Determinants of maternal and fetal exposure and temporal trends of perfluorinated compounds.

In recent years, some perfluorinated compounds (PFCs) have been identified as potentially hazardous substances which are harmful to the environment and human health. According to limited data, PFC levels in humans could be influenced by several determinants. However, the findings are inconsistent. In the present study, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were measured in paired maternal and cord serum samples (N = 237) collected between 1978 and 2001 in Southern Sweden to study the relationship between these and to investigate several potential determinants of maternal and fetal exposure to PFCs. Time trends of PFCs in Swedish women were also evaluated. The study is a part of the Fetal Environment and Neurodevelopment Disorders in Epidemiological Research project. PFOS, PFOA, and PFNA levels (median) were higher in maternal serum (15, 2.1, and 0.24 ng/ml, respectively) than in cord serum (6.5, 1.7, and 0.20 ng/ml, respectively). PFC levels were among the highest in women originating from the Nordic countries and the lowest in women from the Middle East, North Africa, and sub-Saharan Africa. Multiparous women had lower serum PFOA levels (1.7 ng/ml) than primiparous women (2.4 ng/ml). Maternal age, body mass index, cotinine levels, and whether women carried male or female fetuses did not affect serum PFC concentrations. Umbilical cord serum PFC concentrations showed roughly similar patterns as the maternal except for the gestational age where PFC levels increased with advancing gestational age. PFOS levels increased during the study period in native Swedish women. In summary, PFOS levels tend to increase while PFOA and PFNA levels were unchanged between 1978 and 2001 in our study population. Our results demonstrate that maternal country of origin, parity, and gestational age might be associated with PFC exposure

T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+T Cells in HIV Infection

CD8+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing CD8+ T cell differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate T cell exhaustion in part through direct modulation of PD-1. Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4), functional characteristics and memory differentiation of CD8+ T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total CD8+ T cells was elevated in chronically infected individuals and highly associated with a T-betdimEomeshi expressional profile. Interestingly, both resting and activated HIV-specific CD8+ T cells in chronic infection were almost exclusively T-betdimEomeshi cells, while CMV-specific CD8+ T cells displayed a balanced expression pattern of T-bet and Eomes. The T-betdimEomeshi virus-specific CD8+ T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector) characteristics. The transitional and exhausted phenotype of HIV-specific CD8+ T cells was longitudinally related to persistent Eomes expression after antiretroviral therapy (ART) initiation. Strikingly, these characteristics remained stable up to 10 years after ART initiation. This study supports the concept that poor human viral-specific CD8+ T cell functionality is due to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8+ T cells to control the viral replication post-ART cessation

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes

The Obsessive-Compulsive Symptom (OCS) scale of the Child Behavior Checklist: A comparison between Swedish children with Obsessive-Compulsive Disorder from a specialized unit, regular outpatients and a school sample

-To evaluate the discriminative power of various items as reported by parents in the OCS-scale extracted from the Child Behavior Checklist (CBCL) problem scale and to compare findings with outcomes of previous validation studies. Children referred to a specialized child psychiatric Obsessive-Compulsive Disorder (OCD) clinic (OCD group) (n = 185) receiving a formal OCD diagnosis according to DSM IV criteria based on interviews with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were compared to a sample recruited from regular child and adolescent psychiatric outpatient clinics (CPO group) (n = 177). Both samples were compared to a normative school sample (SS group) and all three groups were matched for age and gender. Thirty seven CBCL items, mostly representing core internalizing symptoms and parts of the thought problem scale as well as physical and sleep problems, were first identified. Ten of these items (including all discriminative items in previous validation studies) could distinguish children with OCD from CPO patients. In a subsequent analysis, the results of a logistic regression showed that four CBCL items, “Obsessions,” “Fearful and Anxious,” “Compulsions,” and “Worries” remained significant predictors. These four OCS items and previously used CBCL OCS-scales were further examined by means of ROC-analysis showing that the “Obsessions” and “Compulsions” CBCL items were the strongest predictors. These two CBCL items performed well as screens for OCS symptoms in children and adolescents and the addition of similar CBCL items did not further increase sensitivity or specificity. It is suggested that parental responses on these two items could preferably be used as screen for OCD in children and adolescents in regular child psychiatric clinics

Tools for Outcome-informed management of mental illness : Psychometric properties of instruments of the Swedish clinical multicenter Quality Star cohort

The purpose of this thesis was to investigate the psychometric properties of three global user subjective measures of the ”The Quality Star” clinical review model: Consumer Satisfaction Scale, Global Quality of Life scale, and Perceived Global Distress scale. The mental health implementation context of this review model emphasizes the client as an agent of change, taking part in shared decision making in an empowered role as collaborative partner to the professional clinicians. In Paper I study the patient self-rating Consumer Satisfaction Scale gave results comparable to those obtained by independent interviewer assessors. Out of cost-effective perspective professional time is saved and logistics simplified. In Paper II the visual analogue self-rating Global Quality of Life scale was shown to have satisfactory test-retest reliability, and concurrent validity with the “Life as a whole” item of Manchester Short Assessment of Quality of Life (MANSA). The patients’ conceptualizations of the scale based on associative findings with a number of validating instruments were consistent with expected areas of concern for Serious Mentally Ill persons. Similarly, in Paper III the visual analogue scale the Perceived Global Distress scale, showed acceptable clinical test-retest reliability, and concurrent validity with the MANSA item, “How satisfied are you with your mental health”. In associative analyses it was found that depressive, anxiety, interpersonal and existential elements contributed to the patient´s conceptualization of the construct. In Paper IV, a previous finding suggesting that women were more satisfied with the health care and had better social functioning compared to men was further elaborated investigating the discriminative properties of the subjective instruments. In the multi-centre cohort of 2552 patients it was possible to detect differences between genders and functional levels professionally assessed with the split version of Global Assessment of Functioning rating scale. The General discussion underlines that although subjective measures tend to have strong interrelations, supporting earlier findings, one has to use multiple measures for an optimal management of mental illness as the subjective outcome ratings have to be individually interpreted in a feed-back dialogue with the patient and be compared to observational assessments