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The calculation of the electrical charge transport properties of alkanes C n H 2n S 2 with (n = 4-11) was performed to understand the odd-even effect on its current-voltage response. The extended molecule and broadband limit models were used to describe the molecular junction and covalent coupling with the electrodes. It was shown that among the participating molecular orbitals, HOMO and HOMO-1 are the ones with the most charge transport contribution. Moreover, the odd-even effect is caused by the alternation of the eigenvalues of some frontier orbitals as a function of the number of carbons, especially the HOMO that dominates the electrical transport. It could also be noted that when the current is analyzed outside the resonance, the relationship with the number of carbons exponentially decays, confirming the reports in the literature. To the best of our knowledge, a first principle study of the odd-even effect in symmetric systems composed by linear saturated carbon chains covalently coupled to electrodes has not been reported yet.
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BACKGROUND: Bioprosthetic surgical mitral valve replacement (SMVR) remains an important treatment option in the era of transcatheter valve interventions. We present 10-year clinical outcomes of Medicare beneficiaries undergoing SMVR with a contemporary low-profile mitral porcine valve. METHODS: This is a single-arm observational study using Medicare fee-for-service claims data. De-identified patients undergoing SMVR with the Epic™ Mitral valve (Abbott, Minnesota, USA) in the United States between 1/1/2008-12/31/2019 were selected by ICD-9/10 procedure codes and then linked to a manufacturer device tracking database. All-cause mortality, heart failure (HF) re-hospitalization, and mitral valve reintervention (surgical or transcatheter valve-in-valve) were evaluated at 10-years using the Kaplan Meier method. RESULTS: Among 75,739 Medicare beneficiaries undergoing SMVR during the study period, 14,015 were implanted with the Epic™ Mitral valve, of which 76.5% (10,720) had underlying HF. Mean age was 74±8 years. Survival at 10-years in patients without preoperative HF was 40.4% (95% CI 37.4%-43.4%) compared to 25.4% (95% CI 23.8%-27.0%) for patients with HF (p < 0.001). The 10-year freedom from HF rehospitalization was 51.3% (95% CI 49.4%-53.1%). Freedom from mitral valve reintervention was 91.4% (95% CI 89.7%-92.7%) at 10 years. CONCLUSIONS: This real-world nationwide study of Medicare beneficiaries receiving the Epic™ Mitral valve demonstrates >90% freedom from all-cause valve reintervention and >50% freedom from HF rehospitalization at 10-years post-implant. Long-term survival and HF rehospitalization in this population with mitral valve disease undergoing SMVR was found to be impacted by underlying HF.
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Fibrous dysplasia (FD) is a mosaic non-inheritable genetic disorder of the skeleton in which normal bone is replaced by structurally unsound fibro-osseous tissue. There is no curative treatment for FD, partly because its pathophysiology is not yet fully known. We present a simple mathematical model of the disease incorporating its basic known biology, to gain insight on the dynamics of the involved bone-cell populations, and shed light on its pathophysiology. We develop an analytical study of the model and study its basic properties. The existence and stability of steady states are studied, an analysis of sensitivity on the model parameters is done, and different numerical simulations provide findings in agreement with the analytical results. We discuss the model dynamics match with known facts on the disease, and how some open questions could be addressed using the model.
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Simulación por Computador , Displasia Fibrosa Ósea , Conceptos Matemáticos , Modelos Biológicos , Mutación , Humanos , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/patología , Osteoblastos/patologíaRESUMEN
Background: Nutritional recommendations for patients with type 2 diabetes mellitus (T2DM) and hypertension assume high food security. However, food insecurity is estimated to affect 10% of the US population and more so patients at our student-run free clinic (SRFC). The aims of the study were to (1) assess food security in patients with a diagnosis of T2DM, hypertension, or both and (2) examine the relationship between food security and glycated hemoglobin (HbA1C) or blood pressure at an SRFC. Methods: Eligible participants completed a 10-item food security questionnaire and an item addressing perceived barriers. Most recent HbA1C and blood pressure measurements were gathered. Comparisons were made using univariate or multivariate linear regression analysis. Results: Results from 79 participants showed that 25.3% experienced high food security, 29.1% had marginal food security, 13.9% had low food security, and 30.4% had very low food security. No statistically significant association was found between food security category and HbA1C or blood pressure. However, we did find that approximately 73% of patients experienced some degree of food insecurity. Conclusions: Patients at our SRFC are ethnically and racially diverse, most have a high school education or less, and most have food insecurity. No association between food security category and HbA1C or blood pressure control was found. Providers should consider the degree of food insecurity and incorporate a culturally sensitive approach when making nutritional recommendations.
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BACKGROUND: Maternal obesity (MO) has been shown to adversely affect metabolic, oxidative, reproductive, and cognitive function in offspring. However, it is unclear whether lifestyle modification can ameliorate the metabolic and organ dysfunction programmed by MO and prevent the effects of metabolic syndrome in adulthood. This study aimed to evaluate whether moderate voluntary exercise in the offspring of rats born to obese mothers can ameliorate the adverse effects of MO programming on metabolism and liver function in mid-adulthood. METHODS: Offspring of control (CF1) and MOF1 mothers were fed with a control diet from weaning. Adult males and females participated in 15 min exercise sessions five days/week. Metabolic parameters were analyzed before and after the exercise intervention. Liver oxidative stress biomarkers and antioxidant enzymes were analyzed before and after the intervention. RESULTS: Males showed that CF1ex ran more than MOF1ex and increased the distance covered. In contrast, females in both groups ran similar distances and remained constant but ran more distance than males. At PND 300 and 450, male and female MOF1 had higher leptin, triglycerides, insulin, and HOMA-IR levels than CF1. However, male MOF1ex had lower triglycerides, insulin, and HOMA-IR levels than MOF1. Improvements in liver fat and antioxidant enzymes were observed in CF1ex and MOF1ex males and females compared to their respective CF1 and MOF1 groups. CONCLUSION: These findings suggest that moderate voluntary exercise, even when started in mid-adulthood, can improve metabolic outcomes and delay accelerated metabolic aging in MO-programmed rats in a sex-dependent manner.
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Envejecimiento , Obesidad Materna , Condicionamiento Físico Animal , Animales , Femenino , Masculino , Ratas , Embarazo , Envejecimiento/metabolismo , Obesidad Materna/metabolismo , Estrés Oxidativo , Ratas Wistar , Hígado/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Obesidad/metabolismo , Obesidad/terapia , Obesidad/fisiopatologíaRESUMEN
Cognitive neuroscience has considerable untapped potential to translate our understanding of brain function into applications that maintain, restore, or enhance human cognition. Complex, real-world phenomena encountered in daily life, professional contexts, and in the arts, can also be a rich source of information for better understanding cognition, which in turn can lead to advances in knowledge and health outcomes. Interdisciplinary work is needed for these bi-directional benefits to be realized. Our cognitive neuroscience team has been collaborating on several interdisciplinary projects: hardware and software development for brain stimulation, measuring human operator state in safety-critical robotics environments, and exploring emotional regulation in actors who perform traumatic narratives. Our approach is to study research questions of mutual interest in the contexts of domain-specific applications, using (and sometimes improving) the experimental tools and techniques of cognitive neuroscience. These interdisciplinary attempts are described as case studies in the present work to illustrate non-trivial challenges that come from working across traditional disciplinary boundaries. We reflect on how obstacles to interdisciplinary work can be overcome, with the goals of enriching our understanding of human cognition and amplifying the positive effects cognitive neuroscientists have on society and innovation.
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Neurociencia Cognitiva , Humanos , Investigación Interdisciplinaria , Encéfalo/fisiología , Cognición/fisiología , NeurocienciasRESUMEN
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.
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Displasia Fibrosa Ósea , Células Madre Mesenquimatosas , Transcriptoma , Humanos , Animales , Células Madre Mesenquimatosas/metabolismo , Transcriptoma/genética , Ratones , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/metabolismo , Displasia Fibrosa Ósea/patología , Masculino , Femenino , Citocinas/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Adulto , Persona de Mediana EdadRESUMEN
Background: There is inconclusive evidence regarding the role of irritable bowel syndrome (IBS) in the development of erectile dysfunction (ED), especially among medical students due to high academic stress. Aim: To determine the association between IBS and ED in medical students from a Peruvian university in 2022. Methods: An analytical cross-sectional study was conducted with secondary data analysis on 133 medical students from a university in northern Peru during the 2021-II academic semester. The dependent variable was ED as measured with the 5-item International Index of Erectile Function, and the exposure variable was IBS as assessed with the Rome IV-Bristol questionnaire. Outcomes: The results were the prevalence rates of IBS and ED and the association of these variables. Results: Of the 133 medical students surveyed, the median age was 22 years (IQR, 19-24). The median score on the 5-item International Index of Erectile Function was 21 (IQR, 10-24). The prevalence of ED was 38.4% (95% CI, 30.05%-47.17%). Among the medical students 3% and 9% displayed moderate and severe ED, respectively, and 24.8%, 13.5%, and 24.1% showed moderate depressive, anxious, and severe symptoms. An overall 10.5% had IBS. Medical students with IBS had a 108% higher prevalence of ED than those without the syndrome (prevalence ratio, 2.08; 95% CI, 1.06-4.06). Other confounding variables were not significantly associated (P > .05). Clinical Implications: The results underline the importance of comprehensive sexual and mental health assessment, with an emphasis on the relationship between IBS and ED in medical students. Strengths and Limitations: Strengths include the use of validated and reliable instruments and rigorous biostatistical methods, and this is the first Peruvian investigation to explain the association between IBS and ED in medical students. Limitations include the cross-sectional design and nonprobability sampling, and there may be bias in applying the instruments. Conclusion: This study reveals a significant association between IBS and a higher prevalence of ED in these students.
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Horizontal gene transfer (HGT) is a well-documented strategy used by bacteria to enhance their adaptability to challenging environmental conditions. Through HGT, a group of conserved genetic elements known as mobile genetic elements (MGEs) is disseminated within bacterial communities. MGEs offer numerous advantages to the host, increasing its fitness by acquiring new functions that help bacteria contend with adverse conditions, including exposure to heavy metal and antibiotics. This study explores MGEs within microbial communities along the Yucatan coast using a metatranscriptomics approach. Prior to this research, nothing was known about the coastal Yucatan's microbial environmental mobilome and HGT processes between these bacterial communities. This study reveals a positive correlation between MGEs and antibiotic resistance genes (ARGs) along the Yucatan coast, with higher MGEs abundance in more contaminated sites. The Proteobacteria and Firmicutes groups exhibited the highest number of MGEs. It's important to highlight that the most abundant classes of MGEs might not be the ones most strongly linked to ARGs, as observed for the recombination/repair class. This work presents the first geographical distribution of the environmental mobilome in Yucatan Peninsula mangroves.
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Transferencia de Gen Horizontal , Secuencias Repetitivas Esparcidas , Microbiota , Secuencias Repetitivas Esparcidas/genética , Microbiota/genética , México , Bacterias/genética , Bacterias/clasificación , Proteobacteria/genéticaRESUMEN
Patients with chronic kidney disease (CKD), especially those on dialysis or who have received a kidney transplant (KT), are considered more vulnerable to severe COVID-19. This susceptibility is attributed to advanced age, a higher frequency of comorbidities, and the chronic immunosuppressed state, which may exacerbate their susceptibility to severe outcomes. Therefore, our study aimed to compare the clinical characteristics and outcomes of COVID-19 in KT patients with those on chronic dialysis and non-CKD patients in a propensity score-matched cohort study. This multicentric retrospective cohort included adult COVID-19 laboratory-confirmed patients admitted from March/2020 to July/2022, from 43 Brazilian hospitals. The primary outcome was in-hospital mortality. Propensity score analysis matched KT recipients with controls - patients on chronic dialysis and those without CKD (within 0.25 standard deviations of the logit of the propensity score) - according to age, sex, number of comorbidities, and admission year. This study included 555 patients: 163 KT, 146 on chronic dialysis, and 249 non-CKD patients (median age 57 years, 55.2% women). With regards to clinical outcomes, chronic dialysis patients had a higher prevalence of acute heart failure, compared to KT recipients, furthermore, both groups presented high in-hospital mortality, 34.0 and 28.1%, for KT and chronic dialysis patients, respectively. When comparing KT and non-CKD patients, the first group had a higher incidence of in-hospital dialysis (26.4% vs. 8.8%, p < 0.001), septic shock (24.1% vs. 12.0%, p = 0.002), and mortality (32.5% vs. 23.3%, p = 0.039), in addition to longer time spent in the intensive care unit (ICU). In this study, chronic dialysis patients presented a higher prevalence of acute heart failure, compared to KT recipients, whereas KT patients had a higher frequency of complications than those without CKD, including septic shock, dialysis during hospitalization, and in-hospital mortality as well as longer time spent in the ICU.
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This study aimed to contribute to the development of an embryo-test using the gastropod Lymnaea stagnalis, identified by the Organization for Economic Co-operation and Development (OECD) as a potential invertebrate test animal model. Together with the Potamopyrgus antipodarum, were the first mollusc models to be included in the organization testing guidelines. The focus was on validating an embryo toxicity test to cover the sensitive embryogenesis phase and on obtaining testing information on all of the model life cycle stages, contributing to close an identified gap within this context. Adhering to OECD guidelines, namely the L. stagnalis reproductive test, the study examined mortality rates, abnormality rates, development, growth, hatching rates, hearth rates, and pre-testing media suitability, during the embryogenesis, and the obtained dataset made available for further studies. Cadmium was chosen as the positive test compound due to its well-studied nature and the model's proven sensitivity to the compound, working as a reference compound for the test development. The data were collected in two 12-day assays under consistent conditions, each using 144 L. stagnalis embryos (<24 h old) from 6 egg masses (288 embryos total). Six 48-well microplates were utilized per assay, accommodating five different cadmium concentrations (32, 70, 155, 341, 750 µg/L) and a control group. Recorded parameters encompassed developmental stage, embryo position within the chorion, developmental abnormalities, hatchings, and mortality. Data analysis involved classifying embryos based on developmental stage and position, taking an exploratory approach to define the relevance of the different parameters in the compound hazard assessment during the embryogenesis. Measurements considered embryo area, perimeter, length, height, width, interocular distance, and heart rate. This dataset does not provide treated information but the raw data obtained during the proposed metodological development and toxicity testing process. The purpose of this article is to make the obtained raw data available, clearly defining the acquisition methodology to provide a comparison basis for future or existent works within this context.
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Graphene doped with different transition metals has been recently proposed to adsorb CO2 and help reduce the greenhouse effect. Iron-doped graphene is one of the most promising candidates for this task, but there is still a lack of full understanding of the adsorption mechanism. In this work, we analyze the electronic structure, geometry, and charge redistribution during adsorption of CO2 molecules by single vacancy iron-doped graphene by DFT calculations using the general gradient approximation of Perdew, Burke, and Ernzernhof functional (PBE) and the van der Waals density functional (vdW). To understand the impact of the pyridinic-N coordination of the iron atom, we gradually replaced the neighboring carbon atoms by nitrogen atoms. The analysis indicates that chemisorption and physisorption occur when the molecule is adsorbed in the side-on and end-on orientation, respectively. Adsorption is stronger when pyridinic-N coordination increases, and the vdW functional describes the chemical interactions and adsorption energy differently in relation to PBE without significant structural changes. The development of the chemical interactions with the change of coordination in the system is further investigated in this work with crystal overlap Hamilton population (COHP) analysis.
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Motivated by the implementation of a SARS-Cov-2 sewer surveillance system in Chile during the COVID-19 pandemic, we propose a set of mathematical and algorithmic tools that aim to identify the location of an outbreak under uncertainty in the network structure. Given an upper bound on the number of samples we can take on any given day, our framework allows us to detect an unknown infected node by adaptively sampling different network nodes on different days. Crucially, despite the uncertainty of the network, the method allows univocal detection of the infected node, albeit at an extra cost in time. This framework relies on a specific and well-chosen strategy that defines new nodes to test sequentially, with a heuristic that balances the granularity of the information obtained from the samples. We extensively tested our model in real and synthetic networks, showing that the uncertainty of the underlying graph only incurs a limited increase in the number of iterations, indicating that the methodology is applicable in practice.
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COVID-19 , Pandemias , Humanos , Incertidumbre , COVID-19/epidemiología , Brotes de Enfermedades , SARS-CoV-2RESUMEN
Bone histomorphometry is a well-established approach to assessing skeletal pathology, providing a standard evaluation of the cellular components, architecture, mineralization, and growth of bone tissue. However, it depends in part on the subjective interpretation of cellular morphology by an expert, which introduces bias. In addition, diseases like osteogenesis imperfecta (OI) and fibrous dysplasia are accompanied by changes in the morphology and function of skeletal tissue and cells, hindering consistent evaluation of some morphometric parameters and interpretation of the results. For instance, traditional histomorphometry combined with collagen turnover markers suggested that reduced bone formation in classical OI is accompanied by increased bone resorption. In contrast, the well-documented postpubertal reduction in fractures would be easier to explain by reduced bone resorption after puberty, highlighting the need for less ambiguous measurements. Here we propose an approach to histomorphometry based on in situ mRNA hybridization, which uses Col1a1 as osteoblast and Ctsk as osteoclast markers. This approach can be fully automated and eliminates subjective identification of bone surface cells. We validate these markers based on the expression of Bglap, Ibsp, and Acp5. Comparison with traditional histological and tartrate-resistant acid phosphatase staining of the same sections suggests that mRNA-based analysis is more reliable. Unlike inconclusive traditional histomorphometry of mice with α2(I)-Gly610 to Cys substitution in the collagen triple helix, mRNA-based measurements reveal reduced osteoclastogenesis in 11-wk-old animals consistent with the postpubertal catch-up osteogenesis observed by microCT. We optimize the technique for cryosections of mineralized bone and sections of paraffin-embedded decalcified tissue, simplifying and broadening its applications. We illustrate the application of the mRNA-based approach to human samples using the example of a McCune-Albright syndrome patient. By eliminating confounding effects of altered cellular morphology and the need for subjective morphological evaluation, this approach may provide a more reproducible and accessible evaluation of bone pathology.
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Huesos , Colágeno Tipo I , Modelos Animales de Enfermedad , Osteogénesis Imperfecta , Osteogénesis Imperfecta/patología , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/genética , Animales , Ratones , Huesos/patología , Huesos/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , ARN Mensajero/metabolismo , ARN Mensajero/genética , Osteoclastos/metabolismo , Osteoclastos/patología , Pubertad , Osteoblastos/metabolismo , Osteoblastos/patología , Biomarcadores/metabolismo , OsteogénesisRESUMEN
Maternal obesity predisposes offspring (F1) to cardiovascular disease. To evaluate basal heart function and ischemia-reperfusion (IR) responses in F1 males and females of obese mothers, female Wistar rats (F0) were fed chow or an obesogenic (MO) diet from weaning through pregnancy and lactation. Non-sibling F1 males and females were weaned to chow at postnatal day (PND) 21 and euthanized at PND 550. Offspring of MO mothers (MOF1) rarely survive beyond PND 650. Hearts were immediately isolated from euthanized F1s and subjected to 30 min ischemia with 20 min reperfusion. Retroperitoneal fat, serum triglycerides, glucose, insulin, and insulin resistance were measured. Baseline left ventricular developed pressure (LVDP) was lower in male and female MOF1 than in controls. After global ischemia, LVDP in control (C) male and female F1 recovered 78 and 83%, respectively, while recovery in MO male and female F1 was significantly lower at 28 and 52%, respectively. Following the IR challenge, MO hearts showed a higher functional susceptibility to reperfusion injury, resulting in lower cardiac reserve than controls in both sexes. Female hearts were more resistant to IR. Retroperitoneal fat was increased in male MOF1 vs. CF1. Circulating triglycerides and insulin resistance were increased in male and female MOF1 vs. CF1. These data show that MO programming reduces F1 cardiac reserve associated with age-related insulin resistance in a sex-specific manner.
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Resistencia a la Insulina , Efectos Tardíos de la Exposición Prenatal , Humanos , Ratas , Femenino , Embarazo , Masculino , Animales , Anciano , Resistencia a la Insulina/fisiología , Ratas Wistar , Obesidad , Insulina , Triglicéridos , Dieta Alta en Grasa , Isquemia , ReperfusiónRESUMEN
O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D-binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system.
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Huesos , Homeostasis , Polipéptido N-Acetilgalactosaminiltransferasa , Vitamina D , Animales , Masculino , Ratones , Huesos/anatomía & histología , Huesos/química , Huesos/metabolismo , Calcio/metabolismo , Glicosilación , Homeostasis/genética , Hormona Paratiroidea/metabolismo , Vitamina D/metabolismo , Vitamina D/análogos & derivados , Proteína de Unión a Vitamina D/metabolismoRESUMEN
Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre- and post-treatment in a phase 2 clinical trial of denosumab (NCT03571191) and in murine in vivo and ex vivo preclinical models. Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation, reduced cellularity, and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition. RNA sequencing of human and mouse tissue supported these findings. The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model, which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts. The results from this study demonstrated that, in addition to its expected antiosteoclastic effect, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions. These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.TRIAL REGISTRATION: ClinicalTrials.gov NCT03571191.
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Denosumab , Displasia Fibrosa Ósea , Animales , Humanos , Ratones , Denosumab/farmacología , Displasia Fibrosa Ósea/tratamiento farmacológico , Ligandos , Osteoblastos/metabolismo , Osteogénesis/genéticaRESUMEN
BACKGROUND: Surveys have been used worldwide to provide information on the COVID-19 pandemic impact so as to prepare and deliver an effective Public Health response. Overlapping panel surveys allow longitudinal estimates and more accurate cross-sectional estimates to be obtained thanks to the larger sample size. However, the problem of non-response is particularly aggravated in the case of panel surveys due to population fatigue with repeated surveys. OBJECTIVE: To develop a new reweighting method for overlapping panel surveys affected by non-response. METHODS: We chose the Healthcare and Social Survey which has an overlapping panel survey design with measurements throughout 2020 and 2021, and random samplings stratified by province and degree of urbanization. Each measurement comprises two samples: a longitudinal sample taken from previous measurements and a new sample taken at each measurement. RESULTS: Our reweighting methodological approach is the result of a two-step process: the original sampling design weights are corrected by modelling non-response with respect to the longitudinal sample obtained in a previous measurement using machine learning techniques, followed by calibration using the auxiliary information available at the population level. It is applied to the estimation of totals, proportions, ratios, and differences between measurements, and to gender gaps in the variable of self-perceived general health. CONCLUSION: The proposed method produces suitable estimators for both cross-sectional and longitudinal samples. For addressing future health crises such as COVID-19, it is therefore necessary to reduce potential coverage and non-response biases in surveys by means of utilizing reweighting techniques as proposed in this study.
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COVID-19 , Pandemias , Humanos , Estudios Transversales , Calibración , Encuestas y Cuestionarios , COVID-19/epidemiología , COVID-19/prevención & control , Sesgo , Atención a la SaludRESUMEN
[This corrects the article DOI: 10.3389/fmed.2023.1130218.].