The Cost-Effectiveness of Early Invasive Procedures for Acute Coronary Syndrome in Low-Income Regions: A Prospective Cohort Study in Pakistan.

Background Acute coronary syndrome (ACS) is a significant cause of mortality and morbidity globally, necessitating effective intervention strategies. Early invasive procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are often recommended for high-risk patients. However, their cost-effectiveness in low-income regions remains uncertain, particularly in Pakistan, where healthcare resources are limited. Objective This study aims to evaluate the cost-effectiveness of early invasive procedures compared to standard care for ACS in low-income regions of Pakistan. Methods We conducted a prospective cohort study from January 1, 2021, to January 31, 2021, at four major hospitals in Pakistan: Army Cardiac Center Combined Military Hospital (CMH) Lahore, National Institute of Cardiovascular Diseases in Karachi, Lady Reading Hospital in Peshawar, and Mardan Medical Complex. The participants included 436 patients diagnosed with ACS aged 18 years or older and presenting within 24 hours of symptom onset. The patients were divided into two groups: the early invasive procedure group (n = 218) and the standard care group (n = 218). The primary outcome was the 30-day mortality rate. Secondary outcomes included recurrent myocardial infarctions, hospital readmissions, healthcare costs, and procedural complications. Data were analyzed using SPSS version 25.0 (IBM SPSS Statistics, Armonk, NY), employing descriptive statistics, chi-square tests, independent t-tests, and Kaplan-Meier survival analysis. Results The early invasive procedure group showed a mortality rate of 18 (8%) compared to 33 (15%) in the standard care group, demonstrating a significant reduction in mortality (p = 0.01). Additionally, the average healthcare cost was significantly lower in the early invasive group, with mean costs of Pakistani rupee (PKR) 187,200 (US dollar {USD} 1,200) compared to PKR 280,800 (USD 1,800) in the standard care group (p < 0.01). Recurrent myocardial infarctions occurred in 11 (5%) of the early invasive group versus 26 (12%) in the standard care group (p < 0.05). Hospital readmission rates were lower in the early invasive group, 22 (10%) compared to 39 (18%) in the standard care group (p < 0.05). Healthcare costs were significantly lower in the early invasive group, with mean costs of PKR 187,200 (USD 1,200) compared to PKR 280,800 (USD 1,800) in the standard care group (p < 0.01). Conclusion Early invasive procedures for ACS significantly improve survival rates, reduce complications, and lower healthcare costs in low-income regions of Pakistan. These findings suggest that such strategies should be considered in resource-limited settings to optimize patient outcomes and healthcare resource utilization.

Sustainable synthesis of bakuchiol-mediated gold nanoparticles for drug delivery against bacterial strains and tumor microenvironments, and its in silico target proteins identification.

Introduction: The sustained synthesis of gold nanoparticles (GNPs) has gained significant attention in biomedical applications. In this study, we explored the antibacterial and anticancer potential of bakuchiol-mediated gold nanoparticles (Bak-GNPs). Bakuchiol, a natural compound found in Psoralea corylifolia seeds, serves as both a reducing and stabilizing agent for green synthesis of GNPs. Our objectives include network analysis, molecular docking, synthesis of GNPs, characterization, and antipathogenic and anticancer efficacy of Bak-GNPs against lung and liver cancers. Methods: Protein-protein interaction networks were analyzed to identify effective protein targets for bakuchiol in lung and liver cancers. A molecular docking study was performed to validate the efficacy of the target protein against lung and liver cancer. Furthermore, Bak-GNPs were synthesized using bakuchiol and characterized by various techniques such as UV-visible spectroscopy, dynamic light scattering (DLS), zeta potential transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy, and their potential against pathogens and lung and liver cancers. Results: GNAI3 emerged as the most promising target, with a binding energy of -7.5 kcal/mol compared to PTGER3's -6.9 kcal/mol, different characterization techniques revealed the successful synthesis of Bak-GNPs. Bak-GNPs exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, as confirmed by minimum inhibitory concentration (MIC) values. Bak-GNPs demonstrated significant anticancer effects on A549 (lung cancer) and HepG2 (liver cancer) cells, with IC50 values of 11.19 µg/mL and 6.6 µg/mL, respectively. Induction of apoptosis and inhibition of cell proliferation were observed in both the cell lines. The increased production of reactive oxygen species (ROS) contributes to its anticancer effects. Discussion: This study highlights promising biomedical applications of bakuchiol-mediated GNPs. This green synthesis approach using bakuchiol provides a sustainable method for producing nanoparticles with enhanced biological activities. Further exploration of the pharmacological properties and mechanisms of Bak-GNPs is required to optimize their therapeutic efficacy for clinical use.

Natural sesquiterpene zingiberene exerts ameliorative effects on growth of glioblastoma cells by instigating ROS mediated apoptosis.

Glioblastoma multiforme is the most aggressive and invasive primary brain tumor in adults and its prognosis and survival rate remain poor. Despite substantial improvements in therapy, the 5-year survival rate of glioblastoma patients remains low. Sesquiterpenes have previously been found to be effective in inhibiting the proliferation and growth of breast, gastric and lung cancer cells. Owing to their efficacy, sesquiterpenes have been used in various clinical trials. In the present study, we investigated the anticancer efficacy of a well-known sesquiterpene, Zingiberene, isolated from Zingiber officinale in C6 glioblastoma cells. Zingiberene suppresses the growth and proliferation of C6 cells. Upon treatment of C6 cells with zingiberene, nuclear fragmentation and ROS were qualitatively enhanced compared to untreated control cells. The levels of caspase-3 were also significantly reduced (p<0.01), with a concomitant decline in the mRNA expression of Bax and Bcl-2. On the basis of molecular docking studies, Zingiberene demonstrated good binding energy score of -6.8 and -5.5 Kcal/mol towards Bax and Bcl-2 proteins, respectively. Based on these observations, it was inferred that zingiberene has potential as a plausible therapeutic agent against glioblastoma cells. Detailed mechanistic studies are needed to substantiate and establish the anticancer effects of zingiberene against glioblastoma cells.

Role of Dietary Patterns in the Progression and Management of Heart Failure in Pakistani Patients: A Multicenter Study.

BACKGROUND: Heart failure (HF) is a chronic condition with increasing prevalence in Pakistan due to common cardiovascular risk factors. Dietary interventions are known to influence HF outcomes, but data specific to Pakistani patients are limited. OBJECTIVE: This study aimed to evaluate the impact of dietary patterns on HF progression and management in Pakistani patients, alongside the effects on quality of life and biochemical markers. METHODS: A prospective cohort study was conducted across four medical centers in Pakistan, enrolling 170 HF patients. Dietary patterns were assessed using a validated Food Frequency Questionnaire (FFQ) tailored to the South Asian population. The primary outcomes measured were changes in the ejection fraction, New York Heart Association (NYHA) class, and hospitalization rates. Secondary outcomes included changes in quality of life and biochemical markers. Multivariate logistic regression was used to adjust for confounding variables, and Bonferroni corrections were applied to account for multiple comparisons. RESULTS: Adherence to a heart-healthy diet significantly improved the ejection fraction (from 35% to 38%, p = 0.04), reduced hospitalization rates (22%, p = 0.03), and improved NYHA class (45%, p = 0.05). Subgroup analysis showed a 10% reduction in mortality among patients over the age of 65 (p = 0.01) and 18% in diabetic patients (p = 0.02). CONCLUSION: Dietary interventions play a critical role in HF management among Pakistani patients. Culturally tailored dietary guidelines should be integrated into clinical practice to improve patient outcomes.

Paediatric Early Warning Score to Detect Deterioration in Paediatric Patients at a Tertiary Care Hospital of a Developing Country: A Validation Study.

OBJECTIVE: To test the validity of the paediatric early warning score (PEWS) and to identify the patients with deteriorating clinical conditions who were reviewed by a rapid response team (RRT) and were advised higher level of care. STUDY DESIGN: Observational study. Place and Duration of the Study: Paediatric ward and high dependency unit (HDU) of The Aga Khan University Hospital (AKUH), Karachi, Pakistan, from January 2021 to March 2022. METHODOLOGY: All children aged 1 month to 18 years, admitted with non-surgical diagnoses at AKUH and referred for an RRT consultation were identified by non-probability consecutive sampling. The bedside nurse assessed the PEWS and alerted the clinical team. The patient's further course of action was decided based on the PEWS, detailed systemic examination, and laboratory workup. This aided in deciding the level of care (General ward, HDU, Paediatric Intensive Care Unit) required by the patients. Patients with length of stay >24 hours were included and those with did not resuscitate orders were excluded. RESULTS: Overall 10,032 patients were admitted to the ward and high dependency unit (HDU). Out of which, 323 (3.2%) patients had an RRT call and were included in the study. The median age of the study population was 3.15 years during the study period, and 30.3% were <1 year. System-wise admission diagnoses included respiratory (33.2%) and neurological diseases (16.1%). Median [interquartile range (IQR)] PEWS at RRT call was 2 (IQR, 1-2) on median admission day 2 (IQR, 1-3). The cumulative data at PEWS ≥3 demonstrated an area under the curve of 63% with a sensitivity of 90% and a specificity of 30%. CONCLUSION: PEWS >3 can probably identify the patients at risk of deterioration with excellent sensitivity. KEY WORDS: Paediatrics, Rapid response team, Early warning score.

A Dual Diagnostic Dilemma: Viral Encephalitis and Cerebral Venous Thrombosis.

Herpes encephalitis is caused by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). One of the infrequent complications of herpes encephalitis is cerebral venous thrombosis (CVT) because of the inflammation in the brain parenchyma. We report a unique and challenging case of a 14-year-old female patient presenting with confusion, headache, and fever. On examination, there was no neck rigidity and a negative Kernig's sign with no focal neurological deficits. Systemic examination was done to rule out other systems as a cause for her symptoms, and she was empirically treated as a case of encephalitis. An initial computed tomography (CT) scan of the brain without contrast was normal except for a subtle hypoattenuating area involving the right thalamus. Cerebrospinal fluid (CSF) analysis revealed viral infection while we awaited the results of CSF polymerase chain reaction (PCR) and culture analysis for specific microorganisms. Her Glasgow Coma Scale (GCS) deteriorated following an episode of generalized tonic-clonic seizure, and she was subsequently catheterized and an enteral feeding tube (nasogastric tube) was passed. CSF PCR detected HSV-1. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain with contrast revealed encephalitis with superior sagittal sinus, transverse sinus, straight sinus, and vein of Galen thrombosis yielding a diagnosis of HSV encephalitis with concurrent cerebral venous thrombosis. Hence, this required a very specialized and cautious approach to her treatment. She was started on intravenous acyclovir and subcutaneous enoxaparin, and she recovered over the next few days. She did, however, develop acyclovir-induced renal toxicity in the absence of another offending agent, and the dose of the acyclovir was adjusted accordingly. A diagnosis of CVT, although rarely described, should be systematically suspected in patients with HSV encephalitis presenting with sudden deterioration or unexpected neurological findings in the early phase of treatment or inadequate response to treatment for better management and outcomes.

Clots and bleeds: the outcomes of percutaneous coronary intervention in hemophilia patients with acute coronary syndrome.

BACKGROUND: Hemophilia is a disease characterized by a high risk of bleeding. With advances in treatment, life expectancy and aging-associated diseases such as coronary artery disease have increased. Our primary objective is to assess for major adverse outcomes, mortality, and length of hospital stay in individuals with hemophilia presenting for acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI). METHODS: Our retrospective cohort study analyzed data from the Nationwide Inpatient Sample Database (NIS) for 2018 to investigate the outcomes of ACS management with PCI in adults with and without hemophilia. We used ICD-10 codes to exclude patients with significant comorbidities and identify those with ACS undergoing PCI. Propensity score matching and multivariable logistic regression were employed to account for over 20 baseline characteristics, mitigating confounding factors. RESULTS: The incidence of gastrointestinal bleeding (11.0% vs. 2.8%, p < 0.001), hemorrhagic stroke (10.0% vs. 1.4%, p < 0.001), and retroperitoneal hemorrhage (5.6% vs. 1.4%, p < 0.001) was significantly higher in individuals with hemophilia undergoing PCI compared to those without hemophilia. Additionally, venous thromboembolism (VTE) incidence was notably higher in the hemophilia cohort (6.6% vs. 2.4%, p = 0.027). The hemophilia cohort also experienced a higher mortality rate (7.1% vs. 3.3%, p = 0.037) and longer hospital stays. CONCLUSION: Patients with hemophilia undergoing PCI are at a significantly greater risk of adverse events, increased mortality, and longer hospital stays than the general population. To mitigate the risk of unfavorable outcomes, it is crucial to ensure adequate replenishment of coagulation factors and establish close collaboration between cardiologists and hematologists.

Phytochemical characterization, antimicrobial properties and in silico modeling perspectives of Anacyclus pyrethrum essential oil.

Medicinal plants are used widely in the treatment of various infectious diseases. One of these medical plants is Moroccan plants such as Anacyclus pyrethrum. In this study, the essential oil isolated from the leaves of Anacyclus pyrethrum (APEO) by the hydrodistillation method was analyzed using (GC/MS) analysis. A total of forty-four compounds were identified form the oil and the oxygenated monoterpenes were the most abundant class of compounds. The major identified compound is santolina alcohol (40.7 %), followed by germacrene-D (8.9 %). The in-vitro assessment of the antimicrobial efficacy of APEO encompassed an investigation involving six microbial strains, including two Gram-positive bacteria, four Gram-negative bacteria, and three fungal strains. The findings revealed noteworthy antibacterial and antifungal properties against all examined microorganisms, with inhibitory zone diameters ranging from 25.67 ± 0.06 mm to 25.19 ± 0.03 mm for Gram-positive bacteria and from 22.34 ± 0.01 mm to 14.43 ± 0.02 mm for Gram-negative bacteria, as determined through the disc-diffusion assay. In the case of antifungal activity, inhibitory zones ranged from 24.57 ± 0.04 mm to 18.37 ± 0.06 mm. Further evaluation revealed that the MIC values of Gram-positive bacteria were at the concentration 0.25 % v/v, while MBC values ranged from 0.25 % to 1.0 % v/v. The Gram-negative bacteria exhibited MIC values spanning from 0.5 % to 2.0 % v/v, with MBC values in the range of 0.5 %-2.0 % v/v. For the fungal strains, MIC values ranged from 0.5 % to 1.0 % v/v, while the MFC consistently remained at 1.0 % for all tested fungal strains. The assessment of the MBC/MIC and MFC/MIC ratios collectively indicates that A. pyrethrum EO possesses bactericidal and fungicidal attributes. The in silico study of bioavailability predictions for compounds in APEO based on six physicochemical properties show optimal physiochemical properties including size, lipophilicity, solubility, flexibility, and saturation. α-Pinene, limonene, germacrene D, and (E)-ß-farnesene are non-polar due to their lack of polar groups, and the ADME profile indicates desirable properties for considering these compounds in drug development. Molecular docking investigation indicates that all the compounds of APEO reside well into the binding site of the DNA gyrase B enzyme of Staphylococcus aureus by mediating a number of significant interactions with the binding site residues. The ADME analysis suggested that the major compounds APEO possess desirable properties for further consideration in drug development. In light of these findings, APEO could serve as a natural source for the elaboration of new and active antimicrobial drugs.

Role of therapeutic plasmapheresis in acute liver failure in paediatric patients: A case series.

Paediatric acute liver failure (PALF) is a rare yet severe condition that is associated with high mortality. Apart from liver transplant, no specific therapy exists, particularly in developing countries. Evidence suggests that removal of damage-associated molecular patterns, cytokines, toxins, and other metabolites that accumulate due to impaired liver function can enhance natural recovery. Plasmapheresis can be used to remove these products; however, there is limited evidence to support this approach. This case series discusses three critically ill patients with acute liver failure who underwent plasmapheresis. The patients included a seven-year-old boy (Case 1), a 17-year-old boy (Case 2), and a 16-monthold boy (Case 3). Two patients showed significant improvement in bilirubin level, coagulation profile, inotropes requirement, and Glasgow coma scale score. Unfortunately, one patient with PALF, complicated with multi-organ dysfunction, died due to refractory shock on the fourth day of hospitalisation. Our findings illustrate that early use of therapeutic plasmapheresis in PALF can lead to improvement in clinical outcome. It may serve as a bridging therapy for liver transplant and for the spontaneous regeneration of the patient's liver.

pH-Sensitive Tacrolimus loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease.

Inflammatory Bowel Disease is the chronic tissue inflammation of the lower part of the Gastrointestinal tract (GIT). Conventional therapeutic approaches face numerous challenges, often making the delivery system inadequate for treating the disease. This study aimed to integrate a pH-sensitive polymer and nanostructured lipid carriers (NLCs) to develop a hybrid nanocarrier system. Tacrolimus-loaded NLCs coated with Eudragit® FS100 (TAC-NLCs/E FS100) nanoparticles were prepared via double emulsion technique followed by an aqueous enteric coating technique. Various parameters, such as particle size, entrapment efficiency, and zeta potential were optimized using Design Expert software®. Cetyltrimethyl ammonium bromide (CTAB) was used as a cationic surfactant which induces a positive charge on the nanoparticles. These cationic NLCs can adhere to the mucosal surface, thereby enabling prolonged retention. In vitro drug release was assessed, and the results demonstrated that drug release was retarded at pH 1.2 corresponding to upper GIT pH and maximum drug was released at pH 7.4 (colonic pH). Moreover, we evaluated TAC-NLCs/E FS100 nanoparticles in murine colitis models to gauge the efficacy of both coated and uncoated NLCs formulation. The TAC-NLCs/E FS100 showed a pronounced reduction in induced colitis, as evident from the restoration of morphological features, improved histopathological scores, antioxidant levels, and decreased the levels of proinflammatory cytokines. Thus, pH-sensitive TAC-NLCs/EFS 100 are attributed to the enhanced localization and targeted delivery at the specific site.

A hybrid residue based sequential encoding mechanism with XGBoost improved ensemble model for identifying 5-hydroxymethylcytosine modifications.

RNA modifications play an important role in actively controlling recently created formation in cellular regulation mechanisms, which link them to gene expression and protein. The RNA modifications have numerous alterations, presenting broad glimpses of RNA's operations and character. The modification process by the TET enzyme oxidation is the crucial change associated with cytosine hydroxymethylation. The effect of CR is an alteration in specific biochemical ways of the organism, such as gene expression and epigenetic alterations. Traditional laboratory systems that identify 5-hydroxymethylcytosine (5hmC) samples are expensive and time-consuming compared to other methods. To address this challenge, the paper proposed XGB5hmC, a machine learning algorithm based on a robust gradient boosting algorithm (XGBoost), with different residue based formulation methods to identify 5hmC samples. Their results were amalgamated, and six different frequency residue based encoding features were fused to form a hybrid vector in order to enhance model discrimination capabilities. In addition, the proposed model incorporates SHAP (Shapley Additive Explanations) based feature selection to demonstrate model interpretability by highlighting the high contributory features. Among the applied machine learning algorithms, the XGBoost ensemble model using the tenfold cross-validation test achieved improved results than existing state-of-the-art models. Our model reported an accuracy of 89.97%, sensitivity of 87.78%, specificity of 94.45%, F1-score of 0.8934%, and MCC of 0.8764%. This study highlights the potential to provide valuable insights for enhancing medical assessment and treatment protocols, representing a significant advancement in RNA modification analysis.

PSSM-Sumo: deep learning based intelligent model for prediction of sumoylation sites using discriminative features.

Post-translational modifications (PTMs) are fundamental to essential biological processes, exerting significant influence over gene expression, protein localization, stability, and genome replication. Sumoylation, a PTM involving the covalent addition of a chemical group to a specific protein sequence, profoundly impacts the functional diversity of proteins. Notably, identifying sumoylation sites has garnered significant attention due to their crucial roles in proteomic functions and their implications in various diseases, including Parkinson's and Alzheimer's. Despite the proposal of several computational models for identifying sumoylation sites, their effectiveness could be improved by the limitations associated with conventional learning methodologies. In this study, we introduce pseudo-position-specific scoring matrix (PsePSSM), a robust computational model designed for accurately predicting sumoylation sites using an optimized deep learning algorithm and efficient feature extraction techniques. Moreover, to streamline computational processes and eliminate irrelevant and noisy features, sequential forward selection using a support vector machine (SFS-SVM) is implemented to identify optimal features. The multi-layer Deep Neural Network (DNN) is a robust classifier, facilitating precise sumoylation site prediction. We meticulously assess the performance of PSSM-Sumo through a tenfold cross-validation approach, employing various statistical metrics such as the Matthews Correlation Coefficient (MCC), accuracy, sensitivity, specificity, and the Area under the ROC Curve (AUC). Comparative analyses reveal that PSSM-Sumo achieves an exceptional average prediction accuracy of 98.71%, surpassing existing models. The robustness and accuracy of the proposed model position it as a promising tool for advancing drug discovery and the diagnosis of diverse diseases linked to sumoylation sites.

Insights into tuberculosis burden in Karachi, Pakistan: A concurrent adult tuberculosis prevalence and child Mycobacterium tuberculosis infection survey.

Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission.

Hantavirus-induced cardiac tamponade: A diagnostic dilemma.

Herein we describe a case of a 60-year-old white male from New York City who was admitted to hospital due to worsening dyspnea. He presented with an acute onset of fever, night sweats, and progressively worsening nonproductive cough and orthopnea over the preceding week. Electrocardiogram findings revealed atrial fibrillation. Manifesting signs of hypoperfusion, a trans-esophageal echocardiography was performed, which demonstrated the presence of a cardiac tamponade. An emergency pericardiocentesis was performed, draining 750 cc of serosanguinous content. Laboratory investigations depicted an inflammatory milieu marked by lymphocytic leukocytosis, cardiac function impairment, and remarkably elevated d-dimer and brain natriuretic peptide levels. Notably, high-sensitivity troponin T remained within normal limits. Comprehensive viral panel assays, including COVID-19, Influenza A + B, Respiratory Syncytial Virus, Hepatitis C, HIV, Cytomegalovirus, Coxsackie A + B, and Herpes Simplex Virus, returned negative results. Furthermore, antinuclear factor and rheumatoid factor titers were negative. Blood and fungal cultures, as well as assessments for Mycobacterium tuberculosis, yielded negative findings. On further history-taking, he reported that he had occupational exposure to rat droppings and urine two weeks ago. Serological analysis demonstrated positive hantavirus IgG and IgM antibodies. Supportive management was initiated. Consequently, the patient was discharged asymptomatic, without pericardial effusion. Evaluation after two weeks revealed no recurrence of symptoms.

Exploring stevioside binding affinity with various proteins and receptors actively involved in the signaling pathway and a future candidate for diabetic patients.

Introduction and Background: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels and is one of the main global health concerns. Synthetic sugar substrate has many side effects such as leukemia, bladder cancer, hepatotoxicity, breast cancer, headache, and brain toxicity. The WHO and FDA has recently banned some of the synthetic sugar alternatives due to their carcinogenic effects. Objective and Methodology: Therefore, the main objective of the current study was to investigate the safety and binding affinity of Stevioside with Glucose Transpoter-4 (GLUT-4), Akt, Insulin Receptor (IR) and Insulin Receptor Substrate-1 (IRS-1) to confirmed that Stevioside is one the potent natural sweetener/drug for diabetes. This study delves into the molecular interaction between Stevioside and key diabetic proteins: GLUT-4, Akt, IR and IRS-1. A precise molecular docking approach was used to simulate the binding affinity of Stevioside to these proteins. The pharmacokinetic properties of the molecule should be taken into consideration as important variables throughout the virtual screening process. Results: The result of active site analysis of GLUT-4, Akt, IR and IRS-1 showed a zone of 2158.359 Ǻ2, 579.259 Ǻ2, 762.651 Ǻ2, and 152.167 Ǻ2 and a volume of 2765.094 Ǻ³, 355.567 Ǻ³, 686.806 Ǻ³, and 116.874 Ǻ³, respectively. Docking analysis of the Stevioside compound showed the highest docking energy with scores of -9.9 with GLUT-4, -6.7 with Akt, -8.0 with IR and -8.8 with IRS-1. Studies indicated that it remains undigested by stomach acids and enzymes and is not absorbed in the upper small intestine. Further, tests revealed no hepatotoxicity, AMES toxicity, or skin sensitivity, making it a promising candidate for safe consumption as drug metabolism. Conclusion and Recommendations: Instead of other sugar alternatives, Stevioside will help diabetic patients with a lower chance of infections, lowered blood pressure/blood sugar, and increased glucose uptake in diabetic muscles. Stevioside is a natural sweetener, and the current study recommends its usage in various dietary products for diabetic patients.

Tumour-To-Tumour Metastasis: A Rare Case of Prostate Cancer Metastasising to Primary Lung Adenocarcinoma.

Tumour-to-tumour metastasis (TTM) is a rare phenomenon that clinicians should be aware of when evaluating patients with a history of prostate cancer. We present the diagnosis and management of an 80-year-old former smoker with high-risk prostate cancer, who developed a lung nodule consistent with TTM. The patient had concurrent primary lung adenocarcinoma and metastatic prostate cancer, making this a unique case of dual primary and metastatic malignancies. The complexity of this case highlights the need for comprehensive evaluation and interdisciplinary management in patients with multiple malignancies. The literature review reveals that these are extremely rare occurrences, with most cases involving metastasis to the second primary tumour. Despite the challenges in diagnosing preoperatively, it is important to consider TTM as a possibility in patients with prostate cancer who present with a lung nodule. This report presents one of the few documented cases of TTM. It also reviews relevant cases in the literature and discusses the current situation in relation to established criteria for classifying combination tumours. LEARNING POINTS: Isolated lung metastasis with prostate cancer is exceptionally rare in the literature.Tumour-to-tumour metastasis cases present challenges in sampling and interpreting histopathology.In instances of tumour-to-tumour metastasis, it is vital to consider the patient's clinical history, perform thorough gross examination and obtain appropriate samples to distinguish between the separate tumour components.

Preparation, characterization and functional evaluation of soy protein isolate-peach gum conjugates prepared by wet heating Maillard reaction.

This study was conducted to formulate a conjugate of soy protein isolate (SPI) and peach gum (PG) with improved functional properties, interacting at mass ratios of 1:1, 1:2, 1:3, 2:1, and 2:3 by Maillard reaction via wet heating method. Conjugation efficiency was confirmed by grafting degree (DG) and browning index (BI). Results indicated that DG increased with increasing concentration of PG, and decreased with increasing pH, whereas no remarkable change was observed with increasing reaction time. The conjugates were optimized at a ratio of 1:3. SDS-PAGE confirmed conjugate formation, Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) verified conjugate secondary structural changes, and scanning electron microscopy (SEM) indicated significant overall structural changes. The functional properties, solubility, emulsifying stability, water holding, foaming, and antioxidant activity were significantly improved. This study revealed the wet heating method as an effective approach to improve the functional properties of soy protein.

Navigating the Diagnostic Maze: A Case Report of Immunoglobulin G4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition characterized by significant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells within affected tissues, with or without elevated serum IgG4 levels. The prevalence of IgG4-RD remains largely undetermined due to diagnostic challenges, as the condition is frequently unrecognized or misdiagnosed. This report describes a case of a 63-year-old man who was ultimately diagnosed with this rare condition after an extensive two-year period of elusive symptoms. Initially presenting with intermittent body pains and fluctuating fever, his condition progressively evolved to include severe right orbital swelling with marked tenderness and ecchymosis, recurrent non-tender nodules on his arm, and diminished vision. A detailed review of his medical history prompted the consideration of IgG4-RD, leading to the measurement of serum human IgG4 levels, which were found to be significantly elevated at 1504 mg/L (normal range: 39.2-864 mg/L). Following his diagnosis, treatment with glucocorticoids (0.6 mg/kg for one month) was initiated, resulting in a positive clinical response. This case emphasizes the critical importance of considering less common conditions in the differential diagnosis of patients presenting with complex, multi-system symptoms.