Maternal Perfluoroalkyl Substances, Thyroid Hormones, and DIO Genes: A Spanish Cross-sectional Study.

Results of studies on perfluoroalkyl substances (PFASs) and thyroid hormones (THs) are heterogeneous, and the mechanisms underlying the action of PFASs to target THs have not been fully characterized. We examined the relation between first-trimester maternal PFAS and TH levels and the role played by polymorphisms in the iodothyronine deiodinase 1 (DIO1) and 2 (DIO2) genes in this association. Our sample comprised 919 pregnant Spanish women (recruitment = 2003-2008) with measurements of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4), and we genotyped for single-nucleotide polymorphisms in the DIO1 (rs2235544) and DIO2 (rs12885300) genes. We performed multivariate regression analyses between PFASs and THs and included the interaction term PFAS-genotypes in the models. PFHxS was associated with an increase in TSH (% change in outcome [95% CI] per 2-fold PFAS increase = 6.09 [-0.71, 13.4]), and PFOA and PFNA were associated with a decrease in TT3 (-7.17 [-13.5, -0.39] and -6.28 [-12.3, 0.12], respectively). We found stronger associations between PFOA, PFNA, and TT3 for DIO1-CC and DIO2-CT genotypes, although interaction p-values were not significant. In conclusion, this study found evidence of an inverse association between PFOA and TT3 levels. No clear effect modification by DIO enzyme genes was observed.

A stigmatizing dilemma in the labour room: Irrationality or selfishness?

Nowadays, a considerable number of women have a negative or outright traumatic birth experience. Literature shows that being involved in decision-making and exercising autonomy are important factors in having a positive birth experience. In this article, I explore the hypothesis that some views characteristic of the biomedical model of childbirth may hinder women's involvement in decision-making, leading them to what I have dubbed as a 'stigmatizing dilemma'; that is, to be perceived and treated as either irrational or selfish when trying to exercise their autonomy in the labour room. I suggest that such a stigmatizing dilemma arises when the following views are uncritically and unqualifiedly endorsed: (1) childbirth is a process fraught with risk, particularly to babies; (2) labouring women's reports are unreliable and their subjective perspective does not constitute a valuable source of information; (3) medical knowledge and procedures are the safest means to give birth. In a scenario where (1)-(3) are strongly endorsed, if birthing women act according to instrumental rationality and want the best for their babies, they will be expected to just leave decisions to medical experts. Thus, not following expert directions might lead women to fall under the stigma of either irrationality or selfishness: they could be perceived and treated as either irrational, since they may not seem to seek the best means to accomplish their goal; or selfish, since they may seem to pursue goals other than the baby's health. I examine these stigmas in relation to two ideals: that of disembodied rationality and that of selfless motherhood. I also explore different ways in which the views and prejudices underlying this stigmatizing dilemma could be challenged.

Immune Deficiency in Jacobsen Syndrome: Molecular and Phenotypic Characterization.

Jacobsen syndrome or JBS (OMIM #147791) is a contiguous gene syndrome caused by a deletion affecting the terminal q region of chromosome 11. The phenotype of patients with JBS is a specific syndromic phenotype predominately associated with hematological alterations. Complete and partial JBS are differentiated depending on which functional and causal genes are haploinsufficient in the patient. We describe the case of a 6-year-old Bulgarian boy in which it was possible to identify all of the major signs and symptoms listed by the Online Mendelian Inheritance in Man (OMIM) catalog using the Human Phenotype Ontology (HPO). Extensive blood and marrow tests revealed the existence of thrombocytopenia and leucopenia, specifically due to low levels of T and B cells and low levels of IgM. Genetic analysis using whole-genome single nucleotide polymorphisms (SNPs)/copy number variations (CNVs) microarray hybridization confirmed that the patient had the deletion arr[hg19]11q24.3q25(128,137,532-134,938,470)x1 in heterozygosis. This alteration was considered causal of partial JBS because the essential BSX and NRGN genes were not included, though 30 of the 96 HPO identifiers associated with this OMIM were identified in the patient. The deletion of the FLI-1, ETS1, JAM3 and THYN1 genes was considered to be directly associated with the immunodeficiency exhibited by the patient. Although immunodeficiency is widely accepted as a major sign of JBS, only constipation, bone marrow hypocellularity and recurrent respiratory infections have been included in the HPO as terms used to refer to the immunological defects in JBS. Exhaustive functional analysis and individual monitoring are required and should be mandatory for these patients.

Prenatal perfluoroalkyl substance exposure and neuropsychological development throughout childhood: The INMA Project.

BACKGROUND: Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive. OBJECTIVES: To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood. METHODS: 1240 mother-child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4-5 and 7 years covering four domains: general cognitive, general motor, attention, and working memory. Associations were studied by means of multivariable regression analyses. RESULTS: PFHxS, PFOA, PFOS, and PFNA medians were: 0.6, 2.4, 6.1, and 0.7 ng/mL. Higher PFAS prenatal exposure was associated with worse motor development at 14 months, especially in the case of PFHxS (ß[95%CI]: -1.49[-2.73, -0.24]) and to a lesser extent PFOS (-1.25[-2.62, 0.12]). There was also a marginal positive association between general cognitive development at 4-5 years and PFOS (1.17[-0.10, 2.43]) and PFNA (0.99[-0.13, 2.12]). No clear associations for other neuropsychological outcomes or any sex differences were found. DISCUSSION: This study shows no clear-cut evidence of an association between prenatal PFAS exposure and adverse neuropsychological development in children up to the age of 7 years.

Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: A systematic review of epidemiologic studies.

INTRODUCTION: Thyroid hormones (THs) are especially important for brain maturation and development during the fetal period and childhood. Several epidemiological studies have assessed the possible association between exposure to perfluoroalkyl substances (PFAS) and thyroid outcomes during the early stages of life. We aimed to review this evidence. METHODS: We conducted a systematic review in compliance with the PRISMA Statement (search conducted in PubMed and Embase, as well as in the citations of the selected articles). We chose studies if they dealt with thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxin (T4), or thyroid dysfunctions, and perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) or perfluorononanoic acid (PFNA) measured in the blood of pregnant women and/or children up to 19years old. RESULTS: We included in this review three cross-sectional, one case-control, and six cohort studies (publication: 2011-2015), focusing on prenatal life (n=7), childhood (n=2) or both periods (n=1). We observed a high degree of heterogeneity across studies in terms of sampling time (different gestational weeks, at birth, or childhood), outcomes, adjustment for potential confounders, and statistical approach. We found some evidence of a positive association between PFHxS and PFOS exposure and TSH levels measured in maternal blood, and PFNA and TSH levels measured in the blood of boys aged ≥11years. CONCLUSION: Although there is a small number of studies with comparable data, we found some consistency of a positive association between maternal or teenage male exposure to some PFAS and TSH levels based on the current literature. However, further studies are required to confirm these possible relationships.

La metafísica tras la farmacoterapia: tratando la depresión con fármacos convencionales y psicodélicos / The metaphysics behind pharmacotherapy: treating depression with conventional and psychedelic drugs / A metafísica tras a farmacoterapia: tratando a depressão com fármacos convencionais e psicodélicos

Resumen: El propósito de este artículo es comparar las implicaciones metafísicas de la aproximación psicofarmacológica convencional al tratamiento de la depresión, con las implicaciones de la aproximación mediante drogas psicodélicas. Examinaremos la tesis según la cual el conocimiento sobre cómo actúan sobre nosotros los fármacos moldea nuestra auto-imagen y nuestra comprensión de la psicopatología -y defenderemos que este proceso sólo ocurrir en un entorno adecuado-. Suele afirmarse que la naturaleza de la depresión fue inferida a partir del éxito terapéutico de los antidepresivos; no obstante, los psicodélicos fueron tan exitosos como los antidepresivos y, en cambio, no ejercieron la misma influencia en nuestra visión. Los antidepresivos de primera y segunda generación pudieron influenciar nuestra mirada porque se encontraban en un entorno propicio para ello. Cuestiones sociales, políticas, económicas e incluso metafísicas entraron en juego para llegar a ese resultado. Compararemos el despliegue de estos dos paradigmas suscitados por sendos fármacos: uno, donde los fármacos son vistos como fórmulas mágicas cuya meta es restablecer el equilibrio bioquímico; otro, donde los fármacos son vistos como herramientas terapéuticas capaces de inducir una experiencia capaz de cambiar la vida del paciente, en el contexto apropiado. Revisaremos los factores que contribuyeron al establecimiento de un paradigma reduccionista, tales como las aspiraciones científicas de la psiquiatría y la identificación de las explicaciones biologicistas con el terreno de la objetividad. Finalmente, reflexionaremos sobre el nuevo paradigma que se abre con la investigación contemporánea.

Abstract: This paper aims to explore and compare the metaphysical entailments of the conventional psychopharmacological approach in the treatment of depression to those of a psychedelic approach. We will examine the thesis by which knowledge of how drugs act upon us shapes our self-image and our understanding of psychopathology--and defend that this process can only take place in a supportive environment. It is commonly claimed that the nature of depression was shaped after the therapeutic success of antidepressants; nevertheless, psychedelic drugs were at least as successful as antidepressants, and they didn't end up having the same power to influence our views. It was possible for first and second-generation antidepressants to influence our views because of a supportive environment, where social, political, economic and even metaphysical issues were at play to create that result. We will compare the unfolding of the two paradigms elicited by these two kinds of drugs, one where pills are seen as magic bullets aimed to restore biochemical balance, and another where drugs are seen as therapeutic tools capable of inducing a life-changing experience, provided there is an adequate context. We will review different factors that contributed to the establishment of a reductionist paradigm, such as the aspirations of psychiatry and the assumed objectivity of biologically oriented explanations. Finally, we will reflect on the new paradigm that unfolds with contemporary research.

Resumo: Este trabalho tem como objetivo explorar e comparar as implicações metafísicas da abordagem psicofarmacológica convencional no tratamento da depressão com aqueles de uma abordagem psicodélica. Examinaremos a tese segundo a qual o conhecimento de como as drogas agem sobre nós molda nossa auto-imagem e nossa compreensão da psicopatologia, e defenderemos que este processo só pode ocorrer em um quadro favorável. É comumente alegado que a natureza da depressão foi moldada após o sucesso terapêutico dos antidepressivos; no entanto, as drogas psicodélicas eram pelo menos tão bem sucedidas quanto os antidepressivos, e não acabavam tendo o mesmo poder de influenciar nossas opiniões. Era possível que os antidepressivos de primeira e segunda geração influenciassem nossas visões por causa de um quadro favorável, onde questões sociais, políticas, econômicas e até mesmo metafísicas estavam em jogo para chegar a esse resultado. Compararemos o desenvolvimento dos dois paradigmas promovidos por esses dois tipos de drogas, um onde as pílulas são vistas como fórmulas mágicas destinadas a restaurar o equilíbrio bioquímico e outro onde as drogas são vistas como ferramentas terapêuticas capazes de induzir uma experiência transcendental. Revisaremos diversos fatores que contribuíram para o estabelecimento de um paradigma reducionista, como as aspirações da psiquiatria e a suposta objetividade das explicações biologicamente orientadas. Finalmente, refletiremos sobre o novo paradigma que se desenvolve na pesquisa contemporânea.