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1.
Materials (Basel) ; 17(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39274669

RESUMEN

The dual nature of asphalt binder necessitates improvements to mitigate rutting and fatigue since it performs as an elastic material under the regime of rapid loading or cold temperatures and as a viscous fluid at elevated temperatures. The present investigation assesses the effectiveness of Nano Alumina (NA), Nano Silica (NS), and Nano Titanium Dioxide (NT) at weight percentages of 0, 2, 4, 6, and 8% in asphalt cement to enhance both asphalt binder and mixture performance. Binder evaluations include tests for consistency, thermal susceptibility, aging, and workability, while mixture assessments focus on Marshall properties, moisture susceptibility, resilient modulus, permanent deformation, and fatigue characteristics. NS notably improves binder viscosity by about 138% and reduces penetration by approximately 40.8% at 8% nanomaterial (NM) content, significantly boosting hardness and consistency. NS also enhances Marshall stability and decreases air voids, increasing the mix's durability. For moisture resistance, NS at 8% NM content elevates the Tensile Strength Ratio (TSR) to 91.0%, substantially surpassing the 80% standard. Similarly, NA and NT also show improved TSR values at 8% NM content, with 88.0% and 84.1%, respectively. Additionally, NS, NA, and NT reduce permanent deformation by 82%, 69%, and 64% at 10,000 cycles at 8% NM content, illustrating their effectiveness in mitigating pavement distress. Notably, while higher NM content generally results in better performance across most tests, the optimal NM content for fatigue resistance is 4% for NS and 6% for both NA and NT, reflecting their peak performance against various types of pavement distresses. These results highlight the significant advantages of nanoparticles in improving asphalt's mechanical properties, workability, stability, and durability. The study recommends further field validation to confirm these laboratory findings and ensure that enhancements translate into tangible improvements in real-world pavement performance and longevity.

2.
Front Oncol ; 14: 1403052, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38912065

RESUMEN

Introduction: Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain-containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. Methods: The aim of this study was to evaluate the cellular function and downstream genomic targets of VGLL1 in placental, pancreatic, and breast cancer cells. Functional assays were employed to assess the role of VGLL1 in cellular invasion and proliferation, and ChIP-seq and RNAseq assays were performed to identify VGLL1 target genes and potential impact using pathway analysis. Results: ChIP-seq analysis identified eight transcription factors with a VGLL1-binding motif that were common between all three cell types, including TEAD1-4, AP-1, and GATA6, and revealed ~3,000 shared genes with which VGLL1 interacts. Furthermore, increased VGLL1 expression led to an enhancement of cell invasion and proliferation, which was supported by RNAseq analysis showing transcriptional changes in several genes known to be involved in these processes. Discussion: This work expands our mechanistic understanding of VGLL1 function in tumor cells and provides a strong rationale for developing VGLL1-targeted therapies for treating cancer patients.

3.
Data Brief ; 53: 110224, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38435730

RESUMEN

Permanent deformation in asphalt concrete pavements is pervasive distress [1], influenced by various factors such as environmental conditions, traffic loading, and mixture properties. A meticulous investigation into these factors has been conducted, yielding a robust dataset from uniaxial repeated load tests on 108 asphalt concrete samples. Each sample underwent systematic evaluation under varied test temperatures, loading conditions, and mixture properties, ensuring the data's comprehensiveness and reliability. The materials used, sourced locally, were selected to enhance the study's relevance to pavement constructions in hot climate areas, considering different asphalt cement grades and contents to understand material variability effects on deformation. The detailed dataset created from the experimental program acts as a pivotal resource for refining predictive models and optimizing asphalt concrete mixtures and pavement design strategies, aimed at improving pavement performance and longevity under diverse operational and environmental conditions.

4.
Pak J Med Sci ; 40(3Part-II): 421-426, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38356796

RESUMEN

Objective: This retrospective, cross-sectional analytical study investigated the incidence of tooth agenesis in cleft lip and palate (CLP) patients. Cone Beam Computed Tomography (CBCT) radiographs of the CLP children were examined for congenitally missing teeth. Method: This study was conducted at three radiology centers in Lahore, namely, the Pakistan Jinnah MRI and Body Scan Centre, the University of Lahore Radiology Centres, and Fatima Memorial Hospital, from September 2021 to August 2022. The CLP patients were divided into four groups based on the location of the cleft: Cleft Lip and Palate Right (CLPR), Cleft Lip and Palate Left (CLPL), Bilateral Cleft (CLPB), and Midline Cleft (CLPM), inside and outside the cleft region. Two-way ANOVA was employed to compare the means of agenesis. Tukey's test was utilized to ascertain where the difference lies. The significance level was set at p ≤ 0.05. Results: Moreover, a significant number of missing teeth were found inside the cleft. This study observed the CLPL (42.3%) and CLPR (13.6%) types more in number. Maxillary first premolars were found more missing outside the cleft region in CLPL and CLPB types. Although CLPB and CLPM types revealed a pattern of missing teeth, only a few cases were found in this study. Moreover, mean tooth agenesis was highest (4.5 SD.71) in the CLPM group, followed up by CLPB (2.75 SD 2.49), CLPR (1.23 SD 1.27), and CLPL Group (1.15 SD 1.12). Conclusions: Unilateral cleft lip and palate patients reported significant agenesis patttern compared to bilateral and median cleft cases.

5.
Cureus ; 16(1): e52365, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38230387

RESUMEN

BACKGROUND: ChatGPT is an artificial intelligence-powered chatbot that has demonstrated capabilities in numerous fields, including medical and healthcare sciences. This study evaluates the potential for ChatGPT application in telepharmacy, the delivering of pharmaceutical care via means of telecommunications, through assessing its interactions, adherence to instructions, and ability to role-play as a pharmacist while handling a series of life-like scenario questions. METHODS: Two versions (ChatGPT 3.5 and 4.0, OpenAI) were assessed using two independent trials each. ChatGPT was instructed to act as a pharmacist and answer patient inquiries, followed by a set of 20 assessment questions. Then, ChatGPT was instructed to stop its act, provide feedback and list its sources for drug information. The responses to the assessment questions were evaluated in terms of accuracy, precision and clarity using a 4-point Likert-like scale. RESULTS: ChatGPT demonstrated the ability to follow detailed instructions, role-play as a pharmacist, and appropriately handle all questions. ChatGPT was able to understand case details, recognize generic and brand drug names, identify drug side effects, interactions, prescription requirements and precautions, and provide proper point-by-point instructions regarding administration, dosing, storage and disposal. The overall means of pooled scores were 3.425 (0.712) and 3.7 (0.61) for ChatGPT 3.5 and 4.0, respectively. The rank distribution of scores was not significantly different (P>0.05). None of the answers could be considered directly harmful or labeled as entirely or mostly incorrect, and most point deductions were due to other factors such as indecisiveness, adding immaterial information, missing certain considerations, or partial unclarity. The answers were similar in length across trials and appropriately concise. ChatGPT 4.0 showed superior performance, higher consistency, better character adherence and the ability to report various reliable information sources. However, it only allowed an input of 40 questions every three hours and provided inaccurate feedback regarding the number of assessed patients, compared to 3.5 which allowed unlimited input but was unable to provide feedback. CONCLUSIONS: Integrating ChatGPT in telepharmacy holds promising potential; however, a number of drawbacks are to be overcome in order to function effectively.

6.
Environ Sci Pollut Res Int ; 31(2): 3031-3043, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38079037

RESUMEN

Simultaneous measurement of spironolactone and canrenone in urine and plasma provides valuable insight into renal function, and therapeutic efficacy and can be utilized to identify potential health risks and ensure patient safety throughout treatment. By adopting greener methods to analyze these compounds, significant reductions in the environmental impact of such studies can be achieved. For this purpose, a sensitive and eco-friendly solvent bar microextraction method using natural deep eutectic solvent (NDE) followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed to determine spironolactone and canrenone in urine and plasma samples. The extraction solvents were synthesized using NDE-based terpenoids containing menthol and camphor in various ratios. The extraction efficiency percentage (EE%) of both drugs was measured using response surface methodology (RSM) based on central composite design (CCD), and 29 extraction tests were conducted to determine the optimum conditions. Although all parameters were found to be significant, the extraction and elution times were critical for isolating the target analytes. Under optimized conditions, the linear dynamic ranges for spironolactone (SPI)/canrenone (CAN) were 11.7-104/13.1-104 µg L-1 and 21.7-104/24.6-104 µg L-1 in urine and plasma samples, respectively with R2 ≥ 0.993. The ranges of intra-/interprecision (relative standard deviation (RSD) %, n = 5) were 1.31-9.17%/ 2.4-11% with extraction recovery ≥ 88.6% for both drugs. The comparison findings with previously published methods confirmed that the developed NDE-solvent bar microextraction (SBME)-HPLC-DAD method for spironolactone and canrenone analysis displayed confident sensitivity, feasible operation, and simple analysis. Furthermore, the method's applicability and effectiveness were proven by successfully analyzing spironolactone and its metabolite canrenone in patients' urine and plasma samples.


Asunto(s)
Canrenona , Microextracción en Fase Líquida , Humanos , Canrenona/orina , Espironolactona/orina , Disolventes Eutécticos Profundos , Solventes , Cromatografía Líquida de Alta Presión/métodos , Límite de Detección
7.
Behav Sci (Basel) ; 13(11)2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37998631

RESUMEN

Stigma towards mental illness poses a significant risk for negative mental health outcomes. Efforts have been undertaken to mitigate self-stigma and stigmatizing behaviors among the public; however, few have considered stigma among healthcare providers, including pharmacists. This study aimed to assess the level of stigma towards mental illness, using the 15-item version of the Opening Minds Scale for Health Care Providers (OMS-HC), and associated factors among pharmacy students and was conducted via a printed questionnaire. A total of 125 students participated and the mean total stigma score was 47.9 with 58.4% of the participants scoring above 45, the midpoint of the possible range of scores. The stigma score was independent of participant demographics, except for grade point average. Higher total stigma scores were observed among subjects who have been prescribed a neuropsychiatric drug before, those who believe that pharmacists should have a role in mental healthcare, those who believe that pharmacists are qualified enough to provide mental health support, and those who are willing to seek help from a pharmacist. The results indicate an overall high stigma score among pharmacy students, which highlights the importance of enhancing pharmacy students' awareness and knowledge regarding mental healthcare through incorporating additional courses and/or training programs in pharmacy education curricula.

8.
J Acupunct Meridian Stud ; 16(5): 176-182, 2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37885252

RESUMEN

Background: : Wet cupping (Hijama), a form of alternative medicine, is widely practiced in Middle Eastern countries, especially Saudi Arabia. Although considerable effort has been put into increasing public awareness about the safe and proper practice of wet cupping, studies on the attitudes, knowledge, and awareness levels of the Saudi Arabian public are lacking. Objectives: : This study evaluated public attitudes toward the effectiveness, safety, and expected standards of practicing wet cupping. Methods: : This cross-sectional study was conducted using an online questionnaire and involved 909 complete responses. The respondents were Saudi adults with a mean age of 30.43 ± 11.4 years (males: 42.1%, females: 57.9%). Results: : The study revealed that most participants believed that although wet cupping is a beneficial (84.6%), well-known form of alternative medicine (82.4%) without harmful side effects (63.9%), it is not suitable for treating all diseases (72.3%) or everyone (66.8%). Most participants prefer wet cupping to be done at specialized centers (84.6%) by practitioners with confirmed qualifications (88.6%) using valid and sterile instruments (88.9%). The main demographic factor influencing participant responses was age, which was associated with more positive perceptions. Female, single, college-educated, and middle-aged respondents had more cautious attitudes. Conclusion: : Our results indicate that Saudis support the use of wet cupping as an alternative medicine for select diseases and that individuals have adequate awareness of the practice's safety standards to avoid potential risks.


Asunto(s)
Terapias Complementarias , Ventosaterapia , Adulto , Masculino , Persona de Mediana Edad , Humanos , Femenino , Adulto Joven , Arabia Saudita , Estudios Transversales , Opinión Pública , Terapias Complementarias/métodos
9.
Heliyon ; 9(9): e19591, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37681124

RESUMEN

This study aimed to develop and test a biosensor for detecting radioactive radon gas and lead ions in blood samples collected from donors in Iraq. The biosensor was made up of aptamer, acetic acid, malachite green, and TRIS-HAC, and results were measured using a fluorescence spectrophotometer. This study found that 222Rn in the blood varied between individuals, with higher levels in males and smokers, and the highest concentration found in a male patient with cancer. The biosensor used to detect 222Rn in the blood was effective, sensitive, and low-cost, and the levels detected were within the limits set by the WHO. The study also looked at pb+2, a toxic metal, and found that levels were within permissible limits. The biosensor was also effective in detecting pb+2. The correlations between the variables are generally weak to moderate, and there are some negative relationships between humidity and other variables. There are also some strong positive relationships between temperature (Tin) and temperature (Tout). The results suggest that these variables are not strongly correlated with each other, which is an important finding for understanding their potential effects on health outcomes. However, further validation and testing may be necessary before its widespread use in clinical settings. This study highlights the importance of monitoring these substances in the blood, especially for individuals with occupational exposure to radiation. The biosensor was found to be sensitive, cost-effective, fast to manufacture, and efficient compared to other detection devices. Therefore, the study recommends the use of this biosensor for measuring radon and lead ions in blood samples. The biosensor used in this study could be a useful tool for such monitoring.

10.
Materials (Basel) ; 16(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37687686

RESUMEN

Reflection cracking in asphalt concrete (AC) overlays is a common form of pavement deterioration that occurs when underlying cracks and joints in the pavement structure propagate through an overlay due to thermal and traffic-induced movement, ultimately degrading the pavement's lifespan and performance. This study aims to determine how alterations in overlay thickness and temperature conditions, the incorporation of chopped fibers, and the use of geotextiles influence the overlay's capacity to postpone the occurrence of reflection cracking. To achieve the above objective, a total of 36 prism specimens were prepared and tested using an overlay testing machine (OTM). The variables considered in this study were the thickness of the overlay (40, 50, and 60 mm), temperature (20, 30, and 40 °C), mix type (reference mix and mix modified with 10% chopped fibers by weight of asphalt cement), and the inclusion of geotextile fabric at two positions (one-third of the depth from the base and at the bottom). The research outcomes revealed that a decreased temperature and thicker overlay led to a higher resistance to crack initiation and full propagation, as indicated by the values of critical fracture energy (Gc) and crack progression rate (CPR). Furthermore, the study observed the enhanced crack resistance of overlays in the presence of geotextiles, whether at the bottom or one-third of the depth from the bottom, with superior performance of the former. Despite a slight enhancement in certain properties, the incorporation of chopped fibers in the overlays did not substantially improve the overall performance compared to the reference specimens. Overall, the study provides valuable insights into the variables that influence the ability of AC overlays to mitigate reflection cracking. These findings will aid engineers and designers in making informed decisions regarding overlay design and construction.

11.
Healthcare (Basel) ; 11(5)2023 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36900699

RESUMEN

There is an increasing interest in the therapeutic use of cannabis worldwide, with a number of cannabinoid-derived drugs currently approved by the Food and Drug Administration (FDA) for certain indications. This study was conducted via a printed questionnaire and aimed to explore the attitudes and knowledge regarding the therapeutic use of cannabis and cannabinoids among community pharmacists residing in Amman, Jordan. The results revealed a neutral to low agreement level regarding the medical usefulness of cannabis; however, a higher agreement level was observed for FDA-approved cannabinoid-derived drugs. The majority of the participants reported that they did not learn enough regarding cannabinoids, do not adequately remember what they have learned, and do not actively look for information after graduation. The average percentages of correct identification of cannabis/cannabinoid FDA-approved drug indications, common adverse effects, interacting drugs, and cautions/contraindications were 40.6%, 53%, 49.4%, and 57.3%, respectively, with an overall correct identification rate of 51.1% of the participants. In conclusion, the results indicate an inadequate level of knowledge with a significant room for improvement regarding the various aspects of cannabinoid pharmacology.

12.
Environ Sci Pollut Res Int ; 30(20): 58783-58795, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36997786

RESUMEN

For the first time, copper oxide-coated glass beads (CuO-GBs) were fabricated using physical vapor deposition (PVD) technology for sequestrating Pb2+ ions from solution is addressed. Compared to other coating procedures, PVD offered high-stability uniform CuO nano-layers attached with 3.0-mm glass beads. Heating of copper oxide-coated glass beads after deposition was rather necessary to achieve the best stability of the nano-adsorbent. Detection of nano-size copper oxide on the beads was made by FTIR (intense peak at 655 cm-1 for CuO bond stretching) and XRF (Cu peak at 8.0 keV). Scanning electron micrographs taken at high magnification power indicated the presence of CuO in nano-range deposited over glass beads. The maximum deposited amount of CuO on the beads was 1.1% and accomplished at the following operational conditions: internal pressure 10-5 mmHg, Ar flow rate 8.0 mL/min, voltage 84 V, pre-sputtering time 20 s, total sputtering time 10.0 min, and post-heating temperature 150 °C for 3 h. A univariate analysis indicated that the optimum Pb2+ uptake by CuO-GBs from solution was achieved at pH 7.0-8.0, 7 beads/50 mL, 120-min contact time, and 15-mg/L initial concentration. Kinetic data for Pb2+ uptake was best presented by a pseudo-second-order model with a relative prediction error of 3.2 and 5.1% for GBs and CuO-GBs, respectively. On the other hand, Pb2+ equilibrium isotherms at 25 °C were fairly presented by the Langmuir model, and the predicted saturation values were 5.48 and 15.69 mg/g for GBs and CuO-GBs, respectively. CuO and CuO-GBs had similar Pb2+ saturation values (~ 16 mg/g), although the latter demonstrated 4 times faster kinetic, thanks to fixation CuO on glass beads. Moreover, the chemical stability of copper oxide-coated glass beads was tested under different conditions. Recycling of copper oxide-coated glass beads was also investigated, and 90% of the surface was recovered using 0.01-M HNO3.


Asunto(s)
Cobre , Contaminantes Químicos del Agua , Cobre/química , Plomo , Cinética , Óxidos/química , Adsorción , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno
13.
Molecules ; 27(24)2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36557955

RESUMEN

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common cause of dementia in the elderly. The complexity of AD has hindered the development of either a cure or a disease-modifying therapy to halt the disease progression. Numerous hypotheses were presented in order to explain the mechanisms underlying the pathogenesis of AD. Introduced in 1992, the "Amyloid Cascade Hypothesis" had a huge impact on the field and inspired the rise of various drug candidates, especially amyloid-beta (Aß)-directed drugs; including beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors. Adopted by a number of pharmaceutical companies, the development of BACE1 inhibitors has gained momentum in the past decade with promising results from experimental and early clinical-phase studies. Nevertheless, nearly all BACE1 inhibitors failed in later phases of clinical trials, due to safety and/or efficacy issues, and others were discontinued early in favor of second-generation small-molecule candidates. This paper aims to provide a comprehensive review of all BACE1 inhibitors to ever reach clinical trials, and we discuss the challenges and different perspectives on whether BACE1 inhibitors are to be reconsidered or revitalized in the future.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Anciano , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Péptidos beta-Amiloides/metabolismo , Progresión de la Enfermedad , Precursor de Proteína beta-Amiloide/metabolismo
14.
J Family Med Prim Care ; 11(7): 3414-3422, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36387684

RESUMEN

The scarcity of emergency cases presented to the primary health care centers (PHCCs) makes treating such cases by family physicians more difficult To identify the barriers facing family physicians in PHCCs when facing emergency cases in Riyadh, Saudi Arabia. A cross-sectional descriptive design was deployed in the study among a sample of family physicians. A reliable and valid self-reported questionnaire was used. In addition, an observational sheet was used to investigate the preparedness of PHCCs to deal with emergency situations. The study included 162 PHC physicians. Almost two-thirds of them (65.4%) aged 25-34 years, and 52.5% were females. Middle-aged (25--35 years) physicians (P = 0.030), females (P < 0.001), Saudis (P = 0.027), those attended advanced cardiovascular life support (ACLS) since more than 2 years (P = 0.029), those who had no exposure in working in emergency units (P = 0.029), and less experienced physicians (<1 year) (P = 0.010) showed lower "perceived level of competence in performing emergency skills." The commonest barrier facing physicians during the management of emergency cases in thePHC was lack of appropriate equipment (76.5%), followed by lack of exposure to emergency cases (62.3%) and lack of time (50.6%). Dealing with emergency cases is considered part of the medical practice in PHCCs. For primary care physicians, the level of training in emergency medicine courses is suboptimal particularly advanced trauma life support (ATLS) courses in Riyadh. Inregards to emergency services at the PHC level in Riyadh, most of the items were available; however, defects were reported in some. Knowing the barriers facing doctors during dealing with emergency cases helps in improving and providing integrated medical care.

15.
Front Cell Neurosci ; 16: 905285, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36090792

RESUMEN

Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes. To address this issue, we used the well-described mouse whiskers-to-barrel cortex system, which expresses a number of forms of EDP. We found that all-whisker deprivation induced characteristic experience-dependent Hebbian depression (EDHD) followed by homeostatic upregulation in L2/3 barrel cortex of wild type mice. However, these changes were not seen in mutant animals (IP3R2-/-) that lack the astrocyte-expressed IP3 receptor subtype. A separate paradigm, the single-whisker experience, induced potentiation of whisker-induced response in both wild-type (WT) mice and IP3R2-/- mice. Recordings in ex vivo barrel cortex slices reflected the in vivo results so that long-term depression (LTD) could not be elicited in slices from IP3R2-/- mice, but long-term potentiation (LTP) could. Interestingly, 1 Hz stimulation inducing LTD in WT paradoxically resulted in NMDAR-dependent LTP in slices from IP3R2-/- animals. The LTD to LTP switch was mimicked by acute buffering astrocytic [Ca2+] i in WT slices. Both WT LTD and IP3R2-/- 1 Hz LTP were mediated by non-ionotropic NMDAR signaling, but only WT LTD was P38 MAPK dependent, indicating an underlying mechanistic switch. These results demonstrate a critical role for astrocytic [Ca2+] i in several EDP mechanisms in neocortex.

16.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35955546

RESUMEN

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain and functions as both a primary neurotrophic signal and a neuromodulator. It serves essential roles in neuronal development, maintenance, transmission, and plasticity, thereby influencing aging, cognition, and behavior. Accumulating evidence associates reduced central and peripheral BDNF levels with various neuropsychiatric disorders, supporting its potential utilization as a biomarker of central pathologies. Subsequently, extensive research has been conducted to evaluate restoring, or otherwise augmenting, BDNF transmission as a potential therapeutic approach. Promising results were indeed observed for genetic BDNF upregulation or exogenous administration using a multitude of murine models of neurological and psychiatric diseases. However, varying mechanisms have been proposed to underlie the observed therapeutic effects, and many findings indicate the engagement of disease-specific and other non-specific mechanisms. This is because BDNF essentially affects all aspects of neuronal cellular function through tropomyosin receptor kinase B (TrkB) receptor signaling, the disruptions of which vary between brain regions across different pathologies leading to diversified consequences on cognition and behavior. Herein, we review the neurophysiology of BDNF transmission and signaling and classify the converging and diverging molecular mechanisms underlying its therapeutic potentials in neuropsychiatric disorders. These include neuroprotection, synaptic maintenance, immunomodulation, plasticity facilitation, secondary neuromodulation, and preservation of neurovascular unit integrity and cellular viability. Lastly, we discuss several findings suggesting BDNF as a common mediator of the therapeutic actions of centrally acting pharmacological agents used in the treatment of neurological and psychiatric illness.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Receptor trkB , Animales , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratones , Neuronas/metabolismo , Receptor trkB/metabolismo , Transducción de Señal
17.
Biomed Chromatogr ; 36(11): e5476, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35918842

RESUMEN

A sensitive and simple sample pretreatment method based on a two-phase solvent bar microextraction (SBME) technique coupled with HPLC-diode array detector (DAD) was developed for simultaneous extraction and determination of trace amounts of furosemide and carbamazepine in human urine and plasma samples. The significance of operational factors on carbamazepine and furosemide extraction efficiency % (EE%) was screened using full factorial design (FFD) while central composite design (CCD) was used to model the entire process. A quadratic model was found convenient to correlate the extraction EE% of selected drugs with dominant experimental factors. A Pareto chart was also used to examine the importance of factors on drugs' EE%. The analytical performance of the method in urine and plasma samples demonstrated good linearity (R2 ˃ 0.992) with detection limits ranging from 4.2 to 10.9 µg L-1 , and extraction recovery over 89.45% for both drugs in urine and plasma samples. A comparison against published methods was also performed and the results revealed that the developed method exhibits a confident sensitivity, feasible operation, and simple analysis for both drugs. Finally, the practicability of the validated SBME-HPLC-DAD method was demonstrated by successfully applying it to the analysis of furosemide and carbamazepine in real patient urine samples.


Asunto(s)
Microextracción en Fase Líquida , Benzodiazepinas , Carbamazepina , Cromatografía Líquida de Alta Presión/métodos , Furosemida , Humanos , Microextracción en Fase Líquida/métodos , Solventes
18.
PNAS Nexus ; 1(3): pgac124, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36003074

RESUMEN

Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate the induction of appropriate CD8+ T cell-mediated immune responses to pathogen- and self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in the B and F pockets that interact primarily with amino acids at peptide position 2 and the C-terminus, respectively. Nonpocket peptide-HLA interactions also contribute to peptide binding and stability, but these secondary interactions are thought to be unique to individual HLA allotypes or to specific peptide antigens. Here, we show that two positively charged residues located near the top of peptide-binding cleft facilitate interactions with negatively charged residues at position 4 of presented peptides, which occur at elevated frequencies across most HLA-I allotypes. Loss of these interactions was shown to impair HLA-I/peptide binding and complex stability, as demonstrated by both in vitro and in silico experiments. Furthermore, mutation of these Arginine-65 (R65) and/or Lysine-66 (K66) residues in HLA-A*02:01 and A*24:02 significantly reduced HLA-I cell surface expression while also reducing the diversity of the presented peptide repertoire by up to 5-fold. The impact of the R65 mutation demonstrates that nonpocket HLA-I/peptide interactions can constitute anchor motifs that exert an unexpectedly broad influence on HLA-I-mediated antigen presentation. These findings provide fundamental insights into peptide antigen binding that could broadly inform epitope discovery in the context of viral vaccine development and cancer immunotherapy.

19.
Heliyon ; 8(6): e09768, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35789869

RESUMEN

Background: University student transition from living at home to more independent living which might influence their eating habits. This study aims to assess the effect of psychosocial factors on eating habits among university students. Methods: A cross-sectional study was conducted among 529 students at the University of Sharjah. Participants completed a self-administered questionnaire on dietary habits, social, and psychological factors. The height and weight were also measured. Results: More than one-third of participants were classified as overweight or obese (37.6%) and 39.1% reported not engaging in regular physical activity. Less than half of the participants consumed breakfast daily (45.4%) and 83.2% consumed less than two liters of water per day. Only 28.7% and 34.0% of participants consumed fruits and vegetables daily, respectively. Almost 80% of participants reported eating when they were bored, 83.7% ate when feeling happy, and 56.5% ate when they were sad. Eating habits score was significantly lower among unmarried participants (p = 0.03), those not living with their family (p < 0.001), smokers (p = 0.001), those not engaging in regular physical activity (p < 0.001), and those who reported eating uncontrollably (p = 0.007). Conclusions: Psychosocial factors were important indicators of dietary habits among students. Implementing nutrition education campaigns and health-related courses at the university are recommended.

20.
Front Public Health ; 10: 860835, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35685760

RESUMEN

Background: Non-communicable diseases (NCDs) are the leading causes of mortality globally, accounting for more deaths than all other causes combined. World Health Organization launched its initiative in 2013 to reduce the intake of salt, the number of countries that have national sodium reduction strategies reached to 89 countries in 2017. In 2020, a study conducted in UAE showed more than 65% of the population exceeded WHO recommendations for salt intake. This study aimed to measure effectiveness of using digital platform approach to deliver educational materials to facilitate salt reduction in a sample of UAE population. Methods: A controlled parallel intervention study was conducted in 2020. A sample of 121 participants completed the study and fulfilled the inclusion criteria with female to male ratio of (0.95:1.05). Participants were distributed randomly into three groups Control group, WhatsApp group, and Electronic Brochures group. Educational materials were distributed among participants of WhatsApp and Electronic brochures groups for 6-weeks. 24-h urinary excretion for sodium, potassium and creatinine, were measured in addition to KAP questionnaire and physical activity on two occasions at baseline and endpoint after 10-weeks (6-weeks of educational intervention). Results: Both intervention groups showed a reduction in sodium with 278 mg (p < 0.001) for WhatsApp group (n = 41) and 169 mg (p < 0.018) for Electronic brochures group (n = 41), while Control group didn't show any significant change. Moreover, the percentage of participants exceeding WHO recommendation of sodium intake was significantly reduced at the end of intervention, (p = 0.004). WhatsApp group was more efficient in the percentage of reduction of participants exceeding WHO recommendation compared with baseline, with p = 0.023. A significant reduction in the practice toward adding salt during cooking, use of table salt, adding salt before tasting the foods and use of chicken stocks for both intervention groups was noted with p < 0.05. Intervention groups showed a significant improvement (p < 0.001) in Food and Health related knowledge after 6-weeks of intervention. Conclusion: The digital platform approach such as WhatsApp and Electronic Brochure were effective in salt reduction. This study proves that UAE population is ready to reduce salt intake with appropriate education materials and easy delivery approach.


Asunto(s)
Conducta Alimentaria , Cloruro de Sodio Dietético , Creatinina , Femenino , Humanos , Masculino , Potasio , Sodio
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