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1.
J Clin Med ; 13(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38610897

RESUMO

Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). Conclusions: Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.

2.
J Am Chem Soc ; 146(15): 10899-10907, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38569596

RESUMO

In the long-standing quest to synthesize fundamental building blocks with key functional group motifs, photochemistry in the recent past has comprehensively established its attractiveness. Amino alcohols are not only functionally diverse but are ubiquitous in the biologically active realm of compounds. We developed bench-stable bifunctional reagents that could then access the sparsely reported γ-amino alcohols directly from feedstock alkenes through energy transfer (EnT) photocatalysis. A designed 1,3-linkage across alkenes is made possible by the intervention of a radical Brook rearrangement that takes place downstream to the EnT-mediated homolysis of our reagent(s). A combination of experimental mechanistic investigations and detailed computational studies (DFT) indicates a radical chain propagated reaction pathway.

3.
Environ Int ; 186: 108565, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574403

RESUMO

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.


Assuntos
Ácidos Alcanossulfônicos , Glicemia , Fluorocarbonos , Homeostase , Ácidos Alcanossulfônicos/sangue , Humanos , Fluorocarbonos/sangue , Masculino , Feminino , Idoso , Glicemia/análise , Pessoa de Meia-Idade , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Dieta/estatística & dados numéricos , Idoso de 80 Anos ou mais , Estudos Prospectivos , Poluentes Ambientais/sangue
4.
Sci Total Environ ; 928: 172610, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38642762

RESUMO

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.


Assuntos
Dieta Mediterrânea , Pessoa de Meia-Idade , Humanos , Idoso , Masculino , Feminino , Meio Ambiente , Gases de Efeito Estufa/análise , Eutrofização , Síndrome Metabólica/prevenção & controle
5.
PLoS One ; 19(3): e0297576, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451958

RESUMO

The Peritumoral Brain Zone (PBZ) contributes to Glioblastoma (GBM) relapse months after the resection of the original tumor, which is influenced by a variety of pathological factors. Among those, microglia are recognized as one of the main regulators of GBM progression and probably relapse. Although microglial morphology has been analyzed inside GBM and its immediate surroundings, it has not been objectively characterized throughout the PBZ. Thus, we aimed to perform a thorough characterization of microglial morphology in the PBZ and its likely differentiation not just from the tumor-associated microglia but from control tissue microglia. For this purpose, Sprague Dawley rats were intrastriatally implanted with C6 cells to induce a GBM formation. Gadolinium-based magnetic resonance imaging (MRI) was performed to locate the tumor and to define the PBZ (2 mm beyond the tumor border), thus delimitating the different regions of interest (ROIs: core tumoral zone and immediate interface; contralateral striatum as control). Brain slices were obtained and immunolabeled with the microglia marker Iba-1. Sixteen morphological parameters were measured for each cell, significative differences were found in all parameters when comparing the four ROIs. To determine if PBZ microglia could be morphologically differentiated from microglia in other ROIs, hierarchical clustering analysis was performed, revealing that microglia can be separated into four morphologically differentiated clusters, each of them mostly integrated by cells sampled in each ROI. Furthermore, a classifier based on linear discriminant analysis, including only three morphological parameters, categorized microglial cells across the studied ROIs and showed a gradual transition between them. The robustness of this classification was assessed through principal component analysis with the remaining 13 morphological parameters, corroborating the obtained results. Thus, in this study we provided objective and quantitative evidence that PBZ microglia represent a differentiable microglial morphotype that could contribute to the recurrence of GBM in this area.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Ratos , Animais , Microglia/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Ratos Sprague-Dawley , Recidiva Local de Neoplasia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Glioblastoma/patologia , Recidiva
6.
J Am Heart Assoc ; 13(7): e031915, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533958

RESUMO

BACKGROUND: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. METHODS AND RESULTS: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). CONCLUSIONS: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.


Assuntos
Fibrilação Atrial , Doenças Cardiovasculares , Dieta Mediterrânea , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Fibrilação Atrial/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Átrios do Coração/diagnóstico por imagem , Fatores de Risco de Doenças Cardíacas , Fatores de Risco , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Chempluschem ; : e202300633, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350019

RESUMO

Multicomponent diversity-oriented synthesis (DOS) of conformationally anchored structural peptidomimetics like 2,5-diketopiperazines (2,5-DKP) containing heterocyclic bioisosteres of the amide bond, such as 1,2,3-triazoles and 1,5-disubstituted tetrazoles (1,5-DS-T) is described. Structural peptidomimetics are synthesized from similar available starting materials, via a strategy based on isocyanide-based multicomponent reactions (IMCRs): Ugi-4CR and Ugi-Azide (UA), followed by a one-pot process: SN 2/intramolecular alkyne-azide cycloaddition (IAAC). The sequential aligning of two powerful synthetic tools (IMCR and IAAC) has parallelly contributed to generate anchored conformation and complexity in target molecules, which are considered structural peptidomimetics of 2,5-DKP. Herein, the 1,2,3-triazole ring plays a key role in the preference for the boat conformation. Furthermore, the use of UA reaction generates scaffold diversity at the N-1 α-carbon of the pyrazinone ring, replacing a linear amide bond with a heterocyclic bioisostere such as 1,5-DS-T leading to the synthesis of novel tricyclic peptidomimetics. The DFT calculations confirmed the boat conformation of the synthesized molecules.

8.
Nature ; 628(8007): 277-281, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354832

RESUMO

The formation of galaxies by gradual hierarchical co-assembly of baryons and cold dark matter halos is a fundamental paradigm underpinning modern astrophysics1,2 and predicts a strong decline in the number of massive galaxies at early cosmic times3-5. Extremely massive quiescent galaxies (stellar masses of more than 1011 M⊙) have now been observed as early as 1-2 billion years after the Big Bang6-13. These galaxies are extremely constraining on theoretical models, as they had formed 300-500 Myr earlier, and only some models can form massive galaxies this early12,14. Here we report on the spectroscopic observations with the JWST of a massive quiescent galaxy ZF-UDS-7329 at redshift 3.205 ± 0.005. It has eluded deep ground-based spectroscopy8, it is significantly redder than is typical and its spectrum reveals features typical of much older stellar populations. Detailed modelling shows that its stellar population formed around 1.5 billion years earlier in time (z ≈ 11) at an epoch when dark matter halos of sufficient hosting mass had not yet assembled in the standard scenario4,5. This observation may indicate the presence of undetected populations of early galaxies and the possibility of significant gaps in our understanding of early stellar populations, galaxy formation and the nature of dark matter.

9.
J Phys Chem C Nanomater Interfaces ; 128(6): 2518-2528, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38379916

RESUMO

Poly(p-phenylenevinylene) (PPV) is a staple of the family of conjugated polymers with desirable optoelectronic properties for applications including light-emitting diodes (LEDs) and photovoltaic devices. Although the significant impact of olefin geometry on the steady-state optical properties of PPVs has been extensively studied, PPVs with precise stereochemistry have yet to be investigated using nonlinear optical spectroscopy for quantum sensing, as well as light harvesting for biological applications. Herein, we report our investigation of the influence of olefin stereochemistry on both linear and nonlinear optical properties through the synthesis of all-cis and all-trans PPV copolymers. We performed two-photon absorption (TPA) using a classical and entangled light source and compared both classical TPA and entangled two-photon absorption (ETPA) cross sections of these stereodefined PPVs. Whereas the TPA cross section of the all-trans PPV was expectedly higher than that of all-cis PPV, presumably because of the larger transition dipole moment, the opposite trend was measured via ETPA, with the all-cis PPV exhibiting the highest ETPA cross section. DFT calculations suggest that this difference might stem from the interaction of entangled photons with lower-lying electronic states in the all-cis PPV variant. Additionally, we explored the photoinduced processes for both cis and trans PPVs through time-resolved fluorescence upconversion and femtosecond transient absorption techniques. This study revealed that the sensitivity of PPVs in two-photon absorption varies with classical versus quantum light and can be modulated through the control of the geometry of the repeating alkenes, which is a key stepping stone toward their use in quantum sensing, bioimaging, and the design of polymer-based light-harvesting systems.

10.
TH Open ; 8(1): e1-e8, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38197015

RESUMO

Background In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

11.
Biologicals ; 85: 101740, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38217963

RESUMO

Whooping cough is a disease caused by Bordetella pertussis, whose morbidity has increased, motivating the improvement of current vaccines. Reverse vaccinology is a strategy that helps identify proteins with good characteristics fast and with fewer resources. In this work, we applied reverse vaccinology to study the B. pertussis proteome and pangenome with several in-silico tools. We analyzed the B. pertussis Tohama I proteome with NERVE software and compared 234 proteins with B. parapertussis, B. bronchiseptica, and B. holmessi. VaxiJen was used to calculate an antigenicity value; our threshold was 0.6, selecting 84 proteins. The candidates were depurated and grouped in eight family proteins to select representative candidates, according to bibliographic information and their immunological response predicted with ABCpred, Bcepred, IgPred, and C-ImmSim. Additionally, a pangenome study was conducted with 603 B. pertussis strains and PanRV software, identifying 3421 core proteins that were analyzed to select the best candidates. Finally, we selected 15 proteins from the proteome study and seven proteins from the pangenome analysis as good vaccine candidates.


Assuntos
Bordetella parapertussis , Coqueluche , Humanos , Bordetella pertussis/genética , Coqueluche/prevenção & controle , Proteoma/metabolismo , Vacinologia , Bordetella parapertussis/metabolismo , Vacina contra Coqueluche
12.
Psychol Med ; 54(3): 620-630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37667630

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. METHODS: Participants (n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. RESULTS: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted ß = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women (ß = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008). CONCLUSIONS: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.


Assuntos
COVID-19 , Síndrome Metabólica , Humanos , Feminino , Idoso , COVID-19/epidemiologia , Depressão/psicologia , Síndrome Metabólica/epidemiologia , Sobrepeso/epidemiologia , Obesidade/epidemiologia
13.
Br J Soc Psychol ; 63(1): 87-105, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37427831

RESUMO

Coalitions among individuals and between groups, which have had critical evolutionary benefits for humans, play an important role in contemporary life. One key element of the processes of assessing potential allies is how they may contribute to the perceived physical formidability - fighting ability or the capacity to inflict costs on others - of the alliance. In three studies, focused for the first time on intergroup coalitions, we investigated how qualities of the groups such as status (social prestige) and the relationship between them influence the perceived physical formidability of a coalition (i.e., European Union, EU). Study 1 found that the inclusion of a group with higher or similar (but not lower) status increased the perceived formidability of the EU. Studies 2 and 3 showed that learning that ingroup members recategorized a low-status group within a common-group identity increased the perceived formidability of the EU including that group, compared with the conditions in which either outgroup members recategorized or no information was provided. Study 3 also revealed mediation by fusion - a visceral connection - with outgroup members, which has been relatively unexplored. Taken together, these studies reveal that both, status and social identity processes, may significantly affect the estimations of coalitional formidability.


Assuntos
Processos Grupais , Identificação Social , Humanos , União Europeia
14.
Eur J Prev Cardiol ; 31(5): 629-639, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38102071

RESUMO

AIMS: To evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (Mets). METHODS AND RESULTS: Participants of the PREvención con DIeta MEDiterranea-Plus trial (n = 6874) were randomized 1:1 to an ILI programme based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management or to a control intervention of low-intensity dietary advice. A core echocardiography lab evaluated left atrial (LA) strain, function, and volumes in 534 participants at baseline, 3-year, and 5-year follow-ups. Mixed models were used to evaluate the effect of the ILI on LA structure and function. In the subsample, the baseline mean age was 65 years [standard deviation (SD) 5 years], and 40% of the participants were women. The mean weight change after 5 years was -3.9 kg (SD 5.3 kg) in the ILI group and -0.3 kg (SD 5.1 kg) in the control group. Over the 5-year period, both groups experienced a worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index, and LA emptying fraction over time. Changes in the ILI and control groups were not significantly different for any of the primary outcomes {LA emptying fraction: -0.95% [95% confidence interval (CI) -0.93, -0.98] in the control group, -0.97% [95% CI -0.94, -1.00] in the ILI group, Pbetween groups = 0.80; LA longitudinal strain: 0.82% [95% CI 0.79, 0.85] in the control group, 0.85% [95% CI 0.82, 0.89] in the ILI group, Pbetween groups = 0.24} or any of the secondary outcomes. CONCLUSION: In overweight or obese people with Mets, an ILI had no impact on the underlying structural and functional LA substrate measurements associated with AF risk.


This study evaluated whether an intervention-modifying lifestyle had an effect on the parts of the heart involved in the development of atrial fibrillation (AF), a common problem of the heart rhythm. This intervention was implemented in people who had excessive body weight and the metabolic syndrome (Mets), which is a combination of several cardiovascular risk factors. The lifestyle intervention included promoting a Mediterranean diet low in calories and increasing exercise to facilitate weight loss, and this intervention was compared with a control intervention to follow a healthy diet. We performed repeated studies of the heart structure and function with imaging over a period of 5 years. During the 5 years of the study, both study groups (intervention and control) showed changes in their heart consistent with ageing. However, these changes were not different in those who were receiving the lifestyle intervention. Also, participants who lost more weight, adhered better to the study diet, or did more physical activity, overall did not show any differences in their heart compared with those who did not achieve their lifestyle goals.In conclusion, a lifestyle intervention focusing on weight loss, better diet, and more exercise was not effective in improving parts of the heart potentially involved with the risk of AF.In people with metabolic syndrome, a weight control lifestyle intervention, based on an energy-reduced Mediterranean diet and physical activity, had no effect on the structural and functional cardiac substrate of atrial fibrillation.


Assuntos
Fibrilação Atrial , Síndrome Metabólica , Humanos , Feminino , Idoso , Masculino , Sobrepeso/complicações , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/terapia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Exercício Físico , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/terapia , Estilo de Vida
15.
Angew Chem Int Ed Engl ; 63(7): e202317935, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38117662

RESUMO

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2-selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl-substituted carbon centers. In contrast to radical-based pathways and reactions triggered by hydrometallation via a nickel-hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel-bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.

16.
Urol Res Pract ; 49(6): 406-412, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38078647

RESUMO

OBJECTIVE: Ureteral stenosis in renal transplant patients is a frequent urological complication that involves significant morbidity and may compromise graft function. Despite the common use of minimally invasive techniques, surgery continues to be the definitive treatment for ureteral stenosis, and pyeloureteral anastomosis is an infrequent but effective technique in the management of this pathology and has been described as a safe treatment with a low percentage of complications. METHODS: This is a retrospective study of patients in whom surgical intervention via pyeloureteral anastomosis was carried out in our center in the last 12 years. A descriptive analysis of perioperative management, complications, and functional results is provided. A comparison of renal function at diagnosis and after surgery was made to evaluate the effectiveness of the procedure. RESULTS: Thirteen patients underwent surgery within the described time frame. Time to diagnosis of stenosis was 60 days [interquartile range (IQR) 31-368]. Creatinine at diagnosis was 2.2 mg/dL [IQR 1.9-3] with a glomerular filtration rate, estimated by the modification of diet in renal disease equation, of 29 mL/min/1.73 m2 [IQR 22.6-34.5]. Of these patients, 92.3% underwent percutaneous nephrostomy, and 38.5% also had a ureteral catheter. The mean duration of surgery was 265 minutes [IQR 240-300], and hospital stay was 9 days [IQR 7.5-16]. A double J was placed in all cases, which was maintained for 36 days [IQR 30-49]. Postoperative complications occurred in 15.4% of patients. Serum creatinine 1 year after surgery was 1.6 ± 0.4 mg/dL. Among the patients, 76.9% had no new pyelocalyceal dilatation on follow-up Doppler ultrasound scans at a mean follow-up time of 12 months. The restenosis rate was 23.1%, and all were successfully treated by endoscopic approach. There was an improvement in renal function figures at 1, 3, 6, and 12 months compared to renal function at diagnosis, both in terms of serum creatinine and glomerular filtration rate, with statistically significant results. CONCLUSION: Pyeloureteral anastomosis as a reconstructive technique of the urinary tract in renal transplant patients is an effective and reproducible technique with good long-term results.

17.
Rev. int. androl. (Internet) ; 21(4): 1-9, oct.-dic. 2023. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-226005

RESUMO

Las manifestaciones sexuales de los residentes de centros geriátricos de larga duración no suelen tenerse en cuenta e incluso son desalentadas por el personal asistencial. El objetivo de este estudio fue realizar una revisión sistemática sobre las actitudes, los conocimientos y las percepciones del personal asistencial sobre dichas manifestaciones sexuales. Tras la consulta en distintas bases de datos, 10 artículos científicos publicados entre 2012 y 2022 cumplieron los criterios de inclusión para formar parte de dicha revisión. Este trabajo ha permitido conocer y estructurar la insuficiente literatura científica referida a esta área concreta de la sexualidad en adultos mayores. Se concluye que existe escasa literatura científica y que las áreas revisadas son determinantes en el cuidado diario de adultos mayores institucionalizados. Ampliar en este campo de estudio permitirá crear programas de formación y afrontamiento de las conductas sexuales de los mayores institucionalizados por parte del personal asistencial. (AU)


The sexual manifestations of residents in long-term care facilities are often overlooked and even discouraged by care staff. The aim of this study was to conduct a systematic review of caregivers’ attitudes, knowledge and perceptions of sexual expression. After consulting different databases, ten scientific articles published between 2012 and 2022 met the inclusion criteria to form part of this review. This work has made it possible to identify and structure the insufficient scientific literature on this specific area of sexuality in older adults. It is concluded that there is scarce scientific literature and that the areas reviewed are determinant in the daily care of institutionalised older adults. Expanding in this field of study will allow the creation of training programmes and the creation of programmes for the care staff to deal with the sexual behaviour of institutionalised older adults. (AU)


Assuntos
Humanos , Sexualidade , Conhecimentos, Atitudes e Prática em Saúde , Geriatria , Comportamento Sexual , Envelhecimento , Instituição de Longa Permanência para Idosos
18.
medRxiv ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38106131

RESUMO

Background: The effect of alcohol consumption on cardiovascular health, including atrial fibrillation risk, remains controversial. Evaluating the association of alcohol consumption with circulating atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. Methods: We studied 523 participants from 3 sites for the PREDIMED-Plus study, a weight-loss randomized intervention trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein (NTproBNP), high sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured in fasting serum samples at baseline and years 3 and 5 of follow-up. We calculated alcohol consumption in drinks/day (1 drink = 14 grams alcohol) with validated food frequency questionnaires at each visit. Using multiple linear regression and mixed models we estimated the association of alcohol consumption with log-transformed biomarkers at baseline and longitudinally adjusting for potential confounders. Results: Among 523 participants (mean age: 65 years, 40% female), mean alcohol consumption was 1 drink/day. Cross-sectionally, alcohol consumption was not associated with cardiac biomarker concentrations. Longitudinally, compared to non-consumers, heavy drinkers (≥4 drinks/day) had smaller increases in hsTnT (ß: -0.11, 95%CI: -0.20, -0.01)and PICP (ß: -0.15, 95%CI: -0.30, 0.01) over the 5-year follow-up. In contrast, those who increased alcohol consumption over the 5-year period experienced greater increases in hsCRP (ß: 0.42, 95%CI: 0.11, 0.73) compared to those whose drinking behavior stayed the same. Conclusion: Alcohol consumption was associated with complex changes in circulating biomarkers, including comparatively lower fibrotic and myocardial damage, but higher levels of overall inflammation over time. These results underscore the need for further research to better understand the effects of alcohol on cardiovascular health.

19.
Org Lett ; 25(46): 8320-8325, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-37956189

RESUMO

Despite recent interest in the development of iron-catalyzed transformations, methods that use iron-based catalysts capable of controlling the enantioselectivity in carbon-carbon cross-couplings are underdeveloped. Herein, we report a practical and simple protocol that uses commercially available and expensive iron salts in combination with chiral bisphosphine ligands to enable the regio- and enantioselective (up to 91:9) multicomponent cross-coupling of vinyl boronates, (fluoro)alkyl halides, and Grignard reagents. Preliminary mechanistic studies are consistent with rapid formation of an α-boryl radical followed by reversible radical addition to monoaryl bisphosphine-Fe(II) and subsequent enantioselective inner-sphere reductive elimination. From a broader perspective, this work provides a blueprint to develop asymmetric Fe-catalyzed multicomponent cross-couplings via the use of alkenes as linchpins to translocate alkyl radicals, modify their steric and electronic properties, and induce stereocontrol.

20.
Chem Sci ; 14(45): 13007-13013, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38023494

RESUMO

Enol silyl ethers are versatile, robust, and readily accessible substrates widely used in chemical synthesis. However, the conventional reactivity of these motifs has been limited to classical two electron (2-e) enolate-type chemistry with electrophilic partners or as radical acceptors in one electron (1-e) reactivity leading, in both cases, to exclusive α-monofunctionalization of carbonyls. Herein we describe a mild, fast, and operationally simple one-step protocol that combines readily available fluoroalkyl halides, silyl enol ethers, and, for the first time, hetero(aryl) Grignard reagents to promote selective dicarbofunctionalization of enol silyl ethers. From a broader perspective, this work expands the synthetic utility of enol silyl ethers and establishes bisphosphine-iron catalysis as enabling technology capable of orchestrating selective C-C bond formations with short-lived α-silyloxy radicals with practical implications towards sustainable chemical synthesis.

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