Design, develop, and implement the strategic information system on health, dependence, and healthy aging: an analysis of the Mexican experience.

BACKGROUND: The Decade of Healthy Aging (2021-2030) emerges as a 10 years strategy to improve the lives of older adults, their families, and the communities in which they live. One of the actions defined in this framework is related to improving the measurement, monitoring, and understanding of characteristics, factors, and needs related to aging and health. The aim was to analyze and assess the process of construction and development of the Strategic Information System on Health, Funcional Dependence and Aging (SIESDE, for its acronym in Spanish). SIESDE will provide strategic information in Mexico at the municipal, state, and national levels that support the public policies on healthy aging. METHODS: The system processes and analyzes the data sources of the Health Information Systems and the National System of Statistical and Geographical Information. SIESDE comprises three components: (1) Design, construction, and evaluation of the indicators; (2) storage, management, and visualization, and (3) diffusion and translation of information. RESULTS: A total of 135 indicators were built on seven themes: (1) demographic, socioeconomic, and aging conditions, (2) health, (3) functional dependence, (4) healthy aging, (5) health services, (6) social and physical environments, and (7) complex indicators. CONCLUSIONS: SIESDE is an effective system for providing an overall view of health, aging, and functional dependence.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages.

OBJECTIVE: Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis. METHODS: IgG and IgM serum levels of antibodies against HDL (anti-HDL) and apolipoprotein A1 (anti-ApoA1) were measured in 82 early RA patients, 14 arthralgia individuals and 96 controls. Established RA patients (n = 42) were included for validation. Atherosclerosis and vascular stiffness were measured by Doppler ultrasound. Lipoprotein content, particle numbers and size were measured by H-NMR. Cytokines were measured by immunoassays. A cardiometabolic-related protein panel was evaluated using high-throughput targeted proteomics. RESULTS: Anti-HDL and anti-ApoA1 responses were increased in early RA compared with controls (both P < 0.001) and were comparable to established disease. Only anti-ApoA1 antibodies were increased in arthralgia. IgG anti-HDL and anti-ApoA1 were associated with unfavourable lipoprotein traits in RA and arthralgia, respectively. A similar picture was observed for inflammatory mediators. No associations with clinical features or risk factors were found. IgG anti-HDL were independently associated with atherosclerosis occurrence in early RA, and outperformed patient stratification over conventional algorithms (mSCORE) and their anti-ApoA1 counterparts. Anti-HDL antibodies correlated with proteins involved in immune activation, remodelling and lipid metabolism pathways in early RA. CONCLUSION: Humoral responses against HDL particles are an early event along the arthritis course, although quantitative and qualitative differences can be noticed among stages. These differences informed distinct capacities as biomarkers and underlying pathogenic circuits.

Evaluation of functional warm ischemia time during controlled donation after circulatory determination of death using normothermic regional perfusion (ECMO-TT): A prospective multicenter cohort study.

BACKGROUND: Controlled donation after circulatory determination of death (cDCD) seems an effective way to mitigate the critical shortage of available organs for transplant worldwide. As a recently developed procedure for organ retrieval, some questions remain unsolved such as the uncertainty regarding the effect of functional warm ischemia time (FWIT) on organs´ viability. METHODS: We developed a multicenter prospective cohort study collecting all data from evaluated organs during cDCD from 2017 to 2020. All the procedures related to cDCD were performed with normothermic regional perfusion. The analysis included organ retrieval as endpoint and FWIT as exposure of interest. The effect of FWIT on the likelihood for organ retrieval was evaluated with Relative distribution analysis. RESULTS: A total amount of 507 organs´ related information was analyzed from 95 organ donors. Median donor age was 62 years, and 63% of donors were male. Stroke was the most common diagnosis before withdrawal of life-sustaining therapy (61%), followed by anoxic encephalopathy (21%). This analysis showed that length of FWIT was inversely associated with organ retrieval rates for liver, kidneys, and pancreas. No statistically significant association was found for lungs. CONCLUSIONS: Results showed an inverse association between functional warm ischemia time (FWIT) and retrieval rate. We also have postulated optimal FWIT's thresholds for organ retrieval. FWIT for liver retrieval remained between 6 and less than 11 min and in case of kidneys and pancreas, the optimal FWIT for retrieval was 6 to 12 min. These results could be valuable to improve organ utilization and for future analysis.

Are all ventilators for NIV performing the same? A bench analysis.

Global pandemic due to COVID-19 has increased the interest for ventilators´ use worldwide. New devices have been developed and older ones have undergone a renewed interest, but we lack robust evidence about performance of each ventilator to match appropriate device to a given patient and care environment. The aim of this bench study was to investigate the performance of six devices for noninvasive ventilation, and to compare them in terms of volume delivered, trigger response, pressurization capacity and synchronization in volume assisted controlled and pressure support ventilation. All ventilators were tested under thirty-six experimental conditions by using the lung model ASL5000® (IngMar Medical, Pittsburgh, PA). Two leak levels, two muscle inspiratory efforts and three mechanical patterns were combined for simulation. Trigger function was assessed by measurement of trigger-delay time. Pressurization capacity was evaluated as area under the pressure-time curve over the first 500 ms after inspiratory effort onset. Synchronization was evaluated by the asynchrony index and by incidence and type of asynchronies in each condition. All ventilators showed a good performance, even if pressurization capacity was worse than expected. Leak level did not affect their function. Differences were found during low muscle effort and obstructive pattern. In general, Philips Trilogy Evo/EV300 and Hamilton C3 showed the best results. NIV devices successfully compensate air leaks but still underperform with low muscle effort and obstructive lungs. Clinicians´ must have a clear understanding of the goals of NIV both for devices´ choice and set main parameters to achieve therapy success.

Single-phase CT angiography predicts ASPECTS decay and may help determine when to repeat CT before thrombectomy.

OBJETIVES: Time is relative in large-vessel occlusion acute ischemic stroke (LVO-AIS). We aimed to evaluate the rate of inter-hospital ASPECTS decay in patients transferred from a primary (PSC) to a comprehensive stroke center (CSC); and to identify patients that should repeat computed tomography (CT) before thrombectomy. MATERIALS AND METHODS: This was a retrospective cohort study of consecutive anterior circulation LVO-AIS transferred patients. The rate of ASPECTS decay was defined as (PSC-ASPECTS - CSC-ASPECTS)/hours elapsed between scans. Single-phase CT angiography (CTA) at the PSC was used to classify the collateral score. We compared patients with futile versus useful CT scan re-evaluation. RESULTS: We included 663 patients, of whom 245 (37.0%) repeated CT at a CSC. The median rate of ASPECTS decay was 0.4/h (0.0-0.9). Patients excluded from thrombectomy after a CT scan repeat (n=64) had a median ASPECTS decay rate of 1.18/h (0.83-1.61). Patients with absent collateral circulation had a median rate of 1.51(0.65-2.19). The collateral score was an independent predictor of the ASPECTS decay rate (aß = -0.35; 95%CI -0.45 - -0.19, p<0.001). Age (aOR: 1.04 95% CI 1.02-1.07, p<0.001), NIHSS (aOR: 1.11 95% CI 1.06-1.15, p<0.001), PSC ASPECTS (aOR: 0.74 95% CI 0.60-0.91, p=0.006) and the CTA collateral score (aOR: 0.14 95% CI 0.08-0.22, p<0.001) were independent predictors of the usefulness of a CT scan repeat. CONCLUSIONS: The rate of ASPECTS decay can be predicted by the CTA collateral score, helping in the selection of patients that would benefit from repeating a CT assessment on arrival at the CSC.

The lived experience of psychosis in Nicaragua: a qualitative examination of the views of service users.

BACKGROUND: The experience of psychosis is individual and influenced by a complex intersection of identity, thought processes, perceptions and culture. Little is known about the lived experience of psychosis in Nicaragua. AIM: To explore the subjective experience of psychosis in Nicaragua from the perspectives of service users. METHODS: Focus groups with 28 service users with experience of psychosis. A qualitative analysis using both inductive and deductive approaches was used to analyse these data. RESULTS: Participants mostly attributed the onset of psychosis to external factors such as physical or psychological trauma and highlighted the impact of long-term conflict in the area. Whilst medication was generally viewed positively where this was available participants foregrounded lay and community support networks and engagement in valued activities in their narratives about the management of psychosis. Religious and magical forces were salient in participants' accounts of causal pathways, wider Nicaraguan culture and management practices. Stigma, social exclusion and limited access to formal health services and psychological interventions in particular were the major barriers reported to recovery from psychosis. CONCLUSION: Our findings point to the potential utility of culturally adapted psychological interventions in Nicaragua as well as the value of lay and community workforces in delivering such interventions.

PTPN22 gene functional polymorphism (rs2476601) in older adults with frailty syndrome.

The frailty syndrome is a common clinical marker of vulnerability in older adults conducive to an overall decline in inflammatory stress responsiveness; yet little is known about the genetic risk factors for frailty in elderly. Our aim was to investigate the association between the rs2476601 polymorphism in PTPN22 gene and susceptibility to frailty in Mexican older adults. Data included 630 subjects 70 and older from The Coyoacán cohort, classified as frail, pre-frail, and non-frail following Fried's criteria. Sociodemographic and clinical characteristics were compared between groups at baseline and after a multivariate analysis. The rs2476601 polymorphism was genotyped by TaqMan genotyping assay using real-time PCR and genotype frequencies were determined for each frailty phenotype in all participants and subsets by age range. Genetic association was examined using stratified and interaction analyses adjusting for age, sex and variables selected in the multivariate analysis. Disability for day-life activities, depression and cognitive impairment were associated with the risk of pre-frailty and frailty at baseline and after adjustment. Carrying the T allele increased significantly the risk of frailty in patients 76 and older (OR 5.64, 95% CI 4.112-7.165) and decreased the risk of pre-frailty under no clinical signs of depression (OR 0.53; 95% CI 0.17-1.71). The PTPN22 polymorphism, rs2476601, could be a genetic risk factor for frailty as subject to quality of life. This is the first study analyzing such relationship in Mexican older adults. Confirming these findings requires additional association studies on wider age ranges in populations of older adults with frailty syndrome.

Effect of poor glycemic control in cognitive performance in the elderly with type 2 diabetes mellitus: The Mexican Health and Aging Study.

BACKGROUND: Cognitive impairment is twice more frequent in elderly with type 2 diabetes mellitus (DM). This study was conducted to determine the association between glycemic control and cognitive performance among community-dwelling elderly persons in Mexico. METHODS: Cross-sectional study conducted in individuals aged 60 years or elderly participating in the 2012 Mexican Health and Aging Study. Type 2 DM participants were classified in 3 groups according to their glycated hemoglobin levels (HbA1c): < 7% (intensive control), 7-7.9% (standard control) or ≥ 8% (poor control), and cognitive performance: low (CCCE ≤44 points), intermediate (44.1-59.52 points), or high (≥59.53 points). Multinomial logistic regression models were constructed to determine this association. RESULTS: Two hundred sixteen community-dwelling adults aged 60 and older with type 2 diabetes were selected. Subjects in the low cognitive performance group were older (69.7 ± 6.6 vs 65.86 ± 5.18 years, p < .001) and had a lower educational level (2.5 ± 2.6 vs 7.44 ± 4.15 years, p < .000) when compared to the high cognitive performance participants. HbA1c ≥ 8% was associated with having low (Odds Ratio (OR) 3.17, 95% CI 1.17-8.60, p = .024), and intermediate (OR 3.23, 95% CI 1.27-8.20, p = .014) cognitive performance; this trend was not found for HbA1c 7.0-7.9% group. The multinomial regression analysis showed that the presence of HbA1c ≥ 8% (poor glycemic control) was associated with low (OR 3.17, 95% CI = 1.17-8.60, p = .024), and intermediate (OR 3.23, 95% CI = 1.27-8.20, p = .014) cognitive performance. After adjusting for confounding variables. CONCLUSIONS: Glycemic control with a HbA1c ≥ 8% was associated with worse cognitive performance.

ASSOCIATION OF VITAMIN D WITH MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DEMENTIA IN OLDER MEXICAN ADULTS.

BACKGROUND: It has been proposed that Vitamin D helps reduce the accumulation of cerebral ß-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer's dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (> 65 years). METHODS: Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (> 30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed. RESULTS: We evaluated 208 patients. Mean age was 79 ± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p < 0.001) groups. In the multivariate logistic regression analysis, Vitamin D deficiency was associated with MCI (HR 25.02 [confidence interval 95% 4.48-139]; p < 0.001) and AD (HR 41.7 [5.76-301]; p < 0.001) after adjusting for confounders. CONCLUSIONS: Serum Vitamin D deficiency was associated with MCI and dementia; low levels produced a greater effect over executive functions.

Adaptive biokinetic modelling of iodine-131 in thyroid cancer treatments: implications on individualised internal dosimetry.

Nowadays therapies involving radioiodine (I-131) represent 84% of the total metabolic treatments in Europe, according to the last report of the European Association of Nuclear Medicine in relation to treatment planning for molecular radiotherapy. Last recommendations of the European Council, i.e. 2013/59/Euroatom, mandates that metabolic treatments should be planned according to the radiation doses delivered to individual patients, analogous to external beam radiotherapy. In this work, we present a novel biokinetic model for I-131 that allows on to obtain realistic activity distributions for particular patients with thyroid cancer in absence of metastasis. Other models existing in the literature present either a too simple metabolic description to obtain realistic results or a too complex one for adapting the model to individual patients, and many of these models are not indicated for metabolic treatments. The individualisation of activity distribution is obtained by an optimisation method that adjusts our model to a set of experimental measurements. Significant differences in terms of absorbed doses are observed between our model and the standard generalist models, especially in terms of red marrow absorbed dose.

The diagnosis and management of the haematologic manifestations of lupus.

Haematological manifestations in systemic lupus erythematosus (SLE) are frequently observed. They are diverse and range from mild to severe. Therefore, different treatment approaches are needed from simply keeping vigilant to significant immunosuppression. Most treatment evidence is based on case-reports or small retrospective studies, as few randomized controlled trials have been performed. The development of biological therapy has opened new possible ways to treat the most severe cases but further clinical trials are necessary. In this review we consider the most common and characteristic haematological manifestations of SLE patients, focusing on their pathogenesis and management.

Psychometric properties of the Satisfaction with Life Scale (SWLS): secondary analysis of the Mexican Health and Aging Study.

BACKGROUND: The Satisfaction with Life Scale (SWLS) has been widely used and has proven to be a valid and reliable instrument for assessing satisfaction with life in diverse population groups, however, research on satisfaction with life and validation of different measuring instruments in Mexican adults is still lacking. The objective was to evaluate the psychometric properties of the Satisfaction with Life Scale (SWLS) in a representative sample of Mexican adults. METHODS: This is a methodological study to evaluate a satisfaction with life scale in a sample of 13,220 Mexican adults 50 years of age or older from the 2012 Mexican Health and Aging Study. The scale's reliability (internal consistency) was analysed using Cronbach's alpha and inter-item correlations. An exploratory factor analysis was also performed. Known-groups validity was evaluated comparing good-health and bad-health participants. Comorbidity, perceived financial situation, self-reported general health, depression symptoms, and social support were included to evaluate the validity between these measures and the total score of the scale using Spearman's correlations. RESULTS: The analysis of the scale's reliability showed good internal consistency (α = 0.74). The exploratory factor analysis confirmed the existence of a unique factor structure that explained 54% of the variance. SWLS was related to depression, perceived health, financial situation, and social support, and these relations were all statistically significant (P < .01). There was significant difference in life satisfaction between the good- and bad-health groups. CONCLUSIONS: Results show good internal consistency and construct validity of the SWLS. These results are comparable with results from previous studies. Meeting the study's objective to validate the scale, the results show that the Spanish version of the SWLS is a reliable and valid measure of satisfaction with life in the Mexican context.

VNTR polymorphisms of the IL-4 and IL-1RN genes and their relationship with frailty syndrome in Mexican community-dwelling elderly.

Inflammation is a key event that is closely associated with the pathophysiology of frailty. The relationship of genetic polymorphisms into inflammatory cytokines with frailty remains poorly understood. The aim of this study was to investigate the association between VNTR polymorphisms of the IL-4 and IL-1RN genes with the risk of frailty. We included a sample of 630 community-dwelling elderly aged 70 and older. Both IL-4 and IL-1RN VNTR polymorphisms were genotyped by the polymerase chain reaction (PCR) method. Mean age was 77.7 years (SD = 6.0) and 52.5 % were women. The participants classified as frail were more likely to be older, had lower MMSE score (p < 0.001), and had more disability for IADL (p < 0.001) and ADL (p < 0.001). Genotypic and allelic frequencies for the IL-4 VNTR polymorphism did not show significant differences between study groups (p > 0.05). However, we just observed a significant difference in the allelic frequencies for the A2 allele of the IL-1RN VNTR polymorphism between frail and nonfrail groups (OR 1.84, 95 % CI 1.08-3.12, p = 0.02). In addition, we analyzed the combined effect of the IL-4 and IL-1RN VNTR polymorphisms and their possible association with frailty, where the combined IL-4 (low) -IL-1Ra (high) genotype was identified as a marker of risk to frailty syndrome (OR 7.86, 95 % CI 1.83-33.69, p = 0.006). Our results suggest that both A2 allele and the combined IL-4 (low) -IL-1Ra (high) genotype might be genetic markers of susceptibility to frailty in Mexican elderly.

Angiogenic T cells are decreased in rheumatoid arthritis patients.

OBJECTIVE: The mechanisms underlying the increased cardiovascular risk (CVR) of rheumatoid arthritis (RA) patients remain unclear. Since the recently discovered angiogenic T cells (Tang) could have a role in endothelial repair through cooperating with endothelial progenitor cells (EPC), the main aim of this study was to analyse the Tang and EPC populations in relation to disease-specific features and traditional CVR factors. METHODS: Tang (CD3(+)CD31(+)CXCR4(+)) and EPC (CD34(+)VEGFR2(+)CD133(+)) populations were quantified by flow cytometry in peripheral blood samples from 103 RA patients and 18 matched healthy controls (HC). Clinical features and traditional CVR factors were obtained from clinical records, and 28-joint Disease Activity Score was used for measuring disease activity. Interferon (IFN) α serum levels were measured by immunoassays. RESULTS: Tang and EPC were strongly decreased in RA patients. In HC, but not in patients, both populations were positively correlated and inversely related to low density lipoprotein- and total-cholesterol levels. Sex, diabetes, dyslipidaemia, hypertension or obesity did not significantly influence Tang in patients, although detected in smokers. However, Tang were closely related to disease activity, autoantibody positivity and IFNα levels. Multiple regression analysis adjusted for traditional CVR factors confirmed that only disease activity, age at diagnosis, antinuclear antibody positivity and smoking habit could predict Tang frequency. Finally, patients who had suffered a CV event since their RA diagnosis presented higher Tang decrease and IFNα levels than those who were CV event-free. CONCLUSIONS: Disease-specific parameters, including disease activity, autoantibody profiles and IFNα levels, are associated with Tang decrease in RA, thus probably accounting for CVR.

Red cell distribution width is associated with cardiovascular risk and disease parameters in rheumatoid arthritis.

OBJECTIVE: Since red cell distribution width (RDW) has been associated with cardiovascular (CV) disease and inflammation in several conditions, the main aim of this study was to evaluate its prognostic value in RA patients and its potential associations with clinical features. METHODS: The history of CV events was retrospectively reviewed in 160 RA patients and RDW was recorded at disease onset and 6 and 12 months after diagnosis to calculate the accumulated value [area under the curve (AUC) RDW] and change during the first year (ΔRDW). In addition, RDW was analysed in 110 patients with established disease in relation to clinical features. RESULTS: Increased RDW at diagnosis and AUC RDW were able to predict the occurrence of CV events in RA patients [hazard ratio (HR) 1.247 (95% CI 1.079, 1.441), P = 0.003 and HR 1.038 (95% CI 1.018, 1.059), P = 0.0001, respectively] after adjusting by potential confounding factors. Receiver operating characteristic curve analyses revealed a better power of discrimination for the AUC RDW (P = 3.394 × 10(-5)). In addition, an increase in RDW during the first year was associated with poor CV outcome (P = 0.010). On the other hand, RDW in patients with established RA was significantly associated with disease activity, acute phase reactants and severity. CONCLUSION: RDW at disease onset may be used as an early marker of CV risk in RA, whereas in patients with established disease it was related to the activity of the disease. These findings suggest that RDW can be considered as a surrogate marker of inflammation and, consequently, CV risk in RA patients.

Altered profile of circulating microparticles in rheumatoid arthritis patients.

Microparticles (MPs) could be considered biomarkers of cell damage and activation as well as novel signalling structures. Since rheumatoid arthritis (RA) is characterized by immune and endothelial activation, the main aim of the present study was to analyse MP counts in RA patients. Citrated-blood samples were obtained from 114 RA patients, 33 healthy controls (HC) and 72 individuals with marked cardiovascular (CV) risk without autoimmune manifestations (CVR). MPs were analysed in platelet-poor plasma (PPP) and different subsets were identified by their surface markers: platelet- (CD41+), endothelial- (CD146+), granulocyte- (CD66+), monocyte- (CD14+) and Tang- (CD3+CD31+) derived. Disease activity score (DAS28), clinical and immunological parameters as well as traditional CV risk factors (diabetes, hypertension, dyslipidaemia and obesity) were registered from clinical records and all data were integrated using Principal Component Analysis (PCA). Absolute MP number was increased in RA patients compared with HC and positively correlated with traditional CV risk factors, similar to that of CVR subjects. In addition, frequency of the different MP subsets was different in RA patients and significantly associated with disease features. Moreover, in vitro assays revealed that MPs isolated from RA patients were able to promote endothelial activation and exhibited detrimental effects on human microvascular endothelial cells (HMEC-I) endothelial cell functionality. Circulating MPs from RA patients displayed quantitative and qualitative alterations that are the result of both disease-specific and traditional CV risk factors. Accordingly, this MP pool exhibited in vitro detrimental effects on endothelial cells, thus supporting their role as biomarkers of vascular damage.

C2238 atrial natriuretic peptide molecular variant is associated with endothelial damage and dysfunction through natriuretic peptide receptor C signaling.

RATIONALE: C2238 atrial natriuretic peptide (ANP) minor allele (substitution of thymidine with cytosine in position 2238) associates with increased risk of cardiovascular events. OBJECTIVE: We investigated the mechanisms underlying the vascular effects of C2238-αANP. METHODS AND RESULTS: In vitro, human umbilical vein endothelial cell were exposed to either wild-type (T2238)- or mutant (C2238)-αANP. Cell survival and apoptosis were tested by Trypan blue, annexin V, and cleaved caspase-3 assays. C2238-αANP significantly reduced human umbilical vein endothelial cell survival and increased apoptosis. In addition, C2238-αANP reduced endothelial tube formation, as assessed by matrigel. C2238-αANP did not differentially modulate natriuretic peptide receptor (NPR)-A/B activity with respect to T2238-αANP, as evaluated by intracellular cGMP levels. In contrast, C2238-αANP, but not T2238-αANP, markedly reduced intracellular cAMP levels in an NPR-C-dependent manner. Accordingly, C2238-αANP showed higher affinity binding to NPR-C, than T2238-αANP. Either NPR-C inhibition by antisense oligonucleotide or NPR-C gene silencing by small interfering RNA rescued survival and tube formation of human umbilical vein endothelial cell exposed to C2238-αANP. Similar data were obtained in human aortic endothelial cell with NPR-C knockdown. NPR-C activation by C2238-αANP inhibited the protein kinase A/Akt1 pathway and increased reactive oxygen species. Adenovirus-mediated Akt1 reactivation rescued the detrimental effects of C2238-αANP. Overall, these data indicate that C2238-αANP affects endothelial cell integrity through NPR-C-dependent inhibition of the cAMP/protein kinase A/Akt1 pathway and increased reactive oxygen species production. Accordingly, C2238-αANP caused impairment of acetylcholine-dependent vasorelaxation ex vivo, which was rescued by NPR-C pharmacological inhibition. Finally, subjects carrying C2238 minor allele showed early endothelial dysfunction, which highlights the clinical relevance of our results. CONCLUSIONS: C2238-αANP reduces endothelial cell survival and impairs endothelial function through NPR-C signaling. NPR-C targeting represents a potential strategy to reduce cardiovascular risk in C2238 minor-allele carriers.

Decades of Experience in the Diagnosis of Dengue Fever in the Northwest of Mexico.

BACKGROUND: The State of Baja California Sur is in an arid region of Mexico, the southern half of the Baja California Peninsula. Given its aridity and physical isolation from mainland Mexico, there were no records of dengue fever in the state before 1985. Until now, no data on dengue incidence had been published. OBJECTIVE: To study some epidemiological features of dengue fever in Baja California Sur, Mexico in the last 30 years. METHODS: Total number of cases, general population, sex, age groups, serotypes, mortality, and incidence data were analyzed. RESULTS: There was a 652% increase in reported cases from 2012 through 2014. Age groups mostly affected were adults aged 15-24 and 45-64 years old. CONCLUSIONS: This study makes a thorough analysis of the incidence of dengue and makes recommendations to face the epidemiological challenge.