NR2F2 regulation of interstitial to fetal Leydig cell differentiation in the testis: insights into differences of sex development.

Testicular fetal Leydig cells are a specialized cell type responsible for embryo masculinization. Fetal Leydig cells produce androgens, that induce the differentiation of male reproductive system and sexual characteristics. Deficiencies in Leydig cell differentiation leads to various disorders of sex development and male reproductive defects such as ambiguous genitalia, hypospadias, cryptorchidism, and infertility. Fetal Leydig cells are thought to originate from proliferating progenitor cells in the testis interstitium, marked by genes like Arx , Pdgfra , Tcf21 and Wnt5a . However, the precise mechanisms governing the transition from interstitial cells to fetal Leydig cells remain elusive. Through integrated approaches involving mouse models and single-nucleus multiomic analyses, we discovered that fetal Leydig cells originate from a Nr2f2 -positive non-steroidogenic interstitial cell population. Embryonic deletion of Nr2f2 in mouse testes resulted in disorders of sex development, including dysgenic testes, Leydig cell hypoplasia, cryptorchidism, and hypospadias. We found that NR2F2 promotes the progenitor cell fate while suppresses Leydig cell differentiation by directly and indirectly controlling a cohort of transcription factors and downstream genes. Bioinformatic analyses of single-nucleus ATAC-seq and NR2F2 ChIP-seq data revealed putative transcription factors co-regulating the process of interstitial to Leydig cell differentiation. Collectively, our findings not only highlight the critical role of Nr2f2 in orchestrating the transition from interstitial cells to fetal Leydig cells, but also provide molecular insight into the disorders of sex development as a result of Nr2f2 mutations.

Serologically Confirmed Human Leptospirosis in Colombia, 2015-2020.

Leptospirosis, a bacterial infection transmitted through contact with infected animals or contaminated water sources, imposes a substantial health burden in Colombia. Since 2007, the National Institute of Health (INS) has mandated the notification and confirmation of all suspected leptospirosis cases. This passive surveillance program employs the microscopic agglutination test (MAT) on serum samples to ascertain confirmed cases of leptospirosis infection. However, the absence of a robust surveillance system has hindered our comprehensive understanding of the morbidity, mortality, geographical distribution, species/serovars, and strains responsible for severe disease. Our study aimed to provide an epidemiological overview of MAT-confirmed human leptospirosis cases reported over 6 years (2015-2020) in Colombia. In addition, we offer insights into the status of leptospirosis in the country, focusing on risk factors and proposing potential improvements for diagnosis and disease management. During the 6-year surveillance period, the laboratory at the INS received 3,535 serum samples from suspected human leptospirosis cases, with 880 (25%) confirmed through MAT. The incidence of leptospirosis was calculated at 1.9 cases per 100,000 people, with a higher prevalence among men (82.1%). Furthermore, 54 (6.1%) deaths were confirmed as leptospirosis, and cases were documented across nearly all regions of Colombia. Our findings emphasize the urgent need to strengthen leptospirosis laboratory surveillance, implement effective prevention measures, and enhance diagnostic capabilities in Colombia. The analysis conducted in this study provides the groundwork for estimating the impact of leptospirosis and raises awareness of its significance in public health.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Recovery and Characterization of Spermatozoa in a Neotropical, Terrestrial, Direct-Developing Riparian Frog (Craugastor evanesco) through Hormonal Stimulation.

The Vanishing Rainfrog (Craugastor evanesco) is an endemic and critically endangered frog species of Panama. It is suspected that 90% of the population has disappeared from the wild. Frogs were collected from the wild and brought to a Captive Breeding Program; however, accomplishing regular reproductive events for this species has been difficult. The objective of this study was to determine the effect of hormonal stimulation on the production and quality of C. evanesco spermatozoa, aiming to develop an efficient and safe sperm collection protocol as a tool to help reproduce this endangered species. Mature males received intra-peritoneal injections with one of six hormone treatments, including des-Gly10, D-Ala6, Pro-NHEt9-GnRH-A, Amphiplex or hCG. Urine samples were collected at 10 different time points post-injection. Quality assessments included sperm concentration, percentage motility, percentage forward progressive motility (FPM), osmolality, pH and morphology analysis. Our results indicate that the optimal treatment for the collection of highly concentrated sperm samples of C. evanesco is 4 µg/gbw GnRH, followed by Amphiplex and 2 µg/gbw GnRH as sub-optimal treatments and finally, 6 µg/gbw GnRH and 5 and 10 IU/gbw hCG as non-optimal treatments. GnRH-A at 4 µg/gbw and Amphiplex stimulated the production of samples with the highest sperm concentrations and quality, despite Amphiplex producing lower percentages of intact acrosome and tail. In contrast, hCG concentrations were not reliable inducers of sperm production, consistently showing lower concentrations, higher percentages of sperm abnormalities and more acidic spermic urine than that induced by Amphiplex and GnRH-A. Morphological assessments revealed that C. evanesco spermatozoa have a filiform shape with a large acrosome on the anterior part of an elongated head, a small midpiece and a long tail with two filaments joined together by an undulating membrane.

Demographic and clinical risk factors associated with severity of lab-confirmed human leptospirosis in Colombia, 2015-2020.

BACKGROUND: Leptospirosis is a common zoonoses and is a major global public health threat. Most cases are mild, typically presenting as a non-specific acute febrile illness. However, leptospirosis can have life-threatening manifestations, including pulmonary hemorrhage syndrome, and acute kidney injury. In Colombia, notification and lab-confirmation of suspected human cases are mandatory. However, little is known about the demographic and clinical factors associated with severe leptospirosis, which could help to reduce clinical complications and mortality. Our aim was to identify risk factors associated with severe leptospirosis, intensive care unit (ICU) admission, and mortality in lab-confirmed cases in Colombia, 2015-2020. METHODS AND FINDINGS: We analyzed 201 lab-confirmed human leptospirosis cases by microagglutination test. We used a logistic regression to identify the demographic and clinical risk factors associated with severe leptospirosis, admission to ICU, and death. Most leptospirosis confirmed cases occurred in men (85.6%); the mean age was 36.7 years. We classified severe cases (43.3%) by clinical manifestations as renal (29.9%) and liver (27.4%) failure, multiple-organ failure (24.4%), septic shock (24.4%), Weil syndrome (18.4%), pulmonary hemorrhage (18.4%), and meningitis (2.5%), admitted to the ICU (30.3%), and fatal (8.5%). Clinical conditions associated with severe leptospirosis were dyspnea (OR: 5.54; 95% CI: 1.46 to 20.98), tachycardia (OR:9.69; 95% CI: 15.96 to 58.8), and rash (OR: 10.25; 95% CI: 25.01 to 42.08). CONCLUSIONS: We identified demographic characteristics and clinical symptoms associated with severe leptospirosis in Colombia. We hope these results can support clinicians in providing timely treatment to leptospirosis patients to avoid preventable medical complications or deaths.

Photovoltaic Glass Waste Recycling in the Development of Glass Substrates for Photovoltaic Applications.

Because of the increasing demand for photovoltaic energy and the generation of end-of-life photovoltaic waste forecast, the feasibility to produce glass substrates for photovoltaic application by recycling photovoltaic glass waste (PVWG) material was analyzed. PVWG was recovered from photovoltaic house roof panels for developing windows glass substrates; PVWG was used as the main material mixed with other industrial waste materials (wSG). The glass was casted by air quenching, annealed, and polished to obtain transparent substrates samples. Fluorine-doped tin oxide (FTO) was deposited as back contact on the glass substrates by spray pyrolysis. The chemical composition of the glass materials was evaluated by X-ray fluorescence (XRF), the thermal stability was measured by differential thermal analysis (DTA) and the transmittance was determined by UV-VIS spectroscopy. The surface of the glass substrates and the deposited FTO were observed by scanning electron microscopy (SEM), the amorphous or crystalline state of the specimens were determined by X-ray diffraction (XRD) and the sheet resistance was evaluated by the four-point probe method. The sheet resistance of the deposited FTO on the wSG substrate was 7.84 ± 3.11 Ω/□, lower than that deposited on commercial soda-lime glass (8.48 ± 3.67 Ω/□), meaning that this material could present improved conduction of the produced electrons by the photovoltaic effect. This process may represent an alternative to produce glass substrates from waste materials that could be destined for photovoltaic applications, especially the production of ecological photovoltaic windows.

From Enrico Sertoli to freemartinism: the many phases of the master testis-determining cell†.

Sertoli cells, first identified in the adult testis by Enrico Sertoli in the mid-nineteenth century, are known for their role in fostering male germ cell differentiation and production of mature sperm. It was not until the late twentieth century with the discovery of the testis-determining gene SRY that Sertoli cells' new function as the master regulator of testis formation and maleness was unveiled. Fetal Sertoli cells facilitate the establishment of seminiferous cords, induce appearance of androgen-producing Leydig cells, and cause regression of the female reproductive tracts. Originally thought be a terminally differentiated cell type, adult Sertoli cells, at least in the mouse, retain their plasticity and ability to transdifferentiate into the ovarian counterpart, granulosa cells. In this review, we capture the many phases of Sertoli cell differentiation from their fate specification in fetal life to fate maintenance in adulthood. We also introduce the discovery of a new phase of fetal Sertoli cell differentiation via autocrine/paracrine factors with the freemartin characteristics. There remains much to learn about this intriguing cell type that lay the foundation for the maleness.

Somatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B.

Fate determination and maintenance of fetal testes in most mammals occur cell autonomously as a result of the action of key transcription factors in Sertoli cells. However, the cases of freemartin, where an XX twin develops testis structures under the influence of an XY twin, imply that hormonal factor(s) from the XY embryo contribute to sex reversal of the XX twin. Here we show that in mouse XY embryos, Sertoli cell-derived anti-Mullerian hormone (AMH) and activin B together maintain Sertoli cell identity. Sertoli cells in the gonadal poles of XY embryos lacking both AMH and activin B transdifferentiate into their female counterpart granulosa cells, leading to ovotestis formation. The ovotestes remain to adulthood and produce both sperm and oocytes, although there are few of the former and the latter fail to mature. Finally, the ability of XY mice to masculinize ovaries is lost in the absence of these two factors. These results provide insight into fate maintenance of fetal testes through the action of putative freemartin factors.

Comportamiento de variables clínico epidemiológicas en la atención prenatal / The Characteristics of Clinical-Epidemiological Variables in Prenatal Care

Introducción: La atención prenatal a cada embarazada establece una asistencia médica integral y particularizada, que posibilita determinar y accionar precozmente sobre los factores de riesgo modificables, mediante la vigilancia continua. Objetivo: Describir el comportamiento de la atención prenatal según variables clínico epidemiológicas. Métodos: Estudio observacional descriptivo en el policlínico Pedro del Toro, entre 2014 y 2018. Incluyó 2761 pacientes que representan el total de gestantes en el periodo de estudio que cumplieron los criterios señalados. La información se obtuvo mediante revisión de la base de datos del programa materno infantil, con lo cual se delimitaron las variables que permitieron procesar los datos en una hoja de cálculo EXCEL, utilizando parámetros estadísticos a nivel descriptivo. Resultados: Las gestantes captadas antes de 12 semanas (2442 para 88,44 por ciento) fueron mayoría, primó el rango de 18,9 hasta 25,5 kg/m2 en índice de masa corporal (1657 para 60,01 por ciento). En el parto predominaron gestantes que tenían entre 37 y 41,6 semanas (2531 para 91,66 por ciento) y el rango de peso del recién nacido más relevante fue entre 2500 y 4000 gramos (2443 para 88,48 por ciento). Las edades comprendidas entre 21 a 29 años fueron representativas (1438 para 52,08 por ciento). Conclusiones: De la captación precoz de las embarazadas dependerá, en gran medida, la efectividad de la atención prenatal, a través de la detección oportuna y el seguimiento de todos los elementos que influyen en el bienestar materno fetal(AU)

Introduction: Prenatal care to each pregnant woman establishes a comprehensive and particularized medical assistance, which makes it possible to determine and act early on modifiable risk factors through continuous surveillance. Objective: To describe the characteristics of prenatal care according to clinical-epidemiological variables. Methods: Descriptive and observational study carried out at Pedro del Toro outpatient polyclinic between 2014 and 2018, with 2,761 patients, which represented the total number of pregnant women in the study period who met the indicated criteria. The information was obtained by reviewing the database of the mother and infant program, which permitted to define the variables for processing the data in an Excel worksheet, using statistical parameters at a descriptive level. Results: The pregnant women diagnosed before the twelfth weeks (2442; 88.44 percent) were the majority, with a body mass index range of 18.9 to 25.5 kg/m2 (1657; 60.01 percent). Regarding delivery, pregnant women between 37 and 41.6 weeks predominated (2531; 91.66 percent) and the most relevant newborn weight range was between 2500 and 4000 grams (2443; 88.48 percent). Ages between 21 to 29 years were representative (1438; 52.08 percent). Conclusions: The effectiveness of prenatal care through timely detection and follow-up of all the elements that influence maternal and fetal well-being will depend, to a large extent, on early detection of pregnant women(AU)

Constitutive expression of Steroidogenic factor-1 (NR5A1) disrupts ovarian functions, fertility, and metabolic homeostasis in female mice.

Steroid hormones regulate various aspects of physiology, from reproductive functions to metabolic homeostasis. Steroidogenic factor-1 (NR5A1) plays a central role in the development of steroidogenic tissues and their ability to produce steroid hormones. Inactivation of Nr5a1 in the mouse results in a complete gonadal and adrenal agenesis, absence of gonadotropes in the pituitary and impaired development of ventromedial hypothalamus, which controls glucose and energy metabolism. In this study, we set out to examine the consequences of NR5A1 overexpression (NR5A1+) in the NR5A1-positive cell populations in female mice. Ovaries of NR5A1+ females presented defects such as multi-oocyte follicles and an accumulation of corpora lutea. These females were hyperandrogenic, had irregular estrous cycles with persistent metestrus and became prematurely infertile. Furthermore, the decline in fertility coincided with weight gain, increased adiposity, hypertriglyceridemia, hyperinsulinemia, and impaired glucose tolerance, indicating defects in metabolic functions. In summary, excess NR5A1 expression causes hyperandrogenism, disruption of ovarian functions, premature infertility, and disorders of metabolic homeostasis. This NR5A1 overexpression mouse provides a novel model for studying not only the molecular actions of NR5A1, but also the crosstalk between endocrine, reproductive, and metabolic systems.

Management of Lobular Neoplasia Found on Core Needle Biopsy Performed for Calcifications Using Precise Radiologic-Pathologic Correlation.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rate of calcified lobular neoplasia (LN) versus incidental noncalcified classic LN found on core needle biopsy performed for the evaluation of suspicious calcifications. MATERIALS AND METHODS. This retrospective study included 390 consecutive image-guided breast core needle biopsies with microcalcifications as the target that were performed between December 2009 and July 2017. In 81 of the 390 core biopsies, the highest-risk lesion was LN that then underwent either excision or imaging follow-up. Core biopsy results were compared with excision and imaging follow-up findings. An upgrade of LN was defined as ductal carcinoma in situ or invasive ductal or lobular carcinoma. RESULTS. Of 81 LN diagnosed on core biopsy performed for calcifications, 16 had calcifications within the LN. Fifteen of these 16 cases underwent surgical excision, and three (3/15, 20.0%) were upgraded on excision. Of the 64 core biopsies showing incidental noncalcified LN with benign concordant entities containing calcifications, 42 underwent surgical excision, and one LN (1/42, 2.4%) was upgraded. Twenty-three total lesions (one calcified LN and 22 noncalcified LN) were followed with imaging rather than excision. No cancers were detected among the follow-up group. One case was deemed to have discordant findings on radiologic-pathologic review and was sent for excision, which showed invasive cancer with tubulolobular and lobular features. CONCLUSION. Women undergoing stereotactic core needle biopsy for calcifications revealing noncalcified incidental classic LN and a benign concordant entity that could explain the presence of the target calcifications have a low risk of upgrade and may be followed with imaging. Surgical excision should be offered to women who have LN with calcifications.

Plagues, past, and futures for the Yagan canoe people of Cape Horn, southern Chile.

The manner in which the COVID-19 pandemic has affected the indigenous Yagan people of Navarino Island in southern Chile is the topic of this paper. Like other First Nation communities, these nomadic people suffered decimation and disease in successive encounters with Europeans, and then, in the mid-twentieth century, forced sedentarization by the Chilean State. More recently, the Yagan have fought the expansion of salmon aquaculture to the Island. Making use of a sociomaterial approach, we examine how the threat of past and present viruses and diseases, added to the tragic effects of colonization, become part of a broader sociohistorical debate on the right of coastal peoples to their maritories. Paradoxically, our results suggest that COVID-19 has become part of an assemblage of ethnic revitalization, opening possibilities for the Yagan clans to make some of their envisioned futures possible.

Ramsey hunt syndrome after antimonial treatment for American Cutaneous Leishmaniasis

Abstract Ramsay Hunt Syndrome (RHS), also known as herpes zoster oticus, is caused by the reactivation of varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. Herein, we report a case of Ramsey Hunt Syndrome in a patient after antimonial treatment for Cutaneous Leishmaniasis. The patient presented with microvesicles grouped on an erythematous base, starting in the neck and ascending towards the scalp margin on the right side of the head. The patient also developed grade V peripheral facial palsy the day after initiating the herpes zoster treatment, this outcome corroborated the assumption of Ramsey Hunt Syndrome.

Ramsey hunt syndrome after antimonial treatment for American Cutaneous Leishmaniasis.

Ramsay Hunt Syndrome (RHS), also known as herpes zoster oticus, is caused by the reactivation of varicella zoster virus (VZV) in the geniculate ganglion of the facial nerve. Herein, we report a case of Ramsey Hunt Syndrome in a patient after antimonial treatment for Cutaneous Leishmaniasis. The patient presented with microvesicles grouped on an erythematous base, starting in the neck and ascending towards the scalp margin on the right side of the head. The patient also developed grade V peripheral facial palsy the day after initiating the herpes zoster treatment, this outcome corroborated the assumption of Ramsey Hunt Syndrome.

Aberrant and constitutive expression of FOXL2 impairs ovarian development and functions in mice.

Development and functions of the ovary rely on appropriate signaling and communication between various ovarian cell types. FOXL2, a transcription factor that plays a key role at different stages of ovarian development, is associated with primary ovarian insufficiency and ovarian cancer as a result of its loss-of-function or mutations. In this study, we investigated the impact of aberrant, constitutive expression of FOXL2 in somatic cells of the ovary. Overexpression of FOXL2 that started during fetal life resulted in defects in nest breakdown and consequent formation of polyovular follicles. Granulosa cell differentiation was impaired and recruitment and differentiation of steroidogenic theca cells was compromised. As a consequence, adult ovaries overexpressing FOXL2 exhibited defects in compartmentalization of granulosa and theca cells, significant decreased steroidogenesis and lack of ovulation. These findings demonstrate that fine-tuned expression of FOXL2 is required for proper folliculogenesis and fertility.

In utero exposure to arsenite contributes to metabolic and reproductive dysfunction in male offspring of CD-1 mice.

In utero exposure to arsenite (iAs) is known to increase disease risks later in life. We investigated the effect of in utero exposure to iAs in the drinking water on metabolic and reproductive parameters in male mouse offspring at postnatal and adult stages. Pregnant CD-1 mice were exposed to iAs (as sodium arsenite) in the drinking water at 0 (control), 10 ppb (EPA standard for drinking water), and 42.5 ppm (tumor-inducing dose in mice) from embryonic day (E) 10-18. At birth, pups were fostered to unexposed females. Male offspring exposed to 10 ppb in utero exhibited increase in body weight at birth when compared to controls. Male offspring exposed to 42.5 ppm in utero showed a tendency for increased body weight and a smaller anogenital distance. The body weight in iAs-exposed pups continued to increase significantly compared to control at 3 weeks and 11 weeks of age. At 5 months of age, iAs-exposed males exhibited greater body fat content and glucose intolerance. Male offspring exposed to 10 ppb in utero had higher circulating levels of leptin compared to control. In addition, males exposed to 42.5 ppm in utero exhibited decreased total number of pups born compared to controls and lower average number of litters sired over a six-month period. These results indicate that in utero exposure to iAs at either human relevant concentration or tumor-inducing concentration is a potential cause of developmental origin of metabolic and reproductive dysfunction in adult male mice.

Oviductal Retention of Embryos in Female Mice Lacking Estrogen Receptor α in the Isthmus and the Uterus.

Estrogen receptor α (ESR1; encoded by Esr1) is a crucial nuclear transcription factor for female reproduction and is expressed throughout the female reproductive tract. To assess the function of ESR1 in reproductive tissues without confounding effects from a potential developmental defect arising from global deletion of ESR1, we generated a mouse model in which Esr1 was specifically ablated during postnatal development. To accomplish this, a progesterone receptor Cre line (PgrCre) was bred with Esr1f/f mice to create conditional knockout of Esr1 in reproductive tissues (called PgrCreEsr1KO mice) beginning around 6 days after birth. In the PgrCreEsr1KO oviduct, ESR1 was most efficiently ablated in the isthmic region. We found that at 3.5 days post coitus (dpc), embryos were retrieved from the uterus in control littermates while all embryos were retained in the PgrCreEsr1KO oviduct. Additionally, serum progesterone (P4) levels were significantly lower in PgrCreEsr1KO compared to controls at 3.5 dpc. This finding suggests that expression of ESR1 in the isthmus and normal P4 levels allow for successful embryo transport from the oviduct to the uterus. Therefore, alterations in oviductal isthmus ESR1 signaling and circulating P4 levels could be related to female infertility conditions such as tubal pregnancy.

Fibrilación auricular. Panorámica sobre un tema actualizado / Atrial fibrillation. An update review

La fibrilación auricular (FA) es la arritmia más común en el mundo, con altas mortalidad y morbilidad. Es la primera causa de eventos embólicos como: el deterioro cognitivo, los episodios de insuficiencia cardíaca y la disminución de la calidad de vida, con repercusión socioeconómica y sanitaria. Hoy, se conoce que la FA comienza por ráfagas de descargas eléctricas anormales, que activan rápida e irregularmente las aurículas. La reciente clasificación de la FA en paroxística, persistente o permanente, refleja el deterioro evolutivo de la arritmia. En la actualidad, existe una amplia gama de fármacos para tratar esta patología. Sobresalen los antiarrítmicos y anticoagulantes, aunque la técnica moderna de la ablación con catéter se ha incluido en las guías clínicas, como alternativa o complemento de los fármacos antiarrítmicos, en pacientes seleccionados con FA.

Atrial fibrillation (FA) it is the most common arrhythmia today, presenting high mortality and morbility levels. It is the first cause of embolic events and episodes of heart inadequacy, cognitive deteriorate and poor life quality. It also brings socioeconomic and sanitary consecuences. Today, FA trigers blasts of abnormal electric discharges, which activate auricles quickly and irregularly. Recent classification of the FA as sudden, persistent and permanent lead to an evolving arrhythmia deterioration. In present times, this pathology is treated using a wide range of drugs. Antiarrhythmics and anticoagulants stand out, although the modern technique of ablation with catheter has been included in the clinical guides, either alternative or complement of antiarrhythmics, in patients affected by FA.

Reproductive, Physiological, and Molecular Outcomes in Female Mice Deficient in Dhh and Ihh.

Ovarian development requires coordinate communications among oocytes, granulosa cells, and theca cells. Two Hedgehog (Hh) pathway ligands, Desert hedgehog (Dhh) and Indian hedgehog (Ihh), are produced by the granulosa cells and work together to regulate theca cell specification and development. Mice lacking both Dhh and Ihh had loss of normal ovarian function, which raised the question of which biological actions are specifically controlled by each ligand during folliculogenesis. By comparing the reproductive fitness, hormonal profiles, and ovarian transcriptomes among control, Dhh single-knockout (KO), Ihh KO, and Dhh/Ihh double-knockout (DKO) mice, we examined the specific roles of Dhh and Ihh in these processes. Dhh/Ihh DKO female mice were infertile because of a lack of theca cells and their steroid product androgen. Although Dhh and Ihh KO mice were fertile with normal folliculogenesis, they had decreased androgen production and alterations in their ovarian transcriptomes. Absence of Ihh led to aberrant steroidogenesis and elevated inflammation responses, which were not found in Dhh KO mouse ovaries, implicating that IHH has a greater impact than DHH on the activation of the Hh signaling pathway in the ovary. Our findings provide insight into not only how the Hh pathway influences folliculogenesis but also the distinct and overlapping roles of Dhh and Ihh in supporting ovarian development.

Examen clínico: un método diagnóstico con dificultades en estudiantes de tercer año de la carrera de medicina / Clinical Method: a diagnosis tool with difficulties in students of third year of the medicine career

Introducción: el método clínico es un proceder científico y sistematizado que el médico ha empleado desde sus inicios y continúa vigente, es el arma primordial para el ejercicio de su profesión, considerado como un sistema de pensamiento lógico, ordenado y científico con la finalidad de establecer un diagnóstico e instaurar un tratamiento. Objetivo: comprobar el dominio y aplicación del método clínico de los estudiantes de tercer año de la carrera de Medicina en Moa, durante la rotación de Propedéutica, durante el curso escolar 2015-2016. Método: se realizó un estudio descriptivo observacional, con una muestra integrada por 52 estudiantes, los que constituyeron el 100% de la población estudiada. Se consideraron los resultados por los estudiantes en los exámenes prácticos de la asignatura de Propedéutica. Resultados: El 36,5% obtuvo resultados insatisfactorios en los exámenes, con un índice de calidad del 42,4%; el 65,3% presentó dificultades en el interrogatorio, el 57,6% en el examen físico y el 50,0% de los profesores valoró de regular la interrelación entre: interrogatorio, examen físico, resumen sindromológico y complementarios, considerando que el local de los exámenes tenía buena privacidad en el 85,7%, higiene en el 78,5% e iluminación en el 71,4%. Conclusiones: se demostró que existen dificultades en los estudiantes de tercer año de la carrera de medicina para desarrollar habilidades que reflejen dominio y aplicación del método clínico.

Introduction: the clinical method is a systematized and scientific practice; the doctor has ever used it up to nowadays. This method is of high importance, since it denotes a system of logical, well-ordered and scientific thought to make a diagnosis and give the treatment. Objective: to check the mastery and application of the clinical method of the students of third year of the career of Medicine in Moa, in the Propaedeutic cycle in 2015-2016 school year. Method: an observational descriptive study was carried out, with a sample of 52 students who represented the 100% of the population. The students´ results achieved in the practical exams of the Propaedeutic subject were considered. Results: insufficient results were obtained in the exam in 36.5% of the students, with an index of quality of 42.4%, 65.3% presented difficulties in the medical interview, 57.6% in the physical exam and. The interrelation among medical interview, physical exam, syndromological summary and complementary were assessed as medium by 50.0% of the professors, considering that the place where the exams were developed had good privacy in 85.7%, hygiene in 78.5% and illumination in 71.4%. Conclusions: the study demonstrated that there were difficulties in the students of third year of the medicine career, to develop abilities that show knowledge and use of the clinical method.