Insulin Treatment Does Not Prevent EARLY Autonomic Cardiovascular and Diastolic Dysfunctions in Streptozotocin-Induced Diabetic Rats.

Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk.

The M3 Muscarinic Acetylcholine Receptor Can Signal through Multiple G Protein Families.

The M3 muscarinic acetylcholine receptor (M3R) is a G protein-coupled receptor (GPCR) that regulates important physiologic processes, including vascular tone, bronchoconstriction, and insulin secretion. It is expressed on a wide variety of cell types, including pancreatic beta, smooth muscle, neuronal, and immune cells. Agonist binding to the M3R is thought to initiate intracellular signaling events primarily through the heterotrimeric G protein Gq. However, reports differ on the ability of M3R to couple to other G proteins beyond Gq. Using members from the four primary G protein families (Gq, Gi, Gs, and G13) in radioligand binding, GTP turnover experiments, and cellular signaling assays, including live cell G protein dissociation and second messenger assessment of cAMP and inositol trisphosphate, we show that other G protein families, particularly Gi and Gs, can also interact with the human M3R. We further show that these interactions are productive as assessed by amplification of classic second messenger signaling events. Our findings demonstrate that the M3R is more promiscuous with respect to G protein interactions than previously appreciated. SIGNIFICANCE STATEMENT: The study reveals that the human M3 muscarinic acetylcholine receptor (M3R), known for its pivotal roles in diverse physiological processes, not only activates intracellular signaling via Gq as previously known but also functionally interacts with other G protein families such as Gi and Gs, expanding our understanding of its versatility in mediating cellular responses. These findings signify a broader and more complex regulatory network governed by M3R and have implications for therapeutic targeting.

Luminescent lanthanide mixed N-phthaloylglycinate and terephthalate coordination polymers: Structural and optical properties.

A new class of lanthanide mixed-carboxylate ligands compounds with formula {[Ln2 (phthgly)4 (bdc)(H2 O)6 ]·(H2 O)4 }∞ , labelled as Ln3+ : Eu (1) and Gd (2) coordination polymers (CP) were synthesized under mild reaction conditions between lanthanide nitrate salts and a solution of N-phthaloylglycine (phthgly) and terephthalic (bdc) ligands. The (1) and (2) coordination polymers were formed by symmetric binuclear units, in which phthgly and bdc carboxylate ligands are coordinated to the lanthanide ions by different coordination modes. Surprisingly, all organic ligands participate in hydrogen bonding interactions, forming an extremally rigid crystalline structure. The red narrow emission bands from the 5 D0 →7 FJ transitions of the Eu3+ ion show a high colour purity. The intramolecular energy transfer process from L→Eu3+ ion has been discussed. The experimental intensity parameters (Ω2,4 ) reflect lower angular distortion and polarizability of the chemical environment around the metal ion compared with other Eu3+ compounds reported in the literature. This novel class of coordination polymer offers a more attractive platform for developing luminescent functional materials for different applications.

A proposed model to evaluate how changes in body condition score and the fatty acid profile of a supplement affect physiology and metabolic responses of nonlactating females.

Two experiments were designed to evaluate the effects of altering body condition score (BCS) and the profile of a fatty acid (FA) supplement on the metabolism of Bos indicus Nellore females. In experiment 1, 16 and 24 B. indicus heifers and nonlactating cows, respectively, were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) maintenance diet and BCS loss (MNT-LSS; n = 10), (3) maintenance diet supplemented with calcium salts of soybean oil for 30 d and BCS loss for 40 d (MNT+CFA-LSS; n = 10), and (4) maintenance diet for 30 d and BCS loss for 40 d with a diet containing calcium salts of soybean oil (MNT-LSS+CFA; n = 10). Following the BCS loss period, MNT-LSS, MNT+CFA-LSS, and MNT-LSS+CFA were fed a diet to promote the gain of BCS. In experiment 2, 40 Bos indicus nulliparous heifers were assigned to (1) maintenance diet (MNT-MNT; n = 10), (2) BCS loss followed by a BCS gain (LSS-REM; n = 10), (3) BCS loss followed by a BCS gain diet with CFA of palm oil (LSS-REM+PLM; n = 10), and (4) BCS loss followed by a BCS gain diet with CFA of soybean oil (LSS-REM+SOY; n = 10). Blood samples were obtained for serum haptoglobin and fecal samples for pH (experiment 2 only). In experiment 1, a treatment × day interaction was observed for BCS during the 60-d BCS loss and gain period. Animals assigned to MNT-MNT had a greater BCS than the other treatment groups on d 40 and 60 of the experiment, but no other differences were observed. Moreover, a treatment × day interaction was observed for serum haptoglobin, as on d 60, MNT-LSS had a greater mean serum haptoglobin concentration. In experiment 2, a treatment × day interaction was also observed for BCS. From d -4 to 0, LSS-REM and LSS-REM+SOY had a reduced BCS versus MNT-MNT, but also lower for LSS-REM versus MNT-MNT on d 1, and LSS-REM+PLM versus MNT-MNT on d -1 and 0. For serum haptoglobin, no treatment or treatment × day interaction was observed. A treatment × day interaction was observed for fecal pH. From d -10 to 0, MNT often had a lower fecal pH, but during realimentation, LSS-REM heifers had a reduced fecal pH on d 1, 4, and 10. In summary, we failed to demonstrate an increase in serum haptoglobin due to a BCS loss. Still, supplementation with calcium salts of FA alleviated the increase in haptoglobin and maintained fecal pH at more stable values during realimentation, regardless of the FA profile of the supplement.

New ruthenium(II) complexes with cyclic thio- and semicarbazone: evaluation of cytotoxicity and effects on cell migration and apoptosis of lung cancer cells.

We describe the synthesis, physicochemical characterization, and in vitro antitumor assays of four novel analogous ruthenium(II) complexes with general formula cis-[RuII(N-L)(P-P)2]PF6, where P-P = bis(diphenylphosphine)methane (dppm, in complexes 1 and 2) or bis(diphenylphosphine)ethane (dppe, in complexes 3 and 4) and N-L = 5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (Btsc, in complexes 1 and 3) or 5,6-diphenyltriazine-3-one (Bsc, in complexes 2 and 4). The data were consistent with cis arrangement of the biphosphine ligands. For the Btsc and Bsc ligands, the data pointed to monoanionic bidentate coordination to ruthenium(II) through N,S and N,O, respectively. Single-crystal X-ray diffraction showed that complex 1 crystallized in the monoclinic system, space group P21/c. Determination of the cytotoxicity profiles of complexes 1-4 gave SI values ranging from 1.19 to 3.50 against the human lung adenocarcinoma cell line A549 and the non-tumor lung cell line MRC-5. Although the molecular docking studies suggested that the interaction between DNA and complex 4 was energetically favorable, the experimental results showed that they interacted weakly. Overall, our results demonstrated that these novel ruthenium(II) complexes have interesting in vitro antitumor potential and this study may contribute to further studies in medicinal inorganic chemistry.

Effects of supplementing narasin to Bos indicus heifers during late-gestation and lactation on development of the offspring.

This experiment evaluated the effects of supplementing narasin during late-gestation and lactation on productive and physiological responses of Bos indicus beef heifers and their offspring. Pregnant, nulliparous Nelore heifers (N = 88) that conceived under the same fixed-time artificial insemination protocol and to the same sire were used. Heifers were ranked by maternal ability genomic score, body weight (BW) and body condition score (BCS) and allocated to 44 drylot pens (2 heifers per pen; 10 × 25 m). Pens were ranked by these traits and alternatively assigned to receive (NAR) or not (CON) 0.260 mg of narasin/kg of heifer BW daily (Elanco Saúde Animal, São Paulo, Brazil). Narasin was mixed into a supplement offered at 0.30% of heifer BW from day 0 until heifers weaned their calves (day 316), whereas CON heifers received the same supplement without narasin addition. Heifers received Urochloa brizantha hay and water for ad libitum consumption (days 0 to 316) and calved between days 97 to 112 of the experiment. After calving, heifers and offspring had access to hay and supplement; hence, supplements and narasin were offered according to heifer + calf BW beginning on day 162. No treatment differences were detected (P ≥ 0.18) for heifer BW and BCS during the experiment, although BW loss from day 0 to calving was less (P = 0.04) in NAR compared to CON heifers. Hay intake during the experiment did not differ (P = 0.79) between treatments. Serum IGF-I concentrations were greater (P = 0.05) for NAR heifers on day 60 of the experiment and did not differ (P ≥ 0.28) between treatments 24 h and 30 d after calving (treatment × day interaction; P = 0.04). No treatment effects were detected (P ≥ 0.58) for calf birth BW. Serum concentrations of total protein 24 h after birth were greater (P = 0.04) in calves from NAR compared with CON heifers, and a tendency (P = 0.10) for a similar outcome was noted for serum IgG concentrations. Diarrhea incidence did not differ (P = 0.16) between treatments, although the number of total diarrhea cases per calf were greater (P = 0.03) in the CON offspring. Growth rate of calves from NAR heifers tended (P = 0.08) to be greater, resulting in heavier calves at weaning (P ≤ 0.04) compared with CON offspring. Collectively, these outcomes indicate narasin supplementation to beef heifers as a nutritional alternative to improve cow-calf productivity via developmental programming effects during gestation, as well as direct consumption by their nursing offspring.

Disfunção autonômica cardiovascular e dano renal: papel da inflamação e do estresse oxidativo / Cardiovascular autonomic dysfunction e renal damage: role of inflammation and oxidative stress

Evidências demonstram que não só a elevação da pressão arterial, mas também o aumento da variabilidade da pressão arterial (VPA) pode contribuir para a piora no dano renal e redução da sobrevida em portadores doença renal crônica. Este artigo tem como objetivo revisar o impacto da disfunção autonômica cardiovascular (hiperatividade simpática, prejuízo nasensibilidade dos barorreceptores e/ou aumento da VPA) e sua associação com inflamação e estresse oxidativo no desenvolvimento e progressão do dano renal (AU).

Evidence shows that not only the increase in blood pressure, but also the increase in blood pressure variability (BPV) can contribute to worsening kidney damage and reduced survival in patients with chronic kidney disease. This article aims to review the impact of cardiovascular autonomic dysfunction (sympathetic hyperactivity, impaired baroreflex sensitivity and/or increased BPV) and its association with inflammation and oxidative stress on the development and progression of renal damage (AU).

An in silico method to assess antibody fragment polyreactivity.

Antibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally test our models' performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the models allow us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its functional properties. We provide a companion web-server that offers a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.

Evaluation of different cooling management strategies for lactating Holstein × Gir dairy cows.

Heat stress negatively impacts production, reproduction, and health of ruminants and strategies to alleviate these losses are warranted. Therefore, four experiments evaluated different cooling strategies on vaginal temperature (VT) of Holstein × Gir cows. Experiment 1 compared different amounts of water (2- or 4-L) over a 1-hour period from 1000 to 1100 h and 1600 to 1700 h. Experiment 2 evaluated the effects of sprinkling duration (in hours; 1- or 2-H), whereas Experiment 3 evaluated the effects of water amount (4- or 8-L) applied for 1- or 2-H. Lastly, the effects of a cooling strategy on specific hours of the day, starting at either 0700 (T-1) or 1100 h (T-2; Experiment 4), were evaluated. In all experiments, 12 Holstein × Gir cows were used in a 2 × 2 Latin Square Design containing two periods of 6 days each. Temperature and humidity index (THI) were recorded hourly and VT was recorded every 10-min throughout the experiments. As expected, an hour effect was observed for THI (P < 0.0001), which peaked early in the afternoon. In Experiment 1, a treatment × hour interaction was observed (P < 0.0001) for VT, as animals assigned to receive 4-L had a reduced VT at 1100, 1600, 1700, and 2300 h (P ≤ 0.03). During the cooling applications, cows receiving 4-L for 1 h had a reduced VT from 60 to 150 min (P ≤ 0.04). In Experiment 2, a treatment × hour interaction was observed (P < 0.0001) for VT, as animals assigned to receive 4-L of water for 2-H had a reduced VT at 1200 h (P = 0.05). Moreover, during the cooling process, VT was reduced for 2-H cows from 140 to 170 min after the beginning of the cooling process (P ≤ 0.05). In Experiment 3, animals assigned to receive 4-L + 2H had a reduced VT at 1200, 1700, 1800, and 1900 h (P < 0.001). A treatment × hour interaction was observed (P < 0.0001), as VT was reduced for 4-L + 2-H cows from 130 to 180 min after the beginning of the cooling process (P ≤ 0.05). In Experiment 4, by the time when the first cooling cycle of T-1 was applied (0700 h), T-1 cows consistently had (P ≤ 0.05) a reduced VT up to the hottest hours and greatest THI of the day (1400 and 1500 h). This pattern was maintained until the end of the last cooling cycle, whereas T-2 cows had a reduced VT. In summary, 4 L of water over a 5-min cycle for a period of 2 hours twice a day maintained VT of Holstein × Gir cows at lower levels. Moreover, the hour at which the first cooling cycle starts also should be considered when evaluating the efficacy of a cooling strategy for an entire day.

Two-Dimensional Cartesian Coordinate System Educational Toolkit: 2D-CACSET.

Engineering education benefits from the application of modern technology, allowing students to learn essential Science, Technology, Engineering, and Mathematics (STEM) related concepts through hands-on experiences. Robotic kits have been used as an innovative tool in some educational fields, being readily accepted and adopted. However, most of the time, such kits' knowledge level requires understanding basic concepts that are not always appropriate for the student. A critical concept in engineering is the Cartesian Coordinate System (CCS), an essential tool for every engineering, from graphing functions to data analysis in robotics and control applications and beyond. This paper presents the design and implementation of a novel Two-Dimensional Cartesian Coordinate System Educational Toolkit (2D-CACSET) to teach the two-dimensional representations as the first step to construct spatial thinking. This innovative educational toolkit is based on real-time location systems using Ultra-Wide Band technology. It comprises a workbench, four Anchors pinpointing X+, X-, Y+, Y- axes, seven Tags representing points in the plane, one listener connected to a PC collecting the position of the Tags, and a Graphical User Interface displaying these positions. The Educational Mechatronics Conceptual Framework (EMCF) enables constructing knowledge in concrete, graphic, and abstract levels. Hence, the students acquire this knowledge to apply it further down their career path. For this paper, three instructional designs were designed using the 2D-CACSET and the EMCF to learn about coordinate axes, quadrants, and a point in the CCS.

Comportamiento de la urgencia ginecológica durante la pandemia de COVID-19 / Behavior of the gynecological emergency during the COVID-19 pandemic

INTRODUCCIÓN: La pandemia de COVID-19 ha comportado una disminución de la consulta ginecológica al servicio de urgencia. OBJETIVO: Caracterizar las consultas en el servicio de urgencia ginecológica, evaluando la cantidad de hospitalizaciones, la necesidad de intervención quirúrgica y los factores de morbilidad, entre otros, comparado a la situación con la previa a la pandemia. MÉTODO: Se realizó un estudio de cohorte no concurrente de pacientes hospitalizadas tras una consulta espontánea al servicio de urgencia ginecológica entre las semanas 12 y 28 de 2019 y 2020 en el Hospital Clínico de la Pontificia Universidad Católica, en Santiago (Chile). Se determinaron distintos factores de morbilidad: diagnóstico de ingreso, intervención quirúrgica, complicación operatoria, días de hospitalización, hemoglobina/hematocrito de ingreso y necesidad de transfusión de unidades sanguíneas. RESULTADOS: Hubo 511 consultas al servicio de urgencia entre las semanas 12 y 28 del año 2019, en comparación con 196 el año 2020. En 2019 fueron hospitalizadas 103 mujeres, y en 2020 ingresaron 72 (odds ratio [OR]: 2.3). Disminuyó el ingreso por aborto retenido (24 vs. 12; p = 0.01), mientras que aumentó el ingreso por metrorragia posmenopáusica (9 vs 22; p = 0.01). No hubo cambio en las intervenciones quirúrgicas realizadas (86.4% vs. 84.7%; p = 0.7). Aumentaron los días de hospitalización (2.3 vs. 3.1; p < 0.0001) y la necesidad de transfusión sanguínea (2 vs. 7; p = 0.02; OR: 5.4; intervalo de confianza: 1.09-26). CONCLUSIONES: La pandemia de COVID-19 provocó una disminución en la consulta espontánea por patología ginecológica al servicio de urgencia, provocando un aumento en la relación consulta/ingreso y una mayor morbilidad en las pacientes hospitalizadas, caracterizada por una mayor necesidad de transfusión sanguínea y un aumento de los días de hospitalización.

INTRODUCTION: The COVID-19 pandemic has meant a decrease in gynecological visits to the emergency department. OBJECTIVE: To characterize the attending in the gynecological emergency service, evaluating the amount of admissions, hospitalizations, need for surgical intervention, morbidity factors, among others, compared to the pre-pandemic situation. METHOD: A non-concurrent cohort study of hospitalized patients was carried out through a spontaneous attending to the gynecological emergency service between weeks 12 and 28 of 2019 and 2020 at the Hospital Clínico of the Pontificia Universidad Católica, in Santiago (Chile). Different morbidity factors were measured: admission diagnosis, surgical intervention, surgical complication, hospital stay, admission hemoglobin, and need for transfusion of blood units. RESULTS: A total of 511 visitors to the emergency service were registered between weeks 12 and 28 of 2019, compared to 196 in 2020. In 2019 and 2020, 103 and 72 women were hospitalized respectively (odds ratio [OR]: 2.3). Admission for pregnancy loss decreased (24 vs. 12; p = 0.01), while admission for postmenopausal bleeding increased (9 vs. 22; p = 0.01). There was no change in the surgical interventions performed (86.4% vs. 84.7%; p = 0.7). The hospital stays increased (2.3 vs. 3.1; p < 0.0001) and the need for blood transfusion (2 vs. 7; p = 0.02; OR: 5.4; confidence interval: 1.09-26). CONCLUSIONS: The COVID-19 pandemic caused a decrease in spontaneous attending for gynecological pathology at the emergency service, causing an increase in the attend/admission ratio and greater morbidity in hospitalized patients characterized by a greater need for blood transfusion and an increase on the hospital stay.

Home and Neighborhood Physical Activity Location Availability among African American Adolescent Girls Living in Low-Income, Urban Communities: Associations with Objectively Measured Physical Activity.

Based on the ecological model of active living, the neighborhood environment may relate to individual physical activity (PA) behaviors. The purposes of this study were to (1) generate a replicable neighborhood-level physical activity location availability score (PALAS) from data variables associated with physical activity among adolescents and adults, and apply this score to Baltimore City, Maryland, and (2) determine if relationships exist between PA and PA location availability. Geographic information systems (GISs) were used to create the PALAS. Using linear regression models, we examined relations between objectively measured PA among low-income, urban, predominantly African American adolescent girls (n = 555, 2009-2012 data collection), and the PALAS rating of their neighborhood environment (neighborhood PALAS) and their home neighborhood area (PALAS variables/subcomponents within 0.25 miles of the home). A PALAS map of the study area was created, illustrating neighborhoods varying in availability and variety of PA locations. After adjusting for confounders, a higher neighborhood PALAS (ß = 0.10, p = 0.041) and the presence of a recreation center in the home neighborhood area (ß = 0.46, p = 0.011) were associated with more minutes per day spent in moderate to vigorous PA. Policy makers and stakeholders should consider increasing access to PA locations as a strategy to promote PA among adolescent girls.

In Silico Targeting of the Long Noncoding RNA MALAT1.

RNA targeting has gained traction over the past decade. It has become clear that dysregulation of RNA can be linked to many diseases, leading to a need for new scaffolds recognizing RNA specifically. Long noncoding RNAs are emerging as key controllers of gene expression and potential therapeutic targets. However, traditional targeting methods have overwhelmingly been focused on proteins. In this study, we used a protein computational tool and found several possible targetable pockets in a structurally characterized long noncoding RNA, MALAT1. Screening against those identified pockets revealed several hit compounds. We tested the binding of those compounds to MALAT1 RNA and tRNA as a negative control, using SPR. While several compounds were nonspecific binders, others were able to recognize MALAT1 specifically. One of them, MTC07, has an apparent affinity of 400.2 ± 14.4 µM. Although it has weak affinity, MTC07 is the first compound targeting MALAT1 originating from in silico docking.

Implementation of a MEIoT Weather Station with Exogenous Disturbance Input.

Due to the emergence of the coronavirus disease (COVID 19), education systems in most countries have adapted and quickly changed their teaching strategy to online teaching. This paper presents the design and implementation of a novel Internet of Things (IoT) device, called MEIoT weather station, which incorporates an exogenous disturbance input, within the National Digital Observatory of Smart Environments (OBNiSE) architecture. The exogenous disturbance input involves a wind blower based on a DC brushless motor. It can be controlled, via Node-RED platform, manually through a sliding bar, or automatically via different predefined profile functions, modifying the wind speed and the wind vane sensor variables. An application to Engineering Education is presented with a case study that includes the instructional design for the least-squares regression topic for linear, quadratic, and cubic approximations within the Educational Mechatronics Conceptual Framework (EMCF) to show the relevance of this proposal. This work's main contribution to the state-of-the-art is to turn a weather monitoring system into a hybrid hands-on learning approach thanks to the integrated exogenous disturbance input.

Preoperative ultrasound findings as risk factors of recurrence of pelvic organ prolapse after laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate levator ani muscle avulsion (LAMA) and ballooning as risk factors for recurrence of pelvic organ prolapse (POP) after laparoscopic sacrocolpopexy (SCP). We hypothesize that these ultrasound findings are associated with a higher risk of POP recurrence. METHODS: Retrospective cohort study of patients who underwent laparoscopic SCP between January 2015 and December 2018. Baseline translabial 3D ultrasound of the pelvic floor was performed. Pelvic Floor Distress Inventory (PFDI-20) and the Pelvic Floor Impact Questionnaire (PFIQ-7) were applied. Both univariate and multivariate analyses were carried out. RESULTS: One hundred thirty-four patients were included. On ultrasound, 32% of patients had levator ani muscle avulsion, and 36.5% had ballooning. Mean follow-up time was 16 months. There was a 13.4% anatomic recurrence; five of them (3.7%) also had symptomatic recurrence. After multivariate analysis we found that LAMA and ballooning were not significant: OR 0.99 (95% CI 0.098-10.1; p = 0.99) and OR 1.1 (95% CI 0.99-1.2; p = 0.06), respectively. CONCLUSIONS: LAMA and ballooning on pelvic floor US are not significant risk factors for anatomic POP recurrence after laparoscopic SCP. Laparoscopic SCP has a 13.4% and 3.4% anatomic and symptomatic recurrence rate, respectively, and the majority of patients reported significant improvement in quality of life.

Síndrome de Wiskott-Aldrich asociado a absceso de la glándula tiroides. Informe de caso / Wiskott-Aldrich syndrome associated with thyroid gland abscess. Case report

RESUMEN El Síndrome de Wiskott-Aldrich es una inmunodeficiencia hereditaria poco frecuente, acompañada de trombocitopenia. Así mismo, el absceso de tiroides se presenta raras veces, dados los niveles de iodo, irrigación linfática y lo encapsulado del órgano. El objetivo del presente trabajo es presentar el caso de un paciente con absceso de la glándula tiroides, que además era portador de Síndrome de Wiskott-Aldrich. De sexo masculino y 21 años de edad, fue atendido en el Hospital León Cuervo Rubio, de Pinar del Río. Una semana antes había sufrido un ántrax en la espalda, seguido del aumento de volumen del cuello y signos de compresión, aunque sin indicios de sepsis. Durante la intervención quirúrgica se encontró absceso de la glándula tiroides. El tratamiento oportuno del absceso de tiroides evita consecuencias fatales en enfermos inmunodeprimidos, como el paciente presentado.

ABSTRACT Wiskott-Aldrich Syndrome is a rare inherited immunodeficiency, accompanied by thrombocytopenia. In addition, thyroid abscess occurs rarely, given the levels of iodine, lymphatic irrigation and the encapsulation of the organ. The objective of this work is to present the case of a patient with an abscess of the thyroid gland, who was also a carrier of Wiskott-Aldrich syndrome. A 21 years old male was treated at the León Cuervo Rubio Hospital, in Pinar del Río. A week earlier, he had suffered a anthrax on his back, followed by swelling in his neck and signs of compression, but with no signs of sepsis. During the surgical intervention, an abscess of the thyroid gland was found. Timely treatment of thyroid abscess avoids fatal consequences in immunodeficient patients, such as the patient presented.

Caracterización clínica de las disfunciones de piso pélvico en mujeres chilenas sintomáticas que consultan en un hospital universitario / Clinical characterization of pelvic floor dysfunctions in symptomatic Chilean women who visit an academic hospital

INTRODUCCIÓN: La prevalencia de las disfunciones de piso pélvico (DPP) puede llegar hasta un 25%, y esta incrementando con los años. El objetivo de este estudio es mostrar las características clínicas de pacientes sintomáticas sometidas a cistometría simple en el Hospital La Florida, entre diciembre del 2015 y marzo 2020. MÉTODOS: Es un estudio retrospectivo transversal. Se evaluaron los datos de todos los resultados de cistometrías simples de pacientes derivadas por sintomatología de piso pélvico entre los años 2015 y 2020. RESULTADOS: Se evaluaron 1.211 cistometrías simples. El motivo de derivación más frecuente fue prolapso de órganos pélvicos + incontinencia de orina (IO) (39.6%). 13.5% tuvieron resultado normal. 58% presentó test de esfuerzo positivo. 22.5% tenían prueba de estrés con vejiga vacía positiva. 17.6% presentó IO oculta. 21.9% de IO mixta. De las pacientes derivadas por vejiga hiperactiva o IO mixta, en el 14.2% se constató la presencia de contracciones no inhibidas y en el 34.8% la presencia de urgencia. CONCLUSIONES: Nuestro estudio aporta información sobre las DPP en la mujer chilena en un hospital universitario.

INTRODUCTION: Prevalence of pelvic floor dysfunctions (PFD) can be as high as 25%, and it is increasing over the years. The objective if this study is to show the clinical characteristics of symptomatic patients undergoing simple cystometry at La Florida Hospital, between December 2015 and March 2020. METHODS: This is a cross-sectional study. The data of all simple cystometries of patients derived for pelvic floor symptoms between 2015 and 2020 were evaluated. RESULTS: 1211 simple cystometries were evaluated. The most frequent reason for referral was pelvic organ prolapse + urinary incontinence (UI) (39.6%). 13.% had a normal result. 58% presented positive stress test. 22.% had a positive empty stress test. 17.6% had occult UI. 21.9% mixed UI. Of the patients referred by overactive bladder or mixed UI, 12.2% had detrusor contractions and 34.8% had urgency. CONCLUSIONS: Our study provides information on PFD in Chilean women in a university hospital. .

An Allosteric Modulator of RNA Binding Targeting the N-Terminal Domain of TDP-43 Yields Neuroprotective Properties.

In this study, we targeted the N-terminal domain (NTD) of transactive response (TAR) DNA binding protein (TDP-43), which is implicated in several neurodegenerative diseases. In silico docking of 50K compounds to the NTD domain of TDP-43 identified a small molecule (nTRD22) that is bound to the N-terminal domain. Interestingly, nTRD22 caused allosteric modulation of the RNA binding domain (RRM) of TDP-43, resulting in decreased binding to RNA in vitro. Moreover, incubation of primary motor neurons with nTRD22 induced a reduction of TDP-43 protein levels, similar to TDP-43 RNA binding-deficient mutants and supporting a disruption of TDP-43 binding to RNA. Finally, nTRD22 mitigated motor impairment in a Drosophila model of amyotrophic lateral sclerosis. Our findings provide an exciting way of allosteric modulation of the RNA-binding region of TDP-43 through the N-terminal domain.

Impacto del modelo constructivista para gestionar la innovación universitaria en el deporte / Impacto do modelo construtivista para a gestão da inovação universitária no desporto / Impact of the constructivist model to manage university innovation in sport

Resumen La innovación por proyectos es considerada una de las principales fuentes de impactos de la ciencia y la tecnología, sin embargo, la valoración de estos constituye un problema, aún no resuelto en su totalidad, a pesar de los esfuerzos realizados por diferentes investigadores y organizaciones; a esta realidad no escapan las organizaciones deportivas. El objetivo del presente artículo es valorar el impacto de la innovación por proyectos, gestionados por la Facultad de Cultura Física de Granma, desde un modelo constructivista. La investigación exigió métodos empíricos como revisión de documentos oficiales, la observación y la entrevista, así como el método gráfico multivariado y procedimientos aritméticos; estos últimos permitieron valorar el impacto de las innovaciones como favorable, relevante, sostenible y con rendimiento en fase de saturación, cinco años después de concluir la ejecución financiera de los proyectos usados como muestra.

Resumo A inovação por projetos é considerada uma das principais fontes de impacto da ciência e da tecnologia, porém, a valorização destes é um problema, ainda não totalmente resolvido, apesar dos esforços feitos por diferentes pesquisadores e organizações, esta realidade não escapa às organizações esportivas. O objectivo deste artigo é avaliar o impacto da inovação por projetos, geridos pela Faculdade de Cultura Física de Granma, a partir de um modelo construtivista. A investigação exigiu métodos empíricos como a revisão de documentos oficiais, observação e entrevista, bem como o método gráfico multivariado e procedimentos aritméticos; estes últimos permitiram avaliar o impacto das inovações como favoráveis, relevantes, sustentáveis e com desempenho na fase de saturação, cinco anos após a conclusão da execução financeira dos projetos utilizados como amostra.

Abstract Innovation by projects is considered one of the main sources of impact of science and technology, however, the valuation of these is a problem, not yet fully resolved, despite the efforts made by different researchers and organizations, this reality does not escape the sports organizations. The aim of this article is to assess the impact of innovation by projects, managed by the Faculty of Physical Culture of Granma, from a constructivist model. The research required empirical methods such as the review of official documents, observation and interview, as well as the multivariate graphic method and arithmetic procedures; the latter allowed the impact of the innovations to be evaluated as favourable, relevant, sustainable and with performance in the saturation phase, five years after the financial execution of the projects used as a sample was concluded.

Inotropic and Antiarrhythmic Transmural Actions of Ranolazine in a Cellular Model of Type 3 Long QT Syndrome. / Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3.

Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.