Notes

Multimorbidity along with Social Involvement Is actually Moderated by simply Purpose in Life as well as Living Total satisfaction.
Naked mole-rats (Heterocephalus glaber) inhabit subterranean burrows in savannas and are, thus, unable to access free water. To identify their mechanism of osmoregulation in xeric environments, we molecularly cloned and analyzed the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene encoding the mineralocorticoid receptor (MR), required for hormone-dependent regulation of genes contributing to body fluid homeostasis. Most vertebrates harbor a single MR homolog. In contrast, we discovered that MR is duplicated in naked mole-rats. The amino acid sequence of naked mole-rat MR1 is 90% identical to its mouse ortholog, and MR1 is abundantly expressed in the kidney and the nervous system. MR2 encodes a truncated protein lacking DNA- and ligand-binding domains of MR1 and is expressed in diverse tissues. Although MR2 did not directly transactivate gene expression, it increased corticosteroid-dependent transcriptional activity of MR1. Our results suggest that MR2 might function as a novel regulator of MR1 activity to fine-tune MR signaling in naked mole-rats.There is a strong biological link between the growth hormone (GH) and gonadal systems in growth, development and metabolism; however, regulatory interactions are poorly understood. Advances in estrogen biology and endocrine physiology have provided insights into mechanistic links between the two systems. Estrogens are synthesized from androgens by aromatase which is widely distributed in extragonadal tissues. Local generation of estrogens raise the possibility of paracrine control as an additional level to classical endocrine regulation of the GH system. To explore the mechanistic links, we review the pharmacology of estrogen, the effects of estrogen replacement, antagonism, and the impact of aromatase inhibition on the GH system as well as the metabolic sequelae. In men, estrogens derived from androgens drive the central secretion of GH, independent of the androgen receptor. In hypogonadal women, physiological replacement via a parenteral route evokes no effect while estrogen receptor antagonism and estrogen deprivation induce disparate effects, providing no consistent evidence that estrogens regulate the central secretion of GH via paracrine or endocrine mechanisms. However, delivery of estrogen by the oral route inhibits hepatic IGF-1 production, in turn increasing GH secretion via reduced feedback inhibition. This endocrine route-dependent effect of oral estrogen compounds on hepatic function induces detrimental metabolic effects on hypogonadal women. In conclusion, estrogens regulate the secretion and action of GH via complex paracrine and endocrine interactions and impart metabolic effects in a route- and gender-dependent manner. The metabolic sequelae of compounds mimicking, antagonizing, or depleting estrogens, should be considered in tailoring and optimizing their use.Glucocorticoid receptor (GR) is a key homeostatic regulator involved in governing immune response, neuro-integration, metabolism and lung function. In conjunction with its pivotal role in human biology, GR action is critically linked to the pathology of various disease types, including cancer. While pharmacological activation of GR has been used for the treatment of various liquid cancers, its role in solid cancers is less clearly defined and seems to be cancer-type dependent. This review focuses on the molecular aspects of GR biology, spanning the structural and functional basis of response to glucocorticoids, as well as how this transcription factor operates in cancer, including the implications in disease development, progression and drug resistance.
To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging.

Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI.

Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group.

This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.
This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.The recent genomic characterization of patient specimens has started to reveal the landscape of somatic alterations in clinical prostate cancer (CaP) and its association with disease progression and treatment resistance. The extent to which such alterations impact hallmarks of cancer is still unclear. Here, we interrogate genomic data from thousands of clinical CaP specimens that reflect progression from treatment-naïve, to castration-recurrent, and in some cases, neuroendocrine CaP for alterations in cell cycle-associated and -regulated genes, which are central to cancer initiation and progression. We evaluate gene signatures previously curated to evaluate G1-S and G2-M phase transitions or to represent the cell cycle-dependent proteome. The resulting CaP (stage)-specific overview confirmed the presence of well-known driver alterations impacting, for instance, the genes encoding p53 and MYC, and uncovered novel previously unrecognized mutations that affect others such as the PKMYT1 and MTBP genes. The cancer dependency and drugability of representative genomically altered cell cycle determinants were verified also. Taken together, these analyses on hundreds of often less-characterized cell cycle regulators expand considerably the scope of genomic alterations associated with CaP cell proliferation and cell cycle and isolate such regulatory proteins as putative drivers of CaP treatment resistance and entirely novel therapeutic targets for CaP therapy.
Consensus in acknowledging compulsive buying-shopping disorder (CBSD) as a distinct diagnosis has been lacking. Before research in this area can be advanced, it is necessary to establish diagnostic criteria in order to facilitate field trials.

The study consisted of the following phases (1) operationalization of a broad range of potential diagnostic criteria for CBSD, (2) two iterative rounds of data collection using the Delphi method, where consensus of potential diagnostic criteria for CBSD was reached by an international expert panel, and (3) interpretation of findings taking into account the degree of certainty amongst experts regarding their responses.

With respect to diagnostic criteria, there was clear expert consensus about inclusion of the persistent and recurrent experience of (a) intrusive and/or irresistible urges and/or impulses and/or cravings and/or preoccupations for buying/shopping; (b) diminished control over buying/shopping; (c) excessive purchasing of items without utilizing them for their intended purposes, (d) use of buying-shopping to regulate internal states; (e) negative consequences and impairment in important areas of functioning due to buying/shopping; (f) emotional and cognitive symptoms upon cessation of excessive buying/shopping; and (g) maintenance or escalation of dysfunctional buying/shopping behaviors despite negative consequences. Furthermore, support was found for a specifier related to the presence of excessive hoarding of purchased items.

The proposed diagnostic criteria can be used as the basis for the development of diagnostic interviews and measures of CBSD severity.
The proposed diagnostic criteria can be used as the basis for the development of diagnostic interviews and measures of CBSD severity.
Social media use has become a ubiquitous part of society, with 3.8 billion users worldwide. While research has shown that there are positive aspects to social media engagement (e.g. feelings of social connectedness and wellbeing), much of the focus has been on the negative mental health outcomes which are associated with excessive use (e.g. higher levels of depression/anxiety). While the evidence to support such negative associations is mixed, there is a growing debate within the literature as to whether excessive levels of social media use should become a clinically defined addictive behaviour.

Here we assess whether one hallmark of addiction, the priority processing of addiction related stimuli known as an 'attentional bias', is evident in a group of social media users (N = 100). Using mock iPhone displays, we test whether social media stimuli preferentially capture users' attention and whether the level of bias can be predicted by platform use (self-report, objective smartphone usage data), and whether it is associated with scores on established measures of social media engagement (SMES) and social media 'addiction' severity scales (BSNAS, SMAQ).

Our findings do not provide support for a social media specific attentional bias. While there was a large range of individual differences in our measures of use, engagement, and 'addictive' severity, these were not predictive of, or associated with, individual differences in the magnitude of attentional capture by social media stimuli.

More research is required before social media use can be definitively placed within an addiction framework.
More research is required before social media use can be definitively placed within an addiction framework.
The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours.

This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent's Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. Enfortumab vedotin-ejfv The prognostic value of identifying 'higher-risk' histological subtypes was assessed.
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