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BACKGROUNDNasopharyngeal carriage of pathogenic bacteria precedes invasive disease and higher rates are found in low socioeconomic-status (SES) settings. Local immune responses are important for controlling colonization, but whether SES affects these responses is currently unknown.OBJECTIVEExamining bacterial colonization and cytokine response in nasal mucosa of children from high and low SES.METHODSTwenty-five cytokines were measured in nasal fluid. qPCR was performed to determine carriage and density of Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae), Moraxella catarrhalis (M. catarrhalis) and Staphylococcus aureus (S. aureus).RESULTSThe densities of H. influenzae and S. pneumoniae were increased in low compared to the high SES (p=0.006, p=0.026), with respectively 6 and 67 times higher median densities. Densities of H. influenzae and S. pneumoniae were positively associated with levels of IL-1beta (p=0.002, p=0.008) and IL-6 (pp=0.006). After correcting for bacterial density, IL-6 levels were increased in colonized children from high compared to low SES for both H. influenzae and S. pneumoniae (both p=0.039).CONCLUSIONIncreased density of H. influenzae and S. pneumoniae was observed in low SES children, while IL-6 levels associated with colonization were reduced in these children, indicating that immune responses to bacterial colonization were altered by SES.

Objectives: The relationship between leprosy, stigma and poor mental health is well recognized. The overall objective of this study was to help improve mental wellbeing in people affected by leprosy by gaining more insight into what factors related to cultural, social and personal life influence mental wellbeing amongst people affected by leprosy in the Terai region, Nepal. Methods: We adopted a qualitative approach with purposive sampling to include people affected by leprosy in the Terai region of Nepal. Fourteen people with various leprosy disability grades and two healthcare workers were recruited for in-depth interviews. We used a framework analysis method with characteristics of the Grounded Theory Approach. Predetermined themes were explored, and new themes brought up during the interviews were also analysed. Results: Leprosy-related stigma still persists in the Terai region, negatively influencing mental wellbeing. A higher disability grade can result in a poorer mental wellbeing. Additional key factors influencing mental wellbeing include: people’s feelings and experiences regarding leprosy, family and community, work and culture. Conclusions: The mental wellbeing of the respondents was negatively influenced by direct and indirect consequences of being affected by leprosy. Stigma, disability grade, family, community, work and culture are very important factors that influence mental wellbeing in the Terai region, Nepal. We recommend that interventions should include a combination of strategies, including lay and peer counselling, socio-economic rehabilitation and involvement of community and family to improve the mental wellbeing of those affected. We also recommend using a holistic and gender-specific approach when developing these interventions.

Objective The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TH 2 immune markers in school-aged children in Makassar, Indonesia. Methods A cross-sectional study was performed in five schools where socio-demographic characteristics were recorded. Children's standardised z-scores of body mass index (z-BMI) and age-standardised z-scores of height (z-HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin-like growth factor (IGF-1) and TH 2 immune markers were measured. Results In total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99-4.23) and IGF-1 (GMR 1.45, 95% CI: 1.15-1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49-0.66 and GMR 0.78, 95% CI: 0.63-0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64-0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50-4.78) but no relationship was found with the other TH 2 immune markers. Conclusion Malnutrition is prominent in school-aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.

The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TA cross-sectional study was performed in five schools where socio-demographic characteristics were recorded. Children's standardised z-scores of body mass index (z-BMI) and age-standardised z-scores of height (z-HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin-like growth factor (IGF-1) and TIn total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99-4.23) and IGF-1 (GMR 1.45, 95% CI: 1.15-1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49-0.66 and GMR 0.78, 95% CI: 0.63-0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64-0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50-4.78) but no relationship was found with the other TMalnutrition is prominent in school-aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.La charge de l'insuffisance pondérale reste un problème majeur en Indonésie et parallèlement, la prévalence du surpoids augmente. La malnutrition est un déterminant majeur de la santé et a été associée à des troubles allergiques chez les enfants. Nous avons examiné la relation entre la malnutrition et les marqueurs immunitaires TLa malnutrition est importante chez les enfants d'âge scolaire à Makassar, avec un surpoids associé à une réactivité accrue du SPT. Par conséquent, les interventions devraient se concentrer sur la dénutrition, mais aussi sur le surpoids pour prévenir l'augmentation des troubles allergiques en Indonésie.

Glucocorticoids mediate numerous essential processes in the human body via binding to the glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and GR antagonists can be used to treat many symptoms of glucocorticoid-induced pathology. The purpose of this study was to characterize the tissue-specific properties of the selective GR antagonist CORT125281. We evaluated the antagonistic effects of CORT125281 upon acute and subchronic corticosterone exposure in mice. In the acute corticosterone setting, hypothalamus-pituitary-adrenal-axis activity was investigated by measurement of basal- and stress-induced corticosterone levels, adrenocorticotropic hormone levels and pituitary proopiomelanocortin expression. GR signaling was evaluated by RT-PCR analysis of GR-responsive transcripts in liver, muscle, brown adipose tissue (BAT), white adipose tissue (WAT) and hippocampus. Pretreatment with a high dose of CORT125281 antagonized GR activity in a tissue-dependent manner. We observed complete inhibition of GR-induced target gene expression in the liver, partial blockade in muscle and BAT and no antagonism in WAT and hippocampus. Tissue distribution only partially explained the lack of effective antagonism. CORT125281 treatment did not disinhibit the hypothalamus-pituitary-adrenal neuroendocrine axis. In the subchronic corticosterone setting, CORT125281 partially prevented corticosterone-induced hyperinsulinemia, but not hyperlipidemia and immune suppression. In conclusion, CORT125281 antagonizes GR transcriptional activity in a tissue-dependent manner and improves corticosterone-induced hyperinsulinemia. Tailored dosing of CORT125281 may allow tissue-specific inhibition of GR transcriptional activity.

BackgroundLeprosy, a leading cause of disability, remains endemic in southern Nepal. Alongside physical impairment and stigmatization, many people affected by leprosy suffer from mental health problems.ObjectivesThis study had two objectives: (a) Establishing a baseline level of mental wellbeing and depression among people affected by leprosy in southern Nepal, and (b) Examining factors that influence mental wellbeing and depression in this target group.MethodsA cross-sectional survey was conducted using three interview-administered questionnaires measuring level of depression (PHQ-9), mental wellbeing status (WEMWBS) and level of stigma (5-QSI-AP). Random clustering sampling was used to include leprosy-affected people from Self Help Groups (SHGs) and the reference group was matched based on socio-demographic characteristics. All participants were adults with no additional major morbidities. A sample of 142 persons affected by leprosy and 54 community controls were included.ResultsPeople affected by leprosy participating in SHGs had a significantly lower level of mental wellbeing and higher level of depression than the general population. Both mental wellbeing and depression were influenced by gender and the level of stigma. In addition, the level of depression was associated with the disability grade of leprosy-affected people.ConclusionLeprosy-affected people need mental health-care interventions at different organizational levels, with attention to identifying individuals at increased risk for mental health problems or with additional needs. These findings highlight the demand for further research on specific interventions to improve the mental health of leprosy-affected people.