Pregnancy Outcome in Women With APECED (APS-1) : A Multicenter Study on 43 Females With 83 Pregnancies

Context: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also known as autoimmune polyendocrine syndrome type 1) has a severe, unpredictable course. Autoimmunity and disease components may affect fertility and predispose to maternal and fetal complications, but pregnancy outcomes remain unknown. Objective: To assess fetal and maternal outcomes and course of clinical APECED manifestations during pregnancy in women with APECED. Design and Setting: A multicenter registry-based study including 5 national patient cohorts. Patients: 321 females with APECED. Main Outcome Measure: Number of pregnancies, miscarriages, and deliveries. Results: Forty-three patients had altogether 83 pregnancies at median age of 27 years (range, 17-39). Sixty (72%) pregnancies led to a delivery, including 2 stillbirths (2.4%) and 5 (6.0%) preterm livebirths. Miscarriages, induced abortions, and ectopic pregnancies were observed in 14 (17%), 8 (10%), and 1 (1.2%) pregnancies, respectively. Ovum donation resulted in 5 (6.0%) pregnancies. High maternal age, premature ovarian insufficiency, primary adrenal insufficiency, or hypoparathyroidism did not associate with miscarriages. Women with livebirth had, on average, 4 APECED manifestations (range 0-10); 78% had hypoparathyroidism, and 36% had primary adrenal insufficiency. APECED manifestations remained mostly stable during pregnancy, but in 1 case, development of primary adrenal insufficiency led to adrenal crisis and stillbirth. Birth weights were normal in >80% and apart from 1 neonatal death of a preterm baby, no serious perinatal complications occurred. Conclusions. Outcome of pregnancy in women with APECED was generally favorable. However, APECED warrants careful maternal multidisciplinary follow-up from preconceptual care until puerperium.Peer reviewe

Menstrual function and mental health of medical students during the COVID-19 pandemic: a continuous cross-sectional study

Aim. To assess the impact of new coronavirus infection (NCI) and COVID-19 vaccination on menstrual function in comparison with the frequency of depressive disorders during the COVID-19 pandemic among female students of a medical university. Materials and methods. Data for a continuous transverse (cross-sectional) study were obtained using an online survey. The questions included demographics, characteristics of menstrual function, the history of COVID-19 and vaccinations against it, and the standard CES-D (Center for Epidemiologic Studies Depression Scale) questionnaire. The survey included 1.879 female medical students. The exclusion criteria were age under 18 and over 25 years, hormonal contraceptives, pregnancy, childbirth during the last year, and vaccination after COVID-19. After applying the exclusion criteria, three study groups were formed. Group 1 included female students with a history of NCI (n=140), group 2 included students with no history of NCI, who were initially vaccinated against COVID-19 (n=647), group 3 (control group) included unvaccinated students with no history of NCI (n=55). Results. There were no differences in the prevalence of changes in menstrual function in female students after the NCI (49.3%) and after COVID-19 vaccination (39.6%) compared to the control group (43.6%); p=0.477. The rate of depression in the overall study cohort was 43.3%, without any significant differences between the study groups. Significant predictors of changes in menstrual function during the pandemic were marriage (odds ratio OR 2.33 [1.513.61]), depression (OR 1.72 [1.282.3]), a history of menstrual dysfunction (OR 1.5 [0.121.99]), and later menarche (OR 1.76 [1.023.04]). Multivariate analysis did not show the significance of the history of NCI and vaccination as factors of menstrual dysfunction (OR 1.61 [0.892.90] and OR 0.91 [0.591.41], respectively). Conclusion. During the COVID-19 pandemic, female medical students reported frequent changes in menstrual function and depressive disorders. During the pandemic, the most significant predictors of menstrual disorders in female students were depression, a history of menstrual dysfunction, and marriage. A multicenter prospective study is necessary to clarify the mechanisms of the pandemic's impact on menstrual function

Fabrication of near-zero thermal expansion of fully dense beta-eucryptite ceramics by microwave sintering

Microwave heating is proposed as non-conventional technique for the sintering of optimal lithium aluminosilicate compositions of β-eucryptite system. The coefficient of thermal expansion and mechanical properties of the sintered samples has been studied under the influence of microwave heating. The ad hoc synthesized β-eucryptite together with the microwave sintering technique developed in this work open the opportunity to produce breakthrough materials with low or negative coefficient of thermal expansion and excellent mechanical properties, as a Young s modulus of 110 GPa. The combination of rapid heating with low energy applied by the microwave technology (eco-friendly process) and the dramatic reduction in cycle time allows densification without glass phase formation. Results of the coefficient of thermal expansion of the β-eucryptite ceramics presented here under cryogenic conditions will be of value, for example, in the future design of new composite materials for space applicationsThe authors would like to thank Dr. Emilio Rayon for performing the nanoindentation analysis in the Materials Technology institute (ITM) of the Polytechnic University of Valencia (UPV) and your financial support received of UPV under Projects SP20120621 and SP20120677 and Spanish Government through the Project MONIDIEL (TEC2008-04109). A. Borrell, acknowledges the Spanish Ministry of Science and Innovation for a Juan de la Cierva contract (JCI-2011-10498) and SCSIE of the University of Valencia.Benavente Martínez, R.; Borrell Tomás, MA.; Salvador Moya, MD.; Garcia-Moreno, O.; Penaranda-Foix, FL.; Catalá Civera, JM. (2014). Fabrication of near-zero thermal expansion of fully dense beta-eucryptite ceramics by microwave sintering. Ceramics International. 40(1):935-941. https://doi.org/10.1016/j.ceramint.2013.06.089S93594140

Stretching Actin Filaments within Cells Enhances their Affinity for the Myosin II Motor Domain

To test the hypothesis that the myosin II motor domain (S1) preferentially binds to specific subsets of actin filaments in vivo, we expressed GFP-fused S1 with mutations that enhanced its affinity for actin in Dictyostelium cells. Consistent with the hypothesis, the GFP-S1 mutants were localized along specific portions of the cell cortex. Comparison with rhodamine-phalloidin staining in fixed cells demonstrated that the GFP-S1 probes preferentially bound to actin filaments in the rear cortex and cleavage furrows, where actin filaments are stretched by interaction with endogenous myosin II filaments. The GFP-S1 probes were similarly enriched in the cortex stretched passively by traction forces in the absence of myosin II or by external forces using a microcapillary. The preferential binding of GFP-S1 mutants to stretched actin filaments did not depend on cortexillin I or PTEN, two proteins previously implicated in the recruitment of myosin II filaments to stretched cortex. These results suggested that it is the stretching of the actin filaments itself that increases their affinity for the myosin II motor domain. In contrast, the GFP-fused myosin I motor domain did not localize to stretched actin filaments, which suggests different preferences of the motor domains for different structures of actin filaments play a role in distinct intracellular localizations of myosin I and II. We propose a scheme in which the stretching of actin filaments, the preferential binding of myosin II filaments to stretched actin filaments, and myosin II-dependent contraction form a positive feedback loop that contributes to the stabilization of cell polarity and to the responsiveness of the cells to external mechanical stimuli

Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.publishedVersio

BAMBI Regulates Angiogenesis and Endothelial Homeostasis through Modulation of Alternative TGFβ Signaling

BACKGROUND: BAMBI is a type I TGFβ receptor antagonist, whose in vivo function remains unclear, as BAMBI(-/-) mice lack an obvious phenotype. METHODOLOGY/PRINCIPAL FINDINGS: Identifying BAMBI's functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI(-/-) mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over-expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFβ. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI(-/-) compared to BAMBI(+/+) mice consistent with an endothelial phenotype for BAMBI(-/-) mice. BAMBI's mechanism of action in endothelial cells was examined by canonical and alternative TGFβ signaling in HUVEC with over-expression or knock-down of BAMBI. BAMBI knockdown enhanced basal and TGFβ stimulated SMAD1/5 and ERK1/2 phosphorylation, while over-expression prevented both. CONCLUSIONS/SIGNIFICANCE: Thus we provide a first description of a vascular phenotype for BAMBI(-/-) mice, and provide in vitro and in vivo evidence that BAMBI contributes to endothelial and vascular homeostasis. Further, we demonstrate that in endothelial cells BAMBI interferes with alternative TGFβ signaling, most likely through the ALK 1 receptor, which may explain the phenotype observed in BAMBI(-/-) mice. This newly described role for BAMBI in regulating endothelial function has potential implications for understanding and treating vascular disease and tumor neo-angiogenesis

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.: This work was supported by the British Heart Foundation (BHF; Grants NH/11/1/28922, G1000847, FS/13/29/30024 and FS/18/46/33663), Oxford-Cambridge Centre for Regenerative Medicine (RM/13/3/30159), the UK Medical Research Council (MRC) and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre funding (SS), as well as National Institutes of Health Grants P01HL094374, P01GM081619, R01HL12836 and a grant from the Fondation Leducq Transatlantic Network of Excellence (CEM). J.B. was supported by a Cambridge National Institute for Health Research Biomedical Research Centre Cardiovascular Clinical Research Fellowship and subsequently, by a BHF Studentship (Grant FS/13/65/30441). DI received a University of Cambridge Commonwealth Scholarship. LG is supported by BHF Award RM/l3/3/30159 and LPO is funded by a Wellcome Trust Fellowship (203568/Z/16/Z). NF was supported by BHF grants RG/13/14/30314. NL was supported by the Biotechnology and Biological Sciences Research Council (Institute Strategic Programmes BBS/E/B/000C0419 and BBS/E/B/000C0434). SS and MB were supported by the British Heart Foundation Centre for Cardiovascular Research Excellence. Core support was provided by the Wellcome-MRC Cambridge Stem Cell Institute (203151/Z/16/Z), The authors thank Osiris for provision of the primary mesenchymal stem cells (59

Evaluation of Methods for Obtaining Rendered Animal Fats

The increase of functional food production makes the search for new non-traditional raw materials and the selection of methods for their processing relevant. Methods for obtaining biologically active substances of a lipid nature from valuable raw materials extracted from hunting animals (bear, badger, marmot and beaver) are of particular interest. The purpose of this review is to analyze the existing methods of obtaining rendered fat from raw fat and evaluate them. The objects of analysis were the data of scientific articles, patents and studies on the extraction of the lipid fraction from raw materials of animal origin from 2017 to 2021. In the work, various methods for extracting fats were considered. Their systematization, analyze, and description were carried out, indicating the advantages and disadvantages. The considered methods for extracting lipid components can be used in the process of rendering fat from non-traditional raw materials of animal origin. When using the dry rendering method, the heating of adipose tissue is carried out by the conductive method, which leads to oxidative processes and a decrease in the quality of the finished product. The wet rendering method is carried out by interacting raw fat with a heating agent – water or live steam, which, by varying the temperature and duration of exposure, allows to preserve the properties and quality of the product. Wet rendering methods are the most effective. These methods allow to obtain a high-quality finished product, as well as to produce the maximum yield of valuable lipid components of raw materials. To accelerate the technological process with the wet method of exposure, it is possible to use a biocatalytic method. The results of the research can be used in the development of schemes for obtaining biologically active substances of a lipid nature from valuable expensive raw materials extracted from hunting animals

Prospects for Derivatives of Game Animals

Game animals are a source of biologically active substances that requires a strict resource and biodiversity control. The research objective was to analyze three years of supply, demand, export, and import for brown bear, deer, and musk deer by-products. The review featured Russian and foreign articles on game animals published in 2016–2020, as well as customs information on imports and exports for this raw material. The research methods included systematization, analysis, and description. The population of brown bears in the Russian Federation is constantly growing. In 2018, it increased by 4% compared to 2017. Bear derivatives are in high demand in China, Italy, France, etc. The total number of importers in 2019 exceeded 25. In 2017, deer products were the most popular game derivatives exported from Russia to 35 countries. The biggest importer is China. In 2018, the volume of exports of deer and musk deer derivatives maintained the same value, but the list of importers changed. In 2019, the export volume increased by 1.4 times, and the number of importing countries reached 50. Russia is the leading exporter and importer of raw materials and derivatives from brown bears, deer, and musk deer. The market for game derivatives is actively developing. An increase in the number of predatory game animals, e.g., the brown bear, may adversely affect the local ecosystems, which can be prevented by licensed hunting. The high content of biologically active substances makes it possible to use game raw materials for new functional products