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BACKGROUND: Early mobility (EM) is vital in the intensive care unit (ICU) to counteract immobility-related effects. A multidisciplinary approach is key, as it requires precise initiation knowledge. However, physicians' understanding of EM in adult ICU settings remains unexplored. This study was conducted to investigate the knowledge and clinical competency of physicians working in adult ICUs toward EM. METHODS: This cross-sectional study enrolled 236 physicians to assess their knowledge of EM. A rigorously designed survey comprising 30 questions across the demographic, theoretical, and clinical domains was employed. The criteria for knowledge and competency were aligned with the minimum passing score (70%) stipulated for physician licensure by the medical regulatory authority in Saudi Arabia. RESULTS: Nearly 40% of the respondents had more than 5 years of experience. One-third of the respondents received theoretical knowledge about EM as part of their residency training, and only 4% of the respondents attended formal courses to enhance their knowledge. Almost all the respondents (95%) stated their awareness of EM benefits and its indications and contraindications and considered it safe to mobilize patients on mechanical ventilators. However, 62.3% of the respondents did not support EM for critically ill patients on mechanical ventilators until weaning. In contrast, 51.7% of respondents advised EM for agitated patients with RASS > 2. Only 113 (47.9%) physicians were competent in determining the suitability of ICU patients for EM. For critically ill patients who should be mobilized, nearly 60% of physicians refused to initiate EM. CONCLUSIONS: This study underscores insufficient practical knowledge of ICU physicians about EM criteria, which leads to suboptimal decisions, particularly in complex ICU cases. These findings emphasize the need for enhanced training and education of physicians working in adult ICU settings to optimize patient care and outcomes in critical care settings.
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BACKGROUND/OBJECTIVE(S): Chronic obstructive pulmonary disease (COPD) can precipitate a deterioration of an individual's physical performance and overall health. Evidence suggests that, along with pulmonary functions, several other factors are related to the significant impairment of walking performance in individuals with COPD. This study compared the depressive symptoms, health status, upper and lower extremity functions, and peak oxygen uptake (VO2peak) in a group of individuals with COPD based on walking performance using a cutoff distance of 350 m in the six-minute walking test (6MWT). The study also investigated the associations between these factors and walking performance. MATERIALS AND METHODS: Participants performed the 6MWT according to the guidelines and were classified into high (>350 m; n = 40) or low (<350 m; n = 30) walking performance groups according to distance. The forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were recorded. Participants completed the Patient Health Questionnaire-9 (PHQ-9), St. George's Respiratory Questionnaire (SGRQ), and the Upper and Lower Extremity Functional Index (UEFI/LEFI). Predicted VO2peak was measured using the Duke Activity Status Index (DASI). RESULTS: Seventy participants with a mean age of 63 ± 11 years (20% female) were enrolled in this study. Patients with high walking performance demonstrated significantly better health status than those with low walking performance (SGRQ: 49 ± 25 vs. 56 ± 21, p = 0.03). Participants with low walking performance had lower predicted VO2peak compared to their higher performing counterparts (p = 0.002). The overall model was significant (F(8, 61) = 7.48, p = 0.0006), with PHQ-9, SGRQ, UEFI/LEFI, VO2peak, and FEV1/FVC explaining approximately 49.5% of the variance in the 6MWT distance. CONCLUSION: This study shed light on the association of depressive symptoms, health status, extremity function, and VO2peak with walking performance, providing valuable insights that may impact the management and care of individuals with COPD.
COPD is a global health issue that significantly impairs physical performance, particularly walking.Depressive symptoms, health status, extremity function, and predicted peak oxygen uptake can predict walking performance in patients with COPD, offering insight into potential interventions.
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Depressão , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Nível de Saúde , Volume Expiratório Forçado , Extremidades , Caminhada , Desempenho Físico Funcional , Qualidade de VidaRESUMO
Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is the most specific and widely used questionnaire for assessing health-related quality of life (HRQoL) in chronic heart failure (CHF). This study aimed to examine reliability and validity of the KCCQ in Arabic patients with CHF. Material and Methods: Patients with CHF filled out the Arabic versions of the Minnesota Living with Heart Failure (MLHF) and KCCQ questionnaire, and performed a six-minute walk test (6MWT) on their first visit. On the return, the patients filled out the KCCQ along with the global rating of change (GRC) scale. Internal consistency, test-retest reliability, and construct validity were examined. Results: A total of 101 Arabic patients with CHF, with a mean (SD) age of 55 (11) years old, completed the study. The Cronbach's alpha was 0.97, and the ICC2,1 = 0.95 (95%CI: 0.92 to 0.97, p < 0.001). The Arabic version of KCCQ was correlated with the MLHF (r = -0.57, p = 0.01) and with the 6MWT (r = 0.70, p < 0.001). Conclusions: The Arabic version of KCCQ is a reliable and valid measure of HRQoL, which could be utilized in routine clinical practice for Arabic-speaking patients with CHF.
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Cardiomiopatias , Insuficiência Cardíaca , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Kansas , Reprodutibilidade dos Testes , Insuficiência Cardíaca/complicações , Doença Crônica , Inquéritos e Questionários , PsicometriaRESUMO
OBJECTIVE: To objectively quantify the effect of flattening the crimps in Dacron tube grafts on the radial compliance under pulsatile pressure. We aimed to minimize the dimensional changes in woven Dacron graft tubes by applying axial stretch to the graft. We hypothesize this might reduce the risk of coronary button misalignment in aortic root replacement. METHODS: In an in vitro pulsatile model that delivered systemic circulatory pressures to Dacron tube grafts, we measured oscillatory movements in 26-30 mm Dacron vascular tube grafts before and after flattening the graft crimps. We also describe our surgical methods and clinical experiences in replacing the aortic root. RESULTS: Flattening the crimps in Dacron tubes with axial stretching significantly reduced the mean maximal oscillation distance measured radially during each balloon pulse (3.2 ± 0.8 mm, 95% CI: 2.6, 3.7 mm vs. 1.5 ± 0.5 mm, 95% CI: 1.2, 1.7 mm; P < 0.001). CONCLUSION: The radial compliance of woven Dacron tubes was significantly reduced after flattening the crimps. Applying axial stretch to the Dacron grafts prior to determining the coronary button attachment site can help maintain dimensional stability in the graft, which may reduce the risk of coronary malperfusion in aortic root replacment.
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Tecoma stans (Fam. Bignoniaceae) is also popularly known as yellow bells and yellow trumpet bush in vernacular terminology. Limited and variable data are available from the literature regarding the quantification of luteolin, apigenin and chrysoeriol, which are considered as the most active pharmacological active constituents. High-performance liquid chromatography-photodiode array detection has been developed for the determination of the bioactive flavonoids, luteolin, apigenin and chrysoeriol, from the methanolic extract of the leaves of T. stans. A column packed with a pentafluorophenyl-based stationary phase was used for the separation of the analytes under gradient elution. The detection wavelength was 345 nm. The validation of the method as per the International Council on Harmonisation (ICH) guidelines (ICH 2005) for linearity, accuracy and precision was investigated and found within limits specified by the ICH guidelines. The method was linear over with a good regression coefficient of more than 0.99. The limit of detection of the method was 0.68, 2.97 and 1.76 µg/mL for luteolin, apigenin and chrysoeriol, respectively. In conclusion, a reliable and reproducible method was devised that can be used for the estimation of the said components from T. stans.
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Apigenina , Bignoniaceae , Apigenina/análise , Luteolina/análise , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacologiaRESUMO
Background: While a lack of psychological preparedness and fear of movement may be linked with the anterior cruciate ligament (ACL) re-injury, these variables are rarely addressed throughout the therapy stages via educational sessions. Unfortunately, in terms of reducing fear, increasing function, and returning to play, no research has been done yet on the efficacy of adding organized educational sessions to the rehabilitation programs of soccer players post-ACL reconstruction (ACLR). Therefore, the study's aim was to assess the feasibility and acceptability of adding organized educational sessions to the rehabilitation programs post-ACLR. Methods: A feasibility randomized controlled trial (RCT) was conducted in a specialized sports rehabilitation center. Participants post ACL reconstruction were randomized to either usual care with a structured educational session (intervention group) or usual care alone (control group). This feasibility study investigated three aspects: recruitment, intervention acceptability and randomization, and retention. The outcome measures included Tampa Scale of Kinesiophobia, ACL-Return to Sport after Injury, and International Knee Documentation Committee for knee function. Measurements were done at baseline and one week after the intervention. Results: All of the 36 players who were undergoing rehabilitation post-ACLR at the center at the time of the study were invited to participate in the study. Thirty-five players (97.2%) agreed to participate in the study. The participants responded to some questions about the acceptability of the intervention and randomization and most of them thought they were appropriate. 30 (85.7%) participants completed the follow-up questionnaires one week after the randomization. Conclusion: This feasibility research found that adding a structured educational session to the rehabilitation program for soccer players after ACLR is feasible and acceptable. Full-scale RCTs with longer follow-ups and multiple locations are recommended.
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The role of anxiety and depression in functional performance during walking in patients with chronic obstructive pulmonary disease (COPD) is controversial. In this cross-sectional study, we aimed to assess the effects of anxiety, depression, and health-related quality of life (HRQOL) on the functional performance of this patient population. Seventy COPD patients aged 63 ± 11 years participated in the study. To measure their functional performance, the six-minute walk test (6MWT) was used. Anxiety and depression were assessed using two questionnaires: the Anxiety Inventory for Respiratory Disease (AIR) scale and the Hospital Anxiety and Depression Scale (HADS). The St. George's Respiratory Questionnaire (SGRQ) was used to assess HRQOL. Based on their anxiety levels, the patients were divided into a no anxiety group and a high anxiety group. There were no significant differences between the two groups in terms of pulmonary function profile or smoking status. The mean AIR and HADS (depression) scores were high (12.78 ± 4.07 and 9.90 ± 3.41, respectively). More than one-third of the patients (46%) reported high anxiety levels (above the standard cutoff score of 8). The mean score of the aggregated HADS scale was significantly higher in the high anxiety group (20.87 ± 6.13) than in the no anxiety group (9.26 ± 4.72; p = 0.01). Patients with high anxiety had poorer functional performance (6MWT: 308.75 ± 120.16 m) and HRQOL (SGRQ: 56.54 ± 22.36) than patients with no anxiety (6MWT: 373.76 ± 106.56 m; SGRQ: 42.90 ± 24.76; p < 0.01). The final multivariate model explained 33% of the variance in functional performance after controlling for COPD severity (F = 8.97). The results suggest that anxiety, depression, and poor health status are significantly associated with poor functional performance. This study highlights the need to screen patients with COPD at all stages for anxiety and depression.
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Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Depressão/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Pulmão , Inquéritos e QuestionáriosRESUMO
Depression is the most prevalent and devastating neuropsychiatric disorder. There are several conventional antidepressants used for the treatment of depression. But due to their undesired adverse effects, patient compliance is very poor. Thus, developing novel medications for the treatment of depression is a critical strategic priority for meeting therapeutic demands. Current research is looking for alternatives to traditional antidepressants to reduce undesired side effects and increase efficacy. Phytoconstituents provide a wide research range in antidepressant treatments. In the present article, we have conducted a comprehensive assessment of neurological evidence, which supports the usefulness of phytoconstituents in the treatment of the depressive disorder. Secondary plant metabolites including alkaloids, polyphenols, glycosides, saponins, and terpenoids were found to exhibit antidepressant action. Most of the phytoconstituents were found to mediate their antidepressant effect through the upregulation of brain-derived neurotrophic factor (BDNF), serotonin, noradrenaline, and dopamine. Some were also found to exert antidepressant effects by inhibiting the monoamine oxidase (MAO) activity and hypothalamic-pituitary-adrenal (HPA) axis overactivity.
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Antidepressivos , Serotonina , Humanos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológicoRESUMO
PURPOSE: To translate and cross-culturally adapt the original Duke Activity Status Index (DASI) into the Arabic language and examine its psychometric properties in Arabic speaking patients with Chronic Obstructive Pulmonary Disease (COPD). MATERIALS AND METHODS: The DASI was translated into the Arabic language and tested on 70 Arabic patients with COPD. Patients with COPD completed also the Six-Minute Walk Test (6MWT) and Saint George Respiratory Questionnaire (SGRQ) on the first visit. On the second visit, the patients with COPD completed the Arabic version of DASI along with the global rating of change scale (GRC). The internal consistency, test-retest reliability and construct validity were examined. RESULTS: Seventy Arabic speaking patients with COPD (56 males), mean (SD) age was 63.2 (11.1) year, completed the study. The patients reported no difficulty in understanding and completing the scale. Three items were modified and adapted to the Arabic culture. The Cronbach's alpha was 0.87, and the ICC2,1 was 0.95. The Arabic version of DASI correlated with the 6MWT (r = 0.55), the total score of SGRQ (r = -0.64) and its activity domain (r = -0.67), all p < 0.001. CONCLUSION: The Arabic version of DASI is a simple, quick, reliable, and valid measure of functional capacity in Arabic speaking patients with COPD.Implications for practiceThe Arabic DASI can be used in all Arabic-speaking countries given that the scale was adapted to standard Arabic language.The Arabic DASI would yield similar scores with administrations over time in patients with unchanged condition and stable COPD.This questionnaire could be used for screening of functional capacity in COPD in primary care settings.
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Comparação Transcultural , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Psicometria , Reprodutibilidade dos Testes , Idioma , Inquéritos e QuestionáriosRESUMO
Heart failure (HF) is a serious disorder that affects millions of people worldwide, with a high rate of exercise intolerance, rehospitalization, and death. HF has many underlying causes, including type 2 diabetes mellitus (T2DM), which corresponds with high mortality and short survival among patients with HF. Numerous studies have shown the crucial role of gliflozins, a new generation of blood glucose-lowering medications, in cardiac remodeling, with beneficial impacts on exercise capacity and cardiovascular (CV) mortality, even in non-diabetic individuals. The foundational CV-protective frameworks of these agents are intricate and multifaceted. Dapagliflozin is a new widely used drug and a valuable alternative for patients with T2DM and CV risk factors. Dapagliflozin was approved by the Food and Drug Administration (FDA) in 2019 to lower the risk of HF hospitalization in patients with concurrent T2DM and CV disease or associated risk factors. However, the effects of this new drug on exercise capacity and CV risk still need to be elucidated. The primary objective of this review is to summarize the effect of dapagliflozin on exercise capacity and CV risk in patients with HF.
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The aim of the study was to examine the measurement properties of the Arabic version of the Duke Activity Status Index (DASI) in patients with cardiovascular disease (CVD). A sample of 100 Arab patients with CVD completed the Arabic version of the DASI and underwent an exercise stress test (EST) on the first visit, and the metabolic equivalent (MET) was obtained from each outcome measure. On the second visit, patients with CVD completed the Arabic version of the DASI along with the global rating of change scale (GRC). Reliability, including the internal consistency, test-retest reliability, and construct validity, were examined. Patients with CVD (86 males), mean (SD) age 54.98 (10.2) years, completed the study. The Cronbach's alpha was 0.87, and the intraclass correlation coefficient (ICC2,1) was 0.93. The estimated MET and peak VO2 obtained from the DASI were correlated with the estimated MET and peak VO2 obtained from the EST (r = 0.58, r = 0.56, all p-values < 0.001). The Arabic version of the DASI is a simple, quick, reliable, and valid measure of functional capacity in Arabic-speaking patients with CVD. The DASI may serve as a screening tool for functional capacity in patients with CVD in clinical settings.
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Árabes , Doenças Cardiovasculares , Masculino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Teste de Esforço , PsicometriaRESUMO
BACKGROUND: Severe atherosclerosis of the ascending aorta (SAA) in patients undergoing surgical revascularization by coronary artery bypass grafting (CABG) is becoming an increasing problem as more elderly patients are diagnosed with coronary artery disease. Strokes and other neurologic insults are common complications in this group, with devastating impacts on outcomes and prognoses. HYPOTHESIS: Early detection of the atherosclerotic aorta and the application of a stroke prevention protocol will reduce the risk of stroke in patients with SAA. METHODS: In 2012, we adopted a protocol devised to preemptively detect and manage patients suspected of having SAA. From the time of the application of the protocol, we compared the immediate and late outcomes of CABG in SAA in the 8 years preceding the protocol in a "control" group (30 patients) and in the 8 years following the protocol in a "brain" group (69 patients). RESULTS: More patients with SAA were detected after the initiation of the protocol. They had significantly more history of stroke, renal dysfunction, and left main coronary disease. The percutaneous coronary intervention was utilized more after the protocol (26% vs. 7%) and there was far less utilization of replacement of the ascending aorta (12% vs. 37%). Postoperative stroke rates were significantly less after the protocol (2% vs. 18%), with an almost twofold reduction in stroke associated with SAA even after risk adjustment. The composite endpoints of cardiac death, nonfatal myocardial infarction, and stroke were significantly reduced after initiating the protocol at a median of 2.3 years from the time of revascularization. CONCLUSION: Early detection of SAA and individualized therapeutic strategies for revascularization is effective in reducing athero-embolic brain injury and are associated with better prognosis.
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Doenças da Aorta , Aterosclerose , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Humanos , Idoso , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Intervenção Coronária Percutânea/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Aorta/diagnóstico por imagem , Aorta/cirurgia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico , Doenças da Aorta/diagnóstico , Doenças da Aorta/cirurgia , Aterosclerose/complicações , Aterosclerose/diagnóstico , Aterosclerose/cirurgia , Resultado do TratamentoRESUMO
Type 2 diabetes mellitus (T2D) is a metabolic disorder that knows no boundaries and is spread across the globe. It is one of the most widely spread metabolic disorder, which has now been described as a 'lifestyle' disease. According to the recent study conducted by International Diabetes Federation, the number of diabetic patients will rise from 463 million to 700 million by the year 2045. Conventional therapies often fail to define clear parameters and did not provide early detection in case of diabetes and pre-diabetes. Due to the limitations associated with these therapies, inclination of research is now focused on developing methods or exploring pathways which can overcome these hurdles. Considering these factors, protein tyrosine phosphatase is considered as a promising molecular level legitimate therapeutic target and is known to negatively regulate leptin and insulin signaling pathways. It has shown to be effective in the management of diabetes mellitus in various in vitro and in vivo studies. Various PTP-1B inhibitors have been studied which had shown promising results in the management of diabetes mellitus and associated complications as well. These inhibitors act by increasing insulin sensitivity by inhibiting PTP-1B mediated insulin pathway. In this article we will review the underlying mechanism of protein tyrosine phosphatase and its inhibitors by various PTP 1-B inhibitors for the management of diabetes mellitus and will further throw some light on the challenges and development of these inhibitors.
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Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Resistência à Insulina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Hiperinsulinismo/tratamento farmacológico , Insulina/metabolismo , Resistência à Insulina/fisiologia , Transdução de SinaisRESUMO
The expeditious advancement of Alzheimer's Disease (AD) is a threat to the global healthcare system, that is further supplemented by therapeutic failure. The prevalence of this disorder has been expected to quadrupole by 2050, thereby exerting a tremendous economic pressure on medical sector, worldwide. Thus, there is a dire need of a change in conventional approaches and adopt a novel methodology of disease prevention, treatment and diagnosis. Precision medicine offers a personalized approach to disease management, It is dependent upon genetic, environmental and lifestyle factors associated with the individual, aiding to develop tailored therapeutics. Precision Medicine Initiatives are launched, worldwide, to facilitate the integration of personalized models and clinical medicine. The review aims to provide a comprehensive understanding of the neuroinflammatory processes causing AD, giving a brief overview of the disease interventions. This is further followed by the role of precision medicine in AD, constituting the genetic perspectives, operation of personalized form of medicine and optimization of clinical trials with the 3 R's, showcasing an in-depth understanding of this novel approach in varying aspects of the healthcare industry, to provide an opportunity to the global AD researchers to elucidate suitable therapeutic regimens in clinically and pathologically complex diseases, like AD.
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Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Humanos , Estilo de Vida , Medicina de Precisão/métodosRESUMO
The Timed Up and Go (TUG) is a global measure of mobility and has the ability to detect frail individuals. Frail patients with chronic obstructive pulmonary disease (COPD) are usually undiagnosed. We hypothesised that the TUG would identify frail patients with COPD. Frailty was assessed in 520 patients diagnosed with COPD and 150 controls using a Comprehensive Geriatric Assessment questionnaire and frailty index (FI) was derived. The TUG was used to assess physical mobility. All participants were assessed for lung function and body composition. A ROC curve was used to identify how well TUG discriminates between frail and non-frail patients with COPD. The patients with COPD and controls were similar in age, sex and BMI but the patients with COPD were more frail, mean ± SD FI 0.16 ± 0.08 than controls 0.05 ± 0.03, P < 0.001. Frail patients with COPD had a greater TUG time (11.55 ± 4.03 s) compared to non-frail patients (9.2 ± 1.6 sec), after controlling for age and lung function (F = 15.94, P < 0.001), and both were greater than the controls (8.3 ± 1.2 sec), P < 0.001. The TUG discriminated between frail and non-frail patients with COPD with an area under the curve of 72 (95% CI: 67-76), and a diagnostic odds ratio of 2.67 (95% CI:1.5-4.6), P < 0.001. The TUG showed the ability to discriminate between frail and non-frail patients with COPD, independent of age and severity of the airflow obstruction. The TUG is a simple, easy and quick measure that could be easily applied in restricted settings to screen for frailty in COPD.
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Fragilidade , Doença Pulmonar Obstrutiva Crônica , Idoso , Idoso Fragilizado , Fragilidade/diagnóstico , Humanos , Equilíbrio Postural , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos de Tempo e MovimentoRESUMO
Background: Exercise intolerance in patients with chronic heart failure (CHF) is associated with a number of factors, including breathlessness and respiratory muscle weakness. However, many studies reported controversial results, and as yet there is no study on Arabic patients with CHF. This study aimed to examine the impact of breathlessness and respiratory muscle strength on exercise capacity in Arabic patients with CHF. Methods: This was a cross-sectional study, involving 42 stable adult male patients with CHF with a reduced ejection fraction and 42 controls who were free from cardiorespiratory and neuromuscular diseases. Patients with CHF and the controls underwent respiratory muscle strength tests and a six-minute walk test (6MWT), and the measurements were taken. Dyspnea was recorded using the modified Medical Research Council (mMRC) scale, along with the number of comorbidities. Results: Patients with CHF and controls were similar in age and sex. Patients with CHF had a greater number of comorbidities, a higher dyspnea score, a lower 6MWT score, and lower respiratory muscle strength (p < 0.001). Only 7% of patients with CHF had weak inspiratory muscle strength (<60% of that predicted) and 40% terminated the 6MWT due to dyspnea. The 6MWT was associated with mMRC (rs = −0.548, p < 0.001) but not with respiratory muscle strength (p > 0.05). Conclusions: Exercise intolerance in patients with CHF was associated with dyspnea and was independent of respiratory muscle strength.
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Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood-brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-ß1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.
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Lesões Encefálicas Traumáticas , Doenças Neuroinflamatórias , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Fosfatidilinositol 3-QuinasesRESUMO
Obesity-related metabolic dysfunction, endothelium imbalance, chronic inflammation, immune dysregulation, and its comorbidities may all have a role in systemic inflammation, leading to the pulmonary fibrosis and cytokine storm, which leads to failure of lung function, which is a hallmark of severe SARS-CoV-2 infection. Obesity may also disrupt the function of mucociliary escalators and cooperation of epithelial cell's motile cilia in the airway, limiting the clearance of the coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2). Adipose tissues in obese patients have a greater number of proteases and receptors for SARS-CoV-2 admittance, proposing that they could serve as an accelerator and reservoir for this virus, boosting immunological response and systemic inflammation. Lastly, anti-inflammatory cytokines such as anti-IL-6 and the infusion of mesenchymal stem cells could be used as a modulation therapy of immunity to help COVID-19 patients. Obesity, on the other hand, is linked to the progress of COVID-19 through a variety of molecular pathways, and obese people are part of the SARS-CoV-2 susceptible individuals, necessitating more protective measures.
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COVID-19 , SARS-CoV-2 , Humanos , Inflamação , Morbidade , Obesidade/epidemiologiaRESUMO
Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer's disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.
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Alcaloides , Berberina , Diabetes Mellitus Tipo 2 , Anti-Inflamatórios , Berberina/farmacocinética , Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Nanotecnologia , Preparações FarmacêuticasRESUMO
Immunotherapy, which stimulates the body's immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system. As a result, they have the potential to cause serious, even fatal, inflammatory and immune-related side effects in one or more organs. Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two immunotherapy treatments that are increasingly being used to treat cancer. Following their widespread usage in the clinic, a wave of immune-related adverse events (irAEs) impacting virtually every system has raised concerns about their unpredictability and randomness. Despite the fact that the majority of adverse effects are minimal and should be addressed with prudence, the risk of life-threatening complications exists. Although most adverse events are small and should be treated with caution, the risk of life-threatening toxicities should not be underestimated, especially given the subtle and unusual indications that make early detection even more difficult. Treatment for these issues is difficult and necessitates a multidisciplinary approach involving not only oncologists but also other internal medicine doctors to guarantee quick diagnosis and treatment. This study's purpose is to give a fundamental overview of immunotherapy and cancer-related side effect management strategies.