Cold atmospheric plasma enhances morphological and biochemical attributes of tomato seedlings.

Cold atmospheric plasma (CAP) is a physical technology with notable effects on living organisms. In the present study, tomato seeds (Solanum lycopersicum var. Bassimo Mill.) were exposed to CAP for various time intervals, ranging from 1 to 5 min, in both continuous and intermittent periods, and were compared with a control group that received no CAP treatment. Seedlings grown from treated seeds exhibited improvements in levels of growth traits, photosynthetic pigments, and metabolite contents when compared to the control group. Seedlings from seeds treated with S04 displayed significant increases in shoot and root lengths, by 32.45% and 20.60% respectively, compared to the control group. Moreover, seedlings from seeds treated with S01 showed a 101.90% increase in total protein, whereas those treated with S02 experienced a 119.52% increase in carbohydrate content. These findings highlight the substantial improvements in growth characteristics, photosynthetic pigments, and metabolite levels in seedlings from treated seeds relative to controls. Total antioxidant capacity was boosted by CAP exposure. The activities of enzymes including superoxide dismutase, catalase, and peroxidases were stimulated by S02 and exceeded control treatment by (177.48%, 137.41%, and 103.32%), respectively. Additionally, exposure to S04 increased the levels of non-enzymatic antioxidants like flavonoids, phenolics, saponins, and tannins over the control group (38.08%, 30.10%, 117.19%, and 94.44%), respectively. Our results indicate that CAP-seed priming is an innovative and cost-effective approach to enhance the growth, bioactive components, and yield of tomato seedlings.

Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.

In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise genetic diagnoses and therapeutic discoveries, respectively. We previously discovered that variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined that an intergenic splice product of N OS1AP / Nos1ap and neighboring C1orf226/Gm7694 , which precludes NOS1 binding, is the predominant isoform in mammalian kidney transcriptional and proteomic data. Gm7694 -/- mice, whose allele exclusively disrupts the intergenic product, developed NS phenotypes. In two human NS subjects, we identified causative NOS1AP splice variants, including one predicted to abrogate intergenic splicing but initially misclassified as benign based on the canonical transcript. Finally, by modifying genetic background, we generated a faithful mouse model of NOS1AP -associated NS, which responded to anti-proteinuric treatment. This study highlights the importance of intergenic splicing and a potential treatment avenue in a mendelian disorder.

Recessive variants in MYO1C as a potential novel cause of proteinuric kidney disease.

Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients <25 years of age. Through whole exome sequencing, identification of >65 monogenic causes has rendered insights into disease mechanisms of nephrotic syndrome. Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with ES in a worldwide cohort of 1649 pediatric patients with NS. Results: We identified homozygous missense variants in MYO1C in two unrelated children with nephrotic syndrome (c.292C>T, p.R98W; c.2273 A>T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1Cto be predominantly expressed in podocytes. We then performed structural modeling in molecular viewer PyMol using the super function aligning shared regions within both partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the Myosin Motor Domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants. Conclusion: We here identified recessive variants in MYO1C as a potential novel cause of nephrotic syndrome in children.

Unidirectional barbed sutures vs. interrupted intracorporeal knots in thoracoscopic repair of congenital diaphragmatic hernia in pediatrics.

Background: Intracorporeal suturing knots continue to be one of the most challenging and time-consuming steps in the thoracoscopic repair of congenital diaphragmatic hernia (CDH). Barbed unidirectional knotless sutures are designed to shorten surgical procedures by eliminating the need to tie knots. This work aimed to compare unidirectional barbed sutures and interrupted intracorporeal knots in the thoracoscopic repair of CDH in pediatrics regarding the time required to suture, operative time and complications. Methods: This retrospective study included 139 patients presented with Bochdalek CDH. Patients were classified into early (neonatal) and late presentations. The hernia defect was repaired by unidirectional Barbed sutures (V-LocTM and StratafixTM sutures) in group B or by Conventional interrupted intracorporeal knots in group C. Results: In both early and delayed presentations, the time required to suture (15 and 13 min in group B, 33 and 28 min in group C for neonatal and delayed presentation respectively) was significantly shorter in group B. Complications (visceral perforation, wound infection, and recurrence) insignificantly differed between group B and group C of early presentation. No patients suffered from major complications in both groups. Conclusions: Both unidirectional barbed sutures and intracorporeal knots were safe and effective. However, unidirectional barbed sutures are a time-saving choices for CDH thoracoscopic repair in early and late presentations.

Persistent Hiccups Shortly after Tramadol Intake: A Case Report and Literature Review.

BACKGROUND AND OBJECTIVE: Tramadol can inhibit serotonin and norepinephrine reuptake leading to stimulation of the central component of the hiccup reflex arc. We have found only two previous cases of tramadol-induced hiccups. Additionally, three pharmacovigilance studies have investigated the involvement of tramadol in cases who have developed hiccups as adverse effects. Herein, we have presented a case of a middle-aged male who has developed hiccups shortly after tramadol intake. CASE PRESENTATION: A 35-year-old male complaining of chronic pain in the right knee was treated with tramadol. The individual developed hiccups within 10 hours of the first tramadol dose. The patient tried to stop the hiccups with non-pharmacological measures, such as stopping the air inside the lungs and drinking cold fluids. The patient appeared to concentrate on avoiding hiccups, which he could avoid for some time. However, then, the hiccups would come all at a unique time. The hiccups occurred at a frequency of one hiccup/5-10 seconds, interrupting the patient's nutrition and sleep pattern. Eventually, tramadol was suspected of inducing hiccups, and baclofen was started. CONCLUSION: Tramadol as well as opioids should be considered as a cause of hiccups. We aim to improve awareness about the safety of such drugs among physicians and the proper management of associated risks.

Lauric acid attenuates hepato-metabolic complications and molecular alterations in high-fat diet-induced nonalcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin. Moreover, lauric acid significantly elevated the levels of SOD, GSH, catalase, and IL-10. Additionally, it lowered the hepatic levels of MDA, ROS, MPO, 4-HNE, interleukin (IL)-1ß, and tumor necrosis factor (TNF-α). Furthermore, lauric acid significantly up-regulated the hepatic expression of IRS1, AMPK, PI3K, and SIRT1 genes. In parallel, lauric acid could improve the histopathological picture of the liver and reduce the liver apoptosis via decreasing the expression of annexin V (Anx V). Finally, our data proposed that lauric acid could be an effective candidate for the NAFLD treatment.

Evaluation of Fasting and Probiotics in Reducing Postweaning Stress in Rabbits: Study of their Effects on Biochemical and Gene expression Patterns.

Postweaning stress in mammalian in vivo models leads to significant oxidative stress in the body as well as inducing hormonal disturbance. In this study, we assessed progressive alterations in reactive oxygen species (ROS), which at high levels can show oxidative stress, in addition to oxidative damage to the DNA structure of rabbits. Different groups of rabbits were fasted for 48 h per week for 3 weeks, fed a commercial diet with probiotics added (200 mg of Bacillus licheniformis and Bacillus subtilis), and fasted while being treated with probiotics. The results showed that weaning induced a significant elevation in oxidative stress markers, such as the ROS-related genes malate dehydrogenase 1 (MDH1) and flavin-containing monooxygenase 2 (FMO2), DNA damage, and hormonal disturbance. However, probiotic treatment resulted in significant decreases in the levels of malondialdehyde, cortisol, and triiodothyronine (T3); DNA damage; and apoptosis, as well as changes in the expression of ROS-related genes. On the other hand, supplementation with probiotics reduced these postweaning stress signs in fasted animal models by elevating the genes encoding catalase and superoxide dismutase as well as increasing glutathione peroxidase (GSH-Px), glutathione-s-transferase, alkaline phosphatase, glucose, and thyroxin (T4) levels. The results suggest that supplementation with probiotics accompanied by a fasting program could decrease oxidative stress, ROS genes, and genomic DNA damage and improve the hormonal status that is induced by postweaning stress in mammalian in vivo models.

Insight into prevalence, etiology, and modalities of pediatric chronic dialysis: a comprehensive nationwide analysis.

BACKGROUND: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. METHODS: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. RESULTS: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). CONCLUSIONS: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.

Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of kidney failure in children and adults under the age of 20 years. Previously, we were able to detect by exome sequencing (ES) a known monogenic cause of SRNS in 25-30% of affected families. However, ES falls short of detecting copy number variants (CNV). Therefore, we hypothesized that causal CNVs could be detected in a large SRNS cohort. METHODS: We performed genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on a cohort of 138 SRNS families, in whom we previously did not identify a genetic cause through ES. We evaluated ES and CNV data for variants in 60 known SRNS genes and in 13 genes in which variants are known to cause a phenocopy of SRNS. We applied previously published, predefined criteria for CNV evaluation. RESULTS: We detected a novel CNV in two genes in 2 out of 138 families (1.5%). The 9,673 bp homozygous deletion in PLCE1 and the 6,790 bp homozygous deletion in NPHS2 were confirmed across the breakpoints by PCR and Sanger sequencing. CONCLUSIONS: We confirmed that CNV analysis can identify the genetic cause in SRNS families that remained unsolved after ES. Though the rate of detected CNVs is minor, CNV analysis can be used when there are no other genetic causes identified. Causative CNVs are less common in SRNS than in other monogenic kidney diseases, such as congenital anomalies of the kidneys and urinary tract, where the detection rate was 5.3%. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy of Biofeedback in Paediatric Urology Patients: A Single Centre Experience.

AIM OF THE STUDY: Biofeedback assisted pelvic floor muscle training is an underutilised nonpharmacological treatment in paediatric urology. We reviewed all patients who underwent a course of treatment at our centre to evaluate its efficacy. METHODS: All patients who underwent a full cycle of biofeedback in the paediatric urology department from 2016 to 2023 were identified. Demographics and outcomes following treatment were accessed. RESULTS: 42 patients (28 female) were identified who underwent 8 one-hour sessions on a weekly basis constituted a completed cycle of treatment. Patients were identified for treatment as per local lower urinary tract symptom guidelines and following discussion in a fortnightly urology MDT and including diagnoses of overactive bladder, dysfunctional voiding, and giggle incontinence. Outcomes were measured as successful 29% (continence, normal postvoid residuals, clean intermittent catherization discontinued), partially successful 19% (reduced wetting, abnormal post void residuals, ongoing CIC) and unsuccessful 52% (no change for patient). Age at time of treatment affected likelihood of success: <9 years, 0% success; ≥9 years, 57% [p < 0.05]. There was no significant difference in success for 9-11 years [60%] vs >11 years [56%]. CONCLUSIONS: Biofeedback has shown success with improvement in symptoms in 48% of patients (complete or partial), which increases to 57% success in ≥9 years group. We would advocate its use in these difficult to manage patients with LUTS.

Awareness, Attitudes, and Willingness: A Cross-Sectional Study of Organ Donation in Saudi Arabia.

BACKGROUND: Organ transplantation is inherently dependent on the availability of organ donors. There is a noticeable paucity of literature addressing the rates of organ donation registration and the awareness of Islamic regulations (Fatwa) regarding organ donation within Saudi Arabia. Our study aimed to evaluate the level of organ donation registration, awareness of Islamic regulations, and knowledge of the Saudi Center for Organ Transplantation (SCOT) within the Saudi society. METHODS: We conducted a cross-sectional survey from 30 March to 9 April 2023. This survey aimed to assess the awareness of Islamic (Fatwa) guidance on organ donation, the role of SCOT, and the rate of organ donation registration facilitated through the Tawakkalna app, the official health passport application in Saudi Arabia. RESULTS: Out of 2329 respondents, 21% had registered as potential deceased organ donors, despite 87% acknowledging the importance of organ donation. Awareness of the Islamic Fatwa regarding organ donation was reported by 54.7% of respondents, and 37% recognized the Fatwa's acceptance of brain death criteria. The likelihood of registration as organ donors was higher among Saudi citizens under 45 years of age, females, healthcare workers (HCWs), individuals with higher education, relatives of patients awaiting organ donations, those informed about the Islamic Fatwas, and those willing to donate organs to friends. Conversely, being over the age of 25, Saudi nationality, employment as an HCW, awareness of SCOT, and prior organ donation registration were predictive of a heightened awareness of Islamic Fatwas. However, perceiving the importance of organ donation correlated with a lower awareness of the Fatwas. Significant positive correlations were found between awareness of SCOT, awareness of Fatwas, and registration for organ donation. CONCLUSIONS: While the Saudi population exhibits a high regard for the importance of organ donation, this recognition is not adequately translated into registration rates. The discrepancy may be attributable to limited awareness of SCOT and the relevant Islamic Fatwas. It is imperative to initiate organ donation awareness campaigns that focus on religious authorization to boost organ donation rates and rectify prevalent misconceptions.

Non-operative treatment for simple acute appendicitis (NOTA) in children during the COVID-19 era: new lessons from the pandemic.

Coronavirus (COVID-19) was a pandemic disease that was affecting our medical and surgical daily practice badly. The surgical management of acute appendicitis was the gold standard, but new studies suggest the safety of antibiotic treatment alone. Non-operative treatment for simple acute appendicitis (NOTA) avoids surgery, the risks of general anesthesia, and long hospital stays. It also decreases the risk of exposure to coronavirus. We aimed to study the cost-effectiveness and outcome of NOTA during the COVID-19 pandemic and compared it to single-incision pediatric endo-surgery appendectomy (SIPESA). A prospective cohort study for NOTA of patients from 6 to 12 years old in the COVID-19 pandemic period from April 1st, 2020, to April 30th, 2021, patients were divided into two groups: Group S was managed by SIPESA, and Group N was managed by NOTA. Family education and assurance with detailed explanation were done for early detection of any complications, and we continue monitoring the patients until their complete recovery. Group S had 24 cases (40%), mean age 9.3 years. Group N had 36 cases (60%), mean age 9.1 years. Six cases (17%) in group N were converted to surgical management in the first 6 months of the study. The mean cost dropped from $2736/day to $400/day. The mean psychological stress for the children improved from 4.4 in April to 2 in September. The mean follow-up was 3.5 months. NOTA is a feasible, cost-effective approach, and we recommend it, as we have learned this lesson during the COVID-19 pandemic days.

Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus.

This study aimed to identify BRCA1/2 mutational patterns in the tissue and blood of Egyptian colorectal cancer (CRC) patients and to study the possible correlation of this mutational pattern with Human papillomavirus (HPV) infection. Eighty-two colonoscopic biopsies and forty-six blood samples were collected from Egyptian CRC patients, as well as blood samples of age and sex-matched healthy controls (n = 43) were enrolled. The libraries were performed using Qiaseq Human BRCA1 and BRCA2 targeted DNA panel and sequenced via Ion proton sequencer. Also, the CRC tissues were subjected to conventional PCR targeting the HPV Late 1 (L1) region. Our analysis revealed that the BRCA-DNA damage pathway had been altered in more than 65% of the CRC patients. Comparing tissue and blood samples from CRC patients, 25 somatic mutations were found exclusively in tissue, while 41 germline mutations were found exclusively in blood. Additionally, we identified 23 shared BRCA1/2 pathogenic (PVs) mutations in both blood and tissue samples, with a significantly higher frequency in blood samples compared to tissue samples. The most affected exon in BRCA1 was exon 10, while the most affected exons in BRCA2 were 11, 14, 18, 24, and 27 exons. Notably, we revealed an ethnic-related cluster of polymorphism variants in our population closely related to South Asian and African ethnicities. Novel PVs were identified and submitted to the ClinVar database. HPV was found in 23.8% of the CRC tissues, and 54% of HPV-positive cases had somatic BRCA1/2 PVs. The results of this research point to a possible connection between infection with HPV and BRCA1/2 mutations in the occurrence of colorectal cancer in the Egyptian population, which has a mixed ethnic background. Our data also indicate that liquid biopsy (blood samples) may be more representative than tissue samples for detecting BRCA1/2 mutations. These findings may have implications for cancer screening and the development of personalized, targeted therapies, such as PARP inhibitors, which can effectively target BRCA1/2 mutations.

1D basin modeling and hydrocarbon generation potential of the Late Carboniferous Limburg Group formations, Northwest European Basin, Netherlands.

The Carboniferous rock samples of the Limburg Group formations were studied to investigate the source rock characteristics and the hydrocarbon generative potential. The source rock samples have been collected representing four rock units from three different wells. These samples were analyzed using Rock-Eval pyrolysis results and measured vitrinite reflectance values, and also by generating a one-dimensional basin model of K1 Field. The total organic carbon in these samples varies from 0.31 to 83.56% with a mean of 37.68%, suggesting that Limburg Group formations have excellent potential as a source of hydrocarbons. Kerogen in the Limburg Group formations is type II-III and type III, generate gas prominently. The outcomes of thermal maturation by Tmax and measured vitrinite reflectance reveal that the examined Limburg source rocks are located in the mature zone. The burial and thermal history models show irregular trend patterns due to uplift, erosion, and non-deposition events that took place in the K1 field (where the structural element is Cleaver Bank High). For the Maurits Formation, the oil generation took place at 2011 m at 230.1Ma ago and the top of the gas window was encountered 217.8Ma ago at 2535 m, whereas for the Hospital Ground Formation, the top of the oil window was encountered 186.8Ma ago at 2404 m and the gas generation took place at 2404 m at 161.9Ma ago.

Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition.

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

Common Prognostic Biomarkers and Outcomes in Patients with COVID-19 Infection in Saudi Arabia.

Background: COVID-19 is a respiratory disease that eventually became a pandemic, with 300 million people infected around the world. Alongside the improvement in COVID-19 management and vaccine development, identifying biomarkers for COVID-19 has recently been reported to help in early prediction and managing severe cases, which might improve outcomes. Our study aimed to find out if there is any correlation between clinical severity and elevated hematological and biochemical markers in COVID-19 patients and its effect on the outcome. Methods: We have collected retrospective data on socio-demographics, medical history, biomarkers, and disease outcomes from five hospitals and health institutions in the Kingdom of Saudi Arabia. Results: Pneumonia was the most common presentation of COVID-19 in our cohort. The presence of abnormal inflammatory biomarkers (D-dimer, CRP, troponin, LDH, ferritin, and t white blood cells) was significantly associated with unstable COVID-19 disease. In addition, patients with evidence of severe respiratory disease, particularly those who required mechanical ventilation, had higher biomarkers when compared to those with stable respiratory conditions (p < 0.001). Conclusion: Identifying biomarkers predicts outcomes for COVID-19 patients and may significantly help in their management.

Recessive CHRM5 variant as a potential cause of neurogenic bladder.

Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT. CHRM5 codes for a seven transmembrane-spanning G-protein-coupled muscarinic acetylcholine receptor. CHRM5 is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in Chrm5 knockout mice. We investigated CHRM5 as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with CHRM5 variants could help to further assess the genes' candidate status.

Molecular patterns of egyptian patients with non-squamous non-small-cell lung cancers: a clinicopathological study.

BACKGROUND: Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC. PATIENTS AND METHODS: This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected. RESULTS: The median age of the patients was 57 years (range: 32-79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001). CONCLUSION: Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.

Imatinib mitigates experimentally-induced ulcerative colitis: Possible contribution of NF-kB/JAK2/STAT3/COX2 signaling pathway.

RATIONALE: Ulcerative colitis (UC) is a chronic immune-mediated disease characterized by recurrent inflammation, damage, and alteration of the large intestine's mucosal and submucosal surfaces. The purpose of this research was to evaluate the impact of tyrosine kinase inhibitor (imatinib) on experimentally induced UC in rats via acetic acid (AA). METHODS: Male rats were randomly assigned to four groups: control, AA, AA + imatinib (10 mg/kg), and AA + imatinib (20 mg/kg). Imatinib (10 and 20 mg/kg/day) was orally supplied by oral syringe for one week before induction of UC. On the eighth day, Rats received enemas containing a 4 % solution of acetic acid to induce colitis. One day after inducing colitis, rats were euthanized and their colons were subjected to morphological, biochemical, histological, and immunohistochemical analysis. RESULTS: Imatinib pretreatment significantly decreased macroscopic and histological damage scores, decreased disease activity index as well as colon mass index. In addition, imatinib successfully lowered the levels of malondialdehyde (MDA) in colonic tissues and enhanced superoxide dismutase activity (SOD) and glutathione content (GSH). Imatinib also reduced colonic levels of inflammatory interleukins (IL-23, IL-17, IL-6), JAK2 and STAT3. Furthermore, imatinib suppressed nuclear transcription factor kappa B (NF-kB/p65) level, and COX2 expression in colonic tissues. SIGNIFICANCE: Imatinib may be a viable therapy option for UC as it halts the interaction network of NF-kB/JAK2/STAT3/COX2 signaling pathway.

Outcome of redo orchidopexy after previous laparoscopic orchidopexy.

PURPOSE: Testicular reascent is a recognised complication of orchidopexy, and redo surgery may be required. In this report, we present our experience of redo orchidopexy after initial laparoscopic surgery. METHODS: Patients who had undergone redo orchidopexy following an initial vessel-sparing (VS) or non-vessel sparing (NVS) laparoscopic orchidopexy between 2005 and 2019 were identified. Outcome data, including complications and testicular size, were recorded. RESULTS: The series comprised 23 patients (5: initial bilateral surgery with reascent on one side only; 18: unilateral surgery) with a mean age at original surgery of 3.5 years (range 8 months-6 years) and at redo surgery, 4 years (range 1.5-7 years). VS surgery had been undertaken in 15 and NVS in 8. A tension-free scrotal position was achieved in all cases. There were no complications and no patient required orchidectomy. At a minimum of 6-month follow-up after redo surgery, there were no cases of reascent and there was no change in testicular size/volume (based on clinical examination). CONCLUSION: Redo orchidopexy is an effective treatment following failed laparoscopic orchidopexy and a scrotal testis can be achieved in all cases. Complete testicular atrophy did not occur, but the risk of partial atrophy could not be accurately quantified.