Epstein-Barr Virus BARF1 Is Expressed in Lung Cancer and Is Associated with Cancer Progression.

BACKGROUND: Epstein-Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. METHODS: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were evaluated. RESULTS: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein-Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. CONCLUSIONS: EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression.

Viral Hepatitis in Pregnant Mexican Women: Its Impact in Mother-Child Binomial Health and the Strategies for Its Eradication.

Viral hepatitis is the main cause of infectious liver disease. During pregnancy, a risk of vertical transmission exists both during gestation and at birth. HAV, HBV, and HCV might progress similarly in pregnant and non-pregnant women. In this study, we found a prevalence of 0.22% of viral hepatitis in pregnant women, with a light preponderance of HCV over HAV and HBV. Here, it was observed that acute HAV infection is more symptomatic and has higher risks for the mother and fetus, in a similar manner to what has been reported for HEV. Histopathological alterations were observed in all except one placenta, indicating that it is an important tissue barrier. Regarding the Mexican strategies for viral hepatitis eradication, success may be related to vaccination at birth, whereas for HCV, the national program for eradication is aimed at treating the infection via direct-acting antiviral agents. The HBV strategy has positively impacted pregnant women and their children, diminishing the risk of vertical transmission. The HCV strategy is still in its early years, and it is expected to be just as successful. For acute hepatitis, HAV and HEV, programs promoting hand washing and those aimed at providing clean food and water are applicable as preventive strategies, alongside other programs such as vaccination.

Biosynthesis of Polyhydroalkanoates Doped with Silver Nanoparticles Using Pseudomonas putida and Pseudomonas aeruginosa for Antibacterial Polymer Applications.

In this study, the biosynthesis of polyhydroxyalkanoates (PHAs) was carried out using Pseudomonas putida and Pseudomonas aeruginosa. These PHAs were produced using reagent-grade glycerol and crude glycerol as the carbon sources. The objective was to compare the production of PHAs and to functionalize these polymers with silver nanoparticles to provide antibacterial properties for potential biomedical applications. The findings from the physical and chemical analyses confirmed the successful synthesis and extraction of PHAs, achieving comparable yields using both crude glycerol and reagent-grade glycerol as carbon sources across both strains. Approximately 16% higher PHAs production was obtained using Pseudomonas putida compared to Pseudomonas aeruginosa, and no significant difference was observed in the production rate of PHAs between the two carbon sources used, which means that crude glycerol could be utilized even though it has more impurities. Notably, PHAs functionalized with silver nanoparticles showed improved antibacterial effectiveness, especially those derived from reagent-grade glycerol and the Pseudomonas aeruginosa strain.

Genotipificación del virus del papiloma humano en mujeres embarazadas VPH positivas / Genotyping of human papillomavirus in HPV-positive pregnant women

Resumen Antecedentes: Las embarazadas infectadas por el virus del papiloma humano presentan condiciones médicas que influyen en el curso de la enfermedad y pueden potenciar la posibilidad de transmisión vertical. Objetivo: Identificar los genotipos del virus del papiloma humano más frecuentes en mujeres embarazadas. Método: Estudio retrospectivo, observacional y descriptivo. Se emplearon muestras de raspado cervical. La extracción de material genético se hizo por la técnica de fenol-cloroformo y se amplificó empleando iniciadores universales MY09/MY11. Las muestras positivas se genotipificaron con un kit que detecta 37 genotipos diferentes. Resultados: Se identificaron 341 genotipos. Los más frecuentes fueron 16 (10.3%), 52 (8.8%) y 59 (8.6%). En el 75.9% la detección fue con un genotipo y en el 42.7% se detectaron infecciones múltiples. Conclusiones: Es sabido que la infección por virus del papiloma humano en mujeres embarazadas raramente evolucionará a lesiones invasivas. Se deberán considerar tanto las posibles complicaciones obstétricas a corto y largo plazo, así como las posibles repercusiones en la salud del recién nacido. La detección elevada del genotipo 16 sugiere un seguimiento estrecho para considerar un abordaje óptimo posterior a la gestación.

Abstract Background: Pregnant women infected with human papillomavirus have medical conditions that influence the course of the disease and can increase the possibility of vertical transmission. Objective: To identify the most common human papillomavirus genotypes in pregnant women. Method: Retrospective, observational and descriptive study. Cervical scraping samples were used. The extraction of genetic material was done by the phenol-chloroform technique and was amplified using universal primers MY09/MY11. Positive samples were genotyped with a kit that detects 37 different genotypes. Results: Three hundred forty-one genotypes were identified. The most frequent were 16 (10.3%), 52 (8.8%), and 59 (8.6%). In 75.9% the detection was with one genotype and in 42.7% multiple infections were detected. Conclusions: It is known that human papillomavirus infection in pregnant women will rarely evolve to invasive lesions. Both possible short- and long-term obstetric complications, as well as possible repercussions on the health of the newborn, should be considered. The high detection of genotype 16 suggests close follow-up to consider an optimal post-pregnancy approach.

Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer.

Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in the pathogenesis and progression of OC. Old drugs with antitumoral properties have also been studied in the context of cancer, although their antitumor mechanisms are not fully clear. For instance, the antidiabetic drug metformin has shown pleiotropic effects in several in vitro models of cancer, including OC. Interestingly, metformin has been reported to regulate ncRNAs, which could explain its diverse effects on tumor cells. In this review, we discuss the mechanism of epigenetic regulation described for metformin, with a focus on the evidence of metformin-dependent microRNA (miRNAs) and long non-coding RNA (lncRNAs) regulation in OC.

Conventional and new proposals of GnRH therapy for ovarian, breast, and prostatic cancers.

For many years, luteinizing hormone-releasing hormone or gonadotropin-releasing hormone (GnRH) analogs have been used to treat androgen or estrogen-dependent tumors. However, emerging evidence shows that the GnRH receptor (GnRH-R) is overexpressed in several cancer cells, including ovarian, endometrial, and prostate cancer cells, suggesting that GnRH analogs could exert direct antitumoral actions in tumoral tissues that express GnRH-R. Another recent approach based on this knowledge was the use of GnRH peptides for developing specific targeted therapies, improving the delivery and accumulation of drugs in tumoral cells, and decreasing most side effects of current treatments. In this review, we discuss the conventional uses of GnRH analogs, together with the recent advances in GnRH-based drug delivery for ovarian, breast, and prostatic cancer cells.

Body mass index implications in intrahepatic cholestasis of pregnancy and placental histopathological alterations.

INTRODUCTION AND OBJECTIVES: Intrahepatic cholestasis is a frequent disease during pregnancy. It is unknown if liver function alterations produce specific placental lesions. The aim of this study was to evaluate placental histopathological changes in patients with intrahepatic cholestasis of pregnancy (ICP), and to explore correlations between the placental histopathology and hepatic function alteration or patient comorbidities, and body mass index. PATIENTS AND METHODS: A retrospective cohort study included women with ICP, most of them showing comorbidities such as overweight/obesity, preeclampsia and gestational diabetes. They were attended at the National Institute of Perinatology in Mexico City for three years. Placental histopathological alterations were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement. Data was analyzed using Graph-Pad Prism 5. RESULTS: The results indicated that the placenta of ICP patients showed many histopathological alterations; however, no correlations were observed between the increase in bile acids or liver functional parameters and specific placental lesions. The most frequent comorbidities found in ICP patients were obesity, overweight and preeclampsia. Surprisingly, high percentage of ICP patients did not respond to UDCA treatment independently of the BMI group to which they belonged. CONCLUSION: The data suggest that ICP contribute to placental lesions. In addition, in patients with normal weight, an increase of chorangiosis and a reduced accelerated villous maturation without syncytial knots were observed in comparison with overweight and obese patients. It is necessary to improve the medical strategies in the treatment and liver disfunction surveillance of ICP patients.

Effect of 1,2-propanediol on the Critical Micelle Concentration of Decyltrimethylammonium Bromide at Temperatures from 293.15 K to 308.15 K.

It is well known that polar organic compounds, such as alcohols and polyols, exert an appreciable influence on water structure and thus have important effects on surfactant micellization. These substances are often used to modify the properties of surfactants in aqueous solutions, increasing the practical applications they have in diverse industries. In this work, the critical micelle concentration (CMC) of decyltrimethylammonium bromide (C10TAB) in water and in 1,2-propanediol aqueous solutions was determined from both sound velocity and surface tension measurements as a function of surfactant concentration in the temperature range of (293.15 to 308.15) K. The critical micelle concentration of the surfactant increases as the concentration of 1,2-propanediol becomes higher, while the effect on temperature does not show important changes within the range considered. At the selected temperatures, the standard thermodynamic parameters of micellization suggests that the addition of 1,2-propanediol makes the micellization process less favorable. Thermodynamic analysis suggests that the micelle formation of C10TAB is an entropy-driven process at the temperatures considered in this study.

Photocatalytic Degradation of Dielectric Mineral Oil with PCBs Content Coupled with Algae Treatment.

Insulating oil contaminated with polychlorinated biphenyls (PCBs) is an environmentally important pollutant. This research focused on the establishment of the optimum conditions under which photocatalytic oxidation can be used together with biotreatment using the Nostoc sp. microorganism to degrade PCBs present in used dielectric oils. Among the optimal conditions studied were PCB concentration, initial pH, and titanium dioxide (TiO2) concentration for the photocatalytic step, and PCB concentration and photoperiod for the biotreatment step. The results indicate that the optimal conditions necessary for photocatalytic degradation were a pH of 6.10, 113 mg/L TiO2, and 765 mg/L PCBs, achieving close to 90% removal. For the biotreatment step, the results showed that PCBs progressively inhibited the microbiological growth, with the lowest cellular growth observed in the medium with the highest PCB concentration.

Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells.

One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.

Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis.

BACKGROUND: Leprosy is a chronic infectious disease, still endemic in many countries that may lead to neurological, ophthalmic, and motor sequelae if not treated early. Access to timely diagnosis and multidrug therapy (MDT) remains a crucial element in the World Health Organization's strategy to eliminate the disease as a public health problem. OBJECTIVES: This systematic review aims to evaluate the accuracy of rapid point-of-care (POC) tests for diagnosis of leprosy. METHODS: Searches were carried out in electronic databases (PubMed, EMBASE, CRD, Cochrane Library and LILACS) in April 2021 for patients with suspicion or confirmatory diagnostic of leprosy, classified in multibacillary (MB) or paucibacillary (PB) cases, performing rapid POC serological tests compared to clinical evaluation, smear microscopy and immunohistochemistry analysis. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A meta-analysis was undertaken to generate pooled estimates of diagnostic parameters, presenting sensitivity, specificity and diagnostic odds ratio (DOR) values. The review protocol was registered at PROSPERO, CRD # 42014009658. FINDINGS: From 893 potentially relevant references, 12 articles were included reporting 16 diagnostic tests accuracy studies with 5395 individuals enrolled. Meta-analysis of NDO-LID and PGL-I tests data in MB patients showed sensitivity and specificity [95% confidence interval (CI)] of 0.83 (0.71-0.91), 0.91 (0.72-0.97); and 0.92 (0.86-0.96), 0.93 (0.78-0.98); respectively, with high heterogeneity among the studies. MAIN CONCLUSIONS: Our results can inform policymakers regarding the possibility of implementing accurate, rapid POC tests for leprosy in public health services, especially within primary health care.

Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS.

Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disorder associated with insulin resistance (IR) and obesity. Endometria from women with PCOS present failures in insulin action, glucose uptake and signaling of insulin-sensitizing molecules, such as adiponectin, with consequences for reproduction. Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood. This study addresses the MTF effect, as well as adiponectin agonist action, on levels of molecules associated with insulin and adiponectin signaling pathways in endometrial tissue and cells, as assessed by immunohistochemistry and immunocytochemistry, respectively. Endometrial tissues were obtained from women and divided into five groups: Normal Weight (control); Obesity + IR; Obesity + IR + PCOS; Obesity + IR + MTF; Obesity + IR + PCOS + MTF. Endometrial cells stimulated with TNFα (as obesity-marker) were also used to partially emulate an obesity environment. The results showed low levels of insulin/adiponectin signaling in the endometria from women with obesity, IR and PCOS compared with the control group. MTF re-established these levels, independently of PCOS. TNFα-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin/adiponectin molecules in endometrial cells treated with TNFα were reverted by MTF, similar to what was observed in the case of the adiponectin agonist. Therefore, independently of PCOS, MTF can re-establish levels of molecules involved in insulin/adiponectin signaling in endometrial cells, suggesting an improvement in insulin action and reproductive failures observed in endometria from women with obesity/PCOS.

NGF/TRKA Promotes ADAM17-Dependent Cleavage of P75 in Ovarian Cells: Elucidating a Pro-Tumoral Mechanism.

Nerve growth factor (NGF) and its high-affinity receptor TRKA are overexpressed in epithelial ovarian cancer (EOC) displaying a crucial role in the disease progression. Otherwise, NGF interacts with its low-affinity receptor P75, activating pro-apoptotic pathways. In neurons, P75 could be cleaved by metalloproteinases (α and γ-secretases), leading to a decrease in P75 signaling. Therefore, this study aimed to evaluate whether the shedding of P75 occurs in EOC cells and whether NGF/TRKA could promote the cleavage of the P75 receptor. The immunodetection of the α-secretase, ADAM17, TRKA, P75, and P75 fragments was assessed by immunohisto/cytochemistry and Western blot in biopsies and ovarian cell lines. The TRKA and secretases' inhibition was performed using specific inhibitors. The results show that P75 immunodetection decreased during EOC progression and was negatively correlated with the presence of TRKA in EOC biopsies. NGF/TRKA increases ADAM17 levels and the fragments of P75 in ovarian cells. This effect is abolished when cells are previously treated with ADAM17, γ-secretase, and TRKA inhibitors. These results indicate that NGF/TRKA promotes the shedding of P75, involving the activation of secretases such as ADAM17. Since ADAM17 has been proposed as a screening marker for early detection of EOC, our results contribute to understanding better the role of ADAM17 and NGF/TRKA in EOC pathogenesis, which includes the NGF/TRKA-mediated cleavage of P75.

Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis

BACKGROUND Leprosy is a chronic infectious disease, still endemic in many countries that may lead to neurological, ophthalmic, and motor sequelae if not treated early. Access to timely diagnosis and multidrug therapy (MDT) remains a crucial element in the World Health Organization's strategy to eliminate the disease as a public health problem. OBJECTIVES This systematic review aims to evaluate the accuracy of rapid point-of-care (POC) tests for diagnosis of leprosy. METHODS Searches were carried out in electronic databases (PubMed, EMBASE, CRD, Cochrane Library and LILACS) in April 2021 for patients with suspicion or confirmatory diagnostic of leprosy, classified in multibacillary (MB) or paucibacillary (PB) cases, performing rapid POC serological tests compared to clinical evaluation, smear microscopy and immunohistochemistry analysis. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A meta-analysis was undertaken to generate pooled estimates of diagnostic parameters, presenting sensitivity, specificity and diagnostic odds ratio (DOR) values. The review protocol was registered at PROSPERO, CRD # 42014009658. FINDINGS From 893 potentially relevant references, 12 articles were included reporting 16 diagnostic tests accuracy studies with 5395 individuals enrolled. Meta-analysis of NDO-LID and PGL-I tests data in MB patients showed sensitivity and specificity [95% confidence interval (CI)] of 0.83 (0.71-0.91), 0.91 (0.72-0.97); and 0.92 (0.86-0.96), 0.93 (0.78-0.98); respectively, with high heterogeneity among the studies. MAIN CONCLUSIONS Our results can inform policymakers regarding the possibility of implementing accurate, rapid POC tests for leprosy in public health services, especially within primary health care.

Carotid artery stenting has similar outcomes in men and women.

BACKGROUND: The aim of carotid interventions is to prevent cerebrovascular events. Endovascular treatment (carotid-artery-stenting/CAS) has become established as an alternative to open surgery in some cases. Historically, female sex has been considered as a perioperative risk factor, however, there are few studies regarding this hypothesis when it comes to CAS. OBJECTIVES: To analyze the CAS results in our center adjusted by sex. METHODS: A retrospective cohort study was designed, including patients with carotid atheromatosis operated at a single center from January 2016 to June 2019. Our objective was to compare cardiovascular risk, including myocardial infarction, stroke, and mortality, by sex. Follow-up rates of stent patency, restenosis, stroke, myocardial infarction, and death were reported. RESULTS: 71 interventions were performed in 50 men (70.42%) and 21 women (29.57%). Mean age was 70.50 ± 10.72 years for men and 73.62 ± 11.78 years for women. Cardiovascular risk factors did not differ significantly between sexes. Mean follow-up was 11.28 ± 11.28 months. There were no significant differences in neurological events during follow-up. No adverse cardiological events were detected at any time. Regarding the mortality rate, during medium-term follow up there were 2 neurological related deaths with no significant differences between sexes (p=0.8432). Neither sex had higher rated of restenosis during long term follow-up (5.63% vs. 1.41%, p = 0.9693) or reoperation (1.41% vs. 1.41%, p = 0.4971). All procedures remained patent (<50% restenosis). CONCLUSIONS: Despite the limitations of our study, CAS is a therapeutic option that is as effective and safe in women as in men. No sex differences were observed.

CONTEXTO: As intervenções carotídeas visam prevenir eventos cerebrovasculares. O tratamento endovascular (implante de stent na artéria carótida) se estabeleceu como uma alternativa à cirurgia aberta em alguns casos. Historicamente, o sexo feminino é considerado um fator de risco perioperatório, mas há poucos estudos abordando essa hipótese em casos de stent de carótida. OBJETIVOS: Analisar os resultados do CAS em nosso centro ajustados por sexo. MÉTODOS: Este estudo de coorte retrospectivo incluiu pacientes com ateromatose carotídea operados em um centro de janeiro de 2016 a junho de 2019. Nosso objetivo foi comparar o risco cardiovascular, incluindo infarto do miocárdio, acidente vascular cerebral e mortalidade, de acordo com o sexo. No seguimento, foram descritos patência do stent, reestenose, acidente vascular cerebral, infarto do miocárdio e morte. RESULTADOS: Setenta e uma intervenções foram realizadas: 50 homens (70,42%) e 21 mulheres (29,57%). A média de idade foi de 70,50 ± 10,72 anos nos homens e 73,62 ± 11,78 anos nas mulheres. Os fatores de risco cardiovascular não diferiram significativamente entre os sexos. A média de seguimento foi de 11,28 ± 11,28 meses. Durante o seguimento, não houve diferenças significativas nos eventos neurológicos. Nenhum evento cardiológico adverso foi detectado. Quanto à taxa de mortalidade, durante o seguimento de médio prazo ocorreram 2 óbitos neurológicos sem diferenças significativas entre os sexos (p = 0,8432). Não foi observada maior taxa de reestenose no seguimento de longo prazo (5,63% vs. 1,41%, p = 0,9693) ou de reoperação (1,41% vs. 1,41%, p = 0,4971) ao comparar os dois sexos. Todos os procedimentos permaneceram pérvios (< 50% de reestenose). CONCLUSÕES: Apesar das limitações deste estudo, o stent de carótida em mulheres é uma opção terapêutica tão eficaz e segura quanto em homens. Nenhuma diferença foi observada entre os sexos.

What Are We Measuring When We Evaluate Digital Interventions for Improving Lifestyle? A Scoping Meta-Review.

Background: Lifestyle Medicine (LM) aims to address six main behavioral domains: diet/nutrition, substance use (SU), physical activity (PA), social relationships, stress management, and sleep. Digital Health Interventions (DHIs) have been used to improve these domains. However, there is no consensus on how to measure lifestyle and its intermediate outcomes aside from measuring each behavior separately. We aimed to describe (1) the most frequent lifestyle domains addressed by DHIs, (2) the most frequent outcomes used to measure lifestyle changes, and (3) the most frequent DHI delivery methods. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) Extension for Scoping Reviews. A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Web of Science for publications since 2010. We included systematic reviews and meta-analyses of clinical trials using DHI to promote health, behavioral, or lifestyle change. Results: Overall, 954 records were identified, and 72 systematic reviews were included. Of those, 35 conducted meta-analyses, 58 addressed diet/nutrition, and 60 focused on PA. Only one systematic review evaluated all six lifestyle domains simultaneously; 1 systematic review evaluated five lifestyle domains; 5 systematic reviews evaluated 4 lifestyle domains; 14 systematic reviews evaluated 3 lifestyle domains; and the remaining 52 systematic reviews evaluated only one or two domains. The most frequently evaluated domains were diet/nutrition and PA. The most frequent DHI delivery methods were smartphone apps and websites. Discussion: The concept of lifestyle is still unclear and fragmented, making it hard to evaluate the complex interconnections of unhealthy behaviors, and their impact on health. Clarifying this concept, refining its operationalization, and defining the reporting guidelines should be considered as the current research priorities. DHIs have the potential to improve lifestyle at primary, secondary, and tertiary levels of prevention-but most of them are targeting clinical populations. Although important advances have been made to evaluate DHIs, some of their characteristics, such as the rate at which they become obsolete, will require innovative research designs to evaluate long-term outcomes in health.

Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies. The late diagnosis is frequent due to the absence of specific symptomatology and the molecular complexity of the disease, which includes a high angiogenesis potential. The first-line treatment is based on optimal debulking surgery following chemotherapy with platinum/gemcitabine and taxane compounds. During the last years, anti-angiogenic therapy and poly adenosine diphosphate-ribose polymerases (PARP)-inhibitors were introduced in therapeutic schemes. Several studies have shown that these drugs increase the progression-free survival and overall survival of patients with ovarian cancer, but the identification of patients who have the greatest benefits is still under investigation. In the present review, we discuss about the molecular characteristics of the disease, the recent evidence of approved treatments and the new possible complementary approaches, focusing on drug repurposing, non-coding RNAs, and nanomedicine as a new method for drug delivery.

Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer.

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.

Desenlaces perinatales, en un centro de tercer nivel de México de pacientes con colestasis intrahepática del embarazo / Perinatal outcomes of patients with intrahepatic cholestasis of pregnancy in a third level center in Mexico

Resumen OBJETIVO: Describir la atención, tratamiento, desenlaces perinatales y complicaciones asociadas con la colestasis intrahepática del embarazo. MATERIALES Y MÉTODOS: Estudio de serie de casos, retrospectivo y observacional de pacientes embarazadas, con diagnóstico de colestasis intrahepática atendidas en el Instituto Nacional de Perinatología entre los meses de enero de 2016 a diciembre de 2020. Se evaluaron las características obstétricas, los datos demográficos, clínicos, bioquímicos y de tratamiento, la finalización del embarazo y los desenlaces perinatales. RESULTADOS: Se analizaron 67 casos de colestasis intrahepática que arrojaron una incidencia de 0.57%. La edad promedio de las pacientes fue 29.0 ± 6.8 años, 30 de 67 eran primigestas, 12 tuvieron el antecedente de colestasis intrahepática en el embarazo previo y 7 de óbito. El inicio de la enfermedad fue en el tercer trimestre en 41 de 67 pacientes. En los estudios de bioquímica 32 de 67 tuvieron valores de ácidos biliares entre 10 y 39 μM/L; 12 de las 67: 40-99 μM/L y 23 más de 100 (μM/L). Se administró tratamiento con ácido ursodesoxicólico a 63 de 67 y ante la falta de respuesta se agregó rifampicina. El promedio de semanas de gestación fue 35.6 ± 2.0 semanas con peso promedio de 2397 ± 572 g. Se encontró líquido amniótico con meconio en 10 neonatos y restricción del crecimiento en 20 de 67; se registraron 2 óbitos. CONCLUSIONES: Este es el primer estudio efectuado en México que describe la incidencia de la enfermedad y se utiliza la determinación de los ácidos biliares para establecer el diagnóstico. Los desenlaces perinatales coinciden con lo reportado en la bibliografía.

Abstract OBJECTIVE: To describe the care, treatment, perinatal outcomes and complications associated with intrahepatic cholestasis of pregnancy. MATERIALS AND METHODS: A retrospective and observational case series study of pregnant patients with a diagnosis of intrahepatic cholestasis seen at the National Institute of Perinatology between January 2016 and December 2020. Obstetric characteristics, demographic, clinical, biochemical and treatment data, pregnancy termination and perinatal outcomes were evaluated. RESULTS: Sixty-seven cases of intrahepatic cholestasis were analyzed, yielding an incidence of 0.57%. The mean age of the patients was 29.0 ± 6.8 years, 30 of 67 were primigravidases, 12 had a history of intrahepatic cholestasis in the previous pregnancy and 7 had an abortion. The onset of the disease was in the third trimester in 41 of 67 patients. In biochemistry studies 32 of 67 had bile acid values between 10 and 39 μM/L; 12 of 67: 40-99 μM/L and 23 more than 100 (μM/L). Treatment with ursodeoxycholic acid was administered to 63 of 67 and rifampicin to 4 patients. The mean number of weeks of gestation was 35.6 ± 2.0 weeks with a mean weight of 2397 ± 572 g. Amniotic fluid with meconium was found in 10 neonates and growth restriction in 20 of 67; there were 2 recorded abortions. CONCLUSIONS: This is the first study carried out in Mexico in which the incidence of the disease is described, and the determination of bile acids is used to establish the diagnosis. Perinatal outcomes coincide with those reported in the literature.

Carotid artery stenting has similar outcomes in men and women / Implante de stent na artéria carótida tem desfechos semelhantes em homens e mulheres

Abstract Background The aim of carotid interventions is to prevent cerebrovascular events. Endovascular treatment (carotid-artery-stenting/CAS) has become established as an alternative to open surgery in some cases. Historically, female sex has been considered as a perioperative risk factor, however, there are few studies regarding this hypothesis when it comes to CAS. Objectives To analyze the CAS results in our center adjusted by sex. Methods A retrospective cohort study was designed, including patients with carotid atheromatosis operated at a single center from January 2016 to June 2019. Our objective was to compare cardiovascular risk, including myocardial infarction, stroke, and mortality, by sex. Follow-up rates of stent patency, restenosis, stroke, myocardial infarction, and death were reported. Results 71 interventions were performed in 50 men (70.42%) and 21 women (29.57%). Mean age was 70.50 ± 10.72 years for men and 73.62 ± 11.78 years for women. Cardiovascular risk factors did not differ significantly between sexes. Mean follow-up was 11.28 ± 11.28 months. There were no significant differences in neurological events during follow-up. No adverse cardiological events were detected at any time. Regarding the mortality rate, during medium-term follow up there were 2 neurological related deaths with no significant differences between sexes (p=0.8432). Neither sex had higher rated of restenosis during long term follow-up (5.63% vs. 1.41%, p = 0.9693) or reoperation (1.41% vs. 1.41%, p = 0.4971). All procedures remained patent (<50% restenosis). Conclusions Despite the limitations of our study, CAS is a therapeutic option that is as effective and safe in women as in men. No sex differences were observed.

Resumo Contexto As intervenções carotídeas visam prevenir eventos cerebrovasculares. O tratamento endovascular (implante de stent na artéria carótida) se estabeleceu como uma alternativa à cirurgia aberta em alguns casos. Historicamente, o sexo feminino é considerado um fator de risco perioperatório, mas há poucos estudos abordando essa hipótese em casos de stent de carótida. Objetivos Analisar os resultados do CAS em nosso centro ajustados por sexo. Métodos Este estudo de coorte retrospectivo incluiu pacientes com ateromatose carotídea operados em um centro de janeiro de 2016 a junho de 2019. Nosso objetivo foi comparar o risco cardiovascular, incluindo infarto do miocárdio, acidente vascular cerebral e mortalidade, de acordo com o sexo. No seguimento, foram descritos patência do stent, reestenose, acidente vascular cerebral, infarto do miocárdio e morte. Resultados Setenta e uma intervenções foram realizadas: 50 homens (70,42%) e 21 mulheres (29,57%). A média de idade foi de 70,50 ± 10,72 anos nos homens e 73,62 ± 11,78 anos nas mulheres. Os fatores de risco cardiovascular não diferiram significativamente entre os sexos. A média de seguimento foi de 11,28 ± 11,28 meses. Durante o seguimento, não houve diferenças significativas nos eventos neurológicos. Nenhum evento cardiológico adverso foi detectado. Quanto à taxa de mortalidade, durante o seguimento de médio prazo ocorreram 2 óbitos neurológicos sem diferenças significativas entre os sexos (p = 0,8432). Não foi observada maior taxa de reestenose no seguimento de longo prazo (5,63% vs. 1,41%, p = 0,9693) ou de reoperação (1,41% vs. 1,41%, p = 0,4971) ao comparar os dois sexos. Todos os procedimentos permaneceram pérvios (< 50% de reestenose). Conclusões Apesar das limitações deste estudo, o stent de carótida em mulheres é uma opção terapêutica tão eficaz e segura quanto em homens. Nenhuma diferença foi observada entre os sexos.