Prevention and reduction of excessive use of alcohol represents damages to society in general. In turn, arterial hypertension is the main attributable risk factor premature life lost years and ...disability.
To investigate the relationship between alcohol consumption and high blood pressure in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
A baseline data of total of 7,655 participants volunteers between 35 and 74 years of age, of both genders, in six educational and research institutions of three different regions of the country were interviewed between 2008-2010. Socioeconomic, haemodynamic, anthropometric and health data were collected in the research centers of ELSA-Brasil. The presence of high blood pressure was identified when the systolic blood pressure was ≥140 mm Hg and/or the diastolic was ≥90 mm Hg. Alcohol consumption was estimated and categorized regarding consumption and pattern of ingestion. The Student's t-test, chi-squared and logistic regression tests were used for analysis, including potential co-variables of the model, and a 5% significance level was adopted.
A dose-response relation was observed for the consumption of alcohol (g/week) in systolic blood pressure and diastolic blood pressure. Alcohol consumption was associated with high blood pressure in men who reported moderate (OR = 1.69; 95%CI 1.35-2.11) and excessive (OR = 2.70; 95%CI 2.04-3.59) consumption. Women have nearly three times more chance of presenting elevated blood pressure when presenting excessive consumption (OR = 2.86, 95%CI 1.77-4.63), and binge drinkers who drink more than 2 to 3 times a month have approximately 70% more chance of presenting with elevated blood pressure, after adjusting for consumption of drinks with meals.
The consumption of alcohol beverages increases the odds of elevated blood pressure, especially among excessive drinkers. Therefore alcohol consumption needs a more robust regulation in view of its impact on population health.
To evaluate the association of ultra-processed food (UPF) consumption with gains in weight and waist circumference, and incident overweight/obesity, in the Brazilian Longitudinal Study of Adult ...Health (ELSA-Brasil) cohort.
We applied FFQ at baseline and categorized energy intake by degree of processing using the NOVA classification. Height, weight and waist circumference were measured at baseline and after a mean 3·8-year follow-up. We assessed associations, through Poisson regression with robust variance, of UPF consumption with large weight gain (1·68 kg/year) and large waist gain (2·42 cm/year), both being defined as ≥90th percentile in the cohort, and with incident overweight/obesity.
Brazil.
Civil servants of Brazilian public academic institutions in six cities (n 11 827), aged 35-74 years at baseline (2008-2010).
UPF provided a mean 24·6 (sd 9·6) % of ingested energy. After adjustment for smoking, physical activity, adiposity and other factors, fourth (>30·8 %) v. first (<17·8 %) quartile of UPF consumption was associated (relative risk (95 % CI)) with 27 and 33 % greater risk of large weight and waist gains (1·27 (1·07, 1·50) and 1·33 (1·12, 1·58)), respectively. Similarly, those in the fourth consumption quartile presented 20 % greater risk (1·20 (1·03, 1·40)) of incident overweight/obesity and 2 % greater risk (1·02; (0·85, 1·21)) of incident obesity. Approximately 15 % of cases of large weight and waist gains and of incident overweight/obesity could be attributed to consumption of >17·8 % of energy as UPF.
Greater UPF consumption predicts large gains in overall and central adiposity and may contribute to the inexorable rise in obesity seen worldwide.
Background
Over 30% of local allergic rhinitis (LAR) patients self‐report bronchial symptoms suggestive of asthma, but the relationship between the allergen exposure and the bronchial symptoms has ...not been studied.
Objective
To investigate whether a bronchial counterpart of LAR exists.
Methods
Patients were classified by clinical history, skin prick test/serum specific IgE (sIgE), and nasal allergen provocation test (NAPT) into the LAR, allergic rhinitis (AR), and nonallergic rhinitis (NAR) phenotypes. Twenty‐eight LAR, 18 AR, and 19 NAR patients self‐reporting bronchial symptoms suggestive of asthma and 8 healthy controls (HC) were subjected to a methacholine test (MT) before (Visit 1) and 24 hours after (Visit 3) a bronchial provocation test with Dermatophagoides pteronyssinus (BPT‐DP) (Visit 2). Induced sputum and peripheral blood obtained after each MT were analyzed for immune cell populations, tryptase, ECP, and sIgE.
Results
A positive MT was found in 50% of LAR, 83.3% of AR, 57.89% of NAR, and 0% of HC individuals (P = 0.022 AR vs LAR) at V1. BPT‐DP was positive in 8 LAR and 15 AR patients (28% vs 83.3%, P < 0.001), with no positive responses in NAR and HC. All BPT‐DP+ patients experienced a significant decrease of PC20 at V3 vs V1 (P = 0.016 LAR, P ≤ 0.001 AR). BPT‐DP+ patients also showed a significant increase of eosinophils, monocytes, and ECP in induced sputum at V3 compared with V1.
Conclusion
The results suggest the existence of a new asthma phenotype (local allergic asthma) defined by absence of systemic atopy and positivity to BPT with allergen.
Twenty‐eight percent of patients with house dust mite (HDM)–triggered local allergic rhinitis (LAR) and asthma‐like symptoms display positive bronchial allergen provocation test (BAPT) responses. In LAR patients, BAPT induces a significant increase in the airway hyperresponsiveness together with a recruitment and activation of eosinophils and monocytes. Collectively, these findings suggest the existence of differentiated asthma phenotype defined by the absence of atopy and positive response to BAPT. NAPT: Nasal allergen provocation test
•A novel method for assessing prediction of extremal hydrological events.•Bayesian causal modelling tool for predictive assessment.•Hybridization of Classical and new Hydrology based on Artificial ...Intelligence.•HydroPredicT_Extreme as a new tool for the prediction of potential flooding events.•Applicability to different time scales of extreme and sudden events.
Disastrous losses related to high-flow events have increased dramatically over the past decades largely due to an increase in flood-prone regions settlements and shift in hydrological trends largely due to Climate Change. To mitigate the societal impact of hydrological and hydraulic extremes, knowledge of the processes leading to these extreme events is vital. Hydrological modelling is one of the main tools in this quest for knowledge but comes with uncertainties. For that it is necessary to deeply study the impact of hydrological models’ structure on the magnitude and timing of extreme rainfall-runoff events. This paper is mainly aimed to show the development of a method called “HydroPredicT_Extreme” based on Bayesian Causal Modelling (BCM), a technique within Artificial Intelligence (AI). This method may enhance predictive capacity of extreme rainfall-runoff events. “HydroPredicT_Extreme” follows an iterative methodology that comprise 2 main stages. First one comprises a mixed graphical/analytical method from Hydrograph. This stage is conditioned by two initial constraints which are, a) pluviometry station is representative of hydrograph downstream flow behaviour; b) there must be independence of events. This first stage comprises sub-phases such as: 1.1. Calculation of Response Time (RT) through a mixed graphical/analytical approach, 1.2 Subtraction of RT from the flow series to remove the Rainfall-Flow delay; 1.3 Calculation base flow rate; 1.4 Subtraction base-flow from flow series to work on absolute inputs. Second man stage is called Bayesian Causal Modelling Translation (BCMT) that comprises the 2.1 Learning, 2.2 Training, 2.3 Simulation through BCM modelling, 2.4 Sensitivity Analysis-Validation. This whole methodology will become a digital application and software that could be extrapolated to several similar case studies. This may be coupled with posterior devices for the prevention of catastrophic flood consequences in the form of MultiHazard-Early Warning System (MH-EWS) or others.
Alzheimer's Disease: An Updated Overview of Its Genetics Andrade-Guerrero, Jesús; Santiago-Balmaseda, Alberto; Jeronimo-Aguilar, Paola ...
International journal of molecular sciences,
02/2023, Letnik:
24, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the ...total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in
(
),
(
), or the
(
). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aβ) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.
Detergent-resistant membranes (DRMs) microdomains, or "raft lipids", are key components of the plasma membrane (PM), being involved in membrane trafficking, signal transduction, cell wall metabolism ...or endocytosis. Proteins imbibed in these domains play important roles in these cellular functions, but there are few studies concerning DRMs under abiotic stress. In this work, we determine DRMs from the PM of broccoli roots, the lipid and protein content, the vesicles structure, their water osmotic permeability and a proteomic characterization focused mainly in aquaporin isoforms under salinity (80 mM NaCl). Based on biochemical lipid composition, higher fatty acid saturation and enriched sterol content under stress resulted in membranes, which decreased osmotic water permeability with regard to other PM vesicles, but this permeability was maintained under control and saline conditions; this maintenance may be related to a lower amount of total PIP1 and PIP2. Selective aquaporin isoforms related to the stress response such as PIP1;2 and PIP2;7 were found in DRMs and this protein partitioning may act as a mechanism to regulate aquaporins involved in the response to salt stress. Other proteins related to protein synthesis, metabolism and energy were identified in DRMs independently of the treatment, indicating their preference to organize in DMRs.
Background and purpose
The association between alcohol intake and cognitive decline has been widely studied. Sex differences and cognitive domains affected by alcohol intake patterns make this topic ...complex. The objective of this study was to investigate the effect of alcohol intake on cognition in middle‐aged participants in the Brazilian Longitudinal Study of Adult Health by sex during 4 years of follow‐up.
Methods
A total of 7595 participants (55% women) aged between 50 and 75 years at baseline were assessed. Semantic and phonemic fluency, memory, and executive functions were assessed at baseline (2008–2010) and repeated during Visit 2. Linear mixed models were used to investigate the association between cognition and current abstainers, never drinkers, light drinkers, moderate drinkers, and heavy drinkers.
Results
Heavy alcohol intake accentuated the decline in executive functions for men (β = −0.01, p < 0.05), and in semantic fluency (β = −0.02, p < 0.05) and memory (β = −0.02, p < 0.05) for women. Never drinker men also showed an accentuated decline in semantic fluency (β = −0.02, p < 0.01). Moderate alcohol intake slowed cognitive decline in phonemic fluency for men (β = 0.02, p < 0.01) and women (β = 0.01, p < 0.01), and in executive functions (β = 0.01, p < 0.05) for women.
Conclusions
Having more than 14 drinks per week can impact executive functions in men and memory in women. In addition, alcohol consumption of seven to 14 drinks per week may have a protective effect on gender‐specific cognitive functions. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.
The association between alcohol intake and cognition differently impacts the cognitive domains for men and women in a short period of time. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.
Hypoxia in freshwater ecosystems is spreading as a consequence of global change, including pollution and eutrophication. In the Patagonian Andes, a decline in precipitation causes reduced lake water ...volumes and stagnant conditions that limit oxygen transport and exacerbate hypoxia below the upper mixed layer. We analyzed the molecular and biochemical response of the North Patagonian bivalve
after 10 days of experimental anoxia (<0.2 mg O
/L), hypoxia (2 mg O
/L), and normoxia (9 mg O
/L). Specifically, we investigated the expression of an alternative oxidase (AOX) pathway assumed to shortcut the regular mitochondrial electron transport system (ETS) during metabolic rate depression (MRD) in hypoxia-tolerant invertebrates. Whereas, the AOX system was strongly upregulated during anoxia in gills, ETS activities and energy mobilization decreased less transcription of glycogen phosphorylase (GlyP) and succinate dehydrogenase (SDH) in gills and mantle. Accumulation of succinate and induction of malate dehydrogenase (MDH) activity could indicate activation of anaerobic mitochondrial pathways to support anoxic survival in
. Oxidative stress protein carbonylation, glutathione peroxidase (GPx) expression and apoptotic intensity (caspase 3/7 activity) decreased, whereas an unfolded protein response (HSP90) was induced under anoxia. This is the first clear evidence of the concerted regulation of the AOX and ETS genes in a hypoxia-tolerant freshwater bivalve and yet another example that exposure to hypoxia and anoxia is not necessarily accompanied by oxidative stress in hypoxia-tolerant mollusks.
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•Broccoli root vesicles showed stability and high entrapment efficiency.•Nanoencapsulation with membrane vesicles provide an efficient system for keratinocytes cell ...delivery.•Effectivity is probed by penetrating in skin layers.
During the last few years, membrane vesicles (as exovesicles) have emerged as potential nanocarriers for therapeutic applications. They are receiving attention due to their proteo-lipid nature, size, biocompatibility and biodegradability. In this work, we investigated the potential use of isolated root plasma membrane vesicles from broccoli plants as nanocarriers. For that, the entrapment efficiency and integrity of the vesicles were determined. Also, the delivery of keratinocytes and penetrability through skin were studied. The results show that the broccoli vesicles had high stability, in relation to their proteins, and high entrapment efficiency. Also, the interaction between the vesicles and keratinocytes was proven by the delivery of an encapsulated fluorescent product into cells and by the detection of plant proteins in the keratinocyte plasma membrane, showing the interactions between the membranes of two species of distinct biological kingdoms. Therefore, these results, together with the capacity of brassica vesicles to cross the skin layers, detected by fluorescent penetration, enable us to propose a type of nanocarrier obtained from natural plant membranes for use in transdermal delivery.
Combined PD-1 and CTLA-4-targeted immunotherapy with nivolumab and ipilimumab is effective against melanoma, renal cell carcinoma and non-small-cell lung cancer
. However, this comes at the cost of ...frequent, serious immune-related adverse events, necessitating a reduction in the recommended dose of ipilimumab that is given to patients
. In mice, co-treatment with surrogate anti-PD-1 and anti-CTLA-4 monoclonal antibodies is effective in transplantable cancer models, but also exacerbates autoimmune colitis. Here we show that treating mice with clinically available TNF inhibitors concomitantly with combined CTLA-4 and PD-1 immunotherapy ameliorates colitis and, in addition, improves anti-tumour efficacy. Notably, TNF is upregulated in the intestine of patients suffering from colitis after dual ipilimumab and nivolumab treatment. We created a model in which Rag2
Il2rg
mice were adoptively transferred with human peripheral blood mononuclear cells, causing graft-versus-host disease that was further exacerbated by ipilimumab and nivolumab treatment. When human colon cancer cells were xenografted into these mice, prophylactic blockade of human TNF improved colitis and hepatitis in xenografted mice, and moreover, immunotherapeutic control of xenografted tumours was retained. Our results provide clinically feasible strategies to dissociate efficacy and toxicity in the use of combined immune checkpoint blockade for cancer immunotherapy.
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