The impact of rickets on growth and morbidity during recovery among children with complicated severe acute malnutrition in Kenya: A cohort study

The effects of rickets on children recovery from severe acute malnutrition (SAM) are unknown. Rickets may affect both growth and susceptibility to infectious diseases. We investigated the associations of clinically diagnosed rickets with life‐threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non‐human immunodeficiency virus‐infected Kenyan children with complicated SAM (2–59 months) followed for 1 year posthospital discharge (ClinicalTrials. gov ID NCT00934492). The outcomes were mortality, hospital readmissions, and growth during 12 months. The main exposure was clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230 (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline. Enrolment at an urban site, height‐for‐age and head circumference‐for‐age z scores were associated with rickets. Rickets at study enrolment was associated with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]), any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05, 95% CI [0.73, 1.51]). Rickets was associated with increased height gain (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but not changes in head circumference, mid‐upper arm circumference, or weight. Rickets was common among children with SAM at urban sites and associated with increased risks of severe pneumonia and death. Increased height gain may have resulted from vitamin D and calcium treatment. Future work should explore possibility of other concurrent micronutrient deficiencies and optimal treatment of rickets in this high‐risk population

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades

Prevalence of non Helicobacter pylori species in patients presenting with dyspepsia

<p>Abstract</p> <p>Background</p> <p>Helicobacter species associated with human infection include <it>Helicobacter pylori, Helicobacter heilmannii </it>and <it>Helicobacter felis </it>among others. In this study we determined the prevalence of <it>H. pylori </it>and non-<it>Helicobacter pylori </it>organisms <it>H. felis and H. heilmannii </it>and analyzed the association between coinfection with these organisms and gastric pathology in patients presenting with dyspepsia. Biopsy specimens were obtained from patients with dyspepsia on esophagogastroduodenoscopy (EGD) for rapid urease test, histology and PCR examination for Helicobacter genus specific 16S rDNA, <it>H. pylori </it>phosphoglucosamine mutase (<it>glmM</it>) and urease B (<it>ureB</it>) gene of <it>H. heilmannii </it>and <it>H. felis</it>. Sequencing of PCR products of <it>H. heilmannii </it>and <it>H. felis </it>was done.</p> <p>Results</p> <p>Two hundred-fifty patients with dyspepsia were enrolled in the study. The mean age was 39 ± 12 years with males 162(65%). Twenty-six percent (66 out of 250) were exposed to cats or dogs. PCR for Helicobacter genus specific 16S rDNA was positive in 167/250 (67%), <it>H. pylori glmM </it>in 142/250 (57%), <it>H. heilmannii </it>in 17/250 (6%) and <it>H. felis </it>in 10/250 (4%), respectively. All the <it>H. heilmannii </it>and <it>H. felis </it>PCR positive patients were also positive for <it>H. pylori </it>PCR amplification. The occurrence of coinfection of <it>H. pylori </it>and <it>H. heilmannii </it>was 17(6%) and with <it>H. felis </it>was 10(4%), respectively. Only one out of 66 exposed to pets were positive for <it>H. heilmannii </it>and two for <it>H. felis</it>. Histopathology was carried out in 160(64%) of 250 cases. Chronic active inflammation was observed in 53(56%) (p = 0.001) of the patients with <it>H. pylori </it>infection alone as compared to 3(37%) (p = 0.73) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 3(60%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.66). Intestinal metaplasia was observed in 3(3%)(p = 1.0) of the patients with <it>H. pylori </it>infection alone as compared to 2(25%) (p = 0.02) coinfected with <it>H. heilmannii </it>and <it>H. pylori </it>and 1(20%) coinfected with <it>H. felis </it>and <it>H. pylori </it>(p = 0.15).</p> <p>Conclusion</p> <p>The prevalence of <it>H. heilmannii </it>and <it>H. felis </it>was low in our patients with dyspepsia. Exposure to pets did not increase the risk of <it>H. heilmannii </it>or <it>H. felis </it>infection. The coinfection of <it>H. pylori </it>with <it>H. heilmannii </it>was seen associated with intestinal metaplasia, however this need further confirmation.</p

HCV+ Hepatocytes Induce Human Regulatory CD4+ T Cells through the Production of TGF-β

Background: Hepatitis C Virus (HCV) is remarkably efficient at establishing persistent infection and is associated with the development of chronic liver disease. Impaired T cell responses facilitate and maintain persistent HCV infection. Importantly, CD4 + regulatory T cells (Tregs) act by dampening antiviral T cell responses in HCV infection. The mechanism for induction and/or expansion of Tregs in HCV is unknown. Methodology/Principal Findings: HCV-expressing hepatocytes were used to determine if hepatocytes are able to induce Tregs. The infected liver environment was modeled by establishing the co-culture of the human hepatoma cell line, Huh7.5, containing the full-length genome of HCV genotype 1a (Huh7.5-FL) with activated CD4 + T cells. The production of IFN-c was diminished following co-culture with Huh7.5-FL as compared to controls. Notably, CD4 + T cells in contact with Huh7.5-FL expressed an increased level of the Treg markers, CD25, Foxp3, CTLA-4 and LAP, and were able to suppress the proliferation of effector T cells. Importantly, HCV + hepatocytes upregulated the production of TGF-b and blockade of TGF-b abrogated Treg phenotype and function. Conclusions/Significance: These results demonstrate that HCV infected hepatocytes are capable of directly inducing Tregs development and may contribute to impaired host T cell responses

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.ARIC was carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. CHS was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health The Costa-Rican adult study was supported by grant R01HL081549 from the National Institutes of Health. EURAMIC was supported by the Commission of the European Communities, as a Concerted Action within Directorate General-XII, with additional support from Directorate General-V Europe against Cancer. The national studies were financed by the Dutch Ministry of Health. Ulster Cancer Foundation and Milk Intervention Board. Grant AKT76 from Cancer Research Switzerland. Swiss National Science Foundation Grant 32-9257-87. Spanish FIS and Ministry of Science and Education, and German Federal Health Office EPIC-Norfolk was funded by grants from Medical Research Council and Cancer Research UK. Dr. Imamura also received support from the Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5). HPFS was supported by the NIH grants UM1 CA167552, R01 HL35464, AA11181, HL35464, CA55075, HL60712 and P30 DK46200 The InChianti study was supported as a ‘targeted project’ (ICS 110.1\RS97.71) by the Italian Ministry of Health and in part by the Intramural Research Program of the NIH (Contracts N01-AG-916413 and N01-AG-821336 and Contracts 263 MD 9164 13 and 263 MD 821336) KIND (Kuopio Ischaemic Heart Disease Risk Factor Study) was supported by grants from the Academy of Finland, Helsinki, Finland (grants 41471, 1041086) MCCS (Melbourne Collaborative Cohort Study) recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-MEHC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, and UL1-TR-000040. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetric Genome-Wide Human SNP Array 6.0. NSHDS I & II (The Northern Sweden Health & Disease Study I & II) was supported by the Swedish Cancer Society and the Swedish Research Council NHS (Nurses’ Health Study) was supported by research grants UM1 CA186107, R01 CA49449, R01 HL034594, P01CA87969, R01HL034594, and R01HL088521 of the National Institutes of Health The PHS (Physician’s Health Study) was supported by grant R21 HL088081, CA-34944 and CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595from the National Heart, Lung, and Blood Institute, Bethesda, MD. The 3C (Three-City) study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the University Bordeaux 2 Victor Segalen and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The Three-City study was also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Conseils Régionaux d’Aquitaine et Bourgogne, Fondation de France, Ministry of Research-INSERM Programme “Cohortes et collections de données biologiques”, Agence Nationale de la Recherche (grant number COGINUT ANR-06-PNRA-005), the Fondation Plan Alzheimer (grant number FCS 2009-2012), and the Caisse Nationale pour la Solidarité et l’Autonomie (CNSA) . Dr Samieri was on a grant from the “Fondation Plan Alzheimer” SHHEC (Scottish Heart Health Extended Cohort) study was funded by the Scottish Health Department Chief Scientist Organization; British Heart Foundation; FP Fleming Trust. The authors would like to acknowledge Dr. Roger Tavendale for his work with the Scottish Heart Health Study. SCHS (Singapore Chinese Health Study) was supported by the Singapore National Medical Research Council (grant number: NMRC 1270/2010) and the U.S. NIH (grant numbers: R01CA 144034 and UM1 CA182876) ULSAM 50 and 70 were funded by the Swedish Research Council for Health, Working Life and Welfare (FORTE) Uppsala City Council (ALF) and Swedish Research CouncilThis is the final version of the article. It first appeared from American Medical Association via http://dx.doi.org/10.1001/jamainternmed.2016.292

Relationship between obesity, ethnicity and risk of late stillbirth: a case control study

<p>Abstract</p> <p>Background</p> <p>In high income countries there has been little improvement in stillbirth rates over the past two decades. Previous studies have indicated an ethnic disparity in the rate of stillbirths. This study aimed to determine whether maternal ethnicity is independently associated with late stillbirth in New Zealand.</p> <p>Methods</p> <p>Cases were women with a singleton, late stillbirth (≥28 weeks' gestation) without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two controls with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Women were interviewed in the first few weeks following stillbirth, or at the equivalent gestation for controls. Detailed demographic data were recorded. The study was powered to detect an odds ratio of 2, with a power of 80% at the 5% level of significance, given a prevalence of the risk factor of 20%. A multivariable regression model was developed which adjusted for known risk factors for stillbirth, as well as significant risk factors identified in the current study, and adjusted odds ratios and 95% confidence intervals were calculated.</p> <p>Results</p> <p>155/215 (72%) cases and 310/429 (72%) controls consented. Pacific ethnicity, overweight and obesity, grandmultiparity, not being married, not being in paid work, social deprivation, exposure to tobacco smoke and use of recreational drugs were associated with an increased risk of late stillbirth in univariable analysis. Maternal overweight and obesity, nulliparity, grandmultiparity, not being married and not being in paid work were independently associated with late stillbirth in multivariable analysis, whereas Pacific ethnicity was no longer significant (adjusted Odds Ratio 0.99; 0.51-1.91).</p> <p>Conclusions</p> <p>Pacific ethnicity was not found to be an independent risk factor for late stillbirth in this New Zealand study. The disparity in stillbirth rates between Pacific and European women can be attributed to confounding factors such as maternal obesity and high parity.</p

Comparison of microdilution and standard agar dilution method for determining Penicillin resistance among Spneumoniae

Background: Antibiotic resistance among different microbial organisms is increasing. No study exists from Pakistan comparing methods of determining antibiotic resistance among bacterial isolates.Methods: Ten clinical patient sample strains of S.pneumoniae were used to compare agar dilution with broth microdilution method for determining Minimum Inhibitory Concentrations (MICs) of Penicillin G. Agar dilution was conducted as per National Committee for Clinical Laboratory Standards. Broth microdilution was performed in Brain Heart Infusion broth using sterile plastic microtiter trays with 96 U-shaped wells. In both methods, concentration of Penicillin G ranged from 0.03 to 16g/mL and S.aureus ATCC 29213 with an MIC of 0.25g/mL was used as a control. MIC ≤0.06g/mL was considered sensitivity to antibiotic, MIC 0.12-1.0 intermediate resistance and MIC ≥2 full resistance.Results: Good agreement was found between two methods. Four strains gave identical MICs in both. The other six strains agreed to within one log2 dilution step. Both methods categorized same five strains as Penicillin sensitive and four as Penicillin resistant; one strain was classified as sensitive on agar dilution but resistant on broth microdilution. Broth microdilution was more expensive, tedious and time consuming than the agar dilution with multipoint inoculator. This would limit its clinical applicability in a busy diagnostic lab with a large sample turnover.CONCLUSIONS: We propose agar dilution for the clinical labs in developing countries that use Kirby-Bauer disk diffusion method and want to initiate MIC determination of antibiotics for patient samples