GNAS mutation inhibits growth and induces phosphodiesterase 4D expression in colorectal cancer cell lines.

Approximately 5% of colorectal cancers (CRCs) have a gain-of-function mutation in the GNAS gene, which leads to the activation of cAMP-dependent signaling pathways and associates with poor prognosis. We investigated the effect of an activating GNAS mutation in CRC cell lines on gene expression and cell proliferation in vitro, and tumor growth in vivo. GNAS-mutated (GNASmt) HCT116 cells showed stimulated synthesis of cAMP as compared to parental (Par) cells. The most upregulated gene in the GNASmt cells was cAMP-hydrolyzing phosphodiesterase 4D (PDE4D) as detected by RNA sequencing. To further validate our finding, we analyzed PDE4D expression in a set of human CRC tumors (n = 35) and demonstrated overexpression in GNAS mutant CRC tumors as compared to GNAS wild-type tumors. The GNASmt HCT116 cells proliferated more slowly than the Par cells. PDE4 inhibitor Ro 20-1724 and PDE4D subtype selective inhibitor GEBR-7b further suppressed the proliferation of GNASmt cells without an effect on Par cells. The growth inhibitory effect of these inhibitors was also seen in the intrinsically GNAS-mutated SK-CO-1 CRC cell line having high levels of cAMP synthesis and PDE4D expression. In vivo, GNASmt HCT116 cells formed smaller tumors than the Par cells in nude mice. In conclusion, our findings demonstrate that GNAS mutation results in the growth suppression of CRC cells. Moreover, the GNAS mutation-induced overexpression of PDE4D provides a potential avenue to impede the proliferation of CRC cells through the use of PDE4 inhibitors.

Enhanced wheat productivity in saline soil through the combined application of poultry manure and beneficial microbes.

BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.

The Quest for Two-Dimensional MBenes: From Structural Evolution to Solar-Driven Hybrid Systems for Water-Fuel-Energy Generation and Phototherapy.

The field of 2D materials has advanced significantly with the emergence of MBenes, a new material derived from the MAX phases family, a novel class of materials that originates from the MAX phases family. Herein, this article explores the unique characteristics and morphological variations of MBenes, offering a comprehensive overview of their structural evolution. First, the discussion explores the evolutionary period of 2D MBenes associated with the several techniques for synthesizing, modifying, and characterizing MBenes to tailor their structure and enhance their functionality. The focus then shifts to the defect chemistry of MBenes, electronic, catalytic, and photothermal properties which play a crucial role in designing multifunctional solar-driven hybrid systems. Second, the recent advancements and potentials of 2D MBenes in solar-driven hybrid systems e.g. photo-electro catalysis, hybrid solar evaporators for freshwater and thermoelectric generators, and phototherapy, emphasizing their crucial significance in tackling energy and environmental issues, are explored. The study further explores the fundamental principles that regulate the improved photocatalytic and photothermal characteristics of MBenes, highlighting their promise for effective utilization of solar energy and remediation of the environment. The study also thoroughly assesses MBenes' scalability, stability, and cost effectiveness in solar-driven systems. Current insights and future directions allow researchers to utilize MBenes for sustainable and varied applications. This review regarding MBenes will be valuable to early researchers intrigued with synthesizing and utilizing 2D materials for solar-powered water-energy-fuel and phototherapy systems.

First Report of Wilt Caused by Fusarium nanum (FIESC 25) on Mungbean (Vigna radiata) in Pakistan.

Mungbean, Vigna radia (L.) R. Wilczek, is ranked 2nd next to chickpea (Cicer arietinum) in total cultivation and production in Pakistan. In August of 2022 and 2023, mungbean plants (cv. PRI Mung-2018) were found wilting in a field at the Ayub Agricultural Research Institute, Faisalabad, Pakistan. Wilted leaves turned yellow, died, but remained attached to the stem. Vascular tissue at the base of the stem showed light to dark brown discoloration. Roots were stunted with purplish brown to black discoloration. Symptomatic mungbean plants were collected from fields at five different locations (20 samples/location). Disease incidence was similar among the five fields, ranging from 5 to 10% at each location depending upon type of germplasm and date of sowing. For fungal isolation and morphological identification, symptomatic stem and root tissues were cut into ~5 mm2 pieces with a sterilized blade. Tissues were surface-sterilized for one min in a 0.5% sodium hypochlorite solution, rinsed twice in sterilized water, air dried on sterilized filter paper, and aseptically placed on potato dextrose agar (PDA) containing 0.5 g/L-1 streptomycin sulphate. Plates were incubated for 3-4 days at 25 ± 2°C with a 12-h photoperiod. Single-spore cultures were used for morphological and molecular analyses. Isolates on PDA grew rapidly and produced abundant white aerial mycelium that turned off-white to beige with age. Macroconidia were hyaline, falcate, typically 3-to-6 septate with a pointed apical cell and a foot-shaped basal cell, measuring 24.5-49.5 x 2.7-4.7 µm (n = 40). Globose to obovate chlamydospores measuring 5.8 ± 0.5 µm (n = 40) were produced singly or in chains and were intercalary or terminal and possessed roughened walls. The morphological data indicated the isolates were members of the genus Fusarium (Leslie and Summerell 2006). To obtain a species-level identification, a portion of translation elongation factor 1-α (TEF1), the largest subunit of RNA polymerase (RPB1), and the second largest subunit of RNA polymerase (RPB2) region were PCR amplified and sequenced using EF1/EF2 (O'Donnell et al. 1998), Fa/G2R (Hofstetter et al. 2007), and 5f2/7cr (Liu et al. 1999) primers, respectively. DNA sequences of these genes were deposited in GenBank under accession numbers MW059021, MW059017 and MW059019, respectively. The partial TEF1, RPB1 and RPB2 sequences were queried against the Fusarium MLST database (https://fusarium.mycobank.org/page/Fusarium_identification), using the polyphasic identification tool. The BLASTn search revealed 99.9% identity of the isolate to F. nanum (Xia et al. 2019), formerly FIESC 25 of the F. incarnatum-equiseti species complex (MRC 2610, NRRL 54143; O'Donnell et al. 2018). To confirm pathogenicity, roots of 3-5 leaf stage mungbean seedlings were soaked in a 106 spores ml-1 conidial suspension of the fungus for 15 min and then planted in 10 cm pots containing sterilized soil. Mock-inoculated plants with sterile water served as a negative control. Twenty pots that were used for each inoculated and control treatment were maintained at 25 ± 2°C, 14:8 h photoperiod, and 80% relative humidity in a growth chamber. After 15 days, leaf yellowing, internal browning from the base of stems and root discoloration was observed in all the inoculated plants. The uninoculated negative control plants remained asymptomatic. Fusarium nanum was re-isolated from artificially inoculated plants and identified by colony growth, conidial characteristics on PDA and molecular analyses (TEF1). To our knowledge, this is the first report of wilt caused by F.nanum on mungbean in Pakistan. In Pakistan, mungbean cultivation in irrigated areas has increased in recent years. It has been introduced frequently in citrus orchards, crop rotation of maize and sesame, intercropping with sugarcane and as green manure. However, citrus, maize, sesame and sugarcane are also hosts of Fusarium spp. Therefore, this information warrants sustainable crop protection and may have an impact on further interaction of F. nanum with other wilt pathogens.

Current Evidence and Future Perspectives of the Best Supplements for Cardioprotection: Have We Reached the Final Chapter for Vitamins?

Cardiovascular disease (CVD), a broad-spectrum term comprising coronary artery disease, stroke, hypertension, and heart failure, presents as one of the most significant strains on global healthcare systems. Coronary artery disease, caused by atherosclerosis, has various modifiable risk factors such as dietary changes and exercise. Since these risk factors are found to be linked to oxidative stress and inflammations, the dietary supplementation with vitamins' role in treating and preventing the diseases has been of much debate. With various vitamins having anti-inflammatory and antioxidative properties, studies have explored their correlation with cardiovascular health. Therefore, this narrative review explores and evaluates the benefits and risks of all vitamin supplementations in patients with CVD and provides future recommendations.

Outlining recent updates on influenza therapeutics and vaccines: A comprehensive review.

Influenza virus has presented a considerable healthcare challenge during the past years, particularly in vulnerable groups with compromised immune systems. Therapeutics and vaccination have always been in research annals since the spread of influenza. Efforts have been going on to develop an antiviral therapeutic approach that could assist in better disease management and reduce the overall disease complexity, resistance development, and fatality rates. On the other hand, vaccination presents a chance for effective, long-term, cost-benefit, and preventive response against the morbidity and mortality associated with the influenza. However, the issues of resistance development, strain mutation, antigenic variability, and inability to cure wide-spectrum and large-scale strains of the virus by available vaccines remain there. The article gathers the updated data for the therapeutics and available influenza vaccines, their mechanism of action, shortcomings, and trials under clinical experimentation. A methodological approach has been adopted to identify the prospective therapeutics and available vaccines approved and within the clinical trials against the influenza virus. Review contains influenza therapeutics, including traditional and novel antiviral drugs and inhibitor therapies against influenza virus as well as research trials based on newer drug combinations and latest technologies such as nanotechnology and organic and plant-based natural products. Most recent development of influenza vaccine has been discussed including some updates on traditional vaccination protocols and discussion on next-generation and upgraded novel technologies. This review will help the readers to understand the righteous approach for dealing with influenza virus infection and for deducing futuristic approaches for novel therapeutic and vaccine trials against Influenza.

Potential diagnostic and drug target markers in glioblastoma.

Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known. Herein, we have investigated the gene and protein expression of GCSF, GCSFR, and STAT3 in 21 tissue biopsy samples and also in tumor associated normal tissue (TANT) samples derived from glioblastoma patients, which revealed significantly differential expression of these genes. To validate our findings, we performed a comprehensive integrated analysis of transcriptomic and proteomic profiling of respective genes by retrieving GBM RNA-sequence data from Genome Atlas Databases. GO and KEGG analysis revealed enrichment in disease-related pathways, such as JAK/STAT pathway activation, which were associated with GBM progression. We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.

Grain nutritional and antioxidant profiling of diverse lentil (Lens culinaris Medikus) genetic resources revealed genotypes with high nutritional value.

The lentil (Lens culinaris Medikus ssp. Culinaris) is a self-pollinating, diploid (2n = 2X = 14) crop with a genome size of 4 Gbp. The present study was conducted to provide a database for the evaluation of lentil antioxidant capacity, nutritional quality, and biochemical attributes. For these purposes, lentil germplasm, including 100 exotic and local genotypes from different agro-climatic zones of Pakistan, was collected. Significant variation (p < 0.05) was found among the genotypes under investigation using the Tukey HSD test. Ascorbate peroxidase was highest in ALTINOPARK (2,465 Units/g s. wt.), catalase in LPP 12110 (5,595 Units/g s. wt.), superoxide dismutase in LPP 12105 (296.75 Units/g s. wt.), and peroxidase in NIAB Masoor 2002 (3,170 Units/g s. wt.). Furthermore, NLM 15016 had a maximum total antioxidant capacity of 15.763 mg/g s. wt. The maximum values of total soluble sugars (83.93 mg/g. s. wt.) and non-reducing sugars (74.79 mg/g. s. wt.) were noticed in NLM 15015. The highest reducing sugars were detected in ILL 8006 (45.68 mg/g. s. wt.) ascorbic acid in LPP 12182 (706 µg/g s. wt.), total phenolic content in NLI 17003 (54,600 µM/g s. wt.), and tannins in NLI 17057 (24,563 µM/g s. wt.). The highest chlorophyll a (236.12 µg/g s. wt.), chlorophyll b (317 µg/g s. wt.), total chlorophyll (552.58 µg/g s. wt.), and lycopene (10.881 µg/g s. wt.) were found in NLH 12097. Maximum total carotenoids were revealed in the local approved variety Markaz 2009 (17.89 µg/g s. wt.). Principal component analysis (PCA), correlation analysis (Pearson's test), and agglomerative hierarchical clustering (AHC) were performed to detect the extent of variation in genotypes. In cluster analysis, all genotypes were categorized into three clusters. Cluster II genotypes showed remarkable divergence with cluster III. According to PCA, the contribution of PC-I regarding tested nutritional parameters toward variability was the highest (39.75%) and indicated positive factor loading for the tested nutritional and biochemical parameters. In conclusion, genotype X 2011S 33-34-32 can be used by the food industry in making pasta, multigrain bread, and snacking foods due to its high protein content for meat alternative seekers. Identified genotypes with high nutritional attributes can be utilized to improve quality parameters in the respective lentil breeding lines.

Endoscopic ultrasound-guided gastroenterostomy versus enteral stenting for gastric outlet obstruction: a systematic review and meta-analysis.

Background: The symptoms of gastric outlet obstruction have traditionally been managed surgically or endoscopically. Enteral stenting (ES) is a less invasive endoscopic treatment strategy for this condition. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has recently become a potential alternative technique. Objectives: We conducted a systematic review and meta-analysis of the effectiveness and safety profile of EUS-GE compared with ES. Design: Meta-analysis and systematic review. Data sources and methods: We searched multiple databases from inception to August 2023 to identify studies that reported the effectiveness and safety of EUS-GE compared with ES. The outcomes of technical success, clinical success, and adverse events (AEs) were evaluated. Pooled proportions were calculated using both fixed and random effects models. Results: We included 13 studies with 1762 patients in our final analysis. The pooled rates of technical success for EUS-GE were 95.59% [95% confidence interval (CI), 94.01-97.44, I 2 = 32] and 97.96% (95% CI, 96.06-99.25, I 2 = 63) for ES. The pooled rate of clinical success for EUS-GE was 93.62% (95% CI, 90.76-95.98, I 2 = 54) while for ES it was lower at 85.57% (95% CI, 79.63-90.63, I 2 = 81). The pooled odds ratio (OR) of clinical success was higher for EUS-GE compared to ES at 2.71 (95% CI, 1.87-3.93). The pooled OR of clinical success for EUS-GE was higher compared to ES at 2.72 (95% CI, 1.86-3.97, I 2 = 0). The pooled rates of re-intervention for EUS-GE were lower at 3.77% (95% CI, 1.77-6.46, I 2 = 44) compared with ES, which was 25.13% (95% CI, 18.96-31.85, I 2 = 69). The pooled OR of the rate of re-intervention in the ES group was higher at 7.96 (95% CI, 4.41-14.38, I 2 = 13). Overall, the pooled rate for AEs for EUS-GE was 8.97% (95% CI, 6.88-11.30, I 2 = 15), whereas that for ES was 19.63% (95% CI, 11.75-28.94, I 2 = 89). Conclusion: EUS-GE and ES are comparable in terms of their technical effectiveness. However, EUS-GE has demonstrated improved clinical effectiveness, a lower need for re-intervention, and a better safety profile compared to ES for palliation of gastric outlet obstruction.

Morphometric analysis of chronicity on kidney biopsy: a useful prognostic exercise.

Chronic changes on kidney biopsy specimens include increasing amounts of arteriosclerosis, glomerulosclerosis, interstitial fibrosis and tubular atrophy, enlarged nephron size, and reduced nephron number. These chronic changes are difficult to accurately assess by visual inspection but are reasonably quantified using morphometry. This review describes the various patient populations that have undergone morphometric analysis of kidney biopsies. The common approaches to morphometric analysis are described. The chronic kidney disease outcomes associated with various chronic changes by morphometry are also summarized. Morphometry enriches the characterization of chronicity on a kidney biopsy and this can supplement the pathologist's diagnosis. Artificial intelligence image processing tools are needed to automate the annotations needed for practical morphometric analysis of kidney biopsy specimens in routine clinical care.

Feasibility of replacing fish oil with sunflower oil on the growth, body composition, fatty acid profile, antioxidant activity, stress response, and blood biomarkers of Labeo rohita.

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.

Acute Graft versus Host Disease in Beta Thalassemia Patients Following Allogeneic Haematopoietic Stem Cell Transplantation.

OBJECTIVE: To analyse the frequency, risk factors, and clinical symptoms of acute graft-versus-host disease (aGvHD) in patients with beta-thalassemia major after allogeneic haematopoietic stem cell transplantation (HSCT). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from January 2017 to December 2021. METHODOLOGY: Data were obtained from patients diagnosed with bone and tissue malignancies (BTM) who had undergone haematopoietic stem cell transplantation (HSCT) and experienced aGVHD. Patients who experienced initial graft failure and individuals who underwent subsequent bone marrow transplantation were excluded. RESULTS: Total of 117 patients diagnosed with BTM underwent fully matched HSCT, including 76 (65%) males, and 41 (35%) females. The median age of the patients undergoing transplantation was 7.34±7.32 years and the donors' median age was 7.6±9.85 years. Among the donors, 53 (45.3%) were males and 64 (54.7%) were females. Gender disparity was observed in 46 (39.3%) instances as a female donor matched with a male recipient. A total of 106 individuals underwent bone marrow harvest (BMH); with 5 (4.3%) patients receiving peripheral blood stem cells (PBSC) and 6 (5.2%) patients receiving both BMH and PBSC. Acute GvHD was observed in 50 (42.7%) patients, including 30 (60%) males and 20 (40%) females. Grade I GvHD occurred in 32 (27.3%) individuals, Grade II GvHD in 16 (13.7%) patients, and Grade III GvHD in one (0.8%) patient. It had no statistically significant association with recipient/donor age, gender disparity, the source of the graft source, the dose of stem cells, or the presence of thymoglobulin (TG). CONCLUSION: Acute GvHD was observed in high frequency in Beta-thalassemia patients receiving morrow harvesting proportional to their gender distribution. Associated factors were GvHD prophylaxis measure, mucositis and, CMV reactivation. KEY WORDS: Beta thalassemia major patients, Acute graft versus host disease, Allogeneic haematopoietic stem cell.

Engagement of private health sector in communicable disease and immunization programmes in Pakistan.

Background: In Pakistan, where the burden of communicable diseases remains high, the private sector accounts for 62% of health care provision. Aim: To describe the role of the private sector in communicable disease management in Pakistan and inform a more effective engagement towards achieving Universal Health Coverage. Methods: We searched the literature and available documents on policies, regulations and experiences in private health sector engagement in Pakistan. We interviewed policy level experts regarding the formulation of national health policies and plans and a sample of private providers using a structured questionnaire to assess their awareness of and engagement in communicable disease programmes. Results: Published reports described initiatives to engage the private sector in improving coverage for a package of care and programme-specific initiatives. Pakistan did not have a national policy for structural engagement, and regulations were limited. Policy level experts interviewed perceived the private sector as market-driven and poorly regulated. Thirty-nine percent of private sector providers interviewed were aware or had been trained in procedures or guidelines, and 23% of them had had their performance monitored by government. Conclusion: We recommend that the Ministry of Health provide overall vision for the operations of the public and private health sectors so that both sectors can complement each other towards the achievement of Universal Health Coverage, including for communicable diseases.

Efficacy and Safety of Lotilaner Ophthalmic Solution 0.25% for the Treatment of Demodex Blepharitis: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Demodex blepharitis, often overlooked in ocular surface disease, involves Demodex mites, prevalent ectoparasites on human skin. Current treatments may not effectively eliminate these mites, prompting a need for targeted therapies. Lotilaner, an antiparasitic agent, shows promise. This systematic review and meta-analysis assesses 0.25% lotilaner ophthalmic solution's efficacy in reducing Demodex mite populations and its impact on ocular surface inflammation in Demodex blepharitis patients. METHODS: A comprehensive literature search was performed in the PubMed and Cochrane Library databases from inception until February 2024 to identify relevant trials investigating the use of lotilaner in patients with Demodex blepharitis. The included studies were assessed for quality, and a meta-analysis was conducted to determine the overall treatment effects of lotilaner. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for binary variables. All statistical analyses were performed using the R Statistical Software. RESULTS: Five studies met the inclusion criteria and were included in this systematic review and meta-analysis. Lotilaner demonstrated significant efficacy in Collarette Cure [OR = 6.64; 95 % CI 3.78 to 11.04; p < 0.00001, I2 = 62 %] %], clinically meaningful collarette reduction [OR = 6.21; 95 % CI 3.67 to 10.49; p < 0.00001, I2 = 90 %], and achieving at least 1-grade collarette improvement [OR = 5.12; 95 % CI (2.96 to 8.88); p < 0.00001, I2 = 90 %] compared to the placebo group. The treatment also resulted in mite eradication [OR = 6.18; 95 % CI 4.67 to 6.18; p < 0.00001, I2 = 34 %], reduction in mite density [OR = 9.37; 95 % CI 5.36 to 16.36; p < 0.00001, I2 = 84 %], and erythema cure [OR = 2.29; 95 % CI 2.24 to 3.39; p < 0.00001, I2 = 5 %] and composite cure [OR = 7.05; 95 % CI 3.66 13. 61; p < 0.00001, I2 = 11 %]. The study suggests that lotilaner is a promising therapeutic option for collarette and associated symptoms, but the high heterogeneity in some outcomes and limited long-term data warrant further research to confirm its effectiveness and safety. CONCLUSION: This systematic review and meta-analysis provides robust evidence supporting the efficacy of 0.25% lotilaner ophthalmic solution in treating Demodex blepharitis. Approval of this targeted therapy represents a significant milestone in ophthalmology and offers a promising treatment option for patients with Demodex blepharitis. Eye care professionals should consider the potential benefits of lotilaner in managing and alleviating the symptoms associated with Demodex infestations on the eyelids. Further research and long-term follow-up studies are warranted to assess the safety and effectiveness of lotilaner in treating Demodex blepharitis.

Shaping sustainable pathways: Enhancing mechanical properties of biocomposite through tannic acid treatment of flax fabrics.

Biocomposites developed using natural fibers serve as a sustainable alternative to synthetic composite materials. However, narrowing the performance gap between synthetic composites and biocomposites requires serious efforts. A promising approach is the modification of natural fibers using various chemical treatments. This paper investigates the potential of tannic acid (TA) treatment as a sustainable approach to enhance mechanical performance and reduce moisture absorption of flax fabric-reinforced biocomposites. The methodology involves the treatment of flax woven fabric with tannic acid, a naturally occurring polyphenolic compound, followed by the fabrication of biocomposite using a green epoxy matrix. The variables studied during treatment are TA concentration and processing time. Characterization of untreated and treated flax fabric and its composites was done using various analytical techniques such as FTIR spectroscopy, moisture absorption and mechanical testing (tensile strength, flexural strength, and impact resistance). FTIR spectroscopy of TA-treated flax confirmed attachment of aromatic rings and carbon double bond formation, thus serving for properties enhancement. The mechanical characterization of composites showed that properties are enhanced up to an optimum limit of concentration and processing time i.e., 1 % concentration and 30 min of processing. Moisture absorption of the TA-treated composite also reduced significantly as compared to untreated composites. These findings contribute towards the advancement in sustainable biocomposites and pave the way for their utilization in various applications.

Prognostic role of suPAR in acute pancreatitis: A protocol for systematic review.

BACKGROUND: Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR's prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers. METHODS: A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR's relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR's association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628). RESULTS: Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility. CONCLUSION: suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR's role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.

Green synthesis of pectin-functionalized silver nanocomposites using Carpesium nepalense and evaluation its bactericidal kinetics and hepatoprotective mechanisms.

The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50-110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC50 of 223.7 µg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents.

Effectiveness of mobile health intervention for non alcoholic fatty liver disease- A meta analysis of randomized controlled trials.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Lifestyle modification is the mainstay of management, however, most patients find it difficult to significantly modify their lifestyle. Mobile health is an innovative healthcare system that has an established role in treating chronic diseases like asthma, cancer and cardiovascular disease. Hence, we conducted an updated meta analysis to evaluate the efficacy of mobile health intervention (mHI) for NAFLD. METHODS: Literature search of five electronic databases was performed from the inception of the paper till 15th May, 2024. Studies were included if they met the inclusion criteria; Randomized controlled trials evaluating use of mHI along with standard care in comparison to standard care only for patients with NAFLD over 18 years. Primary outcomes of interest included changes in weight, body mass index (BMI), and liver markers from baseline to post intervention. Risk of bias was evaluated using the Cochrane bias assessment tool while the Mantel-Haenszel Random-effects model on Review manager was used to pool outcomes. RESULTS: Outcomes were pooled from 7 RCTs comprising a total of 621 participants. There was a significant decrease in weight (P < 0.0001), aspartate aminotransferase (AST) (P = 0.002) and alkaline aminotransferase (ALT) (P = 0.0009) from baseline to follow-up in the intervention group as compared to the control group. However, the reduction in BMI was found to be non-significant (P = 0.64). CONCLUSION: Our meta analysis reports that mHI plays an important role in significantly reducing weight and liver markers in patients with NAFLD. Considering that the improvement of these factors plays a key role in the management of the disease, mHI could be the key towards paving better outcomes for patients with NAFLD.