Abdominal wall muscle weakness outcomes after split abdominal flap repair of large congenital diaphragmatic hernias in newborn.

PURPOSE: Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could be any associated abdominal muscle weakness. Our aim is to analyze the evolution of this abdominal muscle wall weakness. METHODS: Retrospective review of CDH repair by SAWMF (internal oblique muscle and transverse) from 2004 to 2023 focusing on the evolution of muscle wall weakness. RESULTS: Eighteen neonates of 148 CDH patients (12,1%) were repaired using SAWMF. Mean gestational age and birth weight were 35.7 ± 3.5 weeks and 2587 ± 816 g. Mean lung-to-head ratio was 1.49 ± 0.28 and 78% liver-up. Seven patients (38%) were prenatally treated by tracheal occlusion. Ninety-four percent of the flaps were used for primary repair and one to repair a recurrence. One patient (5.6%) experienced recurrence. Abdominal muscle wall weakness was present in the form of a bulge. Resolution of weakness at 1, 2 and 3 years was 67%, 89% and 94%, respectively. No patient required treatment for weakness or died. CONCLUSIONS: Abdominal muscular weakness after a split abdominal wall muscle flap repair is not a limitation for its realization since it is asymptomatic and presents a prompt spontaneous resolution. LEVEL OF EVIDENCE: IV.

Delayed Closure of Ventricular Septal Defect with Prolonged Mechanical Support.

Introduction: Ventricular septal defect (VSD) is a severe complication following acute myocardial infarction (MI) resulting from mechanical disruption of the interventricular septum due to extensive myocardial necrosis. Despite advances in management, the mortality rate approaches 50%. We report a case of a 58-year-old male with VSD following MI who was successfully treated with a delayed surgical approach after haemodynamic support using Impella. Case description: A 58-year-old man with type 2 diabetes mellitus and hypertension presented with three days of chest pain. Testing revealed late presenting acute anterior ischaemic infarction and left-to-right shunt in the apical ventricular septum. Urgent cardiac catheterisation showed near-total occlusion of the left anterior descending artery. An Impella CP® was placed before angioplasty with a drug-eluting stent to optimise haemodynamics. After a multidisciplinary discussion, the Impella CP® was upgraded to Impella 5.5®, and surgery was delayed allowing for scar formation. The patient remained in the intensive care unit, where he underwent physical therapy, showing improvements in exercise tolerance by the time of surgery. He underwent a left ventriculotomy with a successful repair via an endocardial patch 28 days after initial presentation. Post-operative recovery was uneventful, with the patient discharged five days later, reporting no physical limitations one month post-discharge. Conclusion: The successful management of VSD post-MI relies on interdisciplinary collaboration, careful timing of surgical intervention and the strategic use of mechanical support devices such as the Impella. This case highlights the potential for favourable outcomes when tailored treatment approaches are employed. LEARNING POINTS: Given the rarity of ventricular septal defects (VSD) post-myocardial infarction (MI), maintaining a high index of suspicion, particularly in patients with anterior infarcts and other high-risk features, is imperative for ensuring early recognition and management of this life-threatening complication.Surgical repair is the treatment of choice for VSD post-MI, offering improved survival rates, particularly when intervention is delayed to allow for myocardial scarring.Mechanical circulatory support devices, such as the Impella, can play a crucial role in bridging patients to surgical repair by providing temporary haemodynamic stabilisation. However, timing is vital, and early initiation of mechanical support can prevent the progression of cardiogenic shock and multi-organ failure.

Nkd1 functions downstream of Axin2 to attenuate Wnt signaling.

Wnt signaling is a crucial developmental pathway involved in early development as well as stem-cell maintenance in adults and its misregulation leads to numerous diseases. Thus, understanding the regulation of this pathway becomes vitally important. Axin2 and Nkd1 are widely utilized negative feedback regulators in Wnt signaling where Axin2 functions to destabilize cytoplasmic ß-catenin, and Nkd1 functions to inhibit the nuclear localization of ß-catenin. Here, we set out to further understand how Axin2 and Nkd1 regulate Wnt signaling by creating axin2gh1/gh1, nkd1gh2/gh2 single mutants and axin2gh1/gh1;nkd1gh2/gh2 double mutant zebrafish using sgRNA/Cas9. All three Wnt regulator mutants were viable and had impaired heart looping, neuromast migration defects, and behavior abnormalities in common, but there were no signs of synergy in the axin2gh1/gh1;nkd1gh2/gh2 double mutants. Further, Wnt target gene expression by qRT-PCR and RNA-seq, and protein expression by mass spectrometry demonstrated that the double axin2gh1/gh1;nkd1gh2/gh2 mutant resembled the nkd1gh2/gh2 phenotype demonstrating that Nkd1 functions downstream of Axin2. In support of this, the data further demonstrates that Axin2 uniquely alters the properties of ß-catenin-dependent transcription having novel readouts of Wnt activity compared with nkd1gh2/gh2 or the axin2gh1/gh1;nkd1gh2/gh2 double mutant. We also investigated the sensitivity of the Wnt regulator mutants to exacerbated Wnt signaling, where the single mutants displayed characteristic heightened Wnt sensitivity, resulting in an eyeless phenotype. Surprisingly, this phenotype was rescued in the double mutant, where we speculate that cross-talk between Wnt/ß-catenin and Wnt/Planar Cell Polarity pathways could lead to altered Wnt signaling in some scenarios. Collectively, the data emphasizes both the commonality and the complexity in the feedback regulation of Wnt signaling.

Artificial neural network-assisted thermogravimetric analysis of thermal degradation in combustion reactions: A study across diverse organic samples.

During gasification the kinetic and thermodynamic parameter depend on both the feedstock and the process conditions. As a result, one needs to enhance the understanding of how to model numerically these parameters using thermogravimetric analyzer. Consequently, there exists a pressing need to computationally devise gasification model that can efficiently account to thermodynamic and kinetic parameter from thermogravimetric data. In this study, we numerically model gasification process kinetic and thermodynamic parameters, which vary with feedstock and operational conditions. Our novel approach involves creating an ANN model in MATLAB using a carefully optimized 8-20-20-10-1 architecture. Based on thermogravimetric analyzer (TGA) data, this model uniquely predicts critical kinetic (activation energy, pre-exponential factor) and thermodynamic parameters (entropy, enthalpy, Gibbs free energy, ignition index, boiling temperature). Our ANN model, trained on over 80 diverse samples with the Levenberg-Marquardt algorithm, excels at prediction, with an MSE of 6.185e-6 and an R2 value exceeding 0.9996, ensuring highly accurate estimates. Based on time, temperature, heating rate, and elemental composition, it accurately predicts thermal degradation. The model can predict TGA curves for many materials, demonstrating its versatility. For instance, it accurately estimates the activation energy for pure glycerol at 73.84 kJ/mol, crude glycerol at 67.55 kJ/mol, 12.12 kJ/mol for coal, and 111.3 kJ/mol for wood. These results, particularly for Kissinger-validated glycerol, demonstrate the model's versatility and efficacy in various gasification scenarios, making it a valuable tool for thermochemical conversion studies.

Study on 3D printed MXene-berberine-integrated scaffold for photo-activated antibacterial activity and bone regeneration.

The repair of mandibular defects is a challenging clinical problem, and associated infections often hinder the treatment, leading to failure in bone regeneration. Herein, a multifunctional platform is designed against the shortages of existing therapies for infected bone deficiency. 2D Ti3C2 MXene and berberine (BBR) are effectively loaded into 3D printing biphasic calcium phosphate (BCP) scaffolds. The prepared composite scaffolds take the feature of the excellent photothermal capacity of Ti3C2 as an antibacterial, mediating NIR-responsive BBR release under laser stimuli. Meanwhile, the sustained release of BBR enhances its antibacterial effect and further accelerates the bone healing process. Importantly, the integration of Ti3C2 improves the mechanical properties of the 3D scaffolds, which are beneficial for new bone formation. Their remarkable biomedical performances in vitro and in vivo present the outstanding antibacterial and osteogenic properties of the Ti3C2-BBR functionalized BCP scaffolds. The synergistic therapy makes it highly promising for repairing infected bone defects and provides insights into a wide range of applications of 2D nanosheets in biomedicine.

In silico exploration of the potential inhibitory activities of in-house and ZINC database lead compounds against alpha-glucosidase using structure-based virtual screening and molecular dynamics simulation approach.

Inhibitors of α-glucosidase have been used to treat type-2 diabetes (T2DM) by preventing the breakdown of carbohydrates into glucose and prevent enhancing glucose conversion. Structure-based virtual screening (SBVS) was used to generate novel chemical scaffold-ligand α-glucosidase inhibitors. The databases were screened against the receptor α-glucosidase using SBVS and molecular dynamics simulation (MDS) techniques in this study. Based on molecular docking studies, three and two compounds of α-glucosidase inhibitors were chosen from a commercial database (ZINC) and an In-house database for this study respectively. The mode of binding interactions of the selected compounds later predicted their α-glucosidase inhibitory potential. Finally, one out of three lead compound from ZINC and one out of two lead compound from In-house database were shortlisted based on interactions. Furthermore, MDS and post-MDS strategies were used to refine and validate the shortlisted leads along with the reference acarbose/α-glucosidase. The Hits' ability to inhibit α-glucosidase was predicted by SBVS, indicating that these compounds have good inhibitory activities. The lead inhibitor's structure may serve as templates for the design of novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is necessary. These insights can help rationally design new effective anti-diabetic drugs.Communicated by Ramaswamy H. Sarma.

Colour, nutritional composition and antioxidant properties of dehydrated carrot (Daucus carota var. sativus) using solar drying techniques and pretreatments.

Carrot is a seasonal perishable tuberous root vegetable which presents a preservation challenge owing to its elevated moisture content. Recently, carrot processing has received more attention because of its many health-promoting qualities and the reduction of postharvest losses in a cost-effective safe way. This study was designed to sort out the effective solar drying technique including pre-treatment that would retain the color and quality characteristics of dehydrated carrot. Carrot slices were subjected to dry using open sun drying (D1), solar drying long chimney (D2), solar drying short chimney (D3) and box solar drying (D4) techniques with the pretreatments of ascorbic acid 1 % (C3), citric acid 5 % (C4), potassium metabisulfite 1 % (C5) and potassium sodium tartrate 0.3 % (C6) before drying. Drying characteristics, nutritional attributes, phytochemicals and antioxidant of the dehydrated carrot samples were compared with the fresh sample and untreated (control) sample. Results showed that D4 was a good drying method to preserve nutritional quality with good appearance. Among the pretreatments, C5 and C4 resulted improved nutritional quality retention, enhanced visual acceptability and enriched antioxidant activities. PCA (Principal Component Analysis) and correlation matrix revealed that D4 with C5 retained the maximum amount of vitamin, minerals, total phenolic content, antioxidant and admirable dehydrated carrot color by inactivating enzymatic reaction. Therefore, box solar drying with potassium metabisulfite pretreatment would be very promising for functional carrot drying retaining acceptable color and nutrition composition.

Missing intrauterine device migrated to terminal ileum resembling adnexal mass: A case report.

INTRODUCTION AND IMPORTANCE: Although IUD has become more popular in recent years, its migration through uterine perforation is a rare but serious complication. PRESENTATION OF CASE: We present the case of a young otherwise healthy woman with a missing IUD that had penetrated terminal ileum. CLINICAL DISCUSSION: The incidence of uterine perforation after IUD insertion has been reported 1.3 to 1.6 per 1000 insertions. Although a rare complication, it can cause serious problems requiring major surgery. CONCLUSION: Uterine perforation and migration of IUD is a rare but serious complication that should be considered in all missing IUD threads.

Green synthesis of silver nanoparticles from plant Fagonia cretica and evaluating its anti-diabetic activity through indepth in-vitro and in-vivo analysis.

One of the most widespread metabolic diseases, Type-2 Diabetes Mellitus (T2DM) is defined by high blood sugar levels brought on by decreased insulin secretion, reduced insulin action, or both. Due to its cost-effectiveness and eco-friendliness, plant-mediated green synthesis of nanomaterials has become more and more popular. The aim of the study is to synthesize AgNPs, their characterizations and further in-vitro and in-vivo studies. Several methods were used to morphologically characterise the AgNPs. The AgNPs were crystalline, spherical, and clustered, with sizes ranging from 20 to 50 nm. AgNPs were found to contain various functional groups using Fourier transform infrared spectroscopy. This study focuses on the green-synthesis of AgNPs from Fagonia cretica (F. cretica) leaves extract to evaluate their synthesized AgNPs for in-vitro and in-vivo anti-diabetic function. For the in-vivo tests, 20 male Balb/C albino-mice were split up into four different groups. Anti-diabetic in-vivo studies showed significant weight gain and a decrease in all biochemical markers (pancreas panel, liver function panel, renal function panel, and lipid profile) in Streptozotocin (STZ)-induced diabetic mice. In vitro anti-diabetic investigations were also conducted on AgNPs, comprising α-amylase, α-glucosidase inhibitions, and antioxidant assays. AgNPs showed antioxidant activity in both the DPPH and ABTS assays. The research showed that the isolated nanoparticles have powerful antioxidant and enzyme inhibitory properties, especially against the main enzymes involved in T2DM.

Assessing Adherence to Royal College of Surgeons Guidelines: A Closed-Loop Audit of Operation Notes in a Tertiary Healthcare Unit.

Introduction Accurate, comprehensive, and legible operation notes are essential for maintaining patient records, supporting healthcare professionals, and facilitating research. The study focused on adherence to Royal College of Surgeons (RCS) guidelines established in 2008. Despite the guidelines, poor documentation practices have been reported globally. This audit seeks to address this issue and enhance documentation quality. Methodology The audit evaluated 19 parameters as defined in the 2014 RCS operative note guidelines. Data collection occurred during the initial cycle, spanning from March to April 2023, encompassing all surgical procedures at Hayatabad Medical Complex (HMC). Subsequently, a re-audit took place in July 2023 to gauge enhancements following a survey and educational intervention that took place in June 2023. The process included the formation of an audit team, securing ethical approval, and implementing a comprehensive methodology for data collection and analysis. The study spanned two data collection cycles to comprehensively assess improvements. Results Comparing initial and re-audit cycles (n = 390 and n = 108, respectively), improvements were observed in several documentation aspects. Parameters such as surgery date, elective/emergency classification, and names of key personnel showed significant enhancement. Notable improvements were also seen in the recording of operative details, complications, extra procedures, and post-operative care instructions. In our department, an educational survey was conducted to gain insights into compliance rates. This survey underscored the significance of adhering to RCS guidelines, identified the factors influencing adherence, and proposed strategies for improvement. Conclusion The audit affirmed the significance of adhering to RCS guidelines for operation note documentation. The study demonstrated improvements in documentation practices, emphasising the importance of accurate records for patient care, research, and ethical standards. The findings validate RCS guidelines as a tool for the identification of defects in documentation and thus as a guide that highlights where improvements are necessary. Addressing challenges identified in this audit can drive the department towards becoming a model for RCS guideline adherence and showcasing high-quality surgical documentation and patient-centred care.

Phytochemicals-based ß-amyloid cleaving enzyme-1 and MAO-B inhibitors for the treatment of Alzheimer's disease: molecular simulations-based predictions.

Alzheimer's disease (AD) is among the highly prevalent neurodegenerative disorder of the aging brain and is allied with cognitive and behavioral abnormalities. Unfortunately, there is very limited drug discovery for the effective management of AD, and the clinically approved drugs have limited efficacy. Consequently, there is an immediate demand for the development of new compounds that have the ability to act as multitarget-directed ligands (MTDLs). As major pathological targets of the disease, the current study aimed to investigate lead natural bioactive compounds including apigenin, epigallocatechin-3-gallate, berberine, curcumin, genistein, luteolin, quercetin, resveratrol for their inhibitory potentials against ß-amyloid cleaving enzyme-1 (BACE1) and monoamine oxidase-B (MAO-B) enzymes. The study compounds were docked against the target enzymes (MAO-B and BACE1) using MOE software and subsequent molecular dynamics simulations (MDS) studies. The molecular docking analysis revealed that these phytochemicals (MTDLs) showed good interactions with the target enzymes as compared to the reference inhibitors. Among these eight phytocompounds, the epigallocatechin-3-gallate compound was an active inhibitor against both drug targets, with the highest docking scores and good interactions with the active residues of the enzymes. Furthermore, the docking result of the active one inhibitor in complex with the target enzymes (epigallocatechin-3-gallate/BACE1, epigallocatechin-3-gallate/MAO-B, reference/BACE1 and reference/MAO-B) were further validated by MDS. According to the findings of our study, epigallocatechin-3-gallate has the potential to be a candidate for use in the treatment of neurological illnesses like AD. This compound has MTDL potential and may be exploited to create new compounds with disease-modifying features.Communicated by Ramaswamy H. Sarma.

Laparoscopy in Low- and Middle-Income Countries: A Survey Study.

INTRODUCTION: An increasing shift towards non-communicable diseases and an existing high surgical burden of disease in low-middle-income countries (LMICs) has impelled the need for implementing laparoscopic surgery, a safe and cost-effective surgical service. However, despite countless benefits, laparoscopic surgery programs remain limited throughout LMICs, and limited understanding is known of healthcare professionals' views regarding the implementation of laparoscopic surgery in their local healthcare environments. Therefore, the purpose of this study is to better understand the perceived challenges and barriers to implementing long-term laparoscopic surgery programs from the perspective of healthcare professionals. METHODS: Upon receiving ethical approval from the McGill University Health Center (MUHC), a nine-question survey (concerning attributes required to establish a successful laparoscopic program in LMICs and to gain insight into what surgeons from LMICs believed were the necessary next steps) was pilot tested amongst faculty members, and subsequently disseminated to healthcare professionals practicing in LMICs. Explicit consent was obtained from the participants before answering the survey.  Results: Thirty-four participants representing a total of 35 countries participated in the survey with the majority having received laparoscopic surgery training. Overall, participant responses were characterized by two major themes. Highlighted in the first theme, Laparoscopic Experience and Training Curriculum, were responses concerning current laparoscopic training and education, improved career opportunities provided by laparoscopic training, and a particular existing potential to incorporate laparoscopic surgery into the current surgical curriculum at various levels of training. Emphasized in the second theme, Challenges and Next Steps, were responses concerning barriers to the implementation of laparoscopic surgery, current institutional capabilities, and the need for improving mentorship through existing surgical societies such as the College of Surgeons of East, Central, and Southern Africa (COSECSA), West African College of Surgeons (WACS), and The Pan-African Academy of Christian Surgeons (PAACS). CONCLUSIONS: A buy-in from the government, hospitals, staff, and industry is crucial for the long-term implementation of laparoscopic surgery in LMICs, which can only be accomplished through increased advocacy and the dissemination of the benefits of minimally invasive surgery both economically and socially.

Identification of 12 hub genes associated to the pathogenesis of osteoporosis based on microarray and single-cell RNA sequencing data.

Osteoporosis is a common disease, especially among the elderly. This study aimed to comprehensively examine the roles of immune microenvironment in osteoporosis pathogenesis. Expression profiles of GSE35959, GSE7158, and GSE13850 datasets were used to analyze differential expression and identify hub genes related to immune features. Based on the single-cell RNA sequencing (scRNA-seq) data of an osteoporosis patient, different cell types were classified and the relation between immune environment and osteoporosis was explored. Twelve hub genes significantly associated with immune features were selected and 11 subgroups were defined using scRNA-seq data. The expression of two hub genes (CDKN1A and TEFM) was greatly altered during the transformation from mesenchymal stem cells (MSCs) to osteoblasts. Chemokines and chemokine receptors were differentially enriched in different cell types. CXCL12 was high-expressed in MSCs. This study emphasized that immune microenvironment played a critical role in the pathogenesis of osteoporosis. Chemokines and chemokine receptors can modify cell development and affect the interactions among different cell types, leading to unbalanced bone remodeling.

In-depth in-vitro and in-vivo anti-diabetic evaluations of Fagonia cretica mediated biosynthesized selenium nanoparticles.

Therapeutic moieties derived from medicinal plants as well as plants-based ecofriendly processes for producing selenium nanoparticles have shown great promise in the management of type 2 diabetes mellitus (T2DM). The current study was aimed to assess the anti-diabetic potentials of Fagonia cretica mediated biogenic selenium nanoparticles (FcSeNPs) using in-vitro and in-vivo approaches. The bio-synthesized FcSeNPs were characterized using various techniques including UV-VIS spectrophotometry and FTIR analysis. The in-vitro efficacy of FcSeNPs were assessed against α-glucosidase, α-amylase enzymes as well as the anti-radical studies were performed using DPPH and ABTS free radicals scavenging assays. For in-vivo studies, 20 Male Balb/C albino-mice were randomly divided into 4 groups (n = 5) including normal group, disease group (Diabetic group with no treatment), control group and treatment group (Diabetic group treated with FcSeNPs). Further, biochemistry markers including pancreas, liver, kidney and lipid profile were assessed for all treatment groups. The FcSeNPs exhibited a dose-dependent inhibition against α-amylase and α-glucosidase at 62-1000 µg mL-1 concentration with IC50 values of 92 and 100 µg mL-1 respectively. In antioxidant experiments, the FcSeNPs demonstrated significant radicals scavenging effect against DPPH and ABTS radicals. In STZ-induced diabetic mice, a considerable decline in blood glucose level was observed after treatment with FcSeNPs. Anti-hyperglycemic effect of FcSeNPs treated animals were high (105 ± 3.22**) as compared to standard drug (128.6 ± 2.73** mg dL-1). Biochemical investigations revealed that all biochemical parameters for pancreas, liver function, renal function panel and lipid profile were significantly lowered in FcSeNPs treated animals. Our findings indicate a preliminary multi-target efficacy for FcSeNPs against type-2 diabetes and thus warrant further detailed studies.

Are Low Weight or Cardiopathy Contraindications for Thoracoscopic Repair of Esophageal Atresia with Tracheoesophageal Fistula?

BACKGROUND: Thoracoscopic repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) is becoming an increasingly widespread technique; there is still controversy about its indication in certain patients. Our objective is to analyze if potential risk factors such as major congenital heart disease (CHD) or low birth weight (LBW) are a limitation to this approach. METHODS: Retrospective study (2017-2021) of patients with EA and distal TEF who underwent thoracoscopic repair were included. Patients with LBW less than 2,000 g or major CHD were compared with the rest. RESULTS: Twenty-five patients underwent thoracoscopic surgery. Nine patients (36%) had major CHD. Five of them (20%) were LBW less than 2,000 g, and only 8% (2/25) presented both risk factors. There were no differences in terms of operative time, conversion rate, tolerance evaluated with gasometric parameters (pO2, pCO2, pH) or complications (anastomotic leak and stricture, both early or during follow-up) in patients with major CHD and LBW (1,473 ± 319 vs. 2,664 ± 402 g). One conversion to thoracotomy was performed in a neonate weighing 1,050 g due to anesthetic intolerance. There was no recurrence of TEF. One patient died at the age of 9 months, due to major uncorrectable heart disease. CONCLUSION: Thoracoscopic repair of EA/TEF is feasible technique in patients with CHD or LBW, with similar results to other patients. The complexity of this technique warrants individualizing the indication in each case. LEVEL OF EVIDENCE: IV.

Recent advances in 2D material-based phototherapy.

Phototherapy, which generally refers to photothermal therapy (PTT) and photodynamic therapy (PDT), has received significant attention over the past few years since it is non-invasive, has effective selectivity, and has few side effects. As a result, it has become a promising alternative to traditional clinical treatments. At present, two-dimensional materials (2D materials) have proven to be at the forefront of the development of advanced nanomaterials due to their ultrathin structures and fascinating optical properties. As a result, much work has been put into developing phototherapy platforms based on 2D materials. This review summarizes the current developments in 2D materials beyond graphene for phototherapy, focusing on the novel approaches of PTT and PDT. New methods are being developed to go above and beyond conventional treatment to fully use the potential of 2D materials. Additionally, the efficacy of cutting-edge phototherapy is assessed, and the existing difficulties and future prospects of 2D materials for phototherapy are covered.

In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House, Chembridge and Zinc Databases by Structure-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations.

Pharmacological strategies to lower the viral load among patients suffering from severe diseases were researched in great detail during the SARS-CoV-2 outbreak. The viral protease Mpro (3CLpro) is necessary for viral replication and is among the main therapeutic targets proposed, thus far. To stop the pandemic from spreading, researchers are working to find more effective Mpro inhibitors against SARS-CoV-2. The 33.8 kDa Mpro protease of SARS-CoV-2, being a nonhuman homologue, has the possibility of being utilized as a therapeutic target against coronaviruses. To develop drug-like compounds capable of preventing the replication of SARS-main CoV-2's protease (Mpro), a computer-aided drug design (CADD) approach is extremely viable. Using MOE, structure-based virtual screening (SBVS) of in-house and commercial databases was carried out using SARS-CoV-2 proteins. The most promising hits obtained during virtual screening (VS) were put through molecular docking with the help of MOE. The virtual screening yielded 3/5 hits (in-house database) and 56/66 hits (commercial databases). Finally, 3/5 hits (in-house database), 3/5 hits (ZINC database), and 2/7 hits (ChemBridge database) were chosen as potent lead compounds using various scaffolds due to their considerable binding affinity with Mpro protein. The outcomes of SBVS were then validated using an analysis based on molecular dynamics simulation (MDS). The complexes' stability was tested using MDS and post-MDS. The most promising candidates were found to exhibit a high capacity for fitting into the protein-binding pocket and interacting with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.

Role of Intravenous Magnesium in the Management of Moderate to Severe Exacerbation of Asthma: A Literature Review.

Asthma is a respiratory disorder marked by bronchial irritation and hyperresponsive airway smooth muscle. According to new research, magnesium's dual activity as an anti-inflammatory and bronchodilator may be important in asthma therapy. The goal of this study was to see how effective intravenous magnesium sulfate is in treating severe acute asthma. In addition to checking Clinicaltrials.gov, we ran a database search in Scopus, Google Scholar, PubMed, and Embase. Studies were chosen based on predetermined inclusion and exclusion criteria to prevent the chance of bias. Most researchers believed that intravenous magnesium sulfate improved symptoms and lung function significantly. Mortality and morbidity data were not available.

In Silico Strategies for Designing of Peptide Inhibitors of Oncogenic K-Ras G12V Mutant: Inhibiting Cancer Growth and Proliferation.

Ras plays a pivotal function in cell proliferation and is an important protein in signal transduction pathways. Mutations in genes encoding the Ras protein drive the signaling cascades essential for malignant transformation, tumour angiogenesis, and metastasis and are responsible for above 30% of all human cancers. There is evidence that N-Ras, K-Ras, and H-Ras play significant roles in human cancer. The mutated K-Ras protein is typically observed in malignant growths. Mutant K-Ras is the most common in lung, colon, and pancreatic cancers. The purpose of this research was to create peptides that inhibit K-Ras G12V. The crystal structure of the mutant K-Ras G12V-H-REV107 complex was obtained from a protein data bank. Further, we used a residue scan approach to create unique peptides from the reference peptide (H-REV107). AMBER molecular dynamics simulations were used to test the stability of the top four proposed peptides (based on binding free energies). Our findings showed that the top four selected peptides had stronger interactions with K-Ras than the reference peptide and have the ability to block the activation function of K-Ras. Our extensive analyses of binding affinities showed that our designed peptide possesses the potential to inhibit K-Ras and to reduce the progression of cancer.

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence.