Seroprevalence of Trypanosoma cruzi among children from Veracruz, Mexico: Epidemiological baseline for a control model based on Chagas disease active transmission / Seroprevalencia de Trypanosoma cruzi en niños de Veracruz, México: línea epidemiológica de base para un modelo de control fundamentado de la transmisión activa de la enfermedad de Chagas.

Introduction. In 2021, the Secretaría de Salud de México and the Pan American Health Organization launched an initiative to interrupt intra-domiciliary vector transmission of Trypanosoma cruzi based on the prevalence of Chagas disease in children. The Mexican State of Veracruz was leading this initiative. Objective. To estimate the seroprevalence of T. cruzi infection among children under 15 years of age from rural areas of Veracruz, México. Materials and methods. We identified eight localities of high priority from the Municipality of Tempoal, Veracruz, for baseline serology. Blood samples were collected on filter paper from 817 individuals between June and August 2017, for screening with a third-generation enzyme immunoassay. Reactive cases were confirmed by indirect hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence tests on peripheral blood serum samples. We calculated seroprevalence and 95% confidence intervals (CI). Results. We confirmed Chagas disease cases in children under 15 years of age with a seroprevalence of 1,9% (95 % CI = 1,12-3,16) in the localities of Citlaltepetl, Cornizuelo, Cruz de Palma and Rancho Nuevo. Conclusions. These results indicate recent transmission of T. cruzi in these communities and allow to establish an epidemiological baseline for the design and implementation of a model focused on geographical areas with active transmission to advance toward the elimination of intra-domiciliary vector transmission of this parasite in Mexico.

Introducción. En el 2021, la Secretaría de Salud de México y la Organización Panamericana de la Salud lanzaron una iniciativa para interrumpir la transmisión vectorial intradomiciliaria de Trypanosoma cruzi, fundamentada en la prevalencia de la enfermedad de Chagas en la población infantil. El estado mexicano de Veracruz fue el pionero de esta iniciativa. Objetivo. Estimar la seroprevalencia de infección por T. cruzi en menores de 15 años de localidades rurales de Veracruz, México. Materiales y métodos. Se identificaron ocho localidades prioritarias para la serología basal del municipio de Tempoal, Veracruz. Entre junio y agosto de 2017, se recolectaron muestras de sangre en papel filtro de 817 individuos para su tamizaje mediante un inmunoensayo enzimático de tercera generación. Los casos reactivos del tamizaje se confirmaron mediante pruebas de hemaglutinación indirecta, ensayo de inmunoabsorción ligado a enzimas e inmunofluorescencia indirecta en muestras de suero. Se calculó la seroprevalencia y su intervalo de confianza (IC) del 95 %. Resultados. En las localidades de Citlaltépetl, Cornizuelo, Cruz de Palma y Rancho Nuevo se confirmaron casos de la enfermedad de Chagas en menores de 15 años con una seroprevalencia de 1,9 % (IC 95 % = 1,12-3,16). Conclusiones. Los resultados indican que estas comunidades presentan transmisión reciente de T. cruzi y permiten establecer una línea epidemiológica de base para el diseño e implementación de un modelo dirigido a aquellas áreas geográficas con transmisión activa. Se espera que dicho modelo contribuya a la eliminación de la transmisión vectorial intradomiciliaria del tripanosomátido en México.

Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues.

Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circadian rhythm. To better understand the physiological and molecular basis of this phenotype, we used Dio3+/+ and Dio3-/- mice of both sexes at different zeitgeber times (ZTs) and analyzed corticosterone and thyroxine (T4) levels, hypothalamic, hepatic, and adipose tissue expression of clock genes, as well as genes involved in the thyroid hormone action or physiology of liver and adipose tissues. Wild type mice exhibited sexually dimorphic circadian patterns of genes controlling thyroid hormone action, including Dio3. Dio3-/- mice exhibited altered hypothalamic expression of several clock genes at ZT12, but did not disrupt the overall circadian profile. Expression of clock genes in peripheral tissues was not disrupted by Dio3 deficiency. However, Dio3 loss in liver and adipose tissues disrupted circadian profiles of genes that determine tissue thyroid hormone action and physiology. We also observed circadian-specific changes in serum T4 and corticosterone as a result of DIO3 deficiency. The circadian alterations manifested sexual dimorphism. Most notable, the time curve of serum corticosterone was flattened in Dio3-/- females. We conclude that Dio3 exhibits circadian variations, influencing the circadian rhythmicity of thyroid hormone action and physiology in liver and adipose tissues in a sex-specific manner. Circadian disruptions in tissue physiology may then contribute to the metabolic phenotypes of DIO3-deficient mice.

Large-scale investigation of white matter structural differences in bilingual and monolingual children: An adolescent brain cognitive development data study.

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive control white matter pathways were used to compare white matter fractional anisotropy (FA) values between bilinguals and monolinguals, controlling for demographic and environmental factors as covariates in the models. Results revealed significantly lower FA values in bilinguals compared to monolinguals across established dorsal and ventral language network pathways bilaterally (i.e., the superior longitudinal fasciculus and inferior frontal-occipital fasciculus) and right-hemispheric pathways in areas related to cognitive control and short-term memory (i.e., cingulum and parahippocampal cingulum). In contrast to the enhanced FA values observed in adult bilinguals relative to monolinguals, our findings of lower FA in bilingual children relative to monolinguals may suggest a protracted development of white matter pathways associated with language and cognitive control resulting from dual language learning in childhood. Further, these findings underscore the need for large-scale longitudinal investigation of white matter development in bilingual children to understand neuroplasticity associated with the bilingual experience during this period of heightened language learning.

Brain connectivity and academic skills in English learners.

English learners (ELs) are a rapidly growing population in schools in the United States with limited experience and proficiency in English. To better understand the path for EL's academic success in school, it is important to understand how EL's brain systems are used for academic learning in English. We studied, in a cohort of Hispanic middle-schoolers (n = 45, 22F) with limited English proficiency and a wide range of reading and math abilities, brain network properties related to academic abilities. We applied a method for localizing brain regions of interest (ROIs) that are group-constrained, yet individually specific, to test how resting state functional connectivity between regions that are important for academic learning (reading, math, and cognitive control regions) are related to academic abilities. ROIs were selected from task localizers probing reading and math skills in the same participants. We found that connectivity across all ROIs, as well as connectivity of just the cognitive control ROIs, were positively related to measures of reading skills but not math skills. This work suggests that cognitive control brain systems have a central role for reading in ELs. Our results also indicate that an individualized approach for localizing brain function may clarify brain-behavior relationships.

Subcortical and cerebellar volume differences in bilingual and monolingual children: An ABCD study.

Research suggests that bilingual children experience an extension or delay in the closing of the sensitive/critical period of language development due to multiple language exposure. Moreover, bilingual experience may impact the development of subcortical regions, although these conclusions are drawn from research with adults, as there is a scarcity of research during late childhood and early adolescence. The current study included 1215 bilingual and 5894 monolingual children from the ABCD Study to examine the relationship between subcortical volume and English vocabulary in heritage Spanish bilingual and English monolingual children, as well as volumetric differences between the language groups. We also examined the unique effects of language usage in bilingual children's subcortical volumes. In general, bilingual children had less cerebellar volume and greater volume in the putamen, thalamus, and globus pallidus than monolingual children. English vocabulary was positively related to volume in the cerebellum, thalamus, caudate, putamen, nucleus accumbens, and right pallidum in all children. Moreover, the positive relationship between vocabulary and volume in the nucleus accumbens was stronger for monolingual adolescents than bilingual adolescents. The results are somewhat in line with existing literature on the dynamic volume adaptation of subcortical brain regions due to bilingual development and experience. Future research is needed to further explore these regions longitudinally across development to examine structural changes in bilingual brains.

Cortical Thickness Is Related to Variability in Heritage Bilingual Language Proficiency.

Research suggests that bilingual experience is associated with gray matter changes, such that initial language gains are associated with expansion and language expertise is associated with renormalization. Previous studies on language proficiency development primarily focused on between-subjects, quasiexperimental comparisons of monolinguals and bilinguals. This study proposes a new paradigm to examine language expertise and cortical thickness within heritage bilinguals (n = 215), as well as between bilinguals and monolinguals (n = 145), using data combined from eight previous magnetic resonance imaging studies. In general, results highlight variability within bilinguals, finding relationships between cortical thickness and English proficiency that are relatively consistent within monolinguals, but inconsistent within bilinguals. In all participants, higher levels of proficiency in English-monolinguals' only language and bilinguals' second but stronger language-were negatively related to cortical thickness. In bilinguals, higher proficiency in the weaker, albeit first learned, language was positively related to cortical thickness. Moreover, there was an interaction between language group and English proficiency in predicting cortical thickness, such that the relationship between proficiency and thickness was stronger in monolinguals than in bilinguals. Findings also demonstrate that the regions associated with language expertise differ between bilinguals and monolinguals. Future directions for cognitive-developmental neuroscience research in bilinguals are suggested, particularly the longitudinal examination of cortical changes in relation to bilingual experiences.

New Organotin (IV) Compounds Derived from Dehydroacetic Acid and Thiosemicarbazides: Synthesis, Rational Design, Cytotoxic Evaluation, and Molecular Docking Simulation.

Organotin complexes were prepared through a one-pot reaction with three components by reacting thiosemicarbazide or 4-methyl-3-thiosemicarbazide or 4-phenylthiosemicarbazide, dehydroacetic acid (DHA) and dibutyl, diphenyl, dicyclohexyl, and bis[(trimethylsilyl)methyl]tin(IV) oxides; all complexes were characterized by infrared (IR), ultraviolet-visible (UV-vis), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. The 119Sn NMR revealed chemical shifts corresponding to a pentacoordinated environment in solution. The X-ray crystallography of the two complexes evidenced the formation of monomeric complexes with a pentacoordinated geometry around tin via three donor atoms from the ligand, the sulfur of the thiol, the nitrogen of the imine group, and the oxygen of the pyran ring. The geometries of the five-coordinated complexes 3a (Bu2SnL3), 3c (Ph2SnL3), and 3d (Cy2SnL3) acid were intermediate between square pyramidal and trigonal bipyramidal, and complex 1a (Bu2SnL1) adopted a bipyramidal trigonal geometry (BPT). The sulforhodamine B assay assessed the cytotoxicity of organotin(IV) complexes against the MDA-MB-231 and MCF-7 (human mammary adenocarcinoma) cell lines and one normal COS-7 (African green monkey kidney fibroblast). The IC50 values evidenced a significant antiproliferative effect on cancer cells; the complexes were more potent than the positive cisplatin control and the corresponding ligands, dehydroacetic acid thiosemicarbazone (L1), dehydroacetic acid-N(4)-methylthiosemicarbazone (L2), and dehydroacetic acid-N(4)-phenylthiosemicarbazone (L3). The IC50 values also indicated that the organotin(IV) complexes were more cytotoxic against the triple-negative breast cell line MDA-MB-231 than MCF-7, inducing significant morphological alterations. The interactions of organotin(IV) 1c (Ph2SnL1), 1d (Cy2SnL1), and 1e (((CH3)3SiCH2)2SnL1) were evaluated with ss-DNA by fluorescence; intensity changes of the fluorescence were indicative of the displacement of ethidium bromide (EB), confirming the interaction of the organotin(IV) complexes with ss-DNA; the results showed a DNA binding affinity. The thermodynamic parameters obtained through isothermal titration calorimetry showed that the interaction of 1c (Ph2SnL1), with ss-ADN, was exothermic. Molecular docking studies also demonstrated that the organotin(IV) complexes were intercalated in DNA by conventional hydrogen bonds, carbon-hydrogen bonds, and π-alkyl interactions. These complexes furthermore showed a greater affinity towards DNA than cisplatin.

Paternal developmental thyrotoxicosis disrupts neonatal leptin leading to increased adiposity and altered physiology of the melanocortin system.

Background: The genetic code does not fully explain individual variability and inheritance of susceptibility to endocrine conditions, suggesting the contribution of epigenetic factors acting across generations. Methods: We used a mouse model of developmental thyrotoxicosis (Dio3-/- mouse) to analyze endocrine outcomes in the adult offspring of Dio3-/- males using standard methods for body composition, and baseline and fasting hormonal and gene expression determinations in serum and tissues of relevance to the control of energy balance. Results: Compared to controls, adult females with an exposed father (EF females) exhibited higher body weight and fat mass, but not lean mass, a phenotype that was much milder in EF males. After fasting, both EF females and males exhibited a more pronounced decrease in body weight than controls. EF females also showed markedly elevated serum leptin, increased white adipose tissue mRNA expression of leptin and mesoderm-specific transcript but decreased expression of type 2 deiodinase. EF females exhibited decreased serum ghrelin, which showed more pronounced post-fasting changes in EF females than in control females. EF female hypothalami also revealed significant decreases in the expression of pro-opiomelanocortin, agouti-related peptide, neuropeptide Y and melanocortin receptor 4. These markers also showed larger changes in response to fasting in EF females than in control females. Adult EF females showed no abnormalities in serum thyroid hormones, but pituitary expression of thyrotropin-releasing hormone receptor 1 and thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd. In EF males, these abnormalities were generally milder. In addition, postnatal day 14 (P14) serum leptin was markedly reduced in EF pups. Discussion: A paternal excess of thyroid hormone during development modifies the endocrine programming and energy balance in the offspring in a sexually dimorphic manner, with baseline and dynamic range alterations in the leptin-melanocortin system and thyroid gland, and consequences for adiposity phenotypes. We conclude that thyroid hormone overexposure may have important implications for the non-genetic, inherited etiology of endocrine and metabolic pathologies.

Functional near infrared spectroscopy detects cortical activation changes concurrent with memory loss in postmenopausal women with Type II Diabetes.

Older adults with Type II Diabetes Mellitus (DM) experience mild cognitive impairment, specifically in the domain of recall/working memory. No consistent causative structural cortical deficits have been identified in persons with DM (PwDM). Memory deficits may be exacerbated in older adult females, who are at the highest risk of cardiovascular decline due to DM. The focus of the current study was to evaluate functional cortical hemodynamic activity during memory tasks in postmenopausal PwDM. Functional Near Infrared Spectroscopy (fNIRS) was used to monitor oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) during memory-based tasks in a cross-sectional sample of postmenopausal women with DM. Twenty-one community-dwelling DM females (age = 65 ± 6 years) and twenty-one age- and sex-matched healthy controls (age = 66 ± 6 years) were evaluated. Working memory performance (via N-back) was evaluated while study participants donned cortical fNIRS. Health state, metabolic data, and menopausal status data were also collected. Deficits in working memory accuracy were found in the DM group as compared to controls. Differences in HbO responses emerged in the DM group. The DM group exhibited altered PFC activity magnitudes and increased functional cortical activity across ROIs compared to controls. HbO and HbR responses were not associated with worsened health state measures. These data indicate a shift in cortical activity patterns with memory deficits in postmenopausal PwDM. This DM-specific shift of HbO is a novel finding that is unlikely to be detected by fMRI. This underscores the value of using non-MRI-based neuroimaging techniques to evaluate cortical hemodynamic function to detect early mild cognitive impairment.

Epigenetic developmental programming and intergenerational effects of thyroid hormones.

Mounting evidence is showing that altered signaling through the nuclear hormone receptor superfamily can cause abnormal, long-term epigenetic changes which translate into pathological modifications and susceptibility to disease. These effects seem to be more prominent if the exposure occurs early in life, when transcriptomic profiles are rapidly changing. At this time, the coordination of the complex coordinated processes of cell proliferation and differentiation that characterize mammalian development. Such exposures may also alter the epigenetic information of the germ line, potentially leading to developmental changes and abnormal outcomes in subsequent generations. Thyroid hormone (TH) signaling is mediated by specific nuclear receptors, which have the ability to markedly change chromatin structure and gene transcription, and can also regulate other determinants of epigenetic marks. TH exhibits pleiotropic effects in mammals, and during development, its action is regulated in a highly dynamic manner to suit the rapidly evolving needs of multiple tissues. Their molecular mechanisms of action, timely developmental regulation and broad biological effects place THs in a central position to play a role in the developmental epigenetic programming of adult pathophysiology and, through effects on the germ line, in inter- and trans-generational epigenetic phenomena. These areas of epigenetic research are in their infancy, and studies regarding THs are limited. In the context of their characteristics as epigenetic modifiers and their finely tuned developmental action, here we review some of the observations underscoring the role that altered TH action may play in the developmental programming of adult traits and in the phenotypes of subsequent generations via germ line transmission of altered epigenetic information. Considering the relatively high prevalence of thyroid disease and the ability of some environmental chemicals to disrupt TH action, the epigenetic effects of abnormal levels of TH action may be important contributors to the non-genetic etiology of human disease.

Pentacoordinated Organotin(IV) Complexes as an Alternative in the Design of Highly Efficient Optoelectronic and Photovoltaic Devices: Synthesis and Photophysical Characterization.

The synthesis of four pentacoordinated organotin(IV) complexes prepared in a one-pot reaction from 2-hydroxy-1-naphthaldehyde, 2-amino-3-hydroxypyridine and organotin oxides is reported. The complexes were characterized by UV-Vis, IR, MS, 1H, 13C and 119Sn NMR techniques. The compound based on 2,2-diphenyl-6-aza-1,3-dioxa-2-stannanaphtho[1,2-h]pyrido[3,2-d]cyclononene revealed the formation of a monomeric complex with a distorted five-coordinated molecular geometry intermediate between the trigonal bipyramidal and square pyramidal. In order to find possible applications in photovoltaic devices, hybrid films of organotin(IV) complexes embedded in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with graphene were deposited. The topographic and mechanical properties were examined. The film with the complex integrated into the cyclohexyl substituent has high plastic deformation, with a maximum stress of 1.69 × 107 Pa and a Knoop hardness of 0.061. The lowest values of 1.85 eV for the onset gap and 3.53 eV for the energy gap were obtained for the heterostructure having the complex with the phenyl substituent. Bulk heterojunction devices were fabricated; these devices showed ohmic behavior at low voltages and a space-charge-limited current (SCLC) conduction mechanism at higher voltages. A value of 0.02 A was found for the maximum carried current. The SCLC mechanism suggests hole mobility values of between 2.62 × 10-2 and 3.63 cm2/V.s and concentrations of thermally excited holes between 2.96 × 1018 and 4.38 × 1018 m-3.

Pneumocystis jirovecii Colonization in Mexican Patients with Chronic Obstructive Pulmonary Disease.

The prevalence of colonization by Pneumocystis jirovecii (P. jirovecii) has not been studied in Mexico. We aimed to determine the prevalence of colonization by P. jirovecii using molecular detection in a population of Mexican patients with chronic obstructive pulmonary disease (COPD) and describe their clinical and sociodemographic profiles. We enrolled patients discharged from our hospital diagnosed with COPD and without pneumonia (n = 15). The primary outcome of this study was P. jirovecii colonization at the time of discharge, as detected by nested polymerase chain reaction (PCR) of oropharyngeal wash samples. The calculated prevalence of colonization for our study group was 26.66%. There were no statistically significant differences between COPD patients with and without colonization in our groups. Colonization of P. jirovecii in patients with COPD is frequent in the Mexican population; the clinical significance, if any, remains to be determined. Oropharyngeal wash and nested PCR are excellent cost-effective options to simplify sample collection and detection in developing countries and can be used for further studies.

Developmental thyroid hormone action on pro-opiomelanocortin-expressing cells programs hypothalamic BMPR1A depletion and brown fat activation.

Thyroid hormone excess secondary to global type 3 deiodinase (DIO3) deficiency leads to increased locomotor activity and reduced adiposity, but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity. To distinguish the underlying contributions to the energy balance phenotype of DIO3 deficiency, we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin (POMC)-expressing cells via cell-specific DIO3 inactivation. These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression, hyperphagia, and increased activity in brown adipose tissue, with adiposity and serum levels of leptin and thyroid hormones remained normal. These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a (BMPR1A), which has been shown to cause similar phenotypes when inactivated in POMC-expressing cells. Our results indicate that developmental overexposure to thyroid hormone in POMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.

Thyroid Hormone Metabolism: A Historical Perspective.

In this article, starting with the recognition that iodine is essential for normal thyroid function and is a component of thyroid hormone (TH) molecules, we discuss the many seminal observations and discoveries that have led to identification of various pathways of TH metabolism and their potential roles in TH economy and action. We then recount evidence that TH metabolism participates in maintaining the appropriate content of active hormone in a TH-responsive tissue or cell. Thus, metabolism of the TH is not merely a means by which it is degraded and eliminated from the body, but an essential component of an intricate system by which the thyroid exerts its multiple regulatory effects on almost all organs and tissues. The article ends with a summary of the current concepts and some outstanding questions that are awaiting answers.

Genetic and Morphological Identification of Spirometra decipiens in Snakes and Domestic Dog Found in Cuba.

Spirometra (Cestoda: Diphyllobothriidea) affects humans and some species of domestic and wild animals which eventually interact with humans. In this article, we report three new cases of Spirometra decipiens (Diesing, 1850) infection observed in two intermediate hosts and one definitive host, in Cuba. Genetic and morphological identification of S. decipiens in two snakes and a domestic dog were carried out by molecular means and routine histological study using hematoxylin-eosin staining, respectively. Taken together, the anatomical location, the host species infected with the specimens and their morphological and genetic features, all the samples were identified as S. decipiens. In each of the three cases, PCR assays using specific primers amplified bands that corresponded to S. decipiens species. To our knowledge, this paper is the first report of S. decipiens in species of Cuban endemic fauna and in the Caribbean islands. These species constitute a real or potential risk of transmission of Spirometra to humans in Cuba.

Thyroid hormone elicits intergenerational epigenetic effects on adult social behavior and fetal brain expression of autism susceptibility genes.

Genetic mutations identified in genome-wide association studies can only explain a small percentage of the cases of complex, highly heritable human conditions, including neurological and neurodevelopmental disorders. This suggests that intergenerational epigenetic effects, possibly triggered by environmental circumstances, may contribute to their etiology. We previously described altered DNA methylation signatures in the sperm of mice that experienced developmental overexposure to thyroid hormones as a result of a genetic defect in hormone clearance (DIO3 deficiency). Here we studied fetal brain gene expression and adult social behavior in genetically normal F2 generation descendants of overexposed mice. The brain of F2 generation E13.5 fetuses exhibited abnormal expression of genes associated with autism in humans, including Auts2, Disc1, Ldlr, Per2, Shank3, Oxtr, Igf1, Foxg1, Cd38, Grid2, Nrxn3, and Reln. These abnormal gene expression profiles differed depending on the sex of the exposed ancestor. In the three-chamber social box test, adult F2 generation males manifested significantly decreased interest in social interaction and social novelty, as revealed by decrease total time, distance traveled and time immobile in the area of interaction with novel strangers. F1 generation mice, compared to appropriate controls also exhibited altered profiles in fetal brain gene expression, although these profiles were substantially different to those in the F2 generation. Likewise adult F1 generation mice showed some abnormalities in social behavior that were sexually dimorphic and milder than those in F2 generation mice. Our results indicate that developmental overexposure to thyroid hormone causes intergenerational epigenetic effects impacting social behavior and the expression of autism-related genes during early brain development. Our results open the possibility that altered thyroid hormone states, by eliciting changes in the epigenetic information of the germ line, contribute to the susceptibility and the missing-but heriTables-etiology of complex neurodevelopmental conditions characterized by social deficits, including autism and schizophrenia.

Thermal Evaluation of Multi-Antenna Systems Proposed to Treat Bone Tumors: Finite Element Analysis.

Microwave ablation is commonly used in soft tissue tumors, but its application in bone tumors has been barely analyzed. Antennas to treat bone tissue (~3 cm2), has been lately designed. Bone tumors at pathological stage T1 can reach 8 cm wide. An antenna cannot cover it; therefore, our goal is to evaluate the thermal performance of multi-antenna arrays. Linear, triangular, and square configurations of double slot (DS) and monopole (MTM) antennas were evaluated. A parametric study (finite element method), with variations in distance between antennas (ad) and bone thickness (bt) was implemented. Array feasibility was evaluated by SWR, ablated tissue volume, etc. The linear configuration with DS and MTM antennas showed SWR ≤ 1.6 for ad = 1 mm−15 mm and bt = 20 mm−40 mm, and ad = 10 mm−15 mm and bt = 25 mm−40 mm, respectively; the triangular showed SWR ≤ 1.5 for ad = 5 mm−15 mm and bt = 20 mm−40 mm and ad = 10 mm−15 mm and bt = 25 mm−40 mm. The square configuration (DS) generated SWR ≤ 1.5 for ad = 5 mm−20 mm and bt = 20 mm−40 mm, and the MTM, SWR ≤ 1.5 with ad = 10 mm and bt = 25 mm−40 mm. Ablated tissue was 4.65 cm3−10.46 cm3 after 5 min. According to treatment time and array configuration, maximum temperature and ablated tissue is modified. Bone tumors >3 cm3 can be treated by these antenna-arrays.

Effects of Nb Additions and Heat Treatments on the Microstructure, Hardness and Wear Resistance of CuNiCrSiCoTiNbx High-Entropy Alloys.

In this research, a set of CuNiCrSiCoTi (H-0Nb), CuNiCrSiCoTiNb0.5 (H-0.5Nb) and CuNiCrSiCoTiNb1 (H-1Nb) high-entropy alloys (HEAs) were melted in a vacuum induction furnace. The effects of Nb additions on the microstructure, hardness, and wear behavior of these HEAs (compared with a CuBe commercial alloy) in the as-cast (AC) condition, and after solution (SHT) and aging (AT) heat treatments, were investigated using X-ray diffraction, optical microscopy, and electron microscopy. A ball-on-disc configuration tribometer was used to study wear behavior. XRD and SEM results showed that an increase in Nb additions and modification by heat treatment (HT) favored the formation of BCC and FCC crystal structures (CS), dendritic regions, and the precipitation of phases that promoted microstructure refinement during solidification. Increases in hardness of HEA systems were recorded after heat treatment and Nb additions. Maximum hardness values were recorded for the H-1Nb alloy with measured increases from 107.53 HRB (AC) to 112.98 HRB, and from 1104 HV to 1230 HV (aged for 60 min). However, the increase in hardness caused by Nb additions did not contribute to wear resistance response. This can be attributed to a high distribution of precipitated phases rich in high-hardness NiSiTi and CrSi. Finally, the H-0Nb alloy exhibited the best wear resistance behavior in the aged condition of 30 min, with a material loss of 0.92 mm3.

DIO3 protects against thyrotoxicosis-derived cranio-encephalic and cardiac congenital abnormalities.

Maternal hyperthyroidism is associated with an increased incidence of congenital abnormalities at birth, but it is not clear which of these defects arise from a transient developmental excess of thyroid hormone and which depend on pregnancy stage, antithyroid drug choice, or unwanted subsequent fetal hypothyroidism. To address this issue, we studied a mouse model of comprehensive developmental thyrotoxicosis secondary to a lack of type 3 deiodinase (DIO3). Dio3-/- mice exhibited reduced neonatal viability on most genetic backgrounds and perinatal lethality on a C57BL/6 background. Dio3-/- mice exhibited severe growth retardation during the neonatal period and cartilage loss. Mice surviving after birth manifested brain and cranial dysmorphisms, severe hydrocephalus, choanal atresia, and cleft palate. These abnormalities were noticeable in C57BL/6J Dio3-/- mice at fetal stages, in addition to a thyrotoxic heart with septal defects and thin ventricular walls. Our findings stress the protecting role of DIO3 during development and support the hypothesis that human congenital abnormalities associated with hyperthyroidism during pregnancy are caused by transient thyrotoxicosis before clinical intervention. Our results also suggest thyroid hormone involvement in the etiology of idiopathic pathologies including cleft palate, choanal atresia, Chiari malformations, Kaschin-Beck disease, and Temple and other cranio-encephalic and heart syndromes.