Comparative efficacy of different surgical techniques for pediatric urolithiasis-a systematic review and meta-analysis.

Background: Prior research has assessed a range of surgical treatments for pediatric urolithiasis, emphasizing the necessity of tailor-made therapeutic approaches. These studies also show the adaptability of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and shock wave lithotripsy (SWL) in managing diverse stone dimensions. The goal of this research was to examine the effectiveness of these varying surgical methods in treating pediatric urolithiasis. Methods: Seven digital databases were explored to gather pertinent studies, following the guidelines established by the PRISMA protocol. The retrieved studies were subsequently scrutinized to draw comparisons between the stone-free rate (SFR) and the rate of complications associated with PCNL, RIRS, and SWL. Results: The SFR evaluation revealed no notable disparity between PCNL and RIRS [odds ratio (OR) 1.43, 95% confidence interval (CI): 0.67-3.05, P=0.36]. However, it was observed that both PCNL and RIRS outperformed SWL in terms of effectiveness (OR 2.51, 95% CI: 1.19-5.29, P=0.02 and OR 2.42, 95% CI: 1.41-4.14, P=0.001 respectively). Regarding the complication rates, no significant differences were observed among the three surgical methods (OR 0.67, 95% CI: 0.49-1.59, P=0.05), albeit with various forms of complications being reported. Certain studies associated PCNL with an elevated rate of complications, specifically urinary tract infections (UTIs) and severe hematuria. Conclusions: Though PCNL and RIRS demonstrated higher effectiveness than SWL in achieving SFR, there was no significant disparity in the rates of complications across all three procedures. The study underscores the significance of personalized treatment plans, taking into account aspects such as the dimension and location of the stone, along with patient-specific characteristics.

Lifestyle and Chemicals: Exploring Behavioral Habits Related to Endocrine Disruptor Exposure Among the General Population of Saudi Arabia.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) interfere with hormonal systems, potentially causing metabolic, reproductive, and neurological issues, as well as hormone-related cancers. Found in everyday products, EDCs accumulate in body tissues over time, with adverse effects depending on the dose and duration of exposure. This study aims to explore behaviors related to EDC exposure among Saudi citizens to assess the need for further risk reduction interventions. METHODOLOGY: This cross-sectional study employed a validated, self-administered online questionnaire to assess daily life behaviors associated with EDC exposure. A total of 563 participants were recruited using convenient sampling through online platforms. RESULTS: The study revealed that a significant majority of participants were aged 18-25 years (48.67%, n=274). On average, participants scored 32.78 out of a maximum of 60 for potential EDC exposure, with scores ranging from 13 to 54 points. The majority (85.26%, n=480) fell into the moderate potential exposure category, while a small minority (4.26%, n=24) exhibited high potential risk based on their reported daily habits, predominantly among male participants (95.83%, n=23). A significant majority (72.65%, n=409) indicated a likelihood of adopting lifestyle changes to reduce exposure to harmful substances. CONCLUSION: This study reveals diverse behavioral patterns linked to endocrine disruptor exposure among the general population in Saudi Arabia. Interestingly, the participants showed a positive attitude and willingness to change their risky behaviors. These findings underscore the necessity for educational programs and public health campaigns aimed at addressing gaps in knowledge. Encouraging the public to adopt behaviors that reduce exposure is essential to minimizing the potential long-term effects of EDCs.

Prevalence of clinically significant prostate carcinoma in Prostate Imaging Reporting and Data System (PIRADS) 3 lesions detected in the peripheral zone on biparametric magnetic resonance imaging (MRI)-a local experience.

AIM: The aim of this study was to determine whether biparametric magnetic resonance imaging (MRI) is effective in the diagnosis of clinically significant prostate cancer in prostate peripheral zone Prostate Imaging Reporting and Data System (PIRADS) 3 lesions without the use of dynamic contrast enhancement. MATERIALS AND METHODS: Patients who underwent biparametric MRI over a 12-month period from January 2022 to December 2022 and were diagnosed with PIRADS 3 lesion in the peripheral zone were included in the study. No patient received dynamic contrast enhancement. Histological analysis was done after performing local anesthetic transperineal biopsy to determine detection rate of clinically significant prostate cancer. Prostate-specific antigen density (PSAD) and biopsy complication rates were also reviewed. RESULTS: Sixty-one out of 688 MRIs (8.8%) performed over the study period had a PIRADS 3 lesion in the peripheral zone where contrast is supposed to add value. Fifty-eight of the 61 went ahead to biopsy, and csPCa (Gleason score: ≥3 + 4, with a max core length of ≥6 mm and above) was diagnosed in 17%. Among those diagnosed with csPCa, 80% had a PSAD of >0.15 ng/ml/cc. No postbiopsy complications were reported. CONCLUSION: Biparametric MRI without contrast offers a reliable alternative to multiparametric MRI with minimum or neglible impact on clinically significant prostate cancer (csPCa) diagnosis in peripheral zone PIRADS 3 lesions, especially when used in conjunction with other factors such as PSAD. There is potential to address health economics and patient burden in prostate cancer investigation.

Role of wearable electrochemical biosensors in monitoring renal function biomarkers in sweat: a review.

Real-time detection of renal biomarkers is crucial for immediate and continuous monitoring of kidney function, facilitating early diagnosis and intervention in kidney-related disorders. This proactive approach enables timely adjustments in treatment plans, particularly in critical situations, and enhances overall patient care. Wearable devices emerge as a promising solution, enabling non-invasive and real-time data collection. This comprehensive review investigates numerous types of wearable sensors designed to detect kidney biomarkers in body fluids such as sweat. It critically evaluates the precision, dependability, and user-friendliness of these devices, contemplating their seamless integration into daily life for continuous health tracking. The review highlights the potential influence of wearable technology on individualized renal healthcare and its role in preventative medicine while also addressing challenges and future directions. The review's goal is to provide guidance to academics, healthcare professionals, and technologists working on wearable solutions for renal biomarker detection by compiling the body of current knowledge and advancements.

Analysis of antibiotic regimens and outcomes in spinal brucellosis: insights from a retrospective cohort study in Makkah, Saudi Arabia.

Background: Brucellosis is a zoonotic disease that is widely spread across the globe, with the number of cases increasing annually. Spinal brucellosis is known to affect about half of patients with brucellosis. Nevertheless, data on the optimal antibiotic regimens for spinal brucellosis are limited. Therefore, this study aims to compare antibiotic treatment regimens for spinal brucellosis at our center in Makkah, Saudi Arabia. Methods: This is a retrospective cohort study of an 11-year period from 2010 to 2021 conducted at a single center in Makkah, Saudi Arabia. All patients with spinal brucellosis were included. Patients were excluded if the duration of the received antibiotic regimen or follow-up was poorly documented. Data analysis was conducted using RStudio (R version 4.1.1). Categorical variables of each regimen used by the patients were presented as frequencies and percentages, while numerical variables were summarized using the median and interquartile range (IQR). Results: A total of 35 patients were included; the median (IQR) age of the patients was 58.0 (48.0 to 63.0) years. The most frequently reported symptoms upon admission included low back pain (83.3%). The most frequently administered regimen was the combination of streptomycin + doxycycline + rifampicin (SDR) (20 patients, 55.6%), followed by the combination of streptomycin + rifampicin + trimethoprim/sulfamethoxazole (SRT) (eight patients, 22.2%). Overall, out of the total 35 patients who received first-line treatment, only six patients experienced therapy failure. Out of the total six patients who experienced first-line treatment failure with SDR (five patients, 83%) and SDT (one patient, 17%), surgery was indicated for three patients. Surgical intervention was deemed necessary in 12 patients (34%). Three patients chose not to undergo surgical intervention but still showed complete improvement upon completing the treatment duration. One patient experienced a postoperative complication, resulting in paraplegia. Conclusions: In this study, we found that among 35 patients, treatment failure was observed only in six patients who received triple therapy. In addition, surgical intervention was indicated in 12 patients; however, three patients refused surgery and improved ultimately after changing or extending the duration of the antibiotic regimen.

Comparing the Scores of The Functional Movement Screen™ in Individuals with Low Back Pain versus Healthy Individuals: A Systematic Review and Meta-Analysis.

Background: The Functional Movement Screen™ (FMS™) is widely used to assess functional movement patterns and illuminate movement dysfunctions that may have a role in injury risk. However, the association between FMS™ scores and LBP remains uncertain. Objective: The purpose of this systematic review and meta-analysis was to examine functional movement scores among patients with low back pain (LBP) and healthy subjects with no LBP and review the validity of the FMS™ tool for screening functional movement among LBP patients. Methods: The systematic review and meta-analysis included papers assessing functional movement among adult patients with LBP using the FMS™ through a literature review of five databases. The search strategy focused used relevant keywords: Functional movement screen AND low back pain. The review included all papers assessing functional movement among LBP adult patients (>18 years old) using the FMS™ published between 2003 to 2023. The risk of bias in the involved studies was evaluated using the updated Cochrane ROB 2 tool. Statistical analysis was conducted using Review Manager software, version 5.4. The meta-analysis included the total FMS™ score and the scores of the seven FMS™ movement patterns. Results: Seven studies were included in this systematic review were considered to have low to unclear risk of bias. The meta-analysis revealed that the LBP group had a significantly lower total FMS™ score than the control group by 1.81 points (95% CI (-3.02, -0.59), p= 0.004). Patients with LBP had a significantly lower score than the control group regarding FMS™ movement patterns, the deep squat (p <0.01), the hurdle step (p <0.01), the inline lunge (P value <0.01), the active straight leg raise (p <0.01), the trunk stability push-up (p=0.02), and the rotational stability screens (p <0.01). Conclusion: Lower scores on the FMS™ are associated with impaired functional movement. Identifying the specific functional movement impairments linked to LBP can assist in the creation of personalized treatment plans and interventions. Further research is needed to assess the association of cofounders, such as age, gender, and body mass index, with the FMS™ score among LBP patients and controls. Level of evidence: 1.

ARISCAT and LAS VEGAS risk scores for predicting postoperative pulmonary complications after cardiac surgery: a cohort study.

Background: Postoperative pulmonary complications (PPCs) could lead to morbidity, mortality, and prolonged hospital stay. Different risk-scoring systems are used to predict the identification of patients at risk of developing PPCs. The diagnostic accuracies of the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) and Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) risk scores are compared in prediction of PPCs taking pulmonary complication as the gold standard in cardiac surgery. Materials and methods: A prospective cohort study with consecutive sampling technique. A total of 181 patients were included. Quantitative data is presented as simple descriptive statistics giving mean and standard deviation, and qualitative variables are presented as frequency and percentages. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracies are also calculated. Results: Total 181 post-cardiac surgery patients were analyzed. The median [interquartile range] of age, height, weight, and BMI were 60.0 [52.0-67.0] years, 163.0 [156.0-168.0] cm, 71.0 [65.0-80.0] kg and 27.3 [24.2-30.4] kg/m2. 127 (70.2%) were male, and 54 (29.8%) were female. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ARISCAT for the prediction of PPCs were (94.9%, 4.65%, 76.1%, 22.9% and 73.4%), whereas LAS VEGAS were (97.1%, 4.65%, 76.5%, 33.3% and 75.1%), respectively. Conclusion: Both the ARISCAT and LAS VEGAS risk scores are of limited value in cardiac surgery patients for the prediction of postoperative pulmonary complications, based on the predicted scores in this study.

Portable on-off visual-mode detection using intrinsic fluorescent zinc-based metal-organic framework for detection of diclofenac in pharmaceutical tablets.

On-site, robust, and quantitative detection of diclofenac (DCF) is highly significant in bioanalysis and quality control. Fluorescence-based metal-organic frameworks (MOFs) play a pivotal role in biochemical sensing, offering a versatile platform for detecting various biomolecules. However, conventional fluorescent MOF sensors often rely on lanthanide metals, which can pose challenges in terms of cost, accessibility, and environmental impact. Herein, an intrinsic blue fluorescent zinc-based metal-organic framework (FMOF-5) was prepared free from lanthanide metals. Coordination-induced emission as an effective strategy was followed wherein a non-fluorescent ligand is converted to a fluorescent one after insertion in a framework. Conventional fluorometry and smartphone-assisted visual methods were employed for the detection of DCF. The fluorescence emission of the FMOF-5 was effectively quenched upon the addition of the DCF, endowing it an "off" condition, which permits the construction of a calibration curve with a wide linear range of 30-670 µM and a detection limit of about 4.1 µM. Other analytical figures of merit, such as linearity, sensitivity, selectivity, accuracy, and precision were studied and calculated. Furthermore, the proposed sensor was successfully applied to quantify DCF in pharmaceutical tablets with reliable recovery and precision. Importantly, the elimination of lanthanide metals from the fluorescence detection system enhances its practicality and sustainability, making it a promising alternative for DCF detection in pharmaceutical analysis applications.

Retinopathy risk factors in patients with type 2 diabetes on liraglutide.

Liraglutide, a glucagon-like peptide 1 receptor agonist, effectively treats type 2 diabetes(T2D) by lowering glucose levels, suppressing glucagon release, and promoting insulin secretion. Liraglutide has been shown to reduce body weight and glycated hemoglobin (HbA1c) levels and improve cardiovascular outcomes. However, evidence regarding the association between liraglutide and diabetic retinopathy in the Middle East is insufficient. Therefore, this study aimed to investigate the characteristics and risk factors of diabetic retinopathy in patients with T2D treated with liraglutide in Saudi Arabia. This retrospective cohort study was conducted on patients (≥14 years) with T2D treated with liraglutide between 2015 and 2021, who had a documented retinopathy assessment at baseline before liraglutide initiation and during follow-up, at King Abdulaziz Medical City (KAMC), Riyadh. Data collection included demographic information, retinopathy status, body mass index (BMI), and HbA1c level at baseline and follow-up after liraglutide use. The study included 181 patients with a mean age of 58.2 (9.8) years. Of these, 72.9% were females. At baseline, the median weight (interquartile range) was 88 (77-100) kg, diabetes duration was 19 (13-23.5) years, and HbA1c level was 9% (8-10%). Total of 69.6% were on insulin, 22.7% were on oral hypoglycemic agents, and 7.7% were on no other medications in addition to liraglutide. After a median of 2 years follow-up, both HbA1c level and weight decreased significantly (P < .001). Seventy-one of the 87 patients (81.6%) without retinopathy at baseline continued to show no retinopathy. Among patients with retinopathy at baseline, 25.5% showed improvement and 44.7% showed no change. In the multivariate binary mixed effect analysis, factors significantly associated with retinopathy were: use of insulin (odds ratio [OR]:2.68; 95% confidence interval [CI]: 1.18-6.09, P = .019), older age (OR:1.03; 95% CI: 1.00-1.06; P = .022), higher HbA1c level (OR:1.17; 95% CI: 1.02-1.34; P = .024), Hypertension (OR:2.56; 95% CI: 1.13-5.76; P=<.0001) and longer diabetes duration (OR:1.04; 95% CI: 1.00-1.08; P = .024). In conclusion, liraglutide use caused significant reductions in the HbA1c level and weight of patients with T2D. Most patients showed no change in retinopathy status after liraglutide use.

Exploitation of erythrosine B as a fluorometric marker for lurasidone determination through electrostatic attraction; application to content uniformity test.

A recently developed antipsychotic drug, lurasidone, was determined using a simple, sensitive, and eco-friendly spectrofluorimetric approach. The suggested approach was based on the quantifiable quenching impact of lurasidone on the inherent fluorescence of erythrosine B in an acidic environment employing a Teorell-Stenhagen buffer (pH 4). Following excitation at 530 nm, the quenching of erythrosine B fluorescence was monitored at 552 nm. The system variables were systematically optimized to enhance the formation of the lurasidone-erythrosine B ion pair for analytical purposes. A linear calibration graph was built in the range of 20-600 ng mL-1 with 0.9998 as a coefficient of correlation. The quantitation and detection limits were 13.5 and 4.5 ng/mL, respectively. The analytical validity of the designed approach was assessed with respect to International Council on Harmonization (ICH) guiding principles. The proposed methodology was employed with high recoveries for assessing lurasidone in bulk powder and its therapeutic tablet dosage form. Additionally, the uniformity of tablet formulations was tested using the developed approach. Finally, the established approach was assessed for its greenness using various tools.

Bioprocessing of camptothecin from Alternaria brassicicola, an endophyte of Catharanthus roseus, with a strong antiproliferative activity and inhibition to Topoisomerases.

Suppression of fungal camptothecin (CPT) biosynthesis with the preservation and successive subculturing is the challenge that impedes fungi from the industrial application, so, screening for a novel fungal isolate with a conceivable stable producing potency of CPT was the main objective of this work. Catharanthus roseus with diverse contents of bioactive metabolites could have a plethora of novel endophytes with unique metabolic properties. Among the endophytes of C. roseus, Alternaria brassicicola EFBL-NV OR131587.1 was the highest CPT producer (96.5 µg/L). The structural identity of the putative CPT was verified by HPLC, FTIR, HNMR and LC-MS/MS, with a molecular mass 349 m/z, and molecular fragmentation patterns that typically identical to the authentic one. The purified A. brassicicola CPT has a strong antiproliferative activity towards UO-31 (0.75 µM) and MCF7 (3.2 µM), with selectivity index 30.8, and 7.1, respectively, in addition to resilient activity to inhibit Topo II (IC50 value 0.26 nM) than Topo 1 (IC50 value 3.2 nM). The purified CPT combat the wound healing of UO-31 cells by ~ 52%, stops their matrix formation, cell migration and metastasis. The purified CPT arrest the cellular division of the UO-31 at the S-phase, and inducing their cellular apoptosis by ~ 20.4 folds, compared to the control cells. Upon bioprocessing with the surface response methodology, the CPT yield by A. brassicicola was improved by ~ 3.3 folds, compared to control. The metabolic potency of synthesis of CPT by A. brassicicola was attenuated with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by the 6th month of storage and 6th generation. Practically, the CPT productivity of the attenuated A. brassicicola was restored by addition of 1% surface sterilized leaves of C. roseus, ensuring the eliciting of cryptic gene cluster of A. brassicicola CPT via the plant microbiome-A. brassicicola interactions. So, for the first time, a novel endophytic isolate A. brassicicola, from C. roseus, was explored to have a relatively stable CPT biosynthetic machinery, with an affordable feasibility to restore their CPT productivity using C. roseus microbiome, in addition to the unique affinity of the extracted CPT to inhibit Topoisomerase I and II.

Molecular docking analysis of some medicinal extracts for pro-apoptotic, antiinflammatory and antioxidative activities using HCC cell lines.

We investigated the biological activities of 14 medicinal plants from Saudi Arabia as anti-inflammatory, antioxidant and anti-proliferative properties using hepatocellular carcinoma (HCC) cell lines. Hexane extracts exhibited the maximum inhibitory activities against albumin denaturation compared with those of other solvents. Baccharoides schimperi hexane extract showed the highest anti-inflammatory while Ocimum basilicum methanol extract showed significantly high hydroxyl radical scavenging activity (p < 0.001). B. schimperi methanol extract showed highest cytotoxicity and anti-proliferation activity (IC50; 25 µg/ml) in hepatocellular carcinoma cell line. Annexin V and caspase-9 activities were induced significantly (p < 0.001) by B. schimperi and the response increased in a dose dependent compared with untreated cells (p < 0.001). The docking scores showed a low docking energy binding of 2-Cyclohexylpiperidine of B. schimperi with COX-2, (-16.62 kcal/mol), high affinity for apoptotic and anti-inflammatory potency It can be concluded that, B. schimperi active ingredients as 2-Cyclohexylpiperidine and phytol contributed to its biological activity.

Impact of total phenolic compounds on ecological and health risks of water and sediments from Timsah Lake, Suez Canal, Egypt.

This study aimed to measure spatial and temporal distributions of total phenolic compounds and their ecological and health hazards using UV-vis spectrophotometers as a low-cost, fast, simple method in water and sediments collected from Timsah Lake, Suez Canal, Egypt, 2022. Also, assessing highly adaptive fungal species associated with contamination is designed. Due to human and environmental activities and industrial waste discharges, Timsah Lake is increasingly threatened by all kinds of pollutants. The results indicated that the seasonal concentration means of the phenolic compounds were winter (0.229) > spring (0.161) > summer (0.124) > autumn (0.131) mg/l and winter (3.08) > summer (2.66) mg/g in water and sediment samples, respectively. The result has shown that the phenol concentrations in all stations were more than 0.005 and 0.1 mg/l for Egyptian National Standards and World Health Organization (WHO) for drinking water but less than the limits of 1 mg/l for wastewater. Notably, the fungi recorded the highest counts during spring, totaling 397 colonies/100 ml of water and 842 colonies/gram of sediment. Four isolates of fungi were identified and deposited in the GenBank database by Aspergillus terreus, Aspergillus terreus, Penicillium roqueforti, and Penicillium rubens under accession numbers OR401933, OR402837, OR402878, and OR424729, respectively. Moreover, ecological risk (RQ) for the total phenolic compounds was > 1 in all investigated stations for water and sediments. The hazard quotient is HQ < 1 in all seasons in water and sediments except winter. The hazard index (HI) in water and sediments for children is higher than for adults. It can be concluded that the low-cost, fast, simple method for determining phenolic content in water and sediment samples, using UV-vis spectrophotometry, was useful for predicting the reactivates of a wide variety of phenol and their derivatives. Furthermore, it can be concluded that Periodic assessments of water quality and strict regulations are necessary to safeguard this vital resource from pollution and ensure the well-being of future generations. Finally, policymakers and water treatment specialists might use the information from this research to reduce these chemical pollutants in Egypt.

Oxidative stress and type 2 diabetes: the development and the pathogenesis, Jordanian cross-sectional study.

Accumulation of reactive oxygen species (ROS) can disrupt the antioxidant defense system, leading to oxidative stress that leads to pathological damage to vital human organs, including hormone-producing glands. Normal physiological function is subsequently disrupted and disorders such as Type 2 Diabetes Mellitus (T2DM) may develop. The critical role of the antioxidant defense system in counteracting ROS and mitigating oxidative stress is fundamental to understanding the pathogenesis of T2DM. In our study, we monitored the oxidant/antioxidant status in a selected Jordanian population to further elucidate this relationship. Our results show higher serum levels of Malondialdehyde (MDA); 0.230 ± 0.05 and 0.207 ± 0.06 µmol/l for the diabetic and the obese groups, respectively, relative to 0.135 ± 0.04 µmol/l for the non-obese healthy group. Lower activity of Catalase (CAT) was recorded among the diabetic (9.2 ± 3.2) and obese groups (11.0 ± 2.8), compared to the non-obese healthy group (12.1 ± 3.5). Significant elevations (P < 0.05) were observed in uric acid concentrations in diabetic and obese subjects: 451 ± 57 mg/dl and 430 ± 51, respectively, versus 342 ± 57 mg/dl in the non-obese healthy group. Moreover, no significant differences were obtained between all the studied groups for the serum albumin and total protein concentrations. Our findings demonstrate the potential role of oxidative stress in the development and occurrence of T2DM.

Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner.

Platelet activation is critical for haemostasis, but if unregulated can lead to pathological thrombosis. Endogenous platelet inhibitory mechanisms are mediated by prostacyclin (PGI2)-stimulated cAMP signalling, which is regulated by phosphodiesterase 3A (PDE3A). However, spatiotemporal regulation of PDE3A activity in platelets is unknown. Here, we report that platelets possess multiple PDE3A isoforms with seemingly identical molecular weights (100 kDa). One isoform contained a unique N-terminal sequence that corresponded to PDE3A1 in nucleated cells but with negligible contribution to overall PDE3A activity. The predominant cytosolic PDE3A isoform did not possess the unique N-terminal sequence and accounted for >99% of basal PDE3A activity. PGI2 treatment induced a dose and time-dependent increase in PDE3A phosphorylation which was PKA-dependent and associated with an increase in phosphodiesterase enzymatic activity. The effects of PGI2 on PDE3A were modulated by A-kinase anchoring protein (AKAP) disruptor peptides, suggesting an AKAP-mediated PDE3A signalosome. We identified AKAP7, AKAP9, AKAP12, AKAP13, and moesin expressed in platelets but focussed on AKAP7 as a potential PDE3A binding partner. Using a combination of immunoprecipitation, proximity ligation techniques, and activity assays, we identified a novel PDE3A/PKA RII/AKAP7 signalosome in platelets that integrates propagation and termination of cAMP signalling through coupling of PKA and PDE3A.

Development of Polymeric Micelles for Combined Delivery of Luteolin and Doxorubicin for Cancer Therapy.

Background: Luteolin (LUT) is a bioactive compound with several pharmacological activities including anticancer effect. Doxorubicin (DOX) is an anthracycline chemotherapeutic drug that have proven to be effective in treating various types of cancers. Polymeric micelles (PMs) containing biologically active materials have emerged as prospective dosage forms with high drug-loading, which can add therapeutic benefit to the poorly water-soluble compounds and novel chemical entities. PMs are effective in delivering several drugs, such as anticancer drugs, antifungal drugs, flavonoids and drugs targeting the brain. The aim of the current study is to develop PMs for LUT and DOX as a combined delivery system for cancer therapy. Methods: PMs were prepared using 2.5% of each of LUT and DOX with varying compositions of Poloxamer 188, Poloxamer 407, Vitamin E (TPGS), Poloxamer 123 and Gellucire 44/14 at room temperature. Particle size, polydispersity index, zeta potential, were achieved using Zetasizer Nano particle size analyzer and the sizes were further confirmed with transmission electron microscopy (TEM). Prepared PMs were further characterized using powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). An MTT assay was performed on breast cancer (MCF-7) cells and liver cancer (HepG2) cells to determine the cytotoxic effect of the different PMs formulations. Results: PMs were successfully developed and optimized using 74.3% Poloxamer 407 with 20.7% Vitamin E (TPGS), and 70% Poloxamer 407 with 25% Gellucire 44/14, respectively. The droplet size and polydispersity index were found to be 62.03 ± 3.99 nm, 91.96 ± 5.80 nm and 0.33 ± 0.05, 0.59± 0.03, respectively for PMs containing TPGS and Gellucire 44/14. Zeta potentials of the PMs containing TPGS and Gellucire 44/14 were recorded as -2.27 ±0.11mV and -7.78 ± 0.10 mV, respectively. The PMs showed a spherical structure with approximately 50-90 nm range evident by TEM analysis. The PXRD spectra of PMs powder presented the amorphization of LUT and DOX. The FTIR spectra of LUT-loaded and DOX-loaded PMs were identical, suggesting consistent PMs composition. The MTT assay showed that the representative combined drug loaded PMs treatment led to a reduction in the viability of MCF-7 and HepG2 cells compared to drug free PMs and pure LUT, DOX alone. Conclusions: PMs with LUT and DOX exhibited significant cytotoxic effects against breast and liver cancer cells and could thus be an important new pharmaceutical formulation to treat cancer.

Acral Folliculocentric Extragenital Lichen Sclerosus: A Case Report.

Introduction: Lichen sclerosus is a chronic inflammatory dermatological condition of unknown etiology, primarily impacting the genital epidermis in individuals of all genders, with a higher prevalence observed among postmenopausal women and prepubescent girls. Additionally, extragenital manifestations occur in approximately 20% of the patients diagnosed with genital lichen sclerosus. Notably, folliculocentric extragenital lichen sclerosus is rare and unusual, with only limited instances documented in existing literature. Case Description: We report a 33 years old lady presented with multiple asymptomatic lesions on the dorsal feet for 1 year and similar lesions on the left hand for 4 months. On examination: folliculocentric, shiny, atrophic papules coalescing into reticulated plaques over the dorsum of both feet and few shiny, flat-topped, pink papules over the dorsum of the left hand. A skin biopsy was performed and confirmed the diagnosis of extragenital lichen sclerosus. Conclusion: Acral folliculocentric extragenital lichen sclerosus is an unusual and rare clinical variant. Clinicopathologic correlation is necessary to establish the correct diagnosis. Contribution to the Literature: Herein, we present an unusual presentation of extragenital lichen sclerosus, and we highlight the importance of considering it in the differential diagnosis of guttate acral skin lesions. We also review and summarize relevant cases from the literature in hope to aid physicians, especially dermatologists, to consider and swiftly reach the diagnosis and offer appropriate management. We also hope to bring about new insights and broaden future research efforts regarding lichen sclerosus especially and atrophic skin disease in general.

Mesenchymal Stem Cell-Conditioned Media Modulate HUVEC Response to H2O2: Impact on Gene Expression and Potential for Atherosclerosis Intervention.

Background: We studied the potential of human bone marrow-derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H2O2. Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory-related genes, namely, TGF-ß1, FOS, ATF3, RAF-1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H2O2, or with varying concentrations of H2O2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real-time polymerase chain reaction (RT-PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H2O2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory-related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H2O2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms.

Enhanced antibacterial activity of a novel silver-based metal organic framework towards multidrug-resistant Klebsiella pneumonia.

The growth and spread of multidrug-resistant bacterial species, such as Klebsiella pneumoniae, pose a serious threat to human health and require the development of innovative antibacterial agents. The search for an acceptable, safe, and efficient antibacterial is a matter of significant concern. In the present work, silver-based metal-organic frameworks (Ag-MOFs) showed efficient antibacterial activity against multidrug-resistant K. pneumoniae (KBP 11) with a minimum inhibitory concentration and minimum bactericidal concentration of 10 µg mL-1. Moreover, the Ag-MOF showed enhanced antibacterial activity compared to silver ions and silver nanoparticles. Our experimental investigation showed that the antibacterial efficacy is attributed to the production of reactive oxygen species and the release of cellular constituents, such as K+ ions and proteins. The MOF scaffold enhances the stability and controlled release of silver ions, enabling sustained antibacterial activity and minimizing the risk of bacterial resistance development. Additionally, the MOF class, due to the high surface area and porous nature, enhances the transfer of bacteria into and on the surface of the MOF.

Surgical and Pre-surgical Factors Affecting Appendectomy Outcomes in Jeddah, Saudi Arabia: A Retrospective Record Review.

BACKGROUND: Appendectomy is the preferred treatment for acute uncomplicated appendicitis and the most common emergency abdominal surgery. While previous studies have investigated variables affecting post-appendectomy complications, local research is limited, and data on complication rates are scarce. Therefore, this study aimed to investigate appendectomy outcomes and the factors influencing them. METHODS: This retrospective record review included all patients who underwent appendectomies at our center between 2013 and 2023, excluding those who underwent appendectomies as part of other procedures. Data were retrieved from the hospital database and recorded on predesigned Google Forms. RESULTS: A total of 556 patients were included. Complications occurred in 60 patients (10.8%); the most common included intra-abdominal collections (n=19, 3.4%), postoperative fever (n=13, 2.3%), and surgical site infections (n=11, 2.0%). The most frequently documented histopathological diagnoses included acute appendicitis (n=402, 72.3%), perforated appendicitis (n=109, 19.6%), and gangrenous appendicitis (n=19, 4.4%). Surgical site infection rates were higher after open appendectomies (6.0% vs. 0.9%, P=0.006), while intra-abdominal collections were more frequent after laparoscopic appendectomies (4.1% vs. 0.0%, P=0.095). Additionally, histopathology results showing complicated or chronic appendicitis were associated with higher complication rates (P<0.001, odds ratio=3.793, 95% confidence interval=1.957-7.350). CONCLUSION: To the best of our knowledge, this is the largest retrospective review of appendectomy cases in Saudi Arabia. However, this study was conducted in a tertiary care center, which may have caused the rates of complications to appear lower than those in primary centers. We recommend a multi-center study be conducted to establish more accurate results.