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1.
Nat Commun ; 12(1): 24, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33402679

RESUMEN

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.


Asunto(s)
Anorexia Nerviosa/genética , Glucemia/metabolismo , Intolerancia a la Glucosa/genética , Proteínas Sustrato del Receptor de Insulina/genética , Resistencia a la Insulina/genética , Insulina/sangre , Factores de Transcripción de Tipo Kruppel/genética , Adulto , Anorexia Nerviosa/sangre , Anorexia Nerviosa/etnología , Anorexia Nerviosa/fisiopatología , Grupo de Ascendencia Continental Europea , Ayuno/sangre , Femenino , Expresión Génica , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/etnología , Intolerancia a la Glucosa/fisiopatología , Humanos , Proteínas Sustrato del Receptor de Insulina/sangre , Factores de Transcripción de Tipo Kruppel/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Caracteres Sexuales , Factores Sexuales , Relación Cintura-Cadera
2.
Chem Biol Interact ; 333: 109321, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33186600

RESUMEN

HPV infections in the oral cavity that progress to cancer are on the increase in the USA. Model systems to study co-factors for progression of these infections are lacking as HPVs are species-restricted and cannot grow in preclinical animal models. We have recently developed a mouse papillomavirus (MmuPV1) oral mucosal infection model that provides opportunities to test, for the first time, the hypothesis that tobacco carcinogens are co-factors that can impact the progression of oral papillomas to squamous cell carcinoma (SCC). Four cohorts of mice per sex were included: (1) infected with MmuPV1 and treated orally with DMSO-saline; (2) infected with MmuPV1 and treated orally with the tobacco carcinogen, dibenzo[def,p]chrysene (DBP); (3) uninfected and treated orally with DMSO-saline, and (4) uninfected and treated orally with DBP. Oral swabs were collected monthly for subsequent assessment of viral load. Oral tissues were collected for in situ viral DNA/RNA detection, viral protein staining, and pathological assessment for hyperplasia, papillomas and SCC at study termination. We observed increased rates of SCC in oral tissue infected with MmuPV1 and treated with DBP when compared to mice treated with DBP or virus individually, each of which showed minimal disease. Virally-infected epithelium showed strong levels of viral DNA/RNA and viral protein E4/L1 staining. In contrast, areas of SCC showed reduced viral DNA staining indicative of lower viral copy per nucleus but strong RNA signals. Several host markers (p120 ctn, p53, S100A9) were also examined in the mouse oral tissues; of particular significance, p120 ctn discriminated normal un-infected epithelium from SCC or papilloma epithelium. In summary, we have confirmed that our infection model is an excellent platform to assess the impact of co-factors including tobacco carcinogens for oral PV cancerous progression. Our findings can assist in the design of novel prevention/treatment strategies for HPV positive vs. HPV negative disease.


Asunto(s)
Crisenos/toxicidad , Progresión de la Enfermedad , Contaminantes Ambientales/toxicidad , Neoplasias de la Boca/patología , Papillomaviridae/fisiología , Humo/efectos adversos , Tabaco/efectos adversos , Animales , Carcinogénesis/efectos de los fármacos , Femenino , Genoma Viral/genética , Masculino , Ratones , Neoplasias de la Boca/virología , Papillomaviridae/genética , Caracteres Sexuales , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología
4.
Ann Otol Rhinol Laryngol ; 130(2): 153-160, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32646280

RESUMEN

OBJECTIVES: To measure the dimensions of the cricoid cartilage in adults and to investigate the age-related change of the dimensions of the cricoid cartilage. METHODS: After performing the multiplanar reconstruction and correcting the slant of the cervical computed tomography scans, the transverse and anteroposterior internal diameters of the inlet (TD-in and APD-in) and outlet (TD-out and APD-out) of the cricoid cartilage were measured, respectively. The angle between the arch and lamina of the cricoid cartilage in the middle sagittal plane was measured. The ratios of transverse to anteroposterior diameter for the inlet (Ratio-in) and outlet (Ratio-out) of the cricoid cartilage were calculated, respectively. RESULTS: A total of 1200 adults were included in this study, with 600 males and 600 females. The TD-in is the smallest cricoid diameter and the APD-in is the largest cricoid diameter. The mean cricoid diameters and the cricoid angle in males were larger than those in females. The cricoid inlet is oval shaped and the cricoid cartilage is "funnel-shaped" in the middle sagittal plane. The shape of the outlet of the cricoid cartilage varies greatly among individuals. In males, the APD-in and APD-out were negatively correlated with age while the Ratio-in and Ratio-out was positively correlated with age. In females, the APD-out were negatively correlated with age while the Ratio-out was negatively correlated with age. CONCLUSIONS: The dimensions of the cricoid cartilage change as age advances in adult population and the sexual dimorphism of the cricoid outlet occurs after 50 years old.


Asunto(s)
Envejecimiento , Cartílago Cricoides/anatomía & histología , Cartílago Cricoides/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Caracteres Sexuales , Tomografía Computarizada por Rayos X
5.
Ann Hematol ; 100(1): 11-25, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33006021

RESUMEN

In recent times, there has been a growing interest in understanding the impact of gender on disease biology and clinical outcomes in Philadelphia-negative chronic myeloproliferative neoplasms. Among those, polycythemia vera (PV) is characterized by increased thrombotic risk, systemic symptoms, and overall reduced survival. Here, we aim to summarize data on whether and to what extent female sex can affect PV biology and outcome. To this end, we will discuss the latest acquisitions in terms of pathogenesis, diagnosis, epidemiology, clinical presentation and symptoms burden, thrombotic risk and related treatment strategies, and prognosis in female patients affected by PV.


Asunto(s)
Hemoglobinas/metabolismo , Policitemia Vera/sangre , Policitemia Vera/diagnóstico , Caracteres Sexuales , Femenino , Hemoglobinas/genética , Humanos , Janus Quinasa 2/sangre , Janus Quinasa 2/genética , Masculino , Policitemia Vera/genética
6.
Toxicol Appl Pharmacol ; 410: 115339, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33221319

RESUMEN

Udenafil is a long-acting oral phosphodiesterase type 5 inhibitor used to treat erectile dysfunction which may also have beneficial effects on cardiovascular diseases. Udenafil is mainly biotransformed to the active metabolite N-dealkylated udenafil via cytochrome P450 3A. The aim of this study was to investigate the gender differences and dose proportionality of the toxicokinetics of udenafil and its metabolite N-dealkylated udenafil in rodents. Udenafil was administered orally by gavage to male and female B6C3F1/N mice (100, 240, 350, and 500 mg/kg) and F344 rats (60, 120, and 240 mg/kg). Plasma concentrations of udenafil and N-dealkylated udenafil were simultaneous measured via liquid chromatography-tandem mass spectrometry. Female mice showed higher systemic exposure to udenafil than male mice, whereas female rats showed lower systemic exposure to udenafil than male rats after repeated administration at high dose. Systemic exposure to the metabolite, N-dealkylated udenafil, was lower in female than male mice and rats. A dose proportionality assessment by power model revealed a lack of dose proportionality in systemic exposure (Cmax, AUC24h and AUCinf) after administration of 100-500 mg/kg of udenafil in mice and 60-240 mg/kg in rats. This study thus demonstrates gender and species differences with regard to the toxicokinetic profiles of udenafil and its active metabolite N-dealkylated udenafil after oral administration of udenafil to mice and rats of both sexes. Our findings suggest the possibility of gender differences in the toxicokinetics of udenafil in humans and suggests that further study is needed in this cohort.


Asunto(s)
Inhibidores de Fosfodiesterasa 5/metabolismo , Inhibidores de Fosfodiesterasa 5/toxicidad , Pirimidinas/metabolismo , Pirimidinas/toxicidad , Caracteres Sexuales , Sulfonamidas/metabolismo , Sulfonamidas/toxicidad , Administración Oral , Animales , Femenino , Masculino , Ratones , Ratas , Ratas Endogámicas F344 , Roedores , Toxicocinética
7.
J Surg Oncol ; 123(1): 236-244, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33084065

RESUMEN

INTRODUCTION: The objective of this study was to characterize time from cancer symptoms to diagnosis and time from diagnosis to surgical treatment among patients undergoing pancreatectomy for cancer. METHODS: Medicare beneficiaries who underwent pancreatectomy for cancer between 2013 and 2017 were identified using the 100% Medicare Inpatient Standard Analytic Files. Mixed effects negative binomial regression models were utilized to determine which factors were associated with the number of weeks to diagnosis and pancreatic resection. RESULTS: Among 7647 Medicare beneficiaries, two-thirds (n = 5127, 67%) had symptoms associated with a pancreatic cancer diagnosis before surgery. Median time from the first symptom to diagnosis was 6 weeks (IQR: 1-25) and the median time from diagnosis to surgery was 4 weeks (IQR: 2-15). In risk-adjusted models, female patients had 13% longer waiting times from identification of a related symptom to pancreatic cancer diagnosis (OR = 1.13, 95% CI: 1.05-1.21) and 12% longer waiting times from diagnosis to surgery (OR = 1.12, 95% CI: 1.07-1.18). Older age was associated with 10% longer waiting times from symptom identification to diagnosis (p < .0001). CONCLUSIONS: Female and older patients had longer wait times between symptom presentation and pancreatic cancer diagnosis. Sex-based disparities in cancer care need to be recognized and addressed by policymakers and health care institutions.


Asunto(s)
Diagnóstico Tardío/estadística & datos numéricos , Pancreatectomía/mortalidad , Neoplasias Pancreáticas/mortalidad , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Medicare , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Pronóstico , Caracteres Sexuales , Tasa de Supervivencia , Estados Unidos
8.
Cancer Invest ; 39(1): 21-24, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33131319

RESUMEN

Gender parity within academic oncology is important. We hypothesized that gender differences exist in subspecialty choice and academic rank among medical oncologists. We performed a cross-sectional study of adult medical oncologists at the top 15 cancer centers. Gender, rank, subspecialty (breast, thoracic, gastrointestinal, and genitourinary) and board certification year were recorded. 570 medical oncologists were identified (60% men; 40% women). More women practice breast oncology (OR 3.1, p < 0.001), but less practice genitourinary oncology (OR 0.37, p < 0.001). 22% of women were full professors vs 34% of men (OR 0.55, p = 0.001). Gender differences persist in academic adult medical oncology.


Asunto(s)
Oncólogos/organización & administración , Caracteres Sexuales , Estudios Transversales , Docentes , Femenino , Humanos , Masculino
9.
Clin Sports Med ; 40(1): 133-145, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33187604

RESUMEN

Female athletes are participating in collision sports in greater numbers than previously. The overall incidence of concussion is known to be higher in female athletes than in male athletes participating in similar sports. Evidence suggests anatomic, biomechanical, and biochemical etiologies behind this sex disparity. Future research on female athletes is needed for further guidance on prevention and management of concussion in girls and women.


Asunto(s)
Traumatismos en Atletas/epidemiología , Conmoción Encefálica/epidemiología , Traumatismos en Atletas/fisiopatología , Conmoción Encefálica/fisiopatología , Femenino , Humanos , Incidencia , Volver al Deporte , Caracteres Sexuales , Factores de Tiempo
10.
Ecotoxicol Environ Saf ; 207: 111299, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32927158

RESUMEN

The analogues of biphenol A (BPA), including bisphenol S (BPS) and bisphenol B (BPB), are commonly used to replace the application of BPA in containers and wrappers of daily life. However, their safeties are questioned due to their similar chemical structure and possible physiological effects as BPA. To investigate the neurotoxic effects of BPA, BPS, and BPB as well as their underlying mechanism, IMR-32 cell line from male and SK-N-SH cell line from female were exposed respectively to BPA, BPS and BPB with concentrations of 1 nM, 10 nM, 100 nM, 1 µM, 10 µM, and 100 µM for 24 h. Additionally, 24 h exposure of BPA combining epigallocatechin gallate (EGCG) (4 µM and 8 µM for IMR-32 and SK-N-SH respectively) were conducted. Results demonstrated that BPs exposure could promote reactive oxygen species production and increase level of malondialdehyde (MDA) while decrease levels of superoxide dismutase (SOD). Intensive study revealed that after exposure to BPA mitochondrial membrane potential (MMP) dropped down and the protein expression levels of Bak-1, Bax, cytochrome c and Caspase-3 were up-regulated but Bcl-2 were down-regulated significantly. Moreover, apoptosis rate was raised and cell activity declined remarkably in the neuroblastoma cells. All the effects induced by BPA could be alleviated by the adding of EGCG, which similar alleviations could be inferred in IMR-32 and SK-N-SH cells induced by BPS and BPB. Furthermore, BPS showed lower neurotoxic effects compared to BPA and BPB. Interestingly, the neurotoxic effects of BPA on IMR-32 cells were significantly higher than those on SK-N-SH cells. In conclusion, the results suggested that BPA, BPS and BPB could induce oxidative stress and apoptosis via mitochondrial pathway in the neuroblastoma cells and male is more susceptible to BPs than female.


Asunto(s)
Apoptosis/efectos de los fármacos , Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Sulfonas/toxicidad , Caspasa 3/metabolismo , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Caracteres Sexuales
11.
J Nutr Health Aging ; 25(1): 84-93, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33367467

RESUMEN

PURPOSE: The present study investigated the correlation between the nutritional status and prognosis of COVID-19 patients, and analyzed the epidemiological characteristics of COVID-19 patients with different nutritional status. METHODS: 429 patients who were diagnosed positive for COVID-19 in Hubei Provincial Hospital of Traditional Chinese Medicine from December 2019 to March 2020 were selected and divided into different groups based on Controlling Nutritional Status (CONUT) score (0-4: the low CONUT score group; 5-12: the high CONUT score group). Multivariate logistic regression analysis was applied to investigate the effects of CONUT score on prognosis. RESULTS: The total score of admission status of patients with higher CONUT score was higher than that of those with lower CONUT score (χ2 = 7.152, P = 0.007). The number of adverse outcomes of female was higher than that of male (χ2 = 10.253, P = 0.001). The number of adverse outcomes was higher for patients with smoking history (P = 0.004) or hypertension (χ2 = 11.240, P = 0.001) than those without. Also, the number of adverse outcomes was higher for older patients than younger ones (χ2 = 15.681, P < 0.001). Patients with adverse outcomes had lower urine red blood cell count than patients without adverse outcomes (χ2 = 5.029, P = 0.025). However, BMI, drinking history and diabetes did not show correlation with the prognosis of COVID-19 (P > 0.05).Among patients ≥ 61 years old, the risk of adverse outcomes in the high CONUT score group was 6.191 times that of the low CONUT score group (OR = 6.191, 95% CI: 1.431-26.785).Among the non-diabetic patients, the risk of adverse outcomes in the high CONUT group was 11.678 times that of the low CONUT group (OR = 11.678, 95% CI: 2.754-49.41).For the patients who had a total score of admission status < 6, the risk of adverse outcomes in the high CONUT score group was 8.216 times that of the low CONUT score group (OR = 8.216, 95% CI: 2.439-27.682). CONCLUSION: COVID-19 patients with good nutritional status showed a small chance to have adverse outcomes. Gender, age, hypertension, the number of urine red blood cell count and CONUT score affected the adverse outcomes of patients.


Asunto(s)
Envejecimiento , /diagnóstico , Correlación de Datos , Recuento de Eritrocitos , Hipertensión/complicaciones , Estado Nutricional , Caracteres Sexuales , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , China , Diabetes Mellitus , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Retrospectivos , Fumar , Adulto Joven
12.
PLoS One ; 15(12): e0242738, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33259511

RESUMEN

OBJECTIVE: Aerobic fitness may be beneficial for neuroanatomical structure. However, few have investigated this in emerging adults while also accounting for potential sex differences. Here we examine aerobic fitness level, sex, and their interaction in relation to cortical thickness, surface area, and volume. METHOD: Sixty-three young adults between the ages of 16-26 were balanced for sex and demonstrated a wide range of aerobic fitness levels. Exclusion criteria included left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal medical issues, prenatal alcohol/illicit drug exposure, or excessive substance use. Participants completed an MRI scan and a graded exercise test to volitional fatigue (VO2 max). Data analyses were run in Freesurfer and data was corrected for multiple comparisons with Monte Carlo simulations at .05. RESULTS: Males demonstrated higher VO2 values. Higher VO2 values were statistically independently related to thinner lateral occipital, superior parietal, cuneus, precuneus, and inferior parietal regions, smaller lateral occipital volume, and larger inferior parietal surface area. Compared to females, males had larger volume in rostral anterior cingulate, lateral occipital, and superior frontal regions, and greater surface area in fusiform, inferior parietal, rostral and caudal anterior cingulate, and superior parietal regions. VO2*Sex interactions revealed higher-fit females had higher inferior parietal, paracentral, and supramarginal surface area, while lower-fit males showed larger surface area in these same regions. CONCLUSIONS: Individuals with higher aerobic fitness performance had thinner cortices, lower volume, and larger surface area in sensorimotor regions than lower fit individuals, perhaps suggesting earlier neuromaturation in higher fit individuals. Larger surface area was associated with higher-fit females and lower-fit males. Thus both sex and aerobic fitness are important in shaping brain health in emerging adults.


Asunto(s)
Encéfalo/fisiología , Prueba de Esfuerzo , Ejercicio Físico/fisiología , Lóbulo Frontal/fisiología , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiología , Femenino , Lóbulo Frontal/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiología , Caracteres Sexuales , Adulto Joven
13.
PLoS One ; 15(12): e0244516, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33382767

RESUMEN

Research on face sensitivity is of particular relevance during the rapidly evolving Covid-19 pandemic leading to social isolation, but also calling for intact interaction and sharing. Humans possess high sensitivity even to a coarse face scheme, seeing faces in non-face images where real faces do not exist. The advantage of non-face images is that single components do not trigger face processing. Here by implementing a novel set of Face-n-Thing images, we examined (i) how face tuning alters with changing display orientation, and (ii) whether it is affected by observers' gender. Young females and males were presented with a set of Face-n-Thing images either with canonical upright orientation or inverted 180° in the image plane. Face impression was substantially impeded by display inversion. Furthermore, whereas with upright display orientation, no gender differences were found, with inversion, Face-n-Thing images elicited face impression in females significantly more often. The outcome sheds light on the origins of the face inversion effect in general. Moreover, the findings open a way for examination of face sensitivity and underwriting brain networks in neuropsychiatric conditions related to the current pandemic (such as depression and anxiety), most of which are gender/sex-specific.


Asunto(s)
Encéfalo/fisiopatología , Reconocimiento Facial , Red Nerviosa/fisiopatología , Orientación , Reconocimiento Visual de Modelos , Caracteres Sexuales , Adolescente , Adulto , Femenino , Humanos , Masculino
14.
Clin Appl Thromb Hemost ; 26: 1076029620982669, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33372807

RESUMEN

Deep venous thrombosis (DVT) is a severe complication of coronavirus disease 2019 (COVID-19). The purpose of this study was to study the prevalence, risk factors, anticoagulant therapy and sex differences of DVT in patients with COVID-19. The enrolled 121 hospitalized non-ventilator patients were confirmed positive for COVID-19. All suspected patients received color Doppler ultrasound (US) to screen for DVT in both lower extremities. Multivariate logistic regression was performed to identify risk factors related to DVT in COVID-19 patients. DVT was found in 48% of the asymptomatic COVID-19 patients with an increased PADUA or Caprini index using US scanning. The multivariate logistic regression determined that age (OR, 1.05; p = .0306), C-reactive protein (CRP) (OR, 1.02; p = .0040), and baseline D-dimer (OR, 1.42; p = .0010) were risk factors among COVID-19 patients. Although the most common DVT location was infrapopliteal (classes I and II), higher mortality in DVT-COVID-19 patients was confirmed. DVT-COVID-19 patients presented significant increases in CRP, neutrophil count, and D-dimer throughout the whole inpatient period compared to non-DVT-COVID-19 patients. Although anticoagulation therapy accelerated the recovery of lymphocytopenia in DVT patients, men DVT-COVID-19 patients with anticoagulant therapy showed significant higher CRP and neutrophil count vs. lymphocyte count (N/L) ratio, but showed lower lymphocyte counts compared to women DVT-COVID-19 patients. DVT is common in COVID-19 patients with high-risk factors, especially for older age and higher CRP and baseline D-dimer populations. It is important to consider sex differences in anticoagulant therapy among DVT-COVID-19 patients.


Asunto(s)
/complicaciones , Trombosis de la Vena/etiología , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Proteína C-Reactiva/análisis , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Caracteres Sexuales
15.
PLoS One ; 15(12): e0243054, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33284828

RESUMEN

BACKGROUND: Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. OBJECTIVE: This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. MATERIALS AND METHODS: A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. RESULTS: Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4-15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05-4.9) and gender (AOR: 2.5; 95% CI: 1.09-5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3-36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. CONCLUSION: The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.


Asunto(s)
Portador Sano/epidemiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones Neumocócicas/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Adulto , Fármacos Anti-VIH/uso terapéutico , Profilaxis Antibiótica , Portador Sano/microbiología , Estudios de Casos y Controles , Estudios Transversales , Etiopía , Femenino , Infecciones por VIH/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Caracteres Sexuales , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/crecimiento & desarrollo , Combinación Trimetoprim y Sulfametoxazol/farmacología
16.
PLoS One ; 15(12): e0242665, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33264334

RESUMEN

Sex-specific transcription characterizes hundreds of genes in mouse liver, many implicated in sex-differential drug and lipid metabolism and disease susceptibility. While the regulation of liver sex differences by growth hormone-activated STAT5 is well established, little is known about autosomal genetic factors regulating the sex-specific liver transcriptome. Here we show, using genotyping and expression data from a large population of Diversity Outbred mice, that genetic factors work in tandem with growth hormone to control the individual variability of hundreds of sex-biased genes, including many long non-coding RNA genes. Significant associations between single nucleotide polymorphisms and sex-specific gene expression were identified as expression quantitative trait loci (eQTLs), many of which showed strong sex-dependent associations. Remarkably, autosomal genetic modifiers of sex-specific genes were found to account for more than 200 instances of gain or loss of sex-specificity across eight Diversity Outbred mouse founder strains. Sex-biased STAT5 binding sites and open chromatin regions with strain-specific variants were significantly enriched at eQTL regions regulating correspondingly sex-specific genes, supporting the proposed functional regulatory nature of the eQTL regions identified. Binding of the male-biased, growth hormone-regulated repressor BCL6 was most highly enriched at trans-eQTL regions controlling female-specific genes. Co-regulated gene clusters defined by overlapping eQTLs included sets of highly correlated genes from different chromosomes, further supporting trans-eQTL action. These findings elucidate how an unexpectedly large number of autosomal factors work in tandem with growth hormone signaling pathways to regulate the individual variability associated with sex differences in liver metabolism and disease.


Asunto(s)
Regulación de la Expresión Génica , Hígado/metabolismo , Caracteres Sexuales , Animales , Sitios de Unión/genética , Cromosomas de los Mamíferos/genética , Ratones de Colaboración Cruzada , Femenino , Hormona del Crecimiento/metabolismo , Mutación INDEL/genética , Masculino , Ratones , Modelos Genéticos , Familia de Multigenes , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo/genética , Secuencias Reguladoras de Ácidos Nucleicos/genética , Factores de Transcripción/metabolismo
17.
Genes (Basel) ; 11(12)2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33271804

RESUMEN

Worldwide COVID-19 epidemiology data indicate differences in disease incidence amongst sex and gender demographic groups. Specifically, male patients are at a higher death risk than female patients, and the older population is significantly more affected than young individuals. Whether this difference is a consequence of a pre-existing differential response to the virus, has not been studied in detail. We created DeCovid, an R shiny app that combines gene expression (GE) data of different human tissue from the Genotype-Tissue Expression (GTEx) project along with the COVID-19 Disease Map and COVID-19 related pathways gene collections to explore basal GE differences across healthy demographic groups. We used this app to study differential gene expression of COVID-19 associated genes in different age and sex groups. We identified that healthy women show higher expression-levels of interferon genes. Conversely, healthy men exhibit higher levels of proinflammatory cytokines. Additionally, young people present a stronger complement system and maintain a high level of matrix metalloproteases than older adults. Our data suggest the existence of different basal immunophenotypes amongst different demographic groups, which are relevant to COVID-19 progression and may contribute to explaining sex and age biases in disease severity. The DeCovid app is an effective and easy to use tool for exploring the GE levels relevant to COVID-19 across demographic groups and tissues.


Asunto(s)
Bases de Datos de Ácidos Nucleicos , Caracteres Sexuales , Programas Informáticos , Transcripción Genética/inmunología , Adolescente , Adulto , Anciano , /inmunología , Femenino , Humanos , Interferones/genética , Interferones/inmunología , Masculino , Persona de Mediana Edad , /inmunología
19.
Rev Med Suisse ; 16(719): 2454-2457, 2020 Dec 16.
Artículo en Francés | MEDLINE | ID: mdl-33325664

RESUMEN

Cardiovascular disease, including myocardial infarction, has been less studied in the female population, leading to higher mortality among women. Differences between the sexes exist in terms of clinical presentation, pathophysiology and even management. This article is a non-systematic review of literature of recent articles addressing this theme. A broader understanding of the peculiarities of coronary syndrome in women improves their management and reduces the inequality of prognosis for women.


Asunto(s)
Enfermedades Cardiovasculares , Caracteres Sexuales , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Infarto del Miocardio , Pronóstico , Factores de Riesgo , Síndrome
20.
Z Psychosom Med Psychother ; 66(4): 402-417, 2020 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-33284065

RESUMEN

LIFE Child Depression - a prospective longitudinal cohort study on the origin of depressive disorders between childhood and early adulthood LIFE Child Depression is a prospective longitudinal study on the origin and course of depressive symptoms and disorders between child- and adulthood. The aim of the study is to identify patterns of developmental courses of symptoms and disorders and to investigate the interplay of psychosocial, biological and genetic risk and protective factors in the development of depressive disorders. The present paper gives an overview on results of the study. The sample was already assessed three times. A clinical sample was recruited from two local child psychiatric in- and outpatient services in Leipzig, a control sample was recruited from a children's health check program at our medical faculty (LIFE Child Health) and from the local registration office. We found some important context- and parent-associated risk factors for depressive disorders, such as negative life events, low socioeconomic status and depression in mothers (but not in fathers). Moreover, we found some characteristic biological and cognitive-emotional characteristics of children with depressive disorders, such as low stress-related cortisol, low evaluation of own performance, and more negative cognitions in dealing with stressful situations, low self-esteem and a general impairment of emotional processing of human faces. Only some of the risk factors were found to be specific to depression. Instead, most of them can be regarded as general risk factors for psychological disorders in childhood. It is also noteworthy, that some of the risk associations were gender-specific and need to be looked at from a differential point of view. Our study gives important indications for prevention for children at risk for depressive disorders as well as for therapeutic approaches.


Asunto(s)
Depresión , Trastorno Depresivo , Adolescente , Niño , Depresión/epidemiología , Depresión/etiología , Trastorno Depresivo/epidemiología , Trastorno Depresivo/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Madres/psicología , Estudios Prospectivos , Caracteres Sexuales , Clase Social , Adulto Joven
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