High-Performance Liquid Chromatography (HPLC) Method Validation for Identifying and Quantifying Rebamipide in Ethosomes.

Introduction The research aimed to develop a robust, high-performance liquid chromatography (HPLC) analytical method for the quantitative assessment of rebamipide encapsulated in ethosomes. Rebamipide, a quinolinone derivative, holds promise as a therapeutic agent for dry eye, but challenges such as low bioavailability and vision clouding post-installation have prompted innovative approaches. Encapsulation in ethosomes, lipid-based nanovesicles, offers a potential solution to enhance ocular bioavailability. Materials and methods The study focused on creating a specific, linear, accurate, precise, and robust HPLC method, addressing entrapment efficiency (%EE), drug content, and drug release of rebamipide in prepared ethosomes. Statistical validation followed International Conference of Harmonization (ICH) specifications. The method's parameters were evaluated within a concentration range of 4-24 µg/ml, with recovery rates indicating accuracy and low % relative standard deviation (RSD) values confirming precision. Limits of detection (LOD) and quantification (LOQ) for rebamipide were determined. Results After preparing the ethosome dosage form by film hydrating method for rebamipide, the rebamipide entrapment efficiency in ethosomes was established at 76% ± 7, while the drug content was found to be 93% ± 6. The drug release process demonstrated zero-order kinetics and five different models of kinetics were applied for a comprehensive analysis. The method exhibited excellent system suitability, specificity, and linearity. Recovery rates for rebamipide ranged from 90% to 100%, and repeatability was confirmed by low %RSD values. The LOD and LOQ for rebamipide were determined to be 1.04 µg/mL and 3.16 µg/mL, respectively. Conclusion The developed HPLC method proved suitable for the quantitative determination of rebamipide in ethosomes, offering rapid and accurate analysis. The results underscore the method's specificity, accuracy, and precision within the specified concentration range. Overall, the validated method contributes to the advancement of ocular drug delivery systems, providing a reliable analytical tool for pharmaceutical research.

Angio-Jet Thrombolysis for Traumatic Inferior Vena Cava Thrombosis; Case Report and Review of Literature.

Background: Inferior vena cava thrombosis (IVC-Th) is a rare clinical entity after blunt abdominal trauma. It has both diagnostic and therapeutic dilemmas. Pulmonary embolism is the most dreadful complication and the leading cause of mortality after IVC-Th. Therefore, accurate prompt diagnosis is crucial. Objective: The aim of this article was to present a case of IVC-Th in a young male patient who had a blunt traumatic abdominal injury after a motor vehicle accident. Case presentation: The patient was brought to emergency department and was successfully managed by angio-jet thrombolysis. He developed a transient contrast nephropathy that was recovered after continuous renal replacement therapy. Several management options have been proposed in the literature, including conservative, endovascular and operative management. Conclusion: Angio-jet is a recent promising technique for managing of venous thrombosis. However, its use in cases of IVC-Th is not extensively discussed in the literature.

Histopathological Changes of Dental Follicles of Impacted Third Molars in Ibb Governorate.

OBJECTIVE: There is a lack of data pertaining to the examination of dental follicles (DFs) in asymptomatic impacted lower third molars (ILTMs) using cone beam computed tomography (CBCT) and histopathological analysis in the Yemeni population. The objective of this study was to explore the DFs of asymptomatic ILTMs through radiological (CBCT) and histological analysis. MATERIALS AND METHODS: This prospective study comprised 60 patients aged 18-50 years with ILTMs. The ILTMs in these patients exhibited a DF with measurements ranging between 3 and 5 mm. CBCT was employed to evaluate the maximum width of the DF surrounding the crown of ILTMs in horizontal, sagittal, and coronal sections. After the extraction, the DFs were examined for any pathological changes and categorized as normal, inflammatory, cystic, or neoplastic. The data analysis was performed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States), and the statistical significance was determined by employing chi-square tests with a significance level of 0.05. RESULTS: In the study, a total of 60 patients were included, with 17 (28.3%) being male and 43 (71.7%) being female. The majority of the patients 26 (43.3%) fell within the age range of 26-35 years. Regarding the angulation of the ILTMs, most of them were mesioangular 45 (75%), followed by vertical 7 (11.7%), horizontal 4 (6.6%), buccoangular 3 (5%), and distoangular 1 (1.6%). Histopathological changes were observed in 44 of the samples (73.3%). The majority of histopathological changes identified in the DFs were dentigerous cysts 26 (59%) followed by odontogenic keratocysts 11 (25%). Thirty-six (81.8%) of histopathological changes were found in females, whereas in only eight samples (18.1%), histological changes were observed in males. This difference was statistically significant (p=0.004). However, there were no statistically significant differences observed in the occurrence of histopathological changes based on age, angulation, and follicle size (p>0.05). CONCLUSION: Follicles in ILTMs varied significantly based on gender, with a higher occurrence in females, and tooth impaction angle, mainly in the mesioangular position. Furthermore, a follicular size of 3-5 mm was associated with a higher incidence of pathological changes. Hence, histopathologic examination is recommended for surgically removed ILTMs irrespective of the follicle size observed in radiographic images.

Original Article--Mid-term Clinical and Hemodynamic Outcomes in Middle Age Patients Post Trifecta™ (Abbott) Aortic Valve Replacement: A Single-center Study.

Background: Trifecta™ is an externally wrapped bovine pericardial aortic valve with a favorable hemodynamic performance and acceptable rate of freedom from structural valve degeneration. However, recent reports of early Trifecta valve failure question its durability. Rheumatic valve disease in young population is predominant, there is no data on the Trifecta performance, durability or safety available worldwide over the middle age population, as well as there are no previous similar reports from Middle East region. We report on mid-term clinical and hemodynamic performance of Trifecta valve in middle age population with small aortic annuls, a single center report. Methods: A retrospective study of all patients who underwent Trifecta™ SAVR between June 2014 and December 2019 at a cardiac center in Riyadh, Saudi Arabia. Hemodynamic performance was analyzed by longitudinal Doppler echocardiography. Results: During a 5.5-year period, a total of 24 patients underwent SAVR with Trifecta™ valves at our heart center. Patients had a median age of 47.1 years (IQR = 37) and male:female ratio of 1:1. Patients had a median EuroScoreII of 2 (IQR = 1). The 19 mm valve was the most frequently used (29.2%) followed by the 21 mm and 23 mm (both 25.0%). Concomitant procedure was (54.2%). All patients survived their operations and most (87.0%) had their symptoms relieved. A 30-day mortality rate of 4.2%. Patients were followed up for a median of 58.5 months (IQR = 38), during which 8.3% required re interventions, giving an overall freedom from re-intervention of 91.7%. The re-intervention after valve implantation was recorded in two (8.3%). These re-interventions were performed 3 years post initial surgery and were due to structural valve deterioration (SVD). The mean gradient reduced significantly from 43.6 ± 23.9 mmHg (median = 41, IQR = 21) at baseline to 13.0 ± 7.4 mmHg (median = 11, IQR = 5) one-week post intervention (p < 0.001). The average mean gradients were stable from post-operation to follow-up (13.0 ± 7.4 vs 14.1 ± 6.4 mmHg). Conclusion: Our study confirms excellent mid-term durability, clinical and hemodynamic performance of the Trifecta™ valve in middle age population, despite the fact of non-statically significant trend-up of transvalvular gradient over the follow up period. Further long-term studies with larger sample-size are warranted to confirm these results.

Evaluation of Serum CA 19-9 as a Diagnostic Marker for Pancreatic Malignancy.

In biliary-pancreatic malignancy, the serum CA 19-9 is considered as a tumor marker. Its high level may indicate the presence of a malignant disorder, but it can also be raised in benign conditions and also in malignancies from other organs. The value may be normal even in malignant condition. This comparative study was conducted in the Department of Surgery of Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from 1st June 2016 to 31st May 2017 to determine the sensitivity and specificity of CA 19-9 as a tumor marker in pancreatic malignancy in our perspective and to establish a cut-off value of CA 19-9 which might prove as a definitive indication of pancreatic malignancy. We found that when the cut off value of CA 19-9 is 38 U/ml (according to ROC curve), the sensitivity, specificity, PPV and NPV were 77.8%, 77.8%, 77.8%, 77.8% respectively. And if the serum CA 19-9 threshold was raised to 100 and 120 to diagnose pancreatic cancer, sensitivity became 72.2% and 66.7% and NPV 76.2% and 73.9% respectively. However, the specificity increased to 88.9% and 94.4% and the PPV increased to 86.7% and 92.3% respectively.

Beneath the Surface: Exploring Hidden Threats of Long-Term Corticosteroid Therapy to Bone Density.

Within the field of medical treatments, corticosteroids are potent substances that efficiently reduce inflammation and immunological responses, making them essential for the management of a wide range of medical ailments. However, continued use of these synthetic drugs presents a serious risk: the onset of osteoporosis brought on by corticosteroids. Determining the complex pathways by which corticosteroids cause a general disturbance in bone metabolism, suppress osteoblast function, increase osteoclast activity, and upset the delicate balance of bone remodelling emphasizes the need for all-encompassing management and prevention approaches. In this review, we aim to expose the complexities of corticosteroid-induced bone loss and urge for personalized, proactive measures to improve long-term therapeutic outcomes.

Extracorporeal Membrane Oxygenation (ECMO) Use as Supportive Therapy in a Patient With Acute Respiratory Distress Syndrome Due to Rupture of a Pulmonary Hydatid Cyst.

Pulmonary echinococcosis is a parasitic infection that accounts for 20% of the infected cases with echinococcosis. Patients may present after a cyst rupture associated with a variety of complications, including acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is known as supportive therapy for patients with respiratory and cardiac failure, including ARDS associated with multiple causes. Parasitic infection associated with ARDS due to cyst rupture managed with ECMO as bridging to definitive surgical intervention is documented in two previous case reports only. Here, we are presenting a 21-year-old female with a pulmonary hydatid cyst complicated by ARDS and managed with ECMO.

Bridging the Gaps: The Transformative Effect of Coronavirus Disease 2019 (COVID-19) on Preventive Measures Among Medical and Health Sciences College Students in Madinah, Saudi Arabia.

Background The global impact of coronavirus disease 2019 (COVID-19) has disrupted the activities of medical and health profession education institutions. This study aimed to determine the impact of COVID-19 on medical and health profession education students' knowledge, attitudes, and practices toward preventive measures and their commitment to precautionary measures before, during, and after the pandemic. Materials and methods A cross-sectional study was carried out from January to March 2023 using an online, structured, validated questionnaire survey to gather information from medical and health sciences students from three universities, encompassing five colleges in Madinah, Saudi Arabia. The minimum required sample size was estimated using the Epi Info software as 380. The data was analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Statistical tests including Student's t-test, chi-squared test, and analysis of variance (ANOVA) test were applied. Results The findings revealed that personal experiences with COVID-19 infection had a significant impact on students' attitudes and commitment to preventive measures (p<0.05). Among the participants, 172 students (45%) reported having contracted COVID-19. Students with clinical exposure showed a higher level of understanding and adherence to preventive measures (248 students, 68%), compared to pre-clinical students (198 students, 52%) (p<0.05). Positive attitudes were observed toward practices such as sneezing etiquette (289 students, 76%) and flu vaccination (314 students, 83%) (p<0.05). However, negative attitudes were observed toward mask-wearing (155 students, 41%) and social distancing (144 students, 38%), particularly among male students (p<0.05). Conclusion The study provided valuable insights into the impact of the COVID-19 pandemic on medical and health sciences students' knowledge, attitudes, and practices toward preventive measures and the importance of introducing COVID-19 prevention measures in the pre-clinical phase as well as mental health support to promote positive attitudes and enhance adherence to preventive measures.

SKping cell cycle regulation: role of ubiquitin ligase SKP2 in hematological malignancies.

SKP2 (S-phase kinase-associated protein 2) is a member of the F-box family of substrate-recognition subunits in the SCF ubiquitin-protein ligase complexes. It is associated with ubiquitin-mediated degradation in the mammalian cell cycle components and other target proteins involved in cell cycle progression, signal transduction, and transcription. Being an oncogene in solid tumors and hematological malignancies, it is frequently associated with drug resistance and poor disease outcomes. In the current review, we discussed the novel role of SKP2 in different hematological malignancies. Further, we performed a limited in-silico analysis to establish the involvement of SKP2 in a few publicly available cancer datasets. Interestingly, our study identified Skp2 expression to be altered in a cancer-specific manner. While it was found to be overexpressed in several cancer types, few cancer showed a down-regulation in SKP2. Our review provides evidence for developing novel SKP2 inhibitors in hematological malignancies. We also investigated the effect of SKP2 status on survival and disease progression. In addition, the role of miRNA and its associated families in regulating Skp2 expression was explored. Subsequently, we predicted common miRNAs against Skp2 genes by using miRNA-predication tools. Finally, we discussed current approaches and future prospective approaches to target the Skp2 gene by using different drugs and miRNA-based therapeutics applications in translational research.

Geochemical Evaluation of Paleocene Source Rocks in the Kohat Sub-Basin, Pakistan.

The Kohat sub-basin is one of the main hydrocarbon-producing sedimentary basins located in the northwest extension of the Indus Basin in Pakistan. It contains numerous proven and potential petroleum from the Cambrian to the Miocene. Conventional petroleum resources have been depleting rapidly over the last couple of years. Therefore, unconventional resources should be explored using a variety of geochemical and geophysical techniques to address the energy demands. Geochemical techniques, including total organic carbon (TOC) assessment, Rock-Eval pyrolysis, organic petrography, and biomarker studies, are essential for evaluating the potential of shale gas reservoirs to delineate future prospects in a basin. The source rock potential of the Paleocene rocks, including the Patala, Lockhart, and Hangu formations of the sub-basin, is evaluated using geochemical analyses on well cuttings from the Tolanj-01 well. The analyses include estimation of total organic carbon (TOC), Rock-Eval pyrolysis, and organic petrography (vitrinite reflectance) to evaluate the organic richness, thermal maturity, kerogen type, hydrocarbon type, and environment of deposition. Other techniques for extractable organic matter (EOM) include solid-liquid chromatographic separation of fractions, gas chromatography (GC-FID)/whole oil chromatography, and gas chromatography-mass spectrometry (GC-MS). The organic matter (TOC, wt %) analysis reveals that 18 (18) samples of the Hangu formation (0.08-1.8 wt %) show poor values, 12 (12) samples of the Lockhart formation (0.05-0.5 wt %) have poor to fair content, and 26 (26) samples of the Patala formation have poor to fair (0.08-0.19 wt %) TOC content. Rock-Eval pyrolysis studies including hydrogen index, oxygen index, Tmax, quantities of free hydrocarbons (S1, mg/g), and hydrocarbons produced from pyrolysis (S2, mg/g) are determined for the well-cut samples (56) of the Paleocene rocks. The hydrogen index values for the Hangu formation are lower than 200, and those for the Lockhart and Patala formations range between 100 and 250. A maceral analysis is also conducted on these samples, which reveal that the majority of the samples of the Paleocene units present in the basin belong to kerogen types II/III. The thermal maturity of the Hangu and Lockhart formations falls in the late-stage oil window, while that of the Patala formation falls in the peak to late oil window. The genetic potential (GP) for these rock units is also determined based on S1 and S2 values, which reveals that it is generally poor except for a few samples of the Hangu and Lockhart formations, which show fair GP values. For the organic petrography (vitrinite reflectance, R0), one sample from each unit is selected, which shows that the Hangu, Lockhart, and Patala formations fall in the category of the mature oil window with their R0 (%) values being 0.95, 0.89, and 0.82, respectively. The extracts (EOM) from these rock units are also analyzed to assess the depositional settings, biological source input, biodegradation, thermal maturity, etc. The greater values of pristine to phytane (Pr/Ph > 1) ratios for Hangu (1.33), Lockhart (1.23), and Patala (1.8) indicate an intermediate condition (suboxic), while a cross-plot of Pr/n-C17-Ph/n-C18 shows that the organic matter is deposited in a transitional setting. The ratios between C19TCT/C19 TCT + C23 TCT and C24 TeCT/C24TeCT + C23TCT biological source inputs are mainly of marine origin. Similarly, the ternary diagram of regular steranes (C27-C28-C29) shows a greater marine input. Lower values of the carbon preference index (CPI1) for Hangu (0.95), Lockhart (0.91), and Patala (1.04) indicate higher thermal maturity of the Paleocene rocks. Similarly, the methylphenanthrene index (MPI-1) values, Moretane index, and Pr/n-C17 vs Ph/n-C18 plots also show higher thermal maturity for these rock extracts.

Multifaceted chemical and bioactive features of Ag@TiO2 and Ag@SeO2 core/shell nanoparticles biosynthesized using Beta vulgaris L. extract.

Due to increasing concerns about environmental impact and toxicity, developing green and sustainable methods for nanoparticle synthesis is attracting significant interest. This work reports the successful green synthesis of silver (Ag), silver-titanium dioxide (Ag@TiO2), and silver-selenium dioxide (Ag@SeO2) nanoparticles (NPs) using Beta vulgaris L. extract. Characterization by XRD, SEM, TEM, and EDX confirmed the successful formation of uniformly distributed spherical NPs with controlled size (25 ± 4.9 nm) and desired elemental composition. All synthesized NPs and the B. vulgaris extract exhibited potent free radical scavenging activity, indicating significant antioxidant potential. However, Ag@SeO2 displayed lower hemocompatibility compared to other NPs, while Ag@SeO2 and the extract demonstrated reduced inflammation in a carrageenan-induced paw edema animal model. Interestingly, Ag@TiO2 and Ag@SeO2 exhibited strong antifungal activity against Rhizoctonia solani and Sclerotia sclerotium, as evidenced by TEM and FTIR analyses. Generally, the findings suggest that B. vulgaris-derived NPs possess diverse biological activities with potential applications in various fields such as medicine and agriculture. Ag@TiO2 and Ag@SeO2, in particular, warrant further investigation for their potential as novel bioactive agents.

Deep transfer learning with fuzzy ensemble approach for the early detection of breast cancer.

Breast Cancer is a significant global health challenge, particularly affecting women with higher mortality compared with other cancer types. Timely detection of such cancer types is crucial, and recent research, employing deep learning techniques, shows promise in earlier detection. The research focuses on the early detection of such tumors using mammogram images with deep-learning models. The paper utilized four public databases where a similar amount of 986 mammograms each for three classes (normal, benign, malignant) are taken for evaluation. Herein, three deep CNN models such as VGG-11, Inception v3, and ResNet50 are employed as base classifiers. The research adopts an ensemble method where the proposed approach makes use of the modified Gompertz function for building a fuzzy ranking of the base classification models and their decision scores are integrated in an adaptive manner for constructing the final prediction of results. The classification results of the proposed fuzzy ensemble approach outperform transfer learning models and other ensemble approaches such as weighted average and Sugeno integral techniques. The proposed ResNet50 ensemble network using the modified Gompertz function-based fuzzy ranking approach provides a superior classification accuracy of 98.986%.

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

Effect of Casein Phosphopeptide-Amorphous Calcium Phosphate, Proanthocyanidin, Carbon Dioxide Laser Remineralization on the Bond Integrity of Composite Restoration Bonded to Caries Affected Dentin.

Objective: Assessment of different remineralizing pretreatment casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), proanthocyanidin (PA), carbon dioxide laser (CO2), eggshell solution (ES) on the shear bond strength (SBS) of resin composite bonded to remineralized carious-affected dentin (CAD). Materials and methods: Eighty human molars were collected with occlusal caries that extended about halfway into the dentin. Using a water-cooled, low-speed cutting saw, a flat, mid-coronal dentin surface was exposed. CAD was differentiated from healthy dentin. Based on the remineralizing agent used on the CAD surface, the teeth were arbitrarily allocated into five groups (n = 10). Group 1: no remineralizing agent, Group 2: CPP-ACP, Group 3: 6.5% PA solution, Group 4: CO2 laser, and Group 5: ES solution. All samples were bonded to composite and light cured and thermocycled. SBS and failure mode analysis were performed using universal testing and stereomicroscope 40 × . Using SPSS, SBS, and failure mode data were analyzed using analysis of variance and Tukey's honesty significant difference (HSD) test Results: Group 3 (6.5% PA solution; 15.59 ± 1.44 MPa) samples established the maximum bond integrity. Nevertheless, Group 1 (No remineralizing agent; 11.19 ± 1.21 MPa) exhibited the minimum outcome of bond strength. Intergroup comparison analysis showed that Group 1 (No remineralizing agent), Group 2 (CPP-ACP), and Group 4 (CO2 laser) established comparable values of bond strength (p > 0.05). Likewise, Group 3 (6.5% PA solution) and Group 5 (EA solution) also revealed equivalent bond integrity (p > 0.05). Conclusions: PA and ES are considered potential remineralizing agents used for caries-affected dentin surfaces in improving bond integrity to composite resin. However, further studies are advocated to extrapolate the findings of this study.

Evaluation of Zygomaticomaxillary Complex Fractures with Gillies Approach in Al-Baha Region of Saudi Arabia: A Cohort Study.

Background: The aim of this study was to evaluate the accuracy of the degree of fracture reduction after open reduction and internal fixation of Zygomaticomaxillary Complex (ZMC) fractures in the Saudi population of the Al-Baha region, using Gillies approach. Further comparison with preoperative and postoperative standardized computed tomography (CT) views with the calculation of residual deformity percentage, which remained after the ZMC rehabilitation. Methods: A 5-year retrospective CT-based study on preoperative and postoperative axial CT scans of 46 male patients with ZMC fractures. The CT measurements were made (in millimeters) at the fracture site of maximum displacement through the anterior orbital rim and orbital floor, posterolateral wall of the maxillary sinus, zygomatic arch, and zygomaticofrontal suture. For the zygomatic arch, measurements were made (in mm) by drawing a tangent to the fractured arch segments and dropping a perpendicular to the inward displaced fractured arch. The total difference in all measured parts between preoperative and postoperative displacement was calculated in percentages. Results: Upon comparison of preoperative and postoperative zygomaticomaxillary complex CTs, three-point fixation at the regions of infraorbital rim, frontozygomatic suture, and posterolateral wall of the maxilla results in a reduction of the fracture sites in the range of 72.85% to 85%. Maximum reduction was noted at the zygomatic arch, that is, 85%, and minimum at the infraorbital rim, that is, 72.85%. The reduction obtained at all four sites was statistically significant, with P values ranging from .011 to .039. Conclusion: Gillies temporal approach and three-point fixation at the regions of the infraorbital rim, frontozygomatic suture, and posterolateral wall of the maxilla results in satisfactory treatment of ZMC fractures and improves patients oral health and quality of life.

Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges.

Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.

External Vs Internal e-Referrals: Results from a Nationwide Epidemiological Study Utilizing Secondary Collected Data.

Background: E-referral systems, streamlining patient access to specialists, have gained global recognition yet lacked a comparative study between internal and external referrals in Saudi Arabia (KSA). Methods: This retrospective study utilized secondary data from the Saudi Medical Appointments and Referrals Centre system. The data covers 2020 and 2021, including socio-demographic data, referral characteristics, and specialties. Logistic regression analysis was used to assess factors associated with external referrals. Results: Out of 645,425 e-referrals from more than 300 hospitals, 19.87% were external. The northern region led with 48.65%. Males were 55%, and those aged 25-64 were 56.68% of referrals. Outpatient clinic referrals comprised 47%, while 61% of referrals were due to a lack of specialty services. Several significant determinants are associated with higher rates of external referral with (p-value <0.001) and a 95% Confidence interval. Younger individuals under 25 exhibit higher referral rates than those aged 25-64. Geographically, compared to the central region, in descending order, there were increasing trends of external referral in the northern, western, and southern regions, respectively (OR = 19.26, OR = 4.48, OR 3.63). External referrals for outpatient departments (OPD) and dialysis services were higher than for routine admissions (OR = 1.38, OR = 1.26). The rate of external referrals due to the lack of available equipment was more predominant than other causes. Furthermore, in descending order, external referrals for organ transplantation and oncology are more frequent than for medical specialties, respectively (OR = 9.39, OR = 4.50). Conclusion: The study reveals trends in e-referrals within the KSA, noting regional differences, demographic factors, and types of specialties regarding external referrals, benefiting the New Model of Care for the 2030 Vision. Findings suggest expanding virtual consultations to reduce external referrals. Strengthening primary care and preventive medicine could also decrease future referrals. Future studies should assess resource distribution, including infrastructure and workforce, to further inform healthcare strategy.

Unconventional Reservoir Characterization of Patala Formation, Upper Indus Basin, Pakistan.

Unconventional hydrocarbon exploration is needed in the current oil and gas crisis scenario. Therefore, the development of conditions for unconventional hydrocarbon exploration is needed. In the Upper Indus Basin (UIB), Pakistan, the Patala Formation is one of the potential candidates for this unconventional exploration. It is a proven source rock at the regional level in the Kohat-Potwar sub-basin of UIB. This study aims to evaluate the shale gas potential of the rock in the Minwal-Joyamair area of the sub-basin. Developing a shale rock physics model is important for exploring and developing shale reservoirs due to the difference between unconventional shale and conventional sand reservoirs. These differences include mineral types, mineral characteristics, matrix pores, and fluid properties. To achieve the study's objectives, an integrated strategy provides for evaluating rock physics parameters, petrophysics, and geochemical analyses. This integrated approach indicates that the Patala Formation is a good potential reservoir for shale gas exploration. The Formation has a significant thickness (around 40-50 m), higher total organic carbon content (02-10%), higher brittleness index (0.44-0.56), and relatively shallow depth (2136-3223 m). These research findings suggested that the presence of organic and quartz-rich lithofacies can be considered as highly favorable "sweet spots" for shale-gas exploration in the UIB, Pakistan. Through proper understanding of the spatial and temporal distribution of these "sweet spots", shale-gas exploration can be developed as an effective strategy to exploit shale gas.

Pediatric Anesthesia Exposure: Decoding Its Neurodevelopmental Implications and Navigating the Nuances.

General anesthesia is fundamental in pediatric medical interventions, but its potential neurodevelopmental impact on children has raised concerns, necessitating a thorough investigation. This systematic review aimed to assess the association between pediatric anesthesia exposure and neurodevelopmental outcomes, focusing on dosage effects and identifying high-risk groups. The study involved an extensive literature search across PubMed, Medline, and Google Scholar, selecting 40 relevant studies from an initial pool of 2,000, based on inclusion criteria that focused on children under 18 years exposed to anesthesia, excluding those with major comorbidities or perioperative physiological insults. It was observed that while a single exposure to anesthesia had minimal impact on general neurodevelopment, repeated or prolonged exposures posed greater concerns. Despite these findings, the study identified gaps in certain areas like adaptive behavior and sensory cognition due to limited data. The conclusion drawn is that although the evidence on anesthesia-induced neurotoxicity in children remains inconclusive, the implications of pediatric anesthesia exposure are significant enough to warrant careful consideration by healthcare professionals, who should balance the procedural benefits against the risks. This study also calls for future research to standardize methodologies and employ consistent, validated neurodevelopmental measurement tools.