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1.
Saudi Pharm J ; 32(6): 102082, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38690210

RESUMO

Background and Objective: Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients. Methods: The multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary. Results: Among 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21-3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95-2.79], p = 0.08). Conclusion: Overall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

2.
Small ; 19(11): e2205763, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36585385

RESUMO

Recent reports on thermal and thermoelectric properties of emerging 2D materials have shown promising results. Among these materials are Zirconium-based chalcogenides such as zirconium disulfide (ZrS2 ), zirconium diselenide (ZrSe2 ), zirconium trisulfide (ZrS3 ), and zirconium triselenide (ZrSe3 ). Here, the thermal properties of these materials are investigated using confocal Raman spectroscopy. Two different and distinctive Raman signatures of exfoliated ZrX2 (where X = S or Se) are observed. For 2D-ZrX2 , Raman modes are in alignment with those reported in literature. However, for quasi 1D-ZrX2 , Raman modes are identical to exfoliated ZrX3 nanosheets, indicating a major lattice transformation from 2D to quasi-1D. Raman temperature dependence for ZrX2 are also measured. Most Raman modes exhibit a linear downshift dependence with increasing temperature. However, for 2D-ZrS2 , a blueshift for A1g mode is detected with increasing temperature. Finally, phonon dynamics under optical heating for ZrX2 are measured. Based on these measurements, the calculated thermal conductivity and the interfacial thermal conductance indicate lower interfacial thermal conductance for quasi 1D-ZrX2 compared to 2D-ZrX2 , which can be attributed to the phonon confinement in 1D. The results demonstrate exceptional thermal properties for Zirconium-based materials, making them ideal for thermoelectric device applications and future thermal management strategies.

3.
Saudi Pharm J ; 31(7): 1210-1218, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37256102

RESUMO

Background: Oseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19. Methods: This multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance. Results: A total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: -0.84, 95%CI: (-1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: -0.27, 95% CI: [-0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality. Conclusion: Oseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.

4.
Saudi Pharm J ; 29(8): 833-842, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34177315

RESUMO

The impact of different sociodemographic and clinical characteristics on the COVID-19-related morbidity and mortality rates have been studied extensively around the world; however, there is a dearth of data on the impact of different clinical and sociodemographic variables on the COVID-19-related outcomes in Saudi Arabia. This study aimed to identify those at high risk of worse clinical outcomes, such as hospitalization and longer length of stay (LOS) among young and middle-aged adults (18 to 55 years). In this questionnaire-based cross-sectional study, 706 patients with real-time polymerase chain reaction (RT-PCR) confirmed COVID-19 infection were interviewed. Patients' demographic characteristics, dietary habits, medical history, and lifestyle choices were collected through phone interviews. Patients with chronic health conditions, such as diabetes and hypertension, reported a higher rate of hospitalization, ICU admission, oxygen-support needs, and a longer period of recovery and LOS. Multiple logistic regression showed that diabetes, hypertension, and pulmonary disease (e.g., asthma and chronic obstructive pulmonary disease (COPD)) were associated with a higher risk of hospitalization and longer LOS. Multiple logistic regression showed that symptoms of breathlessness, loss of smell and/or taste, diarrhea, and cough were associated with a longer recovery period. Similarly, breathlessness, vomiting, and diarrhea were associated with higher rates of hospitalization. The findings of this study confirm the similarity of the factors associated with worse clinical outcomes across the world. Future studies should use more robust designs to investigate the impact of different therapies on the COVID-19-related morbidity and mortality in Saudi Arabia.

5.
J Neurochem ; 153(1): 120-137, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486527

RESUMO

Previous studies documented up-regulation of peptidase neurolysin (Nln) after brain ischemia, however, the significance of Nln function in the post-stroke brain remained unknown. The aim of this study was to assess the functional role of Nln in the brain after ischemic stroke. Administration of a specific Nln inhibitor Agaricoglyceride A (AgaA) to mice after stroke in a middle cerebral artery occlusion model, dose-dependently aggravated injury measured by increased infarct and edema volumes, blood-brain barrier disruption, increased levels of interleukin 6 and monocyte chemoattractant protein-1, neurological and motor deficit 24 h after stroke. In this setting, AgaA resulted in inhibition of Nln in the ischemic hemisphere leading to increased levels of Nln substrates bradykinin, neurotensin, and substance P. AgaA lacked effects on several physiological parameters and appeared non-toxic to mice. In a reverse approach, we developed an adeno-associated viral vector (AAV2/5-CAG-Nln) to overexpress Nln in the mouse brain. Applicability of AAV2/5-CAG-Nln to transduce catalytically active Nln was confirmed in primary neurons and in vivo. Over-expression of Nln in the mouse brain was also accompanied by decreased levels of its substrates. Two weeks after in vivo transduction of Nln using the AAV vector, mice were subjected to middle cerebral artery occlusion and the same outcome measures were evaluated 72 h later. These experiments revealed that abundance of Nln in the brain protects animals from stroke. This study is the first to document functional significance of Nln in pathophysiology of stroke and provide evidence that Nln is an endogenous mechanism functioning to preserve the brain from ischemic injury.


Assuntos
Encéfalo/fisiopatologia , Metaloendopeptidases/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Edema , Regulação da Expressão Gênica , Glicerídeos/farmacologia , Infarto da Artéria Cerebral Média , Masculino , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/genética , Camundongos , Proteínas Recombinantes/efeitos dos fármacos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Transfecção
6.
Methods Mol Biol ; 2616: 21-28, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36715924

RESUMO

A number of animal stroke models have been developed and used over the years to study the pathological mechanisms of this disorder and develop new therapies. Among them, the photothrombotic model of ischemic stroke has been central in various studies focusing on understanding of the basic biology of neural repair, identification and validation of key molecular targets involved in post-stroke recovery, and preclinical testing of various therapeutic approaches. To facilitate uniformity among various experimental groups using this expert-recommended mouse model of choice for stroke recovery studies, in this chapter we describe in detail a low-budget technique to induce photothrombosis in the mouse primary motor cortex. Additionally, we provide tips for conducting this procedure in other cerebral cortical regions of the mouse brain and in rats.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Camundongos , Ratos , Animais , Roedores , Acidente Vascular Cerebral/patologia , Modelos Animais de Doenças , Córtex Cerebral/patologia
7.
Methods Mol Biol ; 2616: 345-353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36715944

RESUMO

The choice of behavioral tests and their proper execution is critically important for experimental and preclinical therapeutic stroke recovery studies, where improvement of impaired neurological function(s) is the main outcome measure. Two tests that focus on spontaneous motor behaviors of the forelimb during gait and exploratory rearing and are expert recommended for stroke recovery studies in mice are grid-walking and cylinder tasks. Both tests have been widely used in various experimental stroke studies to evaluate acute and chronic motor impairment. To facilitate adoption of these tests and consistency of use between different research laboratories, this chapter describes a simple and rigorous protocol and our schemes to successfully perform both tasks in mice and evaluate motor dysfunction and recovery after stroke. In addition, we provide practical tips to minimize experimental bias and acquire data for analyses.


Assuntos
Acidente Vascular Cerebral , Camundongos , Animais , Acidente Vascular Cerebral/terapia , Caminhada , Marcha , Recuperação de Função Fisiológica
8.
J Cardiol Cases ; 28(5): 213-215, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024116

RESUMO

Unicuspid aortic valves (UAV) account for 0.2 % of cardiac valvular disorders and present with early-onset aortic stenosis (AS) during adolescence or early adulthood. We present a case of a 17-year-old male with recurring AS. He was diagnosed with bicuspid aortic valve (BAV) two years previously and treated with balloon valvuloplasty, which relieved symptoms before that. Multimodality imaging work-up revealed the precise morphology of UAV, consistent with the surgical findings. The patient received a St. Jude mechanical valve (St Paul; MN, USA) which resolved his symptoms. A thorough radiologic evaluation is therefore required for the accurate diagnosis of UAVs. While 2-dimensional (2D) transthoracic echocardiography (TTE) often constitutes the initial modality for evaluating UAVs, 3D-TTE, transesophageal echocardiography, and cardiac computed tomography are used as confirmatory diagnostic tools. Balloon valvuloplasty reports good outcomes in BAV but is associated with an increased rate of symptom recurrence, repeated surgical procedures, and higher mortality in UAVs, underscoring the importance of an accurate pre-operative diagnosis. Learning objectives: 1.Unicuspid aortic valve (UAV) should be considered in the differential diagnosis of severe aortic stenosis during childhood.2.3D-transthoracic echocardiogram, transesophageal echocardiogram, and cardiac computed tomography (CT) can confirm the diagnosis of a UAV.3.Cardiac CT can additionally assess for accompanying abnormalities of the great vessels in UAV patients.4.Balloon valvuloplasty reports good outcomes in bicuspid aortic valve but is associated with an increased rate of symptom recurrence in UAV patients.

9.
Cureus ; 15(5): e39253, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37342737

RESUMO

Background The number of people suffering from depression has increased in recent times. In the Aseer region alone, 3.8% of the population suffers from depression, and one of the causes is believed to be dry eye disease (DED). Objectives This research aims to investigate the relationship between depression and dry eye disease among people living in Saudi Arabia's Aseer region. Methodology The study is cross-sectional, and data was collected from 401 participants living in Aseer, Saudi Arabia. Data was collected with the help of a well-structured questionnaire, and results are extracted by analyzing the model using SPSS. Findings The study discovered a positive and significant relationship between dry eye disease and depression. A total of 36.7% of the participants had dry eye symptoms and 23.7% were diagnosed with depression, stress, or anxiety. Conclusion Our study concludes that patients suffering from dry eye disease are more likely to get depressed because, according to our analysis, there is a correlation between dry eye disease and depression. Dry eye disease is a condition that is not only affecting the elderly but the young alike. Saudi Arabia's healthcare authority should create awareness about this health issue with the help of seminars, print, and social media.

10.
Front Neurosci ; 17: 1201971, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456992

RESUMO

Epilepsy is one of the most common neurological disorders affecting people of all ages representing a significant social and public health burden. Current therapeutic options for epilepsy are not effective in a significant proportion of patients suggesting a need for identifying novel targets for the development of more effective therapeutics. There is growing evidence from animal and human studies suggesting a role of impaired brain energy metabolism and mitochondrial dysfunction in the development of epilepsy. Candidate compounds with the potential to target brain energetics have promising future in the management of epilepsy and other related neurological disorders. Creatine is a naturally occurring organic compound that serves as an energy buffer and energy shuttle in tissues, such as brain and skeletal muscle, that exhibit dynamic energy requirements. In this review, applications of creatine supplements in neurological conditions in which mitochondrial dysfunction is a central component in its pathology will be discussed. Currently, limited evidence mainly from preclinical animal studies suggest anticonvulsant properties of creatine; however, the exact mechanism remain to be elucidated. Future work should involve larger clinical trials of creatine used as an add-on therapy, followed by large clinical trials of creatine as monotherapy.

11.
J Family Med Prim Care ; 12(12): 3217-3221, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38361855

RESUMO

Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder characterized by troublesome symptoms, including heartburn and acid regurgitation. GERD is associated with complications such as peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma, and it negatively affects quality of life (QoL). Aims: To assess the factors influencing the QoL of GERD patients in the Aseer region of Saudi Arabia. Settings and Design: This descriptive cross-sectional study used self-administered questionnaires in a study population of patients aged ≥18 years from Aseer, Saudi Arabia, between January 15, 2023-February 15, 2023. Materials and Methods: A previously validated GERD health-related QoL (GERD-HRQoL) questionnaire was used to assess the patients' sociodemographic data, GERD, and GERD-HRQoL. Statistical Analysis Used: Descriptive analysis included describing the frequency distribution and percentage for study variables, including demographic data, GERD-related QoL symptoms, and QoL, which were graphed. Cross-tabulation presented the distribution of GERD-HRQoL scores by their personal data and other factors using the Pearson Chi-square and exact probability tests. Results: Overall, 502 participants previously diagnosed with GERD completed the questionnaire. Participants' were aged 18-65 years (mean age of 31.5 ± 14.6 years), and 384 (76.5%) were male. The most frequent symptom affecting QoL was heartburn (85.9%), followed by postprandial heartburn (84.3%), heartburn while lying down (82.7%), bloating or gassy feelings (79.9%), and heartburn while standing up (77.3%). Conclusions: Our study showed that patients with GERD had a poor QoL due to GERD-related symptoms, mainly heartburn. Younger age, male sex, and lower educational status were associated with lower GERD-HRQoL scores.

12.
Front Med (Lausanne) ; 10: 1237903, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37692775

RESUMO

Background: Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients. Methods: A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate. Results: A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87-1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00-0.47), p = 0.05 and beta coefficient 0.16 (95% CI -0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03]. Conclusion: The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.

13.
Nano Res ; 15(6): 5510-5516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371413

RESUMO

Developing convenient and accurate SARS-CoV-2 antigen test and serology test is crucial in curbing the global COVID-19 pandemic. In this work, we report an improved indium oxide (In2O3) nanoribbon field-effect transistor (FET) biosensor platform detecting both SARS-CoV-2 antigen and antibody. Our FET biosensors, which were fabricated using a scalable and cost-efficient lithography-free process utilizing shadow masks, consist of an In2O3 channel and a newly developed stable enzyme reporter. During the biosensing process, the phosphatase enzymatic reaction generated pH change of the solution, which was then detected and converted to electrical signal by our In2O3 FETs. The biosensors applied phosphatase as enzyme reporter, which has a much better stability than the widely used urease in FET based biosensors. As proof-of-principle studies, we demonstrate the detection of SARS-CoV-2 spike protein in both phosphate-buffered saline (PBS) buffer and universal transport medium (UTM) (limit of detection [LoD]: 100 fg/mL). Following the SARS-CoV-2 antigen tests, we developed and characterized additional sensors aimed at SARS-CoV-2 IgG antibodies, which is important to trace past infection and vaccination. Our spike protein IgG antibody tests exhibit excellent detection limits in both PBS and human whole blood ((LoD): 1 pg/mL). Our biosensors display similar detection performance in different mediums, demonstrating that our biosensor approach is not limited by Debye screening from salts and can selectively detect biomarkers in physiological fluids. The newly selected enzyme for our platform performs much better performance and longer shelf life which will lead our biosensor platform to be capable for real clinical diagnosis usage. Electronic Supplementary Material: Supplementary material (materials and methods for device fabrication, functionalization of In2O3 devices, photographs of the liquid gate measurement setup, mobilities of the nine devices labeled in Fig. 1(b), family curves of I DS-V DS with the liquid gate setup and current change after bubbling the substrate solution (current vs. time curve for S1 antigen detection)) is available in the online version of this article at 10.1007/s12274-022-4190-0.

14.
Front Neurosci ; 16: 951283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968390

RESUMO

Background: Stroke is a leading cause of mortality and disability and one of the most common neurological conditions globally. Many studies focused on vitamin D as a stroke risk factor, but only a few focused on its serum level as a predictor of stroke initial clinical severity and recovery with inconsistent results. The purpose of this study was to assess the relationship between serum vitamin D levels and stroke clinical severity at admission and functional independence and disability at discharge in Saudi Arabia. Methodology: A retrospective cohort study of adult ischemic stroke patients who had their vitamin D tested and admitted within 7 days of exhibiting stroke symptoms at King Abdulaziz Medical City (KAMC) Jeddah, Saudi Arabia. Based on vitamin D level, the patients were categorized into normal [25(OH)D serum level ≥ 75 nmol/L], insufficient [25(OH)D serum level is 50-75 nmol/L], and deficient [25(OH)D serum level ≤ 50 nmol/L]. The primary outcome was to assess the vitamin D serum level of ischemic stroke patients' clinical severity at admission and functional independence at discharge. The National Institute of Health Stroke Scale (NIHSS) was used to assess the clinical severity, whereas the modified Rankin scale (mRS) was used to assess functional independence and disability. Results: The study included 294 stroke patients, out of 774, who were selected based on the inclusion and exclusion criteria. The mean age of the participants was 68.2 ± 13.4 years, and 49.3% were male. The patients' distribution among the three groups based on their vitamin D levels is: normal (n = 35, 11.9%), insufficient (n = 66, 22.5%), and deficient (n = 196, 65.6%). After adjusting for potential covariates, regression analysis found a significant inverse relationship of NIHSS based on 25(OH)D serum level (beta coefficient: -0.04, SE: 0.01, p = 0.003). Patients with deficient serum vitamin D level also had significantly higher odds of worse functional independence in mRS score [OR: 2.41, 95%CI: (1.13-5.16), p = 0.023] when compared to participants with normal vitamin D level. Conclusion: Low vitamin D levels were associated with higher severity of stroke at admission and poor functional independence and disability at discharge in patients with acute ischemic stroke. Further randomized clinical and interventional studies are required to confirm our findings.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34064950

RESUMO

The use of traditional medicinal plants in Saudi Arabia stems mainly from consumers' belief in prophetic medicine. This study was conducted to explore changes in patients' use of dietary or herbal supplements among individuals infected with COVID-19 before and during infection and the association between herbal or dietary supplements and hospitalization. A cross-sectional, questionnaire-based study was conducted enrolling symptomatic patients who had recently recovered from COVID-19. Data were collected through phone interviews, and McNemar's test was used to investigate changes to consumption of dietary or herbal supplements before and during infection. Multivariable logistic regression was used to investigate the association between supplements use during patients' infection and hospitalization. A total of 738 patients were included in this study, of whom 32.1% required hospitalization. About 57% of participants were male with a mean age of 36.5 (±11.9) years. The use of lemon/orange, honey, ginger, vitamin C, and black seed among participants significantly increased during their infection. In contrast, patients using anise, peppermint, and coffee peel before their infection were more likely to stop using them during their infection. In addition, using lemon/orange (p < 0.0001), honey (p = 0.0002), ginger (p = 0.0053), vitamin C (p = 0.0006), black seed (p < 0.0001), peppermint (p = 0.0027), costus (p = 0.0095), and turmeric (p = 0.0012) was significantly higher among nonhospitalized patients than hospitalized ones. However, in the multivariable logistic regression, only use of vitamin C (OR = 0.51; 95% CI 0.33-0.79), peppermint (OR = 0.53; 95% CI 0.31-0.90), and lemon/orange (OR = 0.54; 95% CI 0.33-0.88) was associated with significantly lower odds of hospitalization. The study reveals that patients' consumption of dietary or herbal supplements changed in response to their COVID-19 infection, with hospitalized patients having a lower likelihood of using these supplements. Because some supplements were associated with lower odds of hospitalization, these supplements or their bioactive components should be further investigated as feasible options for COVID-19 treatment.


Assuntos
Tratamento Farmacológico da COVID-19 , Adulto , Estudos Transversais , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Arábia Saudita/epidemiologia , Adulto Jovem
16.
Neuromolecular Med ; 23(4): 471-484, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33590407

RESUMO

Using rigorous and clinically relevant experimental design and analysis standards, in this study, we investigated the potential of histone deacetylase (HDAC) inhibitors panobinostat and entinostat to enhance recovery of motor function after photothrombotic stroke in male mice. Panobinostat, a pan-HDAC inhibitor, is a FDA-approved drug for certain cancers, whereas entinostat is a class-I HDAC inhibitor in late stage of clinical investigation. The drugs were administered every other day (panobinostat-3 or 10 mg/kg; entinostat-1.7 or 5 mg/kg) starting from day 5 to 15 after stroke. To imitate the current standard of care in stroke survivors, i.e., physical rehabilitation, the animals run on wheels (2 h daily) from post-stroke day 9 to 41. The predetermined primary end point was motor recovery measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder tests. In addition, we evaluated the running distance and speed throughout the study, and the number of parvalbumin-positive neurons in medial agranular cortex (AGm) and infarct volumes at the end of the study. Both sensorimotor tests revealed that combination of physical exercise with either drug did not substantially affect motor recovery in mice after stroke. This was accompanied by negligible changes of parvalbumin-positive neurons recorded in AGm and comparable infarct volumes among experimental groups, while dose-dependent increase in acetylated histone 3 was observed in peri-infarct cortex of drug-treated animals. Our observations suggest that add-on panobinostat or entinostat therapy coupled with limited physical rehabilitation is unlikely to offer therapeutic modality for stroke survivors who have motor dysfunction.


Assuntos
Inibidores de Histona Desacetilases , AVC Isquêmico , Animais , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Masculino , Camundongos , Panobinostat/farmacologia , Panobinostat/uso terapêutico , Piridinas
17.
Neural Regen Res ; 16(7): 1244-1251, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33318401

RESUMO

Currently, there is an unmet need for treatments promoting post-stroke functional recovery. The aim of this study was to evaluate and compare the dose-dependent effect of delayed atomoxetine or fluoxetine therapy (starting on post-stroke day 5), coupled with limited physical exercise (2 hours daily voluntary wheel running; post-stroke days 9 to 42), on motor recovery of adult male mice after photothrombotic stroke. These drugs are selective norepinephrine or serotonin reuptake inhibitors indicated for disorders unrelated to stroke. The predetermined primary end-point for this study was motor function measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder tests. Additionally, we quantified the running distance and speed throughout the study, the number of parvalbumin-positive neurons in the medial agranular cortex and infarct volumes. Both sensorimotor tests revealed that neither limited physical exercise nor a drug treatment alone significantly facilitated motor recovery in mice after stroke. However, combination of physical exercise with either of the drugs promoted restoration of motor function by day 42 post-stroke, with atomoxetine being a more potent drug. This was accompanied by a significant decrease in parvalbumin-positive inhibitory interneurons in the ipsilateral medial agranular cortex of mice with recovering motor function, while infarct volumes were comparable among experimental groups. If further validated in larger studies, our observations suggest that add-on atomoxetine or fluoxetine therapy coupled with limited, structured physical rehabilitation could offer therapeutic modality for stroke survivors who have difficulty to engage in early, high-intensity physiotherapy. Furthermore, in light of the recently completed Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) and Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS) trials, our observations call for newly designed studies where fluoxetine or atomoxetine pharmacotherapy is evaluated in combination with structured physical rehabilitation rather than alone. This study was approved by the Texas Tech University Health Sciences Center Institutional Animal Care and Use Committee (protocol # 16019).

18.
Artigo em Inglês | MEDLINE | ID: mdl-34444017

RESUMO

Stigma is a negative feeling affecting many patients with various health conditions, especially the contagious ones such as COVID-19. The Explanatory Model Interview Catalogue (EMIC) is one of the valid and reliable stigma-measuring tools; however, it has not been translated and validated in Arabic. Therefore, the aim of this study was to translate and validate the EMIC in Arabic among a sample of Arabic-speaking adults who recently recovered from COVID-19 in Saudi Arabia. The 12 items of the EMIC scale were forward- and backward-translated and reviewed by all authors to check the face and content validity prior to approving the final version of the Arabic 12-item EMIC. A total of 174 participants aged ≥18 years who contracted COVID-19 and recovered as of 29 July 2020 were interviewed. The Cronbach's alpha of the Arabic version of the 12-item EMIC was 0.79, indicating an acceptable level of internal consistency. Using principal component analysis with varimax rotation, two factors explained more than 60% of the variance of the translated EMIC scale. The mean EMIC score was 5.91, implying a low level of stigma among participants. Married participants (ß = 2.93; 95%CI 0.88 to 4.98, p = 0.005) and those with a family history of mental illness (ß = 2.38; 95%CI 0.29 to 4.46, p = 0.025) were more likely to have higher EMIC scores in comparison to their counterparts who were unmarried and had no family history of mental illness. On the contrary, older adults were less likely to have high EMIC scores (ß = -0.11; 95%CI -0.21 to -0.01, p = 0.03). Future studies with larger samples of patients with COVID-19 and various health conditions should be conducted to examine the validity and reliability of the Arabic version of the EMIC among different patient populations and to unveil the factors that may play a role in patients' feelings of stigmatization in this part of the world.


Assuntos
COVID-19 , Estigma Social , Adulto , Cultura , Humanos , Psicometria , Reprodutibilidade dos Testes , Arábia Saudita , Inquéritos e Questionários
19.
Cureus ; 13(8): e17396, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34584805

RESUMO

Background Globally, attention deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder that affects children. In 2011, there was an ADHD diagnosis prevalence of around 8% among children (4-17 years) in the US. ADHD-affected children are more prone to physical injuries such as physical trauma, accidental poisoning, burns, etc. This study was aimed to evaluate the association of ADHD with severe injuries, the influence of age and gender on this association, and the impact of ADHD medications on the frequency of such injuries. Methodology This study was conducted in three governmental and three private settings in Aseer region. The files of children who were diagnosed with ADHD in the study settings were reviewed for a 12-month time period. Data were extracted from the medical files using a pre-structured data extraction sheet to avoid errors and inter-rater bias. The extracted data included child gender, age, duration of disease, and injury-related data. A brief questionnaire had been applied to mothers regarding mothers' attitudes towards injuries among their children, adherence to medications, as well as the reasons for non-adherence to medications and clinical visits in a non-adherent group during the clinic visit. Results One hundred and sixty-three children with a diagnosis of ADHD completed the study. The affected children were aged between two and 15 years (mean: 7.8 ± 2.9 years). An exact of 116 (71.2%) children were males. An exact of 70 (42.9%) affected children had trauma. The most-reported traumas were superficial injuries (84.3%), burns (48.6%), fractures (37.1%), deep injuries (31.4%), and broken or lost teeth (28.6%). About 52% of the children were adherent to medications and their clinical visits. Among the non-adherent group, the most reported reasons were parents' care and attention (20.5%), followed by the COVID-19 pandemic and delay in visits times (16.7%). Regarding mothers' attitudes towards injuries among children with ADHD, 49.1% of the mothers agreed that there is an association between a child with ADHD and being traumatized while 22.7% said there was no relation. Conclusions In our cohort, the majority of the children with ADHD were boys at primary school age. Association of the history of the disease with trauma was not uncommon, and most injuries were not severe, but burns and deep injuries were reported among considered portions.

20.
Neuroscience ; 461: 57-71, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667592

RESUMO

Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke - requirements that are hardly attainable by stroke survivors. The aim of this study was to directly evaluate and compare the dose-dependent effect of delayed physical rehabilitation (daily 5 h or overnight voluntary wheel running; initiated on post-stroke day 7 and continuing through day 21) on recovery of motor function in the mouse photothrombotic model of ischemic stroke and correlate it with angiogenic potential of the brain. Our observations indicate that overnight but not 5 h access to running wheels facilitates recovery of motor function in mice in grid-walking test. Western blotting and immunofluorescence microscopy experiments evaluating the expression of angiogenesis-associated proteins VEGFR2, doppel and PDGFRß in the peri-infarct and corresponding contralateral motor cortices indicate substantial upregulation of these proteins (≥2-fold) in the infarct core and surrounding cerebral cortex in the overnight running mice on post-stroke day 21. These findings indicate that there is a dose-dependent relationship between the extent of voluntary exercise, motor recovery and expression of angiogenesis-associated proteins in this expert-recommended mouse ischemic stroke model. Notably, our observations also point out to enhanced angiogenesis and presence of pericytes within the infarct core region during the chronic phase of stroke, suggesting a potential contribution of this tissue area in the mechanisms governing post-stroke functional recovery.


Assuntos
Proteínas Angiogênicas , Condicionamento Físico Animal , Acidente Vascular Cerebral , Animais , Modelos Animais de Doenças , Camundongos , Atividade Motora , Recuperação de Função Fisiológica , Regulação para Cima
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