Exploring Genetic Interactions in Colombian Women with Polycystic Ovarian Syndrome: A Study on SNP-SNP Associations.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.

Correlation and concordance of carotid Doppler ultrasound and echocardiography with invasive cardiac output measurement in critically ill patients.

BACKGROUND: Critical care management heavily relies on accurate cardiac output (CO) measurement. Echocardiography has been a mainstay in non-invasive cardiac monitoring; however, its comparability to invasive methods warrants further exploration. Recent studies have suggested the potential of carotid Doppler measurements as a promising approach to estimate CO. Despite this potential, the literature presents mixed outcomes regarding its reliability and accuracy. This study aims to evaluate the correlation and concordance between carotid Doppler ultrasonography and invasive hemodynamic monitoring in estimating CO in critically ill patients. Furthermore, it assesses the concordance and correlation between echocardiography CO and the standard invasive CO measurements. METHODS: This concordance study involved critically ill adults requiring invasive CO measurement. Patients with arrhythmias, severe valvulopathy, pregnancy, and poor acoustic window were excluded. Statistical analyses comprised univariate analysis, Wilcoxon signed-rank test, Spearman correlation, and intraclass correlation coefficient. Ethical approval was granted by the institution's ethics committee. RESULTS: A total of 49 critically ill patients were included, predominantly male (63.27%), with a median age of 57 years. Diagnoses included subarachnoid hemorrhage (53.06%) and heart failure (8.16%). Mean cardiac index was 3.36 ± 0.81 L/min/m2 and mean cardiac output was 5.98 ± 1.47 L/min. Spearman correlation coefficient between echocardiography and invasive CO measurements was 0.58 (p-value = p < 0.001), with an ICC of 0.59 for CO and 0.52 for cardiac index. Carotid measurements displayed no significant correlation with invasive CO. CONCLUSION: There is a moderate correlation and concordance between echocardiography and invasive CO measurements. There is no significant correlation between carotid variables and invasive CO, underscoring the necessity for cautious interpretation and application, particularly in patients with distinctive cerebral blood flow dynamics.

Effects of dietary supplementation of cobiotic based on Agave fructans on growth performance, blood parameters, oxidative damage and immune status of broiler.

This study evaluated the effect of cobiotic (CO) composed of organic fructans powder of Agave tequilana and turmeric powder of Curcuma longa L. as an alternative of antibiotic growth promoters (AGPs) on growth performance, blood parameters, intestinal pH, oxidative stress, and cytokines serum levels of broiler chickens. A total of 135 one-day-old Ross 308 broilers distributed to five experimental groups, which included starter or finisher standard diets without AGPs (CON), CON + 0.25 COLI-ZIN g/kg feed (AGP), CON + 0.1 g Agave fructans/kg feed (AF), CON + 0.5 g turmeric powder/kg feed (TP) and CON + 0.1 g AF + 0.5 g TP /kg feed (CO), for 49 days. AF followed by TP, decreased feed intake, obtaining the best FCR. AGP increased the heterophil-lymphocyte ratio compared to other groups. CO significantly decreased the pH of the cecal content. AF increased IL-10 levels, while TP decreased it. AF decreased the IL-1ß levels. The present study showed that including a cobiotic based on AF and TP or components separately in a broilers diet improved growth performance, modified intestinal and cecum pH, and stimulated the immune system, which suggests CO as a safe alternative to AGP.

Percutaneous Fluoroscopic-Guided Celiac Plexus Approach: Results in a Pig Cadaveric Model.

Celiac plexus block (CPB) and neurolysis (CPN) are used for pain management in people suffering from abdominal tumours or chronic pancreatitis. The fluoroscopically guided approach common in human medicine has not been described in veterinary settings. The aim of this study was to describe a fluoroscopic approach to the celiac plexus (CP) in fresh pig cadavers. Twelve animals were included in the procedure. Cadavers were positioned in sternal position and, under fluoroscopic guidance, a Chiba needle was inserted parasagittal at 6 cm from the spinal midline at the level of the last thoracic vertebra. From the left side, the needle was directed medio-ventrally with a 45° angle towards the T15 vertebral body; once the vertebral body was contacted, the needle was advanced 1 cm ventrally towards the midline. Iodinated contrast was injected to confirm the location. Following this, 2 mL of dye (China ink) was injected. A laparotomy was performed, and dyed tissue was dissected and prepared for both histochemical and immunohistochemical techniques. In 10 out of 12 samples submitted for histological evaluation, nervous tissue belonging to CP was observed. Fluoroscopy guidance allows for feasible access to the CP in swine cadavers in this study. Further studies are warranted to determine the efficacy of this technique in swine and other veterinary species.

Implementation of the Recovery Model and Its Outcomes in Patients with Severe Mental Disorder.

BACKGROUND: The recovery model assumes that the patient can experience personal growth even while maintaining symptoms of a mental disorder. In order to achieve this recovery, the practices of professionals must also change. However, in our setting, there are limited data on the implementation of practices based on the recovery model and their effect on personal recovery. OBJECTIVE: To describe the association between professionals' practices and patients' personal recovery. METHODS: An observational and cross-sectional study in which the Recovery Self-Assessment (RSA) was used to assess the degree of implementation of the different practices and the Recovery Assessment Scale (RAS) was used to assess the personal recovery of 307 patients with severe mental disorders. RESULTS: Patients attended by professionals who followed the recovery model obtained a greater personal recovery (p < 0.001, d = 1.10). The dimension associated with greater recovery was that of working toward life goals. The least implemented dimensions had to do with offering treatment options and patient participation in decision-making. This study was conducted in accordance with STROBE (STrengthening the Reporting of OBservational studies in Epidemiology). CONCLUSIONS: Although this is a cross-sectional study that does not allow us to establish causal relationships, it shows that the model with which mental health professionals work is associated with patients' chances of recovery. We therefore consider that it is important to foster the implementation of practices based on the recovery model within mental health care.

Relationship Between Brugada Syndrome and Ischemic Stroke: A Case Report and Comprehensive Literature Review.

BACKGROUND Brugada syndrome is characterized by specific electrocardiographic changes predisposing individuals to ventricular arrhythmias and sudden cardiac death. Cases of coexisting Brugada syndrome and ischemic stroke are seldom documented, and an underlying pathophysiological link is yet unknown. This article presents a case in which a patient exhibited both Brugada syndrome patterns and an ischemic stroke, prompting a comprehensive literature review to explore the potential association between Brugada syndrome and ischemic stroke. CASE REPORT A 49-year-old man, previously healthy, was admitted to the hospital after being discovered unconscious at his workplace. Physical exam showed low oxygen saturation, fever, and abnormal neurological findings. Head computed tomography revealed a significant posterior circulation ischemic stroke. An electrocardiogram revealed Brugada syndrome type II initially, progressing to type III pattern. Despite efforts, the patient's condition rapidly deteriorated, leading to death within 24 hours. As far as we're aware, Brugada patterns following a posterior circulation ischemic stroke have only been documented in 1 other instance, in which the patient was also diagnosed with atrial fibrillation. CONCLUSIONS Both our literature review and the presented case indicate that Brugada patterns may coexist with and even be associated with ischemic stroke. More extensive research is required to shed light on this potential association. The question of whether Brugada syndrome is a precursor to or a result of ischemic stroke remains unanswered. We propose that patients with ischemic stroke should undergo an evaluation for electrocardiographic signs indicative of Brugada syndrome, particularly if no clear causes, like cardioembolism, are evident.

The diagnostic accuracy of cardiac ultrasound for acute myocardial ischemia in the emergency department: a systematic review and meta-analysis.

BACKGROUND: Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy. METHODS: A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case-control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors. RESULTS: Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0-86.8%) and specificity was 87.3% (95%CI 79.9-92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies. CONCLUSIONS: Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance. PROTOCOL REGISTRATION: PROSPERO (CRD42023392058).

Bedside Ultrasound to Guide the Diagnosis and Treatment of Fulminant Right Heart Failure: A Case Report.

BACKGROUND Right ventricular (RV) failure can result from acute or chronic cardiac or pulmonary conditions, or both, resulting in increased afterload, reduced contractility, changes in preload, ventricular interdependence, or dysrhythmias. Notably, increased afterload, particularly among previously healthy individuals, is often the primary cause of RV failure in cases of pulmonary and cardiac origin. Massive pulmonary thromboembolism is a common cause of impending RV failure, and chronic conditions like atrial septal defects can also contribute to pulmonary hypertension. CASE REPORT A 72-year-old patient, with no known past medical history, presented to the emergency department in profound shock, rapidly progressing to cardiorespiratory arrest. Bedside ultrasound revealed marked right chambers dilatation, severe mitral and tricuspid insufficiency, a large atrial septal defect, mild pericardial effusion, and global hypokinesia. This case illustrates how multiple mechanisms of RV dysfunction can converge, leading to fulminant RV failure and subsequent cardiac arrest, including increased afterload, decreased contractility, dysrhythmias, and ventricular interdependence. CONCLUSIONS This article emphasizes the usefulness of bedside ultrasound in diagnosing and elucidating the causes of circulatory collapse. In this patient, ultrasound played an important role in identifying 3 contributing factors: chronic RV overload from an extensive atrial septal defect, left ventricular impact due to ventricular interdependence, and acute pulmonary thromboembolism. Being aware of these factors, along with the practicality of bedside ultrasound, allowing emergency physicians to make prompt diagnoses and effectively manage RV failure-related emergencies.

SARAF overexpression impairs thrombin-induced Ca2+ homeostasis in neonatal platelets.

Neonatal platelets present a reduced response to the platelet agonist, thrombin (Thr), thus resulting in a deficient Thr-induced aggregation. These alterations are more pronounced in premature newborns. Here, our aim was to uncover the causes underneath the impaired Ca2+ homeostasis described in neonatal platelets. Both Ca2+ mobilization and Ca2+ influx in response to Thr are decreased in neonatal platelets compared to maternal and control woman platelets. In neonatal platelets, we observed impaired Ca2+ mobilization in response to the PAR-1 agonist (SFLLRN) or by blocking SERCA3 function with tert-butylhydroquinone. Regarding SOCE, the STIM1 regulatory protein, SARAF, was found overexpressed in neonatal platelets, promoting an increase in STIM1/SARAF interaction even under resting conditions. Additionally, higher interaction between SARAF and PDCD61/ALG2 was also observed, reducing SARAF ubiquitination and prolonging its half-life. These results were reproduced by overexpressing SARAF in MEG01 and DAMI cells. Finally, we also observed that pannexin 1 permeability is enhanced in response to Thr in control woman and maternal platelets, but not in neonatal platelets, hence, leading to the deregulation of the Ca2+ entry found in neonatal platelets. Summarizing, we show that in neonatal platelets both Ca2+ accumulation in the intracellular stores and Thr-evoked Ca2+ entry through either capacitative channels or non-selective channels are altered in neonatal platelets, contributing to deregulated Ca2+ homeostasis in neonatal platelets and leading to the altered aggregation observed in these subjects.

Characterization of cornea donors at a tissue center in the city of Medellin, Colombia.

The cornea transplant is considered the most frequently performed type of transplant in the world, with a demand that has been increasing in recent years. An observational descriptive study was conducted, focusing on the ocular tissue extracted from cadaveric donors from January 2019 to December 2021 at the Red Cross Eye Bank in Medellin, Colombia. This is the first epidemiological characterization of corneal donor tissues within the eye banks of our city, where high rates of violence-related deaths explain that tissue donors are mostly young individuals. This, in turn, results in excellent counts of endothelial cells and tissue viability in their microscopic studies. Additionally, there are lower rates of discarded tissues compared to similar studies.

Gait analysis: An effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications.

INTRODUCTION: Tissue engineering has emerged as an innovative approach to treat critical-size bone defects using biocompatible scaffolds, thus avoiding complex distraction surgeries or limited stock grafts. Continuous regeneration monitoring is essential in critical-size cases due to the frequent appearance of non-unions. This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up. MATERIALS AND METHODS: The 15-mm metatarsal fragment of eight female merino sheep was surgically replaced by a bioceramic scaffold stabilized with an external fixator. Gait tests were performed weekly by making the sheep walk on an instrumented gangway. The evolution of different kinematic and dynamic parameters was analyzed for all the animal's limbs, as well as asymmetries between limbs. Finally, potential correlation in the recovery of the gait parameters was evaluated through the linear regression models. RESULTS: After surgery, the operated limb has an altered way of carrying body weight while walking. Its loading capacity was significantly reduced as the stance phases were shorter and less impulsive. The non-operated limbs compensated for this mobility deficit. All parameters were normalizing during the consolidation phase while the bone callus was simultaneously mineralizing. The results also showed high levels of asymmetry between the operated limb and its contralateral, which exceeded 150% when analyzing the impulse after surgery. Gait recovery significantly correlated between symmetrical limbs. CONCLUSIONS: Gait analysis was presented as an effective, low-cost tool capable of mechanically predicting the regeneration of critical-size defects treated by tissue engineering, as comparing regeneration processes or novel scaffolds. Despite the progressive normalization as the callus mineralized, the bearing capacity reduction and the asymmetry of the operated limb were more significant than in other orthopedic alternatives.

Immunohistochemical Analysis of Knee Chondral Defect Repair after Autologous Particulated Cartilage and Platelet-Rich Plasma Treatment in Sheep.

This study performs an analysis that will enable the evaluation of the quality, durability, and structure of repaired cartilaginous extracellular matrix tissue using an autologous-based particulated autograft cartilage and platelet-rich plasma treatment (PACI + PRP). A single-blind controlled experiment was conducted on 28 sheep to evaluate the efficacy of the PACI + PRP treatment for cartilage defects. Full-thickness 8 mm diameter defects were created in the weight-bearing area of both knees. The right knees received PACI + PRP. The left knees were treated with Ringer's lactate solution (RLS) or hyaluronic acid (HA) injections. Sheep were euthanized at 9- or 18-months post-surgery. An extensive immunohistochemical analysis was performed to assess collagen types (I, II, III, V, VI, IX, X, XI) and aggrecan positivity. A semiquantitative scoring system provided a detailed evaluation of immunostaining. Collagens and aggrecan scores in the PACI + PRP groups were similar to healthy cartilage. Significant differences were found in collagens associated with matrix maturity (II and V), degradation (IX), structure and mechanics (VI), and hypertrophy (X) between healthy cartilage and RLS- or HA-repaired cartilage. The PACI + PRP treatment advanced the repair cartilage process in chondral defects with mature hyaline cartilage and enhanced the structural and mechanical qualities with better consistent cartilage, less susceptible to degradation and without hypertrophic formation over time.

Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.

Hypoxia is considered to be a stressful physiological condition, which may occur during labor and the later stages of pregnancy as a result of, among other reasons, an aged placenta. Therefore, when gestation or labor is prolonged, low oxygen supply to the tissues may last for minutes, and newborns may present breathing problems and may require resuscitation maneuvers. As a result, poor oxygen supply to tissues and to circulating cells may last for longer periods of time, leading to life-threatening conditions. In contrast to the well-known platelet activation that occurs after reperfusion of the tissues due to an ischemia/reperfusion episode, platelet alterations in response to reduced oxygen exposition following labor have been less frequently investigated. Newborns overcome temporal hypoxic conditions by changing their organ functions or by adaptation of the intracellular molecular pathways. In the present review, we aim to analyze the main platelet modifications that appear at the protein level during hypoxia in order to highlight new platelet markers linked to complications arising from temporal hypoxic conditions during labor. Thus, we demonstrate that hypoxia modifies the expression and activity of hypoxic-response proteins (HRPs), including hypoxia-induced factor (HIF-1), endoplasmic reticulum oxidase 1 (Ero1), and carbonic anhydrase (CIX). Finally, we provide updates on research related to the regulation of platelet function due to HRP activation, as well as the role of HRPs in intracellular Ca2+ homeostasis.

CAPN1 (Calpain1)-Dependent Cleavage of STIM1 (Stromal Interaction Molecule 1) Results in an Enhanced SOCE (Store-Operated Calcium Entry) in Human Neonatal Platelets.

BACKGROUND: Altered intracellular Ca2+ homeostasis in neonatal platelets has been previously reported. This study aims to examine the changes in the Ca2+ entry through the store-operated calcium entry (SOCE) mechanism in neonatal platelets. METHODS: Human platelets from either control women, mothers, and neonates were isolated and, following, were fixed after being treated as required. Platelet samples were analyzed by Western blotting, qRT-PCR, and MALDITOF/TOF. Ca2+ homeostasis was also determined. Culture cells were used as surrogated of platelets to overexpress the proteins of interest to reproduce the alterations observed in platelets. RESULTS: Altered TG (thapsigargin)-evoked SOCE, alternative molecular weight form of STIM1 (stromal interaction molecule 1; s-STIM1 [short STIM1 isoform (478 aa)], around 60 kDa) and overexpression of SARAF (SOCE-associated regulatory factor) were found in neonatal platelets as compared to maternal and control women platelets. s-STIM1 may result due to CAPN1 (calpain1)-dependent processing, as confirmed in platelets and MEG01 cells by using calpeptin and overexpressing CAPN1, respectively. In HEK293 (STIM1 and STIM2 [stromal interaction molecule 2] double knockout) cells transfected either with c-STIM1 (canonical STIM1 [685 aa]), s-STIM1 (478), STIM1B (540), and CAPN1 overexpression plasmids, we found s-STIM1 and c-STIM1, except in cells overexpressing s-STIM1 (478) that lacked CAPN1 target residues. These results and the in silico analysis, lead us to conclude that STIM1 is cleaved at Q496 by CAPN1. Ca2+ imaging analysis and coimmunoprecipitation assay using MEG01 and HEK293 cells overexpressing SARAF together with s-STIM1 (478) reported a reduced slow Ca2+-dependent inactivation, so reproducing the Ca2+-homeostasis pattern observed in neonatal platelets. CONCLUSIONS: CAPN1 may cleave STIM1 in neonatal platelets, hence, impairing SARAF coupling after SOCE activation. s-STIM1 may avoid slow Ca2+-dependent inactivation and, subsequently, results in an enhanced TG-evoked SOCE as observed in neonatal platelets.