Rigor and reproducibility in human brain organoid research: Where we are and where we need to go.

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

In-vitro Cytotoxicity Investigations for Phytoconstituents of Saudi Medicinal Plants With Putative Ocular Effects.

BACKGROUND: Metastatic secondary ocular tumors spread from systemic malignancies, including breast cancer. This study aimed to evaluate the cytotoxicity of extracts from 5 medicinal plants native to Saudi Arabia. METHODS: For preliminary activity screening, cytotoxicity using the MTT assay and selectivity index determinations were made for medicinal plant extracts against various cancer cell-lines. The most promising extract was subjected to GC-MS analysis to determine the phytochemical composition. Clonogenic assays were performed using the most promising extract to confirm the initial results. Finally, western blot analysis was used to determine the modulation in expression of survivin and P27 suppressor genes in the human breast adenocarcinoma (MCF7) cell-line to understand the potential mechanistic properties of the active plant extract. RESULTS: The 5 plant extracts showed various cytotoxic activity levels using IC50. The most active extract was found to be the leaves of Capparis spinosa L. (BEP-07 extract) against the MCF7 breast cancer cell-line (IC50 = 3.61 ± 0.99 µg/ml) and selectivity index of 1.17 compared to the normal human fetal lung fibroblast (MRC5) cells. BEP-07 extract showed a dose dependent clonogenic effect against the MCF7 colonies which was comparable with the effect of doxorubicin. BEP-07 extract caused a significant decrease of survivin and increase in P27 expression compared to control GAPDH at its highest dose (14 µg/ml). The GC-MS chromatogram of Capparis spinosa L. (BEP-07 extract) revealed the existence of 145 compounds, belonging to the diverse classes of phytoconstituents. Fatty acids and their derivatives represent 15.4%, whilst octadecanoic acid, 2,3-dihydroxypropyl ester was the principal component (7.9%) detected. CONCLUSION: Leaves of Capparis spinosa L. (BEP-07 extract) exhibited a significant cytotoxic effect particularly against breast cancer cells. It exhibited this effect through survivin inhibition and via P27 upregulation. The detected phytoconstituents in the plant extract might be involved in tested cytotoxic activity, while further investigations are required to complete the drug candidate profile.

Serological investigation of Coxiella burnetii infection (Query fever) in livestock in Makkah Province, Saudi Arabia.

Background and Aim: Query fever (Q fever) is an endemic zoonotic disease and ruminants are considered to be the primary source of infection in humans. It is caused by Coxiella burnetii which is an obligate intracellular bacterial pathogen with a worldwide distribution. This study estimated the prevalence of Q fever in livestock with a history of abortion in Makkah Province, Saudi Arabia. Material and Methods: Sera from 341 camels, 326 sheep, and 121 goats of either sex from various locations (Makkah, Jeddah, AL-Taif, AL-Qunfudah, AL-Laith, and AL-Kamil) were examined using a Q fever indirect enzyme-linked immunosorbent assay. Results: Among the 788 serum samples, 356 animals had anti-Coxiella burnetii immunoglobulin G antibodies with an overall seroprevalence of 45.4%. Significant differences were observed in seroprevalence between species and locations. Camels had the highest percentage of Q fever-positive sera, with a prevalence of 50.4%, followed by goats (44.6%) and sheep (36.8%), with a high significant difference between animals (p = 0.000). The prevalence was significantly higher in Makkah (65.4%) than in Jeddah (28.8%). Conclusion: C. burnetii infection is prevalent in agricultural animals, especially camels maintained at livestock farms in Makkah province. Therefore, these animals considered as the main source of Q fever infections in Saudi Arabia, which is also a reason for the abortion in these animals. Therefore, there is an urgent need for further studies on Q fever infection with interventional approaches for prevention and control.

Mitochondrial DNA variants and microbiota: An experimental strategy to identify novel therapeutic potential in chronic inflammatory diseases.

We previously demonstrated that mice carrying natural mtDNA variants of the FVB/NJ strain (m.7778 G>T in the mt-Atp8 gene in mitochondrial complex V), namely C57BL/6 J-mtFVB/NJ (B6-mtFVB), exhibited (i) partial protection from experimental skin inflammatory diseases in an anti-murine type VII collagen antibody-induced skin inflammation model and psoriasiform dermatitis model; (ii) significantly altered metabolites, including short-chain fatty acids, according to targeted metabolomics of liver, skin and lymph node samples; and (iii) a differential composition of the gut microbiota according to bacterial 16 S rRNA gene sequencing of stool samples compared to wild-type C57BL/6 J (B6) mice. To further dissect these disease-contributing factors, we induced an experimental antibody-induced skin inflammatory disease in gnotobiotic mice. We performed shotgun metagenomic sequencing of caecum contents and untargeted metabolomics of liver, CD4+ T cell, and caecum content samples from conventional B6-mtFVB and B6 mice. We identified D-glucosamine as a candidate mediator that ameliorated disease severity in experimental antibody-induced skin inflammation by modulating immune cell function in T cells, neutrophils and macrophages. Because mice carrying mtDNA variants of the FVB/NJ strain show differential disease susceptibility to a wide range of experimental diseases, including diet-induced atherosclerosis in low-density lipoprotein receptor knockout mice and collagen antibody-induced arthritis in DBA/1 J mice, this experimental approach is valuable for identifying novel therapeutic options for skin inflammatory conditions and other chronic inflammatory diseases to which mice carrying specific mtDNA variants show differential susceptibility.

Prevalence and Associated Factors of Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy.

Objectives To determine the prevalence of gastroesophageal reflux disease (GERD) after laparoscopic sleeve gastrectomy (LSG) and associated factors. Methods A cross-sectional study was conducted in different regions around the Kingdom of Saudi Arabia between 2022 and 2023. The questionnaire was distributed among patients who underwent LSG at different periods, ranging from six months to more than two years. The questionnaire comprised a risk factor assessment and the GERD-Health-Related Quality of Life (GERD-HRQL) questionnaire. Results A total of 387 participants with a mean age of 35.7±10.95 were included. The study included 225 females (58.1%) and 162 males (41.9%). The mean preoperative body mass index (BMI) was 44.36±8.07 kg/m2, which decreased to 28.78±6.31 kg/m2 postoperatively. Notably, dissatisfaction with general health surged from 17 (24.6%) preoperatively to 165 (42.6%) postoperatively. Despite no significant difference in GERD-HRQL scores in the group who had preoperative symptoms, 282 (72.9%) reported experiencing heartburn, and 289 (74.7%) reported bloating postoperatively. Postoperatively, 203 (52.5%) reported improved quality of life. Moreover, changes in BMI were strongly correlated with heartburn, dysphagia, odynophagia, and bloating. The postoperative prevalence of GERD was 355 (91.7%), with 318 (82.2%) of participants reporting new-onset symptoms. Sex (P=0.013), age (P=0.024), and hypercholesterolemia (P=0.046) were significantly associated with postoperative GERD severity. Conclusions The majority of participants developed GERD symptoms following surgery, with a significant proportion reporting new-onset symptoms. Sex, age, and hypercholesterolemia have emerged as significant factors for postoperative GERD severity.

Development of silver-doped copper oxide and chitosan nanocomposites for enhanced antimicrobial activities.

Antimicrobial resistance (AMR) has emerged as a significant and pressing public health concern, posing serious challenges to effectively preventing and treating persistent diseases. Despite various efforts made in recent years to address this problem, the global trends of AMR continue to escalate without any indication of decline. As AMR is well-known for antibiotics, developing new materials such as metal containing compounds with different mechanisms of action is crucial to effectively address this challenge. Copper, silver, and chitosan in various forms have demonstrated significant biological activities and hold promise for applications in medicine and biotechnology. Exploring the biological properties of these nanoparticles is essential for innovative therapeutic approaches in treating bacterial and fungal infections, cancer, and other diseases. To this end, the present study aimed to synthesize silver@copper oxide (Ag@CuO) nanoparticles and its chitosan nanocomposite (Chi-Ag@CuO) to investigate their antimicrobial efficacy. Various established spectroscopic and microscopic methods were employed for characterization purposes, encompassing scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Subsequently, the antimicrobial activity of the nanoparticles was assessed through MIC (minimum inhibitory concentration), MBC (minimum bactericidal concentration), and well-disk diffusion assays against Pseudomonas aeruginosa, Acinetobacter baumannii Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans. The size of the CuO-NPs, Ag@CuO, and Chi-Ag@CuO NPs was found to be 70-120 nm with a spherical shape and an almost uniform distribution. The nanocomposites were found to possess a minimum inhibitory concentration (MIC) of 5 µg/mL and a minimum bactericidal concentration (MBC) of 250 µg/mL. Moreover, these nanocomposites generated varying clear inhibition zones, with diameters ranging from a minimum of 9 ± 0.5 mm to a maximum of 25 ± 0.5 mm. Consequently, it is evident that the amalgamation of copper-silver-chitosan nanoparticles has exhibited noteworthy antimicrobial properties in the controlled laboratory environment, surpassing the performance of other types of nanoparticles.

Physical Analysis and Mathematical Modeling of the Hydrogen Storage Process in the MmNi4.2Mn0.8 Compound.

The results of an experimental and mathematical study into the MmNi4.2Mn0.8 compound's hydrogen storage properties are presented in the present research. Plotting and discussion of the experimental isotherms (P-C-T) for different starting temperatures (288 K, 298 K, 308 K, and 318 K) were carried out first. Then, the enthalpy and entropy of formation (ΔH0, ΔS0) were deduced from the plot of van't Hoff. Following that, the P-C-T were contrasted with a mathematical model developed via statistical physics modeling. The steric and energetic parameters, such as the number of the receiving sites (n1, n2), their densities (Nm1, Nm2), and the energy parameters (P1, P2) of the system, were calculated thanks to the excellent agreement between the numerical and experimental results. Therefore, plotting and discussing these parameters in relation to temperature preceded their application in determining the amount of hydrogen in each type of site per unit of metal ([H/M]1, [H/M]2) as well as for the entire system [H/M] versus temperature and pressure besides the absorption energies associated with each kind of site (ΔE1, ΔE2) and the thermodynamic functions (free energy, Gibbs energy, and entropy) that control the absorption reaction.

Inspiratory muscle training impact on respiratory muscle strength, pulmonary function, and quality of life in children with chest burn: A randomized controlled trial.

PURPOSE: Respiratory muscle function is compromised in children recovering from chest wall burns, which potentially leads to more impact on exercise capacity and quality of life. This study investigates the effects of an inspiratory muscle training intervention accompanied with a pulmonary rehabilitation program on respiratory muscle strength, lung function, functional capacity, and quality of life in chest burned children. METHODS: Forty children with burns, aged from 10 to 18 years old and total body surface area of 30% to 50%, were randomly allocated to the inspiratory muscle training group (IMT- G: n = 20) or control group (CG: n = 20). They received IMT plus pulmonary rehabilitation or pulmonary rehabilitation with sham IMT, respectively for eight weeks. The outcomes were the respiratory muscle strength measured by maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP); lung functions (FEV1, FVC and FEV1/FVC ratio); functional capacity as well as Pediatric Quality of Life to measure physical and psychosocial functioning. outcome measures were assessed at before and after intervention (after eight weeks). RESULTS: Based on the pre-intervention assessments, we found no significant difference between both groups (p > 0.05). Significant post-intervention differences were reported between both groups in MIP (P = .003), MEP (P = .017), FVC (P = .001), FEV1 (P = .007), FEV1/FVC ratio (P = .028), functional capacity (P = .003), physical domain of QoL (P = .006) and psychological domain of QoL (P = .002) in favor of the IMT group. CONCLUSIONS: Eight weeks of inspiratory muscle training combined with pulmonary rehabilitation program improved children with chest burns' respiratory muscles strength, lung functions, functional capacity, and quality of life. Inspiratory muscle training may be employed in burn rehabilitation programs. It is a safe and effective therapy in chest burned children.

MALDI Imaging Mass Spectrometry Visualizes the Distribution of Antidepressant Duloxetine and Its Major Metabolites in Mouse Brain, Liver, Kidney, and Spleen Tissues.

Imaging mass spectrometry (IMS) is a powerful tool for mapping the spatial distribution of unlabeled drugs and metabolites that may find application in assessing drug delivery, explaining drug efficacy, and identifying potential toxicity. This study focuses on determining the spatial distribution of the antidepressant duloxetine, which is widely prescribed despite common adverse effects (liver injury, constant headaches) whose mechanisms are not fully understood. We used high-resolution IMS with matrix-assisted laser desorption/ionization to examine the distribution of duloxetine and its major metabolites in four mouse organs where it may contribute to efficacy or toxicity: brain, liver, kidney, and spleen. In none of these tissues is duloxetine or its metabolites homogeneously distributed, which has implications for both efficacy and toxicity. We found duloxetine to be similarly distributed in spleen red pulp and white pulp but differentially distributed in different anatomic regions of the liver, kidney, and brain, with dose-dependent patterns. Comparison with hematoxylin and eosin staining of tissue sections reveals that the ion images of endogenous lipids help delineate anatomic regions in the brain and kidney, while heme ion images assist in differentiating regions within the spleen. These endogenous metabolites may serve as a valuable resource for examining the spatial distribution of other drugs in tissues when staining images are not available. These findings may facilitate future mechanistic studies of the therapeutic and adverse effects of duloxetine. In the current work, we did not perform absolute quantification of duloxetine, which will be reported in due course. SIGNIFICANCE STATEMENT: The study utilized imaging mass spectrometry to examine the spatial distribution of duloxetine and its primary metabolites in mouse brain, liver, kidney, and spleen. These results may pave the way for future investigations into the mechanisms behind duloxetine's therapeutic and adverse effects. Furthermore, the mass spectrometry images of specific endogenous metabolites such as heme could be valuable in analyzing the spatial distribution of other drugs within tissues in scenarios where histological staining images are unavailable.

An analysis of conventional and modern packaging approaches for cut flowers: a review article.

Fresh-cut flowers are considered to be one of the most delicate and challenging commercial crops. It is important to take into consideration how to minimize loss during storage and transportation when preserving cut flowers. Many impinging (bad effect) forces can interact to shorten the flowers' vase life. In the flower industry, effective methods need to be developed to extend freshly cut flowers' life. Fresh-cut flowers' vase life can be shortened by a variety of interlocking causes. The flower industry must develop new techniques to extend the flowers' vase lifespan. This review provides comprehensive, up-to-date information on classical, modified atmosphere packaging (MAP), and controlled atmosphere packaging (CAP) displays. According to this review, a promising packaging technique for fresh flowers can be achieved through smart packaging. A smart package is one that incorporates new technology to increase its functionality. This combines active packaging, nanotechnology, and intelligence. This technology makes it easier to keep an eye on the environmental variables that exist around the packaged flowers to enhance their quality. This article offers a comprehensive overview of creative flower-saving packaging ideas that reduce flower losses and assist growers in handling more effectively their flower inventory. To guarantee the quality of flowers throughout the marketing chain, innovative packaging techniques and advanced packaging technologies should be adopted to understand various package performances. This will provide the consumer with cut flowers of standard quality. Furthermore, sustainable packaging is achieved with circular packaging. We can significantly reduce packaging waste's environmental impact by designing reused or recyclable packaging.

Optimization and Detergent Compatibility of Protease Produced from Aspergillus oryzae by Utilizing Agro Wastes.

The biotechnological process called solid-state fermentation (SSF) was applied for hyper production of protease by using a fungal strain called Aspergillus oryzae. From screening of 9 different local substrates (peanut shell, wheat bran, guava leaves, sugar cane bagasse, rice polish, wheat straw, corn straw, reed grass, and rice straw), peanut shells serve as the best substrates for protease production under optimized cultured conditions. The varying physiochemical parameters such as pH (2-9.5), temperature (30-52 °C), incubation time (1-10 days), inoculum size (1-8 mL), moisture level (20-125%), and substrate concentration (1-7 g) were optimized by response surface methodology (RSM). The highest activity of protease was recorded to be 1101.778 U/mL at 660 nm using peanut shell was optimum at pH 8, temperature 52 °C, incubation time 8 days, inoculum size 2 mL, moisture level 20%, and substrate concentration 2 g. The crude form of enzymes produced were further purified through ammonium sulfate precipitation, dialysis, and gel filtration chromatography. Then, purified enzymes were characterized at different pH, temperature, and incubation time. For characterization of purified protease, pH, temperature, and incubation time were 8, 52 °C, and 8 days for peanut shell and was done by one factor at a time method. Hence, isolated enzymes were alkaline in nature, i.e., alkaline proteases. Then, protease produced from peanut shells was applied to locally available detergents to increase their catalytic activity for strain removal. At last, the final results were interpreted in the form of 3D surface and contour plots using Microsoft Excel 2013 and Minitab 17 software. In conclusion, the utilization of A. oryzae and peanut shell as the substrate in the biotechnological process of SSF demonstrated successful hyper production of alkaline protease. The optimized conditions resulted in high enzyme activity and showcased the potential application of the isolated enzymes in improving the catalytic activity of locally available detergents.

Molecular diagnosis for camel raw milk microbiota.

The existence of diverse microbes in unprocessed camel milk poses a significant threat to the well-being of a large population, especially infants and toddlers. The objective of this study was to ascertain the existence of microorganisms in unprocessed raw camel milk by employing a molecular-based technique in combination with a histological examination of bacteria. The identification of microbial species was achieved by employing PCR amplification and sequencing of 16s rRNA gene fragments. Various micorganisms found includes the probiotic Lactobacillus species, Staphylococcus succinic, Macrococcus casealyticus, Bacillus cohnii, and Salinicoccus kunmingensis. To prevent microbial contamination in raw milk, it is necessary to adequately heat or pasteurise the milk and to wash and sterilise the udder before milking the camel. This is because raw milk contains microbes that cause multiple diseases. Moreover, in the current era of the COVID-19 pandemics, ensuring proper sanitary conditions in milk and its derivatives might potentially mitigate the transmission of various diseases among consumers shortly. Keywords: camel, microbiota, 16s rRNA gene, PCR.

Unlocking the Power of Influenza Vaccines for Pediatric Population: A Narrative Review.

The flu, often known as influenza, is a dangerous public health hazard for the pediatric population. Immunization is essential for decreasing the burden of the disease and avoiding complications related to influenza. However, the immunogenicity, efficacy, and safety of different influenza vaccines in children warrant careful evaluation. The purpose of this narrative review is to give a summary of the existing literature on the immunogenicity, efficacy, and safety of several vaccinations against influenza viruses in children. The review incorporates evidence from a range of studies focusing on the outcomes of interest. Immunogenicity studies have shown that influenza vaccines induce a robust immune response in children, primarily through neutralizing antibodies' formation. However, variations in vaccine composition influence the duration and magnitude of immune responses. Safety is a crucial consideration in pediatric vaccination. In children, influenza vaccinations have generally shown a high safety profile, with mild and temporary side effects being the most common. Vaccinations against influenza have shown a modest level of efficacy in avoiding hospitalizations linked to influenza, laboratory-confirmed influenza infections, and serious consequences in children. Live attenuated vaccines have shown higher effectiveness against matched strains compared to inactivated vaccines. In conclusion, this narrative review highlights that receiving influenza vaccination in children aged six to 47 months is very important. While different vaccines exhibit varying immunogenicity, safety profiles, and effectiveness, they all contribute to reducing the burden of influenza among children. Future research should focus on optimizing vaccine strategies, improving vaccine coverage, and evaluating long-term protection.

Unveiling the landscape of resistance against high priority critically important antimicrobials in food-producing animals across Africa: A scoping review.

The rapid population growth in Africa is associated with an increasing demand for livestock products which in turn can lead to antimicrobial use. Antimicrobial usage in animals contributes to the emergence and selection of resistant bacteria which constitutes a serious public health threat. This study aims to review and summarize the available information on highest priority critically important antimicrobials (HPCIAs) resistance in livestock production in Africa. This work will help to inform future policies for controlling antimicrobial resistance (AMR) in the food production chain. A scoping review was conducted according to the Cochrane handbook and following PRISMA 2020 guidelines for reporting. Primary research studies published after 1999 and reporting resistance of Escherichia coli, Enterococcus spp, Staphylococcus aureus, Salmonella spp, and Campylobacter spp to HPCIAs in poultry, cattle, pigs, goats, and sheep in Africa were searched in four databases. A total of 312 articles were included in the review. The majority of the studies (40.7) were conducted in North African countries. More than 49.0% of included studies involved poultry and 26.2% cattle. Cephalosporins and quinolones were the most studied antimicrobial classes. Of the bacteria investigated in the current review, E. coli (41.7%) and Salmonella spp (24.9%) represented the most commonly studied. High levels of resistance against erythromycin in E. coli were found in poultry (MR 96.1%, IQR 83.3-100.0%), cattle (MR 85.7%, IQR 69.2-100.0%), and pigs (MR 94.0%, IQR 86.2-94.0%). In sheep, a high level of resistance was observed in E. coli against nalidixic acid (MR 87.5%, IQR 81.3-93.8%). In goats, the low level of sensibility was noted in S. aureus against streptomycin (MR 86.8%, IQR 19.4-99.0%). The study provides valuable information on HPCIAs resistance in livestock production in Africa and highlights the need for further research and policies to address the public health risk of AMR. This will likely require an investment in diagnostic infrastructure across the continent. Awareness on the harmful impact of AMR in African countries is a requirement to produce more effective and sustainable measures to curb AMR.

Flawless polyaniline coating for preservation and corrosion protection of ancient steel spearheads: an archaeological study from military museum, Al-Qala, Egypt.

The purpose of this research was to examine the viability of applying a flawless polyaniline coating on steel spearheads to preserve them and protect them from corrosion. The spearpoints, thought to be archaeologically significant, were acquired from the Military Museum in Al-Qala, Egypt. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy were used to characterize the spearheads chemical composition and microstructure (EDX). The spearheads were determined to be constructed of steel and to have a coating of ferric oxide and other corrosion products on their exteriors. After that, a flawless polyaniline coating was electrochemically deposited onto the spearpoints in a way that was both quick and cheap. Many types of corrosion tests, such as electrochemical impedance spectroscopy and potentiodynamic polarization (PDP) readings, were used to determine the coating's effectiveness. The steel spearheads' findings revealed a significant improvement in their resistance to corrosion after being coated with flawless polyaniline. The coating served as a barrier, blocking out water and other corrosive substances and slowing the buildup of corrosion byproducts on the spearpoints. In conclusion, our research shows that a flawless polyaniline coating may be an effective anti-corrosion treatment for ancient steel artifacts. The approach is straightforward, cheap, and readily scalable for massive conservation efforts.

Prevalence and Risk Factors of Dry Eye Disease in Association With the Increased Use of Electronic Devices Among University Students in Western Saudi Arabia.

AIM: Dry eye disease (DED) is a prevalent ocular condition that significantly impacts individuals' quality of life and performance. It is charac-terized by the instability of the tear film, which causes ocular surface inflamma-tion and damage that leads to ocular symptoms. However, this study aimed to determine the prevalence of DED and identify associated risk factors among university students in western Saudi Arabia. METHODS: A total of 402 university students participated in this study. The sample size was determined using Raosoft software (Raosoft, Inc., Seattle, WA), considering an estimated student population of 20,000. Data were collected between January and March 2023 through an online questionnaire distributed to the participants. The questionnaire comprised three sections, covering general information, behaviors related to digital device (DD) use, and the validated Arabic version of the Ocular Surface Disease Index (OSDI) questionnaire. OSDI scores were calculated, and the severity of DED was categorized using established cutoff points. RESULTS: Among the 402 university students who took part in the survey, the majority (63.2%) were aged between 21 and 25 years, with females representing the dominant gender (72.9%). Notably, 90.8% of participants reported using DDs at bedtime. Over 60% of students had been using DDs for more than 10 years, and approximately 61.7% reported having more than six hours of daily screen time. Mobile devices were the most commonly used electronic devices (67.2%), and TikTok emerged as the most frequently used application (35.6%). Based on the OSDI criteria, 21.1% of students had mild DED symptoms, 14.9% had moderate symptoms, and 38.6% had severe symptoms. Hence, the prevalence of students exhibiting positive DED symptoms was 74.6%, while 25.4% were negative.

Short and Long-Term Clinical Outcomes in Octogenarian Patients With Non-ST-Elevation Myocardial Infarction: A Comparative Analysis of Revascularization Strategies Versus Medical Management.

INTRODUCTION: As the primary cause of morbidity and mortality among older individuals, cardiovascular disease remains a major concern. Choosing between revascularization and medical management of elderly patients remains controversial. This study aims to evaluate the clinical implications of these treatment approaches in the context of non-ST-elevation myocardial infarction (NSTEMI) in octogenarian patients. METHODS: This observational cohort study involved 41 octogenarian patients who were diagnosed with NSTEMI from 2019 to 2021 and were managed by revascularization (with either percutaneous coronary intervention, coronary artery bypass graft surgery, or both) or conservative medical therapy. All NSTEMI patients were diagnosed based on symptoms, electrocardiographic changes, and cardiac biomarkers. The study compared the short- and long-term outcomes of 13 patients in the revascularization group and 28 in the medical therapy group. RESULTS: Overall, the mean patient age was 84.63 years. Eighteen patients were men (43.9%), and 23 were women (56.1%). The most prevalent disease among the sample was hypertension (34 patients, 82.9%), followed by diabetes mellitus (27 patients, 65.9%) and prior ischemic heart disease (21 patients, 51.2%). Almost all patients in the revascularization-treated group developed complications after the procedure (84.6%), while 46.4% of the patients in the medication-only group developed a complication later on. The revascularization-treated group showed higher mortality rates in both the short- and long-term (23.1% and 38.5%, respectively) compared to the medication-only group, which showed better survival rates numerically in both the short- and long-term (14.3% and 32.1%, respectively). This was not statistically significant. CONCLUSION: Revascularization treatment in elderly patients with NSTEMI was associated with a higher risk of complications and a higher mortality rate compared with conservative medical management. Patients managed with only medications had a better survival rate in both the short- and long-term.

Metabolic bioactivation of antidepressants: advance and underlying hepatotoxicity.

Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, four have been withdrawn from the market due to severe hepatotoxicity, and others carry boxed warnings for idiosyncratic liver toxicity. The clinical and economic implications of antidepressant-induced liver injury are substantial, but the underlying mechanisms remain elusive. Drug-induced liver injury may involve the host immune system, the parent drug, or its metabolites, and reactive drug metabolites are one of the most commonly referenced risk factors. Although the precise mechanism by which toxicity is induced may be difficult to determine, identifying reactive metabolites that cause toxicity can offer valuable insights for decreasing the bioactivation potential of candidates during the drug discovery process. A comprehensive understanding of drug metabolic pathways can mitigate adverse drug-drug interactions that may be caused by elevated formation of reactive metabolites. This review provides a comprehensive overview of the current state of knowledge on antidepressant bioactivation, the metabolizing enzymes responsible for the formation of reactive metabolites, and their potential implication in hepatotoxicity. This information can be a valuable resource for medicinal chemists, toxicologists, and clinicians engaged in the fields of antidepressant development, toxicity, and depression treatment.

A pyrazolopyridine as a novel AhR signaling activator with anti-breast cancer properties in vitro and in vivo.

Breast cancer is one of the main causes of malignancy-related deaths globally and has a significant impact on women's quality of life. Despite significant therapeutic advances, there is a medical need for targeted therapies in breast cancer. Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor mediates responses to environment stimuli, is emerging as a unique pleiotropic target. Herein, a combined molecular simulation and in vitro investigations identified 3-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine (3FPP) as a novel AhR ligand in T47D and MDA-MB-231 breast cancer cells. Its agonistic effects induced formation of the AhR-AhR nuclear translocator (Arnt) heterodimer and prompted its binding to the penta-nucleotide sequence, called xenobiotic-responsive element (XRE) motif. Moreover, 3FPP augmented the promoter-driven luciferase activities and expression of AhR-regulated genes encoding cytochrome P450 1A1 (CYP1A1) and microRNA (miR)-212/132 cluster. It reduced cell viability, migration, and invasion of both cell lines through AhR signaling. These anticancer properties were concomitant with reduced levels of B-cell lymphoma 2 (BCL-2), SRY-related HMG-box4 (SOX4), snail family zinc finger 2 (SNAI2), and cadherin 2 (CDH2). In vivo, 3FPP suppressed tumor growth and activated AhR signaling in an orthotopic mouse model. In conclusion, our results introduce the fused pyrazolopyridine 3FPP as a novel AhR agonist with AhR-specific anti-breast cancer potential in vitro and in vivo.