How safe is high-intensity focused ultrasound? An intriguing solution for obstetric and gynecological diseases: A systematic review.

High-intensity focused ultrasound (HIFU) is a non-surgical and noninvasive treatment modality that depends on external ultrasound energy sources that induce focused mass ablation and protein degeneration in the treatment area via thermal energy penetration under the intact skin. We aim in our study to collectively evaluate the safety of HIFU for the treatment of different obstetric and gynecological diseases in the literature. We searched PubMed, Scopus, and Science Direct databases, without restriction on date or language, from the inception of these databases until January 20, 2024. We also examined the references of the included studies in the Mendeley archive for eligible articles. We found a total of 706 studies. After the screening and selection process, 56 participants were included. Our dichotomous outcomes were pooled in our single-arm meta-analysis as risk ratio (RR) and with 95% confidence interval (CI) while our continuous outcomes were pooled as mean change and 95% CIs. Fixed- or random-effects models were applied depending on the heterogeneity detected. Our systematic review and meta-analysis included 56 studies including 11.740 patients. Depending on the Society of Interventional Radiology (SIR) classification for adverse effects. The results of this meta-analysis for the type A category that did not require clinical intervention found that pain in the treatment site estimated RR with 95% CI: 0.61 (0.33, 0.89), abnormal vaginal discharge 0.16 (0.073, 0.24), low-grade fever (<38 °C) 0.005 (0.002, 0.009). Sensory abnormalities of the lower limbs were examined in 3390 individuals and observed in only 19 patients who experienced gradual relief of symptoms within one month after treatment. Regarding SIR type B, 99 of a total of 6.437 patients had small vesicles and superficial burns with pooled RR and 95% CI: 0.012 (0.007, 0.018). In terms of groin or perianal and lower abdominal pain, our RRs with 95% CIs were 0.1 (0.067, 0.13) and 0.38 (0.25, 0.51). However, vaginal bleeding was detected in only 32 out of a total of 3.017. Major adverse events like lumber disc herniation, thrombocytopenia, and renal failure, were unmentionable. Additionally, our included studies did not record any deaths. HIFU, either alone or in combination with oxytocin or any other enhancing agent, is safe for patients with different gynecological and obstetric diseases. In terms of efficacy, it showed promising results compared with traditional treatment lines. To our knowledge, we are the first and most comprehensive meta-analysis in the literature that has studied the different safety outcomes related to HIFU as a treatment modality for different obstetric and gynecological diseases with a very large sample size, making our evidence strong and less attributed to errors.

Interleukin (IL)-1B and IL-1 receptor antagonist gene polymorphisms in children with primary immune thrombocytopenia.

Background: The pathophysiology and susceptibility of children to primary immune thrombocytopenia (ITP) are linked to polymorphisms of the interleukin (IL)-1B and IL-1 receptor (IL-1R) antagonist genes. PURPOSE: To investigate the association between the susceptibility and severity of primary ITP in children and the IL-1B and IL-1R antagonist gene polymorphisms. METHODS: This comparative case-control study was conducted at the Menoufia University Hospital Hematology and Oncology Unit, Pediatric Department, between August 2022 and September 2023. The children were divided into patients (28 boys, 22 girls) who received hospital and outpatient clinic care and controls (50 healthy age- and sex-matched children). RESULTS: The mutant homozygous GG genotype and mutant G allele of rs16944 of the IL1B gene were considerably greater in patients than in controls (P<0.001). Furthermore, the mutant homozygous II/II genotype and heterozygous I/II genotype of the IL-1R antagonist gene were considerably greater in the case versus control group. The mutant II allele was significantly more prevalent in patients versus controls (P<0.001). CONCLUSION: IL-1B and IL-1R antagonists may have a major impact on the development of immune thrombocytopenia. Furthermore, we found a relationship between IL-1B and IL-1R antagonist gene polymorphisms and the etiology of and children's susceptibility to primary immune thrombocytopenia.

Prescribing Patterns of Psychotropic Medications for Common Psychiatric Disorders in a Mental Health Hospital in Tabuk.

INTRODUCTION: Mental health disorders are often chronic and disabling conditions that impact different populations, irrespective of age, cultural background, or socioeconomic status. This study aimed to describe the prescribing pattern of psychotropic medications in patients with psychiatric disorders. METHODS: This research was a retrospective investigation of psychotropic medication prescribing patterns and conducted at Eradah Mental Health Hospital at Tabuk City, Saudi Arabia. The data were extracted from the electronic medical database of adult patients presenting to the outpatient and inpatient clinics of a mental health hospital between 2020 and 2023. The diagnosis of psychiatric disorders was identified using the International Classification of Diseases 10th Revision (ICD-10) codes version 2019 for mental and behavioral disorders (F00 to F99). RESULTS: The electronic medication records of 526 patients were reviewed, of whom 510 (97%) were Saudi nationals, 368 (69.9%) were males, 235 (44.7%) were between 31 and 40 years of age, and 233 (44.3%) were outpatients. The most common psychiatric diagnoses were schizophrenia (33.3%), followed by bipolar affective disorder (16.9%). A total of 2,153 medication orders for psychotropic medications were quantified. Second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs) were the top prescribed medication classes (1,290, 60%), followed by mood stabilizers (324, 15%). More than one-half of the patients (282, 53.6%) received a combination of antipsychotic and mood stabilizers, and 155 (29.5%) received a combination of antipsychotic and antidepressant medications. No significant differences were observed in prescribing for males and females. CONCLUSION: Schizophrenia was highly prevalent among adult patients who sought mental healthcare. Polypharmacy of psychotropic medication was common depending on the symptoms' severity and comorbid psychiatric diseases.

Enhanced physical properties, antioxidant and antibacterial activity of bio-composite films composed from carboxymethyl cellulose and polyvinyl alcohol incorporated with broccoli sprout seed extract for butter packaging.

This study investigated the development of biodegradable films made from a combination of carboxymethyl cellulose (CMC), Polyvinyl alcohol (PVA), and purified extract of broccoli sprout seed (BSSE). The films were characterized for their color, physical properties, surface morphology, crystallinity, mechanical properties, and thermal properties. The addition of BSSE up to 1.4 % to the film matrix imparted opaque color and increased opacity up to 3.652. The films also became less moisture-absorbent 8.21 %, soluble 19.16 %, and permeable to water vapor 1.531 (× 10-10 g.m-1 s-1 pa-1). By utilizing 0.7 % from BSSE inside films, the surface of the films became smoother but became rough with higher concentrations 2.1 % of BSSE. Fourier transform infrared (FT-IR) analysis showed that there was physical interaction between the BSSE extract and the PV/CM matrix. The films showed good thermal stability, and the incorporation of BSSE improved their ability to preserve the acidity, TBARS, peroxide value, and total color differences of butter during cold storage.

Death and Venous Thromboembolism Analyses among Hospitalized COVID-19-Positive Patients: A Multicenter Study.

BACKGROUND: Coagulation disorders are frequently encountered among patients infected with coronavirus disease 2019 (COVID-19), especially among admitted patients with more severe symptoms. This study aims to determine the mortality rate and incidence and risk factors for venous thromboembolism (VTE) in hospitalized patients with COVID-19. METHODS: This retrospective observational cohort study was conducted from March to July 2020 using a hospital database. All adult patients (>18 years old) with laboratory-confirmed COVID-19 were included. Laboratory data and the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) for SARS-CoV-2 were obtained from medical records. The mortality rate and the incidence of VTE were established as study results. A multivariate logistic regression analysis was performed to identify predictors of thrombotic events. RESULTS: rA total of 1024 confirmed COVID-19 patients were treated, of whom 110 (10.7%) were deceased and 58 patients (5.7%) developed VTE. Death occurred more frequently in patients older than 50 years and those admitted to the intensive care unit (ICU, 95%) and who received mechanical ventilation (62.7%). Multivariate analysis revealed that cancer patients were two times more likely to have VTE (adjusted odds ratio = 2.614; 95% CI = (1.048-6.519); p = 0.039). Other chronic diseases, such as diabetes, hypertension, and chronic kidney disease, were not associated with an increased risk of VTE. CONCLUSIONS: One-tenth of hospitalized COVID-19 patients were deceased, and VTE was prevalent among patients with chronic conditions, such as cancer, despite anticoagulation therapy. Healthcare professionals should closely monitor individuals with a high risk of developing VTE to prevent unwanted complications.

Detection of early prognostic biomarkers for metastasis of Ewing's sarcoma in pediatric patients.

AIMS: Ewing's Sarcoma is an extremely aggressive tumor in children. The disease is associated with highly metastatic rate, especially at the time of diagnosis, contributing to a lower survival rate and poor prognosis. The study aimed to identify predictive biomarkers for metastatic Ewing's sarcoma through in-depth analysis of the plasma proteome profile of pediatric Ewing's sarcoma patients. MAIN METHODS: Plasma samples from Ewing's sarcoma patients and control individuals were profiled using both shotgun and dimethyl-labeled proteomics analysis. Subsequently, Ewing's sarcoma patients were further stratified according to their metastatic state and chemotherapy response. Western blot was used for validation. Univariate and multivariate analyses were performed to determine proteome metastasis predictors. Receiver operating characteristic (ROC) analysis was done to assess the diagnostic significance of the potential plasma Ewing's sarcoma biomarkers. KEY FINDINGS: Our results revealed a set of proteins significantly associated with the metastatic Ewing's sarcoma disease profile. These proteins include ceruloplasmin and several immunoglobulins. Additionally, our study disclosed significant differentially expressed proteins in pediatric Ewing's sarcoma, including CD5 antigen-like, clusterin, and dermcidin. Stable isotope dimethyl labeling and western blot further confirmed our results, strengthening the impact of such proteins in disease development. Furthermore, an unbiased ROC curve evaluated and confirmed the predictive power of these biomarker candidates. SIGNIFICANCE: This study presented potential empirical predictive circulating biomarkers for determining the disease status of pediatric Ewing's sarcoma, which is vital for early prediction.

Comparative outcomes among inlay grafted incised plate, onlay preputial flap and tubularized incised plate urethroplasty for the repair of distal penile hypospadias with a narrow urethral plate.

PURPOSE: We conducted this study, comparing the outcomes among Transverse Onlay Island Flap, inlay grafted incised plate and our previous records of tubularized incised plate urethroplasty (TIPU) in patients with narrow urethral plates, aiming to determine which method of repair provides a good outcome. METHODS: This hybrid study included two datasets. The first from a prospective randomized study evaluating outcomes of two treatment modalities; Inlay graft and only flap for distal hypospadias with shallow urethral plate with 80 patients (40 patients in each group) included, the second based on our previous records of TIPU in 40 patients with distal primary hypospadias with narrow urethral plate. RESULTS: The success rate in inlay graft urethroplasty group (n = 40) was 87.5%; glandular dehiscence occurred in one case (2.5%), fistulas occurred in 2 cases (5%), and narrow meatus occurred in two cases (5%). Success rate in onlay flap urethroplasty group (n = 40) was 82.5%; glandular dehiscence occurred in two cases (5%), fistulas occurred in two cases (5%), and narrow meatus occurred in three cases (7.5%). TIPU group (n = 40) had success rate of 62.5%; glandular dehiscence occurred in eight cases (20%), fistulas occurred in five cases (12.5%), and narrow meatus occurred in seven cases (17.5%), with five cases exhibiting both narrow meatus with fistula. CONCLUSION: Inlay graft and onlay flap urethroplasty for repair of distal penile hypospadias with narrow urethral plate had higher success rate and fewer complications than traditional TIPU. Moreover, operative time was shorter in TIPU.

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes.

Osteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.

Efficacy of dual-task training on stability and function in children with ataxia after medulloblastoma resection: A randomized controlled trial.

BACKGROUND/OBJECTIVE: In children, medulloblastoma (MB) is the most prevalent posterior fossa tumor. The first line of treatment is maximal safe resection. Therefore, symptoms of ataxia are commonly seen. Training the brain on balance and cognitive tasks makes balance more automatic than without cognitive tasks. The goal was to assess the effectiveness of dual-task practice on balance after MB excision in children with ataxia. METHODS: Thirty children with ataxia after MB resection at Children Cancer Hospital Egypt were randomized into two equal groups. Exercises for mobility, balance, and gait training were given to both groups. The research group underwent a specific dual-task program (balance and cognitive). The program ran 3 days per week for 8 weeks. Children were evaluated before and after the treatment regimen using the Scale of Assessment and Rating of Ataxia (SARA), the HUMAC Balance System, Pediatric Balance Scale, and Functional Independent Measurement. All children's legal guardians signed an ethical agreement. RESULTS: A notable improvement in balance was found in the dual group in Pediatric Balance Scale (PBS) (p = .028) and stability test (p = .0001) in favor of the study group. No discernible difference was observed in the Functional Independent Measurement score among the two groups (p = .158), although there was a statistically significant increase in both groups after treatment. CONCLUSION: Dual-task program is more effective than traditional physical therapy alone in improving balance in children with ataxia after MB resection.

Bio-diagnostic performances of microRNAs set related to DNA damage response pathway among hepatitis C virus-associated hepatocellular carcinoma patients.

BACKGROUND: Up to date, a well-defined microRNAs (miRNAs) profile involved in hepatocellular carcinoma (HCC) pathogenesis remains indecisive. Thus, employing miRNAs for HCC diagnosis is demanded for early therapeutic interventions. We aimed to evaluate the usage of miRNAs set related to the SuperPath: miRNAs involved in DNA damage response pathway as effective biomarkers for HCV-related HCC diagnosis. RESULTS: The study enrolled 97 patients with HCV-related HCC, 84 with hepatitis C virus (HCV), 97 with liver cirrhosis (LC), and 84 healthy individuals. Serum miRNA-23a, miRNA-203, miRNA-100-5p, and miRNA-16 were quantified using qRT-PCR experiments, AFP and routine LFTs were estimated via standard techniques. Pathway enrichment analysis along with the construction of miRNAs regulatory network were performed. With respect to healthy individuals, miRNA-203, miRNA-100-5p, and miRNA-16 were significantly downregulated in HCC, HCV, and LC groups, while miRNA-23a showed significant upregulation (p < 0.001). miRNAs exhibited significant correlations with AFP, ALT, AST, and albumin. Also, elevated levels of miRNA-23a were recognized in patients with multiple focal lesions and/or lesion size > 5 cm. Additionally, the diagnostic performance of miRNA-23a expression level at a selected cut-off value of 3.99 overtakes AFP, while expressions of miR-203, miRNA-100-5p, and miRNA-16 represent poor diagnostic outcomes. CONCLUSIONS: Keeping in mind the individual variability and high level of heterogeneity in HCC, our data revealed the diagnostic value of miRNA-23a expression in HCV-related HCC patients. Further extra in silico HCC-specific microRNAs sets are demanded in diagnosis.

Novel treatment of bronchopleural fistula in a lung transplant recipient with endobronchial sealant and endobronchial valve placement via robotic-assisted bronchoscopy.

Bronchopleural fistulas (BPFs) are a dreaded complication following pulmonary surgery. Endobronchial valves (EVs), with endobronchial sealant (ES), instilled with robotic bronchoscopy (RB), allow occlusion of BPF, avoiding surgery. The patient was a 71-year-old woman with a history of chronic obstructive pulmonary disease and bronchiectasis who underwent bilateral lung transplantation and wedge resection of the right middle lobe and left lingula. A BPF was discovered on postoperative day (POD) 21. Conservative measures with chest tubes failed, and robotic-assisted bronchoscopy aided in reaching the bronchial segment and instilling ES, and EV was deployed with the conventional bronchoscope. The pneumothorax was cleared 12 days later, and on POD 56, she was discharged. The RB procedure was successful, with no pneumothorax or BPF symptoms after a median follow-up of POD 284. Robotic endobronchial closure of BPF with EV and ES is an effective treatment option avoiding invasive surgeries.

The effectiveness of tyrosine kinase inhibitor for chronic myeloid leukemia in tuberous sclerosis. A case report and review of literature.

The relationship between chronic myelogenous leukemia (CML) and tuberous sclerosis (TS) is unusual and uncommon. Here, we report a 24-year-old woman diagnosed with TS and later identified with CML, as the second case reported with such coexistence, treated with Nilotinib. This article proposes a hypothesis to explain the association. Therefore, we propose Nilotinib for the treatment of patients with such coexisting diseases. Further studies are warranted to reveal the dynamics between these conditions.

Aspergillus Niger thermostable Cytosine deaminase-dextran conjugates with enhanced structure stability, proteolytic resistance, and Antiproliferative activity.

Cytosine deaminase (CDA) is a prodrug mediating enzyme converting 5-flurocytosine into 5-flurouracil with profound broad-range anticancer activity towards various cell lines. Availability, molecular stability, and catalytic efficiency are the main limiting factors halting the clinical applications of this enzyme on prodrug and gene therapies, thus, screening for CDA with unique biochemical and catalytic properties was the objective. Thermotolerant/ thermophilic fungi could be a distinctive repertoire for enzymes with affordable stability and catalytic efficiency. Among the recovered thermotolerant isolates, Aspergillus niger with optimal growth at 45 °C had the highest CDA productivity. The enzyme was purified, with purification 15.4 folds, molecular mass 48 kDa and 98 kDa, under denaturing and native PAGE, respectively. The purified CDA was covalently conjugated with dextran with the highest immobilization yield of 75%. The free and CDA-dextran conjugates have the same optimum pH 7.4, reaction temperature 37 °C, and pI 4.5, and similar response to the inhibitors and amino acids suicide analogues, ensuring the lack of effect of dextran conjugation on the CDA conformational structure. CDA-Dextran conjugates had more resistance to proteolysis in response to proteinase K and trypsin by 2.9 and 1.5 folds, respectively. CDA-Dextran conjugates displayed a dramatic structural and thermal stability than the free enzyme, authenticating the acquired structural and catalytic stability upon dextran conjugation. The thermal stability of CDA was increased by about 1.5 folds, upon dextran conjugation, as revealed from the half-life time (T1/2). The affinity of CDA-conjugates (Km 0.15 mM) and free CDA (Km 0.22 mM) to deaminate 5-fluorocytosine was increased by 1.5 folds. Upon dextran conjugation, the antiproliferative activity of the CDA towards the different cell lines "MDA-MB, HepG-2, and PC-3" was significantly increased by mediating the prodrug 5-FC. The CDA-dextran conjugates strongly reduce the tumor size and weight of the Ehrlich cells (EAC), dramatically increase the titers of Caspase-independent apoptotic markers PARP-1 and AIF, with no cellular cytotoxic activity, as revealed from the hematological and biochemical parameters.

Mostafa Maged sling technique to treat prolapsed uterus in an easy way (New Technique).

Background: In the female population, pelvic organ prolapse is a common problem that lowers people's quality of life in terms of their health. Depending on the severity of the prolapse and the symptoms, there are many treatment options. Simple observation, vaginal pessaries, or surgical management are all possible treatments. Reconstructive pelvic surgery with or without mesh augmentation and obliterative surgery are two surgical treatments that are available. Due to the contentious concerns surrounding the use of mesh and the rising demand for uterine preservation, surgical practices are currently shifting. Methods: Just two cases are included in this study due to the rarity of this condition. In this study, I introduce a new technique to the literature (Mostafa Maged sling technique) which will be challenging. This technique depends on round ligaments and ovarian ligament to hitch up the whole uterus. Results: There were no difficulties following the procedure. None of the patients required blood transfusions, and there were no signs of dehiscence or incision infection. Non-steroidal antiinflammatory medications were administered to both patients as analgesia. On the first postoperative day, the foley catheters were removed from both patients. Conclusion: A simple and new manueuver is applied in the literature to treat the uterine prolapse. It is easy to learn and easy to perform. We need further studies to compare different techniques including Mostafa Maged sling operation to manage uterine prolapse.

An Edge-Based Selection Method for Improving Regions-of-Interest Localizations Obtained Using Multiple Deep Learning Object-Detection Models in Breast Ultrasound Images.

Computer-aided diagnosis (CAD) systems can be used to process breast ultrasound (BUS) images with the goal of enhancing the capability of diagnosing breast cancer. Many CAD systems operate by analyzing the region-of-interest (ROI) that contains the tumor in the BUS image using conventional texture-based classification models and deep learning-based classification models. Hence, the development of these systems requires automatic methods to localize the ROI that contains the tumor in the BUS image. Deep learning object-detection models can be used to localize the ROI that contains the tumor, but the ROI generated by one model might be better than the ROIs generated by other models. In this study, a new method, called the edge-based selection method, is proposed to analyze the ROIs generated by different deep learning object-detection models with the goal of selecting the ROI that improves the localization of the tumor region. The proposed method employs edge maps computed for BUS images using the recently introduced Dense Extreme Inception Network (DexiNed) deep learning edge-detection model. To the best of our knowledge, our study is the first study that has employed a deep learning edge-detection model to detect the tumor edges in BUS images. The proposed edge-based selection method is applied to analyze the ROIs generated by four deep learning object-detection models. The performance of the proposed edge-based selection method and the four deep learning object-detection models is evaluated using two BUS image datasets. The first dataset, which is used to perform cross-validation evaluation analysis, is a private dataset that includes 380 BUS images. The second dataset, which is used to perform generalization evaluation analysis, is a public dataset that includes 630 BUS images. For both the cross-validation evaluation analysis and the generalization evaluation analysis, the proposed method obtained the overall ROI detection rate, mean precision, mean recall, and mean F1-score values of 98%, 0.91, 0.90, and 0.90, respectively. Moreover, the results show that the proposed edge-based selection method outperformed the four deep learning object-detection models as well as three baseline-combining methods that can be used to combine the ROIs generated by the four deep learning object-detection models. These findings suggest the potential of employing our proposed method to analyze the ROIs generated using different deep learning object-detection models to select the ROI that improves the localization of the tumor region.

Microbial cytosine deaminase is a programmable anticancer prodrug mediating enzyme: antibody, and gene directed enzyme prodrug therapy.

Cytosine deaminase (CDA) is a non-mammalian enzyme with powerful activity in mediating the prodrug 5-fluorcytosine (5-FC) into toxic drug 5-fluorouracil (5-FU), as an alternative directed approach for the traditional chemotherapies and radiotherapies of cancer. This enzyme has been frequently reported and characterized from various microorganisms. The therapeutic strategy of 5-FC-CDA involves the administration of CDA followed by the prodrug 5-FC injection to generate cytotoxic 5-FU. The antiproliferative activity of CDA-5-FC elaborates from the higher activity of uracil pathway in tumor cells than normal ones. The main challenge of the therapeutic drug 5-FU are the short half-life, lack of selectivity and emergence of the drug resistance, consistently to the other chemotherapies. So, mediating the 5-FU to the tumor cells by CDA is one of the most feasible approaches to direct the drug to the tumor cells, reducing its toxic effects and improving their pharmacokinetic properties. Nevertheless, the catalytic efficiency, stability, antigenicity and targetability of CDA-5-FC, are the major challenges that limit the clinical application of this approach. Thus, exploring the biochemical properties of CDA from various microorganisms, as well as the approaches for localizing the system of CDA-5-FC to the tumor cells via the antibody directed enzyme prodrug therapy (ADEPT) and gene directed prodrug therapy (GDEPT) were the objectives of this review. Finally, the perspectives for increasing the therapeutic efficacy, and targetability of the CDA-5-FC system were described.

Metabolomics and Lipidomics Screening Reveal Reprogrammed Signaling Pathways toward Cancer Development in Non-Alcoholic Steatohepatitis.

With the rising incidence of hepatocellular carcinoma (HCC) from non-alcoholic steatohepatitis (NASH), identifying new metabolic readouts that function in metabolic pathway perpetuation is still a demand. The study aimed to compare the metabolic signature between NASH and NASH-HCC patients to explore novel reprogrammed metabolic pathways that might modulate cancer progression in NASH patients. NASH and NASH-HCC patients were recruited and screened for metabolomics, and isotope-labeled lipidomics were targeted and profiled using the EXION-LCTM system equipped with a Triple-TOFTM 5600+ system. Results demonstrated significantly (p ≤ 0.05) higher levels of triacylglycerol, AFP, AST, and cancer antigen 19-9 in NASH-HCC than in NASH patients, while prothrombin time, platelet count, and total leukocyte count were decreased significantly (p ≤ 0.05). Serum metabolic profiling showed a panel of twenty metabolites with 10% FDR and p ≤ 0.05 in both targeted and non-targeted analysis that could segregate NASH-HCC from NASH patients. Pathway analysis revealed that the metabolites are implicated in the down-regulation of necroptosis, amino acid metabolism, and regulation of lipid metabolism by PPAR-α, biogenic amine synthesis, fatty acid metabolism, and the mTOR signaling pathway. Cholesterol metabolism, DNA repair, methylation pathway, bile acid, and salts metabolism were significantly upregulated in NASH-HCC compared to the NASH group. Metabolite-protein interactions network analysis clarified a set of well-known protein encoding genes that play crucial roles in cancer, including PEMT, IL4I1, BAAT, TAT, CDKAL1, NNMT, PNP, NOS1, and AHCYL. Taken together, reliable metabolite fingerprints are presented and illustrated in a detailed map for the most predominant reprogrammed metabolic pathways that target HCC development from NASH.

Experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee: A single institution study with intermediate follow up.

PURPOSE: We present our modified technique of using the inner preputial flap to cover the penile shaft, while removing the subcutaneous tissue of the distal part of the flap to act similar to graft. Herein, we present our experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee. PATIENTS AND METHODS: The current study was a single-institution retrospective study between January 2016 and December 2020. Thirty-one patients with proximal hypospadias with chordee were included and underwent our modified technique. We excluded re-operative hypospadias and incomplete follow-up cases (<6 month of follow up). Patient demographics, outcomes and complications in the form of fistula formation, diverticulum, metal stenosis, stricture formation and glans dehiscence were reviewed. RESULTS: A total of 31 patients were included in the study and underwent our modified technique. The median age was 18 months (9-60) & IQR 15-25). The median follow up was 40 months. Overall, success was achieved in 24 cases (77.4%). Complications occurred in seven cases (22.6%) and included urethrocutanous fistula in three patients (9.7%), diverticulum in two patients (6.5.%), metal stenosis in one patient (3.2%) and glans dehiscence in one patient (3.2%). CONCLUSION: Our technique provides a favourable outcome with a low complication rate for repair of proximal severe hypospadias. LEVEL OF EVIDENCE: Case Series Study (Level IV).

The Importance of Nitric Oxide as the Molecular Basis of the Hydrogen Gas Fumigation-Induced Alleviation of Cd Stress on Ganoderma lucidum.

Whether or not hydrogen gas (H2) can reduce cadmium (Cd) toxicity in Ganoderma lucidum has remained largely unknown. Here, we report that Cd-induced growth inhibition in G. lucidum was significantly alleviated by H2 fumigation or hydrogen-rich water (HRW), evaluated by lower oxidative damage and Cd accumulation. Moreover, the amelioration effects of H2 fumigation were better than of HRW in an optimum concentration of H2 under our experimental conditions. Further results showed that H2-alleviated growth inhibition in G. lucidum was accompanied by increased nitric oxide (NO) level and nitrate reductase (NR) activity under Cd stress. On the other hand, the mitigation effects were reversed after removing endogenous NO with its scavenger cPTIO or inhibiting H2-induced NR activity with sodium tungstate. The role of NO in H2-alleviated growth inhibition under Cd stress was proved to be achieved through a restoration of redox balance, an increase in cysteine and proline contents, and a reduction in Cd accumulation. In summary, these results clearly revealed that NR-dependent NO might be involved in the H2-alleviated Cd toxicity in G. lucidum through rebuilding redox homeostasis, increasing cysteine and proline levels, and reducing Cd accumulation. These findings may open a new window for H2 application in Cd-stressed economically important fungi.