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Klit Lee posted an update 6 months, 3 weeks ago
Multivariate analysis showed that a median testosterone ≥50ng/dL was significantly associated with a decrease in bDFS (HR 6.58, 95%CI 1.28-33.76, p=0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups.
Our results do not support the concept that additional serum testosterone suppression below 20ng/dL is associated with better outcomes than 20-49ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.
Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.
Behavioral disturbances in adolescence are potentially linked to aberrant functioning of the thyroid gland. Accordingly, alterations of the hypothalamic-pituitary-thyroid (HPT) axis might impact psychopathological development. Selleck Piceatannol Yet corresponding research in adolescents with nonsuicidal self-injury (NSSI) and comorbid mental disorders is scarce.
The present study examined HPT axis functioning in adolescents with NSSI compared to healthy controls (HC) using blood-based assays of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and the ratio of these hormones (fT3/fT4 ratio). Cortisol was additionally examined to contrast HPT axis functioning with a well-established biomarker of stress responsivity. Moreover, associations between clinical characteristics, HPT axis and HPA axis functioning were investigated. Female adolescents meeting NSSI criteria according to DSM-5 criteria (n=117) were compared to adolescent HC (n=41). Standardized serum-based endocrinological assays andlescent psychiatry.Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day). The expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors, and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors, and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, are mediated by insulin increase in the dentate gyrus and subsequently activation of its downstream signaling pathway.Plasma levels of the hypotensive peptides of adrenomedullin and atrial and B-type natriuretic peptides (AM, ANP, BNP) are possible biomarkers for cardiovascular diseases. Increased variability of body mass index (BMI) over a certain period of time has been reported to be associated with cardiovascular morbidity or mortality. The aim of this study is to examine clinical significance of those hypotensive peptides as biomarkers by analyzing the relationship between plasma levels of the peptides and year-by-year variability of BMI in the general population without overt cardiovascular diseases. The subjects were 427 local residents (141 males and 286 females) attending their annual health check-up, who had been examined at least 5 times over the preceding period of 10 years. They were divided into two groups of low or high variability by the median of coefficient of variation (CV) of BMI values for each gender. Plasma AM levels of those with high year-by-year variability of BMI were significantly increased, as compared to the group with low variability, in both genders; meanwhile, such a difference was not noted in plasma levels of the natriuretic peptides. No significant differences were found in the basal parameters, which could affect plasma AM level, such as age, BMI, blood pressure or serum creatinine, between two groups. In conclusion, increase in plasma AM was associated with high year-by-year variability of BMI in the general population without overt heart disease. This relationship between the two suggests that increased plasma AM level is a cardiovascular risk marker.The thyroid gland accumulates the rare dietary element iodine and incorporates it into iodinated thyroid hormones, utilising several tightly regulated reactions and molecular mechanisms. Thyroid hormones are essential in vertebrates and play a central role in many biological processes, such as development, thermogenesis and growth. The control of these functions is exerted through the binding of hormones to nuclear thyroid hormone receptors that rule the transcription of numerous metabolic genes. Over the last 50 years, thyroid biology has been studied extensively at the cellular and organismal levels, revealing its multiple clinical implications, yet, a complete molecular understanding is still lacking. This includes the atomic structures of crucial pathway components that would be needed to elucidate molecular mechanisms. Here we review the currently known protein structures involved in thyroid hormone synthesis, regulation, transport, and actions. We also highlight targets for future investigations that will significantly benefit from recent advances in macromolecular structure determination by electron cryo-microscopy (cryo-EM). As an example, we demonstrate how cryo-EM was crucial to obtain the structure of the large thyroid hormone precursor protein, thyroglobulin. We discuss modern cryo-EM compared to other structure determination methods and how an integrated structural and cell biological approach will help filling the molecular knowledge gap in our understanding of thyroid hormone metabolism. Together with clinical, cellular and high-throughput ‘omics’ studies, atomic structures of thyroid components will provide an important framework to map disease mutations and to interpret and predict thyroid phenotypes.