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Nicotine exposure increases the release of glutamate in part through stimulatory effects on pre-synaptic nicotinic acetylcholine receptors (nAChRs). To assess the impact of chronic electronic (e)-cigarette use on these drug dependence pathways, we exposed C57BL/6 mice to three types of inhalant exposures for 3 months; 1) e-cigarette aerosol generated from liquids containing nicotine (ECN), 2) e-cigarette aerosol generated from liquids containing vehicle chemicals without nicotine (Veh), and 3) air only (AC). We investigated the effects of daily e-cigarette exposure on protein levels of α7 nAChR and α4/β2 nAChR, gene expression and protein levels of astroglial glutamate transporters, including glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT), in the frontal cortex (FC), striatum (STR) and hippocampus (HIP). We found that chronic inhalation of ECN increased α4/β2 nAChR in all brain regions, and increased α7 nAChR expression in the FC and STR. The total GLT-1 relative mRNA and protein expression were decreased in the STR. Moreover, GLT-1 isoforms (GLT-1a and GLT-1b) were downregulated in the STR in ECN group. However, inhalation of e-cigarette aerosol downregulated xCT expression in STR and HIP compared to AC and Veh groups. ECN group had increased brain-derived neurotrophic factor in the STR compared to control groups. Finally, mass spectrometry detected high concentrations of the nicotine metabolite, cotinine, in the FC and STR in ECN group. This work demonstrates that chronic inhalation of nicotine within e-cigarette aerosols significantly alters the expression of nAChRs and astroglial glutamate transporters in specific mesocorticolimbic brain regions.

Background: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting. Objective: This study aimed to evaluate the effect of extended‐release paracetamol on preventing fasting headaches. Methods: A randomized, open‐label clinical trial investigated the efficacy of extended‐release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self‐reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan. Results: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (β = −0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42–1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12–0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13–0.82). No adverse effects were observed during the study period. Conclusion: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan. Plain Language Summary: Ramadan is a month in which millions of Muslims fast from dawn to dusk; however, fasting during the day (e.g., for 13 hours) may cause headache and discourage individuals from this spiritual practice and can impact normal productivity, especially during the first week as the body adapts. We tested whether taking extended‐release paracetamol before fasting in the morning could avert fasting‐induced headache. Extended‐release paracetamol can be partially beneficial in delaying, but not necessarily preventing, fasting‐induced headache. [Correction added on 12th September 2024, after the first online publication: The Plain Language Summary has been updated.] [ABSTRACT FROM AUTHOR]

Background: Health literacy-driven interventions in patients with type 2 diabetes have been found to play an important role in achieving glycemic control and enhancing diabetic self-management outcomes. The present study aimed to examine the role of health literacy as a predictor of quality of life among diabetic patients in Jordan. Methods: This cross-sectional study enrolled 400 Type 2 diabetic patients visiting the endocrinology department at the outpatient clinic at Al Basheer Hospital in Amman, Jordan. The data were collected between 1st of August and 28th of December 2023, using the validated Jordanian Diabetic Health Literacy Questionnaire and the EuroQol-5D tool. A quantile regression analysis was conducted to explore the factors associated with health–related quality of life among the study participants. Result: This study included 68.8% females, with a median age of 58 (50–64) years. The median EQ5-D index score was 0.66 (0.41–0.78). Findings from regression analysis indicated as patients' age increased, their quality of life scores significantly decreased (-0.004, 95%CI (-0.006, -0.001), p = 0.002). Additionally, higher JDHLQ scores were significantly associated with higher EQ5-D scores (0.012, 95% CI (0.006–0.018), p<0.001). Moreover, patients with only an elementary education had significantly lower EQ5-D scores compared to those with a postgraduate education (-0.106, 95%CI (-0.190, -0.023), p = 0.013). Conclusion: The findings of the present study emphasize the importance of including health literacy assessments and interventions in the diabetes care plans of patients in Jordan. [ABSTRACT FROM AUTHOR]

Cotton is one of the major cash crop in the agriculture led economies across the world. Cotton leaf diseases affects its yield globally. Determining cotton lesions on leaves is difficult when the area is big and the size of lesions is varied. Automated cotton lesion detection is quite useful; however, it is challenging due to fewer disease class, limited size datasets, class imbalance problems, and need of comprehensive evaluation metrics. We propose a novel deep learning based method that augments the data using generative adversarial networks (GANs) to reduce the class imbalance issue and an ensemble-based method that combines the feature vector obtained from the three deep learning architectures including VGG16, Inception V3, and ResNet50. The proposed method offers a more precise, efficient and scalable method for automated detection of diseases of cotton crops. We have implemented the proposed method on publicly available dataset with seven disease and one health classes and have achieved highest accuracy of 95% and F-1 score of 98%. The proposed method performs better than existing state of the art methods. [ABSTRACT FROM AUTHOR]

A novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Improving health literacy has been found to play a significant role in enhancing medication adherence in patients with type 2 diabetes. Purpose: The present study aims to evaluate health literacy and its association with medication adherence among diabetic patients in Jordan. Patients and Methods: This cross-sectional study included 400 diabetic patients, predominantly female (68.8%), with a median age of 58 years, attending the endocrinology outpatient clinic at Albasheer Hospital in Amman, Jordan, between August and December 2023. Patients were recruited using convenience sampling, including those aged 18 and older, literate, diagnosed with T2DM for at least one year, and on at least one medication for T2DM. Sample size was calculated based on the Events Per Variable (EPV) criterion to ensure sufficient power for logistic regression analysis. Data were collected using two validated instruments: the Jordanian Diabetic Health Literacy Questionnaire (JDHLQ), assessing health literacy, and the Medication Adherence Report Scale (MARS-5), measuring medication adherence. A binary logistic regression model was constructed to identify variables associated with adherence levels. Results: The study enrolled 400 diabetic patients (females =68.8%). While most of the participants (70.3%) reported high adherence levels, results revealed a window for health literacy improvement as the median for the JDHLQ score was 22 (ranging from 18 to 25) out of a maximum possible score of 32. More than half of the participants replied "never" to "I forget to take my medications", followed by "I stop taking my medications for a while". Conclusion: The binary regression model revealed that a higher JDHLQ score significantly increased the odds of a high adherence level. The significant association between improved health literacy and medication adherence necessitates the implementation of educational campaigns for enhancing literacy and hence medication adherence among patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

A synthesized Schiff base ligand 4-{(Z)-[(2-hydroxy-1-naphthyl)methylene]amino}-4-antipyrene (H-NAPP) was confirmed by single crystal diffraction analysis. The H-NAPP was crystalized in the P 21 21 21 space group and orthorhombic crystal system. The Schiff base ligand H-NAPP bears potential donor sites and therefore it was reacted with transition metal ions Co2+, Ni2+, Cu2+, and Zn2+ to yield respective metal complexes. All reaction products were investigated by elemental analyses and IR spectroscopic techniques. The combined spectroscopic characterizations revealed the distorted square planar geometries for all the synthesized metal complexes. The metal complexes were further studied for their thermal stabilities using TG techniques and proved to be thermally cleaved in the temperature range of 30–1,000°C in air. Pseudo-mirrored 2D fingerprint plots were used for the short interatomic interactions in the crystal structure. The major short interatomic interactions involve the hydrogen bonding which covers the Hirshfeld surfaces {H···H, O···H and C···H}. The ligand and complexes were investigated for a potential α-glucosidase inhibitory activity. While relatively inactive throughout, some notable differences were observed and, surprisingly, the ligand was found to be more active than its complexes.

Alteration in glutamate neurotransmission has been found to mediate the development of drug dependence, including nicotine. We and others, through using western blotting, have reported that exposure to drugs of abuse reduced the expression of glutamate transporter-1 (GLT-1) as well as cystine/glutamate antiporter (xCT), which consequently increased extracellular glutamate concentrations in the mesocorticolimbic area. However, our previous studies did not reveal any changes in glutamate/aspartate transporter (GLAST) following exposure to drugs of abuse. In the present study, for the first time, we investigated the effect of chronic exposure to electronic (e)-cigarette vapor containing nicotine, for one hour daily for six months, on GLT-1, xCT, and GLAST expression in frontal cortex (FC), striatum (STR), and hippocampus (HIP) in outbred female CD1 mice. In this study, we also investigated the expression of alpha-7 nicotinic acetylcholine receptor (α-7 nAChR), a major pre-synaptic nicotinic receptor in the glutamatergic neurons, which regulates glutamate release. We found that inhalation of e-cigarette vapor for six months increased α-7 nAChR expression in both FC and STR, but not in the HIP. In addition, chronic e-cigarette exposure reduced GLT-1 expression only in STR. Moreover, e-cigarette vapor inhalation induced downregulation of xCT in both the STR and HIP. We did not find any significant changes in GLAST expression in any brain region. Finally, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, we detected high concentrations of nicotine and cotinine, a major metabolite of nicotine, in the FC tissues of e-cigarette exposed mice. These data provide novel evidence about the effects of chronic nicotine inhalation on the expression of key glial glutamate transporters as well as α-7 nAChR. Our work may suggest that nicotine exposure via chronic inhalation of e-cigarette vapor may be mediated in part by alterations in the glutamatergic system.

Cities worldwide are experiencing substantial urban expansion, leading to environmental degradation. Riyadh is a good example of this, growing at a rapid pace resulting in the urban sprawl becoming environmentally, socially, and economically unsustainable. Urban densification and sustainable revitalization are approaches to limit land usage, accommodate a growing population, and maintain high-quality urban areas, particularly, in the inner city. This process is complex and dynamic and necessitates the involvement of private developers whose engagement plays a critical role in facilitating property redevelopment. This research examines the barriers and drivers that impact developer participation in rejuvenating inner city neighborhoods in Riyadh. The mixed methods of a survey and focus group discussions are used to examine the perspectives of private developers. Three key themes evolved focusing on investment potential, the regulatory environment, and key enablers of urban regeneration. The findings reveal a cautiously optimistic view of these themes, with several challenges and opportunities identified. This research highlights the need for a holistic approach to urban planning for regeneration and land use management, especially in inner-city residential areas. This study adds to the scarce research on urban regeneration in the Middle East context and establishes a foundation for future research. [ABSTRACT FROM AUTHOR]

Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and β-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using β-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography–mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the β-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that β-lactams may be promising drugs for treating fentanyl use disorder. [ABSTRACT FROM AUTHOR]

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multiepitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety. [ABSTRACT FROM AUTHOR]