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Recent studies have demonstrated that the rat adipose tissue expresses some of the components necessary for the production of angiotensin II (Ang II) and the receptors mediating its actions. The aim of this work is to characterize the expression of the renin–angiotensin system (RAS) components in perivascular adipose tissue and to assess differences in the expression pattern depending on the vascular bed and type of adipose tissue. We analyzed Ang I and Ang II levels as well as mRNA levels of RAS components by a quantitative RT-PCR method in periaortic (PAT) and mesenteric adipose tissue (MAT) of 3-month-old male Wistar–Kyoto rats. PAT was identified as brown adipose tissue expressing uncoupling protein-1 (UCP-1). It had smaller adipocytes than those from MAT, which was identified as white adipose tissue. All RAS components, except renin, were detected in both PAT and MAT. Levels of expression of angiotensinogen, Ang-converting enzyme (ACE), and ACE2 were similar between PAT and MAT. Renin receptor expression was five times higher, whereas expression of chymase, AT1a, and AT2receptors were significantly lower in PAT compared with MAT respectively. In addition, three isoforms of the AT1areceptor were found in perivascular adipose tissue. The AT1breceptor was found at very a low expression level. Ang II levels were higher in MAT with no differences between tissues in Ang I. The results show that the RAS is differentially expressed in white and brown perivascular adipose tissues implicating a different role for the system depending on the vascular bed and the type of adipose tissue. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii colonization rates in healthy patients are unclear. Previously published studies suggest that the fungus could play a role in the physiopathology and progression of chronic respiratory diseases., Aims: The goal of this study was to determine the prevalence of colonization by this fungus in the lower respiratory tract of immunocompetent patients who are not at risk of dysbiosis., Methods: The presence of P. jirovecii was confirmed in the bronchoalveolar lavage (BAL) samples from adults who underwent bronchoscopy for non-infectious reasons, had no immunosuppressive factors, and had not been on antibiotic treatment for at least one month. The results were compared with those obtained in the study on the presence of Pneumocystis in environmental dust samples obtained by swabbing surfaces in the participating subjects' domestic settings. Real-time PCR was the technique used for detecting the fungus in both types of samples., Results: A total of 97 BAL samples and 49 domestic environment samples were studied. The medical reasons for needing a bronchoscopy were, mainly, the examination of both pulmonary neoplasm in 55 patients (57%) and diffuse interstitial lung disease in 21 patients (22%). The overall prevalence of P. jirovecii in our population was 7.22% in BAL samples and 0% in domestic samples., Conclusions: The presence of P. jirovecii in the lower respiratory tract is relevantly linked with the patient's immune status, not with an underlying pathology. Prevalence is low in immunocompetent individuals who do not have any infectious pathology and are not having antimicrobial treatments. Our results do not enable us to figure out which the environmental niche of P. jirovecii is., (Copyright © 2024 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Pulmonary surfactant, the primary substance lining the epithelium of the human Lower Respiratory Tract (LRT), is rich in lipids, with dipalmitoyl-phosphatidylcholine (DPPC) being the most abundant. Although surfactants are known to have antifungal activity against some yeast species, the significant presence of species like Malassezia restricta in the lung mycobiome suggests that these yeasts may exhibit some level of lipo-tolerance or even lipo-affinity for pulmonary lipids. This study explored the affinity and tolerance of yeasts, identified as significant members of the lung microbiome, to pulmonary lipids through culture-based methods. Eleven species from the genera Malassezia, Candida (including the new genera Nakaseomyces and Meyerozyma), and Cryptococcus were tested for their growth on media containing pulmonary lipids such as DPPC and commercial porcine surfactant and in other culture medium that contain non-pulmonary lipids such as glycerol monostearate and tweens. The yeasts' lipo-affinity or lipo-tolerance was assessed based on their growth on these lipids compared to standard media, specifically Modified Leeming Notman Agar (MLNA) for Malassezia species and Sabouraud Dextrose Agar (SDA) for the other genera. The addition of DPPC or surfactant to the media enhanced the growth of most Malassezia yeasts and some Cryptococcus species. C. parapsilosis, Meyerozyma guilliermondii and Cryptococcus neoformans s.s. showed similar growth to that on the standard media, while the other yeasts primarily demonstrated lipo-tolerance without lipo-affinity for these compounds. To our knowledge, this is the first report on the influence of pulmonary lipids on the in vitro growth of Malassezia spp. and other yeast members of the lung mycobiome. Some yeasts, such as Malassezia restricta, commonly found in the lower respiratory tract (LRT), exhibit specific affinity for lung lipids like DPPC and commercial porcine surfactant. This finding suggests that lung lipids may play a significant role in shaping the LRT mycobiome., Competing Interests: Declarations. Conflict of interest: None., (© 2024. The Author(s).)

Background: Alzheimer's disease (AD) biomarkers reflect key elements of pathophysiology and improve the diagnostic process. However, their use in routine clinical practice is still limited., Objective: We aimed to assess neurologists' barriers and enablers to early AD diagnosis using core AD biomarkers., Methods: We conducted an online study in collaboration with the Spanish Society of Neurology. Neurologists answered a survey exploring their attitudes towards AD diagnosis using biomarkers in mild cognitive impairment (MCI) or mild AD dementia. Multivariate logistic regression analyses were conducted to determine the association between neurologists' characteristics and diagnostic attitudes., Results: We included 188 neurologists with a mean age (SD) of 40.6 (11.3) years, 52.7% male. Most participants had access to AD biomarkers, mainly in cerebrospinal fluid (CSF) (89.9%,#x0025;, n = 169). The majority of participants (95.2%,#x0025;, n = 179) considered CSF biomarkers useful for an etiological diagnosis in MCI. However, 85.6% of respondents (n = 161) used them in less than 60% of their MCI patients in routine clinical practice. Facilitating patients and their families to plan for the future was the most frequent enabler for the use of biomarkers. Short consultation time and practicalities associated with the programming of a lumbar puncture were the most common barriers. A younger neurologist age (p = 0.010) and a higher number of patients managed weekly (p = 0.036) were positively associated with the use of biomarkers., Conclusion: Most neurologists had a favorable attitude to the use of biomarkers, especially in MCI patients. Improvements in resources and consultation time may increase their use in routine clinical practice.

This study analyzes the relationship between the mycobiome of the Lower Respiratory Tract (LRT) and the fungi in the domestic environment. Samples studied consisted of Broncho-Alveolar Lavage (BAL) from 45 patients who underwent bronchoscopy for different diagnostic purposes, and dust and air from the houses (ENV) of 20 of them (44.4%). Additionally, five bronchoscopes (BS) were also analyzed and negative controls were included for every procedure. All samples were processed for DNA extraction and cultures, which were performed in Sabouraud Dextrose and Potato Dextrose Agar. The fungal Internal Transcribed Spacer (ITS2) was sequenced by the Solexa/Illumina system and sequences were analyzed by QIIME 1.8.0 and compared with the UNITE Database for identification. The similarity between the two fungal communities (BAL and ENV) for a specific patient was assessed via the percentage of coincidence in the detection of specific operational taxonomic units (OTUs), and about 75% of co-occurrence was detected between the mycobiome of the LRT and the houses. Cultures confirmed the presence of the core mycobiome species. However, the low rate of isolation from BAL suggests that most of its mycobiome corresponds to non-culturable cells. This likely depends on the patient's immune system activity and inflammatory status.

Background: Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD., Methods: Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E) department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality., Results: After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04) and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40.4%) versus 20 (52.6%) (P=0.26), and those who went to A&E, at 9 (19.1%) versus 14 (36.8%) (P=0.06), due to exacerbation of COPD were also lower in this group. Intake of antibiotics was higher in the intervention group, whereas use of glucocorticoids was slightly lower, though there were no significant differences (P=0.30). There were also no differences between groups in the length of hospital stay (P=0.154) or overall mortality (P=0.191)., Conclusion: The implementation of a self-management program for patients with advanced COPD reduced exacerbations that required hospital care.

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10(-9) M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

The aim of this study was to determine whether alterations in periadventitial adipose tissue and its anti-contractile effect precede hypertension development. We used 4-week-old male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), which were pre-hypertensive. Vascular function was studied in the perfused mesenteric bed (MB, 1.5 mL/min). MB weight was lower in SHR (8.0 +/- 0.3 mg/g body weight) than in WKY (9.0 +/- 0.3 mg/g body weight) rats. Concentration-response curves to KCI (6 to 75 mmol/L) and to acetylcholine (10(-9) to 10(-5) mol/L) were similar between groups. Contractile responses to serotonin (10(-9) to 10(-5) mol/L) were significantly higher in SHR compared to WKY. 4-Aminopyridine (4-AP, 2 mmol/L), a blocker of Kv channels, induced a similar increase in perfusion pressure in both strains. However, 4-AP (2 mmol/L) significantly increased the contractile response to serotonin (10(-9) to 10(-5) mol/L) only in WKY. The anti-contractile effect of fat was confirmed by a comparison of (+) fat and (-) fat mesenteric arteries, which revealed that 4-AP significantly enhanced contractions only in (+) fat rings from WKY. These results show that alterations in visceral periadventitial fat mass and function in SHR precede hypertension, suggesting a constitutive mechanism independent of age and the hypertensive state.

Objective: Perivascular adipose tissue of normotensive rats releases a transferable factor that induces relaxation by opening voltage-dependent K+ (Kv) channels. The relevance of these observations to hypertension is unknown., Methods and Results: We characterized mesenteric perivascular adipose tissue from 3-month-old Wistar Kyoto rats (WKY) and aged-matched spontaneously hypertensive rats (SHR). Mesenteric bed (MB) weight and MB total lipid content were lower in SHR than in WKY. Freshly isolated MB adipocytes were smaller in SHR. Plasma triglycerides, glycerol, nonesterified free-fatty acids, and cholesterol were also lower in SHR. Plasma and mesenteric leptin were correlated with the quantity of mesenteric fat. To study vascular function, the MB was cannulated and perfused at a constant 2 mL/min flow. The Kv channel blocker 4-aminopyridine (4-AP; 2 mmol/L) increased perfusion pressure less in SHR MB than WKY and was directly correlated with the mesenteric fat amount. In isolated mesenteric artery rings, 4-AP (2 mmol/L) induced a contractile effect that was attenuated in SHR compared with WKY. The anticontractile effects of perivascular fat were reduced in SHR mesenteric artery rings compared with WKY., Conclusions: Differences in visceral perivascular adipose tissue mass and function may contribute to the increased vascular resistance observed in SHR.