A randomised crossover trial on the effects of foot starting position on calf raise test outcomes: Position does matter.

BACKGROUND: This randomised crossover study with repeated measures examined the influence of the three most common foot starting positions used in conducting the calf raise test (CRT) on test outcomes. This study also accounted for the potential influence of gender, age, body mass index (BMI), and level of physical activity on test outcomes. METHODS: Forty-nine healthy individuals (59 % female, 21 ± 4 years) performed single-leg calf raise repetitions in a human movement laboratory in three randomised foot starting positions: flat, 10° incline, and step. The validated Calf Raise application was used to track the vertical displacement of a marker placed on the foot using computer vision. The application extracted the following CRT outcomes from the vertical displacement curve: number of repetitions, peak vertical height, total vertical displacement, and total positive work. Data were analysed using mixed-effects models and stepwise regression. RESULTS: There was a significant main effect (P < 0.001) of foot starting position on all outcomes, with all paired comparisons being statistically significant (P ≤ 0.023). Repetitions, total vertical displacement, and total positive work were greatest in flat and lowest in step, whereas peak vertical height was greatest in incline and lowest in step. Gender (P = 0.021; males>females) and BMI (P = 0.002; lower BMI>higher BMI) significantly influenced the number of repetitions. Gender (P < 0.001; males>females) also influenced total positive work. Age and physical activity levels did not significantly influence CRT outcomes. CONCLUSIONS: CRT foot starting position mattered and significantly affected all CRT outcomes. CRT foot starting position needs consideration when contrasting data in research and practice.

Devices to measure calf raise test outcomes: A narrative review.

BACKGROUND: The calf raise test (CRT) is commonly administered without a device in clinics to measure triceps surae muscle function. To standardise and objectively quantify outcomes, researchers use research-grade or customised CRT devices. To incorporate evidence-based practice and apply testing devices effectively in clinics, it is essential to understand their design, applicability, psychometric properties, strengths, and limitations. Therefore, this review identifies, summarises, and critically appraises the CRT devices used in science. METHODS: Four electronic databases were searched in April 2022. Studies that used devices to measure unilateral CRT outcomes (i.e., number of repetitions, work, height) were included. RESULTS: Thirty-five studies met inclusion, from which seven CRT devices were identified. Linear encoder (n = 18) was the most commonly used device, followed by laboratory equipment (n = 6) (three-dimensional motion capture and force plate). These measured the three CRT outcomes. Other devices used were electrogoniometer, Häggmark and Liedberg light beam device, Ankle Measure for Endurance and Strength (AMES), Haberometer, and custom-made. Devices were mostly used in healthy populations or Achilles tendon pathologies. AMES, Haberometer, and custom-made devices were the most clinician-friendly, but only quantified repetitions were completed. In late 2022, a computer vision mobile application appeared in the literature and offered clinicians a low-cost, research-grade alternative. CONCLUSION: This review details seven devices used to measure CRT outcomes. The linear encoder is the most common in research and quantifies all three CRT outcomes. Recent advances in computer-vision provide a low-cost research-grade alternative to clinicians and researchers via a n iOS mobile application.

Dilemas de la objeción de conciencia en la interrupción voluntaria del embarazo: revisión integrativa de literatura / Dilemmas of conscientious objection in the voluntary interruption of pregnancy: integrative literature review

Introducción: La objeción de conciencia (OC) puede generar un conflicto para los profesionales de la salud en temas como la interrupción voluntaria del embarazo (IVE).Objetivo: Analizar los argumentos contenidos en la evidencia científica para la OC en el contexto de IVE. Método: Revisión integrativa literaria en seis etapas, obtenidos en las bases de datos MEDLINE/PUBMED, ISI Web of Science, LILACS y SciELO publicados entre 2018-2022 en idiomas inglés, portugués y español, ajustada a los requerimientos PRISMA. Los datos fueron resumidos mediante análisis temático. Resultados: A partir de 55 textos, 25 fueron analizados. Un 32% de las publicaciones se realizó en 2020, el 36% son análisis crítico de la literatura, 24% realizadas en Chile y un 32% se obtuvieron de PUBMED. Se obtienen tres categorías de trabajo: 1. Características de la OC. ¿Cómo afecta la OC a la salud pública? 2. La conveniencia de proceder a una regulación del ejercicio de la OC.3. Desafíos en materia de OC. Conclusiones: Se problematiza acerca de los aspectos que sostienen las actitudes profesionales, insistiendo en que, si bien la ley reconoce el ejercicio de OC en el ámbito de la salud, es necesario articular una protección bidireccional, de esta manera la OC se legitima y adquiere coherencia, velando por el derecho a la salud de las mujeres. Así, su argumento reside en el entendiendo que el principal compromiso de los equipos de salud es el bienestar de la salud sexual y reproductiva de las mujeres en todos los contextos. (AU)

Introduction: Conscientious objection (CO) can generate a conflict for health professionals on issues such as voluntary interruption of pregnancy (IVE). Objective: To analyze the arguments in the scientific evidence for CO in IVE. Method: Integrative literary review in six stages, obtained from the MEDLINE/PUBMED, ISI Web of Science, LILACS, and SciELO databases published between 2018-2022 in English, Portuguese, and Spanish, adjusted to PRISMA requirements. Data were summarized using thematic analysis.Results: From 55 texts, 25 were analyzed. 32% of the publications were made in 2020, 36% are critical analyses of the literature, 24% were made in Chile, and 32% were obtained from PUBMED. Three categories of work are accepted: 1. Characteristics of the CO. How does CO affect public health? 2. The advisability of proceeding to a regulation of the exercise of the CO.3. CO challenges. Conclusions: The aspects that support professional attitudes are problematized, insisting that, although the law recognizes the exercise of CO in the health field, it is necessary to articulate bidirectional protection; in this way, CO is legitimized and acquires coherence, ensuring the right to health of women. Thus, his argument resides in the understanding that the main commitment of health teams is the well-being of women's sexual and reproductive health in all contexts. (AU)

[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

Concurrent validity and reliability of a mobile iOS application used to assess calf raise test kinematics.

BACKGROUND: Calf raise test (CRT) is used in rehabilitation and sports medicine to evaluate calf muscle function. The Calf Raise application (CRapp) uses computer-vision algorithms to objectively measure CRT outcomes and replicate laboratory-based metrics that are difficult to measure clinically. OBJECTIVE: To validate the CRapp by examining its concurrent validity and agreement levels against laboratory-based equipment, and its intra- and inter-rater reliability. DESIGN: Observational cross-sectional validation study. METHODS: CRT outcomes (i.e., repetitions, positive work, total height, peak height, fatigue index, and peak power) were assessed in thirteen individuals (6 males, 7 females) on three occasions on both legs using the CRapp, 3D motion capture, and force plate simultaneously. Data were extracted from two markers: below lateral malleolus (n = 77) and on the heel (n = 77). Concurrent validity and agreement were determined from 154 data files using intraclass correlation coefficients (ICC3,k), typical errors expressed as coefficient of variations (CV), and Bland-Altman plots to assess biases and precision. Reliability was assessed using ICC3,1 and CV values. RESULTS: Validity of CRapp outcomes was good to excellent across measures for both markers (mean ICC ≥0.878), precision plots showing good agreement and precision. CV ranged from 0% (repetitions) to 33.3% (fatigue index) and were on average better for the lateral malleolus marker. Inter- and intra-rater reliability were excellent (ICC≥0.949, CV ≤ 5.6%). CONCLUSION: CRapp is valid and reliable within and between users for measuring CRT outcomes in healthy adults. CRapp provides a tool to objectivise CRT outcomes in research and practice, aligning with recent advances in mobile technologies and their increased use in healthcare.

New Insights into Adjuvant Therapy for Localized Colon Cancer.

Currently, clinicopathologic characteristics of colon cancer tumors guide the selection of patients suitable for adjuvant therapy. Circulating tumor DNA (ctDNA) analysis after surgery has a strong correlation with prognosis, and positive ctDNA status defines a subset of patients with high risk of recurrence. Ongoing interventional adjuvant trials in colon cancer including ctDNA analyses will determine the predictive value of ctDNA in the adjuvant setting. For patients with stage III colon cancer, noninferiority of 3 months of adjuvant therapy compared with 6 months has not been demonstrated. However, for selected subgroups, the shorter duration of therapy may limit toxic effects without impairing clinical outcomes.

Effects of an Emotional Education Program on Prisoners: An Experimental Study.

BACKGROUND: Emotional education has beneficial effects on physical and/or emotional health, resulting in a better quality of life. Thus, it is beneficial to provide prisoners with emotional education, because of the difficulties they often have, to attain these benefits. PURPOSE: The aim of the study was to analyze the effects of a nursing intervention program in emotional education for incarcerated persons. METHODS: Experimental study with pretest-posttest repeated measures with a control group was conducted at a penitentiary center in the southeast of Spain. Forty-eight prisoners participated in the emotional education intervention program, and another 48 were part of the control group. The emotional intelligence questionnaire 24-item Trait Meta-Mood Scale, the resilience scale Connor-Davidson Resilience Scale, the Rosenberg Self-Esteem Scale, the Rathus Assertiveness Questionnaire, and the 36-item Short Form Health Survey were utilized. FINDINGS: The intragroup, preintervention and postintervention comparisons in the study group showed improvements in self-esteem (p = 0.00, r = 0.51), resilience (p = 0.00, r = 0.42), assertiveness (p = 0.00, r = 0.46), and emotional intelligence in its dimensions of repair (p = 0.00, r = 0.32) and clarity (p = 0.02, r = 0.22) as well as in most of the quality of life dimensions. Significant intergroup differences were also found in all of these variables, except for attention and emotional clarity dimensions. CONCLUSION: The intervention improved the socioemotional health and quality of life of the prisoners, highlighting the importance of these interventions to be performed by the nursing personnel on a regular basis as a programmed activity within prisons.

Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV-1 that disturb HIV-1 entry. Herein, the most significant advancements in topical microbicide development, trying to mimic the real-life conditions as closely as possible, are discussed. This review also provides the preclinical assays that anionic dendrimers have passed as microbicides because they can improve current antiviral treatments' efficacy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Motor Impairment and Its Influence in Gait Velocity and Asymmetry in Community Ambulating Hemiplegic Individuals.

OBJECTIVES: To determine the most important motor impairments that are predictors of gait velocity and spatiotemporal symmetrical ratio in patients with stroke. DESIGN: Cross-sectional, descriptive analysis study. SETTING: Human performance laboratory of the University of Santo Tomas. PARTICIPANTS: Individuals with chronic stroke (N=55; 34 men, 21 women) who are community dwellers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The gait velocity and spatiotemporal symmetrical ratio (step length; step, stance, swing, single-leg support, and double-leg support stance times) was determined using Vicon motion capture. We also calculated motor impairment of the leg and foot using Brunnstrom's stages of motor recovery, evaluated muscle strength using the scoring system described by Collin and Wade, and assessed spasticity using by the modified Ashworth Scale. RESULTS: Regression analysis showed that plantarflexor strength is a predictor of gait velocity and all temporospatial symmetry ratio. Knee flexor and extensor strength are predictors in single-leg support time and double-leg support time symmetry ratio, respectively. On the other hand, hip adductor and quadriceps spasticity are predictors of swing time and step length symmetry ratio. CONCLUSION: Different motor impairments are predictors of stroke gait abnormality. Interventions should be focused on these motor impairments to allow for optimal gait rehabilitation results.

COVID-19 como psicopatía experimental / COVID-19 as experimental psychopathy

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New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection.

Due to the success of combined antiretroviral therapy (cART) in recent years, the pathological outcome of Human Immunodeficiency Virus type 1 (HIV-1) infection has improved substantially, achieving undetectable viral loads in most cases. Nevertheless, the presence of a viral reservoir formed by latently infected cells results in patients having to maintain treatment for life. In the absence of effective eradication strategies against HIV-1, research efforts are focused on obtaining a cure. One of these approaches is the creation of therapeutic vaccines. In this sense, the most promising one up to now is based on the establishing of the immunological synapse between dendritic cells (DCs) and T lymphocytes (TL). DCs are one of the first cells of the immune system to encounter HIV-1 by acting as antigen presenting cells, bringing about the interaction between innate and adaptive immune responses mediated by TL. Furthermore, TL are the end effector, and their response capacity is essential in the adaptive elimination of cells infected by pathogens. In this review, we summarize the knowledge of the interaction between DCs with TL, as well as the characterization of the specific T-cell response against HIV-1 infection. The use of nanotechnology in the design and improvement of vaccines based on DCs has been researched and presented here with a special emphasis.

Características de los neonatos trasladados al hospital de referencia regional en Asturias / Characteristics of the newborns transferred to the regional reference hospital in Asturias

INTRODUCCIÓN: La regionalización de la asistencia neonatal es un punto importante de la asistencia pediátrica de calidad. Los traslados interhospitalarios neonatales forman parte de esta regionalización. OBJETIVO: Analizar las características de los neonatos trasladados al hospital de referencia en Asturias. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo y descriptivo de los pacientes neonatales trasladados al Servicio de Neonatología del hospital regional de referencia, entre enero de 2017 y diciembre de 2018 en Asturias. RESULTADOS: Se incluyeron 136 pacientes (56 mujeres y 80 varones), lo que supone un traslado cada 5 días, el 1,8% de los neonatos nacidos en los hospitales emisores y el 14,4% de los ingresos en el hospital receptor. El 63,2% ingresaron en la unidad de cuidados intensivos y el 36,7% en la sala de cuidados intermedios, con un tiempo de ingreso medio de 9,5 días. El 20,7% eran prematuros. El peso medio al nacimiento fue de 2.983 g. La edad media al traslado fue de 5 días y el 46,3% de los traslados se realizaron durante las primeras 24 horas de vida. Las causas más frecuentes de traslado fueron: respiratorias (25%), neurológicas (14,7%), digestivas (13,2%) e infecciosas (12,5%). El 38% de los pacientes precisó soporte ventilatorio y el 1,4% falleció durante el ingreso. CONCLUSIONES: Los traslados neonatales interhospitalarios son relativamente frecuentes en nuestra región, siendo el distrés respiratorio y los problemas neurológicos las causas más comunes. El análisis de la regionalización de la asistencia neonatal resulta especialmente importante en regiones con escasa natalidad debido a la crisis demográfica

INTRODUCTION: Regionalization of neonatal care is an important point of quality in pediatric care. Neonatal interhospital transfers between regional hospitals and referral centers are part of this regionalization. OBJECTIVE: To analyze characteristics of newborns transferred from the different regional and private hospitals to theregional reference hospital in Asturias during 2017 and 2018. MATERIALS AND METHODS: An observational, descriptive and retrospective study was conducted, including all neonatal patients transferred fron other Asturian hospital to Neonatology Service of HUCA between January 2017 and December 2018, in Asturias. RESULTS: 136 patients were included (56 female and 80 male), which represents a transfer every 5 days, 1.8% of the 7,563 neonates born in the sending hospitals and 14.4% of the neonatal admissions in the receiving hospital. 63.2% of patients were admitted to the neonatal Intensive Care Unit and 36.7% to the neonatal Intermiediate care room with a mean admission time of 9.5 days. 20.7% were preterm newborns. The average born weight was 2,983 g. 20.6% were less than 2,500 g. Average age at transfer was 5 days, being the 46.3% made during first 24 hours of life. The most frequent causes of transfer were: respiratory (25%) neurological (14.7%), digestive (13.2%) and infectous (12.5%). 38% required ventilatory support and 1,4% died during admission. CONCLUSIONS: Neonatal inter-hospital transfers are relatively frequent in our region, with respiratory distress and neurological problems being the most common causes. The analysis of neonatal care regionalization is especially important in regions with low birth rates due to demographic crisis

Evaluación del servicio de entrega de medicación a domicilio desde la Farmacia Hospitalaria durante la pandemia COVID-19 / Medication home delivery service set up in a Hospital Pharmacy Department during the COVID-19 pandemic

OBJETIVO: Analizar el procedimiento de entrega a domicilio de medicación de dispensación hospitalaria instaurado en el Servicio de Farmacia Hospitalaria (SFH) durante la pandemia COVID-19. Conocer el perfil de pacientes que aceptan la dispensación domiciliaria, analizar por patología las dispensaciones a domicilio y evaluar el grado de satisfacción de los pacientes mediante una encuesta telefónica. MÉTODOS: Estudio observacional, retrospectivo y descriptivo. Se analizaron las entregas de medicación a domicilio desde el SFH en el periodo del 7 de abril al 7 de mayo. Las características clínicas y demográficas de los pacientes se obtuvieron a partir del programa informático de pacientes externos del SFH e historia clínica electrónica. El grado de satisfacción de los pacientes se evaluó mediante la realización de una encuesta telefónica posterior a la entrega a domicilio. RESULTADOS: Se realizaron 2.028 entregas de medicación a domicilio abarcando toda la Comunidad Autónoma de Madrid (CAM), con un grado de aceptación del 76,82%. La patología con mayor número de entregas fue VIH. Los pacientes con enfermedades inmunomediadas fueron los que mayor aceptación reportaron. El 99% de los pacientes se mostraron satisfechos con el servicio. CONCLUSIONES: El servicio de entrega de medicación a domicilio ha sido ampliamente aceptado por los pacientes, mostrando un alto grado de satisfacción con el mismo. Se han evitado desplazamientos al hospital, disminuyendo el riesgo de contagio. Los pacientes demandan la prolongación de este servicio fuera del periodo de pandemia y sugieren que se complemente con una consulta de atención farmacéutica por telefarmacia

OBJECTIVE: To analyze the home delivery process of hospital medication set up in a Hospital Pharmacy Department (HPD) during the COVID-19 pandemic. To asses the profile of patients who accept home delivering, to analyze home dispensations by pathology and to evaluate the patient satisfaction through a telephone survey. METHODS: Observational, retrospective and descriptive study. Medication home delivery from the HPD in the period from April 7 to May 7 was analyzed. Patients demographic and clinical characteristics were obtained from the outpatient software used at the HPD and the electronic medical record. The degree of patient satisfaction was assessed by conducting a telephone survey after home delivery. RESULTS: A total of 2,028 home deliveries were made to the entire Community of Madrid, with an acceptance rate of 76,82%, being HIV the pathology with the highest number of deliveries. Patients with immune-mediated diseases were the ones with the greater acceptance rate. Overall patient satisfaction with the service was 99%. CONCLUSIONS: Medication home delivery service has been widely accepted by patients, showing a high degree of satisfaction. Avoiding trips to the hospital has reduced the risk of contagion. Patients demand the continuation of this service after the pandemic and support Pharmaceutical Care by telepharmacy

Secondary colonic necrosis. Case report.

BACKGROUND: Colonic vascular lesion secondary to verapamil overdose is mediated by free radicals, forming vascular microtrombos and endotoxin generation, being a difficult diagnosis. CLINICAL CASE: A 27-year-old female is admitted with an acute abdomen of 4 days after an event referred for a suicidal attempt due to an overdose of verapamil, operating surgically where there is a right transmural colon necrosis, performing a right hemicolectomy with terminal ileostomy. CONCLUSIONS: Recognize and properly treat an acute abdomen, not always reach an adequate diagnosis, so a thorough history could conclude.

ANTECEDENTES: La lesión vascular colónica secundaria a la sobredosis de verapamilo, es mediada por radicales libres, formando microtrombos vasculares y generación de endotoxinas, siendo un diagnostico difícil. CASO CLÍNICO: Femenino de 27 años, ingresa con abdomen agudo de 4 días posteriores a un evento remitido de intento suicida por sobredosis de verapamilo, interviniéndose quirúrgicamente donde se halla necrosis colónica transmural derecha, realizando hemicolectomía derecha con ileostomía terminal. CONCLUSIONES: Reconocer y tratar de forma adecuada un abdomen agudo, no siempre se suele llegar a un adecuado diagnostico, por lo cual una minuciosa anamnesis lograría concluirlo.

Tratamiento con ondas de choque en un caso de rotura muscular del delgado plantar complicada / Shock wave treatment in a case of complicated plantaris muscle rupture

Las lesiones musculares son frecuentes en el ámbito laboral. Se producen por el mecanismo de traumatismos directos o indirectos bruscos, que ocasiona una rotura de sus fibras, provocando hematomas. Actualmente no existe un modelo único protocolizado de tratamiento. Presentamos el caso de un paciente diagnosticado de rotura muscular completa del delgado plantar por mecanismo traumático indirecto (elongación muscular brusca), con hematoma asociado de gran volumen. Se realizó estudio clínico mediante ecografía, resonancia magnética (RM), escala visual analógica (EVA) para valoración del dolor al inicio y al finalizar el tratamiento (3 semanas), así como la duración de su incapacidad laboral. Recibió terapia con ondas de choque electromagnéticas focales (OCEF) según protocolo. Al finalizar el tratamiento se objetivó una desaparición del hematoma y no hubo complicaciones. Las OCEF pudieran ser una alternativa terapéutica complementaria al tratamiento convencional en esta afección, no obstante, sería necesario proseguir la investigación incluyendo un mayor número de pacientes, y a través de estudios aleatorizados con grupo control

Muscle injuries are frequent in the workplace. They are produced by sudden direct or indirect trauma that involves a rupture of the fibres, causing bruising. Currently, there is no single protocol-based model of treatment. We present the case of a patient diagnosed with complete muscular rupture of the plantaris muscle by an indirect traumatic mechanism (abrupt muscular elongation), with an associated large-volume hematoma. Clinical study consisted of ultrasound, magnetic resonance (MR), pain assessment (VAS) at the beginning and at the end of the treatment (3 weeks), as well as duration of occupational disability. The patient underwent extracorporeal shockwave therapy (ESWT) according to the protocol. At the end of treatment, the hematoma was resolved and there were no complications. ESWT could be a complementary therapeutic alternative to conventional treatment in this entity. However, there is a need for further, randomised controlled studies including a larger number of patients

G1-S4 or G2-S16 carbosilane dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity.

PURPOSE: HIV-1 and herpes simplex virus type-2 (HSV-2) represent two of the most relevant sexually transmitted diseases (STDs) worldwide. Moreover, each year there are >200 million pregnancies worldwide, and more than half are unintended. Continued high rates of unintended pregnancies and spread of HIV-1 and HSV-2 require new approaches to address these problems. G1-S4 and G2-S16 dendrimers emerge as potential candidates for the development of a topical microbicide due to their safety and effectivity against HIV-1 and HSV-2 infection, both in vitro and in vivo. Our goal is to develop a dual topical microbicide to prevent the transmission of STDs and unintended pregnancies. Platycodin D (PD) was selected for its great spermicidal activity, topical application, and biocompatibility. MATERIALS AND METHODS: Toxicology and inhibitory profile of G1-S4/PD and G2-S16/PD were evaluated in vitro and in vivo. Spermicidal activity was assessed by a computer-assisted sperm analysis system (CASA). RESULTS: G1-S4/PD and G2-S16/PD presented >95% of HIV-1 inhibition in TZM-bl cells and peripheral blood mononuclear cells. CASA assessment determined that 0.25 mM of PD with therapeutic concentrations of G1-S4 or G2-S16 was able to induce 100% immobilization of the sperm in 30 seconds. To evaluate the toxicity in vivo, a vaginal toxicity assay was performed in BALB/c mice. No significant changes or damage to the vaginal epithelium after 7 consecutive days of application were observed. CONCLUSION: Our data indicate that G1-S4/PD and G2-S16/PD combinations are promising candidates to be developed for vaginal microbicides with contraceptive activity.

Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.

BACKGROUND: Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. MATERIALS AND METHODS: Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. RESULTS: Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC50 with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. DISCUSSION: A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.

Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients.

OBJECTIVES: Immune dysregulation is a hallmark of HIV and hepatitis C virus (HCV) infections. We aimed to evaluate the relationship between liver stiffness measurement (LSM) and biomarkers of T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy in HIV/HCV-coinfected patients. DESIGN: Cross-sectional study. METHODS: We studied 238 HIV/HCV-coinfected patients, 32 healthy controls, and 39 HIV-monoinfected patients. Patients were stratified according to LSM into four groups: less than 12.5, 12.5-25, 25-40, and more than 40 kPa. T-cell subsets were measured using flow cytometry and plasma biomarkers using immunoassays. RESULTS: HIV/HCV-coinfected patients had higher biomarker levels of immune activation in peripheral blood [T-cell activation (CD4CD38 and CD8CD38), bacterial translocation (soluble CD14), inflammation [IL-1b, IL-6, IL-8, IL-18, IFN-γ-inducible protein 10 (IP-10)] endothelial dysfunction [soluble vascular cell adhesion molecule 1 (sVCAM1), soluble intercellular cell adhesion molecule 1 (sICAM1), and soluble tumor necrosis factor receptor 1 (sTNFR1)], and coagulopathy (plasminogen activator inhibitor-1)] than healthy controls and HIV-monoinfected patients. Moreover, in HIV/HCV-coinfected patients, a direct relationship between LSM and immune activation [T-cell activation (CD8CD38 bacterial translocation (lipopolysaccharide), inflammation (IL-8, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] was found. Subsequently, patients were stratified into different fibrosis stages, finding that patients with cirrhosis who had LSM at least 40 kPa showed higher biomarker values of immune activation [T-cell activation (CD4CD38 and CD8CD38), bacterial translocation (lipopolysaccharide), inflammation (IL-8, IL-6, IP-10), endothelial dysfunction (sVCAM1, sICAM1, and sTNFR1), and coagulopathy (D-dimer)] than patients from the other three groups (<12.5, 12.5-25, and 25-40 kPa). CONCLUSION: T-cell activation, bacterial translocation, inflammation, endothelial dysfunction, and coagulopathy increased with the severity of liver fibrosis in HIV/HCV-coinfected patients, particularly in patients who had LSM at least 40 kPa.

Formación en ecocardiografía: las normas bien establecidas / Training in echocardiography: the well-established standards

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