Assessment of the ABC2-SPH risk score to predict invasive mechanical ventilation in COVID-19 patients and comparison to other scores.

Background: Predicting the need for invasive mechanical ventilation (IMV) is important for the allocation of human and technological resources, improvement of surveillance, and use of effective therapeutic measures. This study aimed (i) to assess whether the ABC2-SPH score is able to predict the receipt of IMV in COVID-19 patients; (ii) to compare its performance with other existing scores; (iii) to perform score recalibration, and to assess whether recalibration improved prediction. Methods: Retrospective observational cohort, which included adult laboratory-confirmed COVID-19 patients admitted in 32 hospitals, from 14 Brazilian cities. This study was conducted in two stages: (i) for the assessment of the ABC2-SPH score and comparison with other available scores, patients hospitalized from July 31, 2020, to March 31, 2022, were included; (ii) for ABC2-SPH score recalibration and also comparison with other existing scores, patients admitted from January 1, 2021, to March 31, 2022, were enrolled. For both steps, the area under the receiving operator characteristic score (AUROC) was calculated for all scores, while a calibration plot was assessed only for the ABC2-SPH score. Comparisons between ABC2-SPH and the other scores followed the Delong Test recommendations. Logistic recalibration methods were used to improve results and adapt to the studied sample. Results: Overall, 9,350 patients were included in the study, the median age was 58.5 (IQR 47.0-69.0) years old, and 45.4% were women. Of those, 33.5% were admitted to the ICU, 25.2% received IMV, and 17.8% died. The ABC2-SPH score showed a significantly greater discriminatory capacity, than the CURB-65, STSS, and SUM scores, with potentialized results when we consider only patients younger than 80 years old (AUROC 0.714 [95% CI 0.698-0.731]). Thus, after the ABC2-SPH score recalibration, we observed improvements in calibration (slope = 1.135, intercept = 0.242) and overall performance (Brier score = 0.127). Conclusion: The ABC2-SPHr risk score demonstrated a good performance to predict the need for mechanical ventilation in COVID-19 hospitalized patients under 80 years of age.

Sex bias in celiac disease: XWAS and monocyte eQTLs in women identify TMEM187 as a functional candidate gene.

BACKGROUND: Celiac disease (CeD) is an immune-mediated disorder that develops in genetically predisposed individuals upon gluten consumption. HLA risk alleles explain 40% of the genetic component of CeD, so there have been continuing efforts to uncover non-HLA loci that can explain the remaining heritability. As in most autoimmune disorders, the prevalence of CeD is significantly higher in women. Here, we investigated the possible involvement of the X chromosome on the sex bias of CeD. METHODS: We performed a X chromosome-wide association study (XWAS) and a gene-based association study in women from the CeD Immunochip (7062 cases, 5446 controls). We also constructed a database of X chromosome cis-expression quantitative trait loci (eQTLs) in monocytes from unstimulated (n = 226) and lipopolysaccharide (LPS)-stimulated (n = 130) female donors and performed a Summary-data-based MR (SMR) analysis to integrate XWAS and eQTL information. We interrogated the expression of the potentially causal gene (TMEM187) in peripheral blood mononuclear cells (PBMCs) from celiac patients at onset, on a gluten-free diet, potential celiac patients and non-celiac controls. RESULTS: The XWAS and gene-based analyses identified 13 SNPs and 25 genes, respectively, 22 of which had not been previously associated with CeD. The X chromosome cis-eQTL analysis found 18 genes with at least one cis-eQTL in naïve female monocytes and 8 genes in LPS-stimulated female monocytes, 2 of which were common to both situations and 6 were unique to LPS stimulation. SMR identified a potentially causal association of TMEM187 expression in naïve monocytes with CeD in women, regulated by CeD-associated, eQTL-SNPs rs7350355 and rs5945386. The CeD-risk alleles were correlated with lower TMEM187 expression. These results were replicated using eQTLs from LPS-stimulated monocytes. We observed higher levels of TMEM187 expression in PBMCs from female CeD patients at onset compared to female non-celiac controls, but not in male CeD individuals. CONCLUSION: Using X chromosome genotypes and gene expression data from female monocytes, SMR has identified TMEM187 as a potentially causal candidate in CeD. Further studies are needed to understand the implication of the X chromosome in the higher prevalence of CeD in women.

Celiac disease (CeD) is an immune-related condition triggered by gluten consumption in genetically susceptible individuals. Women present higher prevalence of CeD than men, but the biological explanation of such difference has not been elucidated. In this study, we investigated whether specific genetic variations on the X chromosome were associated with CeD in each sex. Surprisingly, we found 13 genetic variants and 25 genes significantly linked to CeD in women, but not in men. Additionally, we identified genetic variants on the X chromosome associated with gene expression of monocytes, a type of immune cells that is activated in CeD after gluten intake. Integrating these data with our previous findings, we found that lower expression of a gene termed TMEM187 might be associated with a potential increase in CeD risk in women. Finally, validation experiments confirmed higher TMEM187 levels in blood cells from female CeD patients compared to non-celiac women, while no such difference was seen in males. In summary, our study suggests that the X-chromosome gene TMEM187 may play a key role in CeD development, providing insights into the higher prevalence of CeD in females.

A autodeterminação informativa como contexto normativo para elaboração de diretrizes para a construção de um Relatório de Impacto à Proteção de Dados Pessoais: a proposta de um modelo humanizador para a telemedicina / Informative self-determination as a normative context for the elaboration of guidelines for the Impact Report on Personal Data Protection: the proposal of a humanizing model for telemedicine / La autodeterminación informativa como contexto normativo para la elaboración de lineamentos para la construcción de un Informe de Impacto en Protección de Datos Personales: la propuesta de un modelo humanizador para la telemedicina

Apresentamos e discutimos a construção de um instrumento de compliance para tratamento de dados pessoais e dados pessoais sensíveis do Núcleo Telessaúde UFSC, com base na Lei Geral de Proteção de Dados Pessoais. Trata-se da elaboração de diretrizes para um Relatório de Impacto à Proteção de Dados Pessoais visando à preservação da dimensão humana do dado e à preservação de direitos. A pesquisa foi qualitativa e exploratória, tendo o relato de experiência como metodologia. O levantamento bibliográfico e a análise documental permitiram a investigação, realizada em 2022, de processos, etapas e fluxos do tratamento dos dados. A análise dos dados foi qualitativa, por comparação dos resultados com a legislação vigente e com a adequação ao princípio da autodeterminação informativa. Os resultados demonstraram que as propostas para o relatório contribuíram para um tratamento de dados mais adequado ao ordenamento jurídico e, consequentemente, mais humanizado

We present and discuss the construction of a compliance instrument for the processing of personal data and sensitive personal data of the Telessaúde UFSC Center, based on the General Data Protection Law. It is a model for the elaboration of guidelines for the construction of an Impact Report on the Protection of Personal Data that collaborates to the preservation of the human dimension of data and the preserva-tion of rights. The research was qualitative and exploratory, adopting experience report as methodology. Bibliographical research and documental analysis enabled the investigation of the processes, stages and flows of data processing, carried out in 2022. Data analysis was carried out qualitatively, comparing the results with current legislation and adequacy to the principle of informative self-determination. Results showed that the proposed guidelines for the report contributed to a data processing more appropriate to the legal system and, consequently, more humanized

Presentamos y discutimos la construcción de un instrumento de cumplimiento para el tratamiento de datos personales y datos personales sensibles del Núcleo Telessaúde UFSC, con base en la Ley General de Pro-tección de Datos. Es la preparación de directrices para un Informe de Impacto de Protección de Datos Per-sonales para preservación de la dimensión humana de los datos y preservar los derechos. La investigación cualitativa y exploratoria adoptó un relato de experiencia como metodología. El levantamiento bibliográfico y el análisis documental permitieron la indagación de procesos, etapas y flujos de procesamiento de datos, realizados en 2022. El análisis de datos fue cualitativa, mediante la comparación de los resultados con la legislación vigente y la adecuación al principio de autodeterminación informativa. Los resultados mostra-ron que las directrices propuestas para el informe contribuyó a un tratamiento de datos más adecuado al ordenamiento jurídico y, en consecuencia, más humano

Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk.

Background: Celiac Disease (CeD) is an autoimmune disorder triggered by gluten intake in genetically susceptible individuals. Highest risk individuals are homozygous for the Human Leucocyte Antigen (HLA) DQ2.5 haplotype or DQ2.5/DQ2.2 heterozygous. Both the HLA-DQ2-positive high genetic risk individuals and those that have developed the disease have altered intestinal microbiota, but it remains unclear whether these alterations are a cause or a consequence of CeD. Objective: To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals. Materials and Methods: We performed a bidirectional Two-Sample Mendelian Randomization (2SMR) test using summary statistics from the largest publicly available Genome-Wide Association Study (GWAS) of GM and the summary statistics of the Immunochip CeD study of those individuals with the HLA-DQ2 high-risk haplotype. To test whether changes in GM composition were causally linked to CeD, GM data were used as exposure and CeD data as outcome; to test for reverse causation, the exposure and outcome datasets were inverted. Results: We identified several bacteria from Ruminococcaceae and Lachnospiraceae families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of Veillonellaceae family might be causal in the development of CeD, while alterations in Pasteurellaceae family might be a consequence of the disease itself. Conclusion: Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional.

Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders.

Increasing evidence supports the role of placenta in neurodevelopment and potentially, in the later onset of neuropsychiatric disorders. Recently, methylation quantitative trait loci (mQTL) and interaction QTL (iQTL) maps have proven useful to understand SNP-genome wide association study (GWAS) relationships, otherwise missed by conventional expression QTLs. In this context, we propose that part of the genetic predisposition to complex neuropsychiatric disorders acts through placental DNA methylation (DNAm). We constructed the first public placental cis-mQTL database including nearly eight million mQTLs calculated in 368 fetal placenta DNA samples from the INMA project, ran cell type- and gestational age-imQTL models and combined those data with the summary statistics of the largest GWAS on 10 neuropsychiatric disorders using Summary-based Mendelian Randomization (SMR) and colocalization. Finally, we evaluated the influence of the DNAm sites identified on placental gene expression in the RICHS cohort. We found that placental cis-mQTLs are highly enriched in placenta-specific active chromatin regions, and useful to map the etiology of neuropsychiatric disorders at prenatal stages. Specifically, part of the genetic burden for schizophrenia, bipolar disorder and major depressive disorder confers risk through placental DNAm. The potential causality of several of the observed associations is reinforced by secondary association signals identified in conditional analyses, regional pleiotropic methylation signals associated to the same disorder, and cell type-imQTLs, additionally associated to the expression levels of relevant immune genes in placenta. In conclusion, the genetic risk of several neuropsychiatric disorders could operate, at least in part, through DNAm and associated gene expression in placenta.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

OBJECTIVE: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). METHODS: An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. RESULTS: In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P = 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. CONCLUSIONS: In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

Direct dosimetric comparison of linear accelerator vs. Gamma Knife fractionated stereotactic radiotherapy (fSRT) of large brain tumors.

The purpose of this study was to directly compare the plan quality of Gamma Knife (GK) (Elekta, Stockholm, Sweden)- vs linear accelerator (LINAC)-based delivery techniques for fractionated stereotactic radiotherapy (fSRT) of large brain metastases. Eighteen patients with clinical target volumes (CTVs) larger than 9.5 cc were selected to generate comparative plans for the prescription dose of 9 Gy × 3 fractions, utilizing the Eclipse (Varian, Palo Alto, US) vs Leksell GammaPlan (LGP) (Elekta, Stockholm, Sweden) treatment planning systems (TPS). Each GK plan was first developed using LGP's automatic planning, followed by manual adjustments/refinements. The same MRI and structures, including CTVs and organs at risk, were then DICOM-transferred to the Eclipse TPS. Volumetric Modulated Arc Therapy (VMAT) and Dynamic Conformal Arc (DCA) plans for a Truebeam, with high-definition multi-leaf collimators (MLCs), were developed on these MR images and structures using a single isocenter and 3 non-coplanar arcs. No planning target volume (PTV) margins were added, and no heterogeneity correction was used for either TPS. GK plans were prescribed to the 50% isodose line, and Eclipse VMAT and DCA plans allowed a maximum dose up to 170% and ∼125%, respectively. Gradient index (GI), Paddick Conformity Index (PCI), V20GyRind, and V4GyRind of all 3 techniques were calculated and compared. One-way analysis of variance (ANOVA) was performed to determine the statistical significance of the differences of these planning indices for the 3 planning techniques. A total of eighteen treatment targets were analyzed. Median CTV volume was 14.4 cc (range 9.5 cc - 55.9 cc). Mean ± standard deviation of PCI were 0.85 ± 0.03, 0.90 ± 0.03, and 0.72 ± 0.11 for GK, VMAT and DCA plans, respectively. They were respectively 2.64 ± 0.17, 2.46 ± 0.18, and 2.83 ± 0.48 for GI; 15.33 ± 8.45 cc, 10.47 ± 4.32 cc and 23.51 ± 16 cc for V20GyRind; and 316.28 ± 138.35 cc, 317.81 ± 108.21 cc, and 394.85 ± 142.16 cc for V4GyRind. The differences were statistically significant with p < 0.01 for all indices, except for V4GyRind (p > 0.129). In conclusion, a direct dosimetric comparison using the same MRI scan and contours was performed to evaluate the plan quality of various fSRT delivery techniques for CTV > 9.5 cc. LINAC VMAT plans provided the best dosimetric outcome in regard to PCI, GI, and V20GyRind. GK outcomes were similar to LINAC VMAT plans while LINAC DCA outcomes were significantly worse. Even though GK has a smaller physical penumbra, LINAC VMAT outperformed GK in this study due to enhanced penumbra sharpening and better beam optimization.

Atrial cardiopathy in young adults with embolic stroke of undetermined source: a myocardial deformation imaging analysis.

BACKGROUND: Atrial cardiopathy (AC) has emerged as a potential pathological thrombogenic atrial substract of embolic stroke of undetermined source (ESUS), even in the absence of atrial fibrillation. Left atrium (LA) myocardial deformation analysis may be of value as a subclinical marker of AC and a predictor of ESUS. AIMS: To compare LA mechanical function between ESUS cases and age and sex-matched controls. METHODS: A single-center analytical study with case-control design was performed. Case group was composed by young patients admitted in the Neurology department from January 2017 to June 2021. Control group was composed by age and sex matched controls recruited from the community. All participants performed echocardiogram and a smaller sample underwent cardiac magnetic resonance. RESULTS: We recruited 31 ESUS patients aged between 18 and 65 years and 31 age and sex matched controls. ESUS patients had a significantly higher prevalence of cardiovascular risk factors and patent foramen ovale (PFO). The prevalence of AC was not different between groups. Echocardiogram parameters, including strain analysis, were similar between groups, except for LA appendage (LAA) ostium variation which was significantly lower in ESUS patients (absolute: 6.5vs8.7mm, p<0.001; relative: 44.5%vs53.4%, p=0.002). After exclusion of patients with PFO, all the results were statistically similar. Regarding cardiac magnetic resonance analysis, there were no statistically significant differences between groups. CONCLUSION: This study shows that in our population atria cardiopathy and atrial function was not associated with ESUS.LAA structural and functional abnormalities may play a major role. The role of LAA in ESUS warrants further studies.

Development and validation of the MMCD score to predict kidney replacement therapy in COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is frequently associated with COVID-19, and the need for kidney replacement therapy (KRT) is considered an indicator of disease severity. This study aimed to develop a prognostic score for predicting the need for KRT in hospitalised COVID-19 patients, and to assess the incidence of AKI and KRT requirement. METHODS: This study is part of a multicentre cohort, the Brazilian COVID-19 Registry. A total of 5212 adult COVID-19 patients were included between March/2020 and September/2020. Variable selection was performed using generalised additive models (GAM), and least absolute shrinkage and selection operator (LASSO) regression was used for score derivation. Accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalisation. The temporal validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. The geographic validation cohort had similar age and sex; however, this cohort had higher rates of ICU admission, AKI, need for KRT and in-hospital mortality. Four predictors of the need for KRT were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation and diabetes. The MMCD score had excellent discrimination in derivation (AUROC 0.929, 95% CI 0.918-0.939) and validation (temporal AUROC 0.927, 95% CI 0.911-0.941; geographic AUROC 0.819, 95% CI 0.792-0.845) cohorts and good overall performance (Brier score: 0.057, 0.056 and 0.122, respectively). The score is implemented in a freely available online risk calculator ( https://www.mmcdscore.com/ ). CONCLUSIONS: The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalised COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.

Recovery of Green Polyols from Rigid Polyurethane Waste by Catalytic Depolymerization.

Polyurethane (PU) is one of the most versatile polymers available and can be found in an infinite number of formats ranging from rigid or flexible foams to elastomers. Currently, most Rigid PU Foam (RPUF) waste is landfilled, even though a small amount is mechanically recycled, in which the material is conditioned in size to a very fine powder, which is introduced as a filler. In this work, chemical recycling of two types of rigid PU foams is studied, the major difference being the aliphatic or aromatic nature of the isocyanate used in the synthesis. A solvolysis process is developed, a chemical depolymerization that breaks the chains by means of a chemical agent, a solvent, in the presence of a catalyst and under controlled process conditions. The glycolysis products are purified by vacuum distillation, centrifugation, and acid water treatment, depending on the most suitable process for each waste type. Optimal process conditions are established to obtain high-purity green polyols by performing a set of catalytic glycolysis reactions at laboratory scale with the previously conditioned RPUF waste samples. The physicochemical properties of the polyols, such as hydroxyl value, acid value, average molecular weight (Mn), and viscosity, are analyzed. The chemical structure and thermal stability of the polyols are studied by means of FTIR and TGA, respectively. Partial substitution of the commercial polyol (up to 15 wt.%) by the recycled polyols for RPUF synthesis is studied and characterized.

Determination of Quality Parameters in Mangetout (Pisum sativum L. ssp. arvense) by Using Vis/Near-Infrared Reflectance Spectroscopy.

Pisum sativum L. ssp. arvense, is colloquially called tirabeque or mangetout because it is eaten whole; its pods are recognized as a delicatessen in cooking due to its crunch on the palate and high sweetness. Furthermore, this legume is an important source of protein and antioxidant compounds. Quality control in this species requires the analysis of a large number of samples using costly and laborious conventional methods. For this reason, a non-chemical and rapid technique as near-infrared reflectance spectroscopy (NIRS) was explored to determine its physicochemical quality (color, firmness, total soluble solids, pH, total polyphenols, ascorbic acid and protein content). Pod samples from different cultivars and grown under different fertigation treatments were added to the NIRS analysis to increase spectral and chemical variability in the calibration set. Modified partial least squares regression was used for obtaining the calibration models of these parameters. The coefficients of determination in the external validation ranged from 0.50 to 0.88. The RPD (standard deviation to standard error of prediction ratio) and RER (standard deviation to range) were variable for quality parameters and showed values that were characteristic of equations suitable for quantitative prediction and screening purposes, except for the total soluble solid calibration model.

Reparo percutâneo de valva mitral pelo MitraClip: análise crítico-comparativa dos ensaios clínicos MITRA-FR E COAPT / Percutaneous mitral valve repair by MitraClip: critical-comparative analysis of MITRA-FR and COAPT clinical trials

Introdução: A valvuloplastia é indicada para o tratamento de regurgitação mitral grave, sendo a técnica transcateter uma opção à toracotomia. Testou-se o dispositivo MitraClip para reparo percutâneo da valva mitral em dois ensaios clínicos randomizados com resultados antagônicos: MITRA-FR e COAPT. Objetivo: Analisar as variáveis metodológicas apresentadas pelos ensaios. Método: Revisão crítico-comparativa entre MITRA-FR e COAPT. Resultados: COAPT apresentou taxa de sucesso de 98% e redução na taxa de hospitalização por IC. Já MITRA-FR não demonstrou redução da taxa de mortalidade ou da hospitalização não planejada por IC em um ano. Discussão: A seleção de participantes em COAPT mostrou-se mais criteriosa. Embora COAPT tenha utilizado maior número de clipes por operação, o desfecho primário nos dois ensaios foi semelhante. No COAPT, o acompanhamento medicamentoso foi estabelecido por um comitê, sendo relatado aumento expressivo do uso de betabloqueadores no grupo experimental. Ademais, interesses financeiros podem ter corroborado para os resultados encontrados no COAPT. Conclusão: Os resultados conflitantes de MITRA-FR e COAPT são explicados por diferenças metodológicas, mas o resultado positivo apresentado por COAPT possui maior risco de viés. [au]

Introduction: Valvuloplasty is indicated as treatment for severe mitral regurgitation and the transcatheter technique is an option to thoracotomy. The MitraClip device for percutaneous mitral valve repair has been tested in two randomized clinical trials with conflicting results: MITRA-FR and COAPT. Objective: Analyze the methodological varieties presented by the trials. Method: Critical-comparative review between MITRA-FR and COAPT. Results: COAPT presented a 98% success rate and a reduction of the hospitalization rate for heart failure. Contrarily, the MITRA-FR trial did not present any benefits in the reduction of the mortality rate or in the unplanned hospitalization for heart failure. Discussion: The selection of participants in COAPT was more rigorous. Although COAPT used a higher number of clips per operation, the primary outcome in both trials was similar. In COAPT, medication follow-up was established by a committee, with a significant increase in the use of beta-blockers in the experimental group being reported. Furthermore, financial interests may have corroborated the results found in COAPT. Conclusion: The conflicting results presented by MITRA-FR and COAPT are explained by methodological differences, but the positive result presented by COAPT had more risk of bias [au]

Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers.

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.

Interacciones medicamentosas potenciales en pacientes COVID 19 en tratamiento con lopinavir/ritonavir / Potential drug-drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir

OBJETIVOS: Determinar la prevalencia de interacciones potenciales en pacientes COVID-19 en tratamiento con lopinavir/ritonavir (LPV/r). El objetivo secundario fue elaborar recomendaciones e identificar los factores de riesgo asociados a presentar interacciones potenciales con LPV/r. SUJETOS Y MÉTODOS: Estudio transversal y multicéntrico con la participación de 2 hospitales. Se incluyeron pacientes COVID-19 mayores de 18 años, con ingreso hospitalario y en tratamiento con LPV/r. Se realizó un cribado de las interacciones potenciales relacionadas con LPV/r y la medicación domiciliaria y hospitalaria. Se utilizó como base de datos de consulta Lexicomp® (Uptodate), HIV-drug interacctions y COVID-drug interacctions. RESULTADOS: Se incluyeron 361 pacientes con una media de edad de 62,77 ± 14,64 años, donde el 59,6% (n = 215) fueron hombres. El 62,3% (n=225) tuvieron una o más interacciones potenciales y el 26, 87% (n = 97) 2 o más. Las variables independientes asociadas a presentar ≥ 1 interacciones potenciales fueron la edad (> 65) (OR 1,95; IC 95% 1,06-3,59; P = 0,033), el ingreso en UCI (OR 9,22; IC 95% 1,98-42,93; P = 0,005), la enfermedad previa respiratoria (OR 2,90; IC 95% 1,15-7,36; P = 0,024), psiquiátrica (OR 4,14; IC 95% 1,36-12,61; P = 0,013), la dislipemia (OR 3,21; IC 95% 1,63-6,35; P = 0,001) y el número de fármacos prescrito (OR 4,33; IC 95% 2,40-7,81; P = 0,000). CONCLUSIÓN: La prevalencia de interacciones potenciales en paciente COVID-19 en tratamiento con LPV/r es elevada, comportándose como factores de riesgo asociados la edad (> 65), el ingreso en UCI, la enfermedad previa respiratoria, psiquiátrica y la dislipemia y el número de fármacos prescritos

OBJECTIVES: To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. SUBJECTS AND METHODS: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID-19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. RESULTS: 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥ 1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P =.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P = .005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P =.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P =.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P = .001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P =.000). CONCLUSION: The prevalence of potential interactions in COVD-19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors

Potential drug-drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir.

OBJECTIVES: To determine the prevalence of potential interactions in COVID19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. SUBJECTS AND METHODS: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID 19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. RESULTS: 361 patients with a mean age of 62.77 ±â€¯14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (>65) (OR 1.95; 95% CI 1.06-3.59, P = .033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P = .005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P = .024), psychiatric (OR 4.14; 95 CI% 1.36-12.61; P = .013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P = .001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P = .000). CONCLUSION: The prevalence of potential interactions in COVD 19 patient undergoing treatment with LPV/r is high, with age (>65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.

OBJETIVOS: Determinar la prevalencia de interacciones potenciales en pacientes COVID19 en tratamiento con lopinavir/ritonavir (LPV/r). El objetivo secundario fue elaborar recomendaciones e identificar los factores de riesgo asociados a presentar interacciones potenciales con LPV/r. SUJETOS Y MÉTODOS: Estudio transversal y multicéntrico con la participación 2 hospitales. Se incluyeron pacientes COVID 19 mayores de 18 años, con ingreso hospitalario y en tratamiento con LPV/r. Se realizó un cribado de las interacciones potenciales relacionadas con LPV/r y la medicación domiciliaria y hospitalaria. Se utilizó como base de datos de consulta Lexicomp® (Uptodate), HIV-drug interacctions y COVID-drug interacctions. RESULTADOS: Se incluyeron 361 pacientes con una media de edad de 62,77 ±â€¯14,64 años, donde el 59,6% (n = 215) fueron hombres. El 62,3% (n = 225) tuvieron 1 o más interacciones potenciales y el 26, 87% (n = 97) 2 o más. Las variables independientes asociadas a presentar ≥ 1 interacciones potenciales fueron la edad (> 65) (OR 1,95; IC 95% 1,06­3,59; P = ,033), el ingreso en UCI (OR 9,22; IC 95% 1,98­42,93; P = ,005), la patología previa respiratoria (OR 2,90; IC 95% 1,15­7,36; P = ,024), psiquiátrica (OR 4,14; IC 95% 1,36­12,61; P = ,013), la dislipemia (OR 3,21; IC 95% 1.63­6,35; P = ,001) y el número de fármacos prescrito (OR 4,33; IC 95% 2,40­7,81; P = ,000). CONCLUSIÓN: La prevalencia de interacciones potenciales en paciente COVD 19 en tratamiento con LPV/r es elevada, comportándose como factores de riesgo asociados la edad (>65), el ingreso en UCI, la patología previa respiratoria, psiquiátrica y la dislipemia y el número de fármacos prescritos.

[Potential drug-drug interactions in COVID 19 patients in treatment with lopinavir/ritonavir]. / Interacciones medicamentosas potenciales en pacientes COVID 19 en tratamiento con lopinavir/ritonavir.

OBJECTIVES: To determine the prevalence of potential interactions in COVID-19 patients receiving lopinavir/ritonavir (LPV/r). The secondary objective was to develop recommendations and identify the risk factors associated with presenting potential interactions with LPV/r. SUBJECTS AND METHODS: Cross-sectional and multicenter study with the participation of 2 hospitals. COVID-19 patients over 18 years of age, admitted to hospital and under treatment with LPV/r were included. A screening of potential interactions related to LPV/r and home and hospital medication was carried out. Lexicomp® (Uptodate), HIV-drug interactions and COVID-drug interactions were used as the query database. RESULTS: 361 patients with a mean age of 62.77 ± 14.64 years were included, where 59.6% (n = 215) were men. 62.3% (n = 225) had 1 or more potential interactions and 26, 87% (n = 97) 2 or more. The independent variables associated with presenting ≥1 potential interactions were age (> 65) (OR 1.95; 95% CI 1.06-3.59, P =.033), ICU admission (OR 9.22; CI 95% 1.98-42.93; P =.005), previous respiratory pathology (OR 2.90; 95% CI 1.15-7.36; P =.024), psychiatric (OR 4.14; 95 CI % 1.36-12.61; P =.013), dyslipidemia (OR 3.21; 95% CI 1.63-6.35; P =.001) and the number of drugs prescribed (OR 4.33; 95% CI 2.40-7.81; P =.000). CONCLUSION: The prevalence of potential interactions in COVD-19 patient undergoing treatment with LPV/r is high, with age (> 65), ICU admission, previous respiratory and psychiatric pathology, dyslipidemia and the number of prescribed drugs acting as risk factors.

Multimodal Prussian blue analogs as contrast agents for X-ray computed tomography.

Prussian blue analogs (PBAs) are versatile materials with a wide range of applications. Due to their tunability, intrinsic biocompatibility, as well as low toxicity, these nanoscale coordination polymers have been successfully studied as multimodal contrast agents for multiple imaging techniques. Herein, we report the expanded biomedical application of PBAs to X-ray computed tomography (CT). In our systematic study of the series A{MnII[FeIII(CN)6]} (A = K+, Rb+, Cs+), we showed that derivatives incorporating Rb+ and Cs+ ions in the tetrahedral sites of the parent face-centered cubic cyano-bridged networks exhibited substantially increased X-ray attenuation coefficients, thus yielding significant contrast compared to the clinically approved X-ray contrast agent iohexol at the same concentrations. Additionally, our µ-CT studies revealed that these PBAs could be useful as dual-energy CT contrast agents for different biological specimens by using the lower varying scanning X-ray tube voltages. Finally, in vitro studies using U87-Luc cells treated with PBAs, including cellular CT imaging and bioluminescence cell viability assays, revealed that PBAs were taken up by the glioblastoma cells, with moderate biocompatibility at concentrations below the mM range.

Electronic Structure and Magnetic Interactions in the Radical Salt [BEDT-TTF]2[CuCl4].

The magnetic behavior and electric properties of the hybrid radical salt [BEDT-TTF]2[CuCl4] have been revisited through extended experimental analyses and DDCI and periodic DFT plane waves calculations. Single crystal X-ray diffraction data have been collected at different temperatures, discovering a phase transition occurring in the 250-300 K range. The calculations indicate the presence of intradimer, interdimer, and organic-inorganic π-d interactions in the crystal, a magnetic pattern much more complex than the Bleaney-Bowers model initially assigned to this material. Although this simple model was good enough to reproduce the magnetic susceptibility data, our calculations demonstrate that the actual magnetic structure is significantly more intricate, with alternating antiferromagnetic 1D chains of the organic BEDT-TTF+ radical, connected through weak antiferromagnetic interactions with the CuCl42- ions. Combination of experiment and theory allowed us to unambiguously determine and quantify the leading magnetic interactions in the system. The density-of-states curves confirm the semiconductor nature of the system and the dominant organic contribution of the valence and conduction band edges. This general and combined approach appears to be fundamental in order to properly understand the magnetic structure of these complex materials, where experimental data can actually be fitted from a variety of models and parameters.