted to or attending the OPD in the Department of Medicine or Antiretroviral Therapy (ART) Center (Center of Excellence), Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, from 2018 to 2020. Complete hemogram, CD4 count, and other related-blood investigations were studied. Results The mean age of the study population was 39.9 ± 11.04 years. Of the 134 patients, 75 (56%) were males and 59 (44%) were females. Twelve (9%) patients had a history of injecting drug use (IDU). TLE (tenofovir, lamivudine, efavirenz) regimen was started on 112 (83.6%) patients and the majority of them (69/134 [51.5%]) had a CD4 count of 200 to 499 cells/mm3, which increased significantly 6 months after HAART to 99 to 1,149 cells/mm3, with a mean of 445 ± 217 cells/mm3. There were significant improvements in hemoglobin (Hb) levels, total leukocyte count (TLC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) after HAART indicating a positive correlation with CD4 count (p < 0.05). Thrombocytopenia was observed higher after HAART when compared to baseline. There was a positive correlation between platelet count and CD4 count. However, the mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR) had a negative correlation with CD4 count. Conclusion The study inferred a strong positive correlation between CD4 and Hb levels, TLC, ANC, ALC, and platelet count after HAART with improvement in these values as CD4 count increases. Specific treatment intervention based on the changes in the immunohematological profile trends can help prevent most of the adverse effects on HIV patients in our community

Table_2_Augmenting tomato functional genomics with a genome-wide induced genetic variation resource.xlsx

Induced mutations accelerate crop improvement by providing novel disease resistance and yield alleles. However, the alleles with no perceptible phenotype but have an altered function remain hidden in mutagenized plants. The whole-genome sequencing (WGS) of mutagenized individuals uncovers the complete spectrum of mutations in the genome. Genome-wide induced mutation resources can improve the targeted breeding of tomatoes and facilitate functional genomics. In this study, we sequenced 132 doubly ethyl methanesulfonate (EMS)-mutagenized lines of tomato and detected approximately 41 million novel mutations and 5.5 million short InDels not present in the parental cultivar. Approximately 97% of the genome had mutations, including the genes, promoters, UTRs, and introns. More than one-third of genes in the mutagenized population had one or more deleterious mutations predicted by Sorting Intolerant From Tolerant (SIFT). Nearly one-fourth of deleterious genes mapped on tomato metabolic pathways modulate multiple pathway steps. In addition to the reported GC>AT transition bias for EMS, our population also had a substantial number of AT>GC transitions. Comparing mutation frequency among synonymous codons revealed that the most preferred codon is the least mutagenic toward EMS. The validation of a potato leaf-like mutation, reduction in carotenoids in ζ-carotene isomerase mutant fruits, and chloroplast relocation loss in phototropin1 mutant validated the mutation discovery pipeline. Our database makes a large repertoire of mutations accessible to functional genomics studies and breeding of tomatoes.</p