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1.
Eur Respir J ; 64(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060017

RESUMO

BACKGROUND: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking. METHODS: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed. RESULTS: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h-1. The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up. CONCLUSION: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/complicações , Hipertensão/complicações , Hipertensão/fisiopatologia , Idoso , Estudos Prospectivos , Anti-Hipertensivos/uso terapêutico , Polissonografia , Pressão Positiva Contínua nas Vias Aéreas
2.
Crit Care Med ; 52(8): 1206-1217, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38597721

RESUMO

OBJECTIVES: To investigate the sleep and circadian health of critical survivors 12 months after hospital discharge and to evaluate a possible effect of the severity of the disease within this context. DESIGN: Observational, prospective study. SETTING: Single-center study. PATIENTS: Two hundred sixty patients admitted to the ICU due to severe acute respiratory syndrome coronavirus 2 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was composed of 260 patients (69.2% males), with a median (quartile 1-quartile 3) age of 61.5 years (52.0-67.0 yr). The median length of ICU stay was 11.0 days (6.00-21.8 d), where 56.2% of the patients required invasive mechanical ventilation (IMV). The Pittsburgh Sleep Quality Index (PSQI) revealed that 43.1% of the cohort presented poor sleep quality 12 months after hospital discharge. Actigraphy data indicated an influence of the disease severity on the fragmentation of the circadian rest-activity rhythm at the 3- and 6-month follow-ups, which was no longer significant in the long term. Still, the length of the ICU stay and the duration of IMV predicted a higher fragmentation of the rhythm at the 12-month follow-up with effect sizes (95% CI) of 0.248 (0.078-0.418) and 0.182 (0.005-0.359), respectively. Relevant associations between the PSQI and the Hospital Anxiety and Depression Scale (rho = 0.55, anxiety; rho = 0.5, depression) as well as between the fragmentation of the rhythm and the diffusing lung capacity for carbon monoxide (rho = -0.35) were observed at this time point. CONCLUSIONS: Our findings reveal a great prevalence of critical survivors presenting poor sleep quality 12 months after hospital discharge. Actigraphy data indicated the persistence of circadian alterations and a possible impact of the disease severity on the fragmentation of the circadian rest-activity rhythm, which was attenuated at the 12-month follow-up. This altogether highlights the relevance of considering the sleep and circadian health of critical survivors in the long term.


Assuntos
COVID-19 , Ritmo Circadiano , Sobreviventes , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Estudos Prospectivos , Seguimentos , Ritmo Circadiano/fisiologia , COVID-19/epidemiologia , Sobreviventes/estatística & dados numéricos , Estado Terminal , Respiração Artificial/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Qualidade do Sono , Actigrafia , Tempo de Internação/estatística & dados numéricos , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/epidemiologia , Sono/fisiologia
3.
Photochem Photobiol Sci ; 23(5): 823-837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38568410

RESUMO

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450 nm was used, with doses ranging from 20 to 60 J/cm2 and an NP concentration of 500 µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90-100% eradication of C. albicans.


Assuntos
Antifúngicos , Candida albicans , Luz , Nanopartículas , Titânio , Titânio/química , Titânio/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Nanopartículas/química , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fotoquimioterapia
4.
Neuroimage ; 210: 116532, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958584

RESUMO

BACKGROUND: A proposed mechanism of chronic pain is dysregulation between the main inhibitory (GABA) and excitatory (glutamate) neurometabolites of the central nervous system. The level of these neurometabolites appears to differ in individual studies of people with pain compared to pain-free controls across different pain conditions. However, this has yet to be systematically investigated. AIMS: To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. METHODS: Five databases were searched. Studies were included if they investigated: 1) A pain condition compared to control. 2) Reported GABA, glutamate, glutamine or glutamate/glutamine level. 3) Used 1H-Magnetic Resonance Spectroscopy (Prospero Project ID CRD42018092170). Data extracted included neurometabolite level, pain diagnosis, and spectroscopy parameters. Meta-analyses were conducted to establish the difference in neurometabolite level between participants with pain and pain-free controls for different pain conditions. The MRS-Q was developed from existing clinical consensus to allow for the assessment of quality in the included studies. RESULTS: Thirty-five studies were included investigating combinations of migraine (n = 11), musculoskeletal pain (n = 8), chronic pain syndromes (n = 9) and miscellaneous pain (n = 10). Higher GABA levels were found in participants with migraine compared to controls (Hedge's G 0.499, 95%CI: 0.2 to 0.798). In contrast, GABA levels in musculoskeletal pain conditions (Hedge's G -0.189, 95%CI: 0.530 to 0.153) and chronic pain syndromes (Hedge's G 0.077, 95%CI: 1.612 to 1.459) did not differ from controls. Results for other brain neurometabolites revealed significantly higher levels for glutamate in participants with migraine and Glx in chronic pain syndromes compared to controls. CONCLUSION: These results support the theory that underlying neurometabolite levels may be unique in different pain conditions and therefore representative of biomarkers for specific pain conditions.


Assuntos
Dor Crônica/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Transtornos de Enxaqueca/metabolismo , Dor Musculoesquelética/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ácido gama-Aminobutírico/metabolismo , Dor Crônica/diagnóstico por imagem , Humanos , Transtornos de Enxaqueca/diagnóstico por imagem , Dor Musculoesquelética/diagnóstico por imagem
5.
Cephalalgia ; 38(10): 1672-1686, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29199431

RESUMO

Background Evidence on the medium-term clinical course of recurrent headaches is scarce. This study explored the six-month course and factors associated with non-improvement in migraine compared with tension-type headache and cervicogenic headache. Methods In this longitudinal cohort study, the six-month course of headaches was prospectively examined in participants (n = 37 with migraine; n = 42 with tension-type or cervicogenic headache). Participants underwent physical examination for cervical musculoskeletal impairments at baseline. Participants also completed questionnaires on pain, disability and other self-report measures at baseline and follow-up, and kept an electronic diary for 6 months. Course of headaches was examined using mixed within-between analyses of variance and Markov chain modeling. Multiple factors were evaluated as possible factors associated with non-improvement using regression analysis. Results Headache frequency, intensity, and activity interference in migraine and non-migraine headaches were generally stable over 6 months but showed month-to-month variations. Day-to-day variations were more volatile in the migraine than the non-migraine group, with the highest probability of transitioning from any headache state to no headache (probability = 0.82-0.85). The odds of non-improvement in disability was nearly six times higher with cervical joint dysfunction (odds ratio [95% CI] = 5.58 [1.14-27.42]). Conclusions Headache frequency, intensity, and activity interference change over 6 months, with day-to-day variation being more volatile in migraine than non-migraine headaches. Cervical joint dysfunction appears to be associated with non-improvement for disability in 6 months. These results may contribute to strategies for educating patients to help align their expectations with the nature of their headaches.


Assuntos
Cefaleia , Transtornos de Enxaqueca , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
6.
Cephalalgia ; 38(4): 786-793, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28440672

RESUMO

Background Clear definitions of study populations in clinical trials may facilitate application of evidence to clinical populations. This review aimed to explore definitions of study populations in clinical trials on migraine, tension-type headache, cluster headache, and cervicogenic headache. Methods We performed a systematic review of clinical trials investigating treatment efficacy for migraine, tension-type headache, cluster headache, and cervicogenic headache. We extracted data on diagnosis, inclusion criteria and baseline headache characteristics. Results Of the 229 studies reviewed, 205 studies (89.5%) defined their populations in adherence to the International Classification of Headache Disorders (ICHD) criteria. Some studies ( n = 127, 55.5%) specified diagnosing through interview, clinical examination and diary entry. The most commonly reported inclusion criteria were pain intensity for migraine and tension-type headache studies ( n = 123, 66.1% and n = 21, 67.7%, respectively), episode frequency ( n = 5, 71.4%) for cluster headache studies, and neck-related pain for cervicogenic headache studies ( n = 3, 60%). Few studies reported details on the extent to which diagnostic criteria were present at baseline. Conclusions ICHD is routinely used in defining populations in headache studies. Details of baseline headache characteristics were not as consistently reported.


Assuntos
Ensaios Clínicos como Assunto , Cefaleia/classificação , Cefaleia/terapia , Classificação Internacional de Doenças , Seleção de Pacientes , Humanos
8.
NMR Biomed ; 28(7): 890-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25997981

RESUMO

γ-Aminobutyric acid (GABA) has been implicated in several pain conditions, yet no study has systematically evaluated GABA levels in migraine using (1) H-MRS. The accurate detection, separation and quantification of GABA in individuals with migraine could elucidate the role of this neurotransmitter in migraine pathophysiology. Such information may eventually be useful in the diagnosis and development of more effective treatments for migraine. The aims of this study were therefore to compare the concentration of GABA+ in individuals with migraine with that in asymptomatic individuals, and to determine the diagnostic potential of GABA+ in the classification of those with or without migraine. In this case-control study, GABA+ levels in the brain were determined in 19 participants with migraine and 19 matched controls by (1) H-MRS using Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence. The diagnostic accuracy of GABA+ for the detection of migraine and the optimal cut-off value were determined by receiver operating characteristic analysis. GABA+ levels were significantly higher (p = 0.002) in those with migraine [median, 1.41 institutional units (IU); interquartile range, 1.31-1.50 IU] than in controls (median, 1.18 IU; interquartile range, 1.12-1.35 IU). The GABA+ concentration appears to have good accuracy for the classification of individuals with or without migraine [area under the curve (95% confidence interval), 0.837 (0.71-0.96); p < 0.001]. The optimal GABA+ cut-off value for migraine was 1.30 IU, with a sensitivity of 84.2%, specificity of 68.4% and positive likelihood ratio of +2.67. The outcomes of this study suggest altered GABA metabolism in migraine. These results add to the scarce evidence on the putative role of GABA in migraine and provide a basis to further explore the causal relationship between GABA+ and the pathophysiology of migraine. This study also demonstrates that GABA+ concentration has good diagnostic accuracy for migraine. These findings offer new research and practice directions for migraine diagnosis.


Assuntos
Encéfalo/metabolismo , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ácido gama-Aminobutírico/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurotransmissores/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Regulação para Cima , Adulto Jovem
9.
Br J Pharmacol ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359818

RESUMO

BACKGROUND AND PURPOSE: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications. EXPERIMENTAL APPROACH: We conducted a longitudinal investigation including 119 critical COVID-19 survivors. A comprehensive pulmonary evaluation was performed in the short-term (median = 94.0 days after hospital discharge) and long-term (median = 358 days after hospital discharge). Plasma miRNAs were quantified at the short-term evaluation using the gold-standard technique, RT-qPCR. The analyses combined machine learning feature selection techniques with bioinformatic investigations. Two additional datasets were incorporated for validation. KEY RESULTS: In the short-term, 84% of the survivors exhibited impaired lung diffusion (DLCO  < 80% of predicted). One year post-discharge, 54.4% of this patient subgroup still presented abnormal DLCO . Four feature selection methods identified two specific miRNAs, miR-9-5p and miR-486-5p, linked to persistent lung dysfunction. The downstream experimentally validated targetome included 1473 genes, with heterogeneous enriched pathways associated with inflammation, angiogenesis and cell senescence. Validation studies using RNA-sequencing and proteomic datasets emphasized the pivotal roles of cell migration and tissue repair in persistent lung dysfunction. The repositioning potential of the miRNA targets was limited. CONCLUSION AND IMPLICATIONS: Our study reveals early mechanistic pathways contributing to persistent lung dysfunction in critical COVID-19 survivors, offering a promising approach for the development of targeted disease-modifying agents.

10.
Arch Bronconeumol ; 2024 Sep 03.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39277516

RESUMO

INTRODUCTION: Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients. METHODS: This is an ancillary analysis to the SARAH study, a multicentre observational cohort aiming to evaluate the impact of OSA on RH. Individuals with RH who were undergoing a sleep study and have information on at least one of the SOD variables (vascular, cardiac or renal damage) were selected. Patients were followed-up for three years. RESULTS: In total, 503 subjects were included. The participants were predominantly male, obese, and the median (IQR) apnea-hypopnea index (AHI) was 15.5 (7.90-31.5)events/h. No differences in the presence of vascular or cardiac damage were observed between OSA and non-OSA patients. A lower estimated glomerular filtration rate (eGFR) was observed in participants with OSA than in those without OSA, with an adjusted effect of -8.69mL/min/1.73m2 (-13.59, -3.79; p value<0.001). Kidney damage was also greater in subjects with OSA, with an adjusted OR (95% CI) of 1.77 (1.09, 2.87; p value=0.02). The eGFR showed a linear dose-response relationship with OSA severity. Among patients treated with CPAP, lower eGFR values were observed in noncompliant subjects. CONCLUSIONS: OSA could contribute to worsening renal function in patients with RH. No compliance with CPAP was associated with lower values of eGFR.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36833561

RESUMO

Government is key to promoting physical activity at the population level through policy. The government was one of the physical activity indicators graded for the 2022 Philippine Physical Activity Report Card based on ten physical activity-related policies. This study aimed to evaluate the scope of the policies and to update these policies. Philippine government databases were searched for policies using physical activity-related key terms. Policies found were evaluated using the Wales Active Healthy Kids scoring rubric. The overall grade was converted to a letter grade based on the Global Matrix 4.0 grading system. The authors analyzed the policies' scope and implications to practice and policy. Seven additional policies were found. Considering all 17 policies, the government indicator grade is now A- from the preliminary grade of B. The scope covers promoting physical activity mainly through sports participation and active transport among students, student-athletes, persons with disabilities, and the general population in school and community settings. The gap between government and overall physical activity (F) scores suggests the need for a comprehensive physical activity plan promoting various forms of physical activity and reducing sedentary behavior among all Filipino youth and across various settings. Crucial to achieving change is a well-coordinated, whole-of-systems approach to promoting active healthy lifestyles.


Assuntos
Promoção da Saúde , Esportes , Humanos , Política de Saúde , Jogos e Brinquedos , Exercício Físico
12.
Sleep ; 46(4)2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-36806948

RESUMO

We characterized the polysomnography (PSG) parameters associated with alterations in the circadian blood pressure (BP) pattern aiming to identify the main contributors to explain the nondipper profile in obstructive sleep apnea (OSA). This is an observational prospective-multicenter study that included participants referred to the sleep unit for suspected OSA. Following a PSG study, subjects with an apnea-hypopnea index (AHI) ≥5 events/hr were included. Two groups were established based on the 24-hr ambulatory blood pressure monitoring dipping ratio (DR; night/day BP ratio): dippers (DR ≤ 0.9) and nondippers (DR > 0.9). The cohort consisted of 299 patients: 131 (43.8%) dippers and 168 (56.2%) nondippers. A significant increase in the risk of presenting a nondipper BP pattern was found along with AHI gain [odds ratio (OR) (95% CI) = 1.71 (1.28 to 2.28)]. The best AHI cutoff for predicting nondipper status was 25.2 events/hr, increasing the OR (95% CI) to 3.50 (2.02 to 6.07). The hypopnea index [OR (95% CI) = 1.70 (1.27 to 2.26)], TSat90 [OR (95% CI) = 1.41 (1.06 to 1.87)], and respiratory arousal index [OR (95% CI) = 1.74 (1.30 to 2.34)] were individually associated with the risk of a nondipping pattern. Multivariate variable selection processes identified the respiratory arousal index as the most relevant risk factor for the nondipper profile, beyond classical clinical risk factors and usual PSG metrics.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Apneia Obstrutiva do Sono , Humanos , Pressão Sanguínea/fisiologia , Estudos Prospectivos , Sono
13.
Arch Bronconeumol ; 59(4): 205-215, 2023 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36690515

RESUMO

INTRODUCTION: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. METHODS: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. RESULTS: The median [p25-p75] time from discharge to follow-up was 3.57 [2.77-4.92] months. Median age was 60 [53-67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO<80% and 24% having DLCO<60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO<60% were chronic lung disease (CLD) (OR: 1.86 (1.18-2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37-1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18-1.63)), urea (OR: 1.16 (0.97-1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73-1.06)). Bacterial pneumonia (1.62 (1.11-2.35)) and duration of ventilation (NIMV (1.23 (1.06-1.42), IMV (1.21 (1.01-1.45)) and prone positioning (1.17 (0.98-1.39)) were associated with fibrotic lesions. CONCLUSION: Age and CLD, reflecting patients' baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities.


Assuntos
COVID-19 , Enfisema Pulmonar , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estado Terminal , Seguimentos , COVID-19/complicações , Progressão da Doença , Pulmão/diagnóstico por imagem
14.
Biomed Pharmacother ; 145: 112425, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34800782

RESUMO

INTRODUCTION: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition. OBJECTIVE: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile. MATERIAL AND METHODS: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry. RESULTS: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA. CONCLUSIONS: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Lipidômica , Metabolômica , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Biomarcadores/metabolismo , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Metaboloma , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia
15.
Biomed Pharmacother ; 154: 113617, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36058144

RESUMO

BACKGROUND: Up to 80% of patients surviving acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection present persistent anomalies in pulmonary function after hospital discharge. There is a limited understanding of the mechanistic pathways linked to post-acute pulmonary sequelae. AIM: To identify the molecular underpinnings associated with severe lung diffusion involvement in survivors of SARS-CoV-2-induced ARDS. METHODS: Survivors attended to a complete pulmonary evaluation 3 months after hospital discharge. RNA sequencing (RNA-seq) was performed using Illumina technology in whole-blood samples from 50 patients with moderate to severe diffusion impairment (DLCO<60%) and age- and sex-matched individuals with mild-normal lung function (DLCO≥60%). A transcriptomic signature for optimal classification was constructed using random forest. Transcriptomic data were analyzed for biological pathway enrichment, cellular deconvolution, cell/tissue-specific gene expression and candidate drugs. RESULTS: RNA-seq identified 1357 differentially expressed transcripts. A model composed of 14 mRNAs allowed the optimal discrimination of survivors with severe diffusion impairment (AUC=0.979). Hallmarks of lung sequelae involved cell death signaling, cytoskeleton reorganization, cell growth and differentiation and the immune response. Resting natural killer (NK) cells were the most important immune cell subtype for the prediction of severe diffusion impairment. Components of the signature correlated with neutrophil, lymphocyte and monocyte counts. A variable expression profile of the transcripts was observed in lung cell subtypes and bodily tissues. One upregulated gene, TUBB4A, constitutes a target for FDA-approved drugs. CONCLUSIONS: This work defines the transcriptional programme associated with post-acute pulmonary sequelae and provides novel insights for targeted interventions and biomarker development.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , COVID-19/complicações , COVID-19/genética , Humanos , Pulmão , Síndrome do Desconforto Respiratório/genética , SARS-CoV-2 , Sobreviventes , Tubulina (Proteína)
16.
Ann Am Thorac Soc ; 18(9): 1540-1547, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33662230

RESUMO

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated with OSA might be age dependent. Objectives: To evaluate the association of OSA with the aging process and to determine whether this association is maintained across different age groups. Methods: This was an observational, prospective study including 599 patients with suspected OSA. Five hallmarks of aging were evaluated: alteration of cellular communication (serum CRP [C-reactive protein] concentration), deregulation of nutrient sensing (insulin resistance), telomere attrition (leukocyte telomeric length), mitochondrial dysfunction (leukocyte mitochondrial DNA copy number), and genomic instability (urinary 8-hydroxy-2-deoxyguanosine concentration). For age-stratified analyses, subjects were divided into four groups according to the apnea-hypopnea index (AHI) and the median age (50 yr): young patients without OSA (age < 50 yr old, AHI < 15 events/h), young patients with OSA (age < 50 yr old, AHI ⩾ 15 events/h), older patients without OSA (age ⩾ 50 yr old, AHI < 15 events/h), and older patients with OSA (age ⩾ 50 yr old, AHI ⩾ 15 events/h). Results: A dose-response relationship was found between the AHI, arousal index, and time during the night spent with an oxygen saturation less than 90% and the following hallmarks: alteration of cellular communication, deregulation of nutrient sensing, mitochondrial dysfunction, and genomic instability. Considering age-stratified analyses, OSA was associated with an increase in several hallmarks of aging in young patients, but no significant association of OSA was identified in older patients. Conclusions: In subjects under 50 years of age, OSA is associated with an increase in specific hallmarks of aging, independent of several known confounding factors.


Assuntos
Resistência à Insulina , Apneia Obstrutiva do Sono , Idoso , Envelhecimento , Humanos , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia
17.
J Pain ; 22(12): 1631-1645, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34182103

RESUMO

Treatment outcomes for migraine and other chronic headache and pain conditions typically demonstrate modest results. A greater understanding of underlying pain mechanisms may better inform treatments and improve outcomes. Increased GABA+ has been identified in recent studies of migraine, however, it is unclear if this is present in other headache, and pain conditions. We primarily investigated GABA+ levels in the posterior cingulate gyrus (PCG) of people with migraine, whiplash-headache and low back pain compared to age- and sex-matched controls, GABA+ levels in the anterior cingulate cortex (ACC) and thalamus formed secondary aims. Using a cross-sectional design, we studied people with migraine, whiplash-headache or low back pain (n = 56) and compared them with a pool of age- and sex-matched controls (n = 22). We used spectral-edited magnetic resonance spectroscopy at 3T (MEGA-PRESS) to determine levels of GABA+ in the PCG, ACC and thalamus. PCG GABA+ levels were significantly higher in people with migraine and low back pain compared with controls (eg, migraine 4.89 IU ± 0.62 vs controls 4.62 IU ± 0.38; P = .02). Higher GABA+ levels in the PCG were not unique to migraine and could reflect a mechanism of chronic pain in general. A better understanding of pain at a neurochemical level informs the development of treatments that target aberrant brain neurochemistry to improve patient outcomes. PERSPECTIVE: This study provides insights into the underlying mechanisms of chronic pain. Higher levels of GABA+ in the PCG may reflect an underlying mechanism of chronic headache and pain conditions. This knowledge may help improve patient outcomes through developing treatments that specifically address this aberrant brain neurochemistry.


Assuntos
Dor Crônica/metabolismo , Giro do Cíngulo/metabolismo , Cefaleia/metabolismo , Dor Lombar/metabolismo , Transtornos de Enxaqueca/metabolismo , Tálamo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adulto , Estudos de Casos e Controles , Dor Crônica/diagnóstico por imagem , Estudos Transversais , Feminino , Giro do Cíngulo/diagnóstico por imagem , Cefaleia/diagnóstico por imagem , Cefaleia/etiologia , Humanos , Dor Lombar/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico por imagem , Espectroscopia de Prótons por Ressonância Magnética , Tálamo/diagnóstico por imagem , Traumatismos em Chicotada/complicações
18.
Healthcare (Basel) ; 9(11)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34828556

RESUMO

OBJECTIVE: To determine the relationship between the characteristics and experiences of homeless persons and their state of happiness as a basis for designing appropriate social support strategies. DESIGN: Exploratory observational study with an analytical and descriptive qualitative design. SETTING: Participants were contacted, administered with questionnaires, and interviewed in the street (central and northern areas of the city) or at the "Asociación Calor y Café" center in Granada (Spain) between April 2017 and February 2018. PARTICIPANTS: Selected by intentional sampling, 25 participants completed questionnaires in the first study and 14 of these were administered with questionnaires and interviewed in the second study. METHOD: General and specific questionnaires were administered to determine the state of happiness and other variables. Descriptive statistics were followed by an analysis of the relationships between variables and the content analysis of semi-structured interviews. RESULTS: A feeling of happiness was described by 64% of participants and confirmed by a happiness scale score of 50%. Participants who felt satisfied with their life were 4.5-fold more likely to feel happy (p = 0.021). Expectations for the future were not associated with happiness or satisfaction with life. Content analysis of interviews revealed three main themes: conditions for happiness, own happiness/unhappiness, and self-esteem. CONCLUSIONS: Many homeless people describe themselves as feeling happy and satisfied with their life. Material aspects, affective situations, daily life concerns, and self-esteem predominate in their discourse on happiness.

19.
Health Policy ; 89(1): 37-45, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18550203

RESUMO

OBJECTIVE: The objective of this study was to explore the possible association between the anxiety level of patients and their satisfaction with different aspects of healthcare. METHOD: This analytical cross-sectional study included 301 patients undergoing scheduled trauma surgery from October 2004 to May 2005 at the Virgen de las Nieves University Hospital in Granada (Spain). They completed a sociodemographic and clinical questionnaire before their discharge and, at 15 days after discharge, they responded to an ad hoc questionnaire comprising three items (satisfaction with information received, privacy and comfort of the setting, and friendliness of healthcare professionals), and were scored on an interviewer-administered Zung anxiety scale. Descriptive analysis and unadjusted logistic regression were performed for each factor, followed by multivariate logistic regression to model the association between satisfaction and anxiety with study of confounding variables. RESULTS: For each higher point in the Zung test, patients had a 4% higher risk of feeling dissatisfied with the information received, an 8% higher risk of dissatisfaction with the hospital setting and a 6% higher risk of dissatisfaction with the friendliness of healthcare personnel. CONCLUSION: A higher anxiety level in the patient was associated with greater dissatisfaction with the three healthcare aspects studied.


Assuntos
Ansiedade , Satisfação do Paciente , Pacientes/psicologia , Adulto , Idoso , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Saúde Pública , Espanha
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