A side-by-side comparison of different capacitation media in developing mouse sperm fertilizing ability.

To acquire the ability to fertilize the egg, mammalian spermatozoa must undergo a series of changes occurring within the highly synchronized and specialized environment of the female reproductive tract, collectively known as capacitation. In an attempt to replicate this process in vitro, various culture media for mouse sperm were formulated over the past decades, sharing a similar overall composition but differing mainly in ion concentrations and metabolic substrates. The widespread use of the different media to study the mechanisms of capacitation might hinder a comprehensive understanding of this process, as the medium could become a confounding variable in the analysis. In this context, the present side-by-side study compares the influence of four commonly used culture media (FD, HTF and two TYH versions) on mouse sperm capacitation. We evaluated the induction of protein kinase A phosphorylation pathway, motility, hyperactivation and acrosome reaction. Additionally, in vitro fertilization and embryo development were also assessed. By analyzing these outcomes in two mouse colonies with different reproductive performance, our study provides critical insights to improve the global understanding of sperm function. The results obtained highlight the importance of considering variations in medium composition, and their potential implications for the future interpretation of results.

Impact of Lung Cancer on Health-Related Quality of Life, Financial Toxicity, and Household Economics in Patients From the Public and the Private Healthcare Sector in Argentina.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is Argentina's first cause of cancer death. Most patients have an advanced stage at diagnosis, with poor expected survival. This study aimed to characterize the health-related quality of life (HRQOL) and economic impact of patients treated in the private healthcare sector and compare it with that of the public sector. METHODS: We undertook an observational cross-sectional study that extended a previous study to a referral private center in Argentina. Outcomes included the EuroQol EQ-5D-3L (to assess HRQOL), Comprehensive Score for Financial Toxicity (financial toxicity instrument), Work Productivity and Activity Impairment - General Health (to assess productivity loss), and out-of-pocket expenses in adults diagnosed of NSCLC. RESULTS: We included 30 consecutive patients from a private healthcare center (July 2021 to March 2022), totaling 131 patients (n = 101 from previous public study). The whole sample had low quality of life and relevant economic impact. Patients in the private healthcare sector showed lower disease severity and higher educational level and household income. In addition, private healthcare system patients showed higher utility (0.77 vs 0.73; P < .05) and lower impairment of daily activities (41% vs 59%; P = .01). Private health system patients also showed lower financial toxicity as measured by the Comprehensive Score for Financial Toxicity score (23.9 vs 20.14; P < .05) but showed no differences when financial toxicity was assessed as a dichotomic variable. CONCLUSIONS: Although patients with NSCLC treated in a private healthcare center in Argentina showed a relevant HRQOL and economic impact, this impact was smaller than the one observed in publicly funded hospitals.

Ether lipids and a peroxisomal riddle in sperm.

Sperm are terminally differentiated cells that lack most of the membranous organelles, resulting in a high abundance of ether glycerolipids found across different species. Ether lipids include plasmalogens, platelet activating factor, GPI-anchors and seminolipid. These lipids play important roles in sperm function and performance, and thus are of special interest as potential fertility markers and therapeutic targets. In the present article, we first review the existing knowledge on the relevance of the different types of ether lipids for sperm production, maturation and function. To further understand ether-lipid metabolism in sperm, we then query available proteomic data from highly purified sperm, and produce a map of metabolic steps retained in these cells. Our analysis pinpoints the presence of a truncated ether lipid biosynthetic pathway that would be competent for the production of precursors through the initial peroxisomal core steps, but devoid of subsequent microsomal enzymes responsible for the final synthesis of all complex ether-lipids. Despite the widely accepted notion that sperm lack peroxisomes, the thorough analysis of published data conducted herein identifies nearly 70% of all known peroxisomal resident proteins as part of the sperm proteome. In view of this, we highlight open questions related to lipid metabolism and possible peroxisomal functions in sperm. We propose a repurposed role for the truncated peroxisomal ether-lipid pathway in detoxification of products from oxidative stress, which is known to critically influence sperm function. The likely presence of a peroxisomal-derived remnant compartment that could act as a sink for toxic fatty alcohols and fatty aldehydes generated by mitochondrial activity is discussed. With this perspective, our review provides a comprehensive metabolic map associated with ether-lipids and peroxisomal-related functions in sperm and offers new insights into potentially relevant antioxidant mechanisms that warrant further research.

A novel Xp11.22 duplication involving HUWE1 in a male with syndromic intellectual disability and additional neurological findings.

Sequence variants and duplications in the HECT, UBA and WWE domain -containing 1 (HUWE1) E3 ubiquitin ligase gene have been associated with X-linked mild to severe intellectual disability (ID), but a solid phenotype pattern among the affected males is still remaining to be established. Here, we report a male patient with sporadic, severe and syndromic ID, carrying a novel and unique 842 kb duplication at Xp11.22, including the dosage-sensitive HUWE1 gene and other fifteen curated RefSeq genes. Expression analysis in the patient and his female relatives confirmed increased HUWE1 mRNA levels, with different X-chromosome inactivation patterns among the female carriers. Our patient differs from those previously described by us and others as he presents encephalomalacia at brain Magnetic Resonance Imaging and diffuse bilaterally and synchronous intercritical irritating paroxysms at electroencephalogram. Overall, our clinical, molecular, and neurological findings sum up the previous data, expanding the phenotype spectrum in Xp11.22 copy gains involving the whole HUWE1 gene in both males and female carriers in light of X-chromosome inactivation patterns.

Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation.

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts' integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice's hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by "rejuvenating" the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.

European clinical practice guidelines on the use of chemotherapy for advanced oesophageal and gastric cancers: a critical review using the AGREE II and the AGREE-REX instruments.

PURPOSE: To assess the methodological quality of all relevant and recent European clinical practice guidelines (CPGs) for advanced oesophageal and gastric cancers, and to synthesise their recommendations on the use of chemotherapy. METHODS: We searched PubMed, EMBASE, guidelines repositories, and other sources from 2010 onwards. We appraised quality using AGREE-II and AGREE-REX. RESULTS: 11 CPGs were included (five high, five low, and one moderate quality). Most guidelines showed deficiencies in the domain "applicability", with only three scoring above 60%. Nine did not report having sought the views and preferences of the target population. The lowest scores for AGREE-REX were item Values and Preferences of Target Users (1.6; SD 1.3), and item Values and Preferences of Policy/Decision-Makers (1.8; SD 1.7). The domain Clinical Applicability got the highest score and the domain Implementability got the lowest. CONCLUSIONS: An urgent area of research is how to develop credible and implementable recommendations on the clinical use of CT for advanced oesophageal and gastric cancer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021236753).

Critical Care in SARS-CoV-2 Infected Pregnant Women: A Prospective Multicenter Study.

Evidence suggests that pregnant women are at a higher risk of complications compared to the general population when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the reasons that lead them to need intensive care are not clear. This is a prospective multicenter study of SARS-CoV-2 positive pregnant women, registered by the Spanish Obstetric Emergency Group, with the objective to define the characteristics of the mothers who were admitted to the Intensive Care Unit (ICU) and to investigate the causes and risk factors for ICU admission. A total of 1347 infected pregnant women were registered and analyzed, of whom, 35 (2.6%) were admitted to the ICU. No differences in maternal characteristics or comorbidities were observed between ICU and non-ICU patients, except for in vitro fertilization and multiple pregnancies. The main causes of admission to the ICU were non-obstetric causes (worsening of the maternal condition and respiratory failure due to SARS-CoV-2 pneumonia, 40%) and a combination of coronavirus disease 2019 (COVID-19) symptoms and obstetrical complications (31.4%). The multivariable logistic analysis confirmed a higher risk of ICU admission when pre-eclampsia or hemorrhagic events coexist with pneumonia. The incidence of thromboembolic events and disseminated intravascular coagulation were also significantly higher among patients admitted to the ICU. Therefore, surveillance and rapid intervention should be intensified in SARS-CoV-2 infected pregnant women with the mentioned risk factors and complications. Emphasis should always be placed on anticoagulant therapy in these patients due to the increased thromboembolic risk, C-section surgery and immobilization in the ICU.

Implementing Strategies at the Workplace Level to Increase Colorectal Cancer Screening Uptake in Argentina: A Controlled Interrupted Time-series Study.

Colorectal cancer is the third most common neoplasm. The immunochemical fecal occult blood test (iFOBT) is recommended for screening. The worksite setting has great potential to deliver preventive interventions. We aimed to design and evaluate the feasibility and potential impact of a multicomponent strategy in a workplace [Internal Revenue Agency of the Province of Buenos Aires (ARBA from its acronym in Spanish "Agencia de Recaudación de Buenos Aires") in Argentina].We used a quasi-experimental research design, a controlled interrupted time-series (ITS). The study involved: (i) a preintervention period (July 2015-September 2018); and (ii) an intervention period (October 2018-February 2019). We used semi-structured interviews and focus groups to design the intervention and to ensure feasibility and implementability. We fitted segmented linear regression models to evaluate changes in the monthly rates per 10,000 tests done in ARBA employees and controlling for the proportion of tests done in non-ARBA workers. A total of 1,552 ARBA employees aged 50 or more participated. Overall, iFOBT mean uptake rates were 16 times higher in the intervened during the five-month intervention period, remaining statistically significant after adjusting by the proportion of tests done in the control group (P < 0.001). The effect was higher in women aged 50 to 59 years. Activities were suspended due to the COVID-19 pandemic. A multifaceted workplace-based intervention proved to be feasible and acceptable to increase the uptake of colorectal cancer screening in employees of Argentina. Achieving high implementation rates requires building a healthy relationship with the partner organization, adding their values and views, and establishing agreed-upon mechanisms. PREVENTION RELEVANCE: Employee-facing multifaceted worksite cancer screening interventions are a valuable means to increase knowledge and utilization of workers. The controlled ITS showed that colorectal cancer screening mean uptake rates were 16 times higher in the intervened versus the control population during the intervention period, particularly among women aged 50 to 75.

[Formative research for the design and implementation of a strategy to increase colorectal cancer screening in the workplace in Argentina]. / Investigación formativa para el diseño e implementación de una estrategia para aumentar el rastreo de cáncer colorrectal en el ámbito laboral en Argentina.

The workplace has great potential to disseminate information and implement health promotion activities such as cancer prevention and early detection. Due to the challenges of deploying health interventions in this setting, formative studies are needed to adjust the design and implementation of successful strategies. To inform the intervention's design and implementation and improve the adherence rate to screening with fecal occult blood test in a workplace in Argentina, a formative study was conducted to identify potential barriers and facilitators. The formative study adopted a qualitative methodological design. Interviews were held with 10 individuals in charge of key areas in the institution where the main study was conducted, besides 8 focus groups with workers over 50 years of age. Challenges were identified at the institutional level for the intervention's implementation, such as workers' geographic dispersion and the complexity of the institution's flowchart, as well as at the population level, such as low knowledge about colorectal cancer and diagnostic tests and low risk perception. The facilitators featured the intervention's acceptability and the availability of human and material resources to proceed with the intervention, such as institutional communications channels for disseminating the information and logistics for distribution of diagnostic kits. The formative study allowed identifying resources and potential barriers that informed the intervention's design and implementation.

El ámbito laboral tiene un gran potencial para difundir información e implementar actividades de promoción de la salud, como la prevención y detección temprana del cáncer. Debido al desafío de implementar intervenciones sanitarias en este ámbito, se necesitan investigaciones formativas para adecuar el diseño y la implementación de las estrategias para que sean exitosas. Con el objetivo de informar el diseño e implementación de la intervención, para mejorar la tasa de adherencia al tamizaje con el test de sangre oculta en materia fecal, en un ámbito laboral en Argentina, se realizó una investigación formativa para identificar potenciales barreras y facilitadores. La investigación formativa siguió un diseño metodológico cualitativo. Se realizaron entrevistas con 10 responsables de áreas clave de la institución en que se desarrolló el estudio y 8 grupos focales con trabajadores mayores de 50 años. Se identificaron desafíos para la implementación de la intervención en el nivel institucional, como la dispersión geográfica de los trabajadores y la complejidad del organigrama de la institución, y en el nivel de la población objetivo, como el bajo conocimiento del cáncer colorrectal y de los test diagnósticos, así como la baja percepción de riesgo. Entre los facilitadores se destacaron la aceptabilidad de la intervención, además de la disponibilidad de recursos humanos y materiales para llevar adelante la intervención, como canales de comunicación institucional para la diseminación de información, así como la logística para la distribución de kits diagnósticos. La investigación formativa permitió relevar recursos e identificar potenciales barreras que informaron el diseño y la implementación de la intervención.

O local de trabalho possui grande potencial para divulgar informação e implementar atividades de promoção da saúde, como a prevenção e detecção precoce do câncer. Frente ao desafio de implementar ações sanitárias naquele ambiente, são necessárias pesquisas formativas para adequar a estruturação e a implementação das estratégias para que sejam bem-sucedidas. Com o objetivo de subsidiar a concepção e a implementação da ação, visando melhorar a taxa de aderência ao screening com o teste de sangue oculto nas fezes no ambiente de trabalho na Argentina, foi desenvolvida uma pesquisa formativa para identificar potenciais barreiras e facilitadores. A pesquisa formativa seguiu um formato metodológico qualitativo. Foram realizadas entrevistas com 10 gerentes de áreas chaves da entidade onde foi desenvolvido o estudo e 8 grupos focais, com trabalhadores acima de 50 anos de idade. Foram identificados alguns desafios para a implementação de uma ação em nível institucional, como a dispersão geográfica dos trabalhadores e a complexidade do organograma da entidade, e em termos de população objetiva, como o baixo conhecimento a respeito do câncer colorretal e dos testes diagnósticos, além da baixa percepção de risco. Entre os facilitadores, destacaram-se a aceitabilidade da ação e a disponibilidade de recursos humanos e materiais para levar a cabo a ação, como canais de comunicação institucional, para a divulgação da informação e a logística, para a distribuição dos kits diagnósticos. A pesquisa formativa revelou recursos e identificou potenciais barreiras, ajudando na estruturação e implementação da ação.

Surgical resection versus stereotactic radiosurgery on local recurrence and survival for patients with a single brain metastasis: a systematic review and meta-analysis.

BACKGROUND: Brain metastases (BM) are the most frequent intracranial tumours in adults. In patients with solitary BM, surgical resection (SR) or stereotactic radiosurgery (SRS) is performed. There is limited evidence comparing one treatment over the other. OBJECTIVE: To compare SR versus SRS on patients with solitary BMs, regarding local recurrence (LR) and overall survival (OS) conducting a systematic review and meta-analysis. METHODS: Systematic review of literature following PRISMA guidelines, using the databases of Medline, Clinicaltrials.gov, Embase, Web of Science, Sciencedirect, CINAHL, Wiley Online Library, Springerlink and LILACS. Following study selection based on inclusion and exclusion criteria, data extraction and a critical analysis of the literature was performed according to the GRADE scale. For quantitative analysis, a random effects model was used. Data were synthetized and evaluated on a forest plot and funnel plot. RESULTS: Two randomized clinical trials, four cohort studies and one case-control studies met our inclusion criteria for the qualitative analysis. None was excluded subsequently. Overall, 614 patients with single metastasis were included. Studies had high heterogeneity. Multiple significant variables affecting the outcome were signalized. Meta-analysis showed no significant differences for survival (HR, 1.10; 95% CI, 0.75-1.45) or LR (HR, 0.81; 95% CI, 0.42-1.20). CONCLUSIONS: According to current evidence, in patients with a single small metastasis there is no statistically significant difference in OS or LR among the chosen techniques (SR or SRS). Multiple significant co-variables may affect both outcomes. Different outcomes better than OS should be evaluated in further randomized studies.

Direct Medical Costs, Productivity Loss Costs and Out-Of-Pocket Expenditures in Women with Breast Cancer in Latin America and the Caribbean: A Systematic Review.

OBJECTIVE: Our objective was to conduct a systematic review of the literature to identify, categorise, assess, and synthesise the healthcare costs of patients with breast cancer (BC) and their relatives in Latin America and the Caribbean (LAC). METHODS: In December 2020, we searched for published data in PubMed, LILACS, EMBASE, and other sources, including the grey literature. Studies were eligible if they were conducted in LAC and reported the direct medical costs, productivity loss costs, out-of-pocket expenditure, and other costs to patients with BC and their relatives. No restrictions were imposed on the type of BC population (metastatic BC or human epidermal growth factor receptor 2-positive/negative BC, among others). We summarised the characteristics and methodological approach of each study and the healthcare costs by cancer stage. We also developed and applied an original ad hoc instrument to assess the quality of the cost estimation studies. RESULTS: We identified 2725 references and 63 included studies. In total, 79.3% of the studies solely reported direct medical costs and five solely reported costs to patients and their relatives. Only 14.3% of the studies were classified as of high quality. The pooled weighted average direct medical cost per patient-year (year 2020 international dollars [I$]) by BC stage was I$13,179 for stage I, I$15,556 for stage II, I$23,444 for stage III, and I$28,910 for stage IV. CONCLUSION: This review provides the first synthesis of BC costs in LAC. Our findings show few high-quality costing studies in BC and a gap in the literature measuring costs to patients and their relatives. The high costs associated with the advanced stages of BC call into question the affordability of treatments and their accessibility for patients. Registered in PROSPERO (CRD42018106835).

Health-Related Quality of Life in Patients with Breast Cancer in Latin America and the Caribbean: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Breast cancer (BC) is the most common cancer in women. It imposes a huge disease burden and a significant impact on health-related quality of life (HRQoL). Our study focused on HRQoL of patients with BC in Latin America and the Caribbean (LAC). We conducted a systematic review to identify relevant articles published between 2008 and August 2018. We conducted several meta-analyses and subgroup analyses by country, disease stage, and instrument used (Prospective Register Of Systematic Reviews registration number: CRD42018106835). RESULTS: From 2,265 initial references, we finally included 75 articles (8,806 participants) that assessed HRQoL. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 and B23 modules (34 studies; 8 countries; 4,866 participants) were the most used instruments, followed by the Short Form 36-item, the abbreviated version of the World Health Organization Quality of Life instrument, and the Functional Assessment of Cancer Therapy - Breast instrument. Only four studies reported specific HRQoL data of patients with metastatic disease. Half the studies were rated as having moderate quality (38/75), and 38% (29/75) as high quality. We identified substantial heterogeneity. As expected, the meta-analyses revealed that patients with metastatic disease reported lower HRQoL values and high symptom burden compared with patients at earlier stages. Similar results can be observed when we compared patients with early breast cancer in active treatment phases versus those in follow-up. CONCLUSION: This study provides a synthesis of breast cancer HRQoL reported in LAC and exposes existing evidence gaps. Patients with BC in active treatment or with metastatic disease had worse HRQoL compared with survivors during the follow-up period. IMPLICATIONS FOR PRACTICE: This systematic review provides an exhaustive synthesis of breast cancer health-related quality of life in women in the Latin American and Caribbean region. Patients with breast cancer in active treatment or with metastatic disease had worse health-related quality of life compared with survivors during the different follow-up periods. This study also shows important evidence and methods gaps that can help inform future research.

Intervenciones en ámbito laboral para incrementar el rastreo de cáncer colorrectal evaluación de tecnología sanitaria / Workplace interventions to increase colorectal cancer screening: health technology assessment

INTRODUCCIÓN: El cáncer de colon y recto (CCR) es la tercera neoplasia más frecuente y la cuarta causa de muerte por cáncer a nivel mundial. En Argentina es la segunda neoplasia maligna más frecuente, con el 11,8% de los casos. El objetivo del informe fue evaluar la evidencia sobre la eficacia de intervenciones efectuadas en el ámbito laboral para incrementar el rastreo de CCR. MÉTODOS: Se realizó una búsqueda en bases de datos bibliográficas, buscadores genéricos de Internet y sitios ministeriales de salud y educación nacionales. RESULTADOS: Se incluyeron dos estudios clínicos aleatorizados (ECA) por conglomerados, un ECA, cinco estudios de implementación sin grupo control, reportes de programas y guías de prácticas clínicas de rastreo del CCR desarrollados en países de América y una guía europea. Las intervenciones en el ámbito laboral son eficaces para aumentar la tasa de rastreo. La entrega de kits para test de sangre oculta en materia fecal (TSOMF) fue la intervención más utilizada, seguida por distribución de información y sesiones educativas. Se vio mayor eficacia de las intervenciones en quienes contaban con historia familiar de CCR o recibían información sobre el riesgo individual de desarrollar la enfermedad. Los encuentros educativos en ámbitos laborales son un entorno aceptable para difundir información y distribuir kits para TSOMF. DISCUSIÓN: Un abordaje compuesto por intervenciones en el ámbito laboral podría incrementar la tasa de rastreo de CCR en la población general

Workplace interventions to increase colorectal cancer screening: health technology assessment / Intervenciones en ámbito laboral para incrementar el rastreo de cáncer colorrectal: evaluación de tecnología sanitaria

RESUMEN INTRODUCCIÓN : El cáncer de colon y recto (CCR) es la tercera neoplasia más frecuente y la cuarta causa de muerte por cáncer a nivel mundial. En Argentina es la segunda neoplasia maligna más frecuente, con el 11,8% de los casos. El objetivo del informe fue evaluar la evidencia sobre la eficacia de intervenciones efectuadas en el ámbito laboral para incrementar el rastreo de CCR. MÉTODOS : Se realizó una búsqueda en bases de datos bibliográficas, buscadores genéricos de Internet y sitios ministeriales de salud y educación nacionales. RESULTADOS : Se incluyeron dos estudios clínicos aleatorizados (ECA) por conglomerados, un ECA, cinco estudios de implementación sin grupo control, reportes de programas y guías de prácticas clínicas de rastreo del CCR desarrollados en países de América y una guía europea. Las intervenciones en el ámbito laboral son eficaces para aumentar la tasa de rastreo. La entrega de kits para test de sangre oculta en materia fecal (TSOMF) fue la intervención más utilizada, seguida por distribución de información y sesiones educativas. Se vio mayor eficacia de las intervenciones en quienes contaban con historia familiar de CCR o recibían información sobre el riesgo individual de desarrollar la enfermedad. Los encuentros educativos en ámbitos laborales son un entorno aceptable para difundir información y distribuir kits para TSOMF. DISCUSIÓN : Un abordaje compuesto por intervenciones en el ámbito laboral podría incrementar la tasa de rastreo de CCR en la población general.

ABSTRACT INTRODUCTION : Colorectal cáncer (CRC) is the thirdmost frequent neoplasm and the fourth cause of death from cáncer worldwide. In Argentina it is the second most frequent malignancy, with 11.8% of the cases. The objective of the study was to assess the evidence on the effectiveness of workplace interventions aimed at increasing the screening rate of CRC. METHODS : A search was conducted in bibliographic databases, generic Internet search engines, and national health and education ministry websites. RESULTS : Two cluster randomized clinical trials (RCTs), one RCT, five non-control group implementation studies, program reports and clinical practice guidelines for CRC screening developed in American countries as well as a European guideline were included. Workplace interventions are effective for increasing the rate of screening. The delivery of faecal occult blood test (FOBT) kits was the most frequently usedintervention, followed by information distribution and educational meetings. Interventions were more effective in those who had a family history of CRC or who were informed of the individual risk of developing the disease. Educational meetings in the workplace are an acceptable environment for disseminating information and distributing FOBT kits. DISCUSSION : An approach consisting of workplace interventions could increase the rate of CRC screening in the general population.

Investigación formativa para el diseño e implementación de una estrategia para aumentar el rastreo de cáncer colorrectal en el ámbito laboral en Argentina / Formative research for the design and implementation of a strategy to increase colorectal cancer screening in the workplace in Argentina / Pesquisa formativa para a estruturação e implementação de uma estratégia para aumentar o rastreamento do câncer colorretal no local de trabalho na Argentina

Resumen: El ámbito laboral tiene un gran potencial para difundir información e implementar actividades de promoción de la salud, como la prevención y detección temprana del cáncer. Debido al desafío de implementar intervenciones sanitarias en este ámbito, se necesitan investigaciones formativas para adecuar el diseño y la implementación de las estrategias para que sean exitosas. Con el objetivo de informar el diseño e implementación de la intervención, para mejorar la tasa de adherencia al tamizaje con el test de sangre oculta en materia fecal, en un ámbito laboral en Argentina, se realizó una investigación formativa para identificar potenciales barreras y facilitadores. La investigación formativa siguió un diseño metodológico cualitativo. Se realizaron entrevistas con 10 responsables de áreas clave de la institución en que se desarrolló el estudio y 8 grupos focales con trabajadores mayores de 50 años. Se identificaron desafíos para la implementación de la intervención en el nivel institucional, como la dispersión geográfica de los trabajadores y la complejidad del organigrama de la institución, y en el nivel de la población objetivo, como el bajo conocimiento del cáncer colorrectal y de los test diagnósticos, así como la baja percepción de riesgo. Entre los facilitadores se destacaron la aceptabilidad de la intervención, además de la disponibilidad de recursos humanos y materiales para llevar adelante la intervención, como canales de comunicación institucional para la diseminación de información, así como la logística para la distribución de kits diagnósticos. La investigación formativa permitió relevar recursos e identificar potenciales barreras que informaron el diseño y la implementación de la intervención.

Abstract: The workplace has great potential to disseminate information and implement health promotion activities such as cancer prevention and early detection. Due to the challenges of deploying health interventions in this setting, formative studies are needed to adjust the design and implementation of successful strategies. To inform the intervention's design and implementation and improve the adherence rate to screening with fecal occult blood test in a workplace in Argentina, a formative study was conducted to identify potential barriers and facilitators. The formative study adopted a qualitative methodological design. Interviews were held with 10 individuals in charge of key areas in the institution where the main study was conducted, besides 8 focus groups with workers over 50 years of age. Challenges were identified at the institutional level for the intervention's implementation, such as workers' geographic dispersion and the complexity of the institution's flowchart, as well as at the population level, such as low knowledge about colorectal cancer and diagnostic tests and low risk perception. The facilitators featured the intervention's acceptability and the availability of human and material resources to proceed with the intervention, such as institutional communications channels for disseminating the information and logistics for distribution of diagnostic kits. The formative study allowed identifying resources and potential barriers that informed the intervention's design and implementation.

Resumo: O local de trabalho possui grande potencial para divulgar informação e implementar atividades de promoção da saúde, como a prevenção e detecção precoce do câncer. Frente ao desafio de implementar ações sanitárias naquele ambiente, são necessárias pesquisas formativas para adequar a estruturação e a implementação das estratégias para que sejam bem-sucedidas. Com o objetivo de subsidiar a concepção e a implementação da ação, visando melhorar a taxa de aderência ao screening com o teste de sangue oculto nas fezes no ambiente de trabalho na Argentina, foi desenvolvida uma pesquisa formativa para identificar potenciais barreiras e facilitadores. A pesquisa formativa seguiu um formato metodológico qualitativo. Foram realizadas entrevistas com 10 gerentes de áreas chaves da entidade onde foi desenvolvido o estudo e 8 grupos focais, com trabalhadores acima de 50 anos de idade. Foram identificados alguns desafios para a implementação de uma ação em nível institucional, como a dispersão geográfica dos trabalhadores e a complexidade do organograma da entidade, e em termos de população objetiva, como o baixo conhecimento a respeito do câncer colorretal e dos testes diagnósticos, além da baixa percepção de risco. Entre os facilitadores, destacaram-se a aceitabilidade da ação e a disponibilidade de recursos humanos e materiais para levar a cabo a ação, como canais de comunicação institucional, para a divulgação da informação e a logística, para a distribuição dos kits diagnósticos. A pesquisa formativa revelou recursos e identificou potenciais barreiras, ajudando na estruturação e implementação da ação.

Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: Reversed by anti-TNF-α treatment.

BACKGROUND & AIMS: Chronic hyperammonemia induces neuroinflammation which mediates cognitive impairment. How hyperammonemia induces neuroinflammation remains unclear. We aimed to assess whether: chronic hyperammonemia induces peripheral inflammation, and whether this then contributes to neuroinflammation, altered neurotransmission and impaired spatial learning - before assessing whether this neuroinflammation and impairment is reversible following hyperammonemia elimination or treatment of peripheral inflammation with anti-TNF-α. METHODS: Chronic hyperammonemia was induced by feeding rats an ammonia-containing diet. Peripheral inflammation was analyzed by measuring PGE2, TNF-α, IL-6 and IL-10. We tested whether chronic anti-TNF-α treatment improves peripheral inflammation, neuroinflammation, membrane expression of glutamate receptors in the hippocampus and spatial learning. RESULTS: Hyperammonemic rats show a rapid and reversible induction of peripheral inflammation, with increased pro-inflammatory PGE2, TNF-α and IL-6, followed at around 10 days by reduced anti-inflammatory IL-10. Peripheral anti-TNF-α treatment prevents peripheral inflammation induction and the increase in IL-1b and TNF-α and microglia activation in hippocampus of the rats, which remain hyperammonemic. This is associated with prevention of the altered membrane expression of glutamate receptors and of the impairment of spatial memory assessed in the radial and Morris water mazes. CONCLUSIONS: This report unveils a new mechanism by which chronic hyperammonemia induces neurological alterations: induction of peripheral inflammation. This suggests that reducing peripheral inflammation by safe procedures would improve cognitive function in patients with minimal hepatic encephalopathy. LAY SUMMARY: This article unveils a new mechanism by which chronic hyperammonemia induces cognitive impairment in rats: chronic hyperammonemia per se induces peripheral inflammation, which mediates many of its effects on the brain, including induction of neuroinflammation, which alters neurotransmission, leading to cognitive impairment. It is also shown that reducing peripheral inflammation by treating rats with anti-TNF-α, which does not cross the blood-brain barrier, prevents hyperammonemia-induced neuroinflammation, alterations in neurotransmission and cognitive impairment.

Antecedentes familiares de cáncer de mama y colorrectal en una cohorte de población general en dos ciudades de Argentina / Family History of Breast and Colorectal Cancer in a Population-Based Cohort in two cities of Argentina

INTRODUCCIÓN: Los cánceres de mama (CM) y colorrectal (CCR) presentan una elevada carga de enfermedad en Argentina, por lo que el estudio de la epidemiología de estos tumores constituye una prioridad en salud pública. El objetivo del presente trabajo fue describir la prevalencia de antecedentes familiares de CM y CCR, y estimar la incidencia de los tumores en adultos de 35 a 74 años de dos ciudades de Argentina: Bariloche y Marcos Paz. MÉTODOS: En el marco de la cohorte prospectiva de población general CESCAS I (Estudio de detección y seguimiento de enfermedad cardiovascular y factores de riesgo en el Cono Sur de Latinoamérica), se recolectó información individual sobre antecedentes familiares de CM y CCR en una muestra representativa de las ciudades de Bariloche y Marcos Paz. Los casos de cáncer fueron investigados mediante documentación médica respaldatoria. RESULTADOS: Durante 2016-2017 se obtuvo información de 3245 participantes. El 8,4% de la población reportó antecedente familiar de CCR, y el 15,2% de las mujeres, de CM. La incidencia anual para el período 2011-2017 fue de 55,2/100 000 mujeres de 35 a 74 años (IC95%: 22,8-133,7) para CM y 8,5/100 000 adultos de 35 a 74 años (IC95%: 15,3-96,8) para CCR. CONCLUSIONES: Además de garantizar el acceso universal a los programas de tamizaje, se debe tener en cuenta la importancia de indagar sobre los antecedentes familiares de cáncer para identificar pacientes con riesgo aumentado, que requieren algoritmos particulares de detección temprana y vigilancia.

INTRODUCTION: Breast cancer (BC) and colorectal cancer (CRC) both present a high burden of disease in Argentina. Hence, studying the epidemiology of these tumors constitutes a public health priority. The objective of this study was to describe the prevalence of family history of BC and CRC and to estimate the incidence of these tumors in adults aged between 35 and 74 years from two cities in Argentina: Bariloche and Marcos Paz. METHODS: As part of the prospective population-based cohort CESCAS I (Study of detection and monitoring of cardiovascular disease and risk factors in the Southern Cone of Latin America), individual information on family history of BC and CRC was collected from a representative sample of the cities of Bariloche and Marcos Paz. Cancer cases were investigated using supporting medical documentation. RESULTS: During 2016-2017, information from 3245 participants was obtained. Family history of CRC was reported by 8.4% of the population, and 15.2% of women reported a family history of BC. The annual incidence for the 2011-2017 period was 55.2/100 000 women aged 35 to 74 years (95%CI: 22.8-133.7) for BC and 38.5/100 000 adults aged 35 to 74 years (95%CI: 15.3-96.8) for CRC.CONCLUSIONS: Besides guaranteeing universal access to screening programs, it is important to evaluate family history of cancer to identify patients with increased risk, who require specific early detection and surveillance algorithms.

Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in-coordination in rats with hepatic encephalopathy.

AIMS: Patients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in-coordination. Rats with HE due to portacaval shunts (PCS) show motor in-coordination. We hypothesized that in PCS rats: (i) Motor in-coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone would be due to neuroinflammation; (iii) increasing cGMP would reduce neuroinflammation and GABAergic tone and restore motor coordination. To assess these hypotheses, we assessed if (i) treatment with sildenafil reduces neuroinflammation; (ii) reduced neuroinflammation is associated with reduced GABAergic tone and restored motor coordination. METHODS: Rats were treated with sildenafil to increase cGMP. Microglia and astrocytes activation were analyzed by immunohistochemistry, extracellular GABA by microdialysis, and motor coordination in the beam walking. RESULTS: PCS rats show neuroinflammation in cerebellum, with microglia and astrocytes activation, increased IL-1b and TNF-a and reduced YM-1 and IL-4. Membrane expression of the GABA transporter GAT1 is reduced, while GAT3 is increased. Extracellular GABA and motor in-coordination are increased. Sildenafil treatment eliminates neuroinflammation, microglia and astrocytes activation; changes in membrane expression of GABA transporters; and restores motor coordination. CONCLUSIONS: This study supports an interplay between cGMP-neuroinflammation and GABAergic neurotransmission in impairing motor coordination in PCS rats.

Inmunoserología y métodos moleculares para el diagnóstico de Chagas: revisión sistemática rápida / Immunoserology and molecular techniques for diagnosis of Chagas´ disease: rapid systematic review / Imunoserologia e métodos moleculares para o diagnóstico de Chagas: revisão sistemática rápida

Con el objetivo de incrementar la precisión diagnóstica, la Organización Mundial de la Salud recomienda la realización de dos o más pruebas inmunoserológicas para el diagnóstico de la enfermedad de Chagas en etapa crónica. El objetivo de este trabajo fue realizar una revisión sistemática rápida acerca del desempeño de las técnicas inmunoserológicas y métodos moleculares en la población general. Se identificaron 178 estudios de los cuales fueron incluidos nueve. Las técnicas de ELISA mostraron la mayor sensibilidad (82-98%) y especificidad (96-100%). Los métodos rápidos mostraron valores de sensibilidad entre 88-93% y especificidad 97- 100%, mientras que los métodos moleculares (PCR) presentaron niveles muy variables de sensibilidad (22-92%) y especificidad (70-100%). Estos resultados muestran que las técnicas de ELISA cuentan con una sensibilidad y especificidad adecuadas. La PCR, al igual que los métodos rápidos, mostró una gran variabilidad en los resultados, debido principalmente a la heterogeneidad de la técnicas y profusión de métodos elaborados de manera in house.

In order to increase diagnostic accuracy, the World Health Organization recommends performing two or more immunoserological tests for the diagnosis of Chagas disease in chronic stage. The aim of this work was to make a rapid systematic review of the performance of immunoserological techniques and molecular methods in the general population. A total of 178 studies were identified, nine ofwhich were included. ELISA techniques showed the highest sensitivity (82-98%) and specificity (96-100%). Rapid methods presented values of sensitivity between 88-93% and 97-100% of specificity, while the molecular methods (PCR) showed highly variable levels of sensitivity (22-92%) and specificity (70-100%). These results indicate that ELISA techniques have adequate sensitivity and specificity. PCR, as well as rapid methods, showed great variability in the results, mainly due to the heterogeneity of the techniques and abundance of "in-house" methods.

Visando a aumentar a precisão do diagnóstico, a Organização Mundial da Saúde recomenda executar dois ou mais testes imunoserológicos para o diagnóstico na fase crônica da doença de Chagas. O objetivo deste trabalho foi fazer uma revisão sistemática rápida sobre o desempenho de técnicas imunoserológicas e métodos moleculares na população em geral. Foram identificados 178 estudos dos quais se incluíram nove. Técnicas de ELISA mostraram a maior sensibilidade (82-98%) e especificidade (96-100%). Métodos rápidos apresentaram valores de sensibilidade e especificidade de 88-93% e 97-100%, respectivamente enquanto que os métodos moleculares (PCR) tinham níveis extremamente variáveis de sensibilidade (22-92%) e especificidade (70-100%). Estes resultados mostram que as técnicas de ELISA possuem sensibilidade e especificidade adequadas. A PCR, bem como os métodos rápidos, mostrou grande variabilidade nos resultados, principalmente devido à heterogeneidade das técnicas e profusão de métodos desenvolvidos de modo in house.

In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1ß, NMDA receptors in membrane and working memory in hyperammonemic rats.

Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The underlying mechanisms remain unknown. It also remains unknown whether extracellular cGMP improves neuroinflammation or restores spatial learning in hyperammonemic rats and if it affects differently reference and working memory. The aims of this work were: Spatial working and reference memory were assessed using the radial and Morris water mazes and neuroinflammation by immunohistochemistry and Western blot. Membrane expression of NMDA and AMPA receptor subunits was analyzed using the BS3 crosslinker. Extracellular cGMP was administered intracerebrally using osmotic minipumps. Chronic hyperammonemia induces neuroinflammation in hippocampus, with astrocytes activation and increased IL-1ß, which are associated with increased NMDA receptors membrane expression and impaired working memory. This process is not affected by extracellular cGMP. Hyperammonemia also activates microglia and increases TNF-α, alters membrane expression of AMPA receptor subunits (increased GluA1 and reduced GluA2) and impairs reference memory. All these changes are reversed by extracellular cGMP. These results show that extracellular cGMP modulates spatial reference memory but not working memory. This would be mediated by modulation of TNF-α levels and of membrane expression of GluA1 and GluA2 subunits of AMPA receptors.