Methionine and choline supply during the peripartal period alter polymorphonuclear leukocyte immune response and immunometabolic gene expression in Holstein cows.

Polymorphonuclear leukocytes (PMNL) are the first responders upon pathogen invasion and hence play an important role in inflammatory and immune responses. Rumen-protected methionine (MET) and choline (CHOL) during the peripartal period affect the immune response and inflammatory status in dairy cows to different extents. We aimed to examine the effect of MET and CHOL supply on expression of genes regulating key PMNL functions and associations with whole-blood immune challenge. Thirty multiparous Holstein cows from a larger cohort randomly assigned from -21 to 30 d relative to parturition to a basal control (CON) diet, CON plus MET at a rate of 0.08% of dry matter, or CON plus CHOL at 60 g/d were used. Blood was sampled at -10, 7, and 30 d relative to parturition for inflammatory biomarker analyses and PMNL isolation. Neutrophil and monocyte phagocytosis and oxidative burst in vitro were assessed in whole blood at 1, 7, and 28 d. Although neutrophil and monocyte phagocytosis did not differ, oxidative burst in neutrophils and monocytes was greater in MET-supplemented cows relative to CON cows. Compared with CON, PMNL adhesion and migration-related genes (ITGAM, ITGB2, ITGA4) were downregulated in response to MET and CHOL. Expression of CADM1 and SELL was also lower in MET-supplemented cows compared with CON cows but not in CHOL cows. In contrast, compared with CON cows, the expression of ICAM1 was lower in CHOL but not MET cows. Similar to adhesion and migration-related genes, cows receiving MET- or CHOL-supplemented diets had lower expression of inflammation-related genes (IL1ß, IL10RA, NFKB1, STAT3, TLR2). However, expression of IRAK1 and TLR4 was lower in MET- but not CHOL-supplemented cows. Plasma taurine concentration was greater in MET cows compared with CHOL and CON cows, suggesting a better redox status in plasma. In agreement with plasma taurine, oxidative stress-related genes (CBS, CTH, GPX1, GSS, SOD2) in PMNL were lower in response to MET and to CHOL supply. Overall, immunometabolic gene expression profile and blood biomarker analyses suggest an overall better redox status in PMNL during the transition period in response to MET and CHOL supply. These adaptations in PMNL might be beneficial for mounting a better bactericidal response upon challenge.

Aetiologies of diarrhoea in adults from urban and rural treatment facilities in Bangladesh.

The objective of our analysis was to describe the aetiology, clinical features, and socio-demographic background of adults with diarrhoea attending different urban and rural diarrhoeal disease hospitals in Bangladesh. Between January 2010 and December 2011, a total of 5054 adult diarrhoeal patients aged ⩾20 years were enrolled into the Diarrhoeal Disease Surveillance Systems at four different hospitals (two rural and two urban) of Bangladesh. Middle-aged [adjusted odds ratio (aOR) 0·28, 95% confidence interval (CI) 0·23-0·35, P < 0·001] and elderly (aOR 0·15, 95% CI 0·11-0·20, P < 0·001) patients were more likely to present to rural diarrhoeal disease facilities than urban ones. Vibrio cholerae was the most commonly isolated pathogen (16%) of the four pathogens tested followed by rotavirus (5%), enterotoxigenic Escherichia coli (ETEC) (4%), and Shigella (4%). Of these pathogens, V. cholerae (19% vs. 11%, P < 0·001), ETEC (9% vs. 4%, P < 0·001), and rotavirus (5% vs. 3%, P = 0·013) were more commonly detected from patients presenting to urban hospitals than rural hospitals, but Shigella was more frequently isolated from patients presenting to rural hospitals than urban hospitals (7% vs. 2%, P < 0·001). The isolation rate of Shigella was higher in the elderly than in younger adults (8% vs. 3%, P < 0·001). Some or severe dehydration was higher in urban adults than rural adults (P < 0·001). Our findings indicate that despite economic and other progress made, conditions facilitating transmission of V. cholerae and Shigella prevail in adults with diarrhoea in Bangladesh and further efforts are needed to control these infections.

Determinants of percent expenditure of household income due to childhood diarrhoea in rural Bangladesh.

There is limited information on percent expenditure of household income due to childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged <5 years with acute diarrhoea were studied. Percent expenditure was calculated as total expenditure for the diarrhoeal episode divided by monthly family income, multiplied by 100. Overall median percent expenditure was 3·04 (range 0·01-94·35). For Vibrio cholerae it was 6·42 (range 0·52-82·85), for enterotoxigenic Escherichia coli 3·10 (range 0·22-91·87), for Shigella 3·17 (range 0·06-77·80), and for rotavirus 3·08 (range 0·06-48·00). In a multinomial logistic regression model, for the upper tertile of percent expenditure, significant higher odds were found for male sex, travelling a longer distance to reach hospital (⩾median of 4 miles), seeking care elsewhere before attending hospital, vomiting, higher frequency of purging (⩾10 times/day), some or severe dehydration and stunting. V. cholerae was the highest and rotavirus was the least responsible pathogen for percent expenditure of household income due to childhood diarrhoea.

Aetiology and clinical features of dysentery in children aged <5 years in rural Bangladesh.

The study identified the common aetiological agents and prominent clinical features of dysentery cases in children aged <5 years and compared this to non-dysentery diarrhoeal cases from the same population. From January 2010 to December 2011, 2324 children aged <5 years received treatment at Kumudini Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric children, aetiology could not be determined for over half (61%). Shigella spp. accounted for 32% of dysentery cases. Significant associations were found between presence of blood in stool and: child age (24-59 months) [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.49-3.27], no treatment of drinking water at home (OR 2.00, 95% CI 1.09-3.67), vomiting (OR 0.19, 95% CI 0.14-0.25), abdominal pain (OR 4.68, 95% CI 3.24-6.77), straining (OR 16.45, 95% CI 11.92-22.69), wasting (OR 1.66, 95% CI 1.15-2.41), and presence of Shigella in stool (OR 6.25, 95% CI 4.20-9.29) after controlling for confounders. This study makes it clear that appropriate public health strategies are needed to reduce the burden of dysentery in Bangladesh.

Geographical diversity in seasonality of major diarrhoeal pathogens in Bangladesh observed between 2010 and 2012.

The study aimed to determine the geographical diversity in seasonality of major diarrhoeal pathogens among 21 138 patients enrolled between 2010 and 2012 in two urban and two rural sites in Bangladesh under the surveillance system of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Distinct patterns in seasonality were found for rotavirus diarrhoea which peaked in winter across the sites (December and January) and dipped during the rainy season (May) in urban Dhaka, August in Mirpur and July in Matlab, equated by time-series analysis using quasi-Poisson regression model. Significant seasonality for shigellosis was observed in Dhaka and rural Mirzapur. Cholera had robust seasonality in Dhaka and Matlab in the hot and rainy seasons. For enterotoxogenic Escherichia coli (ETEC) diarrhoea, clearly defined seasonality was observed in Dhaka (summer). Understanding the seasonality of such pathogens can improve case management with appropriate therapy, allowing policy-makers to identify periods of high disease burden.

Role of Doppler Ultrasound in Diagnosis of Hepatocellular Carcinoma with Histopathological Correlation.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the leading cause (possibly third) of cancer mortality. In a present scenario, HCC displays a challenging clinical problem worldwide. Good-quality ultra sound with careful evaluation of the hepatobiliary system can be a screening examination for HCC in patients at risk. The aim of the study was to determine the diagnostic accuracy of the Doppler sonography for differentiation of hepatocellular carcinoma (HCC) from other focal liver lesions. It was a cross-sectional survey, conducted in the Department of Radiology& Imaging, Mymensingh Medical College, Mymensingh, Bangladesh from January 2017 to December 2018. A total of 70 patients with space occupying lesions on ultrasound were included in this study while pregnant women were excluded. All patients were examined by gray scale ultrasonography, color Doppler and FNAC. To visualize the blood flow, standard color Doppler sonography was used for each lesion. Within the lesions, pulsed Doppler samples were assessed whenever possible on the basis of pulsatile flow & finally resistive index (RI) of intra-tumoral and peritumoral arterial flow was studied. After evaluating by Doppler sonography (CDFI and Spectral analysis), FNAC was done and the specimen was sent to the Department of Pathology for Cytopathological examination. Cytopathology were assessed for confirmation of positive and negative cases of HCC. The detection rate of arterial flow in malignant tumors was 85.1% and in benign lesions were 30.4%. Doppler spectrum analysis showed that the resistive index in primary malignant tumors were 0.76±0.12 and in metastatic tumors were 0.80±0.12 and below 0.6 in benign lesions. The difference was significant (p<0.001). This difference was related with its Cytopathological report. The arterial flow identified by CDFI within the liver lesion with RI >0.6 can be regarded as a criterion of malignant tumors and RI<0.6 can be regarded as benign lesions. This study concluded that the combination of color Doppler flow imaging and RI are more useful in differential diagnosis of liver neoplasms.

Effects of intrauterine growth restriction and postnatal nutrition on pediatric asthma in Bangladesh.

Numerous studies have investigated the risk of developing asthma due to early-life experiences and environmental exposures. However, the influence of intrauterine growth restriction and postnatal undernutrition on childhood wheezing/asthma remains unclear. Thus, we examined the effects of both small for gestational age (SGA) and postnatal stunted growth on ever asthma among children in the rural areas in Bangladesh.Multiple follow-up studies were conducted in a cohort of randomized clinical trial of nutrition interventions during pregnancy (the MINIMat trial). Overall, 1208 and 1697 children were followed-up for asthma at 4.5 and 10 years, respectively. Anthropometric measurements were obtained at various intervals from birth to 10 years of age. Ever asthma was identified using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire.Results showed that SGA was significantly associated with increased risk of ever asthma at 4.5 and 10 years after adjusting for sex, body mass index, socioeconomic status, family history of asthma, gestational age at birth, mother's parity, mother's age at birth and intervention trial arm [odds ratio (OR)=1.97 (95% confidence interval (CI): 1.34-2.90) and 1.86 (95% CI: 1.18-2.72)]. For the postnatal effect of undernutrition, stunting at 1 and 2 years was significantly associated with ever asthma at 4.5 and 10 years [1 year: OR=1.77 (95% CI: 1.22-2.57) and OR=1.72 (95% CI: 1.16-2.56), 2 years: OR=1.49 (95% CI: 1.06-2.10) and OR=1.41 (95% CI: 1.02-1.96)].In conclusion, SGA and undernutrition during infancy has an influence on childhood asthma among children in Bangladesh, indicating the need for nutritional interventions early in life.

Broiler chick thrombocyte response to lipopolysaccharide.

The effect of lipopolysaccharide (LPS) on the expression of proinflammatory cytokines, interleukin (IL)-1beta, IL-6, and IL-12 in broiler chick thrombocytes was investigated. At 4 wk of age, blood samples were collected, and isolated thrombocytes were incubated with LPS for 1 h. Ribonucleic acid was extracted from the cells to examine the expression of the proinflammatory cytokines using real-time reverse transcription PCR. It was found that expressions of IL-1beta, IL-6, and IL-12 in thrombocytes were unaffected by diets containing corticosterone and vitamin C fed to chicks. However, LPS exposure did increase the expressions of these cytokines. The fact that thrombocytes are so abundant and can be stimulated by LPS makes them primary effector cells in innate host defenses against bacterial infections in chickens.

Birth weight influences the kidney size and function of Bangladeshi children.

Early-life conditions influence organ growth patterns and their functions, as well as subsequent risk for non-communicable chronic diseases in later life. A limited number of studies have determined that in Bangladesh, kidney size relates to its function among children as a consequence of the maternal and postnatal conditions. The present study objectives were to determine early-life conditions in relation to childhood kidney size and to compare their influences on kidney function. The study was embedded in a population-based prospective cohort of 1067 full-term singleton live births followed from fetal life onward. Kidney volume was measured by ultrasound in children at the age of 4.5 years (range 45-64 months), and the estimated glomerular filtration rate (eGFR) was assessed at the age of 9 years (range 96-116 months). The mean (s.d.) kidney volume of children at 4.5 years was 64.2 (11.3) cm3, with a significant mean difference observed between low birth weight and normal birth weight children (P<0.001). The multivariable model showed, changes in status from low birth weight to normal birth weight children, with kidney volume increases of 2.92 cm3/m2, after adjusting for the child's age, sex, maternal age and early pregnancy body mass index, and socio-economic index variables. One-unit change in kidney volume (cm3/m2) improved the eGFR to 0.18 ml/min/1.73 m2. The eGFR in low birth weight children was 5.44 ml/min/1.73 m2 less than that in normal birth weight children after adjustments. Low birth weight leads to adverse effects on kidney size and function in children.

Lipopolysaccharide induced Interleukin-6 production is mediated through activation of ERK 1/2, p38 MAPK, MEK, and NFκB in chicken thrombocytes.

Thrombocytes express Toll-like receptor 4 and apparently use both mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathways for nuclear signaling. However, it is not well known if the same enzyme systems found in mammalian cells are fully functional in chickens. Therefore, kinase inhibitors were used with thrombocytes to block kinases in lipopolysaccharide (LPS) stimulated cells to determine if interleukin (IL)-6 expression and production would be diminished. Results demonstrated that extracellular-signal-regulated kinase (ERK)1/2 and p38 MAPK pathways influence gene expression of IL-6 through treatment with either ERK or p38 MAPK inhibitor. In addition, thrombocyte lysates from cells treated with ERK, p38, mitogen-activated protein kinase kinase (MEK)1/2 and inhibitor of nuclear factor kappa-B kinase (IKK) inhibitor showed different levels of the phosphorylated form of ERK1/2, p38 and NFκB. Furthermore, IL-6 gene expression and production were significantly upregulated in LPS stimulated thrombocytes relative to all inhibitor-treated cells.

Bacterial and viral induction of chicken thrombocyte inflammatory responses.

Thrombocytes express Toll-like receptors (TLRs) that detect bacterial or viral pathogens to signal the release of cytokines and mediators. We examined inflammatory responses when thrombocytes were exposed to four TLR ligands. Treatment of thrombocytes with TLR ligands demonstrates differential effects on gene expression of interleukin (IL)-6. Among the TLR ligands examined, lipopolysaccharide stimulation led to the most significant up-regulation of the IL-6 gene and a significant amount of active IL-6 in thrombocyte culture media. Lipoteichoic acid stimulation led to only marginal up-regulation of IL-6 gene expression. Although gene expression of inducible nitric oxide synthase (iNOS) did not increase due to different ligand exposure, a low level constitutive expression of iNOS was observed in all cases. Only thrombocytes treated with polyinosinic-polycytidylic acid and thymidine homopolymer phosphorothioate oligodeoxynucleotides induced rapid, significant production of nitric oxide. We also observed that thrombocytes are able to respond faster upon TLR ligand exposure compared to MQ.NCSU macrophages.

A comparative examination of thrombocyte/platelet immunity.

Among the cells in the blood vascular system, platelets in mammals and thrombocytes in lower vertebrates are the source of crucial mediators in hemostatic functions. Although these cells have been known to be primarily involved in thrombosis and hemostasis, platelets and thrombocytes have been shown recently to have roles in inflammatory functions and the immune response in general. Thrombocytes/platelets are widely recognized contributors to inflammatory responses upon stimulation with various microbial stimulants. In recent years, the role of platelets has been shown in adaptive immune responses. Therefore, thrombocytes/platelets should be considered as specialized immune cells that not only resemble innate effector cells in function but also have a role in affecting adaptive immunity through cellular contact and interaction with antigen presenting cells and lymphocytes.

Childhood malnutrition in households with contemporary siblings: a scenario from urban Bangladesh.

This study aimed to determine the effect of the presence of under-5 siblings (⩾ 1) in a household on childhood malnutrition in urban Bangladesh. During 2000 and 2013, a total of 16,948 under-5 children were enrolled in the Diarrhoeal Disease Surveillance of icddr,b. Under-5 siblings were categorised as ⩾ 1 and none except the child himself. In univariate analysis, the presence of siblings was associated with 1.13 (risk ratios=1.13; 95% CI:1.06-1.20) times higher risk of being stunted, 1.17 (1.09-1.25) times for wasted and 1.19 (1.13-1.26) times underweight compared with their peers who did not have siblings. In multivariate analysis, such associations remained significant for stunting (1.08; 1.01-1.15), wasting (1.12; 1.04-1.21) and underweight (1.13, 1.06-1.19) after controlling for possible confounders such as age of child, sex, parental education, maternal employment, family size, wealth quintile and time (year). The presence of under-5 siblings increases the risk of malnutrition in children in urban Bangladesh.

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

OBJECTIVE: A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. METHODS: 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. RESULTS: Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. CONCLUSION: Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.