Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

The present studies assessed the level of tumor necrosis factor receptor (TNFR) expression in peripheral blood mononuclear cells (PBMCs) subsets from patients with chronic HCV undergoing interferon α/ribavirin-based therapy (Ifn/R). Methods. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs) in PBMC from 39 HCV+ patients and 21 control HCV− patients. Further subset analysis of HCV + patients (untreated (U), sustained virological responders (SVR), and nonresponders (NR)/relapsers (Rel)) PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. Results. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV(−) patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. Conclusion. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR

Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats

BACKGROUND: Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Chlorotriazine herbicides are rapidly metabolized in plants and animals to form a group of metabolites that are detected both in the environment and in exposed animals. The extent to which these metabolites are responsible directly for the observed health effects is not understood. OBJECTIVES: Our goal was to determine if a mixture of ATR metabolites, in proportions found in the environment, might produce developmental effects in Long-Evans rats following exposure late in pregnancy. METHODS: We administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on gestation days 15–19, using 0 and 100 mg ATR/kg bw/day as negative and positive controls, respectively. RESULTS: We observed no significant effect of acute AMM exposure on body weight gain in dams during the dosing period, weight loss in pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone. However, as with ATR, we detected delayed mammary gland development, evaluated by whole mount analysis, as early as PND4 in all treatment groups. CONCLUSIONS: Our data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to bw or associated with pubertal timing

Determinants of Multimethod Contraceptive Use in a Sample of Adolescent Women Diagnosed with Psychological Disorders

Objective. Despite recommendations for concurrent use of contraceptives and condoms to prevent unintended pregnancy and STIs, multimethod contraceptive use among women is poor. This study examined individual-, interpersonal-, and environmental-level factors that predict multimethod use among sexually active adolescent women diagnosed with psychological disorders. Methods. This multisite study analyzed data from 288 sexually active adolescent women who provided sociodemographic, psychosocial, and behavioral data related to birth control and condom use. Results. 34.7% of the participants reported multimethod use in the past three months. Controlling for empirically and theoretically relevant covariates, a multivariable logistic regression identified self-efficacy, multiple partners, pregnancy history, parental communication, parental norms about sex, and neighborhood cohesion as significant predictors of multimethod use. Conclusions. While continued targeted messages about multi-method contraceptive use are imperative at the individual level, an uptake in messages targeting interpersonal- and environmental-level factors such as adolescents' parents and the broader community is urgently needed

Raising children on a vegan diet: Parents’ opinion on problems in everyday life

A growing number of Italian families are adopting a vegan diet (VD) for their offspring from infancy for various reasons, with health benefits and ethics being the most common reasons. Barriers to effective communication with primary care pediatricians (PCPs) are perceived by many parents and, depending on the actors involved and the environment, a VD may affect social interactions in everyday life. A national cross‐sectional survey was conducted between July and September 2020. Parents of children following a VD completed an online questionnaire. Data from 176 Italian parents were collected. About 72% (71.8%) of the children included in this study had been on a VD since weaning. Parents did not inform their primary care pediatricians (PCP) about the VD in 36.2% of the cases. In 70.8% of the cases, PCPs were perceived as skeptical or against a VD. About 70% (71.2%) of the parents relied on medical dietitians, and 28.2% on nutritionists/dietitians for dietary counseling. Parents administered an individual B12 supplement in 87.2% of the cases. To the best of our knowledge, this survey is the first which explores the relationship between vegan parents and their PCPs, the parental management of their children’s diet and problems regarding the implementation of a VD in everyday life

Life satisfaction and mental health problems (18 to 35 years)

Background: Previous research has found that mental health is strongly associated with life satisfaction. In this study we examine associations between mental health problems and life satisfaction in a birth cohort studied from 18 to 35 years. Method: Data were gathered during the Christchurch Health and Development Study, which is a longitudinal study of a birth cohort of 1265 children, born in Christchurch, New Zealand, in 1977. Assessments of psychiatric disorder (major depression, anxiety disorder, suicidality, alcohol dependence and illicit substance dependence) using DSM diagnostic criteria and life satisfaction were obtained at 18, 21, 25, 30 and 35 years. Results: Significant associations (p < 0.01) were found between repeated measures of life satisfaction and the psychiatric disorders major depression, anxiety disorder, suicidality, alcohol dependence and substance dependence. After adjustment for non-observed sources of confounding by fixed effects, statistically significant associations (p < 0.05) remained between life satisfaction and major depression, anxiety disorder, suicidality and substance dependence. Overall, those reporting three or more mental health disorders had mean life satisfaction scores that were nearly 0.60 standard deviations below those without mental health problems. A structural equation model examined the direction of causation between life satisfaction and mental health problems. Statistically significant (p < 0.05) reciprocal associations were found between life satisfaction and mental health problems.Conclusions: After adjustment for confounding, robust and reciprocal associations were found between mental health problems and life satisfaction. Overall, this study showed evidence that life satisfaction influences mental disorder, and that mental disorder influences life satisfaction

The Landsat Data Continuity Mission Operational Land Imager (OLI) Sensor

The Landsat Data Continuity Mission (LDCM) is being developed by NASA and USGS and is currently planned for launch in January 2013 [1]. Once on-orbit and checked out, it will be operated by USGS and officially named Landsat-8. Two sensors will be on LDCM: the Operational Land Imager (OLI), which has been built and delivered by Ball Aerospace & Technology Corp (BATC) and the Thermal Infrared Sensor (TIRS)[2], currently being built and tested at Goddard Space Flight Center (GSFC) with a planned delivery of Winter 2012. The OLI covers the Visible, Near-IR (NIR) and Short-Wave Infrared (SWIR) parts of the spectrum; TIRS covers the Thermal Infrared (TIR). This paper discusses only the OLI instrument and its pre-launch characterization; a companion paper covers TIRS

Note on the special fillet fatty acid composition of the dwarf carp (Cyprinus carpio carpio) living in thermal Lake Hévíz, Hungary

Fatty acid (FA) composition of the fillet and the intestinal content of dwarf common carp (Cyprinus carpio carpio) living in Lake Hévíz was determined in wintertime collected samples and results were compared to widespread literature data on carp. Fillet FA profile of the thermally adapted (28 oC) Hévíz dwarf carps differed from profiles originated from divergent culture and feeding conditions in the overall level of saturation. Fillet myristic acid proportions largely exceeded all literature data in spite of poor dietary supply. Fillet fatty acid results indicate the effects of thermal adaptation (high saturation level) and the correlative effects of feed components rich in omega-3 fatty acids, with special respect to docosahexaenoic acid. With the application of discriminant factor analysis the Hévíz sample was accurately differentiated from the literature data on carp fillet fatty acid profile, mostly based on C14:0, C18:1 n9, C18:2 n6, C20:1 n9 and C20:4 n6 FAs. In summary, fillet FA profile suggested thermal adaptation, location specificity and the ingestion of algal and bacterial material

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Familial Glucocorticoid Receptor Haploinsufficiency by Non-Sense Mediated mRNA Decay, Adrenal Hyperplasia and Apparent Mineralocorticoid Excess

Primary glucocorticoid resistance (OMIM 138040) is a rare hereditary disease that causes a generalized partial insensitivity to glucocorticoid action, due to genetic alterations of the glucocorticoid receptor (GR). Investigation of adrenal incidentalomas led to the discovery of a family (eight affected individuals spanning three generations), prone to cortisol resistance, bilateral adrenal hyperplasia, arterial hypertension and hypokalemia. This phenotype exacerbated over time, cosegregates with the first heterozygous nonsense mutation p.R469[R,X] reported to date for the GR, replacing an arginine (CGA) by a stop (TGA) at amino-acid 469 in the second zinc finger of the DNA-binding domain of the receptor. In vitro, this mutation leads to a truncated 50-kDa GR lacking hormone and DNA binding capacity, devoid of hormone-dependent nuclear translocation and transactivation properties. In the proband's fibroblasts, we provided evidence for the lack of expression of the defective allele in vivo. The absence of detectable mutated GR mRNA was accompanied by a 50% reduction in wild type GR transcript and protein. This reduced GR expression leads to a significantly below-normal induction of glucocorticoid-induced target genes, FKBP5 in fibroblasts. We demonstrated that the molecular mechanisms of glucocorticoid signaling dysfunction involved GR haploinsufficiency due to the selective degradation of the mutated GR transcript through a nonsense-mediated mRNA Decay that was experimentally validated on emetine-treated propositus' fibroblasts. GR haploinsufficiency leads to hypertension due to illicit occupation of renal mineralocorticoid receptor by elevated cortisol rather than to increased mineralocorticoid production reported in primary glucocorticoid resistance. Indeed, apparent mineralocorticoid excess was demonstrated by a decrease in urinary tetrahydrocortisone-tetrahydrocortisol ratio in affected patients, revealing reduced glucocorticoid degradation by renal activity of the 11β-hydroxysteroid dehydrogenase type 2, a GR regulated gene. We propose thus that GR haploinsufficiency compromises glucocorticoid sensitivity and may represent a novel genetic cause of subclinical hypercortisolism, incidentally revealed bilateral adrenal hyperplasia and mineralocorticoid-independent hypertension