Oral polio vaccine response in breast fed infants with malnutrition and diarrhea

Oral vaccines for polio (OPV) and rotavirus are less effective in children in the developing world. The reasons for this are not well understood. We tested for risk factors for poor response to OPV in infants from an urban slum of Dhaka, Bangladesh. Diminished serum neutralizing response to OPV, but not failure of intramuscularly administered vaccines, was associated with malnutrition, diarrhea, and shorter breastfeeding duration. Children with malnutrition (WAZ <−2) had significantly lower OPV 3 titers (p = 0.029). Children who had 2 or more diarrhea episodes during the 1st months of life were more than twice as likely to experience OPV failure as those who had 1 diarrhea episode or no diarrhea (p = 0.0245). In contrast, each additional month in exclusive breastfeeding was associated with an increase in OPV 3 titer by 0.41 (p = 0.0072) and 0.16 (p = 0.0065) at the 25th and 50th percentiles of OPV 3 titers respectively. These data are consistent with a defect in induction of immunity in the gut for OPV but not parenteral vaccines, a defect that may be amenable to intervention in part via promotion of exclusive breastfeeding.     

Robot‐assisted laparoscopic retroperitoneal lymph node dissection for left clinical stage I non‐seminomatous germ cell testicular cancer: Focus on port placement and surgical technique

The aim of our report was to describe the feasibility of robotic retroperitoneal lymph node dissection in the contemporary era. We suggest the linear port location and 90° robotic docking as the main key to minimizing instrument clashing and improving the range of surgical accessibility.     

Epidemiological Investigation of the Jaundice Outbreak in Lalkuan,Nainital District,Uttarakhand

Background:

In March 2013, cases of acute hepatitis were reported from Lalkuan, Nainital district. We investigated the outbreak to identify the source of infection and to facilitate control measures.

Objectives:

To study the distribution of hepatitis cases, to find the source of infection, and to initiate the control measures in the affected area.

Materials and Methods:

We defined a case of acute hepatitis as those cases that had jaundice with at least one of the following symptoms: Dark urine, fever, pain in abdomen, vomiting, and loss of appetite in the affected area between January and March 2013. Door-to-door survey was carried out. Thirteen blood samples were randomly collected from jaundice cases for immunoglobulin M (IgM) antibody for hepatitis A virus (HAV) and hepatitis E virus (HEV). Water samples were collected to test residual chlorine.

Results:

Total 2,785 individuals were surveyed; of which 240 were suffering from acute viral hepatitis (attack rate (AR) = 8.61%). Out of 13 serum samples, 10 were found positive for HEV IgM antibodies and three cases had IgM antibodies for both HAV and HEV, which confirmed a hepatitis E outbreak. The difference in attack rate of hepatitis of both the sexes was statistically significant (P < 0.001). The attack rate was significantly higher in age groups >12 years of age (P < 0.001). Environmental investigation also confirmed the sewage contamination of drinking water in the distribution system. The attack rate was much higher (29.4%) among those who were exposed to the leaking pipeline than the nonexposed (χ² = 574.26, P < 0.01).

Conclusion:

HEV was confirmed as the major etiological agent in this outbreak that was transmitted by contaminated drinking water. The recognition of early warning signals, timely investigation, and application of specific control measures can contain the outbreak.     

2-Phenylindole and Arylsulphonamide: Novel Scaffolds Bactericidal against Mycobacterium tuberculosis

相似文献   

An overview of new antitubercular drugs,drug candidates,and their targets

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship.     

Chronic Granulomatous Disease: Two Decades of Experience From a Tertiary Care Centre in North West India

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57 %) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.     

Exploring the therapeutic mechanisms of Cassia glauca in diabetes mellitus through network pharmacology,molecular docking and molecular dynamics

Cassia glauca is reported as anti-diabetic medicinal plant and is also used as an ethnomedicine. However, its mode of action as an anti-diabetic agent has not been clearly elucidated. Hence, the present study investigated the probable mechanism of action of C. glauca to manage diabetes mellitus via network pharmacology and molecular docking and simulations studies. The reported bioactives from C. glauca were retrieved from an open-source database, i.e. ChEBI, and their targets were predicted using SwissTargetPrediction. The proteins involved in the pathogenesis of diabetes were identified from the therapeutic target database. The targets involved in diabetes were enriched in STRING, and the pathways involved in diabetes were identified concerning the KEGG. Cytoscape was used to construct the network among bioactives, proteins, and probably regulated pathways, which were analyzed based on edge count. Similarly, molecular docking was performed using the Glide module of the Schrodinger suite against majorly targeted proteins with their respective ligands. Additionally, the drug-likeness score and ADMET profile of the individual bioactives were predicted using MolSoft and admetSAR2.0 respectively. The stability of these complexes were further studied via molecular dynamics simulations and binding energy calculations. Twenty-three bio-actives were retrieved from the ChEBI database in which cassiarin B was predicted to modulate the highest number of proteins involved in diabetes mellitus. Similarly, GO analysis identified the PI3K-Akt signaling pathway to be primarily regulated by modulating the highest number of gene. Likewise, aldose reductase (AKR1B1) was majorly targeted via the bioactives of C. glauca. Similarly, docking study revealed methyl-3,5-di-O-caffeoylquinate (docking score −9.209) to possess the highest binding affinity with AKR1B1. Additionally, drug-likeness prediction identified cassiaoccidentalin B to possess the highest drug-likeness score, i.e. 0.84. The molecular dynamics simulations and the MMGBSA indicate high stability and greater binding energy for the methyl-3,5-di-O-caffeoylquinate (ΔG_bind = −40.33 ± 6.69 kcal mol⁻¹) with AKR1B1, thus complementing results from other experiments. The study identified cassiarin B, cassiaoccidentalin B, and cinnamtannin A2 as lead hits for the anti-diabetic activity of C. glauca. Further, the PI3K-Akt and AKR1B1 were traced as majorly modulated pathway and target, respectively.

Cassia glauca is reported for anti-diabetic action and is also used as an ethnomedicine.     

Gender differences,outcomes and trends among nonagenarian with atrial fibrillation: insight from National Inpatient Sample database

BACKGROUND Nonagenarians(NG),individuals aged≥90 years,constitute an increasing proportion of hospitalizations presenting with atrial fibrillation(AF).However,not much is known about demographics,clinical outcomes,and trends of hospitalizations.Therefore,we analyzed data about hospitalizations and clinical outcomes among NGs with AF over ten years from 2005 to 2014 using a publically available database,the National Inpatient Sample.METHODS All hospitalizations and major outcomes of subjects≥90 years with a primary diagnosis of AF(ICD-9-CM code 427.31)over a ten-year period were assessed in this study by multivariate logistic regression analysis.RESULTS There were more females than males(176,268 females,51,384 males)in this analysis.The number of hospitalizations for AF among NG increased by 50%(17,295 in 2005 to 25,830 in 2014).Males were more likely to undergo cardioversion(6.14%of males vs.5.06%of females,P<0.0001).Over this period,in-hospital mortality declined from 3.21%in 2005 to 2.38%in 2014(P=0.0041),with higher in-hospital mortality in males(3.23%in males vs.2.76%in females,P=0.0138),mean length of hospitalization decreased from 4.53 days to 4.13 days(P<0.0001),the prevalence of congestive heart failure fell from 0.48%to 0.23%(P=0.0257),and the use of anticoagulation increased from 6.09%to 14.54%(P<0.0001).In a multivariate analysis,hospital admission on the weekend,Elixhauser comorbidity index,CHA2DS2VASc score,acute respiratory failure,and the length of hospital stay were associated with a higher risk of in-hospital mortality.CONCLUSIONS From 2005 to 2014,AF-related hospitalizations among NGs increased,more so in in females population,mortality trends improved,rates of anticoagulation increased,and cardioversions increased.Despite the decreasing trend of in-hospital mortality since 2005,the relatively high mortality rate in males warrants further studies.