The prognostic importance of obstructive sleep apnea (OSA) severity and other polysomnographic parameters in patients with resistant hypertension (RHT) has never been evaluated. We aimed to assess it ...in a prospective cohort of 422 individuals with RHT. OSA presence/severity was ascertained by complete polysomnography (PSG) at baseline. Multivariable Cox regressions assessed the risks associated with OSA severity and other PSG parameters (apnea-hypopnea index, sleep duration, nocturnal hypoxemia and periodic limb movements) for the primary (total cardiovascular events CVEs and all-cause mortality) and secondary outcomes (major CVEs). In the subgroup of patients with moderate/severe OSA, the risks associated with CPAP treatment were also estimated in relation to untreated individuals. One-hundred and eighty-six participants (44%) had no/mild OSA and 236 (56%) had moderate/severe OSA, and 67 of them were CPAP-treated. Over a mean follow-up of 5 years, there were 46 CVEs (37 major ones) and 44 all-cause deaths. Neither the presence of moderate/severe or severe OSA, nor being untreated during follow-up, was associated with significant excess risks for any outcome in relation to the subgroup with no/mild OSA. Similarly, no other PSG-derived parameter predicted any adverse outcome. Otherwise, CPAP treatment was associated with non-significant risk reductions of 37% for total CVEs, 49% for major CVEs and 63% for all-cause mortality in relation to those who remained untreated during follow-up. In conclusion, the presence/severity of OSA and its related PSG parameters were not associated with worse cardiovascular/mortality prognosis in patients with RHT. However, CPAP treatment might be protective in individuals with moderate/severe OSA.
Single-pixel imaging is an imaging technique that has recently attracted a lot of attention from several areas. This paper presents a study on the influence of the Hadamard basis ordering on the ...image reconstruction quality, using simulation and experimental methods. During this work, five different orderings, Natural, Walsh, Cake-cutting, High Frequency and Random orders, along with two different reconstruction algorithms, TVAL3 and NESTA, were tested. Also, three different noise levels and compression ratios from 0.1 to 1 were evaluated. A single-pixel camera was developed using a digital micromirror device for the experimental phase. For a compression ratio of 0.1, the Cake-cutting order achieved the best reconstruction quality, while the best contrast was achieved by Walsh order. For compression ratios of 0.5, the Walsh and Cake-cutting orders achieved similar results. Both Walsh and Cake-cutting orders reconstructed the images with good quality using compression ratios from 0.3. Finally, the TVAL3 algorithm showed better image reconstruction quality, in comparison with NESTA, when considering compression ratios from 0.1 to 0.5.
Heliconius butterflies are widely distributed across the Neotropics and have evolved a stunning array of wing color patterns that mediate Müllerian mimicry and mating behavior. Their rapid radiation ...has been strongly influenced by hybridization, which has created new species and allowed sharing of color patterning alleles between mimetic species pairs. While these processes have frequently been observed in widespread species with contiguous distributions, many Heliconius species inhabit patchy or rare habitats that may strongly influence the origin and spread of species and color patterns. Here, we assess the effects of historical population fragmentation and unique biology on the origins, genetic health, and color pattern evolution of two rare and sparsely distributed Brazilian butterflies, Heliconius hermathena and Heliconius nattereri.
We assembled genomes and re-sequenced whole genomes of eight H. nattereri and 71 H. hermathena individuals. These species harbor little genetic diversity, skewed site frequency spectra, and high deleterious mutation loads consistent with recent population bottlenecks. Heliconius hermathena consists of discrete, strongly isolated populations that likely arose from a single population that dispersed after the last glacial maximum. Despite having a unique color pattern combination that suggested a hybrid origin, we found no genome-wide evidence that H. hermathena is a hybrid species. However, H. hermathena mimicry evolved via introgression, from co-mimetic Heliconius erato, of a small genomic region upstream of the color patterning gene cortex.
Heliconius hermathena and H. nattereri population fragmentation, potentially driven by historical climate change and recent deforestation, has significantly reduced the genetic health of these rare species. Our results contribute to a growing body of evidence that introgression of color patterning alleles between co-mimetic species appears to be a general feature of Heliconius evolution.
The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI ...With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial.
We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c HbA1c: < 6.0% < 42 mmol/mol, 6.0%-6.4% 42-47 mmol/mol; pre-diabetes mellitus, and ≥ 6.5% ≥ 48 mmol/mol; diabetes mellitus), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n = 2907 35%) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P < 0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre-diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, > 6.5%) and known diabetes mellitus compared with those with HbA1c < 6.0% was 1.39 (1.17-1.64); P < 0.001 and 1.64 (1.43-1.87); P < 0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 1.10-1.47; P < 0.001) compared with those with HbA1c < 6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial.
In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c < 6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
The objective of this study was to evaluate the effect of body image dissatisfaction on symptoms of depressive disorder in adolescents. This is a cross-sectional study that included 2,162 adolescents ...ages 18-19 born in São Luís, Maranhão, Brazil, which was part of the joint RPS cohort (Brazilian birth cohorts of Ribeirão Preto-SP, Pelotas-RS, and São Luís-MA). Socioeconomic characteristics, nutritional status, mental health, and body image characteristics were evaluated. Body image was assessed by Stunkard's silhouettes scale. The presence of symptoms indicative of depressive disorder was investigated through a diagnostic interview MINI (Mini International Neuropsychiatric Interview). A theoretical model was built in a Directed Acyclic Graph (DAG) in order to investigate the relationship between the variables of the study. The relationship was estimated weighting the inverse probability of selection for the variables of adjustment: sex and nutritional status. Among the dissatisfied adolescents due to overweight, 66.54% were girls, 32.85% were overweight, and 11.99% were obese (P<0.01). There was a significant association between dissatisfaction due to overweight and symptoms of depressive disorder (P=0.01), and there was no evidence of the same association with dissatisfaction due to thinness. Therefore, only dissatisfaction due to overweight was associated with the symptoms of depressive disorder in the evaluated adolescents.
The increasing knowledge on the genetic basis of disease has allowed the development of promising gene-targeted therapies that can be applied to numerous diseases. Such genetic-based approaches ...involve the use of nucleic acids as therapeutic agents, either for the insertion or repair and regulation of specific genes. However, the clinical application of these large and charged molecules remains highly dependent on the development of delivery systems capable of mediating efficient cellular uptake. Since the first observations, two decades ago, that some protein-derived domains can translocate across biological membranes, a wide group of peptides called cell-penetrating peptides (CPPs) have been considered one of the most promising tools to improve non-invasive cellular delivery of therapeutic molecules. The mechanistic basis of CPP and CPP conjugate cellular uptake remains controversial. However, biophysical studies on the interactions of CPPs with membrane models have contributed to unravel the mechanisms underlying CPP membrane translocation as well as to propose relationships between those mechanisms and CPP efficiency in mediating cargo delivery. In this review, representative examples of CPPs were gathered from the most recent literature in order to emphasize the contributions of chemists, biophysicists and cell biologists towards the rational design of increasingly more efficient delivery systems. In this context, the present review aims at giving an overview of some of the most significant CPP families and their biological applications as nucleic acid delivery systems.
We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber ...with a fiducial mass of (1.30±0.01) ton, resulting in a 1.0 ton yr exposure. The energy region of interest, 1.4,10.6 keV_{ee} (4.9,40.9 keV_{nr}), exhibits an ultralow electron recoil background rate of 82_{-3}^{+5}(syst)±3(stat) events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6 GeV/c^{2}, with a minimum of 4.1×10^{-47} cm^{2} at 30 GeV/c^{2} and a 90% confidence level.
The XENON1T dark matter experiment Aalbers, J.; Alfonsi, M.; Amaro, F. D. ...
The European physical journal. C, Particles and fields,
12/2017, Letnik:
77, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid ...xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.
•The aging process encompasses the development of a heightened inflammatory status in the brain.•Environmental triggers, like stress, infection and poor diet contribute to neuroimmune senescence and ...“inflammaging”.•Microglia in the aged brain experience an augmented inflammatory profile and impaired defensive and housekeeping roles.•Microglia dysfunction impacts normal brain homeostasis, promoting circuitry dysfunction and cognitive impairment.•Better control of our diet, physical activity and stress levels are cost-effective strategies to promote healthy aging.
Among all major organs, the brain is one of the most susceptible to the inexorable effects of aging. Throughout the last decades, several studies in human cohorts and animal models have revealed a plethora of age-related changes in the brain, including reduced neurogenesis, oxidative damage, mitochondrial dysfunction and cell senescence. As the main immune effectors and first responders of the nervous tissue, microglia are at the center of these events. These cells experience irrevocable changes as a result from cumulative exposure to environmental triggers, such as stress, infection and metabolic dysregulation. The age-related immunosenescent phenotype acquired by microglia is characterized by profound modifications in their transcriptomic profile, secretome, morphology and phagocytic activity, which compromise both their housekeeping and defensive functions. As a result, aged microglia are no longer capable of establishing effective immune responses and sustaining normal synaptic activity, directly contributing to age-associated cognitive decline and neurodegeneration. This review discusses how lifestyle and environmental factors drive microglia dysfunction at the molecular and functional level, also highlighting possible interventions to reverse aging-associated damage to the nervous and immune systems.
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