Levo-thyroxine Replacement in Obese Adults: the Role of Metabolic Variables and Aging on Thyroid Testing Abnormalities.

CONTEXT: General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. OBJECTIVE: We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. SETTING: Tertiary care center. DESIGN: Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (4.2 mU/L). RESULTS: LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0.05). Compared with the euthyroid obese group, LT4 users showed higher adiposity, similar insulin resistance, but a healthier lipid profile. In multivariable analyses, LT4 dose was predicted by fat-free mass, hypothyroidism cause, and sex (P < 0.0001 to < 0.05). Risk of LT4 overreplacement increased with younger age (OR 0.96; 95% CI 0.94 to 0.99), higher LT4 dose (OR 2.98; 95% CI 1.44 to 6.14), and lower BMI (OR 0.93; 95% CI 0.88 to 0.99). Male sex increased the likelihood of LT4 underreplacement (OR 2.37; 95% CI 1.10 to 5.11). CONCLUSIONS: Obesity is associated with milder rates of inadequate LT4 treatment compared with nonobese populations. LT4 adequacy increases with aging. Age, body composition, and sex are main determinants of LT4 requirements in obesity. Copyright © 2019 Endocrine Society

Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging

mice are adaptive. mice.Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s) in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R

The Genome of Ganderma lucidum Provide Insights into Triterpense Biosynthesis and Wood Degradation

BACKGROUND: Ganoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: The genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi. CONCLUSIONS/SIGNIFICANCE: The genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy

Prader-Willi syndrome: A primer for clinicians

The advent of sensitive genetic testing modalities for the diagnosis of Prader-Willi syndrome has helped to define not only the phenotypic features of the syndrome associated with the various genotypes but also to anticipate clinical and psychological problems that occur at each stage during the life span. With advances in hormone replacement therapy, particularly growth hormone children born in circumstances where therapy is available are expected to have an improved quality of life as compared to those born prior to growth hormone

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Expression of ER-D5 and EGFr in laryngeal carcinoma and in pre-malignant epithelium

The expression of estrogen receptors was biochemically assessed in a series of 46 cases of consecutive laryngeal carcinomas. ER-D5 and EGFr were also immunohistochemically detected in 44 and 46 cases respectively. There was no correlation between the expression of these molecules and the typical anatomo-clinical prognostic parameters of laryngeal tumors. The concomitant expression of estrogen receptors, ER-D5 and EGFr was also investigated in normal, hyperplastic and dysplastic epithelium. An increasing expression of ER-D5 and EGFr from normal to hyperplastic and dysplastic epithelium was noted. These data suggest a possible role of hormone receptors in the laryngeal carcinogenesis

Immunohistochemial typing of spindle cells tumors of larynx: a single entity or distinct histotypes?

Lane originally described polypoid tumors of the upper aerodigestive tract, showing a pseudosarcomatous overgrowth and minimal foci of squamous cell carcinoma (SCC), and pursuing a relatively indolent clinical course. Subsequent studies questioned the separation of polypoid SCC with prominent stroma as a clinicopathologic entity distinct from other laryngeal spindle cell neoplasms and included polypoid squamous cell carcinoma in the heterogeneous group of the so-called spindle cell carcinomas. This study was aimed at morphologically and immunohistochemically characterizing a series of laryngeal tumors with spindle cell features to assess whether the identification of different subtypes is feasible and of clinical relevance. Polypoid squamous cell carcinomas (four cases) were characterized by a prominent spindle cell component, including myofibroblasts, which expressed vimentin and, focally, smooth-muscle actin but not epithelial antigens, associated with minimally invasive SCC. These features reliably allowed distinction of polypoid SCC from spindle cell carcinoma (eight cases) and fibro- and leiomyosarcoma (one case each), whereas widely invasive SCCs with prominent stroma (five cases) shared some morphologic and immunophenotypic features with polypoid squamous cell carcinoma. In view of the distinctive histologic and immunohistochemical features of the tumors with spindle cell component reported herein and of the still unsettled prognosis of these tumors, we suggest keeping them as separate entities. In our opinion, this separation is justified by the apparently different prognosis of distinct histotypes

Cathepsin D in laryngeal carcinoma: preliminary report

The biological activity of tumor cells seems to be related to some peptides produced in the same neoplastic cytoplasms. Cathepsin D is considered one of these proteins, which is able to promote mitosis and tumor invasion. The effects of cathepsin D have been studied in tumors of the breast, ovary and endometrium, and in few cases of laryngeal cancer. Using an immunohistochemical method, we have attempted to evaluate cathepsin D expression in 17 cases of laryngeal squamous cell carcinoma in comparison with the presence of the same protein in the adjacent normal laryngeal mucosa and in inflammatory cells surrounding the tumor. In 11 cases, cathepsin D was present in more than 50% of neoplastic cells, in 4 cases positive cells were 30-50% of all neoplastic cells, in the last 2 cases less than 30% of neoplastic cells expressed the antigen. In normal respiratory epithelium the expression of cathepsin D was limited to the apex of cells. In flat metaplastic epithelium, we observed a positive reaction of basal and parabasal cells. Such positivity became diffuse to all cellular layers in dysplastic foci. A minimal positivity was also detected in salivary glands and ducts. A strong positivity was present in macrophages around and among tumor cells. Our findings suggest that cathepsin D plays a role in cancerogenesis and growth of laryngeal squamous cell carcinoma. The expression of cathepsin D also in normal and inflammatory cells may influence the quantitation of this antigen in studies in which cytosolic levels of cathepsin D are measured after protein extraction