Unraveling the non-fitness status of NK cells: Examining the NKp30 receptor and its isoforms distribution in HIV/HCV coinfected patients.

BACKGROUND: HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. RESULTS: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56brigth subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. CONCLUSIONS: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage.

Effect of antiretroviral therapy on decreasing arterial stiffness, metabolic profile, vascular and systemic inflammatory cytokines in treatment-naïve HIV: A one-year prospective study.

INTRODUCTION: Cardiovascular disease is a major cause of death among people living with HIV (PLH). Non-treated PLH show increased levels of inflammation and biomarkers of vascular activation, and arterial stiffness as a prognostic cardiovascular disease risk factor. We investigated the effect of one year of ART on treatment-naïve HIV(+) individuals on arterial stiffness and inflammatory and vascular cytokines. METHODS: We cross-sectionally compared aortic stiffness via tonometry, inflammatory, and vascular serum cytokines on treatment-naïve (n = 20) and HIV (-) (n = 9) matched by age, sex, metabolic profile, and Framingham score. We subsequently followed young, treatment-naïve individuals after 1-year of ART and compared aortic stiffness, metabolic profile, and inflammatory and vascular serum biomarkers to baseline. Inflammatory biomarkers included: hs-CRP, D-Dimer, SAA, sCD163s, MCP-1, IL-8, IL-18, MRP8/14. Vascular cytokines included: myoglobin, NGAL, MPO, Cystatin C, ICAM-1, VCAM-1, and MMP9. RESULTS: Treatment-naïve individuals were 34.8 years old, mostly males (95%), and with high smoking prevalence (70%). Baseline T CD4+ was 512±324 cells/mcL. cfPWV was similar between HIV(-) and treatment-naïve (6.8 vs 7.3 m/s; p = 0.16) but significantly decreased after ART (-0.52 m/s; 95% CI -0.87 to -0.16; p0.006). Almost all the determined cytokines were significantly higher compared to controls, except for MCP-1, myoglobin, NGAL, cystatin C, and MMP-9. At follow-up, only total cholesterol and triglycerides increased and all inflammatory cytokines significantly decreased. Regarding vascular cytokines, MPO, ICAM-1, and VCAM-1 showed a reduction. D-Dimer tended to decrease (p = 0.06) and hs-CRP did not show a significant reduction (p = 0.17). CONCLUSION: One year of ART had a positive effect on reducing inflammatory and vascular cytokines and arterial stiffness.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report.

BACKGROUND: Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical. CASE PRESENTATION: We present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. CONCLUSION: The purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Diseño y validación del cuestionario de autocuidado preventivo del pie diabético NAPD / Design and validation of diabetic foot preventive self-care questionnaire NAPD / Desenvolvimento e validação do questionário de autocuidado preventivo do pé diabético NAPD

Objetivo: Realizar el diseño y la validación del cuestionario "Nivel de autocuidado en la prevención del pie diabético" en términos de su contenido, constructo, confiabilidad y sen-sibilidad. Material y método: Estudio psicométrico desarrollado en tres fases: diseño del instrumento, a partir de las categorías teóricas que surgen de 8 entrevistas a personas con diabetes mellitus; validación aparente y de contenido, contando con la participación de 20 jueces expertos; y, validez del constructo, confiabilidad y sensibilidad, contando con 158 mediciones del instrumento. Resultados: El proceso de teorización dio origen a la versión inicial del cuestionario con 23 ítems; sin embargo, en la validación facial y de contenido requirió mejorías en la redacción y retirar un ítem, cambios que se efectuaron siguiendo las observaciones de los expertos tales como: Índice de Validez de Contenido de 0.88 y Kappa de Fleiss de 0.7606 (p=0.000). Finalmente se obtuvo la versión 2 del cuestionario NAPD.V2 con 22 ítems agrupados en 5 dimensiones: automanejo de la diabetes, percepción sobre el pie diabético, impacto emocional de la enfermedad, el cuidado rutinario de los pies y la percep-ción sobre el soporte social. Además, el análisis factorial exploratorio mostró una adecuada validez del constructo y su confiabilidad evidenció buen rendimiento -Alfa de Cronbach de 0,942- y una sensibilidad significativa sobre la -prueba Wilcoxon p=0.000-. Conclusiones: Tras el diseño y la validación se obtiene el cuestionario NAPD.V2 con propiedades psi-cométricas adecuadas para ser usado en la población con diabetes mellitus colombiana

Objective: Carry out the design and validation of the questionnaire "Level of self-care in the prevention of diabetic foot" in terms of its content, construct, reliability and sensitivity. Ma-terial and method: Psychometric study developed in three phases: design of the instrument, based on the conceptualized theoretical categories of 8 interviews with people with diabetes mellitus; face and content validity, with the participation of 20 expert judges; and construct validity, reliability, and sensitivity, through 158 instrument measurements. Results: The the-orization process gave rise to the initial version of the questionnaire with 23 items; however, the face and content validity required improvements in writing and removing an item, these changes were made following the experts' observations such as: Content Validity Index of 0.88 and Fleiss' Kappa of 0.7606 (p = 0.000). Finally, the second version of the questionnaire was made with 22 items grouped in 5 dimensions: self-management of diabetes, perception of the diabetic foot, emotional impact of the disease, routinary foot care and perception of so-cial support. Furthermore, the exploratory factor analysis showed adequate construct validity, and its reliability evidenced good performance -Cronbach's Alpha of 0.942- and significant sensitivity -Wilcoxon test p = 0.000-. Conclusions: After design and validation, a question-naire with adequate psychometric properties was obtained to be used in the Colombian pop-ulation with diabetes mellitus

Objetivo: Desenvolver e validar o questionário "Nível de autocuidado na prevenção do pé di-abético" em termos de conteúdo, construto, confiabilidade e sensibilidade. Material e méto-do: Estudo psicométrico desenvolvido em três fases: desenvolvimento do instrumento, a par-tir das categorias teóricas que surgiram de oito entrevistas à pessoas com Diabetes Mellitus; validação aparente e de conteúdo, contando com a participação de vinte juízes expertos; e, validez de construto, confiabilidade e sensibilidade com a realização de 158 medições do in-strumento. Resultados: O processo de teorização deu origem à versão inicial do questionário com 23 itens; entretanto, a validação facial e de conteúdo sugeriu melhorar a redação e tirar um item, mudanças efetivadas seguindo o parecer dos expertos: índice de validez de con-teúdo de 0,88 e Kappa de Fleiss de 0,7606 (p=0,000). Finalmente, obteve-se a versão 2 do questionário NAPD.V2 com 22 itens agrupados em cinco dimensões: autogestão do diabetes, percepções do pé diabético, impacto emocional da doença, cuidados rotineiros com os pés e percepção do apoio social. Além disso, o analise fatorial exploratório mostrou adequada validação de construto e a confiabilidade do questionário evidencio bom rendimento (Alpha de Cronbach=0,92) e uma sensibilidade significativa na prova de Wilcoxon p=0,000. Con-clusões: Obteve-se o questionário NAPD.V2 posterior a procedimentos de desenvolvimento e validação obtendo propriedades psicométricas adequadas para o seu uso na população com diabetes mellitus colombiana

Prevalence and risk factors of chronic kidney disease in an HIV positive Mexican cohort.

BACKGROUND: HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors. METHODS: A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made. RESULTS: One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4+ T cells count < 200 cells/µL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7. CONCLUSIONS: Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.

Ginecomastia: Consideraciones médicas y quirúrgicas en cirugía general / Gynecomastia: Medical and surgical considerations in general surgery

La ginecomastia, definida como el crecimiento del tejido glandular mamario en los hombres, aparece desde la etapa neonatal hasta la senil, puede ser unilateral o bilateral, y es de causa multifactorial, incluyendo aquellos pacientes asociados al uso de medicamentos, donde predomina un desbalance en la relación testosterona­estrógeno. Relativamente, la idiopática es la más frecuente. La mayoría involucionan espontáneamente, las neonatales por perdida del influjo transplacentario en las primeras semanas, y las puberales entre 12 a 24 meses. Se presenta como un aumento del tamaño mamario, asintomático o con hipersensibilidad por inflamación durante el crecimiento del tejido fibroglandular mamario, con una repercusión psicológica enorme, sobre todo en la etapa de la adolescencia. El estudio y manejo es interdisciplinario y se ofrece de acuerdo con las condiciones y la etiología. Aquellos pacientes púberes en quienes no involuciona reciben tratamientos médicos, o tratamientos quirúrgicos cuando falla la terapéutica o hay presión social, e incluso radioterapia en casos donde desarrollan ginecomastia con hipersensibilidad al tratamiento hormonal del cáncer de próstata

Gynecomastia, defined as the growth of breast glandular tissue in men, appears from the neonatal to senile stage, can be unilateral or bilateral, and is of multifactorial cause, including those patients associated with the use of medications, where an imbalance in the testosterone ­ estrogen ratio. Relatively, idiopathic is the most common. Most regress spontaneously, neonatals due to loss of transplacental influx in the first weeks, and pubertal ones between 12 to 24 months. It presents as an increase in breast size, asymptomatic or with hypersensitivity due to inflammation during the growth of the mammary fibroglandular tissue, with an enormous psychological repercussion, especially in adolescence. The study and management is interdisciplinary and offered according to conditions and etiology. Those pubertal patients in whom it does not regress receive medical treatments, or surgical treatments when therapy fails or there is social pressure, and even radiotherapy in cases where they develop gynecomastia with hypersensitivity to hormonal treatment of prostate cancer

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico.

BACKGROUND: The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. METHODOLOGY/PRINCIPAL FINDINGS: We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78-30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4-76.2) / 96.2% (95% CI, 93.2-98.0) for IAHE, 91.3% (95% CI, 84.2-96.0) / 90.9% (95% CI, 87.0-94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0-95.3) / 92.3% (95% CI, 88.6-95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3-72.5)/ 89.5% (95%CI, 86.0-93.0), 65.9% (95%CI, 56.0-75.8)/ 89.0% (95%CI, 85.2-92.9), 62.1% (95%CI, 44.4-79.7)/ 82.6% (95%CI, 71.7-93.6) and 34.9% (95%CI, 24.8-46.2)/ 67.3% (95%CI, 60.6-73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9-74.7)/ 58.8% (95%CI, 53.2-64.5), 70.8% (95%CI, 61.3-80.2)/ 52.9% (95%CI, 46.8-59.1), 71.4% (95%CI, 54.7-88.2)/ 40.4% (95%CI, 26.4-54.5) and 18.1% (95%CI, 10.5-28.1)/ 90.4% (95%CI, 85.5-94.0), respectively. CONCLUSIONS/SIGNIFICANCE: The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Aortic stiffness and central hemodynamics in treatment-naïve HIV infection: a cross-sectional study.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a greater risk of cardiovascular disease (CVD). HIV infection causes a chronic inflammatory state and increases oxidative stress which can cause endothelial dysfunction and arterial stiffness. Aortic stiffness measured by carotid femoral-pulse wave velocity (cfPWV) and central hemodynamics are independent cardiovascular risk factors and have the prognostic ability for CVD. We assessed cfPWV and central hemodynamics in young individuals with recent HIV infection diagnosis and without antiretroviral therapy. We hypothesized that individuals living with HIV would present greater cfPWV and central hemodynamics (central systolic blood pressure and pulse pressure) compared to uninfected controls. METHODS: We recruited 51 treatment-naïve individuals living with HIV (HIV(+)) without previous CVD and 51 age- and sex-matched controls (HIV negative (-)). We evaluated traditional CVD risk factors including metabolic profile, blood pressure (BP), smoking, HIV viral load, and CD4+ T-cells count. Arterial stiffness and central hemodynamics were evaluated by cfPWV, central systolic BP, and central pulse pressure (cPP) via applanation tonometry. RESULTS: HIV(+) individuals presented a greater prevalence of smoking, reduced high-density lipoprotein cholesterol, and body mass index. 65.9% of HIV(+) individuals exhibited lymphocyte CD4+ T-cells count < 500 cells/µL. There was no difference in brachial or central BP between groups; however, HIV(+) individuals showed significantly lower cPP. We observed a greater cfPWV (mean difference = 0.5 m/s; p < 0.01) in HIV(+) compared to controls, even after adjusting for heart rate, mean arterial pressure and smoking. CONCLUSION: In the early stages of infection, non-treated HIV individuals present a greater prevalence of traditional CVD risk factors, arterial stiffness, and normal or in some cases central hemodynamics.

Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. CASE PRESENTATION: A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. CONCLUSION: The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.

Vólvulo de la vesícula biliar / Gallbladder volvulus

El vólvulo, o torsión de la vesícula biliar, es una enfermedad de la sexta a la octava décadas de la vida, condición excepcional por su poca frecuencia y síntomas atípicos. Dado que tiende a confundirse con la colecistitis de origen no litiásico, su diagnóstico suele ser intraoperatorio y puede llegar a causar complicaciones graves, como la gangrena y la sepsis biliar e incluso la muerte. Pese a que hace 120 años se hizo el primer reporte de caso, en la actualidad se notifican cada vez más casos en la población añosa. En este artículo se presentan dos casos clínicos de vólvulo de la vesícula biliar y se hace una revisión de la literatura

Volvulus, or torsion of the gallbladder, is a disease of the sixth to eighth decades of life, an exceptional condition due to its infrequent and atypical symptoms.Since it tends to be confused with non-lithiasic cholecystitis, its diagnosis is usually intraoperative and can lead to serious complications such as gangrene and biliary sepsis, even death.Although the first case was reported 120 years ago, more cases are reported in the elderly population.In this article, two clinical cases of gallbladder volvulus are presented and a review of the literature is made

Efecto protector del Desmodium molliculum EAM (manayupa) en ratas con toxicidad hepática inducida por naproxeno / Protective effect of Desmodium molliculum EAM (manayupa) in rats with naproxen-induced liver toxicity

Objetivo. Verificar el efecto protector del extracto acuoso de hojas y tallos de Desmodium molliculum EAM (manayupa), en la toxicidad hepática inducida por el naproxeno en ratas Ratus novergicus variedad Wistar albino, hembras. Materiales y métodos. Estudio experimental. Se utilizaron 36 ratas hembras de 250 ± 10 g, divididas en seis grupos de seis: A (control -); B (control + naproxeno); patrón C (silimarina 100 mg / kg) y 3 experimental (EAM): D 80 mg/kg; E 160 mg/kg y F 240 mg/kg). Los grupos B, C, D, E, F recibieron por vía oral naproxeno 27,38 mg, los primeros cinco días y durante 14 días. El efecto protector hepático se determinó mediante el análisis bioquímico: GOT, GPT, GGT, proteínas totales, albúmina sérica, fosfatasa alcalina y creatinina. Resultados. Se encontró que el grupo B perdió peso (180,65 ± 6,5 g), bilirrubina total (0,76 ± 0,4) bilirrubina directa (1.7 ± 0,8), TGO (160 ± 10,4) y TGP (412 ± 20,4) alto, comparado con el grupo A, C, D, E y F. Conclusiones. El EAM tiene efecto protector sobre la toxicidad hepática inducida por naproxeno en ratas, evidenciado por los parámetros bioquímicos.

Objective. To verify the protective effect of the aqueous extract of leaves and stems of Desmodium molliculum EAM (manayupa), on the hepatic toxicity induced by Naproxen in rats Ratus novergicus albino Wistar variety, females. Materials and methods. 36 female rats of 250 ± 10 g were used, divided into six groups of six: A (Control -), B (Control + Naproxen), Pattern C (Silymarin 100 mg / kg) and 3 Experimental (EAM): D 80 mg / kg, E 160 mg / kg and F 240 mg / kg). Groups B, C, D, E, F orally received Naproxen 27.38 mg, the first five days and for 14 days. The hepatic protective effect was determined by the biochemical analysis: GOT, GPT, GGT, total proteins, serum albumin, alkaline phosphatase, creatinine. Results. group B was found to lose weight (180.65 ± 6.5 g), total bilirubin (0.76 ± 0.4) direct bilirubin (1.7 ± 0.8), TGO (160 ± 10.4) and TGP (412 ± 20.4) high, compared to group A, C, D, E and F. Conclusion. EAM has a protective effect on hepatic toxicity induced by naproxen in rats, evidenced by biochemical parameters.

HPV genotypes detected by linear array and next-generation sequencing in anal samples from HIV positive men who have sex with men in Mexico.

The incidence of anal cancer has been rising, especially in HIV+ patients and has been associated with HPV infection. HIV+ patients are more at risk of HPV coinfection and are seven times more likely to have persistent HPV infection; moreover, HIV+ men have an increased risk of developing anal cancer compared to HIV+ women. The development of screening strategies for the detection of HPV in HIV+ men is of major importance; however, there is not enough information about the HPV genotypes and variants that are colonizing the anal epithelia of HIV+ men in diverse geographical regions. Therefore, this work was aimed at identifying HPV genotypes present in the anal epithelium of HIV+ men who have sex with men (MSM), with or without anal lesions (n = 75). For HPV genotyping, two approaches were performed: Linear Array HPV Genotyping Test and next-generation sequencing (NGS). In general, the six most frequent HPV genotypes found by Linear Array were HPV6, 62, 61, 81, 16 and 51. On the other hand, employing NGS, a total of 36 HPV genotypes belonging to both alpha and beta genera were found. The genotypes with the greatest number of reads, according to the diagnostic group, were: HPV81, 45, 6, 51 and 61 in MSM without anal lesions (WAIN); HPV6, 61, 70, 62 and 66 in MSM with atypical lesions (AAL); HPV6, 11, 66, 81 and 61 in MSM with anal intraepithelial neoplasia grade I (AIN I); and HPV16, 81, 58, 61 and 52 with AIN III. Additionally, a great diversity of L1 variants was observed, especially in genotypes HPV16, 58, 61, 52, 45 and 59.

Building trophic specializations that result in substantial niche partitioning within a young adaptive radiation.

Dietary partitioning often accompanies the increased morphological diversity seen during adaptive radiations within aquatic systems. While such niche partitioning would be expected in older radiations, it is unclear how significant morphological divergence occurs within a shorter time period. Here we show how differential growth in key elements of the feeding mechanism can bring about pronounced functional differences among closely related species. An incredibly young adaptive radiation of three Cyprinodon species residing within hypersaline lakes in San Salvador Island, Bahamas, has recently been described. Characterized by distinct head shapes, gut content analyses revealed three discrete feeding modes in these species: basal detritivory as well as derived durophagy and lepidophagy (scale-feeding). We dissected, cleared and stained, and micro-CT scanned species to assess functionally relevant differences in craniofacial musculoskeletal elements. The widespread feeding mode previously described for cyprinodontiforms, in which the force of the bite may be secondary to the requisite dexterity needed to pick at food items, is modified within both the scale specialist and the durophagous species. While the scale specialist has greatly emphasized maxillary retraction, using it to overcome the poor mechanical advantage associated with scale-eating, the durophage has instead stabilized the maxilla. In all species the bulk of the adductor musculature is composed of AM A1. However, the combined masses of both adductor mandibulae (AM) A1 and A3 in the scale specialist were five times that of the other species, showing the importance of growth in functional divergence. The scale specialist combines plesiomorphic jaw mechanisms with both a hypertrophied AM A1 and a slightly modified maxillary anatomy (with substantial functional implications) to generate a bite that is both strong and allows a wide range of motion in the upper jaw, two attributes that normally tradeoff mechanically. Thus, a significant feeding innovation (scale-eating, rarely seen in fishes) may evolve based largely on allometric changes in ancestral structures. Alternatively, the durophage shows reduced growth with foreshortened jaws that are stabilized by an immobile maxilla. Overall, scale specialists showed the most divergent morphology, suggesting that selection for scale-biting might be stronger or act on a greater number of traits than selection for either detritivory or durophagy. The scale specialist has colonized an adaptive peak that few lineages have climbed. Thus, heterochronic changes in growth can quickly produce functionally relevant change among closely related species.

Coarctation Index Predicts Recurrent Aortic Arch Obstruction Following Surgical Repair of Coarctation of the Aorta in Infants.

Recurrent aortic arch obstruction (RAAO) remains a major cause of morbidity following surgical neonatal repair of coarctation of the aorta (CoA). Elucidating predictors of RAAO can identify high-risk patients and guide postoperative management. The Coarctation index (CoA-I), defined as the ratio of the diameter of the narrowest aortic arch segment to the diameter of the descending aorta, has been used to help diagnose RAAO in neonates following the Norwood Procedure. We sought to assess the predictive value of the CoA-I on RAAO after CoA repair in infants with biventricular circulation. Clinical, surgical, and echocardiographic data of infants with biventricular circulation following neonatal CoA repair between 2010 and 2014 were evaluated. RAAO was defined using a composite quantitative outcome variable: a blood pressure gradient >20, a peak aortic arch velocity >3.5 m/s by echocardiogram, or a catheter-measured peak-to-peak gradient >20 within 2 years of surgery. Univariate and multivariate logistic regression analyses were used. Of the 68 subjects included in the analysis, 15 (22%) met criteria for RAAO. In the multivariate model, only CoA-I (OR 35.89, 95% CI 6.08-211.7, p < 0.0001) and use of patch material (OR 9.26, 95% CI 1.57-54.66, p = 0.014) were associated with increased risk of RAAO. The odds of developing RAAO was higher in patients with a CoA-I less than 0.7 (OR 33.8, 95% CI 5.7-199.5, p < 0.001). Postoperative CoA-I may be used to predict RAAO in patients with biventricular circulation after repair of CoA. Patients with a CoA-I less than 0.7 or patch aortoplasty warrant close follow-up.

Acciones educativas dirigidas a mejorar la percepción de riesgo del embarazo en adolescentes / Educational actions aimed at improving the risk perception about pregnancy in adolescents

Introducción: El inicio precoz de las relaciones sexuales y poco o ningún uso de anticonceptivos la primera vez, y los altos índices de embarazo temprano y abortos, son rasgos distintivos en los adolescentes de hoy. Objetivo: Evaluar las acciones educativas dirigidas a mejorar la percepción de riesgo del embarazo en adolescentes. Métodos: Estudio descriptivo realizado en la Secundaria Básica Mario Acevedo Francia en Quemado de Güines en septiembre de 2009 hasta setiembre de 2010. El universo lo constituían 461 adolescentes de ambos sexos y finalmente la muestra quedó conformada por 90 adolescentes. Se diseñaron e implementaron un grupo de acciones educativas (discusiones grupales, demostraciones, sociodramas y otros) sobre prevención del embarazo en la adolescencia. Se tuvieron en cuenta los principios éticos correspondientes. Resultados: El mayor porcentaje 73,3 (n= 66) de adolescentes inició precozmente la práctica de las relaciones sexuales. Una cifra estimada, 73,3 por ciento (n= 65) refirió no usar anticonceptivos en estas prácticas. La imitación contribuyó al inicio precoz de las relaciones sexuales con penetración vaginal. El 80,0 por ciento (n= 72) del grupo consideró alto el riesgo el embarazo, aborto e infecciones de transmisión sexual y cifras similares, la maternidad y paternidad como una responsabilidad de ambos miembros de la pareja. Conclusiones: las acciones educativas desarrolladas contribuyen a mejorar la percepción de riesgo del embarazo en adolescentes. Estas intervenciones elevan el nivel de conocimientos e incentivan cambios en los estilos de vida. Se obtuvo un alto nivel de satisfacción con las acciones desarrolladas(AU)

Introduction: The early onset of sexual relations and the little use or non use of condoms during the first time, and the high early pregnancy and abortion indexes are distinctive features of adolescents nowadays. Objective: To evaluate educational actions to improve the risk perception about pregnancy in adolescents. Methods: Descriptive study conducted in Mario Acevedo France junior high school in Quemado de Güines in September of 2009-2010 academic year. The universe was made up of 461 adolescents of both sexes and the final sample was 90 adolescents. A group of educational actions (group discussions, demonstrations, social dramas and others) on prevention of pregnancy in adolescence were designed and implemented. The respective ethical principles were taken into account. Results: The highest percentage of adolescents (73.3 percent, n= 66) began early their sexual relations. A rough estimated figure, that is, 73.3 percent (n= 65) mentioned non use of contraceptives in their sexual relations. Imitating contributes to the early onset of the sexual relationships with vaginal penetration. Eighty percent (n= 72) of the group believed that the risk of pregnancy, abortion and sexual infection was high, whereas a similar number mentioned parenthood and motherhood as shared responsibility of both members of the couple. Conclusions: The implemented educational actions contribute to improve the risk perception about pregnancy in adolescents. This type of interventions increases the level of knowledge and encourages changes in life styles. High level of satisfaction was observed with these actions(AU)

Low Proteolytic Clipping of Histone H3 in Cervical Cancer.

Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes. Recently, a potential mechanism, which regulates gene expression at transcriptional levels is the proteolytic clipping of histone H3. However, until now this process in CC has not been reported. Using HeLa cells as a model of CC and human samples from patients with CC, we identify that the H3 cleavage was lower in CC compared with control tissue. Additionally, the histone H3 clipping was performed by serine and aspartyl proteases in HeLa cells. These results suggest that histone H3 clipping operates as part of post-translational modification system in CC.

Serum Levels of MicroRNA-206 and Novel Mini-STR Assays for Carrier Detection in Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is an X-linked neuromuscular disorder in which the detection of female carriers is of the utmost importance for genetic counseling. Haplotyping with polymorphic markers and quantitation of creatine kinase levels (CK) allow tracking of the at-risk haplotype and evidence muscle damage, respectively. Such approaches are useful for carrier detection in cases of unknown mutations. The lack of informative markers and the inaccuracy of CK affect carrier detection. Therefore, herein we designed novel mini-STR (Short Tandem Repeats) assays to amplify 10 loci within the DMD gene and estimated allele frequencies and the polymorphism information content among other parameters in 337 unrelated individuals from three Mexican populations. In addition, we tested the utility of the assays for carrier detection in three families. Moreover, given that serum levels of miR-206 discern between DMD patients and controls with a high area under the curve (AUC), the potential applicability for carrier detection was assessed. The serum levels of miR-206 of non-carriers (n = 24) and carriers (n = 23) were compared by relative quantitation using real-time PCR (p < 0.05), which resulted in an AUC = 0.80 in the Receiver Operating Characteristic curve analysis. In conclusion, miR-206 has potential as a "liquid biopsy" for carrier detection and genetic counseling in DMD.

Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway.

[Intracellular signaling mechanisms in thyroid cancer]. / Mecanismos de señalización intracelular en cáncer de tiroides.

BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated¼ (MAPK) which consist of «modules¼ of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. OBJECTIVE: To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. CONCLUSIONS: Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway.