Modulating protein unfolding and refolding via the synergistic association of an anionic and a nonionic surfactant.

HYPOTHESIS: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation. EXPERIMENTS: In this work, the behavior of three model proteins (human growth hormone, bovine serum albumin, and ß-lactoglobulin) was investigated in the presence of the anionic surfactant sodium dodecylsulfate, the nonionic surfactant ß-dodecylmaltoside, and mixtures of both surfactants. The transitions occurring to the proteins were determined using intrinsic fluorescence spectroscopy and far-UV circular dichroism. Based on these results, we developed a detailed interaction model for human growth hormone. Using nuclear magnetic resonance and contrast-variation small-angle neutron scattering, we studied the amino acid environment and the conformational state of the protein. FINDINGS: The results demonstrate the key role of surfactant cooperation in defining the conformational state of the proteins, which can shift away or toward the folded state depending on the nonionic-to-ionic surfactant ratio. Dodecylmaltoside, initially a non-interacting surfactant, can unexpectedly associate with sodium dodecylsulfate-unfolded proteins to further impact their conformation at low nonionic-to-ionic surfactant ratio. When this ratio increases, the protein begins to retrieve the folded state. However, the native conformation cannot be fully recovered due to remnant surfactant molecules still adsorbed to the protein. This study demonstrates that the conformational landscape of the protein depends on a delicate interplay between the surfactants, ultimately controlled by the ratio between them, resulting in unpredictable changes in the protein conformation.

Characterization of Quaternary-Ammonium-Based Ionogel Membranes for Application in Proton Exchange Membrane Fuel Cells.

In recent years, the quest to advance fuel cell technologies has intensified, driven by the imperative to reduce reliance on hydrocarbon-derived fuels and mitigate pollutant emissions. Proton exchange membranes are a critical material of fuel cell technologies. The potential of ionic liquid-based polymer inclusion membranes or ionogels for proton exchange membrane fuel cells (PEMFCs) has recently appeared. Thermal stability, SEM-EDX characterization, NMR and IR characterization, thermogravimetric analysis, ion exchange capacity, and water uptake are key properties of these membranes which need to be investigated. In this work, ionogel based on quaternary ammonium salts, such as [N8,8,8,1+][Cl-], [N8,8,8,1+][Br-], and [N8-10,8-10,8-10,1+][Cl-] in various compositions with poly(vinyl chloride) are extensively studied and characterized based on those key properties. The best properties were obtained when a quaternary ammonium cation was combined with a bromide anion. Finally, ionogels are tested in microbial fuel cells. Microbial fuel cells based on the ionogel reach a maximum of 147 mW/m2, which represents 55% of the reference membrane (Nafion 212). These results indicate that we still have the possibility of improvement through the appropriate selection of the cation and anion of the ionic liquid. Overall, the promise of ionogel membranes as a viable alternative in fuel cell applications has been demonstrated.

Fragility of overactive bladder medication clinical trials: A systematic review.

PURPOSE: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied. MATERIALS AND METHODS: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression. RESULTS: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001). CONCLUSIONS: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile.

Evaluation of a catch-up strategy for the vaccination in patients with hepatitis C virus.

Vaccination in patients with advanced chronic liver disease (ACLD) is an essential part of their comprehensive healthcare. These individuals may have impaired phagocytic function and diminished production of opsonizing antibodies, resulting in increased susceptibility to bacterial infections, particularly pneumococcal pneumonia. Similarly, there is an increased risk of fulminant hepatitis due to hepatitis A and B viruses. The Ministry of Health updated specific vaccination recommendations for this group in 2018.

Electric Bicycle Injuries and Hospitalizations.

This cross-sectional study investigates injury trends associated with electric bicycles in the US from 2017 to 2022.

Real-World Complications of the SpaceOAR Hydrogel Spacer: A Review of the Manufacturer and User Facility Device Experience Database.

OBJECTIVE: To characterize adverse events related to use of the perirectal spacing agent SpaceOAR, we examined the Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried for "SpaceOAR" and "Augmenix" from June 2015 (when SpaceOAR was approved by the Food and Drug Administration) to October 2022. Reports were reviewed for adverse events (AEs), operative procedures performed because of the AE, and changes to the radiation plan. AEs were categorized using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: Six hundred fifty-four reports were reviewed. Eighty-four were excluded and 4 reports reviewed 2 separate cases of SpaceOAR administration. Five hundred seventy-four cases were ultimately included. Three deaths were reported (0.5% of all AEs). One point six percent of cases represented CTCAE grade 4 injuries (life-threatening consequences; urgent intervention indicated), 15.9% grade 3 (severe but not immediately life-threatening; hospitalization), 24.2% grade 2 (moderate; local/noninvasive intervention), and 57% of events were CTCAE grade 1 (mild; asymptomatic or mild symptoms). Bowel diversion occurred in 29 cases (9%). CONCLUSION: Both asymptomatic (n = 311) and debilitating (n = 12) complications of SpaceOAR hydrogel use were identified. Death, gel embolization, anaphylaxis, rectal ulcerations, and infections requiring bowel or urinary diversions were among the complications reviewed. Providers should consider these potential complications before perirectal spacer administration and during patient counseling.

Terminal efficiency, Lag and dropout in cohorts from 2007 to 2014 of dental students at the University of Costa Rica / Eficiencia terminal, rezago y abandono en las cohortes del 2007 al 2014 de estudiantes de Odontología de la Universidad de Costa Rica

Abstract Determine the terminal efficiency, lag and dropout in the cohorts of students who entered the dentistry career at the Faculty of Dentistry at University of Costa Rica in the lapse 2007 to 2014. Data from 736 files were collected. The variables considered were sex, admission age, nationality, marital status, children, admission note, domicile and high school. The data was collected from the Student Application System, the physical files, and the data base from the Supreme Court of Elections of Costa Rica. Descriptive statistics, bivariate and multivariate analysis were made, which were implemented from two logistic regression models. 98% of the students were Costa Rican, 68% women, 79% entered according to the admission note, 43% entered with an age of 18 years or less, 50% came from a public school, 77% resided in the Greater Metropolitan Area and 95% were single and remained without children. The average terminal efficiency was 6%; 46% of students have graduated with lag, 16% are still enrolled and 32% dropped out. Sex, age, admission note, and motherhood are sociodemographic variables that are associated with terminal efficiency and dropout. The average terminal efficiency in the cohorts from 2007 to 2014 in the courses at the Faculty of Dentistry University of Costa Rica was very low, almost half of the students graduated with lag and about a third dropped out the studies. The grade from the admission note seems to be a predictor of students'academic behavior, higher grade had more chances of graduating and less likely to dropout.

Resumen Determinar la eficiencia terminal, el rezago y el abandono en las cohortes de los estudiantes que ingresaron a la carrera de Odontología de la Facultad de Odontología UCR en el período 2007 al 2014. Se recopilaron los datos de 736 expedientes. Las variables consideradas fueron: sexo, edad de ingreso, nacionalidad, estado civil, hijos, lugar y colegio de procedencia, y nota de examen de admisión. Los datos se recopilaron del Sistema de Aplicaciones Estudiantiles, los expedientes físicos y del Tribunal Supremo de Elecciones de Costa Rica. Se realizó estadística descriptiva, análisis bivariado y multivariado que se implementó a partir de dos modelos de regresión logística. El 98% de los estudiantes fueron costarricenses, el 68% mujeres, el 79% ingresó según la nota de admisión, el 43% ingresó con una edad de 18 años o menos, el 50% provenía de un colegio público, el 77% residía en la gran área Metropolitana y el 95% eran solteros y permanecieron sin hijos. La eficiencia terminal en promedio fue de 6%; el 46% de los estudiantes se han graduado con rezago, el 16% continúan matriculados y el 32% hizo abandono de los estudios. El sexo, la edad, la nota del examen de admisión y la maternidad son variables sociodemográficas que se asocian con la eficiencia terminal y el abandono. El promedio de la eficiencia terminal en las cohortes del 2007 al 2014 en la carrera de Odontología de la Facultad de Odontología UCR fue muy bajo, casi la mitad de los estudiantes se han graduado con rezago y cerca de un tercio hizo abandono de los estudios. La nota del examen de admisión parece ser un predictor en el comportamiento académico de los estudiantes: a mayor nota más posibilidades de graduarse y menos de abandonar la carrera.

NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.

Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. Results: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells. Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.

Polymeric Inclusion Membranes Based on Ionic Liquids for Selective Separation of Metal Ions.

In this work, poly(vinyl chloride)-based polymeric ionic liquid inclusion membranes were used in the selective separation of Fe(III), Zn(II), Cd(II), and Cu(II) from hydrochloride aqueous solutions. The ionic liquids under study were 1-octyl-3-methylimidazolium hexafluorophosphate, [omim+][PF6-] and methyl trioctyl ammonium chloride, [MTOA+][Cl-]. For this purpose, stability studies of different IL/base polymer compositions against aqueous phases were carried out. Among all polymer inclusion membranes studied, [omim+][PF6-]/PVC membranes at a ratio of 30/70 and [MTOA+][Cl-]/PVC membranes at a ratio of 70/30 were able to retain up to 82% and 48% of the weight of the initial ionic liquid, respectively, after being exposed to a solution of metal ions in 1 M HCl for 2048 h (85 days). It was found that polymer inclusion membranes based on the ionic liquid methyl trioctyl ammonium chloride allowed the selective separation of Zn(II)/Cu(II) and Zn(II)/Fe(III) mixtures with separation factors of 1996, 606 and, to a lesser extent but also satisfactorily, Cd(II)/Cu(II) mixtures, with a separation factor of 112. Therefore, selecting the appropriate ionic liquid/base polymer mixture makes it possible to create polymeric inclusion membranes capable of selectively separating target metal ions.

Dental anxiety and oral health-related quality of life before and after non-surgical periodontal treatment.

OBJECTIVES: To (1) investigate dental anxiety (DA) and oral health-related quality of life (OHRQOL) before and after non-surgical periodontal treatment (NSPT) and (2) determine correlations between these patient-reported measures. MATERIALS AND METHODS: Demographics, smoking habits, dental pain, Modified Corah's Dental Anxiety Scale (MDAS), and Oral Health Impact Profile (OHIP-14) were assessed in eighty-two participants. RESULTS: Mean age was 48.3 years ± 11.5. At baseline, 8.5% reported being active smokers. Of non-smokers, 11% reported being an ex-smoker. After NSPT, 11.0% reported smoking. Patients' maximal pain in the last month decreased after therapy. Before treatment, participants reported higher DA. Extreme DA was observed in 8.5% of participants before therapy. Afterwards, 2.4% of participants reported extreme DA. Fear of having a foreign object in the mouth decreased after NSPT. All OHIP-14 scores, except functional limitation, improved post-treatment. Higher DA was associated with worse OHRQoL before treatment. After treatment, total MDAS score was associated with OHIP-14 global score, physical pain, psychological disability, and social disability. Worse MDAS sub-scores were associated with a higher OHIP-14 global score. Individuals with "normal/slight anxiety" had a significant improvement in OHRQoL, whereas people in the "moderate and extreme anxiety" group did not report a significant improvement. Patients diagnosed with generalized periodontitis (GP) stage III grade B and GP stage IV grade B reported less anxiety after NSPT. CONCLUSIONS: Associations of MDAS subcategories with OHIP-14 domain scores were found before and after therapy. DA decreases and OHRQoL enhances after NSPT in patients with "normal/slight" anxiety to dental treatment. Dental practitioners should plan strategies to cope with anxiety to dental treatment and prevent decreases in OHRQoL. CLINICAL RELEVANCE: Within the limitations of this study, DA and OHRQoL were positively correlated in patients with periodontitis, before and after NSPT, using the MDAS and OHIP-14 questionnaires. The results of our study suggest that treatment is effective in terms of alleviating DA and improving oral health, along with quality of life, in patients that report "normal/slight" anxiety to dental treatment. Nonetheless, results must be interpreted with caution since patients are generally anxious before any type of dental treatment. DA may not just be confined to NSPT per se. According to our results, evaluation of both outcomes should be an integral part of routine periodontal clinical evaluation and periodontal reevaluation of initial therapy. It is important that clinicians learn to identify patients that suffer from anxiety and take time to explain the treatment procedures to the patient, to strive for patient's emotional well-being before, during, and after dental care services. The use of specific questionnaires for both DA and OHRQoL may be more appropriate to demonstrate the psychological and quality of life differences due to periodontal disease and NSPT.

Upper gastrointestinal bleeding and Rigler triad.

Gallstone ileus is a rare complication of cholelithiasis, characterized by mechanical bowel obstruction due to a biliary calculus originating from a bilioenteric fistula. The Rigler triad, consisting of aerobilia, ectopic gallstone, and intestinal obstruction, is rarely observed in its complete form. We present the case of a 92-year-old male with a history of acute lithiasic cholecystitis who presented to the Emergency department with acute epigastric pain. Initial evaluation revealed gallbladder dilatation, gallstones, and gallbladder wall thickening suggestive of acute cholecystitis. During hospitalization, the patient experienced an episode of hematemesis, leading to the diagnosis of a cholecystoduodenal fistula and a large blood clot in the duodenal bulb. Further imaging showed an ectopic gallstone causing small bowel obstruction. The patient underwent urgent surgery for stone extraction, followed by endoscopic intervention for the bleeding vessel identified at a subsequent gastroscopy. Unfortunately, the patient had a poor postoperative course and passed away seven days later. This case report highlights the exceptional occurrence of both the Rigler triad and upper gastrointestinal bleeding in a patient with gallstone ileus. Surgical intervention is crucial for the initial resolution of intestinal obstruction, followed by cholecystectomy and repair of the bilioenteric fistula. Awareness of these rare presentations is important for timely diagnosis and appropriate management of this uncommon complication of cholelithiasis.

Las mutaciones missense en el dominio ROD2 de la filamina C muestran un fenotipo con miocardiopatía restrictiva/hipertrófica y miocardio en dientes de sierra / ROD2 domain filamin C missense mutations exhibit a distinctive cardiac phenotype with restrictive/hypertrophic cardiomyopathy and saw-tooth myocardium

Introducción y objetivos Recientemente se han descrito mutaciones missense en la filamina C (FLNC) como causa de miocardiopatía. Los conocimientos sobre la patogenicidad y la correlación genotipo-fenotipo son escasos. Nuestro objetivo es describir un fenotipo cardiaco distintivo relacionado con mutaciones missense en el dominio ROD2 de FLNC (FLNC-mRod2). Métodos Incluimos 21 familias independientes con fenotipo de miocardiopatía hipertrófica (MCH)/miocardiopatía restrictiva (MCR) portadoras de variantes missense en FLNC-mRod2. Se estudió clínicamente a los portadores, además de hacer un cribado en cascada. Se analizó histológicamente el tejido miocárdico de tres corazones explantados y se comparó con un corazón portador de un truncamiento de FLNC y con un control sano. Se transfectaron plásmidos con mutaciones missense de FLNC y se analizaron mediante microscopía confocal. Resultados En 11 familias (52%) con 20 individuos evaluados (37 [23,7-52,7] años), 15 casos presentaron un fenotipo cardiaco consistente en una superposición de MCH-MCR e hipertrabeculación ventricular izquierda (apariencia de dientes de sierra). Durante una mediana de seguimiento de 6,49 años presentaron principalmente insuficiencia cardiaca avanzada (16 (80%) disfunción diastólica, 3 trasplantes cardiacos, 3 muertes por insuficiencia cardiaca) en ausencia de alteraciones de la conducción cardiaca o miopatía esquelética. Un total de 6 familias presentaban segregación genotipo-fenotipo leve, y las restantes eran mutaciones de novo. Se observó una remodelación de la matriz extracelular y distribución de la FLNC diferencial en los cardiomiocitos. Las células HT1080 y H9c2 no revelaron agregados citoplasmáticos de FLNC. Conclusiones Las variantes en FLNC-mRod2 exhiben una alta prevalencia de fenotipo solapado de MCR, MCH e hipertrabeculación en dientes de sierra, con una remodelación histopatológica cardiaca distintiva (AU)

Introduction and objectives Missense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. Methods We recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. Results Eleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. Conclusions FLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling (AU)

Training and implementation of handheld ultrasound technology at Georgetown Public Hospital Corporation in Guyana: a virtual learning cohort study

A virtual point-of-care ultrasound (POCUS) education program was initiated to introduce handheld ultrasound technology to Georgetown Public Hospital Corporation in Guyana, a low-resource setting. We studied ultrasound competency and participant satisfaction in a cohort of 20 physicians-in-training through the urology clinic. The program consisted of a training phase, where they learned how to use the Butterfly iQ ultrasound, and a mentored implementation phase, where they applied their skills in the clinic. The assessment was through written exams and an objective structured clinical exam (OSCE). Fourteen students completed the program. The written exam scores were 3.36/5 in the training phase and 3.57/5 in the mentored implementation phase, and all students earned 100% on the OSCE. Students expressed satisfaction with the program. Our POCUS education program demonstrates the potential to teach clinical skills in low-resource settings and the value of virtual global health partnerships in advancing POCUS and minimally invasive diagnostics.

Dehydrofluorination Process of Poly(vinylidene difluoride) PVdF-Based Gel Polymer Electrolytes and Its Effect on Lithium-Sulfur Batteries.

Gel polymer electrolytes (GPEs) are emerging as suitable candidates for high-performing lithium-sulfur batteries (LSBs) due to their excellent performance and improved safety. Within them, poly(vinylidene difluoride) (PVdF) and its derivatives have been widely used as polymer hosts due to their ideal mechanical and electrochemical properties. However, their poor stability with lithium metal (Li0) anode has been identified as their main drawback. Here, the stability of two PVdF-based GPEs with Li0 and their application in LSBs is studied. PVdF-based GPEs undergo a dehydrofluorination process upon contact with the Li0. This process results in the formation of a LiF-rich solid electrolyte interphase that provides high stability during galvanostatic cycling. Nevertheless, despite their outstanding initial discharge, both GPEs show an unsuitable battery performance characterized by a capacity drop, ascribed to the loss of the lithium polysulfides and their interaction with the dehydrofluorinated polymer host. Through the introduction of an intriguing lithium salt (lithium nitrate) in the electrolyte, a significant improvement is achieved delivering higher capacity retention. Apart from providing a detailed study of the hitherto poorly characterized interaction process between PVdF-based GPEs and the Li0, this study demonstrates the need for an anode protection process to use this type of electrolytes in LSBs.

Sociodemographic and academic characteristics of the admission profile of students, faculty of dentistry, University of Costa Rica 2007-2014 / Características sociodemográficas y académicas del perfil de ingreso de estudiantes de la Facultad de Odontología de la Universidad de Costa Rica 2007-2014

The objective of this research was to determine some of the sociodemographic and academic characteristics of the students who entered the Dentistry career in the period 2007 to 2014. Data was collected from 673 student files. The variables considered were sex, admission age, marital status, children, nationality, place of origin, high school of origin, and admission exam score. The data was obtained from the database of the Student Applications System, the physical files, and the Supreme Electoral Tribunal of Costa Rica. Descriptive statistics were performed, establishing the absolute and relative frequency of the variables. The Mann-Whitney test was used to determine if there were statistically significant differences between the admission exam and the established sociodemographic variables (p<0,05, IC 95%). 68,4% of the students are female. The average age was 18.4 years (SD=2,41). 99,0% of the students are from Costa Rica. 99,3% were single and only 0,9% had children. The largest number of students entered through an admission exam (78.9%) and 50.7% studied at a public high school. Regarding the address, 77.9% of the subjects resided in the Greater Metropolitan Area. The average grade of the admission exam was 613,8 (SD=49,95). There was a statistically significant difference between the entrance exam grade and the different types of high schools of origin. The group of students who entered to train as Dentists at the University of Costa Rica from 2007 to 2014 was a population with an average age of entry of 18,4 years, Costa Rican, predominantly female, single, without children, from geographic areas within the Greater Metropolitan Area (GMA), graduated from public schools with an average admission exam grade of 612,2.

El objetivo de esta investigación fue determinar algunas de las características sociodemográficas y académicas de los estudiantes que ingresaron a la carrera de Odontología en el período 2007 al 2014. Se recopilaron los datos de 673 expedientes de los estudiantes. Las variables consideradas fueron: sexo, edad de ingreso, estado civil, hijos, nacionalidad, lugar de procedencia, colegio de procedencia y nota de examen de admisión. Los datos se obtuvieron de la base de datos del Sistema de Aplicaciones Estudiantiles (SAE), los expedientes físicos y del Tribunal Supremo de Elecciones de Costa Rica. Se realizó estadística descriptiva estableciendo la frecuencia absoluta y relativa de las variables. Se empleó el test de Mann Whitney para determinar si existían diferencias estadísticamente significativas entre el examen de admisión y las variables sociodemográficas establecidas (p<0,05, IC 95%). El 68,4% de los estudiantes pertenecen al sexo femenino. La edad promedio fue de 18,4 años (DS=2,41). El 99,0% de los discentes son de nacionalidad costarricense. El 99,3% eran solteros y sólo el 0,9% tenían hijos. La mayor cantidad de estudiantes ingresaron por examen de admisión (78,9%) y el 50,7% cursó sus estudios en un colegio público. Respecto al domicilio, el 77,9% de los sujetos residían en el Gran Área Metropolitana. El promedio de nota del examen de admisión fue de 613,8 (DS=49,95). Hubo una diferencia estadísticamente significativa entre la nota del examen de admisión y los diferentes tipos de colegios de procedencia. El grupo de estudiantes que ingresaron a formarse como Odontólogos en la Universidad de Costa Rica en el periodo de 2007 al 2014 fue una población con un promedio una edad de ingreso de 18,4 años predominantemente femenina, costarricense, soltera, sin hijos, proveniente de áreas geográficas dentro del Gran Área Metropolitana (GAM), egresadas de colegios públicos con un promedio de nota de examen de admisión de 612,2.

ROD2 domain filamin C missense mutations exhibit a distinctive cardiac phenotype with restrictive/hypertrophic cardiomyopathy and saw-tooth myocardium.

INTRODUCTION AND OBJECTIVES: Missense mutations in the filamin C (FLNC) gene have been reported as cause of inherited cardiomyopathy. Knowledge of the pathogenicity and genotype-phenotype correlation remains scarce. Our aim was to describe a distinctive cardiac phenotype related to rare missense FLNC variants in the ROD2 domain. METHODS: We recruited 21 unrelated families genetically evaluated because of hypertrophic cardiomyopathy (HCM)/restrictive cardiomyopathy (RCM) phenotype carrying rare missense variants in the ROD2 domain of FLNC (FLNC-mRod2). Carriers underwent advanced cardiac imaging and genetic cascade screening. Myocardial tissue from 3 explanted hearts of a missense FLNC carrier was histologically analyzed and compared with an FLNC-truncating variant heart sample and a healthy control. Plasmids independently containing 3 FLNC missense variants were transfected and analyzed using confocal microscopy. RESULTS: Eleven families (52%) with 20 assessed individuals (37 [23.7-52.7]) years showed 15 cases with a cardiac phenotype consisting of an overlap of HCM-RCM and left ventricular hypertrabeculation (saw-tooth appearance). During a median follow-up of 6.49 years, they presented with advanced heart failure: 16 (80%) diastolic dysfunction, 3 heart transplants, 3 heart failure deaths) and absence of cardiac conduction disturbances or skeletal myopathy. A total of 6 families had moderate genotype-phenotype segregation, and the remaining were de novo variants. Differential extracellular matrix remodeling and FLNC distribution among cardiomyocytes were confirmed on histology. HT1080 and H9c2 cells did not reveal cytoplasmic aggregation of mutant FLNC. CONCLUSIONS: FLNC-mRod2 variants show a high prevalence of an overlapped phenotype comprising RCM, HCM and deep hypertrabeculation with saw-tooth appearance and distinctive cardiac histopathological remodeling.

Hydration in Deep Eutectic Solvents Induces Non-monotonic Changes in the Conformation and Stability of Proteins.

The preservation of labile biomolecules presents a major challenge in chemistry, and deep eutectic solvents (DESs) have emerged as suitable environments for this purpose. However, how the hydration of DESs impacts the behavior of proteins is often neglected. Here, we demonstrate that the amino acid environment and secondary structure of two proteins (bovine serum albumin and lysozyme) and an antibody (immunoglobulin G) in 1:2 choline chloride:glycerol and 1:2 choline chloride:urea follow a re-entrant behavior with solvent hydration. A dome-shaped transition is observed with a folded or partially folded structure at very low (<10 wt % H2O) and high (>40 wt % H2O) DES hydration, while protein unfolding increases between those regimes. Hydration also affects protein conformation and stability, as demonstrated for bovine serum albumin in hydrated 1:2 choline chloride:glycerol. In the neat DES, bovine serum albumin remains partially folded and unexpectedly undergoes unfolding and oligomerization at low water content. At intermediate hydration, the protein begins to refold and gradually retrieves the native monomer-dimer equilibrium. However, ca. 36 wt % H2O is required to recover the native folding fully. The half-denaturation temperature of the protein increases with decreasing hydration, but even the dilute DESs significantly enhance the thermal stability of bovine serum albumin. Also, protein unfolding can be reversed by rehydrating the sample to the high hydration regime, also recovering protein function. This correlation provides a new perspective to understanding protein behavior in hydrated DESs, where quantifying the DES hydration becomes imperative to identifying the folding and stability of proteins.

Gingival state and presence of red complex bacteria in 12-Year-Old schoolchildren / Estado gingival y presencia de bacterias del complejo rojo en escolares de 12 años

Abstract The objective of this study was to determine the gingival state and presence of red complex bacteria in saliva samples of 12-year-old schoolchildren. A calibrated periodontist evaluated biofilm index (BI) (Silness and Löe, 1964), presence of calculus, and gingival index (GI) (Silness and Löe, 1967) in sixty two 12-year-old students of Carmen Lyra School. Saliva samples were collected from each student. The DNA of each sample was extracted and amplified by the polymerase chain reaction (PCR) technique, using specific primers. The BI was 1.18. Calculus was present in 40.40% of the schoolchildren examined; 19.4% was supragingival calculus and 21% both supragingival and subgingival calculus. The GI was 0.97, which according to Silness and Löe is mild gingivitis. Gingivitis was present in 96.8% of the children examined. Regarding the PCR tests: 18 of the samples (31.58%) did not present any of the bacteria analyzed and the remaining 39 samples (68.42%) were positive for at least the presence of red complex bacteria. Within the limitations of this study, it is concluded that the prevalence of gingivitis and calculus is high in the sample examined, and the gingival state observed in the study population, may be related to the presence of red complex bacteria.

Resumen El objetivo de este estudio era determinar el estado gingival y la presencia de bacterias del complejo rojo en muestras de saliva de niños de 12 años de la Escuela Carmen Lyra. Una periodoncista calibrada evaluó en 62 estudiantes de 12 años de la Escuela Carmen Lyra, el índice de biofilme (IB) (Silness y Löe, 1964), la presencia de cálculo y el índice gingival (IG) (Silness y Löe, 1967). Se recolectaron muestras de saliva de cada estudiante. El ADN de cada muestra fue extraído y amplificado por medio de la prueba PCR, empleando primers específicos, para determinar la presencia de bacterias del complejo rojo. El IB fue de 1.18. El cálculo estuvo presente en el 40.40% de la muestra, se encontró 19.4% de cálculo en supragingival y 21% tanto en supragingival como en subgingival. El IG fue de 0.97, que de acuerdo con Silness y Löe es una gingivitis leve. La gingivitis estuvo presente en el 96.8 % de los niños examinados. Con respecto a las pruebas PCR: 18 de las muestras (31.58 %) no presentaron ninguna de las bacterias analizadas y las 39 muestras restantes (68.42%) fueron positivas por lo menos a la presencia de las bacterias del complejo rojo. Dentro de las limitaciones de este estudio, se concluye que la prevalencia de gingivitis y cálculo es alta en la muestra examinada y el estado gingival observado puede estar relacionado con la presencia de bacterias del complejo rojo.

Chronic cannabis use affects cerebellum dependent visuomotor adaptation.

BACKGROUND: Cannabis is one of the most commonly used substances in the world. However, its effects on human cognition are not yet fully understood. Although the cerebellum has the highest density of cannabinoid receptor type 1 (CB1R) in the human brain, literature on how cannabis use affects cerebellar-dependent learning is sparse. This study examined the effect of chronic cannabis use on sensorimotor adaptation, a cerebellar-mediated task, which has been suggested to depend on endocannabinoid signaling. METHODS: Chronic cannabis users (n = 27) with no psychiatric comorbidities and healthy, cannabis-naïve controls (n = 25) were evaluated using a visuomotor rotation task. Cannabis users were re-tested after 1 month of abstinence (n = 13) to assess whether initial differences in performance would persist after cessation of use. RESULTS: Cannabis users showed lower adaptation rates compared to controls at the first time point. However, this difference in performance did not persist when participants were retested after one month of abstinence (n = 13). Healthy controls showed attenuated implicit learning in the late phase of the adaptation during re-exposure, which was not present in cannabis users. This explains the lack of between group differences in the second time point and suggests a potential alteration of synaptic plasticity required for cerebellar learning in cannabis users. CONCLUSIONS: Overall, our results suggest that chronic cannabis users show alterations in sensorimotor adaptation, likely due to a saturation of the endocannabinoid system after chronic cannabis use.

Impact of SARS-Cov-2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry.

AIMS: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. METHODS AND RESULTS: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). CONCLUSIONS: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.