Genetic Analysis of High Bone Mass Cases from the BARCOS Cohort of Spanish Postmenopausal Women

The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM

Test rápidos de antígenos para la detección del SARS-CoV-2: Revisión narrativa

The rapid identificationand isolation of COVID-19 patients has become the cornerstone for the control of the recent outbreak. Real-time quantitative polymerase chain reaction is routinely used to confirm COVID-19 diagnosis and is considered the gold standard due to high sensitivity and specificity. Nevertheless, it usually takes several days and a relatively higher cost. Antigen tests based have emerged to cope with such disadvantages, by offering rapid results, an easy-to-use procedure, and low costs. The objective of the narrative review was to provide up-to-date data about CE-marked rapid antigen tests (RATs) for COVID-19. Given their large number, the study only focused on representative and widely used in Spain (Standard Q, Nadal, Panbio, CerTest, and Wondfo). RATs have become a very useful and validated tool for controlling the spread of COVID-19 allowing the rapid identification of active infection and isolation of positive patients. The present revision of the literature has demonstrated that sensitivity and specificity of all available RATs in Spain are high and accomplish European regulations and WHO recommendations.La rápida identificación y aislamiento de los pacientes por COVID-19 se ha convertido en un reto para el control de la pandemia. La reacción en cadena de la polimerasa cuantitativa a tiempo real se utiliza de manera rutinaria para confirmar el diagnóstico de COVID-19 y se considera el estándar de referencia por su alta sensibilidad y especificidad. Sin embargo, normalmente lleva varios días y los costes son relativamente altos. Los test de antígeno son una herramienta rápida, fácil de realizar y de bajo coste. El objetivo de la revisión narrativa es proporcionar información actualizada sobre los test rápidos de antígenos (TRA) para COVID-19 con marcado europeo. Dado su gran número, el estudio solo se enfoca en aquellos representativos y ampliamente empleados en España (Standard Q, Nadal, Panbio, CerTest y Wondfo). Los TRA se han convertido en una herramienta validada muy útil para controlar la diseminación de la COVID-19, al permitir la identificación rápida de la infección activa y el aislamiento de pacientes positivos. La presente revisión de la literatura ha demostrado que la sensibilidad y especificidad de los TRA disponibles en España son altas y cumplen con la regulación europea y las recomendaciones de la OMS

Is there less alteration of smell sensation in patients with omicron SARS-CoV-2 variant infection?

The ongoing pandemic Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern in terms of public health Within the symptoms secondary to SARS-CoV-2 infection, hyposmia and anosmia have emerged as characteristic symptoms during the onset of the pandemic. Although many researchers have investigated the etiopathogenesis of this phenomenon, the main cause is not clear. The appearance of the new variant of concern Omicron has meant a breakthrough in the chronology of this pandemic, presenting greater transmissibility and less severity, according to the first reports. We have been impressed by the decrease in anosmia reported with this new variant and in patients reinfected or who had received vaccination before becoming infected. Based on the literature published to date, this review proposes different hypotheses to explain this possible lesser affectation of smell. On the one hand, modifications in the SARS-CoV-2 spike protein could produce changes in cell tropism and interaction with proteins that promote virus uptake (ACE-2, TMPRSS2, and TMEM16F). These proteins can be found in the sustentacular cells and glandular cells of the olfactory epithelium. Second, due to the characteristics of the virus or previous immunity (infection or vaccination), there could be less systemic or local inflammation that would generate less cell damage in the olfactory epithelium and/or in the central nervous system

Serum albumin is a strong predictor of sepsis outcome in elderly patients

The incidence of sepsis is disproportionately higher in elderly adults, and age is an independent predictor of mortality. Retrospective analysis was conducted among patients admitted to the emergency department in a tertiary teaching hospital from January 2016 to June 2017. To study the prognosis determinants of sepsis among elderly patients attended in the emergency room of a tertiary care hospital. As secondary objectives, we aimed to describe the causes of sepsis, the general outcome, and the general characteristics of these patients. Two hundred thirty-five episodes data of patients admitted throughout the 15-month study period who were diagnosed with sepsis, severe sepsis or septic shock, were included. Throughout the study cohort, 51 patients (21.7%) fulfilled the criteria of severe sepsis or septic shock. All-cause mortality was 11 patients (4.7%) on day 14 and 27 (11.5%) on day 30. Prognosis factors associated with 30-day mortality were the following: albumin level < 2.6 g/dl (first quartile of the overall population), odds ratio (OR 3.26, 95% CI 12-9.41; p = 0.029), Charlson comorbidity index (OR 1.23, 95% CI 1.04-1.45; p = 0.012), C-reactive protein on admission (OR 1.04, 95% CI 0.99-1.08; p = 0.062), and non-adequacy of the initial antimicrobial therapy (OR 3.3, 95% CI 1.06-10.4; p = 0.039). Among elderly patients with sepsis, strong predictors of mortality such as albumin could be considered as part of prognosis and future potential interventions. Adequacy of antimicrobial therapy at admission must be one of the objectives in the treatment of sepsis, also in the elderly, since it is an independent predictor of mortality

Numbers game and immune geography as determinants of coronavirus pathogenicity

info:eu-repo/semantics/publishedVersio

Anti-SARS-COV-2 specific immunity in HIV immunological non-responders after mRNA-based COVID-19 vaccination

Individuals infected with the human immunodeficiency virus type 1 (HIV-1) belong to the group of people most vulnerable to SARS-CoV-2 infections and the associated disease COVID-19. Here we describe SARS-CoV-2-specific antibody and cellular immune responses in a small cohort of immunological non-responder HIV-1 patients (HIV-INRs) after receiving the COVID-19 mRNA-based BioNTech/Pfizer vaccine. Compared to the control group of vaccinated healthy individuals that all developed a virus-specific immune response, 5 of 10 vaccinated HIV-1 patients showed insufficient immune responses. The lack of response was not directly correlated with patients CD4 cell counts. Three of the five non-responders that agreed to receive a booster vaccination subsequently generated a virus-specific response. Thus, even HIV-INRs can be efficiently vaccinated against COVID-19 but may require a follow-up by virus-specific immune monitoring to guarantee clinical vaccine benefits.The authors are supported by Spanish Melanoma Group Grant (GEM) (III Beca GEM para Grupos Emergentes), the Spanish Ministry of Science and Innovation grant no. PID2019-106323RB-I00 AEI//10.13039/501100011033, the “Unidad de Excelencia María de Maeztu”, funded by the MCIN and the AEI (DOI: 10.13039/501100011033); Ref: CEX2018-000792-M and by a FIS Project “PI19/00019” funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union

Effect of the tumor suppressor miR-320a on viability and functionality of human osteosarcoma cell Llnes compared to primary osteoblasts

The miR-320a regulates a number of genes involved in various physiological processes. In particular, it has been reported as a tumor suppressor in several types of human cancers and involved in osteoporotic fracture and osteoblast function. Hence, the role of miR-320a has been evaluated in tumor cells and in primary cells in a separated context, but its effect has never been explored in a comparative manner. The present study aims to evaluate the cellular effects of miR-320a on human osteosarcoma cell lines (MG-63 and U2OS) compared to that on primary human osteoblasts (hOBs). miR-320a was either overexpressed or inhibited in all cell lines, and cell proliferation and viability were analyzed. Additionally, the effects of miR-320a on matrix mineralization, alkaline phosphatase activity, and oxidative stress were also evaluated in order to assess osteoblast functionality. In osteosarcoma cells, miR-320a overexpression reduced cell viability and proliferation, while in hOB cell viability was not affected and proliferation even was increased. The overexpression of miR-320a in both osteosarcoma cells and hOBs reduced the mineralization capacity. Finally, an increased oxidative stress was detected in all cells after miR-320a overexpression mainly in osteosarcoma. In conclusion, the overexpression of miR-320a increased stress oxidation levels, which could be involved in the reduced osteoblast performance, even though the cell viability was only affected in osteosarcoma cells.This research was supported by the CIBER on Frailty and Healthy Ageing (CIBERFES; grant number: CB16/10/00245), the CIBERER (grant number: U720), FEDER funds, and grants from the Science and Innovation Ministry (ISCIII; grant numbers: PI16/01860 and PI13/00116; SAF2016-75948-R). L.D.-U. was granted with a PFIS predoctoral fellowship from the ISCIII

The use of microindentation for the study of bone properties in type 1 diabetes mellitus patients

Diabetes mellitus is associated with a higher risk of fracture. In this study, we analysed the bone quality of premenopausal women with type 1 diabetes mellitus by microindentation. No differences in bone quality were identified between patients and healthy controls, suggesting that intensive insulin therapy can preserve bone health. Purpose: To compare the bone quality of women with type 1 diabetes mellitus (T1DM) and healthy controls, and to determine the relationship with bone mineral density (BMD). Methods: This was a cross-sectional study of 45 premenopausal women with T1DM and 21 healthy controls, matched according to age and BMI. Clinical parameters, BMD and bone tissue mechanical properties (assessed using the bone material strength index [BMSi]) were evaluated in each group using microindentation. In T1DM patients, glycosylated haemoglobin (HbA1c), the number of hypoglycaemic events and the status of chronic complications were also analysed. Results: No differences in BMSi or BMD between T1DM patients and healthy controls were identified. In the T1DM patients, the mean HbA1c was 7.52% ± 1.00% and the mean time elapsed since diagnosis was 22.6 ± 12.2 years. Eight patients (17.7%) met the criteria for metabolic syndrome (MetS), and microvascular complications were present in 12 patients (26.7%). Neither the number of features of MetS present nor the presence of microangiopathy was found to be associated with BMSi. Conclusions: T1DM premenopausal patients showed bone tissue properties comparable to those shown by controls. Further larger-scale studies should be conducted to confirm these results