Selecting postoperative adjuvant systemic therapy for early-stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays.

Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

Genomic ancestry and cancer among Latin Americans.

Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

Cross-cultural validation into Portuguese of a questionnaire to assess computer vision syndrome in workers exposed to digital devices / Validação intercultural em português de um questionário para avaliar a síndrome visual do computador em trabalhadores expostos a dispositivos digitais

ABSTRACT Purpose: As digital devices are increasingly used at work, valid and reliable tools are needed to assess their effect on visual health. This study aimed to translate, cross-culturally adapt, and validate the Computer Vision Syndrome Questionnaire (CVS-Q©) into Portuguese. Methods: A 5-phase process was followed: direct translation, synthesis of translation, back-translation, consolidation by an expert committee, and pretest. To run the pretest, a cross-sectional pilot study was conducted with 26 participants who completed the prefinal Portuguese version of the CVS-Q© and were asked about difficulties, comprehensibility, and suggestions to improve the questionnaire. To evaluate the reliability and validity of the Portuguese version of the CVS-Q©, a cross-sectional validation study was performed in a different sample (280 workers). Results: In the pretest, 96.2% had no difficulty in completing it, and 84.0% valued it as clear and understandable. CVS-Q© in Portuguese (Questionário da Síndrome Visual do Computador, CVS-Q PT©) was then obtained. Validation revealed the scale's good internal consistency (Cronbach's alpha=0.793), good temporal stability (intraclass correlation coefficient=0.847; 95% CI 0.764-0.902, kappa=0.839), adequate sensitivity and specificity (78.5% and 70.7%, respectively), good discriminant capacity (area under the curve=0.832; 95% CI 0.784-0.879), and adequate convergent validity with the ocular surface disease index (Spearman correlation coefficient=0.728, p<0.001). The factor analysis provided a single factor accounting for 37.7% of the explained common variance. A worker who scored ≥7 points would have computer vision syndrome. Conclusions: CVS-Q PT© can be considered an intuitive and easy-to-understand tool with good psychometric properties to measure computer vision syndrome in Portuguese workers exposed to digital devices. This questionnaire will assist in making decisions on preventive measures, interventions, and treatment and comparing exposed populations in different Portuguese-speaking countries.

RESUMO Objetivos: À medida que a utilização de equipamentos digitais no emprego aumenta, a avaliação do seu efeito na saúde visual necessita de ferramentas válidas e robustas. Este estudo teve como objetivo traduzir, adaptar culturalmente e validar para português o Questionário da Síndrome Visual do Computador (CVS-Q©). Métodos: O procedimento foi realizado em 5 fases: tradução direta, síntese da tradução, tradução inversa, consolidação por um painel de especialistas, e pré-teste. Para fazer o pré-teste foi realizado um estudo piloto transversal aplicado a uma amostra de 26 participantes que completaram a versão pré-final da versão portuguesa do CVS-Q©, questionando por dificuldades, compreensão e sugestões de melhoria do questionário. Para avaliar a confiança e validade da versão portuguesa do CVS-Q© foi realizado um estudo transversal de validação em uma amostra diferente (280 funcionários). Resultados: No préteste, 96.2% dos participantes não apresentaram dificuldades no preenchimento do questionário, enquanto 84.0% indicaram que era claro e compreensível. Obteve-se, então, o CVS-Q© em português (Questionário da Síndrome Visual do Computador, CVS-Q PT©). A sua validação revelou uma boa consistência interna da sua escala (Cronbach's alpha=0.793), boa estabilidade tem poral (coeficiente de correlação interclasse=0.847; 95% CI 0.764-0.902, kappa=0.839), sensibilidades e especificidades adequadas (78.5% e 70.7%, respetivamente), boa capacidade de discriminação (área abaixo da curva=0.832; 95% CI 0.784-0.879), e uma adequada validade da convergência com o índice de doença da superfície ocular (ocular surface disease index - OSDI; coeficiente de correlação de Spearman=0.728, p<0.001). A análise fatorial revelou um único fator responsável por explicar a variância comum em 37.7%. Um funcionário com uma pontuação ≥7 pontos sofria de síndrome visual do computador. Conclusão: O CVS-Q PT© pode ser considerada uma ferramenta intuitiva, de fácil interpretação e com boas pro priedades psicométricas para avaliar a síndrome visual do computador em funcionários portugueses expostos a ecrãs digitais. Este questionário facilitará as decisões sobre medidas preventivas, intervenções e tratamento, e a comparação entre as populações expostas em diferentes países de língua portuguesa.

Expanded Access Study of Palbociclib Plus Letrozole for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer in Latin America for Whom Letrozole Therapy is Deemed Appropriate.

BACKGROUND AND OBJECTIVES: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor that is approved in the United States for the treatment of hormone receptor‒positive (HR+)/human epidermal growth factor receptor‒2 negative (HER2-) advanced breast cancer (ABC). The objectives of this expanded access trial were to provide palbociclib in combination with letrozole to patients with HR+/HER2- ABC in Argentina, Brazil, Colombia, and Mexico who were candidates for letrozole therapy before commercial availability of palbociclib, and to evaluate the safety and tolerability of palbociclib plus letrozole. PATIENTS AND METHODS: Postmenopausal women aged ≥ 18 years with HR+/HER2- ABC were eligible to participate in this study. Patients received palbociclib 125 mg once daily (3/1 schedule) and letrozole 2.5 mg once daily (continuous schedule). Safety, objective response rate (ORR), and duration of treatment were evaluated. RESULTS: A total of 130 patients were treated with palbociclib plus letrozole (Argentina, n = 33; Brazil, n = 35; Colombia, n = 28; Mexico, n = 34). The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (70.0%), leukopenia (34.6%), anemia (33.8%), decreased neutrophil count (27.7%), and thrombocytopenia (24.6%); 22.3% of patients required a palbociclib dose reduction due to adverse events (AEs). Serious AEs were reported in 32 patients (24.6%). The ORR was 24.8% (95% confidence interval 17.6‒33.2), and the median duration of treatment was 10.6 months (range 0.1‒29.3). CONCLUSION: Palbociclib in combination with letrozole was generally well tolerated with a clinically manageable safety profile; the observed ORR supported treatment benefit in Latin American women with HR+/HER2- ABC. TRIAL REGISTRY: ClinicalTrials.gov, NCT02600923.

This study was done to learn more about the safety of 2 medicines together for women with advanced breast cancer after menopause. All 130 women in the study had the most common kind of breast cancer and were from Argentina, Brazil, Colombia, and Mexico. Everyone took 2 oral medicines called palbociclib and letrozole during the study. The researchers looked for any side effects experienced by the women while taking these medicines together. Another goal of the study was to see how well the treatment worked. Blood tests showed 70.0% of women had a side effect where they had a lower number of a type of white blood cell called a neutrophil. In total, 34.6% of women had low levels of another white blood cell called a leukocyte. These blood test results can mean a person is more likely to get infections. Serious side effects were experienced by 24.6% of the women, which meant these were life-threatening, caused lasting problems, or they needed hospital care. To cope with their side effects, 22.3% of the women switched to a lower palbociclib dose; 24.8% of the women had an overall response, which meant they either had a decrease in their tumor size or all cancer signs disappeared from their body. The most common length of time in the study was 10.6 months and the longest time was 29.3 months. The results of this study support using palbociclib plus letrozole to treat women who live in Latin America with advanced breast cancer after menopause.

Reflexiones de las 4 funciones de enfermería e impactos en América Latina / Reflections on the 4 nursing functions and impacts in Latin America / Reflexões sobre as 4 funções e impactos da enfermagem na América Latina

La enfermería reconocida como disciplina profesional cuenta con conocimientos dirigidos al cuidado de la vida humana, su desarrollo la ha diferenciado de otras disciplinas dándole visibilidad particular desde cuatro funciones: gestión, enseñanza, investigación y atención clínica. Para lo cual se generó una reflexión sobre los impactos positivos y negativos del evolucionar de enfermería en América Latina ante estas funciones, desde la gestión se evidencia avances importantes desde el liderazgo gremial y organizacional, pero retrocesos en el escalamiento político, e institucional. Existe brecha de la formación profesional en comparación a otras regiones, aun así, el crecimiento de programas educativos ha dado la posibilidad de la profesionalización, pero debate el reto de la calidad, la disparidad formativa y la oferta centrada en el paradigma clínico. En el campo investigativo se resalta la creación de programas doctorales y post graduales que amplían la generación de conocimiento, pero también se evidencian barreras en la transferencia y visibilidad colectiva del conocimiento. En el área clínica espacio con mayor abordaje de las acciones formativas y laborales del profesional, cuenta con grandes retos en su crecimiento, organización, escalamiento, seguridad y precariedad laboral. En esa perspectiva la comunidad U-Nursing LatAm se ha integrado para aportar a la región en estos retos. Finalmente se concluye que la mayoría de los desafíos son relacionados con las habilidades sociales y blandas que deben potencializarse en el plano personal y colectivo. Todas las situaciones requieren tener una valoración directa de las posibilidades de fortalecer y mejorar la enfermería desde cada país de la región, teniendo en cuenta las cuatro funciones.

Circulating MicroRNAs as a Tool for Diagnosis of Liver Disease Progression in People Living with HIV-1.

MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding specific cell mRNA targets, preventing their translation. miRNAs are implicated in the regulation of important physiological and pathological pathways. Liver disease, including injury, fibrosis, metabolism dysregulation, and tumor development disrupts liver-associated miRNAs. In addition to their effect in the originating tissue, miRNAs can also circulate in body fluids. miRNA release is an important form of intercellular communication that plays a role in the physiological and pathological processes underlying multiple diseases. Circulating plasma levels of miRNAs have been identified as potential disease biomarkers. One of the main challenges clinics face is the lack of available noninvasive biomarkers for diagnosing and predicting the different stages of liver disease (e.g., nonalcoholic fatty liver disease and nonalcoholic steatohepatitis), particularly among individuals infected with human immunodeficiency virus type 1 (HIV-1). Liver disease is a leading cause of death unrelated to acquired immunodeficiency syndrome (AIDS) among people living with HIV-1 (PLWH). Here, we review and discuss the utility of circulating miRNAs as biomarkers for early diagnosis, prognosis, and assessment of liver disease in PLWH. Remarkably, the identification of dysregulated miRNA expression may also identify targets for new therapeutics.

Intervención educativa sobre cuidado espiritual para estudiantes de licenciatura en enfermería y obstetricia / Spiritual care educational intervention for undergraduate nursing and midwifery students

Para los estudiantes de enfermería es indispensable la formación en el cuidado espiritual para identificar y satisfacer las propias necesidades espirituales y las de las personas que cuidarán, la dimensión espiritual es inherente al ser humano, para abordarla se requieren conocimientos que lleven a la reflexión e interés en la atención desde una perspectiva integral.

For nursing students, training in spiritual care is essential to identify and satisfy their own spiritual needs and those of the people they will care for; the spiritual dimension is inherent to the human being, and to address it requires knowledge that leads to reflection and interest in care from an integral perspective.

Single nucleotide polymorphisms in PNPLA3, ADAR-1 and IFIH1 are associated with advanced liver fibrosis in patients co-infected with HIV-1//hepatitis C virus.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), insulin resistance and liver fibrosis are prevalent in individuals co-infected with HIV type 1 (HIV-1)/hepatitis C virus (HCV), even after HCV eradication. Our aim was to evaluate single nucleotide polymorphisms (SNPs) associated with advanced liver fibrosis in HIV-1/HCV co-infected patients. DESIGN/METHODS: In a cohort of 102 participants, we genotyped 16 SNPs in 10 genes previously associated with NAFLD and the innate immune response and correlated the genotypes with liver fibrosis and fat accumulation. RESULTS: Multinomial logistic regression analysis identified three metabolic parameters that were significantly associated with advanced liver fibrosis (stage F3-F4): albumin [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69-0.91, P = 0.001], percentage of visceral fat area (PVFA) (OR 1.06, 95% CI 1.01-1.12, P = 0.03) and BMI (OR 1.47, 95% CI 1.22-1.77, P < 0.0001). After adjustment for sex, albumin, PVFA and BMI, we found that three SNPs were significantly associated with advanced fibrosis, one each in PNPLA3/rs738409 (P = 0.016), ADAR-1/rs1127313 (P = 0.029) and IFIH1/rs1990760 (P = 0.033). CONCLUSION: Our results indicate that genotyping for these SNPs can be a useful predictive tool for liver fibrosis progression and liver fat accumulation in patients co-infected with HIV-1/HCV.

Optimizing treatment selection, and sequencing decisions for Management of HR-Positive, HER2-Negative advanced breast cancer - Proceedings from breast cancer expert group meeting.

PURPOSE: The therapeutic landscape of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents and their combinations with endocrine therapies. In this scenario, optimizing treatment selection and sequencing is daunting for clinicians. The purpose of this review is to provide evidence-based answers to key clinical questions on treatment selection and sequencing for the management of HR + HER2 - mBC. DESIGN: A panel of nine key opinion leaders from Argentina, Brazil, Colombia, Mexico, Moscow, Singapore, South Korea, Taiwan, and UAE convened in October 2018. They reviewed the literature and formulated answers to clinical questions on optimizing the management of HR + HER2 - mBC. RESULTS: Evidence-based answers were formulated for: (1) optimal initial treatment choice; (2) ovarian function suppression, optimal endocrine partner, and role of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (in premenopausal women); (3) better first-line standard of care than aromatase inhibitors; (4) preferred second-line treatment; (5) treatment of oligometastatic disease; (6) factors influencing first-line single-agent endocrine therapy choice; (7) influence of endocrine resistance on treatment selection; (8) optimal maintenance regimen in visceral crisis; and (9) need for a breast cancer registry for patients with HR + HER2 - mBC. The panel also proposed a treatment-sequencing algorithm for the management of HR + HER2 - mBC. CONCLUSION: The current article will serve as a comprehensive guide for optimizing the management of HR + HER2 - mBC. The proposed breast cancer registry will help identify unmet needs and develop strategic regional policies to help improve access to optimized care for HR + HER2 - mBC.

Discovery and Development of Antiviral Therapies for Chronic Hepatitis C Virus Infection.

At the beginning of this decade, an estimated 71 million people were living with chronic hepatitis C virus (HCV) infection worldwide. After the acute stage of HCV infection, 18-34% of individuals exhibit spontaneous clearance. However, the remaining 66-82% of infected individuals progress to chronic HCV infection and are at subsequent risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Chronic hepatitis C progression is generally slow during the first two decades of infection, but can be accelerated during this time in association with advancing age and cofactors, such as heavy alcohol intake and human immunodeficiency virus (HIV) co-infection. Since acute HCV infection is generally asymptomatic, HCV goes undiagnosed in a significant percentage of infected individuals. In 2014, direct-acting antiviral (DAA) therapy for chronic HCV was developed, which has increased the cure rates to nearly 100%. DAA therapy is among the best examples of success in the fight against viral infections. DAAs have transformed HCV management and have opened the door for the global eradication of HCV.

Optimizing the management of HER2-negative metastatic breast cancer in the era of PARP inhibitors-proceedings from breast cancer expert group meeting.

The therapeutic landscape of human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents such as poly-ADP ribose polymerase inhibitors (PARPi), novel chemotherapeutic agents, immunotherapy, and endocrine therapies. In this scenario, optimizing the appropriate treatment sequence is a daunting task for clinicians. To develop evidence-based answers to key clinical questions on treatment selection and appropriate treatment sequence for the management of patients with HER2- mBC in the era of PARPi, a breast cancer expert group meeting was convened. The expert panel comprised of eight key opinion leaders from Argentina, Brazil, Colombia, Egypt, Mexico, Moscow, South Korea, and the United Arab Emirates, who convened and reviewed the literature, discussed the clinical practices across the participating regions, and formulated answers to key clinical questions for optimizing the management of HER2- mBC. In this review, evidence-based answers have been provided pertaining to (I) the specific mBC population to be considered for BRCA testing, optimal time point of BRCA testing, and genetic counselling in mBC patients; (II) the role of PARPi versus platinum therapy in HER2- mBC patients in the metastatic setting; (III) sequencing treatment in metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive HER2- mBC patients, and defining the place of PARPi in the sequencing algorithms; and (IV) the need for a breast cancer registry for patients with HER2- mBC. This expert review will serve as a comprehensive guide to clinicians for optimizing BRCA testing and managing patients with BRCA mutation (BRCAm) and HER2- mBC. The data collected from the proposed HER2- mBC registry will help understand the treatment practices, identify unmet needs, and develop strategic policies regionally to help improve access to optimized care of HER2- mBC.

Importancia del control glucémico durante el perioperatorio en pacientes con diabetes mellitus / Importance of glycemic control during the perioperative period in patients with diabetes mellitus

Resumen: La diabetes mellitus se ha convertido en un problema de salud pública en el mundo, ya que su incidencia y prevalencia se ha incrementado de manera exponencial en las últimas décadas, lo que ha traído consigo un aumento en las complicaciones agudas y crónicas asociadas a su diagnóstico tardío y poco apego a su tratamiento. Los pacientes con diabetes mellitus tienen una mayor probabilidad de requerir una cirugía en comparación con la población general, quienes podrían llegar a presentar complicaciones graves asociadas al evento quirúrgico como hipertensión, cardiopatía isquémica, nefropatía y neuropatía autonómica, las cuales se deben a un incremento de la resistencia a la insulina y a la hiperglucemia. Por lo anterior, el control metabólico es pieza clave en la conducta perioperatoria del paciente con diabetes mellitus donde la participación de un equipo multidisciplinario (médico internista, cirujano y anestesiólogo) definan de manera conjunta las mejores estrategias quirúrgicas y anestésicas para un mejor desenlace previo, durante y posterior a la cirugía.

Abstract. Diabetes mellitus has become a public health problem worldwide, its incidence and prevalence have exponentially increased in recent decades, bringing with it an increase in acute and chronic complications associated with late diagnosis and failure of adherence to treatment. Patients with diabetes mellitus are more likely to require surgery compared to the general population, they may have serious complications associated with the surgical event such as hypertension, ischemic heart disease, nephropathy and autonomic neuropathy, due to an increase in insulin resistance and hyperglycemia. Therefore, metabolic control is a key element in the perioperative behavior of patients with diabetes mellitus where the joint collaboration of a multidisciplinary team (internist, surgeon and anesthesiologist) to define the best surgical and anesthetic strategies for a better outcome before, during and after surgery.

Therapy Implications of Hepatitis C Virus Genetic Diversity.

Hepatitis C virus (HCV) is an important human pathogen with a high chronicity rate. An estimated 71 million people worldwide are living with chronic hepatitis C (CHC) infection, which carries the risk of progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Similar to other RNA viruses, HCV has a high rate of genetic variability generated by its high mutation rate and the actions of evolutionary forces over time. There are two levels of HCV genetic variability: intra-host variability, characterized by the distribution of HCV mutant genomes present in an infected individual, and inter-host variability, represented by the globally circulating viruses that give rise to different HCV genotypes and subtypes. HCV genetic diversity has important implications for virus persistence, pathogenesis, immune responses, transmission, and the development of successful vaccines and antiviral strategies. Here we will discuss how HCV genetic heterogeneity impacts viral spread and therapeutic control.

Perception about barriers and facilitators of the school-based HPV vaccine program of Manizales, Colombia: A qualitative study in school-enrolled girls and their parents.

In 2012, Colombia implemented a school-based HPV vaccination program of a 3-dose series for nine year old girls. Following a mass psychogenic response after vaccination in a Colombian town, vaccination rates dropped from 80% in 2012-2013 to 5% in 2016. The study aimed to identify barriers and facilitators of HPV vaccine uptake among girls eligible for vaccination in the initial years of vaccine implementation from 2012 to 2014, and their parents. We conducted 19 individual qualitative interviews and 18 focus groups with an average of 5 girls, in Manizales, Colombia between 2016 and 2017. In total, 49 girls from six schools and 58 of their parents participated in the study. Participants had some degree of awareness about cervical cancer, especially among those of middle and upper socioeconomic level. However, the vaccine was known as a prevention measure only after pap-smears and condoms. The main facilitator for vaccine uptake for parents was the desire to prevent diseases in general and for girls, it was facilitated by receiving positive information about the vaccine. The main barriers for vaccine uptake or for three doses completion were the event in Carmen de Bolivar, fear of adverse effects and fear of needles. Girls and parents stated that they received little or no information from schools or health care services about the HPV vaccine prior to vaccination. Our results suggest that improving HPV vaccination rates in Colombia will require a comprehensive education program including mass media information about HPV vaccine.

Aspectos de seguridad en el tratamiento del dolor con analgésicos antiinflamatorios no esteroideos / Security issues in pain management with nonsteroidal anti-inflammatory drugs

Resumen Los antiinflamatorios no esteroideos (AINE) son el grupo farmacológico que más se consume globalmente con o sin prescripción médica, sobre todo para el tratamiento sintomático de diversos padecimientos que cursan con dolor agudo o crónico. La estructura química de los AINE es heterogénea, por lo que comparten efecto antipirético, antiinflamatorio y analgésico a través de su capacidad para inhibir las prostaglandinas proinflamatorias. El conocimiento de que existen múltiples variaciones en cuanto a los perfiles de riesgo que presentan los AINE obliga a individualizar su uso en función de la patología de base, las características particulares del paciente y la experiencia del médico. Los AINE se deben utilizar en ciclos cortos y con las dosis más bajas posibles, tratando de mantenerlos en un rango de eficacia clínica y vigilando en específico las complicaciones gastrointestinales, cardiovasculares, renales, hepáticas y hematológicas derivadas de los mismos. El objetivo de este trabajo es revisar los aspectos de seguridad en el tratamiento analgésico crónico con AINE.

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide, with or without medical prescription, mostly for the symptomatic treatment of a widely range of diseases characterized by acute or chronic pain. NSAIDs have a heterogenous chemical structure that gives them antipyretic, anti-inflammatory and analgesic properties through their ability to inhibit proinflammatory prostaglandins. The variability in risk profiles among NSAIDs forces the medical community to individualize their use based on the personal characteristics of the patients as well as the expertise of the physician. NSAIDs should be used for short cycles of treatment with the lowest doses possible, using them in a range of clinical efficacy, with specific monitoring of gastrointestinal, cardiovascular, renal hepatic and hematologic complications. The objective of this work is to review the safety aspects of the treatment with NSAIDs in chronic analgesic management.

First survey on zoonotic helminthosis in urban brown rats (Rattus norvegicus) in Spain and associated public health considerations.

The brown rat, Rattus norvegicus, with a worldwide distribution, is the most commensal species among synanthropic rodents, since its main habitat, in urban as well as in rural areas, is always linked to humans. Therefore, people living in close proximity to rodent populations can be exposed to infection. Whereas bacteria and viruses are the best known rat-associated zoonoses in urban environments, the role of brown rats as reservoirs for helminth parasites and the associated risk for humans are less well known. Specifically, this role has not been analyzed in Spain to date. A total of 100 R. norvegicus trapped in the sewage system (n = 85), and parks (n = 15) of Barcelona was examined. The overall prevalence of helminth infection was 85%. The helminths found were Hymenolepis nana (17%), H. diminuta (33%) (Cestoda), Calodium hepaticum (17%), Eucoleus gastricus (28%), Aonchotheca annulosa (12%), Trichosomoides crassicauda (7%), Nippostrongylus brasiliensis (46%), Heterakis spumosa (62%), Gongylonema neoplasticum (20%) (Nematoda) and Moniliformis moniliformis (6%) (Acanthocephala). Five of the ten helminth species are considered zoonotic parasites, with rats acting as reservoirs for human infection, i.e. H. nana, H. diminuta, C. hepaticum, G. neoplasticum and M. moniliformis. G. neoplasticum and M. moniliformis are reported for the first time in urban rats in Europe. H. nana, H. diminuta and C. hepaticum are the most widespread species in European cities. For H. nana and C. hepaticum, rats act as effective spreaders of the human infective stage (eggs). For H. diminuta, G. neoplasticum and M. moniliformis, rats act as indirect reservoirs of the zoonoses since the eggs shed by the rats are infective for their insect intermediate hosts only. Medical practitioners need to be made aware of the range of parasites carried by rats, as there is a realistic likelihood that ill health currently caused by rat infestations may be misdiagnosed.

HIV-1 Protease Evolvability Is Affected by Synonymous Nucleotide Recoding.

One unexplored aspect of HIV-1 genetic architecture is how codon choice influences population diversity and evolvability. Here we compared the levels of development of HIV-1 resistance to protease inhibitors (PIs) between wild-type (WT) virus and a synthetic virus (MAX) carrying a codon-pair-reengineered protease sequence including 38 (13%) synonymous mutations. The WT and MAX viruses showed indistinguishable replication in MT-4 cells or peripheral blood mononuclear cells (PBMCs). Both viruses were subjected to serial passages in MT-4 cells, with selective pressure from the PIs atazanavir (ATV) and darunavir (DRV). After 32 successive passages, both the WT and MAX viruses developed phenotypic resistance to PIs (50% inhibitory concentrations [IC50s] of 14.6 ± 5.3 and 21.2 ± 9 nM, respectively, for ATV and 5.9 ± 1.0 and 9.3 ± 1.9, respectively, for DRV). Ultradeep sequence clonal analysis revealed that both viruses harbored previously described mutations conferring resistance to ATV and DRV. However, the WT and MAX virus proteases showed different resistance variant repertoires, with the G16E and V77I substitutions observed only in the WT and the L33F, S37P, G48L, Q58E/K, and L89I substitutions detected only in the MAX virus. Remarkably, the G48L and L89I substitutions are rarely found in vivo in PI-treated patients. The MAX virus showed significantly higher nucleotide and amino acid diversity of the propagated viruses with and without PIs (P < 0.0001), suggesting a higher selective pressure for change in this recoded virus. Our results indicate that the HIV-1 protease position in sequence space delineates the evolution of its mutant spectrum. Nevertheless, the investigated synonymously recoded variant showed mutational robustness and evolvability similar to those of the WT virus.IMPORTANCE Large-scale synonymous recoding of virus genomes is a new tool for exploring various aspects of virus biology. Synonymous virus genome recoding can be used to investigate how a virus's position in sequence space defines its mutant spectrum, evolutionary trajectory, and pathogenesis. In this study, we evaluated how synonymous recoding of the human immunodeficiency virus type 1 (HIV-1) protease affects the development of protease inhibitor (PI) resistance. HIV-1 protease is a main target of current antiretroviral therapies. Our present results demonstrate that the wild-type (WT) virus and a virus with recoded protease exhibited different patterns of resistance mutations after PI treatment. Nevertheless, the developed PI resistance phenotypes were indistinguishable between the recoded virus and the WT virus, suggesting that the HIV-1 strain with synonymously recoded protease and the WT virus are equally robust and evolvable.

ADAR1 affects HCV infection by modulating innate immune response.

The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I. Here, we describe ADAR1 role as a regulator of innate and antiviral immune function in HCV infection, both in vitro and in patients. Polymorphisms within ADAR1 gene were found significantly associated to poor clinical outcome to HCV therapy and advanced liver fibrosis in a cohort of HCV and HIV-1 coinfected patients. Moreover, ADAR1 knockdown in primary macrophages and Huh7 hepatoma cells enhanced IFN and IFN stimulated gene expression and increased HCV replication in vitro. Overall, our results demonstrate that ADAR1 regulates innate immune signaling and is an important contributor to the outcome of the HCV virus-host interaction. ADAR1 is a potential target to boost antiviral immune response in HCV infection.

Efficacy and safety of Levetiracetam vs. other antiepileptic drugs in Hispanic patients with glioblastoma.

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.