Awareness About the Benefits of Post-bariatric Surgery in Diabetic Patients in Makkah Almukarramah, Saudi Arabia.

AIM: To measure awareness about the benefits of post-bariatric surgery, which is a shortening of the gut in order to lose weight in diabetic patients in the Makkah region, Saudi Arabia. METHODS: A cross-sectional survey was conducted among diabetic patients aged 18-65 from February to July 2023. An online questionnaire via Google Forms was distributed and used to assess the participants' awareness of the benefits of post-bariatric surgery for diabetic patients. RESULTS: Overall, 388 participants (56.40% female, 43.60% male) were surveyed. Most participants (91.5%) showed awareness of gastric sleeve surgery, while a significant proportion (85.8%) recognized obesity as a disease. A majority of participants (80.90%) showed awareness of the association between obesity, diabetes, and high blood pressure. However, only 46.10% of participants showed awareness of eligibility criteria associated with bariatric surgery. The majority recognized the effectiveness of bariatric surgery for weight loss but did not consider it the first choice, emphasizing a preference for non-surgical weight loss strategies. CONCLUSION: Participants demonstrated good knowledge about obesity and its implications for health. They also demonstrated good knowledge about bariatric surgery as an effective weight reduction method but expressed a preference for non-surgical methods, which reflects their awareness of the complications of bariatric surgery. However, the results showed a lack of awareness of postoperative indications and lifestyle changes, thus highlighting the need for comprehensive patient education and counseling.

Therapeutic Effects of Thymoquinone on Alzheimer's Disease through Modulating Amyloid-beta Neurotoxicity and Neuro-inflammatory Cytokine Levels.

Alzheimer's disease (AD) is a neurodegenerative disease that involves several impaired neuronal pathways. Modulating the amyloid-beta (ß-amyloid) system is being tested to treat AD. Amyloid-beta neurotoxicity is associated with neuroinflammation and plaque formation, further progressing to AD. Protecting neurons from ß-amyloid neurotoxicity could be an efficient strategy for the treatment of AD. Thymoquinone (TQ) is an active ingredient in Nigella sativa (NS) and has shown effective therapeutic properties in AD models. TQ was able to attenuate the behavioral dysfunctions in AD models. Moreover, TQ could attenuate the neuroinflammation properties in animals with AD. In addition, studies have shown that TQ could modulate ß -amyloid neurotoxicity, an effect associated with improved AD behavioral symptoms. In this review, we highlighted the therapeutic effects of TQ on the progression of AD through modulating ß-amyloid neurotoxicity and neuro-inflammatory cytokine levels. Other phenolic compounds also present in NS improved behavioral and neuronal impairments in AD models, supporting TQ's anti-Alzhiemer's efficacy.

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS.

OBJECTIVES: To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 µm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v). RESULTS: The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r2>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27). CONCLUSION: This study showed that the gender factor might play a crucial role in nicotine metabolism.

Effects of Chronic Inhalation of Electronic Cigarette Vapor Containing Nicotine on Neurobehaviors and Pre/Postsynaptic Neuron Markers.

Nicotine-exposed animal models exhibit neurobehavioral changes linked to impaired synaptic plasticity. Previous studies highlighted alterations in neurotransmitter levels following nicotine exposure. Vesicular glutamate transporter (VGLUT1) and vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) are essential for the transport and release of glutamate and GABA, respectively, from presynaptic neurons into synapses. In our work, an e-cigarette device was used to deliver vapor containing nicotine to C57BL/6J mice for four weeks. Novel object recognition, locomotion, and Y-maze tests were performed to investigate the behavioral parameters. Protein studies were conducted to study the hippocampal expression of VGLUT1, VGAT, and postsynaptic density protein 95 (PSD95) as well as brain cytokine markers. Long-term memory and locomotion tests revealed that e-cigarette aerosols containing nicotine modulated recognition memory and motor behaviors. We found that vapor exposure increased VGLUT1 expression and decreased VGAT expression in the hippocampus. No alterations were found in PSD95 expression. We observed that vapor-containing nicotine exposure altered certain brain cytokines such as IFNß-1 and MCP-5. Our work provides evidence of an association between neurobehavioral changes and altered hippocampal VGLUT1 and VGAT expression in mice exposed to e-cigarette vapors containing nicotine. Such exposure was also associated with altered neurobehaviors, which might affect neurodegenerative diseases.

Elucidation of the Molecular Mechanisms Underlying Sorafenib-Induced Hepatotoxicity.

Sorafenib is a small, orally-active multikinase inhibitor that is most frequently used for the management of renal cell carcinoma, hepatocellular carcinoma, and radioactive iodine-resistant thyroid carcinoma. However, recent reports have associated sorafenib with hepatotoxicity that can limit its clinical application, although the mechanism of hepatotoxicity is still to be elucidated. Thus, our study was designed to explore the molecular mechanisms underlying sorafenib-induced hepatotoxicity in an in vivo model. Twenty male adult Wistar rats were randomly placed into two groups; the first group received an oral dose of normal saline (vehicle), and the second received sorafenib (30 mg/kg) once daily for twenty-one consecutive days. After twenty-one days, liver tissues and blood samples were used for gene expression, protein expression, and biochemical analysis. Sorafenib treatment resulted in markedly increased levels of alanine aminotransferase and alkaline phosphatase, which indicate the presence of liver damage. Additionally, sorafenib administration induced the inflammatory and oxidative stress marker NF-κB-p65, while antioxidant enzymes were attenuated. Moreover, sorafenib caused upregulation of both gene and protein for the apoptotic markers cleaved Caspase-3, Bax, and Bid, and downregulation of the antiapoptotic protein Bcl-2. In conclusion, our findings suggest that sorafenib administration is associated with hepatotoxicity, which might be due to the activation of oxidative stress and apoptotic pathways.

Next generation sequencing to determine the cystic fibrosis mutation spectrum in Palestinian population.

An extensive molecular analysis of the CF transmembrane regulator (CFTR) gene was performed to establish the CFTR mutation spectrum and frequencies in the Palestinian population, which can be considered as an understudied population. We used a targeted Next Generation Sequencing approach to sequence the entire coding region and the adjacent sequences of the CFTR gene combined with MLPA analysis of 60 unrelated CF patients. Eighteen different CF-causing mutations, including one previously undescribed mutation p.(Gly1265Arg), were identified. The overall detection rate is up to 67%, and when we consider only CF patients with sweat chloride concentrations >70 mEq/L, we even have a pickup rate of 92%. Whereas p.(Phe508del) is the most frequent allele (35% of the positive cases), 3 other mutations c.2988+1Kbdel8.6Kb, c.1393-1G>A, and p.(Gly85Glu) showed frequencies higher than 5% and a total of 9 mutations account for 84% of the mutations. This limited spectrum of CF mutations is in agreement with the homozygous ethnic origin of the Palestinian population. The relative large portion of patients without a mutation is most likely due to clinical misdiagnosis. Our results will be important in the development of an adequate molecular diagnostic test for CF in Palestine.

Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia.

Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Recently PTHrP has been shown to be an early-response gene that may be involved in cellular proliferation or differentiation. In addition, PTHrP has been implicated in the pathogenesis of bone metastases. Bone metastases are a significant complication in patients with prostate cancer. We compared the expression of PTHrP by immunohistochemical staining using a monoclonal antibody directed against epitope between amino acids [53-64] in benign prostatic hyperplasia (BPH) with that in various stages of prostate cancer. Tissue sections were obtained on formalin-fixed paraffin-embedded blocks from BPH, well-differentiated prostate cancer, poorly differentiated prostate cancer, lymph node metastases (n = 15 each), and normal prostate (n = 2). In the normal prostate tissue there was no staining observed. In BPH, 13 of 15 tissue samples were positive for PTHrP immunoreactivity. An average of 33% of the cells stained positive with 1+ intensity. All samples from prostate cancer stained positive for PTHrP. In the samples from well-differentiated prostate cancer, an average of 87% of cells stained positive for PTHrP, whereas 100% of cells were positive in poorly differentiated and metastatic tumors. The intensity of staining was 3+ in well-differentiated tumors and 4+ in poorly differentiated tumors. Therefore, the expression of PTHrP is enhanced in prostate cancer as compared with BPH and is greater in poorly differentiated carcinoma as compared with the well-differentiated tumors. The role of PTHrP in the pathogenesis of prostate cancer deserves further study.

The incidence and clinical significance of intravenous fat emulsion contamination during infusion.

So that the actual contamination rate of intravenous fat emulsions, as well as the type of microbial contamination, could be quantified, 103 bottles of 10% fat emulsion were collected near infusion completion from patients' bedsides. All samples were cultured and compared according to actual hanging time, in addition to the amount and type of microbial contamination. Recovered organisms included Escherichia coli, Staphylococcus epidermidis, diphtheroids, and Micrococcus. Sample analysis failed to demonstrate significant differences in extrinsic microbial contamination rate or organism multiplication between samples infusing for less than or equal to 12 hr and those infusing longer. Although these products support microbial growth, the contaminants introduced into the infusate by environmental or touch contamination yielded minimal colony growth. No patient developed signs or symptoms of bacteremia during the study period. Therefore, infusion of intravenous fat emulsion products over extended periods of time in this study did not increase the risk of developing infectious complications.