Primary Hyperparathyroidism: The Influence of Bone Marrow Adipose Tissue on Bone Loss and of Osteocalcin on Insulin Resistance

OBJECTIVES: Bone marrow adipose tissue has been associated with low bone mineral density. However, no data exist regarding marrow adipose tissue in primary hyperparathyroidism, a disorder associated with bone loss in conditions of high bone turnover. The objective of the present study was to investigate the relationship between marrow adipose tissue, bone mass and parathyroid hormone. The influence of osteocalcin on the homeostasis model assessment of insulin resistance was also evaluated. METHODS: This was a cross-sectional study conducted at a university hospital, involving 18 patients with primary hyperparathyroidism (PHPT) and 21 controls (CG). Bone mass was assessed by dual-energy x-ray absorptiometry and marrow adipose tissue was assessed by 1H magnetic resonance spectroscopy. The biochemical evaluation included the determination of parathyroid hormone, osteocalcin, glucose and insulin levels. RESULTS: A negative association was found between the bone mass at the 1/3 radius and parathyroid hormone levels (r = -0.69;

Strategies to augment non-immune system based defence mechanisms against gastrointestinal diseases in pigs

AbstractOur study addresses the first two weeks of the weaning period of piglets during which stressful physiological and environmental conditions experienced by the animals can promote the proliferation of pathogens in the digestive tract. The aim of the study was to identify new feeding strategies that result in boosting the gastrointestinal tract (GIT) microbiota of piglets and improve growth performance, reducing the negative impact of weaning. In order to identify a new synbiotic combination, 12 new putative probiotic strains of Bifidobacterium spp. and three non-digestible oligosaccharides [NDO] were screened in newly weaned piglets. The ability to increase the level of autochthonous bifidobacteria and improve growth performance were assessed. Bifidobacteria strains with a similar ability to develop in the hindgut showed a different effect on piglet performance depending on the dose in which they were provided. Our data support the idea that the presence of fructo-oligosaccharides would stimulate the occurrence of bifidobacteria in the caecum. It was shown that dietary intake of nitrate can generate salivary nitrite, which in turn is acidified in the stomach and could have antimicrobial activity against swallowed pathogens. The efficacy of the resulting synbiotic formula was improved by adding nitrate as antimicrobial. To enhance probiotic survival during gastric transit, a novel technology of microencapsulation was developed and applied to bacteria. The final synbiotic, containing the strain RA 18 of Bifidobacterium animalis subsp. lactis [1011cfu/day], the prebiotic Actilight® [4% of the diet], and nitrate [150mg KNO3/kg feed/day] was tested in organic weaned piglets reared under field conditions. Results show that the strain Ra 18 had a probiotic effect in organic weaned piglets, as it colonized and remained detectable in faecal samples until two weeks after addition. The use of our synbiotic formula improved weight gain, feed efficiency and health status of the weaned piglets

General practitioners’ classification of patients with medically unexplained symptoms

In encounters between general practitioners (GPs) and patients with medically unexplained symptoms (MUS), the negotiation of the sick role is a social process. In this process, GPs not only use traditional biomedical diagnostic tools but also rely on their own opinions and evaluations of a patient’s particular circumstances in deciding whether that patient is legitimately sick. The doctor is thus a gatekeeper of legitimacy. This article presents results from a qualitative interview study conducted in Denmark with GPs concerning their approach to patients with MUS. We employ a symbolic interaction approach that pays special attention to the external validation of the sick role, making GPs’ accounts of such patients particularly relevant. One of the article’s main findings is that GPs’ criteria for judging the legitimacy of claims by those patients that present with MUS are influenced by the extent to which GPs are able to constitute these patients as people with social problems and problematic personality traits

A CHEOPS-enhanced view of the HD 3167 system

A. C. C. and T. G. W. acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1.Much remains to be understood about the nature of exoplanets smaller than Neptune, most of which have been discovered in compact multi-planet systems. With its inner ultra-short period planet b aligned with the star and two larger outer planets d-c on polar orbits, the multi-planet system HD 3167 features a peculiar architecture and offers the possibility to investigate both dynamical and atmospheric evolution processes. To this purpose we combined multiple datasets of transit photometry and radial velocimetry (RV) to revise the properties of the system and inform models of its planets. This effort was spearheaded by CHEOPS observations of HD 3167b, which appear inconsistent with a purely rocky composition despite its extreme irradiation. Overall the precision on the planetary orbital periods are improved by an order of magnitude, and the uncertainties on the densities of the transiting planets b and c are decreased by a factor of 3. Internal structure and atmospheric simulations draw a contrasting picture between HD 3167d, likely a rocky super-Earth that lost its atmosphere through photo-evaporation, and HD 3167c, a mini-Neptune that kept a substantial primordial gaseous envelope. We detect a fourth, more massive planet on a larger orbit, likely coplanar with HD 3167d-c. Dynamical simulations indeed show that the outer planetary system d-c-e was tilted, as a whole, early in the system history, when HD 3167b was still dominated by the star influence and maintained its aligned orbit. RV data and direct imaging rule out that the companion that could be responsible for the present-day architecture is still bound to the HD 3167 system. Similar global studies of multi-planet systems will tell how many share the peculiar properties of the HD 3167 system, which remains a target of choice for follow-up observations and simulations. © 2022 EDP Sciences. All rights reserved.Publisher PDFPeer reviewe

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability

Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal fring as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family signifcantly linked to 7q36. We identifed and validated a chromosomal inversion of ca. 4 Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identifed signifcantly more rare variants—nonsense, frameshift, and missense—in early-onset Alzheimer’s disease (EOAD, p value=0.03, OR=2.21 95% CI 1.05–4.82) and frontotemporal dementia (FTD, p=0.006, OR=2.59, 95% CI 1.28–5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel Kv4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p<0.001 and p<0.0001) leading to a loss of protein. Reduced DPP6 and/or Kv4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to caus

Universal DNA methylation age across mammalian tissues

DATA AVAILABILITY STATEMENT : The individual-level data from the Mammalian Methylation Consortium can be accessed from several online locations. All data from the Mammalian Methylation Consortium are posted on Gene Expression Omnibus (complete dataset, GSE223748). Subsets of the datasets can also be downloaded from accession numbers GSE174758, GSE184211, GSE184213, GSE184215, GSE184216, GSE184218, GSE184220, GSE184221, GSE184224, GSE190660, GSE190661, GSE190662, GSE190663, GSE190664, GSE174544, GSE190665, GSE174767, GSE184222, GSE184223, GSE174777, GSE174778, GSE173330, GSE164127, GSE147002, GSE147003, GSE147004, GSE223943 and GSE223944. Additional details can be found in Supplementary Note 2. The mammalian data can also be downloaded from the Clock Foundation webpage: https://clockfoundation.org/MammalianMethylationConsortium. The mammalian methylation array is available through the non-profit Epigenetic Clock Development Foundation (https://clockfoundation.org/). The manifest file of the mammalian array and genome annotations of CpG sites can be found on Zenodo (10.5281/zenodo.7574747). All other data supporting the findings of this study are available from the corresponding author upon reasonable request. The chip manifest files, genome annotations of CpG sites and the software code for universal pan-mammalian clocks can be found on GitHub95 at https://github.com/shorvath/MammalianMethylationConsortium/tree/v2.0.0. The individual R code for the universal pan-mammalian clocks, EWAS analysis and functional enrichment studies can be also found in the Supplementary Code.SUPPLEMENTARY MATERIAL 1 : Supplementary Tables 1–3 and Notes 1–6.SUPPLEMENTARY MATERIAL 2 : Reporting SummarySUPPLEMENTARY MATERIAL 3 : Supplementary Data 1–14.SUPPLEMENTARY MATERIAL 4 : Supplementary Code.Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.https://www.nature.com/nataginghj2024Zoology and EntomologySDG-15:Life on lan