Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", and "Clinical trials". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.

Effect of two esthetic digitally produced materials used in fabrication of extracoronal attachments on the stresses Induced in removable partial dentures.

BACKGROUND: Preservation of the remaining structures while maintaining an esthetic appearance is a major objective in removable partial prosthodontics. So, the aim of the current study was to compare the stresses induced on the supporting structures by two digitally produced esthetic core materials; Zirconia and Polyetheretherketone when used as an extracoronal attachment in distal extension removable partial dentures using strain gauge analysis. METHODS: A mandibular Kennedy class II stone cast with the necessary abutments' preparations was scanned. The mandibular left canine and first premolar teeth were virtually removed. An acrylic mandibular left canine and first premolar teeth were prepared with heavy chamfer finish line and scanned. Virtual superimposition of the acrylic teeth in their corresponding positions was done. Two strain gauge slots were designed: distal to the terminal abutment and in the residual ridge. Two models and two sets of scanned teeth were digitally printed. The printed teeth were then placed in their corresponding sockets in each model and scanned. The attachment design was selected from the software library and milled out of Zirconia in the model ZR and Polyetheretherketone in the model PE. Five removable partial dentures were constructed for each model. The strain gauges were installed in their grooves. A Universal testing machine was used for unilateral load application of 100 N (N). For each removable partial denture, five measurements were made. The data followed normal distribution and were statistically analyzed by using unpaired t test. P value < 0.05 was considered to be statistically significant. RESULTS: During unilateral loading unpaired t test showed statistically significant difference (p = 0.0001) in the microstrain values recorded distal to the abutment between the models ZR (-1001.6 µÎµ ± 24.56) and PE (-682.6 µÎµ ± 22.18). However, non statistically significant difference (p = 0.3122) was observed in the residual ridge between them; ZR (16.2 µÎµ ± 4.53) and PE (15 µÎµ ± 3.74). CONCLUSIONS: In removable partial dentures, Polyetheretherketone extracoronal attachment induces less stress on the supporting abutments compared to the zirconia one with no difference in the stresses induced by them on the residual ridge.

Corneal densitometry changes after femtosecond laser-assisted intracorneal ring segments implantation in keratoconus.

Background: Intrastromal corneal ring segments are commonly implanted in the corneas of eyes with mild-to-moderate keratoconus; however, changes in corneal densitometry (CD) after implantation are a matter of debate in the current literature. We evaluated the changes in CD 1 and 3 months after femtosecond laser-assisted Keraring implantation. Methods: This retrospective, non-comparative, multicenter, case series study included patients with keratoconus who underwent femtosecond laser-assisted implantation of double segments with 90° and 160° arc lengths or two 160° arc length Keraring segments. Demographic and baseline clinical ophthalmic data were recorded. Corneal topography and tomography data acquired using a Pentacam HR Scheimpflug tomography system (Pentacam High Resolution; Oculus, Wetzlar, Germany) with a best-fit sphere were used as a reference surface. Using the Pentacam HR, CD measurements were acquired over a corneal area of 12 mm in total and at four concentric zones (0-2, 2-6, 6-10, and 10-12 mm) of three corneal stromal depths: 120 µm of the anterior corneal stromal layer, 60 µm of the posterior corneal stromal layer, and the central layer of stroma lying between these two layers. Results: We included 40 eyes of 40 patients, including 8 (20%) male and 32 (80%) female individuals, with a mean (standard deviation) age of 21.0 (6.4) years. We observed a significant improvement in the topographic values of steep keratometry (K), flat K, maximum K, and corneal astigmatism (all P < 0.05), but not in the mean K, thinnest corneal pachymetry, corneal thickness at the apex, back elevation, or front elevation (all P > 0.05). The mean total anterior, central, and posterior CD differed significantly among the time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05) and no difference between those of the 1-month and 3-month postoperative visits (all P > 0.05). The mean CD for the anterior layer in the central, paracentral, and mid-peripheral zones, and the central layer in all four zones, differed significantly among time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05), which remained unchanged from the 1-month to the 3-month postoperative visit (all P < 0.05), except for the central 2-6-mm zone, which decreased significantly from the 1-month to the 3-month postoperative visit (P < 0.001). The CD of the central 10-12-mm zone did not differ significantly in each pairwise comparison (all P > 0.05). In contrast, CD for the posterior layer in the paracentral zone decreased significantly from the preoperative to the 1-month and 3-month postoperative visits but increased, to a lesser extent, from the 1-month to the 3-month postoperative visit (all P < 0.05). Conclusions: Femtosecond laser-assisted Keraring implantation significantly changes CD, with improvement in most topography parameters. Further longitudinal studies with larger sample sizes are required to verify these preliminary findings.

Persistence of COVID-19 Human Milk Antibodies After Maternal COVID-19 Vaccination: Systematic Review and Meta-Regression Analysis.

The World Health Organization (WHO) declared COVID-19 a pandemic. The Centers for Disease Control and Prevention (CDC), WHO, and American College of Obstetricians and Gynecologists (ACOG) recommend vaccination of pregnant and lactating women, aiming to protect both mothers and their infants through transplacental and human milk antibody transmission. This study aims to assess the quantity of antibodies in human milk and determine the effect of time, vaccine type, and dose on antibody level. Single-arm prospective observational studies reporting the COVID-19-specific antibody level in human milk after COVID-19 vaccination during pregnancy or lactation were included. PubMed, Scopus, Cochrane, EBSCO, and Web of Science were searched from December 2019 to November 22, 2022. Data were extracted in a uniform Google sheet. A total of 2657 studies were identified. After the removal of duplicates and screening, 24 studies were included in the systematic review and meta-regression. Human milk COVID-19-specific antibody levels increased with subsequent vaccine doses, as reflected by a positive relationship for the second (coefficient=0.91, P-value 0.043 for IgA and coefficient=1.77, P-value 0.009 for IgG) and third (coefficient=1.23, P-value 0.0029 for IgA and coefficient=3.73, P-value 0.0068 for IgG) doses. The antibody level exhibited a weak positive relationship with the follow-up time (coefficient=0.13, P-value 0.0029 for IgA and coefficient=0.18, P-value 0.016 for IgG). Only one of the 38 infants showed detectable COVID-19 IgM and IgA antibody levels in their blood. There was an increase in the neutralizing activity of COVID-19 antibodies in human milk following the COVID-19 vaccination. From the analysis of published data, we found high positive levels of antibodies in human milk that increased with subsequent doses. Additionally, the human milk antibodies exhibit a positive neutralizing effect. Only one infant had detectable COVID-19 IgM+IgA antibodies in the blood. Further research is needed to discuss infant protection through a mother's vaccination.

Uracil-selective Cross-linking in RNA and Inhibition of miRNA Function by 2-Amino-6-vinyl-7-deazapurine Deoxynucleosides.

MicroRNAs (miRNAs) regulate gene expression through RNA interference. Consequently, miRNA inhibitors, such as anti-miRNA oligonucleotides (AMOs), have attracted attention for treating miRNA overexpression. To achieve efficient inhibition, we developed 2-amino-6-vinylpurine (AVP) nucleosides that form covalent bonds with uridine counterparts in RNA. We demonstrated that mRNA cross-linked with AVP-conjugated antisense oligonucleotides with AVP were protected from gene silencing by exogenous miRNA. However, endogenous miRNA function could not be inhibited in cells, probably because of slow cross-linking kinetics. We recently developed ADpVP, an AVP derivative bearing a 7-propynyl group-which boasts faster reaction rate than the original AVP. Here, we synthesized dADpVP-a deoxy analog of ADpVP-through a simplified synthesis protocol. Evaluation of the cross-linking reaction revealed that the reaction kinetics of dADpVP were comparable to those of ADpVP. In addition, structural analysis of the cross-linked adduct discovered N3 linkage against uridine. Incorporating dADpVP into two types of miRNA inhibitors revealed a marginal impact on AMO efficacy yet improved the performance of target site blockers. These results indicate the potential of cross-linking nucleosides for indirect miRNA function inhibition.

The Role of Platelet Rich Plasma in Vertebrogenic and Discogenic Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

Emerging Trends in Non-Protein Amino Acids as Potential Priming Agents: Implications for Stress Management Strategies and Unveiling Their Regulatory Functions.

Plants endure the repercussions of environmental stress. As the advancement of global climate change continues, it is increasingly crucial to protect against abiotic and biotic stress effects. Some naturally occurring plant compounds can be used effectively to protect the plants. By externally applying priming compounds, plants can be prompted to trigger their defensive mechanisms, resulting in improved immune system effectiveness. This review article examines the possibilities of utilizing exogenous alpha-, beta-, and gamma-aminobutyric acid (AABA, BABA, and GABA), which are non-protein amino acids (NPAAs) that are produced naturally in plants during instances of stress. The article additionally presents a concise overview of the studies' discoveries on this topic, assesses the particular fields in which they might be implemented, and proposes new avenues for future investigation.

Assessment of the Effect of Surface Modification of Metal Oxides on Silver Nanoparticles: Optical Properties and Potential Toxicity.

Silver nanoparticles (AgNPs) have garnered significant interest due to their distinctive properties and potential applications. Traditional fabrication methods for nanoparticles often involve high-energy physical conditions and the use of toxic solvents. Various green synthesis approaches have been developed to circumvent these issues and produce environmentally benign nanoparticles. Our study focuses on the green synthesis of AgNPs using L-ascorbic acid and explores the modification of their properties to enhance antibacterial and anticancer effects. This is achieved by coating the nanoparticles with Zinc oxide (ZnO) and Silica oxide (SiO2), which alters their optical properties in the visible spectrum. The synthesized formulations-AgNPs, zinc oxide-silver nanoparticles (Ag@ZnO), and silica oxide-silver nanoparticles (Ag@SiO2) core/shell nanoparticles-were characterized using a suite of physicochemical techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta potential measurement, UV-Vis spectroscopy, Refractive Index Measurements, and Optical Anisotropy Assessment. TEM imaging revealed particle sizes of 11 nm for AgNPs, 8 nm for Ag@ZnO, and 400 nm for Ag@SiO2. The Zeta potential values for Ag@ZnO and Ag@SiO2 were measured at -17.0 ± 5 mV and -65.0 ± 8 mV, respectively. UV-Vis absorption spectra were recorded for all formulations in the 320 nm to 600 nm wavelength range. The refractive index of AgNPs at 404.7 nm was 1.34572, with slight shifts observed for Ag@ZnO and Ag@SiO2 to 1.34326 and 1.37378, respectively. The cytotoxicity of the nanocomposites against breast cancer cell lines (MCF-7) was assessed using the MTT assay. The results indicated that AgNPs and Ag@ZnO exhibited potent therapeutic effects, with IC50 values of 494.00 µg/mL and 430.00 µg/mL, respectively, compared to 4247.20 µg/mL for Ag@SiO2. Additionally, the antibacterial efficacy of AgNPs was significantly enhanced under visible light irradiation. Ag@ZnO demonstrated substantial antibacterial activity both with and without light exposure, while the Ag@SiO2 nanocomposites significantly reduced the inherent antibacterial activity of silver. Conversely, the Ag@ZnO nanocomposites displayed pronounced antibacterial and anticancer activities. The findings suggest that silver-based nanocomposites, particularly Ag@ZnO, could be practical tools in water treatment and the pharmaceutical industry due to their enhanced therapeutic properties.

The Influence of Zinc Oxide Nanoparticles and Salt Stress on the Morphological and Some Biochemical Characteristics of Solanum lycopersicum L. Plants.

Salinity reduces crop yields and quality, causing global economic losses. Zinc oxide nanoparticles (ZnO-NPs) improve plant physiological and metabolic processes and abiotic stress resistance. This study examined the effects of foliar ZnO-NPs at 75 and 150 mg/L on tomato Kecskeméti 549 plants to alleviate salt stress caused by 150 mM NaCl. The precipitation procedure produced ZnO-NPs that were characterized using UV-VIS, TEM, STEM, DLS, EDAX, Zeta potential, and FTIR. The study assessed TPCs, TFCs, total hydrolyzable sugars, total free amino acids, protein, proline, H2O2, and MDA along with plant height, stem width, leaf area, and SPAD values. The polyphenolic burden was also measured by HPLC. With salt stress, plant growth and chlorophyll content decreased significantly. The growth and development of tomato plants changed by applying the ZnO-NPs. Dosages of ZnO-NPs had a significant effect across treatments. ZnO-NPs also increased chlorophyll, reduced stress markers, and released phenolic chemicals and proteins in the leaves of tomatoes. ZnO-NPs reduce salt stress by promoting the uptake of minerals. ZnO-NPs had beneficial effects on tomato plants when subjected to salt stress, making them an alternate technique to boost resilience in saline soils or low-quality irrigation water. This study examined how foliar application of chemically synthesized ZnO-NPs to the leaves affected biochemistry, morphology, and phenolic compound synthesis with and without NaCl.

BECN1 mRNA expression in breast cancer tissue; significant correlation to tumor grade.

Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.

Effect of breeding season and age on follicular dynamics and hemodynamics in embryo donor mares subjected to luteolysis after embryo flushing.

Background: Mares are the only companion animals simulating women in the large diameter of their follicles. Horses start reproduction at the age of three years, and some of them live for >30 years, so aging influences their reproductive capacity. Mares are sensitive to summer heat stress as they can sweat like humans. Aim: The current work aimed to study the effects of age (young versus senile), season (cold versus hot), and the hormonal treatments during embryo collection on the dominant and subordinate follicular dynamics and hemodynamics and circulating ovarian hormones in embryo donor mares ovulated twice spontaneously before inducing ovulation for flushing embryos. Methods: Spontaneous oestrous cycles were studied for young mares (<10 years; N = 6) or senile (>20 years; N = 5) during months of the cold season (November to April) and hot season (May to August). In young embryo donor mares, oestrous cycles after inducing ovulation and luteolysis were studied using Doppler ultrasound. Estradiol (E2), progesterone (P4), nitric oxide (NO), total cholesterol, and lactate dehydrogenase (LDH) were measured in blood serum. Results: A decrease in the dominant follicle antrum diameter (p > 0.05) and LDH (p = 0.016) was observed after inducing luteolysis in young embryo donor mares. Both human chorionic gonadotropin (hCG) and PGF2α treatments increased dominant follicle area (p = 0.0001), antrum area (p = 0.001), perimeter (p = 0.001), granulosa area (p = 0.0001), cholesterol (p = 0.0001), NO (p = 0.0001), and E2 (p = 0.0001). The dominant follicle area, antrum area, perimeter, color area, granulosa area, LDH, cholesterol, NO, and E2 increased (p = 0.0001) during the oestrous cycles of the hot season, but the circulatory % (p = 0.0001) declined. Senile mares had lower dominant follicle area (p = 0.002), antrum area (p = 0.0001), granulosa area (p > 0.05), LDH (p = 0.001), cholesterol (p = 0.0001), NO (p = 0.0001), and E2 (p = 0.0001) but higher circulatory % (p = 0.0001) and color area % (p = 0.023). The dominant follicle possesses the largest diameter, area, perimeter, granulosa area, and color area but the lowest circulatory % during spontaneous oestrous cycles, after inducing ovulation, or luteolysis with significant effects of the day of the spontaneous oestrous cycles on their dynamics and hemodynamics. Conclusion: During hot months, mares treated with hCG ovulated 24 hours later and prostaglandin-induced luteolysis was followed by new ovulation five days later. Follicles ovulated during the hot months were larger than those ovulated during the cold months and both had nearly the same color area %. Senile mares ovulated follicles with a lower area and antrum area but a higher color area %, so senile mares can be used as embryo or oocyte donors during the hot season.

Effect of different fabrication workflows on the passive fit of screw-retained bar splinting two interforaminal implants: a parallel blinded randomised clinical trial.

BACKGROUND: To clinically compare the effect of the conventional and the digital workflows on the passive fit of a screw retained bar splinting two inter-foraminal implants. METHODS: The current study was designed to be a parallel triple blinded randomised clinical trial. Thirty six completely edentulous patients were selected and simply randomized into two groups; conventional group (CG) and digital group (DG). The participants, investigator and outcome assessor were blinded. In the group (CG), the bar was constructed following a conventional workflow in which an open top splinted impression and a lost wax casting technology were used. However, in group (DG), a digital workflow including a digital impression and a digital bar milling technology was adopted. Passive fit of each bar was then evaluated clinically by applying the screw resistance test using the "flag" technique in the passive and non passive situations. The screw resistance test parameter was also calculated. Unpaired t-test was used for intergroup comparison. P-value < 0.05 was the statistical significance level. The study protocol was reviewed by the Research Ethics Committee in the author's university (Rec IM051811). Registration of the clinical trial was made on clinical trials.gov ID NCT05770011. An informed consent was obtained from all participants. RESULTS: Non statistically significant difference was denoted between both groups in all situations. In the passive situation, the mean ± standard deviation values were 1789.8° ± 20.7 and1786.1° ± 30.7 for the groups (CG) and (DG) respectively. In the non passive situation, they were 1572.8° ± 54.2 and 1609.2° ± 96.9. Regarding the screw resistance test parameter, they were 217° ± 55.3 and 176° ± 98.8. CONCLUSION: Conventional and digital fabrication workflows had clinically comparable effect on the passive fit of screw retained bar attachments supported by two dental implants.

Prospective comparison of tadalafil 5 mg, dapoxetine 30 mg, and the combination of both in the treatment of premature ejaculation.

Objective: To compare the efficacy of tadalafil alone, dapoxetine alone, and tadalafil with dapoxetine as a combination therapy for the treatment of premature ejaculation. Patients and Methods: Eligible patients attended our andrology clinic with premature ejaculation were randomly allocated into three groups: group A (92 participants) received on-demand tadalafil, 5 mg; group B (91 participants) were given on-demand dapoxetine, 30 mg; and group C (89 participants) received on-demand combination of tadalafil, 5 mg, and dapoxetine, 30 mg. We assessed the changes in the intravaginal ejaculatory latency time (IELT) and the satisfaction scores 1, 2, and 3 months after treatment. Results: Highly statistically significant improvements were found in the mean IELT and satisfaction scores 1, 2, and 3 months post-treatment in all groups (P = <0.001). Post hoc analysis suggested this improvement was more pronounced in group C (P < 0.001). Conclusion: Both tadalafil and dapoxetine are effective in the treatment of patients with premature ejaculation, but the combination of both drugs gives better results.

The Impact of Salinity on Crop Yields and the Confrontational Behavior of Transcriptional Regulators, Nanoparticles, and Antioxidant Defensive Mechanisms under Stressful Conditions: A Review.

One of the most significant environmental challenges to crop growth and yield worldwide is soil salinization. Salinity lowers soil solution water potential, causes ionic disequilibrium and specific ion effects, and increases reactive oxygen species (ROS) buildup, causing several physiological and biochemical issues in plants. Plants have developed biological and molecular methods to combat salt stress. Salt-signaling mechanisms regulated by phytohormones may provide additional defense in salty conditions. That discovery helped identify the molecular pathways that underlie zinc-oxide nanoparticle (ZnO-NP)-based salt tolerance in certain plants. It emphasized the need to study processes like transcriptional regulation that govern plants' many physiological responses to such harsh conditions. ZnO-NPs have shown the capability to reduce salinity stress by working with transcription factors (TFs) like AP2/EREBP, WRKYs, NACs, and bZIPs that are released or triggered to stimulate plant cell osmotic pressure-regulating hormones and chemicals. In addition, ZnO-NPs have been shown to reduce the expression of stress markers such as malondialdehyde (MDA) and hydrogen peroxide (H2O2) while also affecting transcriptional factors. Those systems helped maintain protein integrity, selective permeability, photosynthesis, and other physiological processes in salt-stressed plants. This review examined how salt stress affects crop yield and suggested that ZnO-NPs could reduce plant salinity stress instead of osmolytes and plant hormones.

Nintedanib in Combination With Chemotherapy in the Treatment of Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Lung cancer remains a major global health challenge, contributing to substantial morbidity and mortality rates. Nintedanib, a tyrosine kinase inhibitor, has demonstrated potential as a treatment for lung cancer. We aim to evaluate nintedanib's efficacy in treating patients with non-small cell lung cancer (NSCLC), depending on the available evidence. Our search for relevant articles was conducted on PubMed, Cochrane Library, Scopus, and Web of Science for randomized controlled trials (RCTs) that involved adult patients with NSCLC up to August 15, 2023. These trials compared the combination of nintedanib and chemotherapy to either placebo plus chemotherapy or chemotherapy alone. Our main outcomes include progression-free survival (PFS) and overall survival (OS). We utilized the Review Manager Software V.5.4 (The Cochrane Collaboration) to analyze all relevant data. Three identified trials, which included 2270 patients, fulfilled the inclusion criteria. Our analysis showed significantly improved PFS (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.71-0.88, P < 0.0001) in patients receiving nintedanib compared to placebo. However, OS was not statistically significant (HR = 0.96; 95% CI 0.88-1.05, P = 0.35). In conclusion, a combination of nintedanib and chemotherapy in treating patients with NSCLC was associated with improved PFS than chemotherapy alone but not with improved OS. Further clinical trials assessing nintedanib in the setting of NSCLC are necessary before any further recommendations can be made.

Effect of different framework materials on stresses induced in distal extension removable partial dentures: A strain gauge analysis.

PURPOSE: Evaluation of the strain transmitted to the abutments and residual ridge by polyetherketoneketone material compared to the cobalt-chromium one in distal extension removable partial dentures (RPDs) to fulfill the objective of preservation of the supporting structures. MATERIALS AND METHODS: A virtual model simulating a Kennedy class I partially edentulous mandibular arch was designed. Two models, one for each group, were printed. Five RPDs were made in each group. In group CR, the framework was milled from a cobalt-chromium alloy. While in group PK, it was milled from a polyetherketoneketone blank. Strain gauge rosettes were bonded distal to the last abutment and posteriorly in the distal end of the residual ridge. Unilateral vertical and oblique loadings were applied. Mann-Whitney U test was used for inter-group comparisons while the Friedman test was used for intra-group comparisons and corrected by Wilcoxon Signed-Rank Sum. The significance level was set at p ≤ 0.05. RESULTS: During unilateral vertical load application, a statistically significant difference was found between both groups distal to the abutment in the loaded and unloaded sides as well as the residual ridge on the unloaded side. During oblique load application, a statistically significant difference was found between both groups in all slots. CONCLUSION: Polyetherketoneketone material induces less stress on the abutments and more stress on the residual ridges compared to the cobalt-chromium ones. Therefore, it may be recommended for weak abutments supporting RPDs.

The Association Between Preoperative Insulin-Like Growth Factor 1 Levels and the Total Body Weight Loss in Women Post Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Despite the well-described optimal initial clinical response of sleeve gastrectomy (SG) in the treatment of obesity, some patients do not achieve optimal initial clinical response. Insulin-like growth factor-1 (IGF-1) has currently shown an association with post-bariatric surgery weight loss. This study aimed to assess the IGF-1 levels in female patients with obesity, the change after surgery, and their association with the metabolic profile and weight loss after surgery. PATIENTS AND METHODS: This was a prospective study that was conducted on adult female patients who were recruited for SG. The patients underwent clinical and laboratory investigations that included the IGF-1 measurement. At the 1-year follow-up, the same clinical and laboratory measures were repeated. RESULTS: This study included 100 female patients. At the 1-year follow-up, there was a statistically significant reduction in body mass index (BMI) (p < 0.001), fasting HbA1C levels (p < 0.001), and triglycerides (p < 0.001), as well as a statistically significant increase in HDL (p < 0.001) and IGF-1 (p < 0.001). Multiple regression analysis revealed that, among the patients baseline characteristics, the significant predictors for the percentage of total weight loss (%TWL) were the patients' BMI (p < 0.001) and IGF-1 levels (p < 0.001). The ROC curve showed that an IGF1 cutoff value of ≤ 23 ng/ml detected suboptimal initial clinical response, with a sensitivity of 95.35% and a specificity of 100%. CONCLUSION: This study underscores the significant impact of SG on weight loss and metabolic improvements in female patients. Baseline IGF-1 levels emerged as a crucial predictor of optimal initial clinical response.

Prevalence of new onset erectile dysfunction among Damietta governorate men after contracting COVID-19.

BACKGROUND: Several reports showed that sexual function was affected during and after the COVID-19 pandemic. AIMS: The objective of the study was to demonstrate whether a realistic association exists between the COVID-19 pandemic and erectile dysfunction (ED) among a sampled Egyptian population in Damietta governorate. METHODS: This cross-sectional study consisted of 330 adult males diagnosed with COVID-19 infection. They were categorized in three age groups (18-29, 30-39, and 40-50 years, respectively). COVID-19-confirmed cases were assessed by the Arabic version of the International Index of Erectile Function questionnaire (IIEF) scores. RESULTS: The prevalence of ED according to the IIEF was 55.1%. The ED was categorized into mild ED which represents 25.8% of the patients, mild to moderate which represents 22.4% of the patients, moderate which represents 7% of the patients, and severe which represents 0% of the patients. We found a significant negative correlation between the age of the patients and the IIEF score. Also, we found an association between the severity of COVID-19 infection and the IIEF score. CONCLUSION: An association of new-onset ED in men who suffered COVID-19 infection was established. This may be due to virus-induced endothelial cell dysfunction; however, an underlying mechanism and causation have not yet been clearly elucidated. While it appears that COVID-19 infection may be a risk factor for ED, additional research is needed to establish causality.

Predictors of acute kidney injury after percutaneous nephrolithotomy in adult patients: prospective observational study.

PURPOSE: To assess the frequency and the predictive factors of Acute Kidney injury (AKI) in patients undergoing percutaneous nephrolithotomy (PNL). METHODS: A prospective observational work. Demographic, preoperative laboratory data, stone characteristics, and intraoperative and postoperative data were gathered. Perioperative AKI had been defined as an elevation in serum creatinine by ≥ 0.3 mg/dl within 48 h, or ≥ 1.5 times baseline, or urine volume less than 0.5 ml/ kg/hour for 6 hours. A multivariate logistic regression analysis was performed to determine the predictive factors of AKI. ROC curves were utilized to determine the cutoff values of the risk variables. P-values were deemed statistically significant when they were less than 0.05. RESULTS: A total of 418 participants had been involved. The frequency of AKI was 13.9, and 17.2% of patients with AKI developed CKD. The risk factors were age > 46.5 years, smoking, BMI > 28.5 kg/m2, hypertension, diabetes, utilization of angiotensin-converting enzyme inhibitors (ACEI), haemoglobin < 10.8 gm/dl, baseline creatinine > 1.41 mg/dl, eGFR < 65.2 ml/min./1.73 m2, serum uric acid > 5.2 mg/dl, stone volume > 1748 mm3, large tract size, long operative time, and intra-operative bleeding. Patients with AKI had a notably extended duration of hospitalization (3.2 days ± 0.45 vs 2.1 ± 0.42, p < 0.001). CONCLUSIONS: Perioperative AKI occurred in 13.9% of individuals undergoing PNL. Identification and optimization of the risk factors and meticulous technique during PNL procedures should be attempted to decrease the risk of AKI.