Nanoformulation of dasatinib cannot overcome therapy resistance of pancreatic cancer cells with low LYN kinase expression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult to treat tumors. The Src (sarcoma) inhibitor dasatinib (DASA) has shown promising efficacy in preclinical studies of PDAC. However, clinical confirmation could not be achieved. Overall, our aim was to deliver arguments for the possible reinitiating clinical testing of this compound in a biomarker-stratifying therapy trial for PDAC patients. We tested if the nanofunctionalization of DASA can increase the drug efficacy and whether certain Src members can function as clinical predictive biomarkers. METHODS: Methods include manufacturing of poly(vinyl alcohol) stabilized gold nanoparticles and their drug loading, dynamic light scattering, transmission electron microscopy, thermogravimetric analysis, Zeta potential measurement, sterile human cell culture, cell growth quantification, accessing and evaluating transcriptome and clinical data from molecular tumor dataset TCGA, as well as various statistical analyses. RESULTS: We generated homo-dispersed nanofunctionalized DASA as an AuNP@PVA-DASA conjugate. The composite did not enhance the anti-growth effect of DASA on PDAC cell lines. The cell model with high LYN expression showed the strongest response to the therapy. We confirm deregulated Src kinetome activity as a prevalent feature of PDAC by revealing mRNA levels associated with higher malignancy grade of tumors. BLK (B lymphocyte kinase) expression predicts shorter overall survival of diabetic PDAC patients. CONCLUSIONS: Nanofunctionalization of DASA needs further improvement to overcome the therapy resistance of PDAC. LYN mRNA is augmented in tumors with higher malignancy and can serve as a predictive biomarker for the therapy resistance of PDAC cells against DASA. Studying the biological roles of BLK might help to identify underlying molecular mechanisms associated with PDAC in diabetic patients.

Hematological indices in psoriatic enthesopathy: relation to clinical and ultrasound evaluation.

BACKGROUND: Enthesopathy is considered a crucial aspect of assessment and outcome in psoriatic arthritis (PsA). Musculoskeletal ultrasound (MSUS) is a critical tool for accurately detecting enthesitis. Recent research focuses on identifying simple biomarkers for detecting and monitoring psoriatic enthesopathy. Red cell distribution width (RDW), mean platelet volume (MPV), and neutrophil/lymphocyte ratio (NLR) are components of a complete blood count (CBC) and are reliable bio-inflammatory markers in various rheumatic diseases. AIM OF WORK: To measure MPV, RDW, and NLR in psoriatic enthesopathy and determine their relationship to disease activity and MSUS findings. PATIENTS AND METHODS: This study focused on 30 people with psoriatic arthritis (PsA) as per CASPAR criteria, along with 20 control subjects. Enthesopathy was evaluated clinically using the Leeds Enthesitis Index (LEI). The modified Disease Activity Index of Psoriatic Arthritis (DAPSA28) was calculated, and RDW, MPV, NLR, CRP, and ESR were measured. Each enthesis in LEI was radiologically assessed using plain radiography and MSUS according to OMERACT definitions. RESULTS: There was a significant relationship between clinical tenderness, the presence of enthesophytes on plain radiography, and MSUS findings at entheses sites (p < 0.001 for each). Psoriatic patients had higher levels of RDW and MPV (p < 0.001 and 0.01, respectively) than controls, with no significant differences in NLR (p = 0.189) between the two groups. RDW and MPV levels were positively correlated with the DAPSA28 score. CONCLUSION: Monitoring PsA disease activity can be improved by considering RDW and MPV as reliable indicators and using them to screen for psoriatic enthesopathy with MSUS indices. Key points • Clinically identifying enthesitis in patients with PsA can be challenging. Imaging MSUS indices hold promise for objective analysis, but there is no consensus on which indices to use in clinical trials and daily practice. • Patients with psoriatic enthesopathy have higher RDW and MPV levels, which are positively correlated with DAPSA28 score. • RDW and MPV can be considered in the turn of improved screening of psoriatic enthesopathy with MSUS scores.

Item analysis: the impact of distractor efficiency on the difficulty index and discrimination power of multiple-choice items.

BACKGROUND: Distractor efficiency (DE) of multiple-choice questions (MCQs) responses is a component of the psychometric analysis used by the examiners to evaluate the distractors' credibility and functionality. This study was conducted to evaluate the impact of the DE on the difficulty and discrimination indices. METHODS: This cross-sectional study was conducted from April to June 2023. It utilizes the final exam of the Principles of Diseases Course with 45 s-year students. The exam consisted of 60 type A MCQs. Item analysis (IA) was generated to evaluate KR20, difficulty index (DIF), discrimination index (DIS), and distractor efficiency (DE). DIF was calculated as the percentage of examinees who scored the item correctly. DIS is an item's ability to discriminate between higher and lower 27% of examinees. For DE, any distractor selected by less than 5% is considered nonfunctional, and items were classified according to the non-functional distractors. The correlation and significance of variance between DIF, DI, and DE were evaluated. RESULTS: The total number of examinees was 45. The KR-20 of the exam was 0.91. The mean (M), and standard deviation (SD) of the DIF of the exam was 37.5(19.1), and the majority (69.5%) were of acceptable difficulty. The M (SD) of the DIS was 0.46 (0.22), which is excellent. Most items were excellent in discrimination (69.5%), only two were not discriminating (13.6%), and the rest were of acceptable power (16.9%). Items with excellent and good efficiency represent 37.3% each, while only 3.4% were of poor efficiency. The correlation between DE and DIF (p = 0.000, r= -0.548) indicates that items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and vice versa. The correlation between DE and DIS is significantly negative (P = 0.0476, r=-0.259). In such a correlation, items with efficient distractors are associated with low-discriminating items. CONCLUSIONS: There is a significant moderate negative correlation between DE and DIF (P = 0.00, r = -0.548) and a significant weak negative correlation between DE and DIS (P = 0.0476, r = -0.259). DIF has a non-significant negative correlation with DIS (P = 0.7124, r = -0.0492). DE impacts both DIF and DIS. Items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and discriminating items. Improving the quality of DE will decrease the number of NFDs and result in items with acceptable levels of difficulty index and discrimination power.

A prospective analysis of thulium laser enucleation in benign prostatic hyperplasia comparing low- and high-power approaches for prostates exceeding 80 g.

INTRODUCTION AND OBJECTIVES: To compare the perioperative and functional outcomes of low-power and high-power thulium:YAG VapoEnucleation (ThuVEP) of the prostate for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml). PATIENTS AND METHODS: A prospective analysis of 80 patients with symptomatic BPO and prostatic enlargement (more than 80 ml) was conducted. They were divided randomly into two groups (40 patients in each group). One group was treated with low-power ThuVEP, and the other group was treated with high-power ThuVEP. All patients were assessed preoperatively and early postoperatively, and 12-month follow-up data were analyzed. The complications were noted and classified according to the modified Clavien classification system. RESULTS: The mean age at surgery was 68 (± 6.1) years, and the mean prostate volume was 112 (± 20.1) cc, and there were no differences between the groups (p = 0.457). The mean operative time was 88.4 ± 11.79 min for group A and 93.4 ± 16.34 min for group B, while the mean enucleation time was 59.68 ± 7.24 min for group A and 63.13 ± 10.75 min for group B. There were no significant differences between the groups regarding catheterization time and postoperative stay. The quality of life (QoL), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), postvoiding residual urine (PVR), and prostate volume improved significantly after treatment and were not significantly different between those treated with the different energies. The incidence of complications was low and did not differ between both the groups. CONCLUSION: Low-power ThuVEP is feasible, safe, and effective with comparable results with high-power ThuVEP in the treatment of BPO.

Safety and efficacy of chimeric antigen receptor T-cell therapy for acute myeloid leukemia: A subgroup based meta-analysis.

INTRODUCTION: Acute myeloid leukemia (AML) is a significant hematological malignancy in the United States, with a high mortality rate and limited treatment options. CAR T-cell therapy, a new and promising treatment, is being investigated for its efficacy and safety in AML. This meta-analysis aims to assess the safety and efficacy of CAR T-cell therapy in AML, considering various subgroups such as study location, study design, prior transplantation status, conditioning regimen, and CAR T-cell source. METHODS: We conducted a comprehensive literature review across multiple databases, adhering to PRISMA guidelines and focusing on studies concerning CAR T-cell therapy in AML. We included original articles in English and excluded non-original reviews, abstracts, and non-English studies. The risk of bias was assessed using the Cochrane ROBINS-I tool. Statistical analysis involved meta-analysis with Cochrane's Q-test and I² statistic, using both fixed-effect and random-effects models, and assessed for publication bias. RESULTS: Our search yielded studies encompassing 57 AML patients treated with CAR T-cell therapy. The meta-analysis revealed a 48% incidence of complete remission with CAR T-cell therapy, varying significantly across subgroups based on study design, location, prior transplantation, conditioning regimen, and CAR T-cell source. The highest complete remission rates were observed in patients from China, those who had undergone prior hematopoietic cell transplantation, and those treated with fludarabine and cyclophosphamide conditioning regimen. Adverse events included graft-versus-host disease (7%) and cytokine release syndrome (53%). CONCLUSIONS: This meta-analysis highlights the potential of CAR T-cell therapy in AML treatment, especially when integrated with certain prior treatments and conditioning regimens. The findings suggest a higher efficacy in patients with previous hematopoietic cell transplantation and specific conditioning regimens. Further large-scale, randomized trials are essential to confirm these findings and establish CAR T-cell therapy as a standard treatment for AML.

Linkages between the Sustainable Development Goals and health in Somalia.

BACKGROUND: The Sustainable Development Goals (SDGs) adopted in 2015 compromises 17 universal and indivisible goals for sustainable development, however the interactions between the SDGs in Somalia is not known which is vital for understanding potential synergies and trad-offs between the SDGs. Hence, this study aims to identify and classify the linkages between the SDGs with a focus on health and well-being (SDG 3) in Somalia. METHODS: Following the SDG Synergies approach, 35 leading experts from the public and private sectors as well as academia and civil society gathered for a 2-day workshop in Mogadishu and scored the interactions between the individual SDGs on a seven point-scale from - 3 to + 3. From this, a cross-impact matrix was created, and network models were used to showcase the direct and indirect interactions between the SDGs with a focus on SDG 3 (good health and well-being). RESULTS: Many promoting and a few restricting interactions between the different SDGs were found. Overall, SDG 16 (peace, justice, and strong institutions) influenced the other SDGs the most. When second-order interactions were considered, progress on SDG 16 (peace, justice, and strong institutions) showed the largest positive impact on SDG 3 (good health and well-being). SDG 3 (good health and well-being) was heavily influenced by progress on other SDGs in Somalia and making progress on SDG 3 (good health and well-being) positively influenced progress on all other SDGs. CONCLUSION: The findings revealed that in Somalia, the interactions between the SDGs are mostly synergistic and that SDG 16 (peace, justice, and strong institutions) has a strong influence on progress on other SDGs as well as progress on SDG 3 (good health and well-being). This study highlights the need for a multisectoral strategy to accelerate progress on the SDGs in Somalia in general, and particularly SDG 3 (good health and well-being).

Physicians' Practices in Diabetic Nephropathy in Primary Healthcare Centers in Jazan City, Saudi Arabia, 2023.

Background and Objectives: Diabetes is one of the most common diseases dealt with by physicians in primary healthcare centers (PHCs). The disease is associated with macrovascular and microvascular complications, especially in those with long disease duration and uncontrolled diabetic nephropathy, which is one of the most common microvascular complications among diabetic patients. This investigation assessed the practices of physicians working at PHCs in terms of diabetic nephropathy screening, management, and referral. Materials and Methods: This study is a cross-sectional investigation targeting physicians working at PHCs in the Jazan region of Saudi Arabia between March and August of 2023. Data were collected via a self-administered questionnaire, which was distributed via online platforms. The questionnaire included sections measuring physicians' demographic data and associated factors regarding training, the availability of resources, and practices in diabetic nephropathy, including screening, management, and referral. Chi-squared tests were used to assess associations between the practices of physicians and the measured demographics. Result: A total of 234 physicians participated in the investigation. The median age of the participants was 35 years. The adherence level of practice toward diabetic nephropathy according to American Diabetes Association (ADA) guidelines ranged from 40 points (the highest adherence level of participants) to 19 points (the lowest adherence level of participants), with a median of 33 points. Higher adherence levels were noted among physicians in Saudi Arabia, physicians with higher education levels, physicians specializing as family physicians or diabetologists, physicians who reported attending online and on-site training at diabetic centers, physicians who reported continuous access to urine and serum creatinine tests, and physicians who reported continuous access to the American Diabetes Association guidelines (p < 0.05). Conclusions: There are several factors associated with the level of adherence in diabetic nephropathy practice, such as physicians' education level, specialty, training, and access to guidelines. The findings suggest the need for more training for PHC physicians in the care of patients affected by or at risk of diabetic nephropathy.

Venous sinus stenting for idiopathic intracranial hypertension: An updated Meta-analysis.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure and primarily affects obese women of reproductive age. Venous sinus stenting (VSS) is a surgical procedure used to treat IIH, but its safety and efficacy are still controversial. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Multiple databases were searched for studies evaluating the safety and efficacy of VSS in IIH patients and meta-analysis was performed to pool the data. RESULTS: A total of 36 studies involving 1066 patients who underwent VSS were included. After VSS, a significant reduction in trans-stenotic gradient pressure was observed. Patients also showed significantly lower cerebrospinal fluid (CSF) opening pressure. Clinical outcomes demonstrated improvement in tinnitus (95%), papilledema (89%), visual disturbances (88%), and headache (79%). However, 13.7% of patients experienced treatment failure or complications. The treatment failure rate was 8.35%, characterized by worsening symptoms and recurrence of IIH. The complications rate was 5.35%, including subdural hemorrhage, urinary tract infection, stent thrombus formation, and others. CONCLUSION: VSS appears to be a safe and effective treatment option for IIH patients who are unresponsive to medical therapy or have significant visual symptoms. However, long-term outcomes and safety of the procedure require further investigation.

The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

Data on the axial response of steel tubes infilled with rubberised alkali-activated concrete.

The presented data cover experimental and numerical axial load-shortening results of steel tubes infilled with rubberised alkali-activated concrete. The experimental data are obtained from 36 concrete filled steel tube specimens with circular and square cross-sections, length-to-diameter/width ratios of 2 and 4, and three different rubber contents in the concrete infill. The data from the numerical assessment cover the axial load-shortening response of over 300 finite element models. These cover a wide range of concrete infill strengths and rubber contents, steel tube grades, specimen widths, and steel tube wall thicknesses. Detailed descriptions of the material and methods, experimental testing, and numerical modelling procedures are also provided. The data reported herein supports the discussion in the research article "Axial compressive behaviour of composite steel elements incorporating rubberised alkali-activated concrete," and in the case of the numerical parametric assessment, give for the first time the full axial load-shortening response of all the models considered.

CCN3, POSTN, and PTHLH as potential key regulators of genomic integrity and cellular survival in iPSCs.

Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes' roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.

Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

Prediction of delayed cerebral ischemia followed aneurysmal subarachnoid hemorrhage. A machine-learning based study.

INTRODUCTION: Delayed Cerebral Ischemia (DCI) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH) that can lead to poor outcomes. Machine learning techniques have shown promise in predicting DCI and improving risk stratification. METHODS: In this study, we aimed to develop machine learning models to predict the occurrence of DCI in patients with aSAH. Patient data, including various clinical variables and co-factors, were collected. Six different machine learning models, including logistic regression, multilayer perceptron, decision tree, random forest, gradient boosting machine, and extreme gradient boosting (XGB), were trained and evaluated using performance metrics such as accuracy, area under the curve (AUC), precision, recall, and F1 score. RESULTS: After data augmentation, the random forest model demonstrated the best performance, with an AUC of 0.85. The multilayer perceptron neural network model achieved an accuracy of 0.93 and an F1 score of 0.85, making it the best performing model. The presence of positive clinical vasospasm was identified as the most important feature for predicting DCI. CONCLUSIONS: Our study highlights the potential of machine learning models in predicting the occurrence of DCI in patients with aSAH. The multilayer perceptron model showed excellent performance, indicating its utility in risk stratification and clinical decision-making. However, further validation and refinement of the models are necessary to ensure their generalizability and applicability in real-world settings. Machine learning techniques have the potential to enhance patient care and improve outcomes in aSAH, but their implementation should be accompanied by careful evaluation and validation.

Insight into the Epidemiology of the Adult-onset Systemic Autoimmune Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients.

BACKGROUND/OBJECTIVE: Although systemic autoimmune rheumatic diseases (SARDs) seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity of data compared with the developed countries. Furthermore, most of the studies addressed a particular disease. This work aimed to shed light on the relative frequency and epidemiology of the different adult-onset SARDs in Egypt. METHODS: This is a retrospective hospital-based study including six university hospitals providing free health care services: Cairo, Alexandria, Tanta, Ismailia, Beni-Suef and Assiut University Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient departments between January 2000 and December 2021 were retrospectively reviewed. Data about the patient's diagnosis, gender, age at disease onset, year of disease onset and residence were collected. RESULTS: The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behçet's disease (BD) and spondyloarthropathies (SPA) represented the main SARDs in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect females; males are mainly affected by axial SPA and BD. There is an increasing incidence of SARDs during the study period. CONCLUSION: The study revealed the high burden of SARDs in Egypt, helping better allocation of economic resources for the management of diseases of the highest prevalence and those affecting the young reproductive age groups. Increased public and medical staff awareness about SARDs is recommended to help early referral of patients to rheumatologists and, hence, better estimation of their epidemiology.

Rapid and Ultrasensitive Colorimetric Biosensors for Onsite Detection of Escherichia coli O157:H7 in Fluids.

This study presents a breakthrough in the field of onsite bacterial detection, offering an innovative, rapid, and ultrasensitive colorimetric biosensor for the detection of Escherichia coli (E. coli) O157:H7, using chemically modified melamine foam (MF). Different from conventional platforms, such as 96-well plates and fiber-based membranes, the modified MF features a macroporous reticulated three-dimensional (3D) framework structure, allowing fast and free movement of large biomolecules and bacteria cells through the MF structure in every direction and ensuring good accessibility of entire active binding sites of the framework structure with the target bacteria, which significantly increased sensitive and volume-responsive detection of whole-cell bacteria. The biosensing platform requires less than 1.5 h to complete the quantitative detection with a sensitivity of 10 cfu/mL, discernible by the naked eye, and an enhanced sensitivity of 5 cfu/mL with the help of a smartphone. Following a short enrichment period of 1 h, the sensitivity was further amplified to 2 cfu/mL. The biosensor material is volume responsive, making the biosensing platform sensitivity increase as the volume of the sample increases, and is highly suitable for testing large-volume fluid samples. This novel material paves the way for the development of volume-flexible biosensing platforms for the record-fast, onsite, selective, and ultrasensitive detection of various pathogenic bacteria in real-world applications.

Pharmacy practice in hospital settings in GCC countries: Pharmacists' medication therapy monitoring activities.

Purpose: Our study aims to provide an overview of medication therapy monitoring practices carried out by pharmacists in hospitals across the Gulf Cooperation Council (GCC) countries. Methods: This is a cross-sectional questionnaire-based study of hospitals located in the GCC. Questions were adopted from the American Society of Health-System Pharmacists (ASHP) national survey. Frequency analyses were used to examine the number and percentages of specific responses to the survey questions. Results: A total of 64 hospitals participated in this survey, reflecting an overall response rate of 52.0%. Almost half of participating hospitals (48.4%) were from Saudi Arabia. Among the 64 participating hospitals, 54.7% monitored their patients daily, 40.6% assigned pharmacists to patient care units for at least eight hours per day, and 42.2% held pharmacists accountable for medication-related outcomes. Moreover, the criteria used to identify patients requiring monitoring, 35.9% relied on the list of high-risk medications, 26.5% relied on specific medical services, 21.9% relied on directions from the hospital committee, and 17.2% relied on lab abnormalities. The most frequently utilized method for monitoring adverse drug events (ADEs) was through notifications from nurses or physicians, observed in 60.9% of participating hospitals. Conclusion: The survey emphasizes the need for hospitals in the GCC to promote increased pharmacist accountability for medication-related outcomes, explore technological solutions to enhance monitoring efficiency and extend the presence of pharmacists in patient care units beyond the current level.

Alveolar ridge splitting and simvastatin loaded xenograft for guided bone regeneration and simultaneous implant placement: randomized controlled clinical trial.

OBJECTIVES: The present study goal was to assess clinically and radiographically using simvastatin (SMV) loaded xenograft for guided bone regeneration (GBR) around simultaneously placed implants with alveolar ridge splitting in patients with horizontally atrophic jaw defect. MATERIALS AND METHODS: Randomized distribution of the twenty-two patients into two groups (11 patients each) was performed. Group I participants received alveolar ride splitting (ARS) with GBR using SMV gel mixed bone graft and a barrier membrane with simultaneous implant placement. Group II received the same treatment protocol without SMV gel. At the baseline, 6- and 9-months post-surgery, clinical and radiological alterations were assessed. RESULTS: Six months after therapy, PES records of group I were statistically significantly improved than those of group II (P < .001). Group I exhibited statistically significant expansion of the alveolar ridge over group II after 6 and 9 months (P < .001). When compared to group II over the evaluation interval between 6 and 9 months, group I demonstrated statistically substantially minimal loss of the mean marginal bone level (P < .001). At the 6- and 9-month observation periods, bone density gain was considerably higher in group I than that in group II (P < .001). CONCLUSION: Alveolar ridge splitting along with GBR-augmented SMV improve the clinical and radiographical outcomes around dental implant over GBR alone. CLINICAL RELEVANCE: Augmenting GBR with SMV in alveolar ridge splitting could boost implant osseointegration and enhance peri-implant tissue changes. CLINICAL TRIAL REGISTRATION: NCT05020405.

Pharmacogenetic study of phosphatase and tensin homolog polymorphism (rs701848) in childhood epilepsy: relation to circulating Wnt signaling.

OBJECTIVE: The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels. METHODS: This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqManTM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured. RESULTS: Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p = 0.006 with OR (95%CI) = 1.962(1.206-3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type (p = 0.020). CONCLUSION: We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels.

Modulatory mechanisms of copperII-albumin complex toward N-nitrosodiethylamine-induced neurotoxicity in mice via regulating oxidative damage, inflammatory, and apoptotic signaling pathways.

N-nitrosodiethylamine (ND) is an extremely toxic unavoidable environmental contaminant. CopperII-albumin (CuAB) complex, a newly developed Cu complex, showed antioxidant and anti-inflammatory potential. Hereby, we explored the plausible neuroprotective role of CuAB complex toward ND-evoked neurotoxicity in mice. Twenty-four male mice were sorted into 4 groups (6 mice each). Control group, mice were administered oral distilled water; and CuAB group, mice received CuAB complex at a dose of 817 µg/kg orally, three times weekly. In ND group, ND was given intraperitoneally (50 mg/kg body weight, once weekly for 6 w). CuAB+ND group, mice were administered a combination of CuAB and ND. The brain was quickly extracted upon completion of the experimental protocol for the evaluation of the oxidative/antioxidative markers, inflammatory cytokines, and histopathological examination. Oxidative stress was induced after ND exposure indicated by a reduction in GSH and SOD1 level, with increased MDA level. In addition, decreased expression of SOD1 proteins, Nrf2, and 5-HT mRNA expression levels were noticed. An apoptotic cascade has also been elicited, evidenced by overexpression of Cyt c, Cl. Casp 3. In addition, increased regulation of proinflammatory genes (TNF-α, IL-6, iNOS, Casp1, and NF-κB (p65/p50); besides, increment of protein expression of P-IKBα and reduced expression of IKBα. Pretreatment with CuAB complex significantly ameliorated ND neuronal damage. Our results recommend CuAB complex supplementation because it exerts neuroprotective effects against ND-induced toxicity.