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Cardiovascular disease (CVD) is a common comorbidity observed in patients with coronavirus disease 2019 (COVID-19), which is associated with increased severity and mortality. However, the effects of biological sex on CVD-associated mortality in patients with COVID-19 are poorly established, particularly among Hispanic/Latin Americans. We examined the association of preexisting CVD with COVID-19 mortality in hospitalized Latin American men and women. This multicenter study included Mexican patients hospitalized with a positive diagnosis of COVID-19. The main outcome was in-hospital mortality. Multivariable regression analyses were used to calculate the adjusted odds ratio with 95% confidence interval for mortality in women and men. Of 81,400 patients with a positive diagnosis for SARS-CoV-2 infection, 28,929 (35.54%) hospitalized patients were evaluated. Of these, 35.41% (10,243) were women. In-hospital death was higher in men than in women. In relation to CVD between the sexes, women had a higher incidence of CVD than men (4.69 vs. 3.93%

Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal function, circulating magnesium levels, and mortality in patients with COVID-19 remains unclear. In this retrospective cohort study, we characterized 390 hospitalized patients with COVID-19 that were categorized according to their body mass index (BMI). Patients were clinically characterized and biochemical parameters, renal function, and electrolyte markers measured upon admission. We found that in patients who died, BMI was associated with reduced estimated glomerular filtration rate (eGFR, Rho: −0.251, p = 0.001) and serum magnesium levels (Rho: −0.308, p < 0.0001). Multiple linear regression analyses showed that death was significantly associated with obesity (p = 0.001). The Cox model for obese patients showed that magnesium levels were associated with increased risk of death (hazard ratio: 0.213, 95% confidence interval: 0.077 to 0.586, p = 0.003). Thus, reduced renal function and lower magnesium levels were associated with increased mortality in obese COVID-19 patients. These results suggest that assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce mortality among obese COVID-19 patients.

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of β-cell function (HOMA-β), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR

Closed spinal dysraphism (SD) is a type of neural tube defect originating during early embryonic development whereby the neural tissue of the spinal defect remains covered by skin, often coinciding with markers of cutaneous stigmata. It is hypothesized that these events are caused by multifactorial processes, including genetic and environmental causes. We present an infant with a unique congenital midline lesion associated with a closed SD. Through comprehensive molecular profiling of the intraspinal lesion and contiguous skin lesion, an internal tandem duplication (ITD) of the kinase domain of the fibroblast growth factor receptor 1 (

Synpolydactyly 1 (SPD; MIM# 186000), also called syndactyly type II (SDTY2), is a genetic limb malformation characterized by polydactyly with syndactyly involving the webbing of the third and fourth fingers, and the fourth and fifth toes. It is caused by heterozygous alterations in HOXD13 with incomplete penetrance and phenotypic variability. In our study, a five-generation family with an SPD phenotype was enrolled in our Rare Disease Genomics Protocol. A comprehensive examination of three generations using Illumina short-read whole-genome sequencing (WGS) did not identify any causative variants. Subsequent WGS using Pacific Biosciences (PacBio) long-read HiFi Circular Consensus Sequencing (CCS) revealed a heterozygous 27-bp duplication in the polyalanine tract of HOXD13. Sanger sequencing of all available family members confirmed that the variant segregates with affected individuals. Re-analysis of an unrelated family with a similar SPD phenotype uncovered a 21-bp (7-alanine) duplication in the same region of HOXD13. Although ExpansionHunter identified these events in most individuals in a retrospective analysis, low sequence coverage due to high GC content in the HOXD13 polyalanine tract makes detection of these events challenging. Our findings highlight the value of long-read WGS in elucidating the molecular etiology of congenital limb malformation disorders. This article is protected by copyright. All rights reserved.

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.

Clinicians often omit or underuse several techniques while delivering therapy. These omissions can be due to unconscious factors (e.g., clinician's anxiety), or due to clinicians' deliberate decisions (e.g., modifying therapy believing that such modifications are on the patients' best interests). However, little is known about whether patients consider these modifications necessary. The main aim of this study was to explore the opinions about the important aspects of CBT according to both patients' and clinicians' perspectives. It also aimed to determine whether clinicians' anxiety influenced such preferences. To achieve these aims, two groups of participants were approached-CBT clinicians (n = 83) and CBT patients (n = 167). An online survey with a list of techniques commonly used in CBT was developed for each group, who indicated the importance they attributed to the techniques. Additionally, clinicians completed an anxiety measure. Results indicated that clinicians valued all "change-oriented" techniques and several "interpersonal engagement" techniques more than the patients. The only technique preferred by patients was "relaxation". Higher levels of clinician anxiety were associated with a lower preference for "behavioural experiments" and "exposure". In conclusion, clinicians are encouraged to plan therapy in collaboration with the patient, as well as to discuss the rationale for the implemented techniques.

Background and objectives Clinicians often fail to deliver the best psychological treatments available, especially if they perceive their patients as fragile or vulnerable. This fragility might be interpreted by clinicians through their internalised gender stereotypes (e.g. female patients are less resilient to a demanding treatment) or according to their patients' emotional state (e.g. the patient is too delicate to endure the most stress-inducing aspects of therapy). The aim of this study was to test experimentally whether patients’ characteristics influenced therapy delivery. Some clinician characteristics were also considered. Methods This was an experimental, vignette-based study that evaluated clinicians' likelihood of utilizing several techniques commonly used in CBT by manipulating patients' mood and gender. Clinicians’ personality traits were also included as covariates. Results Anxious patients were the most likely to receive the techniques, especially exposure and other behavioural techniques. Therapists delivered more techniques to male patients, while angry and calm female patients were the least likely to receive the techniques. Therapists were more likely to deliver talking techniques to female patients. Clinicians’ firmness and empathy had an effect on CBT delivery. Limitations Future vignette-based studies should validate and pilot the vignettes. Technique clustering should also be based in factor analysis or similar methods. Direct observational methods might be more reliable than self-report. Conclusion The findings suggest that clinicians treat their patients differently, either consciously or inadvertently. These differences are likely to be related to clinicians’ own concerns and gender stereotypes about their patients.

Craniopharyngiomas (CPs) are cystic, encapsulated, slow-growing epithelial tumors. CPs can be aggressive forms invading and resorting surrounding structures of adjacent brain tissue, where Rosenthal fibers (RFs) are expressed. The aim of this study was to investigate the ultrastructure of these fibers in human biopsies and compare it with an experimental toxic model produced by the cortical infusion of the oil cyst fluid ("Oil machinery" fluid or OMF) from CPs to rats. For this purpose, the CPs from ten patients were examined by light and electron microscopy. OMF was administered to rats intracortically. Immunohistochemical detection of glial fibrillary acidic protein (GFAP) and vimentin was assessed. In both freshly obtained CPs and rat brain tissue, the presence of abundant cellular debris, lipid-laden macrophages, reactive gliosis, inflammation and extracellular matrix destruction were seen. Ultrastructural results suggest focal pathological disturbances and an altered microenvironment surrounding the tumor-brain junction, with an enhanced presence of RFs in human tumors. In contrast, in the rat brain different degrees of cellular disorganization with aberrant filament-filament interactions and protein aggregation were seen, although RFs were absent. Our immunohistochemical findings in CPs also revealed an enhanced expression of GFAP and vimentin in RFs at the peripheral, but not at the central (body) level. Through these findings we hypothesize that the continuous OMF release at the CPs boundary may cause tissue alterations, including damaging of the extracellular matrix, and possibly contributing to RFs formation, a condition that was not possible to reproduce in the experimental model. The presence of RFs at the CPs boundary might be considered as a major criterion for the degree of CPs invasiveness to normal tissue. The lack of RFs reactivity in the experimental model reveals that the invasive component of CPs is not present in the OMF, although the fluid per se can exert tissue damage.

Objective Research has shown that clinicians underuse or omit techniques that constitute an essential part of evidence-based therapies. However, it is not known whether this is the case in DBT for eating disorders. The aims of this study were; 1) exploring the extent to which DBT techniques were used by self-identified DBT clinicians treating eating disorders; 2) determining whether therapists fell into distinct groups, based on their usage of DBT techniques; and 3) examining whether clinician characteristics were related to the use of such techniques. Method Seventy-three clinicians offering DBT for eating disorders completed an online survey about their use of specific DBT techniques. They also completed measures of personality and intolerance of uncertainty. Results In relation to the first aim, the pattern of use of DBT techniques showed a bimodal distribution — most were used either a lot or a little. Considering the second aim, clinicians fell into two groups according to the techniques that they delivered — one characterized by a higher use of DBT techniques and the other by a higher use of techniques that were specific to the treatment of eating disorders, rather than DBT methods. Finally, more experienced clinicians were more likely to be in the ‘DBT technique-focused’ group. Discussion DBT clinicians are encouraged to implement both sets of techniques (DBT techniques and standard techniques for the treatment of eating disorders) in an integrated way. Training, supervision and the use of manuals are recommended to decrease therapist drift in DBT.

Blastocystis spp is a common intestinal parasite of humans and animals that has been associated to the etiology of irritable bowel syndrome (IBS); however, some studies have not found this association. Furthermore, many biological features of Blastocystis are little known. The objective of present study was to assess the generation times of Blastocystis cultures, from IBS patients and from asymptomatic carriers. A total of 100 isolates were obtained from 50 IBS patients and from 50 asymptomatic carriers. Up to 50 mg of feces from each participant were cultured in Barret's and in Pavlova's media during 48 h. Initial and final parasitological load were measured by microscopy and by quantitative PCR. Amplicons were purified, sequenced and submitted to GenBank; sequences were analysed for genetic diversity and a Bayesian inference allowed identifying genetic subtypes (ST). Generation times for Blastocystis isolates in both media, based on microscopic measures and molecular assays, were calculated. The clinical symptoms of IBS patients and distribution of Blastocystis ST 1, 2 and 3 in both groups was comparable to previous reports. Interestingly, the group of cases showed scarce mean nucleotide diversity (π) as compared to the control group (0.011±0.016 and 0.118±0.177, respectively), whilst high gene flow and small genetic differentiation indexes between different ST were found. Besides, Tajima's D test showed negative values for ST1-ST3. No statistical differences regarding parasitological load between cases and controls in both media, as searched by microscopy and by qPCR, were detected except that parasites grew faster in Barret's than in Pavlova's medium. Interestingly, slow growth of isolates recovered from cases in comparison to those of controls was observed (p