RESUMEN
STAT3 gain-of-function (GOF) variants results in a heterogeneous clinical syndrome characterized by early onset immunodeficiency, multi-organ autoimmunity, and lymphoproliferation. While 191 documented cases with STAT3 GOF variants have been reported, the impact of individual variants on immune regulation and the broad clinical spectrum remains unclear. We developed a Stat3p.L387R mouse model, mirroring a variant identified in a family exhibiting common STAT3 GOF symptoms, and rare phenotypes including pulmonary hypertension and retinal vasculitis. In vitro experiments revealed increased STAT3 phosphorylation, nuclear migration, and DNA binding of the variant. Our Stat3p.L387R model displayed similar traits from previous Stat3GOF strains, such as splenomegaly and lymphadenopathy. Notably, Stat3p.L387R/+ mice exhibited heightened embryonic lethality compared to prior Stat3GOF/+ models and ocular abnormalities were observed. This research underscores the variant-specific pathology in Stat3p.L387R/+ mice, highlighting the ability to recapitulate human STAT3 GOF syndrome in patient-specific transgenic murine models. Additionally, such models could facilitate tailored treatment development.
Asunto(s)
Modelos Animales de Enfermedad , Mutación con Ganancia de Función , Factor de Transcripción STAT3 , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Animales , Ratones , Humanos , Mutación con Ganancia de Función/genética , Femenino , Masculino , Ratones Transgénicos , Fenotipo , Fosforilación , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Asynchronous online lecture has become a common teaching method in medical education, especially during the COVID-19 pandemic. However, the effectiveness and students' attitudes towards this method under this special circumstance have not been exclusively studied. Hence, we aimed to evaluate these aspects of cardiovascular physiology teaching in an undergraduate medical curriculum. METHODS: We analysed and compared the academic achievement and attitudes of 613 medical students on cardiovascular physiology between pre-COVID-19 and COVID-19 years in which different teaching methods were implemented. In addition, we also explored the importance of teaching methods and teachers by subgroup analysis to evaluate whether they influenced the academic achievement and attitudes of students. RESULTS: Overall students' academic achievement was significantly higher when lectures were taught by the traditional method than by the asynchronous online method. Moreover, subgroup analysis revealed that teachers were also a factor influencing students' academic achievement. Although most students had positive attitudes towards asynchronous online lectures, overall satisfaction was slightly higher when all lectures were taught by the traditional method than by the asynchronous online method. CONCLUSIONS: Asynchronous online lectures might not be an effective teaching method especially during the abrupt change in education. Under the 'new normal' medical education, not only teaching methods but also teachers are the essential keys to the success in academic achievement and attitudes of undergraduate medical students.
Asunto(s)
COVID-19 , Estudiantes de Medicina , COVID-19/epidemiología , Fenómenos Fisiológicos Cardiovasculares , Humanos , Pandemias , SARS-CoV-2 , EnseñanzaRESUMEN
BACKGROUND: Pre-clerkship medical curriculums consist of a series of organ system-based courses and lectures but often lack an integration between organ systems. Such integration could be beneficial for clerkship years and students' future career. Hence, we aimed to share our process of organising an integrative teaching approach in a large class of pre-clerkship medical students and to reflect the students' perspective toward the teaching process in this observational study. In addition, we tested effectiveness of this integrative approach compared with the traditional teaching (lecture). METHODS: We organised a two-dimensional (2D)-integrative teaching for 309 students in selected topics of cardiovascular physiology of the medical curriculum of the Faculty of Medicine, Chulalongkorn University, Thailand. The first dimension of integration is the incorporation of physiology of other organ systems into the cardiovascular physiology class. The second is the integration of multiple teaching methods and strategies, including small group discussion, student presentation, wrap-up, quiz, and question-and-answer sessions. Unless opting out, students evaluated this integrative teaching by filling in a questionnaire. The summative scores were also used to determine their comprehensive understandings of the content. RESULTS: The course evaluation showed that most students (81.9-91.2%) had positive attitudes toward all organised sessions, i.e. this teaching method helps promote their basic and applied physiology knowledge, critical thinking, information searching, presentation, and teamwork skills. In general, students at all performance levels attained higher scores in the summative exam for the 2D-integrative-class-relevant questions (74.4±16.1%) than for the lecture-pertinent questions (65.2±13.6%). CONCLUSIONS: In a large class size of pre-clerkship students, 2D-integrative teaching strategies with careful planning and preparation can be successfully implemented, based on positive attitudes and relatively high summative scores of students in this study. Hence, this comprehensive teaching could be incorporated in current medical curriculums, particularly for the complex learning topics.
Asunto(s)
Fisiología , Estudiantes de Medicina , Fenómenos Fisiológicos Cardiovasculares , Curriculum , Humanos , Aprendizaje , Fisiología/educación , Enseñanza , TailandiaRESUMEN
To maintain a thermal balance when experiencing cold, humans reduce heat loss and enhance heat production. A potent and rapid mechanism for heat generation is shivering. Research has shown that women prefer a warmer environment and feel less comfortable than men in the same thermal condition. Using the Blanketrol® III, a temperature management device commonly used to study brown adipose tissue activity, we tested whether the experimental temperature (TE) at which men and women start to shiver differs. Twenty male and 23 female volunteers underwent a cooling protocol, starting at 24⯰C and gradually decreasing by 1-2⯰C every 5â¯min until an electromyogram detected the shivering or the temperature reached 9⯰C. Women started shivering at a higher TE than men (11.3⯱â¯1.8⯰C for women vs 9.6⯱â¯1.8⯰C for men, Pâ¯=â¯0.003). In addition, women felt cool, scored by a visual analogue scale, at a higher TE than men (18.3⯱â¯3.0⯰C for women vs 14.6⯱â¯2.6⯰C for men, Pâ¯<â¯0.001). This study demonstrates a sex difference in response to cold exposure: women require shivering as a source of heat production earlier than men. This difference could be important and sex should be considered when using cooling protocols in physiological studies.
Asunto(s)
Tiritona , Sensación Térmica , Adolescente , Adulto , Temperatura Corporal , Regulación de la Temperatura Corporal , Frío , Femenino , Humanos , Masculino , Caracteres Sexuales , Temperatura Cutánea , Adulto JovenRESUMEN
OBJECTIVE: 1) To determine rectal temperature (Tre) and fluid loss (FL) of obese men (OM) compared to non-obese men (NM) during exercise in cool conditions (CC) and hot and humid conditions (HC), and 2) to investigate the effects of cold water (CW; 0.5 ± 0.5°C) ingestion before exercise in HC in OM MATERIAL AND METHOD: Twelve OM and 12 NM completed 2 treadmill exercise sessions, in CC and HC, in a randomized order Each session was performed for 30 minutes at 45-50% of heart rate reserve with a 5-minute warm up and 5-minute cool down. RESULTS: There were no differences in Tre in response to exercise between OM and NM both in CC (OM 37.77 ± 0.08°C, NM 37.68 ± 0.08°C; p = 0.463) and in HC (OM 37.82 ± 0.06°C, NM 37.85 ± 0.06°C; p = 0.725). Heart rate, perceived exertion and thermal sensations were not significantly different between OM and NM. However, compared to NM, fluid loss (FL) was approximately 160 mL greater in OM (OM 443.33 ± 98.65 mL, NM 283.33 ± 108.15 mL; p ≤ 0.001) in CC, and was 194 mL greater (OM 632.50 ± 126.57 mL, NM 438.33 ± 126.62 mL; p ≤ 0.001) in HC. In HC, the 12 OM performed additional 2 bouts of exercise, with CW vs. ambient temperature water (AW; 30.5 ± 0.5°C) ingestions prior to the start of exercise. Precooling with CW ingestion, compared to AW ingestion, showed no significant difference in Tre but CW was able to reduce FL (CW 646.67 ± 139.82 mL, AW 735 ± 126.95 mL; p = 0.010). CONCLUSION: OM may continuously exercise about 30 minutes at moderate intensity in HC without the increase of Tre to dangerous levels. However, OM should drink approximately 200 mL more water in HC and 160 mL more water in CC than NM. Precooling with CW ingestion is a good method of reducing risk of exertional heat illnesses in obese individuals during exercise in HC, as it decreases the amount of FL induced by exercise.
Asunto(s)
Temperatura Corporal , Frío , Ejercicio Físico , Obesidad , Equilibrio Hidroelectrolítico , Agua/administración & dosificación , Adulto , Prueba de Esfuerzo , Frecuencia Cardíaca , Calor , Humanos , Humedad , Masculino , Adulto JovenRESUMEN
BACKGROUND: To decrease preventable maternal mortality, providing health education to all parties is mandatory. Good knowledge, including awareness of pregnant women regarding obstetric danger signs (ODS), leads to appropriate practices and services. The knowledge of ODS varies among countries and regions. Since the data in rural regions of Thailand remains unavailable, this study aimed to identify the prevalence of good ODS knowledge and associated factors among pregnant women attending antenatal services at a Thai community hospital. METHODS: We performed a cross-sectional, analytical study in 415 singleton pregnant women who visited the antenatal clinic at Wang Saphung Hospital, Loei, Thailand. A well-trained research assistant interviewed all participants using the data record form containing twenty items on the demographic and obstetric data and sixteen items on ODS knowledge. An ODS score of at least 75% (12 points) was considered a good level of knowledge. RESULTS: A total of 275 participants (66.27%) had good knowledge of ODS. The most recognized ODS was vaginal bleeding whereas the least recognized ODS during pregnancy was convulsion; the least recognized ODS during labor and delivery was retained placenta. Multivariate regression analysis showed that the predictive factors of good OBS knowledge included a higher education level, maternal age of at least 20 years, and having medical personnel as a source of knowledge. CONCLUSIONS: In a rural setting of Thailand, two-thirds of pregnant women had good ODS knowledge. Identifying those at risk for fair and poor ODS knowledge and prompt management for the vulnerable subgroups might help decrease maternal mortality.
Asunto(s)
Complicaciones del Trabajo de Parto , Mujeres Embarazadas , Embarazo , Femenino , Humanos , Adulto Joven , Adulto , Atención Prenatal , Tailandia/epidemiología , Estudios Transversales , Hospitales Comunitarios , Complicaciones del Trabajo de Parto/epidemiología , Complicaciones del Trabajo de Parto/diagnóstico , Conocimientos, Actitudes y Práctica en SaludRESUMEN
BACKGROUND: During the COVID-19 pandemic, pre-clerkship medical education, including all physiology classes, was obliged to change to online teaching due to limitations of on-site (face-to-face) classes. However, the effectiveness of online teaching in non-lecture physiology topics during the COVID-19 pandemic has not been thoroughly investigated. METHOD: We conducted a prospective study to evaluate the students' academic achievement and opinions on online teaching during the COVID-19 academic year. Academic achievement of 312 students in the COVID-19 year was compared with that of 299 students in the pre-COVID-19 year. Student opinions regarding social interactions and the preferred learning method were also collected. RESULTS: We found that student academic achievement in the non-lecture physiology topics, assessed by summative scores, was 4.80±0.92 percent higher in the pre-COVID-19 year than in the COVID-19 year (P < 0.01, Cohen's d = 0.42). Students rated that online classes tended to reduce their interactions with peers and teachers; however, students preferred online learning over traditional on-site learning. CONCLUSIONS: This study pointed out that students' academic performance related to the physiology topics taught by online non-lecture methods during the COVID-19 pandemic was lower than their performance when the topics were taught by the traditional (on-site) methods, although students reported that they preferred the online teaching. Hence, we suggest that medical teachers should deliberately plan and utilise a variety of tools and techniques when developing online non-lecture classes to preserve the interactivity of the classes, which might overcome this gap in students' academic performance.
Asunto(s)
Rendimiento Académico , COVID-19 , Educación a Distancia , Estudiantes de Medicina , Humanos , COVID-19/epidemiología , Pandemias , Estudios Prospectivos , Educación de Pregrado en Medicina , Estudiantes de Medicina/psicologíaRESUMEN
Muscle atrophy is common in patients with increased glucocorticoid exposure. Glucocorticoid effects are often sex-specific, and while different glucocorticoid responses between male and female subjects are reported, it is unclear why this is. In this study, we evaluated the effects of corticosterone and synthetic glucocorticoid treatment on muscle atrophy in male and female mice. We found that corticosterone treatment reduced grip strength in female mice only, whereas muscle mass was reduced in both sexes. Skeletal muscle transcriptional responses to corticosterone treatment were more pronounced and widespread in male mice. Synthetic glucocorticoid treatment reduced grip strength in both sexes, while female mice were more sensitive to muscle atrophy than male mice. To evaluate the role of androgens, chemically-castrated male mice were treated with synthetic glucocorticoids. We observed additively reduced muscle mass, but did not observe any interaction effects. Although sex differences in glucocorticoid responses in skeletal muscle are partly influenced by androgen signaling, further studies are warranted to fully delineate the underlying mechanisms.
Asunto(s)
Corticosterona , Glucocorticoides , Andrógenos/farmacología , Animales , Corticosterona/farmacología , Femenino , Glucocorticoides/farmacología , Humanos , Masculino , Ratones , Músculo Esquelético , Atrofia Muscular , Caracteres SexualesRESUMEN
Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.
Asunto(s)
Tejido Adiposo Pardo/fisiología , Glucocorticoides/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Factores Sexuales , Adipocitos Marrones/citología , Andrógenos/metabolismo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Homeostasis , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Metabolismo de los Lípidos , Lípidos/química , Masculino , Ratones , Obesidad/complicaciones , Ratas , Caracteres Sexuales , TermogénesisRESUMEN
Brown adipose tissue (BAT) is a metabolically active organ that exhibits sex-differential features, that is, being generally more abundant and active in females than in males. Although sex steroids, particularly estrogens, have been shown to regulate BAT thermogenic function, the underlying molecular mechanisms contributing to sexual dimorphism in basal BAT activity have not been elucidated. Therefore, we assessed the transcriptome of interscapular BAT of male and female C57BL/6J mice by RNA sequencing and identified 295 genes showing ≥2-fold differential expression (adjusted P < 0.05). In silico functional annotation clustering suggested an enrichment of genes encoding proteins involved in cell-cell contact, interaction, and adhesion. Ovariectomy reduced the expression of these genes in female BAT toward a male pattern whereas orchiectomy had marginal effects on the transcriptional pattern, indicating a prominent role of female gonadal hormones in this sex-differential expression pattern. Progesterone was identified as a possible upstream regulator of the sex-differentially expressed genes. Studying the direct effects of progesterone in vitro in primary adipocytes showed that progesterone significantly altered the transcription of several of the identified genes, possibly via the glucocorticoid receptor. In conclusion, this study reveals a sexually dimorphic transcription profile in murine BAT at general housing conditions and demonstrates a role for progesterone in the regulation of the interscapular BAT transcriptome.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Progesterona/farmacología , Caracteres Sexuales , Transcriptoma/genética , Adipocitos Marrones/efectos de los fármacos , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Línea Celular , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Masculino , Ratones Endogámicos C57BL , Reproducibilidad de los Resultados , Programas Informáticos , Transcripción Genética/efectos de los fármacos , Transcriptoma/efectos de los fármacosRESUMEN
Prolonged exposure to glucocorticoids (GCs) causes various metabolic derangements. These include obesity and insulin resistance, as inhibiting glucose utilization in adipose tissues is a major function of GCs. Although adipose tissue distribution and glucose homeostasis are sex-dependently regulated, it has not been evaluated whether GCs affect glucose metabolism and adipose tissue functions in a sex-dependent manner. In this study, high-dose corticosterone (rodent GC) treatment in C57BL/6J mice resulted in nonfasting hyperglycemia in male mice only, whereas both sexes displayed hyperinsulinemia with normal fasting glucose levels, indicative of insulin resistance. Metabolic testing using stable isotope-labeled glucose techniques revealed a sex-specific corticosterone-driven glucose intolerance. Corticosterone treatment increased adipose tissue mass in both sexes, which was reflected by elevated serum leptin levels. However, female mice showed more metabolically protective adaptations of adipose tissues than did male mice, demonstrated by higher serum total and high-molecular-weight adiponectin levels, more hyperplastic morphological changes, and a stronger increase in mRNA expression of adipogenic differentiation markers. Subsequently, in vitro studies in 3T3-L1 (white) and T37i (brown) adipocytes suggest that the increased leptin and adiponectin levels were mainly driven by the elevated insulin levels. In summary, this study demonstrates that GC-induced insulin resistance is more severe in male mice than in female mice, which can be partially explained by a sex-dependent adaptation of adipose tissues.
Asunto(s)
Glucemia/metabolismo , Corticosterona/toxicidad , Resistencia a la Insulina , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adipoquinas/genética , Adipoquinas/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Insulina/farmacología , Leptina/genética , Leptina/metabolismo , Masculino , Ratones , Factores SexualesRESUMEN
BACKGROUND: The thermoneutral zone (TNZ) is a species-specific range of ambient temperature (T a), at which mammals can maintain a constant body temperature with the lowest metabolic rate. The TNZ for an adult mouse is between 26 and 34 °C. Interestingly, female mice prefer a higher T a than male mice although the underlying mechanism for this sex difference is unknown. Here, we tested whether gonadal hormones are dominant factors controlling temperature preference in male and female mice. METHODS: We performed a temperature preference test in which 10-week-old gonadectomized and sham-operated male and female C57BL/6J mice were allowed to choose to reside at the thermoneutral cage of 29 °C or an experimental cage of 26, 29, or 32 °C. RESULTS: All mice preferred a T a higher than 26 °C, especially in the inactive phase. Choosing between 29 and 32 °C, female mice resided more at 32 °C while male mice had no preference between the temperatures. Hence, the preferred T a for female mice was significantly higher (0.9 ± 0.2 °C) than that for male mice. However, gonadectomy did not influence the T a preference. CONCLUSIONS: Female mice prefer a warmer environment than male mice, a difference not affected by gonadectomy. This suggests that thermal-sensing mechanisms may be influenced by sex-specific pathways other than gonadal factors or that the thermoregulatory set point has already been determined prior to puberty.