Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption.

Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results in lasting neurological deficits and an increased risk of autism. The impact of blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects of blood after neurovascular damage in preterm infants. Here, we show that fibrinogen, a blood-clotting protein, plays a central role in impairing neonatal cerebellar development. Longitudinal MRI of preterm infants revealed that cerebellar bleeds were the most critical factor associated with poor cerebellar growth. Using inflammatory and hemorrhagic mouse models of neonatal cerebellar injury, we found that fibrinogen increased innate immune activation and impeded neurogenesis in the developing cerebellum. Fibrinogen inhibited sonic hedgehog (SHH) signaling, the main mitogenic pathway in cerebellar granule neuron progenitors (CGNPs), and was sufficient to disrupt cerebellar growth. Genetic fibrinogen depletion attenuated neuroinflammation, promoted CGNP proliferation, and preserved normal cerebellar development after neurovascular damage. Our findings suggest that fibrinogen alters the balance of SHH signaling in the neurovascular niche and may serve as a therapeutic target to mitigate developmental brain injury after CNS hemorrhage.

5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies.

Monosomy 7 and del(7q) are among the most common and poorly understood genetic alterations in myelodysplastic neoplasms and acute myeloid leukemia. Chromosome band 7q22 is a minimally deleted segment in myeloid malignancies with a del(7q). However, the rarity of "second hit" mutations supports the idea that del(7q22) represents a contiguous gene syndrome. We generated mice harboring a 1.5 Mb germline deletion of chromosome band 5G2 syntenic to human 7q22 that removes Cux1 and 27 additional genes. Hematopoiesis is perturbed in 5G2+/del mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with KrasG12D, NrasG12D, or the MOL4070LTR retrovirus in leukemogenesis. 5G2+/del mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).

Changes in cardiovascular health and white matter integrity with aerobic exercise, cognitive and combined training in physically inactive healthy late-middle-aged adults: the "Projecte Moviment" randomized controlled trial.

INTRODUCTION: This is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits. METHODS: 109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements. RESULTS: A decrease in BMI (SMD = - 0.32, p = 0.039), waist circumference (SMD = - 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = - 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = - 0.34, p = 0.031) and DBP (SMD = - 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = - 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group. CONCLUSIONS: We found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT031123900.

Defining blood-induced microglia functions in neurodegeneration through multiomic profiling.

Blood protein extravasation through a disrupted blood-brain barrier and innate immune activation are hallmarks of neurological diseases and emerging therapeutic targets. However, how blood proteins polarize innate immune cells remains largely unknown. Here, we established an unbiased blood-innate immunity multiomic and genetic loss-of-function pipeline to define the transcriptome and global phosphoproteome of blood-induced innate immune polarization and its role in microglia neurotoxicity. Blood induced widespread microglial transcriptional changes, including changes involving oxidative stress and neurodegenerative genes. Comparative functional multiomics showed that blood proteins induce distinct receptor-mediated transcriptional programs in microglia and macrophages, such as redox, type I interferon and lymphocyte recruitment. Deletion of the blood coagulation factor fibrinogen largely reversed blood-induced microglia neurodegenerative signatures. Genetic elimination of the fibrinogen-binding motif to CD11b in Alzheimer's disease mice reduced microglial lipid metabolism and neurodegenerative signatures that were shared with autoimmune-driven neuroinflammation in multiple sclerosis mice. Our data provide an interactive resource for investigation of the immunology of blood proteins that could support therapeutic targeting of microglia activation by immune and vascular signals.

Cultural adaptations to a telephone genetic counseling protocol and booklet for Latina breast cancer survivors at risk for hereditary breast and ovarian cancer.

Telephone genetic counseling (TGC) is accepted as standard clinical care for people seeking hereditary cancer risk assessment. TGC has been shown to be non-inferior to in-person genetic counseling, but trials have been conducted with a predominantly highly educated, non-Hispanic White population. This article describes the process of culturally adapting a TGC protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at risk for hereditary breast and ovarian cancers. The adaptation process included two phases. Phase 1 involved a review of the literature and recommendations from an expert team including community partners. Phase 2 included interviews and a pilot with the target population (n = 14) to collect feedback about the adapted protocol and booklet following steps from the Learner Verification and Revision Framework. We describe the adaptation process and report the main adaptations following the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME). Adaptations in Phase 1 were responsive to the target population needs and characteristics (e.g., delivered in Spanish at an appropriate health literacy level, addressing knowledge gaps, targeting cultural values). Phase 2 interviews were crucial to refine details (e.g., selecting words) and to add components to address GCT barriers (e.g., saliva sample video). Cultural adaptations to evidence-based TGC protocols can increase the fit and quality of care for historically underserved populations. As TGC visits become routine in clinical care, it is crucial to consider the needs of diverse communities to adequately promote equity and justice in cancer care.

This article describes the process of adapting a telephone genetic counseling protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at increased risk for hereditary breast and ovarian cancer (HBOC). The cultural adaptation process followed two phases. In the first phase, the authors reviewed the literature and obtained insights from interdisciplinary experts. In the second phase, the authors received iterative feedback from fourteen Latina women who were breast cancer survivors, spoke Spanish as a first language, and met criteria to be considered at increased risk for HBOC. Revisions to the protocol and visual aid booklet were conducted iteratively following feedback from the expert team, after the first five women reviewed the booklet, after the second five women reviewed the booklet, and after the final four women completed the entire culturally adapted telephone genetic counseling protocol with the booklet. The final adaptations to the protocol and visual aid booklet were responsive to the target population's needs. Most adaptations made were regarding content. For example, simplifying the material presented, adding culturally relevant images, and developing a video explaining how to collect a saliva sample. Culturally adapting health interventions can improve health outcomes in historically marginalized populations and promote equity.

Automated Systems for Calculating Arteriovenous Ratio in Retinographies: A Scoping Review.

There is evidence of an association between hypertension and retinal arteriolar narrowing. Manual measurement of retinal vessels comes with additional variability, which can be eliminated using automated software. This scoping review aims to summarize research on automated retinal vessel analysis systems. Searches were performed on Medline, Scopus, and Cochrane to find studies examining automated systems for the diagnosis of retinal vascular alterations caused by hypertension using the following keywords: diagnosis; diagnostic screening programs; image processing, computer-assisted; artificial intelligence; electronic data processing; hypertensive retinopathy; hypertension; retinal vessels; arteriovenous ratio and retinal image analysis. The searches generated 433 articles. Of these, 25 articles published from 2010 to 2022 were included in the review. The retinographies analyzed were extracted from international databases and real scenarios. Automated systems to detect alterations in the retinal vasculature are being introduced into clinical practice for diagnosis in ophthalmology and other medical specialties due to the association of such changes with various diseases. These systems make the classification of hypertensive retinopathy and cardiovascular risk more reliable. They also make it possible for diagnosis to be performed in primary care, thus optimizing ophthalmological visits.

Laparoscopic Management of Cesarean Scar Pregnancy after Medical Treatment Failure Using Laparoscopic Bulldog Clamps.

Cesarean scar pregnancies are a rare complication of pregnancy, with an incidence rate of approximately 1 in 2000 pregnancies. Numerous treatment alternatives have been proposed and published for cesarean scar pregnancies (CSPs), including medical management with local or systemic methotrexate injection, resection through hysteroscopic, vaginal, abdominal or laparoscopic approach, and dilation and curettage. Concomitant strategies for achieving hemostasis/bleeding control have been attempted, including uterine artery embolization, the placement of a Foley balloon catheter, injection of vasopressin, and less commonly reported, the use of vascular clamps. We describe a case of failed medical management of a CSP, followed by laparoscopic resection with the use of vascular clamps to minimize bleeding. This approach can be considered for minimizing blood loss in the laparoscopic management of cesarean ectopic pregnancies.

Evolución de la prevalencia de arteriopatía periférica en la práctica clínica: Estudio descriptivo poblacional con bases de datos reales (SIDIAP-CMBD) / Evolution of the prevalence of peripheral artery disease in clinical practice: A descriptive population study with real databases (SIDIAP-CMBD)

Objetivo: Evaluar, con datos de práctica clínica real (SIDIAP y CMBD), la evolución de la prevalencia de arteriopatía periférica (AP) en la población catalana y los factores de riesgo cardiovascular presentes en las personas con esta patología. Diseño: Estudio longitudinal descriptivo poblacional. Emplazamiento: Atención primaria. Participantes: Pacientes que figuran en SIDIAP y CMBD con diagnóstico de arteriopatía periférica entre los años 2008 y 2018 ≥ 35 años, así como aquellos sin diagnóstico, pero con un registro del ITB < 0,9 en SIDIAP. Intervenciones y mediciones: Variable principal AP (CIE-9, CIE-10). Datos sociodemográficos, factores de riesgo y patología cardiovascular, consumo de fármacos y eventos cardiovasculares prevalentes en el momento del diagnóstico. Resultados: Se contabilizaron 141.520 pacientes. Un 75% tenía hipertensión, un 58% eran fumadores o exfumadores y un 23% tuvieron un infarto de miocardio. La prevalencia global fue aumentando desde el 1,2% en 2008 hasta el 3,1% en 2018. La prevalencia de AP aumentó con la edad, con un incremento moderado en edades tempranas, y más pronunciado en > 55 años, rebasando el 10% en > 85 años. Conclusión: Se trata de un estudio poblacional donde se observa que la evolución de la prevalencia de arteriopatía periférica ha presentado un incremento constante durante los años 2008 a 2018, siendo superior en varones especialmente a partir de los 55 años. Los estudios con grandes bases de datos pueden facilitar el diseño y la implementación de nuevas políticas en los sistemas nacionales de salud.(AU)

Objective: To evaluate, with real world data (SIDIAP and CMBD), the evolution of the prevalence of peripheral arterial disease (PAD) in the Catalan population and the cardiovascular risk factors present in people with this pathology. Design: Longitudinal descriptive population study. Site: Primary health care. Participants: Patients listed in SIDIAP and CMBD with a diagnosis of peripheral artery disease between 2008 and 2018 ≥ 35 years, as well as those without a diagnosis, but with an ABI < 0.9 in SIDIAP. Interventions and main measurements: Main variable AP (ICD-9, ICD-10). Sociodemographic data, risk factors and cardiovascular disease, drug use and prevalent cardiovascular events at the time of diagnosis. Results: 141,520 patients were studied. 75% had hypertension, 58% were smokers or former smokers, and 23% had a myocardial infarction. The global prevalence increased from 1.15% in 2008 to 3.10% in 2018. The prevalence of PAD increased with age, with a moderate increase at younger ages, and more pronounced in > 55 years, exceeding 10% in > 85 years. Conclusion: This is a population study where it is observed that the evolution of the prevalence of peripheral artery disease has presented a constant increase during the years 2008–2018, being higher in men, especially from 55 years of age. Studies with large databases can facilitate the design and implementation of new policies in national health systems.(AU)

[Evolution of the prevalence of peripheral artery disease in clinical practice: A descriptive population study with real databases (SIDIAP-CMBD)]. / Evolución de la prevalencia de arteriopatía periférica en la práctica clínica: Estudio descriptivo poblacional con bases de datos reales (SIDIAP-CMBD).

OBJECTIVE: To evaluate, with real world data (SIDIAP and CMBD), the evolution of the prevalence of peripheral arterial disease (PAD) in the Catalan population and the cardiovascular risk factors present in people with this pathology. DESIGN: Longitudinal descriptive population study. SITE: Primary health care. PARTICIPANTS: Patients listed in SIDIAP and CMBD with a diagnosis of peripheral artery disease between 2008 and 2018 ≥ 35 years, as well as those without a diagnosis, but with an ABI < 0.9 in SIDIAP. INTERVENTIONS AND MAIN MEASUREMENTS: Main variable AP (ICD-9, ICD-10). Sociodemographic data, risk factors and cardiovascular disease, drug use and prevalent cardiovascular events at the time of diagnosis. RESULTS: 141,520 patients were studied. 75% had hypertension, 58% were smokers or former smokers, and 23% had a myocardial infarction. The global prevalence increased from 1.15% in 2008 to 3.10% in 2018. The prevalence of PAD increased with age, with a moderate increase at younger ages, and more pronounced in > 55 years, exceeding 10% in > 85 years. CONCLUSION: This is a population study where it is observed that the evolution of the prevalence of peripheral artery disease has presented a constant increase during the years 2008-2018, being higher in men, especially from 55 years of age. Studies with large databases can facilitate the design and implementation of new policies in national health systems.

Higher Arm Versus Lower Arm Systolic Blood Pressure and Cardiovascular Outcomes: a Meta-Analysis of Individual Participant Data From the INTERPRESS-IPD Collaboration.

BACKGROUND: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration. METHODS: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. RESULTS: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P<0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P<0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P<0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs). CONCLUSIONS: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42015031227.

Supervised physical activity in patients with symptomatic peripheral arterial disease: protocol for a randomized clinical trial (ARTPERfit Study).

INTRODUCTION: Peripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC). METHODS AND ANALYSIS: This study will be performed in Mataró Hospital's vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention. ETHICS AND DISSEMINATION: The study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations. TRIAL REGISTRATION NUMBER: NCT04578990.

The Non-pregnant and Pregnant Human Cervix: a Systematic Proteomic Analysis.

Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR.

Lens-vault analysis and its correlation with other biometric parameters using swept-source OCT

Purpose: To measure lens vault (LV) and to assess its correlation with various ocular parameters in healthy eyes, using for all measurements the same high-resolution swept-source optical coherence tomographer (SS-OCT).Methods: We prospectively recruited 67 Caucasian healthy patients whose mean age was 41.9 ± 12.4 years; only their right eye was included in the study. Data were all recorded with the ANTERION SS-OCT and comprised, for each patient, 5 consecutive measurements of LV, anterior chamber depth (ACD), lens thickness (LT), axial length (AL), white-to-white (WTW) distance, central corneal thickness (CCT), anterior chamber volume (ACV) and spur-to-spur (STS) distance.Results: Mean LV was 0.26 ± 0.23 mm (ranging from -0.24 to 0.78 mm). Data analysis revealed a statistically significant negative correlation between LV and ACD (R=-0.80, p < 0.001), AL (R = -0.36, p = 0.002), and ACV (R = -0.68, p < 0.001), and a positive correlation between LV and LT (R = 0.67, p < 0.001), and age (R = 0.53, p < 0.001). In contrast, no statistically significant correlation was found between LV and WTW (R=-0.17, p = 0.15), CCT (R = 0.11, p = 0.36) or STS (R=-0.10, p = 0.41).Conclusions: Taking into account our findings about intra-parameter correlation levels, we believe that LV should be measured and analyzed together with other ocular parameters in clinical routine practice both for diagnosis and for some refractive surgeries. (AU)

Lens-vault analysis and its correlation with other biometric parameters using swept-source OCT.

PURPOSE: To measure lens vault (LV) and to assess its correlation with various ocular parameters in healthy eyes, using for all measurements the same high-resolution swept-source optical coherence tomographer (SS-OCT). METHODS: We prospectively recruited 67 Caucasian healthy patients whose mean age was 41.9 ±â€¯12.4 years; only their right eye was included in the study. Data were all recorded with the ANTERION SS-OCT and comprised, for each patient, 5 consecutive measurements of LV, anterior chamber depth (ACD), lens thickness (LT), axial length (AL), white-to-white (WTW) distance, central corneal thickness (CCT), anterior chamber volume (ACV) and spur-to-spur (STS) distance. RESULTS: Mean LV was 0.26 ± 0.23 mm (ranging from -0.24 to 0.78 mm). Data analysis revealed a statistically significant negative correlation between LV and ACD (R=-0.80, p < 0.001), AL (R = -0.36, p = 0.002), and ACV (R = -0.68, p < 0.001), and a positive correlation between LV and LT (R = 0.67, p < 0.001), and age (R = 0.53, p < 0.001). In contrast, no statistically significant correlation was found between LV and WTW (R=-0.17, p = 0.15), CCT (R = 0.11, p = 0.36) or STS (R=-0.10, p = 0.41). CONCLUSIONS: Taking into account our findings about intra-parameter correlation levels, we believe that LV should be measured and analyzed together with other ocular parameters in clinical routine practice both for diagnosis and for some refractive surgeries.

Factores asociados al resultado citológico positivo en pruebas de Papanicolau en mujeres atendidas en la Liga peruana de lucha contra el cáncer / Factors associated with a positive cytological result in Papanicolau tests in women attended In the Liga Peruana de Lucha contra el Cancer

Objetivo: Evaluar los factores asociados a un resultado de citología cervical positiva en la prueba de Papanicolau en una muestra de mujeres peruanas en Lima, Perú - 2013. Material y métodos: Se realizó un estudio transversal analítico que incluyó a mujeres con edades entre 21 a 64 años y empleó la prueba de Papanicolaou para evaluar la citología cervical. Se incluyó factores sociodemográficos y antecedentes de la mujer obtenidos de la historia clínica de las pacientes. Se realizaron modelos lineales generalizados de familia Poisson con varianzas robustas para evaluar los factores asociados a la citología positiva. La medida de asociación reportada fue la razón de prevalencia (RP) con sus respectivos intervalos de confianza al 95% (IC95%). Resultados: Se incluyeron a 11110 mujeres en el análisis con una edad media de 41,5±10,9 años y la prevalencia de un resultado positivo en la prueba de Papanicolau fue de 2,8%. En el modelo ajustado, se halló que tener entre 21 a 30 años (RPa=1,97;IC95%:1,30-3,00), 31 a 40 años (RPa=2,56;IC95%:1,76-3,72) y 41 a 50 años (RPa=2,16;IC95%:1,47-3,17), ser soltera (RPa=1,41;IC95%:1,10-1,83), viuda o divorciada (RPa=1,90;IC95%:1,27-2,87), haber tenido inicio de vida sexual antes de los 16 años (RPa=1,30;IC95%:1,01-1,68) o entre los 16 a 19 años (RPa=1,69;IC95%:1,22-2,36) se asoció a una mayor probabilidad de presentar un resultado de citología cervical positivo. Conclusiones: El cáncer de cuello uterino representa un problema de salud pública en Perú, por lo que identificar sus factores asociados es útil para mejorar las estrategias de tamizaje, priorizando grupos de mayor riesgo.

Objetive:To evaluate the factors associated with a positive cervical cytology result in the Pap smear test in a sample of Peruvian women from Lima, Peru - 2013. : We conducted an analytical cross-sectional Material and Methodsstudy including women from 21 to 64 years and we used the Pap smear test to evaluate cervical cytology. We included sociodemographic and medical history variables obtained from medical records of the patients. We elaborated generalized linear models from Poisson family with robust variances to evaluate the factors associated with positive cytology. The association measure reported was the prevalence ratio (PR) with their respective 95% confidence intervals (95%CI). We analyzed 11110 women with a mean age of 41.5 ± 10.9 Results: years and a prevalence of a positive Pap smear test of 2.8%. In the adjusted model, we found that women between 21 and 30 years old (aPR=1.97; 95%CI:1.30-3.00), 31 to 40 years (aPR=2.56; 95%CI:1.76 -3.72) and 41 to 50 years (aPR=2.16; 95%CI:1.47-3.17), single (aPR=1.41; 95%CI:1.10-1.83), widowed or divorced (aPR=1.90; 95%CI:1.27-2.87), with a sexual life onset before 16 years (aPR=1.30; 95%CI:1.01- 1.68) or between 16 and 19 years (aPR=1.69; 95%CI:1.22-2.36) had a greater prevalence of a positive cervical cytology result. Cervical cancer is a public health problem in Peru, then, identifying the factors associated will allow us to Conclusions:improve screening strategies and prioritize groups at higher risk.

Relationship between Retinal Microvasculature, Cardiovascular Risk and Silent Brain Infarction in Hypertensive Patients.

OBJECTIVE: The aims of this study are to analyze the role of artery-vein ratio AVR assessment using VesselMap 2 software (Imedos Systems) and cardiovascular risk evaluation by means of REGICOR in the prediction of silent brain infarction (SBI) in middle-age hypertensive patients from the ISSYS study. MATERIAL AND METHODS: A cross-sectional study with 695 patients with hypertension aged 50 to 70 years who participated in the project Investigating Silent Strokes in HYpertensives: a Magnetic Resonance Imaging Study (ISSYS), was conducted in two Primary Care Centres of Barcelona. Participants agreed to a retinography and an MRI to detect silent brain infarction (SBI). The IMEDOS software was used for the semiautomatic caliber measurement of retinal arteries and veins, and the AVR was considered abnormal when <0.66. The REGICOR score was calculated for all patients. RESULTS: Multivariate logistic regression analysis was used to evaluate the impact of AVR and REGICOR scores on SBI. The OR (odds ratio) for a high REGICOR score and an abnormal AVR were 3.16 and 4.45, respectively. When analysing the interaction of both factors, the OR of an abnormal AVR and moderate REGICOR score was 3.27, whereas with a high REGICOR score it reached 13.07. CONCLUSIONS: The measurement of AVR in patients with hypertension and with a high REGICOR score can contribute to the detection of silent brain infarction.

Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality: Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration.

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.

Sex-Specific Protective Effects of APOE ε2 on Cognitive Performance.

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (ß = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and ß = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.

Colitis ulcerativa fulminante complicada con megacolon tóxico / Fulminant ulcerative colitis complicated with toxic megacolon

Presentamos un caso de abdomen agudo secundario a megacolon tóxico perforado como debut de colitis ulcerativa que requirió múltiples intervenciones quirúrgicas y estancia prolongada en la unidad de cuidados intensivos. El megacolon tóxico es una complicación infrecuente y potencialmente fatal de la colitis ulcerativa, siendo más raro aún como debut en un paciente sin antecedentes y con solo un factor de riesgo identificado, considerándolo una oportunidad para compartir su estudio y abordaje. El diagnóstico de megacolon tóxico se configura de acuerdo con los criterios propuestos por Jalan. Aunque el tratamiento inicial es médico con corticoterapia endovenosa, un porcentaje importante de pacientes precisará abordaje quirúrgico.

We present a case of acute abdomen secondary to perforated toxic megacolon in a patient with new-onset ulcerative colitis (UC) that required multiple surgical interventions and prolonged intensive care unit stay. Toxic megacolon is a rare but potentially fatal complication of UC, being even rarer in new-onset UC in a patient with no history and only one risk factor identified, considering this an opportunity to share its study and approach. The diagnosis of toxic megacolon is based on the criteria proposed by Jalan. Although the initial treatment is medical therapy with intravenous corticosteroids, surgical management is necessary for a significant majority of patients.

Long-Term Morbidity and Mortality after First and Recurrent Cardiovascular Events in the ARTPER Cohort.

BACKGROUND: Cardiovascular events are a major cause of mortality and morbidity worldwide. The risk of recurrence after a first cardiovascular event has been documented in the international literature, although not as extensively in a Mediterranean population-based cohort with low cardiovascular risk. There is also ample, albeit contradictory, research on the recurrence of stroke and myocardial infarctions (MI) after a first event and the factors associated with such recurrence, including the role of pathological Ankle-Brachial Index (ABI). METHODS: The Peripheral Arterial ARTPER study is aimed at deepening our knowledge of patient evolution after a first cardiovascular event in a Mediterranean population with low cardiovascular risk treated at a primary care centre. We study overall recurrence, cardiac and cerebral recurrence. We studied participants in the ARTPER prospective observational cohort, excluding patients without cardiovascular events or with unconfirmed events and patients who presented arterial calcification at baseline or who died. In total, we analyzed 520 people with at least one cardiovascular event, focusing on the presence and type of recurrence, the risk factors associated with recurrence and the behavior of the ankle-brachial index (ABI) as a predictor of risk. RESULTS: Between 2006 and 2017, 46% of patients with a first cardiovascular event experienced a recurrence of some type; most recurrences fell within the same category as the first event. The risk of recurrence after an MI was greater than after a stroke. In our study, recurrence increased with age, the presence of peripheral arterial disease (PAD), diabetes and the use of antiplatelets. Diabetes mellitus was associated with all types of recurrence. Additionally, patients with an ABI < 0.9 presented more recurrences than those with an ABI ≥ 0.9. CONCLUSIONS: In short, following a cardiac event, recurrence usually takes the form of another cardiac event. However, after having a stroke, the chance of having another stroke or having a cardiac event is similar. Lastly, ABI < 0.9 may be considered a predictor of recurrence risk.