Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we examined genetically normal F2 generation descendants of mice that were developmentally overexposed to thyroid hormone due to a Dio3 mutation. Hypothalamic gene expression profiling in postnatal day 15 F2 descendants on the paternal lineage of ancestral male and female T3-overexposed mice revealed, respectively, 1089 and 1549 differentially expressed genes. A large number of them, 675 genes, were common to both sets, suggesting comparable epigenetic effects of thyroid hormone on both the male and female ancestral germ lines. Oligodendrocyte- and neuron-specific genes were strongly overrepresented among genes showing, respectively, increased and decreased expression. Altered gene expression extended to other brain regions and was associated in adulthood with decreased anxiety-like behavior, increased marble burying and reduced physical activity. The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2. Thus, developmental levels of thyroid hormone influence the epigenetic information of the germ line, disproportionately affecting genes with critical roles in early brain development, and leading in future generations to disease-relevant alterations in postnatal brain gene expression and adult behavior.

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects.

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW.

MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated With the Absence of a Functional Type 3 Deiodinase.

Mice deficient in the type 3 deiodinase (D3KO mice) manifest impaired clearance of thyroid hormone (TH), leading to elevated levels of TH action during development. This alteration causes reduced neonatal viability, growth retardation, and central hypothyroidism. Here we examined how these phenotypes are affected by a deficiency in the monocarboxylate transporter 8 (MCT8), which is a major contributor to the transport of the active thyroid hormone, T3, into the cell. MCT8 deficiency eliminated the neonatal lethality of type 3 deiodinase (D3)-deficient mice and significantly ameliorated their growth retardation. Double-mutant newborn mice exhibited similar peripheral thyrotoxicosis and increased brain expression of T3-dependent genes as mice with D3 deficiency only. Later in neonatal life and adulthood, double-mutant mice manifested central and peripheral TH status similar to mice with single MCT8 deficiency, with low serum T4, elevated serum TSH and T3, and decreased T3-dependent gene expression in the hypothalamus. In double-mutant adult mice, both thyroid gland size and the hypothyroidism-induced rise in TSH were greater than those in mice with single D3 deficiency but less than those in mice with MCT8 deficiency alone. Our results demonstrate that the marked phenotypic abnormalities observed in the D3-deficient mouse, including perinatal mortality, growth retardation, and central hypothyroidism in adult animals, require expression of MCT8, confirming the interdependent relationship between the TH transport into cells and the deiodination processes.

Acupuntura en el adulto mayor ansioso ante el tratamiento estomatológico versus tratamiento convencional / Acupuncture in elderly people anxious about the stomatological treatment versus the conventional treatment

Fundamento: la población cubana envejece y en pocos años será la más longeva de América Latina. La ansiedad es frecuente en el adulto mayor que acude a estomatología y constituye una barrera en la relación médico-paciente. Objetivo: evaluar la eficacia de la acupuntura en el paciente adulto mayor con ansiedad ante el tratamiento estomatológico en la clínica Ismael Clark y Mascaró de Camagüey, de enero a octubre de 2014. Métodos: se realizó un ensayo clínico controlado. El universo estuvo constituido por 100 ancianos y se realizó un muestreo aleatorio simple a doble ciego a 60 pacientes senescentes muy ansiosos ante el tratamiento estomatológico, que dieron su consentimiento para participar en la investigación. Hubo homogeneidad en la selección de los sujetos para conformar los grupos I (tratados con acupuntura) y II (tratados con benzodiacepinas). Hubo homogeneidad en el uso y la frecuencia de los instrumentos seleccionados para realizar las mediciones e interpretaciones. La observación objetiva, evitó sesgos. Se comparó la evolución clínica de la ansiedad al aplicar el test IDARE inicial y final. Se utilizó el paquete estadístico SPSS para Windows versión 21.0. Se aplicaron la estadística descriptiva y la inferencial no paramétrica conocida como Mann Whitney, con una significación de 0,05. Resultados: predominó el sexo femenino entre 65 y 69 años. El temor, el temblor, la irritabilidad y la tensión muscular fueron algunas de las variables clínicas observadas. Los niveles de ansiedad iniciales fueron altos pero al finalizar los tratamientos los síntomas clínicos y la ansiedad disminuyeron en ambos grupos. Conclusiones: el tratamiento con acupuntura resultó ser más eficaz para disminuir la ansiedad del adulto mayor ante el tratamiento estomatológico.

Background: Cuban population is growing old and, in a few years, will be the most long-lived in Latin America. Anxiety is frequent in the elderly person who comes to the stomatology service. It is a barrier to the doctor-patient relationship. Objective: to asses the effectiveness of acupuncture in elderly people anxious about the stomatological treatment in Ismael Clark y Mascaró Clinic in Camagüey from January to October, 2014. Methods: a controlled clinical trial was conducted. The universe was composed of 100 patients. A simple randomized, double-blind sampling was made to 60 aging patients that were very anxious about the stomatological treatment and agreed to participate in the research. There was homogeneity in the selection of the participants to compose the groups I (treated with acupuncture) and II (treated with benzodiazepines). There was also homogeneity in the use of the instruments selected to conduct the measure and the interpretations. The objective observation avoided skewness. The clinical evolution of anxiety was compared applying the initial and final IDARE test. The SPSS software package for Windows, version 21.0, was used. The descriptive statistics and the nonparametric statistical inference, known as Mann Whitney, were applied with a statistically significant result of 5, 05. Results: female sex between 65 and 69 years old predominated. Fear, trembling, irritability and muscular tension were some of the clinical variables observed. The levels of anxiety were high but at the end of the treatments the clinical symptoms and anxiety decreased in both groups. Conclusions: the treatment with acupuncture turned out to be very effective in decreasing anxiety in elderly people facing a stomatological treatment.

Acupuntura en el adulto mayor ansioso ante el tratamiento estomatológico versus tratamiento convencional / Acupuncture in elderly people anxious about the stomatological treatment versus the conventional treatment

Fundamento: la población cubana envejece y en pocos años será la más longeva de América Latina. La ansiedad es frecuente en el adulto mayor que acude a estomatología y constituye una barrera en la relación médico-paciente.Objetivo: evaluar la eficacia de la acupuntura en el paciente adulto mayor con ansiedad ante el tratamiento estomatológico en la clínica Ismael Clark y Mascaró de Camagüey, de enero a octubre de 2014.Métodos: se realizó un ensayo clínico controlado. El universo estuvo constituido por 100 ancianos y se realizó un muestreo aleatorio simple a doble ciego a 60 pacientes senescentes muy ansiosos ante el tratamiento estomatológico, que dieron su consentimiento para participar en la investigación. Hubo homogeneidad en la selección de los sujetos para conformar los grupos I (tratados con acupuntura) y II (tratados con benzodiacepinas). Hubo homogeneidad en el uso y la frecuencia de los instrumentos seleccionados para realizar las mediciones e interpretaciones. La observación objetiva, evitó sesgos. Se comparó la evolución clínica de la ansiedad al aplicar el test IDARE inicial y final. Se utilizó el paquete estadístico SPSS para Windows versión 21.0. Se aplicaron la estadística descriptiva y la inferencial no paramétrica conocida como Mann Whitney, con una significación de 0,05.Resultados: predominó el sexo femenino entre 65 y 69 años. El temor, el temblor, la irritabilidad y la tensión muscular fueron algunas de las variables clínicas observadas. Los niveles de ansiedad iniciales fueron altos pero al finalizar los tratamientos los síntomas clínicos y la ansiedad disminuyeron en ambos grupos.Conclusiones: el tratamiento con acupuntura resultó ser más eficaz para disminuir la ansiedad del adulto mayor ante el tratamiento estomatológico(AU)

Background: Cuban population is growing old and, in a few years, will be the most long-lived in Latin America. Anxiety is frequent in the elderly person who comes to the stomatology service. It is a barrier to the doctor-patient relationship.Objective: to asses the effectiveness of acupuncture in elderly people anxious about the stomatological treatment in Ismael Clark y Mascaró Clinic in Camagüey from January to October, 2014.Methods: a controlled clinical trial was conducted. The universe was composed of 100 patients. A simple randomized, double-blind sampling was made to 60 aging patients that were very anxious about the stomatological treatment and agreed to participate in the research. There was homogeneity in the selection of the participants to compose the groups I (treated with acupuncture) and II (treated with benzodiazepines). There was also homogeneity in the use of the instruments selected to conduct the measure and the interpretations. The objective observation avoided skewness. The clinical evolution of anxiety was compared applying the initial and final IDARE test. The SPSS software package for Windows, version 21.0, was used. The descriptive statistics and the nonparametric statistical inference, known as Mann Whitney, were applied with a statistically significant result of 5, 05.Results: female sex between 65 and 69 years old predominated. Fear, trembling, irritability and muscular tension were some of the clinical variables observed. The levels of anxiety were high but at the end of the treatments the clinical symptoms and anxiety decreased in both groups.Conclusions: the treatment with acupuncture turned out to be very effective in decreasing anxiety in elderly people facing a stomatological treatment(AU)

Differential recruitment of executive control regions during phonological competition in monolinguals and bilinguals.

Behavioral research suggests that monolinguals and bilinguals differ in how they manage within-language phonological competition when listening to language. The current study explored whether bilingual experience might also change the neural resources recruited to control spoken-word competition. Seventeen Spanish-English bilinguals and eighteen English monolinguals completed an fMRI task in which they searched for a picture representing an aurally presented word (e.g., "candy") from an array of four presented images. On competitor trials, one of the objects in the display shared initial phonological overlap with the target (e.g., candle). While both groups experienced competition and responded more slowly on competitor trials than on unrelated trials, fMRI data suggest that monolinguals, but not bilinguals, activated executive control regions (e.g., anterior cingulate, superior frontal gyrus) during within-language phonological competition. We conclude that differences in how monolinguals and bilinguals manage competition may result from bilinguals' more efficient deployment of neural resources.

Expert athletes activate somatosensory and motor planning regions of the brain when passively listening to familiar sports sounds.

The present functional magnetic resonance imaging study examined the neural response to familiar and unfamiliar, sport and non-sport environmental sounds in expert and novice athletes. Results revealed differential neural responses dependent on sports expertise. Experts had greater neural activation than novices in focal sensorimotor areas such as the supplementary motor area, and pre- and postcentral gyri. Novices showed greater activation than experts in widespread areas involved in perception (i.e. supramarginal, middle occipital, and calcarine gyri; precuneus; inferior and superior parietal lobules), and motor planning and processing (i.e. inferior frontal, middle frontal, and middle temporal gyri). These between-group neural differences also appeared as an expertise effect within specific conditions. Experts showed greater activation than novices during the sport familiar condition in regions responsible for auditory and motor planning, including the inferior frontal gyrus and the parietal operculum. Novices only showed greater activation than experts in the supramarginal gyrus and pons during the non-sport unfamiliar condition, and in the middle frontal gyrus during the sport unfamiliar condition. These results are consistent with the view that expert athletes are attuned to only the most familiar, highly relevant sounds and tune out unfamiliar, irrelevant sounds. Furthermore, these findings that athletes show activation in areas known to be involved in action planning when passively listening to sounds suggests that auditory perception of action can lead to the re-instantiation of neural areas involved in producing these actions, especially if someone has expertise performing the actions.

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats.

BACKGROUND: Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. METHODS: Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. RESULTS: The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. CONCLUSIONS: This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.

Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis.

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T(3) results in a serum T(3) level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T(3) and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.

Rescue treatment with terlipressin in children with refractory septic shock: a clinical study.

INTRODUCTION: Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock. METHODS: We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours. RESULTS: Sixteen children (age range, 1 month-13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12-52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16-43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37-93) to 77 (42-100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1-4) to 1 (0-2.5) microg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case. CONCLUSION: TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock.

Type 3 deiodinase is critical for the maturation and function of the thyroid axis.

Developmental exposure to appropriate levels of thyroid hormones (THs) in a timely manner is critical to normal development in vertebrates. Among the factors potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus, placenta, and fetal and neonatal tissues. To determine the physiological role of D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit delayed 3,5,3'-triiodothyronine (T3) clearance, a markedly elevated serum T3 level, and overexpression of T3-inducible genes in the brain. From postnatal day 15 to adulthood, D3KO mice demonstrate central hypothyroidism, with low serum levels of 3,5,3',5'-tetraiodothyronine (T4) and T3, and modest or no increase in thyroid-stimulating hormone (TSH) concentration. Peripheral tissues are also hypothyroid. Hypothalamic T3 content is decreased while thyrotropin-releasing hormone (TRH) expression is elevated. Our results demonstrate that the lack of D3 function results in neonatal thyrotoxicosis followed later by central hypothyroidism that persists throughout life. These mice provide a new model of central hypothyroidism and reveal a critical role for D3 in the maturation and function of the thyroid axis.

Fracturas del acetábulo. Resultados del tratamiento a corto y mediano plazo / Acetabular fractures. Results of treatment at short and mid terms

El presente es un estudio ambiespectivo, transversal y descriptivo donde se revisan los expedientes clínicos y radiográficos de 45 pacientes con 48 fracturas, seguidos en promedio por 17 meses. El protocolo diagnóstico de los pacientes incluyó las proyecciones básicas de Judet así com TAC, y el seguimiento se llevó a cabo mediante controles radiográficos cada 2 meses. Los resultados mostraron 41 pacientes hombres y 4 mujeres. La edad promedio fue de 50 años, con un rango de 16 a 84 años. El mecanismo de lesión más frecuente fueron las caídas de altura, seguidos de los accidentes automovilísticos. De acuerdo a la clasificación de Tile se reportan lesiones tipo A en 68.5 por ciento, lesiones tipo B en 18.75 por ciento y lesiones tipo C en 18.75 por ciento. Se presentó un 20 por ciento de luxaciones coxofemorales. El manejo conservador se utilizó en 16 fracturas (A1=6; A3=7 y B1.1=3). El manejo quirúrgico se realizó en 32 acetábulos, utilizando el acceso ilioinguinal en 11 casos, el acceso posterior de Kocher en 16 casos y 5 accesos combinados. El seguimiento mostró un resultado clínico excelente en 29 por ciento, los resultados clínicos buenos en 62.5 por ciento, resultados regulares en 6.2 por ciento y malos en 2 por ciento. La osificación herotópica se presentó en 4 pacientes, todos del tipo II de Brooker