Economic and financial viability of a pig farm in central semi-tropical Mexico: 2022-2026 prospective.

To estimate the economic and financial viability of a pig farm in central sub-tropical Mexico within a 5-year planning horizon, a Monte Carlo simulation model was utilized. Net returns were projected using simulated values for the distribution of input and product processes, establishing 2021 as base scenario. A stochastic modelling approach was employed to determine the economic and financial outlook. The findings reveal a panorama of economic and financial viability. Net income increased by 555%, return on assets rose from 3.36% in 2022 to 11.34% in 2026, and the probability of decapitalization dropped from 58% to 13%, respectively in the aforesaid periods. Similarly, the probability of obtaining negative net income decreased from 40% in 2022 to 18% in 2026. The technological, productive, and economic management of the production unit allowed for a favorable scenario within the planning horizon. There is a growing interest in predicting the economic sectors worth investing in and supporting, considering their economic and development performance. This research offers both methodological and scientific evidence to demonstrate the feasibility of establishing a planning schedule and validating the suitability of the pork sector for public investment and support.

Smartwatch-derived sleep and heart rate measures complement step counts in explaining established metrics of MS severity.

BACKGROUND: Passive remote monitoring of patients with MS (PwMS) with sensor-based wearable technologies promises near-continuous evaluation with high ecological validity. Step counts correlate strongly with traditional measures of MS severity. We hypothesized that remote monitoring of sleep and heart rate will yield complementary information. METHODS: We recruited 31 PwMS and 31 age- and sex-matched healthy volunteers (HV) as part of the dreaMS feasibility study (NCT04413032). Fitbit Versa 2 smartwatches were worn for 6 weeks and provided a total of 25 features for activity, heart rate, and sleep. Features were selected based on their pairwise intercorrelation (Pearson |r| < 0.6), test-retest reliability (intraclass correlation coefficient ≥ 0.6 or median coefficient of variation < 0.2) and group comparisons between HV and PwMS with moderate disability (expanded disability status scale (EDSS) ≥ 3.5) (rank-biserial |r| ≥ 0.5). These selected features were correlated with clinical reference tests (EDSS, timed 25-foot walk (T25FW), MS-walking scale (MSWS-12)) in PwMS, and multivariate models adjusted for age, sex, and disease duration were compared. RESULTS: We analyzed 28 PwMS (68% female, mean age 44 years, median EDSS 3.0) and 26 HV in our primary analysis. The objectively selected features discriminated well between HV and PwMS with moderate disability with rank-biserial r = 0.83 for Total number of steps, 0.51 for Deep sleep proportion, -0.51 for Median heart rate, 0.85 for Proportion very active, and 0.65 for Total number of floors. In PwMS they correlated strongly with the three clinical reference tests EDSS (strongest Spearman ρ = -0.75 for Proportion very active), T25FW (-0.75 for Total number of floors), and MSWS-12 (-0.72 for Total number of floors). Deep sleep proportion and Median heart rate complemented Total number of steps in explaining the variance of reference tests. CONCLUSIONS: Activity, deep sleep and heart rate measures can be derived reliably from smartwatches and contain independent clinically meaningful information about MS severity, highlighting their potential for continuous passive monitoring in both clinical trials and clinical care of PwMS.

Aspectos clínicoepidemiológicos de pacientes con cáncer de mama del Policlínico 28 de septiembre / Clinical-Epidemiological Aspects of Patients with Breast Cancer and from the Policlínico 28 de Septiembre of Santiago de Cuba

Introducción: El cáncer de mama es considerado como un serio problema de salud pública por la alta prevalencia tanto en países desarrollados como en desarrollo. Son escasos los estudios clínico-epidemiológicos actualizados en el área de salud del Policlínico 28 de septiembre relacionados con dicha entidad clínica. Objetivo: Caracterizar desde el punto de vista clínico y epidemiológico a pacientes con cáncer de mama del área de salud perteneciente al Policlínico 28 de septiembre. Métodos: Estudio descriptivo en una serie de 35 mujeres mayores de 30 años con diagnóstico confirmado de cáncer de mama. Las variables estudiadas comprendieron edad, antecedentes familiares de cáncer de mama, factores de riesgo generales y hormonales, signos y síntomas clínicos, resultados de estudio ecográfico y diagnóstico histopatológico. Se utilizó el porcentaje como medida de resumen. Resultados: El 42,8 por ciento de la muestra objeto de estudio estuvo comprendido en el grupo de edad de 40-49 años. El 65,7 por ciento del total de mujeres tenía antecedentes familiares de cáncer de mama. La menarquía precoz (54,2 por ciento) y la nuliparidad (48,5 por ciento) representaron los factores de riesgo de mayor incidencia. El 57,1 por ciento de las lesiones diagnosticadas correspondieron a carcinomas en estadío I y IIa. Conclusiones: El cáncer de mama constituye un serio problema de salud en mujeres mayores de 30 años pertenecientes al Policlínico 28 de septiembre del municipio Santiago de Cuba(AU)

Introduction: Breast cancer is considered a serious public health concern due to its high prevalence in both developed and developing countries. There are few updated clinical-epidemiological studies carried out in the health area of the Policlínico Docente 28 de Septiembre related to this clinical entity. Objective: To characterize, from the clinical and epidemiological point of view, the patients with breast cancer and from the health area belonging to the Policlínico Docente 28 de Septiembre. Methods: A descriptive study was carried out with a series of 35 women aged more than 30 years and with a confirmed diagnosis of breast cancer. The variables studied included age, family history of breast cancer, general and hormonal risk factors, clinical signs and symptoms, ultrasound findings and histopathological diagnosis. Percentage was used as summary measure. Results: 42.8 percent of the study sample was in the age group 40-49 years old. Of the total number of women, 65.7 percent had a family history of breast cancer. Early menarche (54.2 percent) and nulliparity (48.5 percent) represented the risk factors with the highest incidence. 57.1 percent of the diagnosed lesions corresponded to stage I and IIA carcinomas. Conclusions: Breast cancer is a serious health problem in women older than 30 years and belonging to the Policlínico Docente 28 de Septiembre, of Santiago de Cuba Municipality(AU)

Satisfacción de prescriptores y usuarios de fitofármacos en un servicio de estomatología de Santiago de Cuba / Satisfaction of prescriptors and phytopharmaco users in a stomatology service of Santiago de Cuba i: en

Introducción: La satisfacción de prescriptores y usuarios es un aspecto importante a tener en cuenta durante la prescripción de fitofármacos. Objetivo: Evaluar la satisfacción de prescriptores y usuarios de fitofármacos en un servicio de estomatología. Métodos: Se realizó una investigación observacional, descriptiva y transversal de 35 prescriptores y 22 usuarios de fitofármacos, seleccionados a través de un muestreo probabilístico aleatorio simple, atendidos en el Servicio de Estomatología del Policlínico Docente 30 de Noviembre de Santiago de Cuba, desde marzo del 2020 hasta igual mes del 2021. Las variables analizadas fueron categoría ocupacional del prescriptor, satisfacción de prescriptores y satisfacción de usuarios; para las 2 últimas se establecieron criterios, indicadores y estándares. Asimismo, se emplearon la encuesta como método para la recogida de la información y el porcentaje como medida de resumen. Resultados: En cuanto a la categoría ocupacional, 20 prescriptores (57,1 %) resultaron ser estomatólogos especialistas de primer grado en estomatología general integral. Al evaluar la satisfacción de estos prescriptores, se observó que en un solo criterio el indicador superó ligeramente (91,4 %) el estándar prefijado (90,0 %) y en el resto los valores fueron inferiores a 50,0 %. La evaluación de la satisfacción de los usuarios arrojó que en ningún indicador se alcanzó el estándar prefijado de 90,0 %. Conclusiones: En la institución señalada la satisfacción de prescriptores y usuarios de fitofármacos resultó inadecuada.

Introduction: Prescriptors' and users' satisfaction is an important aspect to take into account during the phytopharmaco prescription. Objective: To evaluate the satisfaction of prescriptors and phytopharmaco users in a stomatology service. Methods: An observational, descriptive and cross-sectional investigation of 35 prescriptors and 22 phytopharmaco users was carried out. They were selected through a simple random probabilistic sampling and assisted in the Stomatology Service of 30 de Noviembre Teaching Polyclinic in Santiago de Cuba, from March, 2020 to the same month in 2021. The analyzed variables were occupational category of the prescriptor, prescriptors satisfaction and users satisfaction; for the last 2 variables, approaches, indicators and standards were established. Likewise, the survey as information collection method and the percentage as summary measure were used. Results: As for the occupational category, 20 prescriptors (57.1%) were first degree specialist stomatologist in general comprehensive stomatology. When evaluating the satisfaction of these prescriptors it was observed that in a single approach the indicator overcame discreetly (91.4%) the preset standard (90.0%) and in the rest the values were inferior to 50.0%. The evaluation of the users' satisfaction showed that in any indicator the preset standard of 90.0% was accomplished. Conclusions: In the appointed institution the prescriptors' and phytopharmaco users' satisfaction was inadequate.

Assessment of cognitive performance in multiple sclerosis using smartphone-based training games: a feasibility study.

BACKGROUND: Cognitive impairment occurs in up to 70% of people with MS (pwMS) and has a large impact on quality of life and working capacity. As part of the development of a smartphone-app (dreaMS) for monitoring MS disease activity and progression, we assessed the feasibility and acceptance of using cognitive games as assessment tools for cognitive domains. METHODS: We integrated ten cognitive games in the dreaMS app. Participants were asked to play these games twice a week for 5 weeks. All subjects underwent a battery of established neuropsychological tests. User feedback on acceptance was obtained via a five-point Likert-scale questionnaire. We correlated game performance measures with predetermined reference tests (Spearman's rho) and analyzed differences between pwMS and Healthy Controls (rank biserial correlation). RESULTS: We included 31 pwMS (mean age 43.4 ± 12.0 years; 68% females; median Expanded Disability Status Scale score 3.0, range 1.0-6.0) and 31 age- and sex-matched HC. All but one game showed moderate-strong correlations with their reference tests, (|rs|= 0.34-0.77). Performance improved in both groups over the 5 weeks. Average ratings for overall impression and meaningfulness were 4.6 (range 4.2-4.9) and 4.7 (range 4.5-4.8), respectively. CONCLUSION: Moderate-strong correlations with reference tests suggest that adaptive cognitive games may be used as measures of cognitive domains. The practice effects observed suggest that game-derived measures may capture change over time. All games were perceived as enjoyable and meaningful, features crucial for long-term adherence. Our results encourage further validation of adaptive cognitive games as monitoring tools for cognition in larger studies of longer duration. STUDY REGISTER: ClinicalTrials.gov: NCT04413032.

Validación de una estrategia didáctica para las relaciones interdisciplinarias entre Farmacología y asignaturas clínicas estomatológicas

Introducción: La validación de estrategias didácticas para favorecer las relaciones interdisciplinarias en el proceso enseñanza aprendizaje, resulta necesaria para su posterior aplicación en la práctica pedagógica y posible generalización. Objetivo: Validar una estrategia didáctica para las relaciones interdisciplinarias en el proceso enseñanza aprendizaje de las asignaturas clínicas, con la Farmacología en la carrera Estomatología. Métodos: Se realizó una investigación educativa entre enero y junio de 2022. Se asumieron métodos teóricos (analítico-sintético, inductivo-deductivo y sistematización), empíricos (consulta a expertos) y matemáticos-estadísticos (estadística descriptiva). Se seleccionó a los expertos según el nivel de competencia. Se elaboró y aplicó un cuestionario para valorar 16 aspectos de la estrategia en términos de: muy adecuado, bastante adecuado, adecuado, poco adecuado y no adecuado. Los criterios valorativos emitidos por los expertos se procesaron mediante el modelo matemático de Torgerson y se determinó el nivel de consenso de los expertos mediante el cálculo del coeficiente de concordancia de Kendall. Resultados: El coeficiente de competencia promedio de los expertos fue alto. De los 16 aspectos valorados, uno resultó "bastante adecuado" y el resto, "muy adecuado". Se estimó concordancia significativa entre los expertos consultados. Conclusiones: Los resultados de la consulta a expertos apuntan al reconocimiento del valor científico, teórico y práctico, de la estrategia didáctica diseñada para favorecer las relaciones interdisciplinarias en el proceso enseñanza aprendizaje de las asignaturas clínicas, con la Farmacología en la carrera Estomatología y le otorgan validez.

Introduction: The validation of didactic strategies to favor interdisciplinary relationships in the teaching-learning process is necessary for their subsequent application in pedagogical practice and possible generalization. Objective: To validate a didactic strategy for interdisciplinary relationships in the teaching-learning process of clinical subjects, with Pharmacology in the Stomatology career. Methods: Educational research was carried out, between January and June, 2022. Theoretical methods (analytical-synthetic, inductive-deductive and systematization), empirical (consultation to experts) and mathematical-statisticians (descriptive statistics). The experts were selected according to the level of competence. A questionnaire was developed and applied to assess 16 aspects of the strategy, in terms of: very suitable, quite suitable, suitable, not very suitable and not suitable. The evaluative criteria issued by the experts were processed using the Torgerson mathematical model and the level of consensus of the experts was determined by calculating the Kendall concordance coefficient. Results: The average competence coefficient of the experts turned out to be high. Of the 16 aspects assessed, one was "fairly adequate" and the rest, "very adequate". Significant agreement was estimated between the experts consulted Conclusions: The results of the expert consultation point to the recognition of the scientific, theoretical and practical value of the didactic strategy designed to favor interdisciplinary relationships in the teaching-learning process of clinical subjects with Pharmacology in the Stomatology career, and give validity to the same.

Reliability and acceptance of dreaMS, a software application for people with multiple sclerosis: a feasibility study.

BACKGROUND: There is an unmet need for reliable and sensitive measures for better monitoring people with multiple sclerosis (PwMS) to detect disease progression early and adapt therapeutic measures accordingly. OBJECTIVE: To assess reliability of extracted features and meaningfulness of 11 tests applied through a smartphone application ("dreaMS"). METHODS: PwMS (age 18-70 and EDSS ≤ 6.5) and matched healthy volunteers (HV) were asked to perform tests installed on their smartphone once or twice weekly for 5 weeks. Primary outcomes were test-retest reliability of test features (target: intraclass correlation [ICC] ≥ 0.6 or median coefficient of variation [mCV] < 0.2) and reported meaningfulness of the tests by PwMS. Meaningfulness was self-assessed for each test on a 5-point Likert scale (target: mean score of > 3) and by a structured interview. CLINICALTRIALS: gov Identifier: NCT04413032. RESULTS: We included 31 PwMS (21 [68%] female, mean age 43.4 ± 12.0 years, median EDSS 3.0 [range 1.0-6.0]) and 31 age- and sex-matched healthy volunteers. Out of 133 features extracted from 11 tests, 89 met the preset reliability criteria. All 11 tests were perceived as highly meaningful to PwMS. CONCLUSION: The dreaMS app reliably assessed features reflecting key functional domains meaningful to PwMS. More studies with longer follow-up are needed to prove validity of these measures as digital biomarkers in PwMS.

Spliceosomic dysregulation unveils NOVA1 as a candidate actionable therapeutic target in pancreatic neuroendocrine tumors.

Dysregulation of the splicing machinery is emerging as a hallmark in cancer due to its association with multiple dysfunctions in tumor cells. Inappropriate function of this machinery can generate tumor-driving splicing variants and trigger oncogenic actions. However, its role in pancreatic neuroendocrine tumors (PanNETs) is poorly defined. In this study we aimed to characterize the expression pattern of a set of splicing machinery components in PanNETs, and their relationship with aggressiveness features. A qPCR-based array was first deployed to determine the expression levels of components of the major (n = 13) and minor spliceosome (n = 4) and associated splicing factors (n = 27), using a microfluidic technology in 20 PanNETs and non-tumoral adjacent samples. Subsequently, in vivo and in vitro models were applied to explore the pathophysiological role of NOVA1. Expression analysis revealed that a substantial proportion of splicing machinery components was altered in tumors. Notably, key splicing factors were overexpressed in PanNETs samples, wherein their levels correlated with clinical and malignancy features. Using in vivo and in vitro assays, we demonstrate that one of those altered factors, NOVA1, is tightly related to cell proliferation, alters pivotal signaling pathways and interferes with responsiveness to drug treatment in PanNETs, suggesting a role for this factor in the aggressiveness of these tumors and its suitability as therapeutic target. Altogether, our results unveil a severe alteration of the splicing machinery in PanNETs and identify the putative relevance of NOVA1 in tumor development/progression, which could provide novel avenues to develop diagnostic biomarkers and therapeutic tools for this pathology.

Mucosal Leishmaniasis of the lip: Report of an Exuberant case in a Young man.

BACKGROUND: Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania. Mucosal leishmaniasis has been described as secondary to the cutaneous form; however, isolated mucosal involvement can also occur. Specifically, mucosal leishmaniasis of the lip is poorly described and its diagnosis challenges clinicians. METHODS: We herein report a case of mucosal leishmaniasis affecting the lower lip without cutaneous involvement in a 20-year-old Venezuelan man. The patient had no relevant past medical history. Clinically, a mass-like lesion with ulcerations and crusts was observed. RESULTS: Microscopically, the lesion was composed of granulomatous inflammation along with macrophages containing intracytoplasmic inclusions similar to round-shaped Leishmania. The species Leishmania (Viannia) braziliensis was confirmed. Treatment with meglumine antimonate was effective. The lesion healed satisfactorily, and no side effects or recurrences were observed. CONCLUSION: Clinicians should be aware of isolated forms of mucosal leishmaniasis of the lip, even in cases where the cutaneous lesion is undetected or clinically manifests as self-limiting. Knowing the endemic areas in the scenario of the dynamics of the ecoepidemiology of leishmaniasis is also essential for surveillance and counselling of the population.

Prevalence of gestational diabetes and gestational hypertension in pregnant women with pregestational obesity / Prevalencia de diabetes e hipertensión gestacional en embarazadas con obesidad pregestacional

Resumen OBJETIVO: Describir la prevalencia de diabetes gestacional e hipertensión arterial en pacientes embarazadas con obesidad pregestacional. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo llevado a cabo en mujeres embarazadas con diagnóstico previo de obesidad (índice de masa corporal superior a 29.99) y con control prenatal. Parámetros evaluados: estilo de vida (alimentación, actividad física, consumo de alcohol, tabaco o alguna toxicomanía) y características físicas, clínicas y bioquímicas durante el embarazo actual por trimestre (índice de masa corporal, glucosa, presión arterial sistólica y diastólica). El diagnóstico de diabetes gestacional se estableció mediante una prueba de tolerancia a la glucosa entre las semanas 24 y 28 de embarazo. La hipertensión gestacional se diagnosticó por cifras de presión arterial mayores e iguales a 140-90 mmHg a partir de la semana 20 de embarazo y en ausencia de proteinuria. El análisis estadístico incluyó porcentajes, promedios e intervalos de confianza. RESULTADOS: La prevalencia de diabetes gestacional en embarazadas con obesidad fue 13.7% (IC95%: 9.6 a 17.9) y la de hipertensión gestacional en embarazadas con obesidad 7.4% (IC95%: 4.3 a 10.6). CONCLUSIÓN: La obesidad es un factor conocido de riesgos, en particular de diabetes e hipertensión en el embarazo. Su alta prevalencia hace necesario implementar campañas de prevención que favorezcan su reducción.

Abstract OBJECTIVE: To describe the prevalence of gestational diabetes and arterial hypertension in pregnant patients with pre-pregnancy obesity. MATERIALS AND METHODS: Retrospective, cross-sectional and descriptive study in pregnant women with a diagnosis of obesity prior to pregnancy (body mass index greater than 29.99) and with prenatal care. The sample size was 269 pregnant women. Lifestyle (diet, physical activity, alcohol, tobacco or drug addiction) and physical, clinical and biochemical characteristics during the current pregnancy were evaluated by gestational trimester (body mass index, glucose, systolic and diastolic blood pressure). The diagnosis of gestational diabetes was established by a glucose tolerance test between the 24th and 28th week of gestation and gestational hypertension was diagnosed by blood pressure figures greater than or equal to 140/90 mmHg from the 20th week of gestation and in the absence of proteinuria. Statistical analysis included percentages, means, and confidence intervals. RESULTS: The prevalence of gestational diabetes in obese pregnant women was 13.7% (95%CI: 9.6-17.9) and the prevalence of gestational hypertension in obese pregnant women was 7.4% (95%CI: 4.3-10.6). CONCLUSION: Obesity is a known risk factor, particularly for diabetes and hypertension in pregnancy. Its high prevalence makes it necessary to implement prevention campaigns to reduce it.

Calidad de la prueba parcial de un curso propio sobre diátesis hemorrágicas en la carrera Estomatología

Introducción: Dentro de los grandes desafíos que la formación universitaria en el sector salud enfrenta hoy, está el implementar y validar instrumentos de evaluación efectivos. Objetivo: Evaluar la calidad de la prueba parcial del curso propio Bases morfofuncionales de las principales diátesis hemorrágicas en Estomatología, de la Facultad de Estomatología, Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022. Método: Estudio observacional analítico y transversal, en 30 exámenes correspondientes a la prueba parcial del curso propio Bases morfofuncionales de las principales diátesis hemorrágicas en Estomatología, plan de estudio E, carrera de Estomatología, Facultad de Estomatología, Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022. Se analizó la correspondencia del fondo de tiempo y la cantidad de ítems explorados en el examen, se calcularon índices de dificultad y de discriminación de incisos y preguntas, coeficiente de discriminación biserial puntual y de consistencia interna. Resultados: Existió correspondencia adecuada entre el fondo de tiempo asignado a los contenidos de las temáticas y la cantidad de ítems explorados en el examen. Predominaron los reactivos con índice de dificultad media y buen poder de discriminación. La consistencia interna de las preguntas de modo individual fue excelente, pero la del examen en general fue baja. Conclusiones: La calidad del examen parcial del curso propio Bases morfofuncionales de las principales diátesis hemorrágicas en Estomatología, aplicado en la Facultad de Estomatología, Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022, fue poco adecuada.

Introduction: One of the challenges facing universities of health sciences today is the implementation and validation of effective tools for evaluation. Objective: To evaluate the quality of the partial exams of an in-house course in Morphofunctional bases of the most common hemorrhagic diathesis in Stomatology, Facultad de Estomatología, Universidad de Ciencias Médicas de Santiago de Cuba, course 2022. Method: An analytical and transversal observational study was carried out. For the study, it was selected 30 of the partial exams implemented in the in-house Morphofunctional bases of the most common hemorrhagic diathesis in Stomatology course, type (E) course syllabus, Stomatology career, Facultad de Estomatología, Universidad de Ciencias Médicas de Santiago de Cuba, course 2022. Correspondence between scheduled time and the number of items used in the test was assessed, and also, difficulty index and discrimination index for items and questions, point-biserial item discrimination coefficient and internal consistency coefficient were calculated. Results: There was an adequate correspondence between the time scheduled for the topics and the number of items used in the exam. Items with a moderate difficulty index and high degree of discrimination index predominated. The internal consistency of the individual questions was excellent, but the exam in general was low. Conclusions: The quality of the partial exam of the in-house course Morphofunctional bases of the main hemorrhagic diathesis treated in Stomatology, giving in the Faculty of Stomatology, University of Medical Sciences of Santiago de Cuba, course 2022, was inadequate.

Introdução: Entre os grandes desafios que a educação universitária na área da saúde enfrenta hoje, está a implementação e validação de instrumentos de avaliação eficazes. Objetivo: Avaliar a qualidade do teste parcial do curso Bases morfofuncionais da diátese hemorrágica principal em Estomatologia, da Facultad de Estomatología de la Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022. Método: Estudo observacional analítico e transversal, em 30 exames correspondentes à prova parcial do próprio curso Bases morfofuncionais da diátese hemorrágica principal em Estomatologia, plano de estudos E, carreira de Estomatologia de la Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022. A correspondência do analisou-se o fundo de tempo e o número de itens explorados no exame, calcularam-se índices de dificuldade e discriminação de subseções e questões, coeficiente de discriminação bisserial pontual e consistência interna. Resultados: Houve correspondência adequada entre o tempo destinado aos conteúdos dos temas e o número de itens explorados no exame. Predominaram os itens com índice de dificuldade médio e bom poder de discriminação. A consistência interna das questões individuais foi excelente, mas a do exame como um todo foi baixa. Conclusões: A qualidade do exame parcial das Bases Morfofuncionais da diátese hemorrágica principal do curso de Estomatologia, aplicado na Facultad de Estomatología de la Universidad de Ciencias Médicas de Santiago de Cuba, curso 2022, não foi adequada.

Neurotoxicidad en trabajadores petroquímicos con bajos índices de exposición a disolventes orgánicos.

OBJETIVO: Estimar el desempeño neuropsicológico y su asociación con la exposición a disolventes orgánicos (DO) en trabajadores petroquímicos en México. Material y méto-dos. Estudio transversal en 203 trabajadores: 102 expuestos a DO y 101 no expuestos. Se evaluó el desempeño neuropsi-cológico con Neurobehavioral Core Test Battery y la exposición a DO con la medición de metabolitos de exposición para tolueno, xilenos y benceno. RESULTADOS: Los trabajadores expuestos presentaron un peor desempeño en todas las pruebas (p<0.05), excepto en la prueba de Santa Ana. Esto se corroboró con modelos de regresión; los trabajadores expuestos a DO tuvieron un mayor número de errores y realizaron las pruebas en mayor tiempo (p<0.05), además de presentar mayores probabilidades de padecer síntomas de neurotoxicidad (OR: 2.93; IC95%: 0.96, 8.96). Conclusio-nes. La exposición ocupacional a disolventes orgánicos, aun a niveles permitidos por la normatividad mexicana vigente, se relacionó con un menor desempeño neuropsicológico.

Neurotoxicidad en trabajadores petroquímicos con bajos índices de exposición a disolventes orgánicos / Neurotoxicity among petrochemical workers with low exposure indexes to organic solvents

Resumen: Objetivo: Estimar el desempeño neuropsicológico y su asociación con la exposición a disolventes orgánicos (DO) en trabajadores petroquímicos en México. Material y métodos: Estudio transversal en 203 trabajadores: 102 expuestos a DO y 101 no expuestos. Se evaluó el desempeño neuropsicológico con Neurobehavioral Core Test Battery y la exposición a DO con la medición de metabolitos de exposición para tolueno, xilenos y benceno. Resultados: Los trabajadores expuestos presentaron un peor desempeño en todas las pruebas (p<0.05), excepto en la prueba de Santa Ana. Esto se corroboró con modelos de regresión; los trabajadores expuestos a DO tuvieron un mayor número de errores y realizaron las pruebas en mayor tiempo (p<0.05), además de presentar mayores probabilidades de padecer síntomas de neurotoxicidad (OR: 2.93; IC95%: 0.96, 8.96). Conclusiones: La exposición ocupacional a disolventes orgánicos, aun a niveles permitidos por la normatividad mexicana vigente, se relacionó con un menor desempeño neuropsicológico.

Abstract: Objective: To estimate the neuropsychological performance and its association with exposure to organic solvents (OS) among petrochemical workers in Mexico. Materials and methods: Cross-sectional study including 203 workers: 102 exposed to OS and 101 non-exposed. Neuropsychological performance was evaluated with Neurobehavioral Core Test Battery. Exposure to OS was evaluated with the metabolites from exposure to toluene, xylenes and benzene. Results: Exposed workers presented with a worse performance in all tests (p<0.05), except for Santa Ana test. This was corroborated with regression models; workers exposed to OS had a higher number of mistakes and performed the tests in longer time (p<0.05), together with having greater odds of neurotoxicity symptoms (OR: 2.93; 95%CI: 0.96, 8.96). Conclusions: Occupational exposure to organic solvents, even at levels allowed by current Mexican standards, was related to an impaired neuropsychological performance.

Dependencia endotelial del efecto de canfenol plus 3 % sobre el músculo liso vascular arterial / Endothelial dependence of the effect of 3 % camphenol plus on arterial vascular smooth muscl

RESUMEN Introducción: el canfenol plus, es un derivado clorado del fenol empleado de forma habitual como medicación intraconducto durante los tratamientos pulporradiculares en Estomatología. Son escasos los estudios en relación con sus efectos sobre el músculo liso vascular arterial y la participación del endotelio en estos. Objetivo: determinar la dependencia endotelial del efecto de canfenol plus 3 % sobre el músculo liso vascular arterial. Material y Métodos: se realizó una investigación experimental preclínica utilizando 26 anillos de carótida externa desprovistos de endotelio vascular. Las preparaciones realizadas se colocaron en baño de órganos, registrándose la tensión desarrollada por el músculo liso vascular tras la adición de acetilcolina, así como de soluciones de canfenol plus 3 % durante diferentes intervalos de tiempo. La dependencia entre ambas tensiones, se determinó a través de un modelo de regresión lineal simple. Resultados: tras la preactivación con solución Krebs concentrada de iones potasio, la adición de 10 μl de acetilcolina y canfenol plus 3 %, indujeron una discreta, pero significativa vasorrelajación de la musculatura lisa vascular. El modelo de regresión lineal elaborado, demostró la dependencia entre las variables tensión producida por acetilcolina y tensión producida por el fármaco al décimo minuto, corroborando la implicación del endotelio vascular en dicho efecto relajante. Conclusiones: el canfenol plus 3 %, produjo in vitro, un efecto vasorrelajante sobre la musculatura lisa de anillos de carótida externa, dependiente de endotelio y a partir de un factor relajante o hiperpolarizante derivado de este.

ABSTRACT Introduction: Camphenol plus is a chlorinated phenol derivative commonly used as intracanal medication during pulporradicular treatments in Dentistry. Studies in relation to its effects on arterial vascular smooth muscle and the involvement of the endothelium in them are scarce. Objective: To determine the endothelial dependence of the effect of 3 % camphenol plus on arterial vascular smooth muscle. Material and Methods: A preclinical experimental research was carried out using 26 external carotid artery rings devoid of vascular endothelium. The preparations made were placed in an organ bath, recording the tension developed by the vascular smooth muscle after the addition of acetylcholine, as well as 3 % Camphenol plus solutions during different intervals of time. The dependence between both tensions was determined through a simple linear regression model. Results: After pre-activation with Krebs concentrated potassium ion solution, the addition of 10 μl of acetylcholine and 3 % camphenol plus induced a discrete but significant vasorelaxation of the vascular smooth muscle. The linear regression model developed demonstrated the dependence between the variables tension produced by acetylcholine and tension produced by the drug at the tenth minute, corroborating the involvement of the vascular endothelium in that vasorelaxant effect. Conclusions: It is concluded that 3 % Camphenol plus in vitro, produced a vasorelaxant effect on the smooth muscle of external carotid rings dependent on endothelium and from a relaxing or hiperpolarizing factor derived from it.

Canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por Camphenol Plus

RESUMEN Introducción: El Camphenol Plus es un derivado clorofenólico empleado como medicación intraconducto durante los tratamientos pulporradiculares en Estomatología. Son escasos los reportes científicos sobre el papel de los canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por dicho medicamento. Objetivo: Determinar el papel de los canales de iones potasio en la dinámica contráctil del músculo liso arterial inducida por Camphenol Plus. Método: Se realizó una investigación experimental preclínica en el Instituto de Fisiología "Oscar Langerdorff", Facultad de Medicina, Universidad de Rostock, Alemania, entre octubre y diciembre de 2018, con el empleo de 30 anillos de aorta obtenidos de 10 ratas Wistar (n=10). Las preparaciones biológicas se colocaron en baño de órganos y se preactivaron con solución Krebs concentrada en iones potasio, registrándose luego la tensión desarrollada por el músculo liso vascular tras la adición de soluciones de Camphenol Plus durante diferentes intervalos de tiempo. Se utilizaron las pruebas de Wilcoxon y U de Mann-Whitney. Resultados: El 31,4 % de la musculatura lisa vascular se relajó por acción del Camphenol Plus tras la preactivación con solución Krebs concentrada en iones potasio. El mayor descenso del tono vascular se produjo con el uso de soluciones del medicamento al 7 % entre el primer y tercer minutos. Conclusiones : El efecto vasorrelajante in vitro producido por Camphenol Plus sobre el músculo liso arterial está mediado por canales de iones potasio sensibles a voltaje, a calcio y a trifosfato de adenosina del endotelio vascular y el sarcolema.

ABSTRACT Introduction: Camphenol Plus is a chlorophenolic derivative commonly used as an intra - duct medication for pulporadicular treatments in Dentistry. Scientific reports about the use of this medication on the role of potassium ion channels in the contractile dynamics of induced arterial smooth muscle are low. Objective: To determine the role of potassium ion channels in the contractile dynamics of Camphenol Plus - induced arterial smooth muscle. Method: A preclinical experimental investigation was performed at the "Oscar Langerdorff" Institute of Physiology, Rostock University Medical Center, Rostock, Germany, between October and December 2018. A total of 30 aortic rings obtained from 10 Wistar rats (n=10) were used. The biological preparations were placed in an organ bath and preactivated with Krebs solution concentrated in potassium ions, afterwards it was recorded the tension developed by the vascular smooth muscle after applying the Camphenol Plus solutions in different time intervals. The Mann-Whitney U test and Wilcoxon test were applied. Results: The 31.4% of vascular smooth muscle was relaxed by the effect of Camphenol Plus after preactivation with Krebs solution concentrated in potassium ions. The greatest decrease in vascular tone occurred between the first and third minutes after the use of the drug solutions prepared at 7 %. Conclusions: The in vitro vasorelaxant effect produced by the Camphenol Plus medication on arterial smooth muscle is mediated by the potassium ion channels sensitive to voltage, calcium and the adenosine triphosphate of the vascular endothelium and sarcolemma.

RESUMO Introdução: Camphenol Plus é um derivado clorofenólico utilizado como medicação intracanal durante tratamentos pulporradiculares em Estomatologia. Existem poucos relatos científicos sobre o papel dos canais iônicos de potássio na dinâmica contrátil do músculo liso arterial induzida pela referida droga. Objetivo: Determinar o papel dos canais iônicos de potássio na dinâmica contrátil do músculo liso arterial induzida por Camphenol Plus. Método: Uma investigação experimental pré-clínica foi realizada no Instituto de Fisiologia "Oscar Langerdorff" da Faculdade de Medicina da Universidade de Rostock, Alemanha, entre outubro e dezembro de 2018, utilizando 30 anéis aórticos obtidos de 10 ratos Wistar (n=10). As preparações biológicas foram colocadas em banho de órgãos e pré-ativadas com solução de Krebs concentrada em íons potássio, registrando-se então a tensão desenvolvida pelo músculo liso vascular após a adição de soluções de Camphenol Plus em diferentes intervalos de tempo. Foram utilizados os testes U de Wilcoxon e Mann-Whitney. Resultados: 31,4% da musculatura lisa vascular relaxada pela ação do Camphenol Plus após pré-ativação com solução de Krebs concentrada em íons potássio. A maior diminuição do tônus vascular ocorreu com o uso de soluções medicamentosas a 7% entre o primeiro e o terceiro minutos. Conclusões: O efeito vasorrelaxante in vitro produzido pelo Camphenol Plus no músculo liso arterial é mediado por canais de íons de potássio sensíveis à voltagem, trifosfato de cálcio e adenosina do endotélio vascular e do sarcolema.

Efectividad de la regeneración tisular guiada en lesiones de furcación dentarias mandibulares

RESUMEN Introducción: La lesión de furcación se define como la reabsorción patológica del hueso interradicular, con la consiguiente exposición de la furca, el aumento del riesgo de pérdida ósea y la aparición de defectos óseos difíciles de tratar, los que pueden mejorar con el uso de membranas a través de la regeneración tisular guiada. Objetivo: Determinar la efectividad de la regeneración tisular guiada en lesiones de furca dentarias mandibulares en la Clínica Estomatológica Provincial "Mártires del Moncada", de Santiago de Cuba, durante el periodo septiembre de 2018 a diciembre de 2019. Método: Se realizó un estudio cuasi-experimental de intervención terapéutica con una muestra de 20 pacientes con lesiones de furca mandibulares, seleccionados por muestreo no probabilístico intencional. Se conformaron 2 grupos aleatorios por orden de llegada de 10 pacientes cada uno. Un grupo estudio recibió la terapia regenerativa y un grupo control fue tratado de forma convencional. Ambos, cumplieron con el criterio diagnóstico y fueron examinados antes y después de los tratamientos a los 6 meses y al año. Resultados: Al evaluar al año de tratamiento, en el grupo I, el sangrado desapareció y la profundidad al sondaje disminuyó al menos 1 mm en el 100% de los casos, la ganancia de inserción tipo I se logró en el 60% de ellos, con marcada superioridad sobre el grupo control. Conclusiones: El tratamiento con regeneración tisular guiada demuestra ser efectivo en los pacientes tratados con lesión de furcación a diferencia del tratamiento convencional.

ABSTRACT Introduction: The furcation lesion is defined as a pathological resorption of the interradicular bone, with the consequent exposure of the furcation, increased risk of bone loss and the onset of difficult-to-treat bone defects, which can be improved with the use of membranes through guided tissue regeneration. Objective: To determine the effectiveness of guided tissue regeneration in mandibular dental furcation lesions at the Clínica Estomatológica Provincial "Mártires del Moncada" in Santiago de Cuba, from Septembre 2018 to December 2019. Method: A quasi-experimental study of therapeutic intervention was carried out with a sample of 20 patients with mandibular furcation lesions and selected by non-probabilistic purposive sampling. One cluster (study group) received regenerative therapy and the other cluster (control group) was treated conventionally. Both met the diagnostic criteria and were examined before and after the treatments (6 months after treatment and 1 year after treatment). Results: after assessed the year of treatment, in group I (study group), bleeding disappeared and probing depth decreased by at least 1 mm in 100% of the cases, type I insertion gain was achieved in 60% of them, with a marked superiority in the control group. Conclusions: Treatment with guided tissue regeneration has been shown to be effective in patients treated with furcation lesions in contrast to conventional treatment.

RESUMO Introdução: A lesão de furca é definida como a reabsorção patológica do osso interradicular, com a conseqüente exposição da furca, aumento do risco de perda óssea e aparecimento de defeitos ósseos de difícil tratamento, que podem melhorar com o uso de membranas através da regeneração tecidual guiada. Objetivo: Determinar a eficácia da regeneração tecidual guiada em lesões de furca dentária mandibular na Clínica Estomatológica Provincial "Mártires del Moncada", Santiago de Cuba, durante o período de setembro de 2018 a dezembro de 2019. Método: Foi realizado um quasi-estudo experimental de intervenção terapêutica com amostra de 20 pacientes com lesões de furca mandibular, selecionados por amostragem não probabilística intencional. 2 grupos randomizados foram formados em ordem de chegada de 10 pacientes cada. Um grupo de estudo recebeu terapia regenerativa e um grupo controle foi tratado de forma convencional. Ambos preencheram os critérios diagnósticos e foram examinados antes e depois dos tratamentos aos 6 meses e 1 ano. Resultados: Ao avaliar um ano de tratamento, no grupo I, o sangramento desapareceu e a profundidade de sondagem diminuiu em pelo menos 1 mm em 100% dos casos, o ganho de inserção tipo I foi alcançado em 60% deles, com acentuada superioridade sobre o grupo de controle. Conclusões: O tratamento com regeneração tecidual guiada mostra-se eficaz em pacientes tratados com lesão de furca, ao contrário do tratamento convencional.

Problemas que limitan la interdisciplinariedad entre la Farmacología y las asignaturas clínicas en Estomatología / Problems that limit interdisciplinary between Pharmacology and Stomatology clinical subjects

RESUMEN Fundamento: El desarrollo de la interdisciplinariedad entre la unidad curricular Farmacología y las asignaturas clínicas de la Disciplina Principal Integradora en la carrera Estomatología, resulta indispensable para la formación integral del futuro egresado. Objetivo: Identificar los problemas que limitan el desarrollo de la interdisciplinariedad entre la Farmacología y las asignaturas clínicas de la Disciplina Principal Integradora en la carrera Estomatología. Metodología: Se realizó un estudio observacional descriptivo transversal entre noviembre y diciembre de 2020 en la Facultad de Estomatología de la Universidad de Ciencias Médicas de Santiago de Cuba. Se consideraron como unidades de análisis: actividades docentes y directivos académicos, se seleccionó una muestra aleatoria en ambos casos (n=18 y n=8, respectivamente). Se estudiaron las variables: relaciones interdisciplinarias con la Farmacología (se observa, no se observa y se observa poco), categoría docente, categoría científica, grado académico/científico, grado de especialización y opinión de directivos académicos (siempre, a veces y nunca). Como instrumento de medición se empleó guía de observación y de entrevista, respectivamente. Se empleó el porcentaje como medida de resumen. Resultados: En más del 50 % de las actividades docentes de las asignaturas clínicas de la Disciplina Principal Integradora, no se observa las relaciones interdisciplinarias con la Farmacología. En las entrevistas realizadas a los directivos académicos, predominó la opinión: nunca. Conclusiones: Las insuficiencias didácticas, metodológicas, académicas e investigativas identificadas, limitan el desarrollo de la interdisciplinariedad entre la unidad curricular Farmacología y las asignaturas clínicas de la Disciplina Principal Integradora en la carrera Estomatología.

ABSTRACT Background: The development of interdisciplinarity between the curricular Pharmacology unit and the clinical subjects of the Main discipline in the Stomatology career is essential for the integral formation of the future graduate. Objective: To identify the problems that limit the development of interdisciplinarity between Pharmacology and the clinical subjects of the Main Comprehensive Discipline in the Stomatology career. Methodology: A cross-sectional descriptive observational study was conducted between November and December 2020 in the Stomatology Faculty at the Santiago de Cuba University of Medical Sciences. The following were considered as analysis units: teaching activities and academic directors, a random sample was selected in both cases (n=18 and n=8, respectively). The following variables were studied: interdisciplinary relations with Pharmacology (observed, not observed and little observed), teaching category, scientific category, academic/scientific degree, specialization degree and the academic directors´ opinion (always, sometimes and never). Observation and interview guides were used respectively as measurement instruments. Percentage was used as a summary measure. Results: In more than 50 % of the teaching activities of the clinical subjects of the Main Comprehensive Discipline, interdisciplinary relations with Pharmacology are not observed. In the interviews conducted with academic managers, the prevailed opinion was never. Conclusions: The didactic, methodological, academic and research inadequacies identified, limit the development of interdisciplinarity between the curricular unit Pharmacology and the clinical subjects of the Main Comprehensive Discipline in the Stomatology career.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Efecto del 4-Clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar / Effect of 4-Chlorophenol on the vascular smooth muscle of the abdominal aorta of Wistar rats

Introducción: Uno de los derivados de los clorofenoles más utilizado en Estomatología, lo constituye el p-clorofenol (4-clorofenol), empleado como agente antibacteriano en la desinfección del conducto radicular durante el tratamiento pulporradicular. Son escasos los reportes científicos sobre sus efectos en la musculatura lisa vascular arterial y la regulación del flujo sanguíneo local. Objetivo: Determinar el efecto del 4-clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar. Material y Métodos: Se realizó una investigación experimental preclínica, utilizando 30 anillos de aorta abdominal (porción superior) obtenidos de ratas Wistar adultas. Las preparaciones de unos 5 mm se colocaron en baño de órganos, registrándose la tensión desarrollada por el músculo liso vascular tras la adición de 4-clorofenol en diferentes concentraciones y durante diferentes intervalos de tiempo. Resultados: El 4-clorofenol, tras la preactivación del musculo liso vascular de anillos de aorta abdominal, indujo relajación del vaso, la que se incrementó durante todo el tiempo de estudio y al aumento de la concentración del medicamento. Existieron diferencias significativas entre los valores de tensión promedios registrados en los diferentes intervalos de tiempo con los de la tensión base inicial. Conclusiones: El p-clorofenol indujo in vitro, relajación del músculo liso vascular de aorta abdominal de ratas Wistar(AU)

Introduction: In Dentistry, p-chlorophenol (4-chlorophenol) is one of the most widely used derivatives of chlorophenols. It is used as an antibacterial agent in root canal disinfection during pulp-radicular treatment. There are few scientific reports on its effects on vascular smooth musculature and the regulation of local blood flow. Objective: To determine the effect of 4-chlorophenol on vascular smooth muscle of abdominal aorta from Wistar rats. Material and Methods: A preclinical experimental research was carried out using 30 abdominal aortic rings (upper portion) obtained from adult Wistar rats. The preparations of about 5 mm were placed in an organ bath, recording the tension developed by the vascular smooth muscle after the addition of 4-chlorophenol at different concentrations and during different time intervals. Results: The results demonstrate that 4-Chlorophenol induced vasorelaxation after the preactivation of the vascular smooth muscle of the abdominal aortic rings, which increased during the entire study time and with increased drug concentration. There were significant differences among average tension values registered at different intervals of time in relation to the initial base tension. Conclusions: It is concluded that in vitro, p-chlorophenol induced relaxation of abdominal aorta vascular smooth muscle in Wistar rats(AU)

Efecto del Camphenol Plus sobre el músculo liso vascular de vena porta en ratas Wistar / Effect of Camphenol Plus on portal vein vascular smooth muscle in Wistar rats

RESUMEN Introducción: uno de los antisépticos comúnmente empleado en Estomatología desde el pasado siglo y que mantiene su uso hasta la actualidad, lo constituye el Camphenol Plus. Son escasos los reportes científicos de su efecto sobre el endotelio y la dinámica contráctil del músculo liso vascular, en especial de tejidos venosos como la vena porta hepática. Objetivo: determinar el efecto del Camphenol Plus sobre el músculo liso vascular de la vena porta. Métodos: se realizó una investigación experimental preclínica, con la utilización de 21 venas porta obtenidas de ratas Wistar. Las preparaciones realizadas se colocaron en baño de órganos, se registró la tensión desarrollada por el músculo liso vascular tras la adición de diez microlitros de Camphenol Plus, en diferentes concentraciones y durante diferentes intervalos de tiempo. Resultados: el Camphenol Plus, tras la preactivación del musculo liso vascular de la vena porta, indujo vasorelajación, la que se incrementó durante todo el tiempo de estudio y según el incremento de las concentraciones del medicamento. Existieron diferencias significativas entre los valores de tensión promedios registrados en los diferentes intervalos de tiempo con los de la tensión espontánea basal y la tensión base inicial. Conclusiones: el Camphenol Plus, indujo "in vitro", relajación de la musculatura lisa de la vena porta a través de un acoplamiento excitación-contracción de tipo farmacomecánico.

ABSTRACT Introduction: Camphenol Plus is one of the antiseptics commonly used in Dentistry since the last century and still in use today. There are few scientific reports of its effect on the endothelium and contractile dynamics of vascular smooth muscle, especially in venous tissues such as the hepatic portal vein. Objective: to determine the effect of Camphenol Plus on the vascular smooth muscle of the portal vein. Methods: a preclinical experimental investigation was carried out using 21 portal veins obtained from Wistar rats. The preparations were placed in an organ bath and the tension developed by the vascular smooth muscle was recorded after the addition of ten microliter of Camphenol Plus, at different concentrations and during different time intervals. Results: Camphenol Plus, after the preactivation of the vascular smooth muscle of the portal vein, induced relaxation, which increased throughout the study time and according to the increase in drug concentrations. There were significant differences between the average tension values recorded in the different time intervals with those of the basal spontaneous tension and the initial baseline tension. Conclusions: Camphenol Plus induced "in vitro" relaxation of portal venous smooth muscles through a pharmacomechanical excitation-contraction coupling.