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1.
Circ Res ; 134(11): 1451-1464, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38639088

RESUMEN

BACKGROUND: Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension. METHODS: To test this hypothesis, we studied CypD acetylation in patients with essential hypertension, defined a pathogenic role of CypD acetylation in deacetylation mimetic CypD-K166R mutant mice and endothelial-specific GCN5L1 (general control of amino acid synthesis 5 like 1)-deficient mice using an Ang II (angiotensin II) model of hypertension. RESULTS: Arterioles from hypertensive patients had 280% higher CypD acetylation coupled with reduced Sirt3 (sirtuin 3) and increased GCN5L1 levels. GCN5L1 regulates mitochondrial protein acetylation and promotes CypD acetylation, which is counteracted by mitochondrial deacetylase Sirt3. In human aortic endothelial cells, GCN5L1 depletion prevents superoxide overproduction. Deacetylation mimetic CypD-K166R mice were protected from vascular oxidative stress, endothelial dysfunction, and Ang II-induced hypertension. Ang II-induced hypertension increased mitochondrial GCN5L1 and reduced Sirt3 levels resulting in a 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. Treatment with mitochondria-targeted scavenger of cytotoxic isolevuglandins (mito2HOBA) normalized GCN5L1/Sirt3 ratio, reduced CypD acetylation, and attenuated hypertension. The role of mitochondrial acetyltransferase GCN5L1 in the endothelial function was tested in endothelial-specific GCN5L1 knockout mice. Depletion of endothelial GCN5L1 prevented Ang II-induced mitochondrial oxidative stress, reduced the maladaptive switch of vascular metabolism to glycolysis, prevented inactivation of endothelial nitric oxide, preserved endothelial-dependent relaxation, and attenuated hypertension. CONCLUSIONS: These data support the pathogenic role of CypD acetylation in endothelial dysfunction and hypertension. We suggest that targeting cytotoxic mitochondrial isolevuglandins and GCN5L1 reduces CypD acetylation, which may be beneficial in cardiovascular disease.


Asunto(s)
Endotelio Vascular , Hipertensión , Mitocondrias , Sirtuina 3 , Animales , Femenino , Humanos , Masculino , Ratones , Acetilación , Angiotensina II , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/enzimología , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas del Tejido Nervioso , Estrés Oxidativo , Sirtuina 3/metabolismo , Sirtuina 3/genética
2.
Anesthesiology ; 141(3): 511-523, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38759157

RESUMEN

BACKGROUND: The best approaches to supplemental oxygen administration during surgery remain unclear, which may contribute to variation in practice. This study aimed to assess determinants of oxygen administration and its variability during surgery. METHODS: Using multivariable linear mixed-effects regression, the study measured the associations between intraoperative fraction of inspired oxygen and patient, procedure, medical center, anesthesiologist, and in-room anesthesia provider factors in surgical cases of 120 min or longer in adult patients who received general anesthesia with tracheal intubation and were admitted to the hospital after surgery between January 2016 and January 2019 at 42 medical centers across the United States participating in the Multicenter Perioperative Outcomes Group data registry. RESULTS: The sample included 367,841 cases (median [25th, 75th] age, 59 [47, 69] yr; 51.1% women; 26.1% treated with nitrous oxide) managed by 3,836 anesthesiologists and 15,381 in-room anesthesia providers. Median (25th, 75th) fraction of inspired oxygen was 0.55 (0.48, 0.61), with 6.9% of cases less than 0.40 and 8.7% greater than 0.90. Numerous patient and procedure factors were statistically associated with increased inspired oxygen, notably advanced American Society of Anesthesiologists classification, heart disease, emergency surgery, and cardiac surgery, but most factors had little clinical significance (less than 1% inspired oxygen change). Overall, patient factors only explained 3.5% (95% CI, 3.5 to 3.5%) of the variability in oxygen administration, and procedure factors 4.4% (95% CI, 4.2 to 4.6%). Anesthesiologist explained 7.7% (95% CI, 7.2 to 8.2%) of the variability in oxygen administration, in-room anesthesia provider 8.1% (95% CI, 7.8 to 8.4%), medical center 23.3% (95% CI, 22.4 to 24.2%), and 53.0% (95% CI, 52.4 to 53.6%) was unexplained. CONCLUSIONS: Among adults undergoing surgery with anesthesia and tracheal intubation, supplemental oxygen administration was variable and appeared arbitrary. Most patient and procedure factors had statistical but minor clinical associations with oxygen administration. Medical center and anesthesia provider explained significantly more variability in oxygen administration than patient or procedure factors.


Asunto(s)
Terapia por Inhalación de Oxígeno , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estados Unidos , Estudios Retrospectivos , Anciano , Terapia por Inhalación de Oxígeno/métodos , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Estudios de Cohortes , Oxígeno/administración & dosificación , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Intubación Intratraqueal/métodos , Anestesiólogos/estadística & datos numéricos , Anestesia General/métodos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos
3.
Appetite ; 197: 107308, 2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38508419

RESUMEN

Alcohol consumption continues to be prevalent and is on the rise in many countries, posing a grave risk for the health and wellbeing of millions and creating a strain on health services worldwide. A hopeful trend has emerged, however, as consumers' growing preference for healthier, sustainable lifestyles has led traditional alcoholic brands to innovate, launching reduced or non-alcoholic (NoLo) options. This aligns with the SDGs and is reflected in NoLo spirits representing four of Spain's top ten disruptive innovations of 2022. This paper uses a mixed methodology in a qualitative-quantitative sequential approach to gain insight into this phenomenon. The study involved 13 in-depth interviews with HoReCa (an acronym for Hotels, Restaurants, and Caterings) professionals and four focus groups among consumers. Second, behavioral reasoning theory (BRT) was used in a quantitative study aiming to explore motivations for and against consuming NoLo spirits. Data from a survey of 620 participants was conducted and analyzed using SEM-PLS to measure the antecedents of consumer's behavioral intention towards NoLo spirits and to gauge the potential for marketing opportunities. The research reveals that the purchase intention of NoLo spirits is strongly related to health consciousness, while enjoying the effects of alcohol for fun and entertainment, and the social pressure to drink hinders its consumption. In addition, it was found that "reasons for" are more substantial than "reasons against" the consumption of those beverages, differing significantly by age group. Results offer implications for theory and practice, including recommendations for practitioners and regulators willing to improve sustainability in the industry. Further, this paper helps augment the innovation adoption literature by using BRT in the paradoxical context of consumers' increasing alcohol abuse despite their professed attempts to adopt healthier lifestyles.


Asunto(s)
Consumo de Bebidas Alcohólicas , Alcoholismo , Humanos , Bebidas , Mercadotecnía , Comportamiento del Consumidor
4.
Parasitol Res ; 123(6): 243, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874599

RESUMEN

Diphyllobothriosis, a fish-borne zoonosis in South America, is mainly caused by the Pacific broad tapeworm Adenocephalus pacificus Nybelin, 1931, a parasite of considerable concern in fishery resources due to its impact on public health. A new diphyllobothrid, Diphyllobothrium sprakeri Hernández-Orts et al. Parasites Vectors 14:219, 2021, was recently described from sea lions from the Pacific Coast, but marine fish acting as intermediate hosts are unknown. The objective of this study was to confirm the presence of plerocercoid larvae of Diphyllobothriidae Lühe, 1910 (Cestoda: Diphyllobothriidea) in nine fish species of commercial importance in Peru. Of a total of 6999 fish (5861 Engraulis ringens, 853 Sciaena deliciosa, 6 Sciaena callaensis, 171 Scomber japonicus, 40 Trachurus murphyi, 40 Ariopsis seemanni, 18 Merluccius peruanus, 5 Sarda chiliensis, and 5 Coryphaena hippurus), 183 were infected with plerocercoid larvae, representing a total prevalence of 2.61% and a mean intensity of 3.2. Based on mtDNA cox1 sequences of 43 plerocercoids, a phylogenetic analysis revealed that 41 belong to A. pacificus and two to D. sprakeri. These findings are first molecular data for D. sprakeri larvae, and the infections of E. ringens and T. murphyi by plerocercoid larvae represent the first records of intermediate/paratenic hosts for this species. Hence, the findings of the current study enhance our understanding of the presence of diphyllobothriid species in commercial fish from the Southeastern Pacific Ocean and their potential impact on seafood safety for local human populations.


Asunto(s)
Enfermedades de los Peces , Peces , Larva , Animales , Perú/epidemiología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/epidemiología , Peces/parasitología , Prevalencia , Larva/clasificación , Larva/crecimiento & desarrollo , Larva/genética , Filogenia , Infecciones por Cestodos/veterinaria , Infecciones por Cestodos/parasitología , Infecciones por Cestodos/epidemiología , Cestodos/genética , Cestodos/clasificación , Cestodos/aislamiento & purificación , Diphyllobothrium/genética , Diphyllobothrium/clasificación , Diphyllobothrium/aislamiento & purificación , Difilobotriosis/epidemiología , Difilobotriosis/parasitología , Difilobotriosis/veterinaria , ADN de Helmintos/genética
5.
Sensors (Basel) ; 24(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38257659

RESUMEN

Low back pain (LBP) is a significant global health challenge due to its high prevalence, and chronicity and recurrence rates, with projections suggesting an increase in the next years due to population growth and aging. The chronic and recurrent nature of LBP, responsible for a significant percentage of years lived with disability, underscores the need for effective management strategies, including self-management strategies advocated by current guidelines, to empower patients and potentially improve healthcare efficiency and clinical outcomes. Therefore, the aim of this study was to analyze the added value of face-to-face visits in patients with chronic LBP undergoing a self-management program based on therapeutic exercises on pain intensity, disability, quality of life and treatment adherence and satisfaction. A randomized clinical trial was conducted, allocating 49 patients into a experimental group with a mobile health (mHealth) app usage and face-to-face sessions and 49 patients into an active control group without face-to-face sessions. Pain intensity, disability and quality of life were assessed at baseline, 4 weeks postintervention and 12 weeks postintervention. Patients' satisfaction and adherence were assessed at the end of the study. The multivariate general model revealed no statistically significant time × group interaction for any outcome (p > 0.0068) but mental quality of life (p = 0.006). Within-group differences revealed significant improvements for all the clinical indicators (all, p < 0.001). Patients allocated to the experimental group reported greater satisfaction and adherence (both, p < 0.001) compared to the control group. The use of mHealth apps such as Healthy Back® as part of digital health initiatives may serve as a beneficial approach to enhance the management of LBP.


Asunto(s)
Dolor de la Región Lumbar , Aplicaciones Móviles , Humanos , Dolor de la Región Lumbar/terapia , Calidad de Vida , Envejecimiento , Salud Digital
6.
Medicina (Kaunas) ; 60(3)2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38541128

RESUMEN

Background and Objectives: Addressing deep carious lesions poses significant challenges in daily dental practice due to the inherent complexity of their treatment. Traditionally, complete removal of carious tissues has been the norm, potentially leading to pulp tissue exposure and subsequent pulpitis. In contemporary dentistry, there is a growing preference for minimally invasive techniques, such as selective removal, offering a more conservative approach with enhanced predictability and success rates. Materials and Methods: Our study commenced with a comprehensive systematic review. After that, we performed a meta-analysis focused exclusively on randomized controlled trials involving permanent dentition. Our investigation incorporated seven selected articles, which scrutinized success rates and the incidence of pulp exposure in minimally invasive techniques (MIT) versus conventional techniques (CT). Statistical analysis employed U Mann-Whitney and Wilcoxon tests to interpret the results. Results: Although the difference did not reach statistical significance, MIT demonstrated marginally superior success rates compared to CT. Furthermore, MIT exhibited a lower percentage of pulp exposure when contrasted with CT. However, due to the limited sample size, statistical significance for this difference could not be established. Conclusions: Minimally invasive techniques for caries removal emerge as a conservative and promising approach to safeguard pulp tissues in comparison to conventional techniques. The need for additional randomized controlled trials is emphasized to unequivocally establish the superior success rates of these procedures over their conventional counterparts.


Asunto(s)
Caries Dental , Dentición Permanente , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Caries Dental/terapia , Caries Dental/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Genome Res ; 30(12): 1802-1814, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33203765

RESUMEN

Recombination is a main source of genetic variability. However, the potential role of the variation generated by recombination in phenotypic traits, including diseases, remains unexplored because there is currently no method to infer chromosomal subpopulations based on recombination pattern differences. We developed recombClust, a method that uses SNP-phased data to detect differences in historic recombination in a chromosome population. We validated our method by performing simulations and by using real data to accurately predict the alleles of well-known recombination modifiers, including common inversions in Drosophila melanogaster and human, and the chromosomes under selective pressure at the lactase locus in humans. We then applied recombClust to the complex human 1q21.1 region, where nonallelic homologous recombination produces deleterious phenotypes. We discovered and validated the presence of two different recombination histories in these regions that significantly associated with the differential expression of ANKRD35 in whole blood and that were in high linkage with variants previously associated with hypertension. By detecting differences in historic recombination, our method opens a way to assess the influence of recombination variation in phenotypic traits.


Asunto(s)
Cromosomas/genética , Biología Computacional/métodos , Drosophila melanogaster/genética , Proteínas/genética , Recombinación Genética , Animales , Línea Celular , Simulación por Computador , Bases de Datos Genéticas , Humanos , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Selección Genética
8.
Anesth Analg ; 137(5): 996-1006, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37678264

RESUMEN

BACKGROUND: Renal ischemia and reperfusion (IR) contribute to perioperative acute kidney injury, and oxygen is a key regulator of this process. We hypothesized that oxygen administration during surgery and renal IR would impact postoperative kidney function and injury in mice. METHODS: Mice were anesthetized, intubated, and mechanically ventilated with a fraction of inspired oxygen (F io2 ) 0.10 (hypoxia), 0.21 (normoxia), 0.60 (moderate hyperoxia), or 1.00 (severe hyperoxia) during 67 minutes of renal IR or sham IR surgery. Additional mice were treated before IR or sham IR surgery with 50 mg/kg tempol, a superoxide scavenger. At 24 hours, mice were sacrificed, and blood and kidney collected. We assessed and compared kidney function and injury across groups by measuring blood urea nitrogen (BUN, primary end point), renal histological injury, renal expression of neutrophil gelatinase-associated lipocalin (NGAL), and renal heme oxygenase 1 ( Ho-1 ), peroxisome proliferator-activated receptor gamma coactivator 1-α ( Pgc1-α ), and glutathione peroxidase 4 ( Gpx-4 ) transcripts, to explore potential mechanisms of any effect of oxygen. RESULTS: Hyperoxia and hypoxia during renal IR surgery decreased renal function and increased kidney injury compared to normoxia. Baseline median (interquartile range) BUN was 22.2 mg/dL (18.4-26.0), and 24 hours after IR surgery, BUN was 17.5 mg/dL (95% confidence interval [CI], 1.3-38.4; P = .034) higher in moderate hyperoxia-treated animals, 51.8 mg/dL (95% CI, 24.9-74.8; P < .001) higher in severe hyperoxia-treated animals, and 64.9 mg/dL (95% CI, 41.2-80.3; P < .001) higher in hypoxia-treated animals compared to animals treated with normoxia ( P < .001, overall effect of hyperoxia). Hyperoxia-induced injury, but not hypoxia-induced injury, was attenuated by pretreatment with tempol. Histological injury scores, renal NGAL staining, and renal transcription of Ho-1 and suppression of Pgc1- α followed the same pattern as BUN, in relation to the effects of oxygen treatment. CONCLUSIONS: In this controlled preclinical study of oxygen treatment during renal IR surgery, hyperoxia and hypoxia impaired renal function, increased renal injury, and impacted expression of genes that affect mitochondrial biogenesis and antioxidant response. These results might have implications for patients during surgery when high concentrations of oxygen are frequently administered, especially in cases involving renal IR.

9.
J Cardiothorac Vasc Anesth ; 37(9): 1683-1690, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37244820

RESUMEN

OBJECTIVES: This study aimed to determine whether blood pressure control in the early postoperative period was associated with postoperative delirium in the cardiovascular intensive care unit (ICU). DESIGN: Observational cohort study. SETTING: Single large academic institution with a high volume of cardiac surgery. PARTICIPANTS: Cardiac surgery patients admitted to the cardiovascular ICU after surgery. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: A total of 517 cardiac surgery patients had mean arterial pressure (MAP) data recorded minute-by-minute for 12 postoperative hours. The time spent in each of the 7 prespecified blood pressure bands was calculated, and the development of delirium was recorded in the ICU. A multivariate Cox regression model was developed using the least absolute shrinkage and selection operator approach to identify associations between time spent in each MAP range band and delirium. Compared with the reference band of 60-to-69 mmHg, longer durations spent in 3 bands were independently associated with a lower risk of delirium: 50-to-59 mmHg band (adjusted hazard ratio [HR] 0.907 [per 10 minutes]; 95% CI 0.861-0.955); 70-to-79 mmHg band (adjusted HR 0.923 [per 10 minutes]; 95% CI 0.902-0.944); 90-to-99 mmHg band (adjusted HR 0.898 [per 10 minutes]; 95% CI 0.853-0.945). CONCLUSIONS: The MAP range bands above and below the authors' reference band of 60-to- 69 mmHg were associated with decreased risk of ICU delirium development; however, this was difficult to reconcile with a plausible biologic mechanism. Therefore, the authors did not find a correlation between early postoperative MAP control and increased risk of the development of ICU delirium after cardiac surgery.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Delirio , Humanos , Presión Sanguínea , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Estudios de Cohortes , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Unidades de Cuidados Intensivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo
10.
Sensors (Basel) ; 23(14)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37514795

RESUMEN

The study aimed to investigate the effects of footwear on the electromyographic (EMG) activity of pelvic floor muscles (PFMs) and internal oblique (IO) muscles during running at different speeds. The study also aimed to explore the correlation between EMG activity of PFMs and IO muscles and participants' morphological characteristics. Ten nulliparous female runners were included in the study. The participants ran for 90 s at speeds of 9, 11, and 13 km/h wearing both traditional and minimalist shoes. EMG outcomes were presented as a percentage of maximum voluntary contraction (%MVC). Comparative analysis was conducted using the Wilcoxon rank test. Correlational analysis was performed using the Rho-Spearman correlation coefficient. The %MVC for the IO muscles was significantly lower when using minimalist shoes compared to traditional shoes (p = 0.04). No statistically significant differences were found for the PFMs (p > 0.05). The study also observed large correlations between age and %MVC of the PFMs and IO muscles (rho = -0.64; p = 0.04). Minimalist shoes decreased the activity of IO muscles in female runners. However, no significant differences in EMG activity of PFMs were found when comparing traditional and minimalist footwear. The long-term effects of minimalist footwear on EMG activity of PFMs and IO muscles, as well as their relationship to morphological characteristics, require further investigation.


Asunto(s)
Pie , Carrera , Humanos , Femenino , Pie/fisiología , Músculos Oblicuos del Abdomen , Zapatos , Diafragma Pélvico , Carrera/fisiología , Fenómenos Biomecánicos/fisiología
11.
Int J Mol Sci ; 24(20)2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37895147

RESUMEN

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.


Asunto(s)
Enfermedad de Erdheim-Chester , Humanos , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/genética , Proteínas Proto-Oncogénicas B-raf/genética , Mutación , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genética
12.
Bull Environ Contam Toxicol ; 110(5): 89, 2023 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-37140760

RESUMEN

In the present study, livers, kidneys and adipose tissue of Yellow-legged Gull (Larus michahellis) were collected. Samples were used to determine relationships between heavy metals/metalloids in liver and kidneys (Hg, Cd, Pb, Se and As) or persistent organic pollutants in adipose tissue (7 PCBs and 11 organochlorine pesticides) with biomarkers of oxidative stress (CAT, GPx, GR, GSH, GST, MDA) analysed in both internal organs. Three possible influencing variables have been studied: age, sex and sampling area. As a result, statistically significant differences (P < 0.05, P < 0.01) were only found according to the sampling area, with differences among the three studied areas found in both organs. Significant positive correlations (P < 0.01) were found in liver (Hg vs. GST; Se vs. MDA) and in kidney (As vs. GR; As vs. GPx; PCB52 vs. CAT; PCB138 vs. CAT). The scarcity in correlations suggests that the levels of pollutants found in animals were not high enough to trigger an effect at the oxidative level.


Asunto(s)
Charadriiformes , Hidrocarburos Clorados , Mercurio , Metales Pesados , Animales , Monitoreo del Ambiente , Metales Pesados/análisis , Hidrocarburos Clorados/análisis , Mercurio/análisis
13.
Am J Physiol Heart Circ Physiol ; 323(5): H917-H933, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36083796

RESUMEN

We have shown that excessive endothelial cell stretch causes release of growth arrest-specific 6 (GAS6), which activates the tyrosine kinase receptor Axl on monocytes and promotes immune activation and inflammation. We hypothesized that GAS6/Axl blockade would reduce renal and vascular inflammation and lessen renal dysfunction in the setting of chronic aortic remodeling. We characterized a model of aortic remodeling in mice following a 2-wk infusion of angiotensin II (ANG II). These mice had chronically increased pulse wave velocity, and their aortas demonstrated increased mural collagen. Mechanical testing revealed a marked loss of Windkessel function that persisted for 6 mo following ANG II infusion. Renal function studies showed a reduced ability to excrete a volume load, a progressive increase in albuminuria, and tubular damage as estimated by periodic acid Schiff staining. Treatment with the Axl inhibitor R428 beginning 2 mo after ANG II infusion had a minimal effect on aortic remodeling 2 mo later but reduced the infiltration of T cells, γ/δ T cells, and macrophages into the aorta and kidney and improved renal excretory capacity, reduced albuminuria, and reduced evidence of renal tubular damage. In humans, circulating Axl+/Siglec6+ dendritic cells and phospho-Axl+ cells correlated with pulse wave velocity and aortic compliance measured by transesophageal echo, confirming chronic activation of the GAS6/Axl pathway. We conclude that brief episodes of hypertension induce chronic aortic remodeling, which is associated with persistent low-grade inflammation of the aorta and kidneys and evidence of renal dysfunction. These events are mediated at least in part by GAS6/Axl signaling and are improved with Axl blockade.NEW & NOTEWORTHY In this study, a brief, 2-wk period of hypertension in mice led to progressive aortic remodeling, an increase in pulse wave velocity, and evidence of renal injury, dysfunction, and albuminuria. This end-organ damage was associated with persistent renal and aortic infiltration of CD8+ and γ/δ T cells. We show that this inflammatory response is likely due to GAS6/Axl signaling and can be ameliorated by blocking this pathway. We propose that the altered microvascular mechanical forces caused by increased pulse wave velocity enhance GAS6 release from the endothelium, which in turn activates Axl on myeloid cells, promoting the end-organ damage associated with aortic stiffening.


Asunto(s)
Hipertensión , Enfermedades Renales , Animales , Humanos , Ratones , Albuminuria/prevención & control , Angiotensina II/farmacología , Aorta/metabolismo , Colágeno , Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Ácido Peryódico , Proteínas Proto-Oncogénicas/metabolismo , Análisis de la Onda del Pulso , Proteínas Tirosina Quinasas Receptoras/metabolismo , Tirosina Quinasa del Receptor Axl
14.
Circ Res ; 126(4): 439-452, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-31852393

RESUMEN

RATIONALE: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in the regulation of metabolic and antioxidant functions which are associated with hypertension, and cardiovascular disease risk factors diminish Sirt3 level. OBJECTIVE: We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction in hypertension, but increased Sirt3 protects vascular function and decreases hypertension. METHODS AND RESULTS: To test the therapeutic potential of targeting Sirt3 expression, we developed new transgenic mice with global Sirt3OX (Sirt3 overexpression), which protects from endothelial dysfunction, vascular oxidative stress, and hypertrophy and attenuates Ang II (angiotensin II) and deoxycorticosterone acetate-salt induced hypertension. Global Sirt3 depletion in Sirt3-/- mice results in oxidative stress due to hyperacetylation of mitochondrial superoxide dismutase (SOD2), increases HIF1α (hypoxia-inducible factor-1), reduces endothelial cadherin, stimulates vascular hypertrophy, increases vascular permeability and vascular inflammation (p65, caspase 1, VCAM [vascular cell adhesion molecule-1], ICAM [intercellular adhesion molecule-1], and MCP1 [monocyte chemoattractant protein 1]), increases inflammatory cell infiltration in the kidney, reduces telomerase expression, and accelerates vascular senescence and age-dependent hypertension; conversely, increased Sirt3 expression in Sirt3OX mice prevents these deleterious effects. The clinical relevance of Sirt3 depletion was confirmed in arterioles from human mediastinal fat in patients with essential hypertension showing a 40% decrease in vascular Sirt3, coupled with Sirt3-dependent 3-fold increases in SOD2 acetylation, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity, VCAM, ICAM, and MCP1 levels in hypertensive subjects compared with normotensive subjects. CONCLUSIONS: We suggest that Sirt3 depletion in hypertension promotes endothelial dysfunction, vascular hypertrophy, vascular inflammation, and end-organ damage. Our data support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertension.


Asunto(s)
Hipertensión Esencial/metabolismo , Corazón/fisiopatología , Inflamación/metabolismo , Proteínas Mitocondriales/metabolismo , Estrés Oxidativo , Sirtuina 3/metabolismo , Angiotensina II , Animales , Acetato de Desoxicorticosterona , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Hipertensión Esencial/inducido químicamente , Hipertensión Esencial/genética , Femenino , Inflamación/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Mitocondrias Cardíacas/genética , Mitocondrias Cardíacas/metabolismo , Proteínas Mitocondriales/genética , Miocardio/metabolismo , Miocardio/patología , Sirtuina 3/genética
15.
Acta Derm Venereol ; 102: adv00825, 2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36444563

RESUMEN

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicles. The aim of this case-control study was to assess whether HS is associated with disturbances in trabecular bone score, bone mineral density, bone remodelling markers, and calciotropic hormones. A total of 81 patients and 79 controls of similar age and sex were included. Demographic, anthropometric, laboratory data, trabecular bone score, bone mineral density, serum 25-hydroxyvitamin D (25OHD), serum amino-terminal pro-peptide of type 1 collagen (PINP), and C-terminal telopeptide of type 1 collagen (CTX) concentrations were assessed in both groups. Patients with HS had lower serum 25OHD levels than controls, and approximately 62% of them had vitamin D deficiency. Serum PINP was increased and CTX was decreased in patients with HS. Fully adjusted trabecular bone score values were lower in patients with HS compared with controls. Adjusted lumbar bone mineral density was similar in HS and controls, whilst total hip bone mineral density was lower in patients with HS. There were no statistical differences regarding disease severity in terms of 25OHD, serum turnover markers, bone mineral density, or trabecular bone score values. This study shows that patients with HS have lower trabecular bone score and total hip bone mineral density values than population-based controls. In addition, the prevalence of vitamin D deficiency is high in subjects with HS.


Asunto(s)
Hidradenitis Supurativa , Deficiencia de Vitamina D , Humanos , Estudios de Casos y Controles , Colágeno Tipo I , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Folículo Piloso
16.
Sensors (Basel) ; 22(7)2022 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-35408360

RESUMEN

(1) Background: As breast cancer studies suggest, a high percentage of breast density (PBD) may be related to breast cancer incidence. Although PBD screening is one of the strongest predictors of breast cancer risk, X-ray-based mammography evaluation is subjective. Therefore, new objective PBD measuring techniques are of interest. A case study analyzing the PBD of thirteen female participants using a bioimpedance-based method, the anomalies tracking circle (ATC), is described in this paper. (2) Methods: In the first stage, the breast bioimpedance of each participant was measured. Then, the participant breast density was determined by applying a mammogram just after the breast bioimpedance measurement stage. In the third stage, the ATC algorithm was applied to the measured bioimpedance data for each participant, and a results analysis was done. (3) Results: An ATC variation according to the breast density was observed from the obtained data, this allowed the use of classification techniques to determine the PBD. (4) Conclusions: The described breast density method is a promising approach that might be applied as an auxiliary tool to the mammography in order to obtain precise and objective results for evaluation of breast density and with that determine potential breast cancer risk.


Asunto(s)
Densidad de la Mama , Neoplasias de la Mama , Algoritmos , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Mamografía/métodos
17.
Death Stud ; 46(8): 1909-1922, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33428556

RESUMEN

This study explores how Mayan people from Guatemala and Swedes view and behave toward death. Using an interpretative phenomenological analysis, 10 participants from each culture were interviewed to elucidate the most relevant and important emerging themes. The Mayan approach to death is based on a collective perspective in which consultations with Elders, ancient traditions, and rituals help provide answer to most existential inquiries surrounding death. In contrast, the Swedish approach is based on an individualistic, rational analysis with a focus on life instead of death, but also showing openness to new perspectives on death.


Asunto(s)
Actitud , Conducta Ceremonial , Anciano , Guatemala , Humanos , Suecia
18.
Int J Mol Sci ; 23(12)2022 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-35742886

RESUMEN

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Tuberculosis Meníngea , Animales , Barrera Hematoencefálica/metabolismo , Encéfalo , Enfermedades del Sistema Nervioso Central/metabolismo , Epitelio , Ratones
19.
BMC Oral Health ; 22(1): 262, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35764990

RESUMEN

BACKGROUND: Health literacy is a main factor in health for its improvement, allowing the individuals to have a greater capacity to engage and participate in collective health promotion actions. The evaluation of functional health literacy is essential to determine the ability that each individual has to understand basic health information. The present study aimed to perform the translation and cross-cultural adaptation of the Rapid Estimate of Adult Literacy in Dentistry-30 to the Portuguese language and test the reliability and validity of this version. METHODS: After translation and cultural adaptation, the instrument was applied to a group of individuals that participate in the program Atividade Senior, developed by the municipality of Viseu, Portugal. The final sample was composed by 206 participants that accepted responding to the translated version of the instrument. Statistical validation was accomplished to complete the process and obtain the final instrument. One question was removed for the creation of the final instrument with 29 questions, therefore being named Rapid Estimate of Adult Literacy in Dentistry-29 PT. RESULTS: The Rapid Estimate of Adult Literacy in Dentistry-29 PT presented good internal reliability. Cronbach's alpha ranged from 0.89 to 0.90 when words were deleted individually. The analysis of test-retest reliability revealed excellent reproducibility. We can verify that the Rapid Estimate of Adult Literacy in Dentistry-29 PT scale for assessment of oral health literacy among older adults presents an acceptable internal consistency, with a global Cronbach´s alpha of 0.894. CONCLUSIONS: The new scale can be applied to assess oral health literacy among older Portuguese adults, presenting an acceptable internal consistency and is validated to assess oral health literacy and is crucial in epidemiological studies.


Asunto(s)
Odontología , Alfabetización en Salud , Lenguaje , Anciano , Etnicidad , Conocimientos, Actitudes y Práctica en Salud , Humanos , Portugal , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
20.
Medicina (Kaunas) ; 58(1)2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-35056400

RESUMEN

Background and Objectives: Tactile sensibility is an important characteristic for evaluating the masticatory efficiency in different occlusal situations. When a tooth is extracted, relevant proprioceptors from the periodontal ligament get lost; and after the rehabilitation of this abscess by means of oral prosthesis, this sensibility decreases influencing masticatory function. Osseoperception is a sensitive phenomenon associated with dental implants that allows an increased tactile sensibility to those wearing implant prostheses. The purpose of this study was to determine the difference in tactile sensibility values between implant prosthesis, complete dentures, and natural teeth through a review of the available literature. Materials and Methods. In order to dissect the information, 24 articles from 2004 to 2021 were analyzed from MEDLINE, PubMed Central, and Web of Science databases. These articles were directly related to measuring tactile sensibility in different situations and demonstrating the influence of osseoperception in an improved masticatory function. Results: Tactile sensibility in implant prosthesis is slightly reduced compared with natural dentition but presents improved values with regard to complete dentures. Conclusions: Implant prosthesis are more effective during masticatory function than complete dentures, as they present an increased tactile sensibility, very similar to that present in natural dentition. This enhanced sensibility in implants is due to the osseoperception phenomenon.


Asunto(s)
Boca Edéntula , Tacto , Humanos , Células Receptoras Sensoriales
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