Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection

Normal levels of CD4(+) regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4(+) regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4(+) regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4(+) regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4(+) T cells. CD4(+) T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-beta and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion.     

Low adherence to exclusive breastfeeding in Eastern Uganda: A community-based cross-sectional study comparing dietary recall since birth with 24-hour recall

Background  

Exclusive breastfeeding is recommended as the best feeding alternative for infants up to six months and has a protective effect against mortality and morbidity. It also seems to lower HIV-1 transmission compared to mixed feeding. We studied infant feeding practices comparing dietary recall since birth with 24-hour dietary recall.     

Prevalence of Anemia,Iron-Deficiency Anemia,and Associated Factors among Children Aged 1–5 Years in the Rural,Malaria-Endemic Setting of Popokabaka,Democratic Republic of Congo: A Cross-Sectional Study

Iron deficiency (ID), the leading cause of anemia and the most common nutritional deficiency globally, is not well reported among children in malaria-endemic settings, and little is known about its contribution to anemia in these settings. We aimed to assess the prevalence of anemia, the role of ID using multiple parameters, and the factors associated with anemia in a malaria-endemic rural area. We conducted a community-based cross-sectional study of 432 children aged 1–5 years from the Popokabaka Health Zone, Democratic Republic of Congo. Sociodemographic characteristics, medical history, anthropometric parameters, and biochemical parameters were considered. Hemoglobin and malaria prevalence were assessed using rapid finger-prick capillary blood testing in the field. Venous blood samples were analyzed for serum ferritin, serum iron, total iron-binding capacity, and C-reactive protein (CRP) in a laboratory. Anemia was found in 294 out of 432 (68%) patients. Malaria was found in 375 out of 432 (87%), and ID in 1.8% according to diagnosis by adjusted ferritin only and in 12.9% according to transferrin saturation. ID indicators were not significantly correlated with low hemoglobin levels. Malaria, fever, and CRP > 5 mg/L were major factors associated with anemia in Popokabaka. Anemia control should focus on treating inflammatory conditions and infectious diseases among children in such settings.     

Pharmacokinetics of salmeterol and its main metabolite α-hydroxysalmeterol after acute and chronic dry powder inhalation in exercising endurance-trained men: Implications for doping control

As of 2020, use of beta₂-agonist salmeterol is restricted by the World Anti-Doping Agency (WADA) and is only permitted by inhalation at therapeutic doses not exceeding 200 μg in 24 h. In contrast to beta₂-agonists salbutamol and formoterol, WADA has not established a urine threshold for salmeterol despite its muscle hypertrophic actions observed in animals. Herein, we investigated plasma (0–4 h) and urine (0–24 h) concentrations (by ultra-high-performance liquid chromatography–tandem mass spectrometry [UHPLC–MS/MS]) of salmeterol and α-hydroxysalmeterol after dry powder inhalation at supratherapeutic (400 μg) and high therapeutic (200 μg) doses, and after seven consecutive days of therapeutic inhalation (200 μg × day⁻¹) in 11 healthy endurance-trained men. During each trial, participants inhaled salmeterol before 1½ h moderate-intensity cycling. Mean ± SD maximum urine concentrations of salmeterol unadjusted for specific gravity reached 4.0 ± 1.6, 2.1 ± 1.5, and 2.2 ± 1.1 ng × ml⁻¹ for 400 μg, 200 μg, and seven consecutive days of 200 μg, respectively, with corresponding maximum urine concentrations of α-hydroxysalmeterol being 11.6 ± 6.1, 5.7 ± 4.6, and 6.5 ± 2.6 ng × ml⁻¹. Within the relevant window for doping control (first 6 h post-inhalation), the present data (119 samples), along with 64 biobank urine samples, showed that a combined salmeterol and α-hydroxysalmeterol urine threshold with equal cut-offs of 3.3 ng × ml⁻¹ was superior to a salmeterol-only threshold to discriminate therapeutic (200 μg) from supratherapeutic use (400 μg) with a sensitivity of 24% with 0% false positives when applying the WADA technical document (TD2019DL.v2) method of specific gravity adjustment. Thus, a combination of urine salmeterol and α-hydroxysalmeterol concentrations may be suitable for discriminating between therapeutic and supratherapeutic prohibited inhalation of salmeterol.     

Adaptation rate of 6-sulfatoxymelatonin and cognitive performance in offshore fleet shift workers: a field study

Purpose  

To determine the total phase delay and adaptation rate of 6-sulfatoxymelatonin (aMT6s) on subjective and objective sleep quality and cognitive performance after 7 days of working night shifts (1800–0600 hours). The subjects studied were offshore fleet workers (N = 7).     

Reaching families where a parent has a mental disorder: Using big data to plan early interventions

neuropsychiatrie - Children who grow up with a parent who has a mental health problem (25%) are at increased risk of developing (health) problems themselves. One approach to reach...     

Association of maternal HIV-1 severity with dental caries: an observational study of uninfected 5- to 7-yr-old children of HIV-1-infected mothers without severe immune suppression

Treatment programs to prevent perinatal and postnatal HIV-1 transmission have become available in sub-Saharan Africa, leading to an emerging population of HIV-1 exposed uninfected (HEU) children. Exposure to HIV-1 in utero and during breastfeeding may increase the risk of morbidity and mortality in HEU children. This study estimated the association of the severity of maternal HIV-1 infection as assessed by CD4 count and viral load at baseline (7 d postpartum), with  dmft count of their 5- to 7-yr-old HEU offspring. A follow-up study was conducted of HIV-1-infected mother–HEU children pairs (n = 164) from the Ugandan site of the ANRS 12341-PROMISE- PEP trial (ClinicalTrials.gov, number NCT00640263). HIV-1-infected mothers were interviewed and the HEU children were examined for caries using the World Health Organization's survey methods for field conditions and the dmft index. Directed acyclic graphs and negative binomial regression were used for analyses. The prevalence of 1 or more dmft was 48%. Negative binomial regression showed no association between the dmft count and maternal CD4 counts 7 d postpartum but a 10% lower dmft count with longer breastfeeding duration was found. Maternal CD4 count at birth was not associated with the dental caries experience in uninfected children born to women without severe immune suppression, while there appeared to be a protective effect of high viral load and breastfeeding duration.     

The effects of individual factors and school environment on mental health and prejudiced attitudes among Norwegian adolescents

Introduction  

The aim was to examine the prevalence of mental health difficulties and prejudices toward mental illness among adolescents, and to analyze possible school and school class effects on these issues.