Objective Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular ...remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years. Methods MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls. Results PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age ( P = .015), hypertension ( P = .021), and ankle-brachial index ( P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality ( P < .03). Conclusions Our results suggest that MMP-10 is associated with severity and poor outcome in PAD.
Rationale
Experimental studies and epidemiological data in adults suggest that somatomedin‐C (insulin‐like growth factor‐1, IGF‐1) may play a role in asthma by modulating airway inflammation, ...bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood.
Methods
We established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF‐1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API.
Results
Complete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API–. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API– children. API+ children had higher birth weight and significantly higher IGF‐1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API–, p = .01). In the multivariable analysis, IGF‐1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF‐1 = 1.03 1.0–1.06, p = .015).
Conclusions
Higher insulin‐like growth factor‐1 in cord blood is associated with asthma risk in the preschool years.
The relationship between structure and corrosion inhibition of a series of 30 imidazol, benzimidazol, and pyridine derivatives has been established through the investigation of quantum descriptors ...calculated with PBE/6-311++G**. A quantitative structure–property relationship model was obtained by examination of these descriptors using a genetic functional approximation method based on a multiple linear regression analysis. Our results indicate that the efficiency of corrosion inhibitors is strongly associated with aromaticity, electron donor ability, and molecular volume descriptors. In order to calibrate and validate the proposed model, we performed electrochemical impedance spectroscopy (EIS) studies on imidazole, 2-methylimidazole, benzimidazole, 2-chloromethylbenzimidazole, pyridine, and 2-aminopyridine compounds. The experimental values for efficiency of corrosion inhibition are in good agreement with the estimated values obtained by our model, thus confirming that our approach represents a promising and suitable tool to predict the inhibition of corrosion attributes of nitrogen containing heterocyclic compounds. The adsorption behavior of imidazole or benzimidazole heterocyclic molecules on the Fe(110) surface was also studied to elucidate the inhibition mechanism; the aromaticity played an important role in the adsorbate–surface complex.
An inverse CeO2/Cu2O/Cu(111) catalyst is able to activate methane at room temperature producing C, CHx fragments and COx species on the oxide surface. The addition of water to the system leads to a ...drastic change in the selectivity of methane activation yielding only adsorbed CHx fragments. At a temperature of 450 K, in the presence of water, a CH4 → CH3OH catalytic transformation occurs with a high selectivity. OH groups formed by the dissociation of water saturate the catalyst surface, removing sites that could decompose CHx fragments, and generating centers on which methane can directly interact to yield methanol.
Parkinson's disease is a neurodegenerative process characterized by numerous motor and nonmotor clinical manifestations for which effective, mechanism-based treatments remain elusive. Here we discuss ...a series of critical issues that we think researchers need to address to stand a better chance of solving the different challenges posed by this pathology.
Over the past decade, “omics” approaches have advanced our understanding of the molecular programming of the airways in humans. Several studies have identified potential molecular mechanisms that ...contribute to early life epigenetic reprogramming, including DNA methylation, histone modifications, microRNAs, and the homeostasis of the respiratory mucosa (epithelial function and microbiota). Current evidence supports the notion that early infancy is characterized by heightened susceptibility to airway genetic reprogramming in response to the first exposures in life, some of which can have life‐long consequences. Here, we summarize and analyze the latest insights from studies that support a novel epigenetic paradigm centered on human maturational and developmental programs including three cardinal elements: genes, environment, and developmental timing. The combination of these factors is likely responsible for the functional trajectory of the respiratory system at the molecular, functional, and clinical levels.
The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few ...studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic
Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSS-induced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR-223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD.
Summary The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many ...clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made.
Introduction
High altitude pulmonary edema (HAPE) is a form of acute noncardiogenic pulmonary edema caused by altitude‐related hypoxia seen in children as well as in adults. In this systematic review ...we focus in HAPE occurring in children and adolescents.
Methods
A systematic review was conducted including publications in children 0–18 years of age from three databases up to June 2022.
Results
Thirty‐five studies representing 210 cases were found. The mean age was 9.8 ± 3.6 years with a male/female ratio of 2.6. The peak age incidence was seen in children between 6 and 10 years old. Only two children (0.9%) were ≤2 years old. The mean altitude in 166 cases was 2861 masl. Only 17 cases (8.1%) occurred at altitudes below 2500 masl. Regarding the different HAPE subtypes there was a predominance of re‐entry HAPE (R‐HAPE) with 58%, followed by classic HAPE (C‐HAPE) with 37.6%. The mean time between arrival and onset of symptoms was 16.5 h. The mortality rate was 1.4%. In 10/28 (36%) of C‐HAPE cases there was a structural cardiac/pulmonary anomaly compared to 1/19 (5%) in R‐HAPE (p < 0.01). HAPE recurrence was found in 46 cases (21.9%). The involvement in the chest X‐rays was seen predominantly in the apices and in the right lung.
Conclusions
R‐HAPE was the most common HAPE subtype; HAPE peak age was found between 6 and 10 years of age; HAPE was more frequent in males and was rare in children under 2 years old; associated HAPE structural abnormalities were more common in C‐HAPE than in R‐HAPE.
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