Germline Variants in Sporadic Pituitary Adenomas.

Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.

Synchronizing positive effect of vitamin C and chromium on hyper lipidemia, hyperglycemia, liver enzymes and BMI of diabetes mellitus type 2 patients.

This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.

Effect of Salvia hispanica (Chia seeds) and Foeniculum vulgare (Fennel seeds) against weight-loss and lipid profile in obese human subjects.

Increased levels of bad cholesterol in the body result in increasing blood pressure and weight gain. The rate of mortality in people, especially who are obese, is increasing due to absence of organic sources of fiber in their diets. Chia and fennel seeds are rich sources of fiber. The objective of this study was to evaluate the combined effect of Salvia hispanica (Chia seeds) and Foeniculum vulgare (Fennel seeds) against weight-loss and lipid profile in obese human subjects. The research was conducted on obese people aged 25 to 40 years at the Jinnah Hospital Lahore. The study design was randomized control trial (RCT). The sample size was calculated and was divided in-to two groups. With the duration of study being 3 months, pre-testing of all the participants was done. Group 1 was control group, given placebo treatment and Group 2 was an intervention group and given chia and fennel seeds. Post-testing was done and data were analyzed. Results showed that chia and fennel seeds have significant effect (p <0.05) on BMI and lipid profile hence, both are beneficial for lowering body weight and improving LDL, HDL, serum triglycerides and total cholesterol levels.

Ethanolic extract of Euphorbia royleana Boiss. reduces metastasis of breast cancer cells and inhibits tumor progression in vivo.

Metastasis is the most devastating attribute of breast cancer (BC) that leads to high mortality. It is a complex process of tumor cell migration, invasion, and angiogenesis. In this study, we evaluated the effect of ERA on BC metastasis and BC progression in vivo. The transwell invasion/migration and wound healing assays showed that ERA treatment significantly reduced the invasion and migration of BC cell lines. The expression of mesenchymal (E-cadherin and N-cadherin), matrix metalloproteinases (MMP2, MMP9), and stemness markers (Oct3) were down-regulated by ERA. Furthermore, ERA down-regulated angiogenic chemokines (CXCL1/2/3, CXCL5, and CXCL12) expression in the highly metastatic MDA-MB-231 cell line. The clonogenic survival of BC cells was also reduced by ERA treatment. Strikingly, ERA prevented DMBA-induced tumor growth in Swiss albino mice as depicted by a high animal survival rate (84%) in the ERA group and histopathological analysis. Conclusively, this study revealed that ERA possesses anti-metastatic potential and also reduces the growth of BC in vivo. Moreover, the GC-MS data revealed the presence of biologically active compounds (Lupeol, Phytol, phytosterol) and some rare (9, 19-Cyclolanost) phyto metabolites in ERA extract. However, further studies are suggestive to identify and isolate the therapeutic agents from ERA to combat BC and metastasis.

Nitrogen-Doped Graphene-Supported Nickel Nanoparticles Reveal Low Dehydrogenation Temperature and Long Cyclic Life of Magnesium Hydrides.

Magnesium hydride (MgH2) is a promising hydrogen storage candidate due to its large capacity; however, high dehydrogenation temperature and slow kinetic rates are the main bottlenecks. Herein, we proposed a strategy for designing nitrogen-doped graphene-supported Ni nanoparticles (NPs) (Ni@NC) to tackle these problems. The results showed that the MgH2 + 15 wt % Ni@NC nanocomposite reduced the on-set dehydrogenation temperature to 195 °C, which was 175 °C lower than pristine MgH2. In addition, MgH2 + 15 wt % Ni@NC achieved 1.7 and 6.5 wt % desorption capacities at 225 and 300 °C, respectively, while absorbing 5.5 wt % hydrogen at 100 °C. The MgH2 + 15 wt % Ni@NC nanocomposite showed high cyclic stability, achieving 98.0% capacity retention after 100 cycles at 270 °C with negligible loss in capacity. This remarkable hydrogen storage performance can be attributed to the homogeneous distribution of Ni NPs on N-doped graphene layers, in situ formed Mg2NiH2 NPs, and multiphasic regions, promoting the nucleation and growth process during hydrogenation/dehydrogenation, which stabilized and improved the cyclic stability. This strategy paves the way to developing high-performance MgH2 for large-scale applications.

Optimizing lung cancer classification through hyperparameter tuning.

Artificial intelligence is steadily permeating various sectors, including healthcare. This research specifically addresses lung cancer, the world's deadliest disease with the highest mortality rate. Two primary factors contribute to its onset: genetic predisposition and environmental factors, such as smoking and exposure to pollutants. Recognizing the need for more effective diagnosis techniques, our study embarked on devising a machine learning strategy tailored to boost precision in lung cancer detection. Our aim was to devise a diagnostic method that is both less invasive and cost-effective. To this end, we proposed four methods, benchmarking them against prevalent techniques using a universally recognized dataset from Kaggle. Among our methods, one emerged as particularly promising, outperforming the competition in accuracy, precision and sensitivity. This method utilized hyperparameter tuning, focusing on the Gamma and C parameters, which were set at a value of 10. These parameters influence kernel width and regularization strength, respectively. As a result, we achieved an accuracy of 99.16%, a precision of 98% and a sensitivity rate of 100%. In conclusion, our enhanced prediction mechanism has proven to surpass traditional and contemporary strategies in lung cancer detection.

Evaluating the Efficiency of Black Soldier Fly (Hermetia illucens) Larvae in Converting Mackerel Head Waste into Valuable Resources.

The seafood processing industry generates significant waste, including mackerel heads (MH), constituting 20-32% of total waste. This study explored the potential of utilizing MH as a feed source for black soldier fly larvae (BSF larvae). BSF larvae are known for their ability to efficiently convert organic materials into nutrient-rich biomass. Five concentrations of MH (0, 10, 20, 30, 40, and 50% in chicken feed) were fed to BSF larvae for eight days. After harvesting, their growth, MH conversion efficiency, nutritional content, and heavy metals reduction potential were measured. BSF larvae showed optimal growth when fed with a feed containing 20% MH, resulting in a 14.36-fold increase in weight compared to the control group, as determined by the Fisher's Least Significant Difference Test. BSF larvae maintained a survival rate of 99.33%. With the lowest feed conversion ratio (FCR) of 2.09 at 20% MH, feed efficiency was improved by up to 65.15%, and feed reduction up to 73.53%. MH enhanced lipid and protein content in BSF larvae. Furthermore, BSF larvae in this study showed higher polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as other amino acids which are required for breeding animals. The current study highlights the potential of MH as a feed source for BSF larvae, improving nutritional biomass. It also suggests BSF larvae as an eco-friendly option for handling seafood processing waste and as an alternative feed source for animals.

Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan. METHODS: We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors. FINDINGS: Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93). CONCLUSION: We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community-acquired pneumonia.

Secondary metabolic profiling, antioxidant potential, enzyme inhibitory activities and in silico and ADME studies: a multifunctional approach to reveal medicinal and industrial potential of Tanacetum falconeri.

Tanacetum falconeri is a significant flowering plant that possesses cytotoxic, insecticidal, antibacterial, and phytotoxic properties. Its chemodiversity and bioactivities, however, have not been thoroughly investigated. In this work, several extracts from various parts of T. falconeri were assessed for their chemical profile, antioxidant activity, and potential for enzyme inhibition. The total phenolic contents of T. falconeri varied from 40.28 ± 0.47 mg GAE/g to 11.92 ± 0.22 mg GAE/g in various extracts, while flavonoid contents were found highest in TFFM (36.79 ± 0.36 mg QE/g extract) and lowest (11.08 ± 0.22 mg QE/g extract) in TFSC (chloroform extract of stem) in similar pattern as found in total phenolic contents. Highest DPPH inhibition was observed for TFFC (49.58 ± 0.11 mg TE/g extract) and TFSM (46.33 ± 0.10 mg TE/g extract), whereas, TFSM was also potentially active against (98.95 ± 0.57 mg TE/g) ABTS radical. In addition, TFSM was also most active in metal reducing assays: CUPRAC (151.76 ± 1.59 mg TE/g extract) and FRAP (101.30 ± 0.32 mg TE/g extract). In phosphomolybdenum assay, the highest activity was found for TFFE (1.71 ± 0.03 mg TE/g extract), TFSM (1.64 ± 0.035 mg TE/g extract), TFSH (1.60 ± 0.033 mg TE/g extract) and TFFH (1.58 ± 0.08 mg TE/g extract), while highest metal chelating activity was recorded for TFSH (25.93 ± 0.79 mg EDTAE/g extract), TFSE (22.90 ± 1.12 mg EDTAE/g extract) and TFSC (19.31 ± 0.50 mg EDTAE/g extract). In biological screening, all extracts had stronger inhibitory capacity against AChE while in case of BChE the chloroform extract of flower (TFFC) and stem (TFSC) showed the highest activities with inhibitory values of 2.57 ± 0.24 and 2.10 ± 0.18 respectively. Similarly, TFFC and TFSC had stronger inhibitory capacity (1.09 ± 0.015 and 1.08 ± 0.002 mmol ACAE/g extract) against α-Amylase and (0.50 ± 0.02 and 0.55 ± 0.02 mmol ACAE/g extract) α-Glucosidase. UHPLC-MS study of methanolic extract revealed the presence of 133 components including sterols, triterpenes, flavonoids, alkaloids, and coumarins. The total phenolic contents were substantially linked with all antioxidant assays in multivariate analysis. These findings were validated by docking investigations, which revealed that the selected compounds exhibited high binding free energy with the enzymes tested. Finally, it was found that T. falconeri is a viable industrial crop with potential use in the production of functional goods and nutraceuticals.

Almond shell-derived biochar decreased toxic metals bioavailability and uptake by tomato and enhanced the antioxidant system and microbial community.

The effectiveness of almond shell-derived biochar (ASB) in immobilizing soil heavy metals (HMs) and its impact on soil microbial activity and diversity have not been sufficiently studied. Hence, a pot study was carried out to investigate the effectiveness of ASB addition at 2, 4, and 6 % (w/w) on soil biochemical characteristics and the bioavailability of Cd, Cu, Pb, and Zn to tomato (Solanum lycopersicum L.) plants, as compared to the control (contaminated soil without ASB addition). The addition of ASB promoted plant growth (up to two-fold) and restored the damage to the ultrastructure of chloroplast organelles. In addition, ASB mitigated the adverse effects of HMs toxicity by decreasing oxidative damage, regulating the antioxidant system, improving soil physicochemical properties, and enhancing enzymatic activities. At the phylum level, ASB addition enhanced the relative abundance of Actinobacteriota, Acidobacteriota, and Firmicutes while decreasing the relative abundance of Proteobacteria and Bacteroidota. Furthermore, ASB application increased the relative abundance of several fungal taxa (Ascomycota and Mortierellomycota) while reducing the relative abundance of Basidiomycota in the soil. The ASB-induced improvement in soil properties, microbial community, and diversity led to a significant decrease in the DTPA-extractable HMs down to 41.0 %, 51.0 %, 52.0 %, and 35.0 % for Cd, Cu, Pb, and Zn, respectively, as compared to the control. The highest doses of ASB (ASB6) significantly reduced the metals content by 26.0 % for Cd, 78.0 % for Cu, 38.0 % for Pb, and 20.0 % for Zn in the roots, and 72.0 % for Cd, 67.0 % for Cu, 46.0 % for Pb, and 35.0 % for Zn in the shoots, as compared to the control. The structural equation model predicts that soil pH and organic matter are driving factors in reducing the availability and uptake of HMs. ASB could be used as a sustainable trial for remediation of HMs polluted soils and reducing metal content in edible plants.

Potential role of Citrus bergamia flower essential oil against oral pathogens.

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.

Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder.

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.

Efficacy and Nuances of Precision Molecular Engineering for Hodgkin's Disease to a Gene Therapeutic Approach.

Gene therapy is a particularly useful treatment for nervous system genetic diseases, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease (HD). Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL. HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed disease. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2,5)-derived ALCL genetic treatment for Hodgkin's disease.

Autosomal recessive spinocerebellar ataxia type 4 due to a novel homozygous mutation in the VPS13D gene in a Saudi family.

Vacuolar protein sorting 13 homolog D (VPS13D) gene encodes a protein involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. This study reports a novel homozygous mutation (c.12494T>C p.Ile4165Thr) in the VPS13D gene in a Saudi female diagnosed with autosomal recessive spinocerebellar ataxia type 4 (SCAR4). The patient's clinical presentation, including progressive weakness, ataxia, and numbness, aligns with SCAR4 characteristics. The comprehensive evaluation, comprising neurological examination, brain MRI, and genetic testing, revealed distinctive features consistent with autosomal recessive inheritance. The genetic mutation spectrum enrichment emphasizes the intricate interplay of genetic factors in SCAR4. Although no specific treatment exists, rehabilitation and supportive therapy remain central. The identified mutation contributes valuable insights for clinical management and genetic counseling, urging the ongoing collection of VPS13D gene mutation data to explore genotype-phenotype correlations in spinocerebellar ataxias. This study underscores the importance of multidisciplinary care and lays the foundation for future research directions in understanding and treating SCAR4.

Nutritional Composition and Safety Aspects of Deep-Sea Whelks (Buccinum tenuissimum Kuroda).

The deep-sea whelk Buccinum tenuissimum Kuroda is highly sought-after as food in East Asian countries, notably, Korea and Japan. However, it lacks official recognition as a food product in Korea. This study aimed to assess its nutritional composition and safety for the potential development of seafood products. The nutritional analysis revealed high protein (13.54-20.47 g/100 g whelk), fat (0.85-8.59 g/100 g whelk), carbohydrate (1.55-12.81 g/100 g whelk), and dietary fiber (1.25-1.95 g/100 g whelk) contents in both muscle and gut samples, with energy contents ranging from 339.11 ± 1.64 to 692.00 ± 3.21 kJ/100 g. Key minerals, including iron, potassium, calcium, and sodium, and essential fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, omega-3, and omega-6 fatty acids, were abundant, making it a potential supplementary food. Notably, heavy metal levels met the Korean standards for seafood safety. No trans fats, radioactivity concerning the radioactive isotopes 134Cs/137Cs and 131I, or pathogenic bacteria were detected. This confirms the safety and nutritional value of deep-sea whelks, suggesting their potential for developing seafood products rich in beneficial components, which could enhance nutrition and food security while contributing to economic growth.

Efficacy and safety of laparoscopic Heller's myotomy versus pneumatic dilatation for achalasia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Achalasia has several treatment modalities. We aim to compare the efficacy and safety of laparoscopic Heller myotomy (LHM) with those of pneumatic dilatation (PD) in adult patients suffering from achalasia. METHODS: We searched Cochrane CENTRAL, PubMed, Web of Science, SCOPUS and Embase for related clinical trials about patients suffering from achalasia. The quality appraisal and assessment of risk of bias were conducted with GRADE and Cochrane's risk of bias tool, respectively. Homogeneous and heterogeneous data was analyzed under fixed and random-effects models, respectively. RESULTS: The pooled analysis of 10 studies showed that PD was associated with a higher rate of remission at three months, one year, three years and five years (RR = 1.25 [1.09, 1.42] (p = 0.001); RR = 1.13 [1.05, 1.20] (p = 0.0004); RR = 1.48 [1.19, 1.82] (p = 0.0003); RR = 1.49 [1.18, 1.89] (p = 0.001)), respectively. LHM was associated with lower number of cases suffering from adverse events, dysphagia and relapses (RR = 0.50 [0.25, 0.98] (p = 0.04); RR = 0.33 [0.16, 0.71] (p = 0.004); RR = 0.38 [0.15, 0.97] (p = 0.04)), respectively. There is no significant difference between both groups regarding the lower esophageal pressure, perforations, remission rate at two years, Eckardt score after one year and reflux. CONCLUSION: PD had higher remission rates than LHM at three months, one year and three years, but not at two years or five years. More research is needed to determine whether PD has a significant advantage over LHM in terms of long-term remission rates.

Potential of melatonin and Trichoderma harzianum inoculation in ameliorating salt toxicity in watermelon: Insights into antioxidant system, leaf ultrastructure, and gene regulation.

Melatonin (MT) is an extensively studied biomolecule with dual functions, serving as an antioxidant and a signaling molecule. Trichoderma Harzianum (TH) is widely recognized for its effectiveness as a biocontrol agent against many plant pathogens. However, the interplay between seed priming and MT (150 µm) in response to NaCl (100 mM) and its interaction with TH have rarely been investigated. This study aimed to evaluate the potential of MT and TH, alone and in combination, to mitigate salt stress (SS) in watermelon plants. The findings of this study revealed a significant decline in the morphological, physiological, and biochemical indices of watermelon seedlings exposed to SS. However, MT and TH treatments reduced the negative impact of salt stress. The combined application of MT and TH exerted a remarkable positive effect by increasing the growth, photosynthetic and gas exchange parameters, chlorophyll fluorescence indices, and ion balance (decreasing Na+ and enhancing K+). MT and TH effectively alleviated oxidative injury by inhibiting hydrogen peroxide formation in saline and non-saline environments, as established by reduced lipid peroxidation and electrolyte leakage. Moreover, oxidative injury induced by SS on the cells was significantly mitigated by regulation of the antioxidant system, AsA-GSH-related enzymes, the glyoxalase system, augmentation of osmolytes, and activation of several genes involved in the defense system. Additionally, the reduction in oxidative damage was examined by chloroplast integrity via transmission electron microscopy (TEM). Overall, the results of this study provide a promising contribution of MT and TH in safeguarding the watermelon crop from oxidative damage induced by salt stress.

Obesity and Risk of Hypertension in Preadolescent Urban School Children: Insights from a Developing Country.

Background: Childhood obesity and hypertension are growing concerns globally, especially in developing countries. This study investigated the association between overall and central obesity at baseline, and prehypertension or hypertension at follow-up among preadolescent school children in Karachi, Pakistan. Methods: This is a sub study with cohort design embedded within a feasibility trial on School Health Education Program in Pakistan (SHEPP) in preadolescent aged 6-11 years, attending two private schools, were enrolled from 2017 to 2019. Hypertension or prehypertension at follow-up were the outcomes and obesity or central obesity at baseline were the exposure variables. Hypertension was defined as systolic blood pressure and/or diastolic blood pressure ≥ 95th percentile for age, sex, and height. Obesity was defined as body mass index for-age and sex ≥ 95th percentile, whereas central obesity was determined by waist circumference measurements ≥ 85th percentile of age, sex, and height specific cut-offs. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to identify risk factors for hypertension and prehypertension. Results: Analysis was conducted for 908 participants, evenly distributed with 454 boys and 454 girls. Hypertension was observed in 19.8% of the preadolescents, with rates of 18.5% in boys and 21.0% in girls. Prehypertension was found in 16.8% of preadolescents, with 18% among boys and 16% among girls. Additionally, 12.8% of preadolescents were classified as obese and 29.8% had central obesity. Obesity at baseline was associated with hypertension (OR 8.7, 95% CI 3.5, 20.4) in the final model after adjusting for age, gender, physical activity, sedentary behavior, fruits, vegetable intake and hypertension at baseline. Central obesity at baseline also yielded high odds, with prehypertension (OR 1.9, 95% CI 1.4, 2.8) and hypertension (OR 2.7, 95% CI 1.9, 3.9) in the final model. Conclusion: This study highlights a concerning prevalence of hypertension and prehypertension among preadolescent school-going children. Obesity and central obesity at baseline emerged as significant predictive factors for hypertension within this cohort. The findings emphasize the urgency of implementing comprehensive school health education programs aimed at early detection and effective management of hypertension during childhood and adolescence in school settings.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study.

BACKGROUND: Households are considered ideal settings for studying the transmission dynamics of an infectious disease. METHODS: A prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. RESULTS: We enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0-18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4-45.5) and fatigue (aOR, 9.3; 95% CI, 3.8-22.7) were associated with SARS-CoV-2 transmission. CONCLUSIONS: We observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

Efficacy and safety of terlipressin and albumin vs. noradrenaline and albumin in adult patients with hepatorenal syndrome: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients. MATERIALS AND METHODS: Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min). RESULTS: Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05). CONCLUSIONS: Noradrenaline is a safe alternative medical therapy for HRS.