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Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (sham). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p

Background: This study aimed to evaluate the utility of various blood parameters in predicting oesophageal varices in patients with cirrhosis of liver. Methods: In this retrospective study, laboratory parameters like platelet count, haemoglobin level, serum alanine aminotransferase (ALT) aspartatae aminotransferase (AST) creatinine, albumin, international normalised ratio (INR) and bilirubin were collected from the medical records of patients with cirrhosis who underwent endoscopy for variceal bleeding. The predictors of oesophageal varices from these indices were calculated. Results: One hundred and sixty five patients (mean age 57.5 ± 10.7 years; males) were studied. Sixty seven patients (40.6%) had no oesophageal varices. Of the patients with varices (n = 98), 41 (24.8%) had small and 57 (34.5%) had large varices. Compared with patients without oesophageal varices, those with varices had significantly elevated serum aspartate aminotransferase (P = 0.018), serum bilirubin (P = 0.0001) and significantly low serum albumin (P = 0.0001). Platelet count was < 200,000/mm3 in patients with small and < 100,000/mm3 in patients with large varices (P = 0.0001). Prothrombin time-INR (PT-INR) was higher in patients with small varices compared to those with large varices compared to those with small varices (P = 0.0001). Sensitivity and specificity for PT-INR (area under curve [AUC] = 0.823) were 86% and 74%, respectively, and for platelet counts were (AUC = 0.813) 83% and 64%, respectively. Conclusions: Univariate analysis showed serum bilirubin, serum albumin, haemoglobin, platelet count were statistically significant. However, PT-INR and platelet counts showed high sensitivity and specificity.

The present study was conducted to evaluate the effect of dietary supplementation of vitamin E on semen quality in White Pekin ducks. The drakes were randomly assigned to three experimental groups at 20 weeks of age based on the treatments followed, as T1 (Basal diet), T2 (Basal diet + 100 mg vitamin E/kg diet), and T3 (Basal diet + 200 mg vitamin E/ kg diet). Semen was collected once in four days and was subjected to various microscopic and macroscopic parameters. There was no significant difference in semen volume and appearance score among the experimental treatments. The pH of semen was found slightly alkaline in all three treatments. Most samples were white in colour and were medium thick or thick in consistency.The major contaminants observed were faeces and uric acid crystals. Significantly (p

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

In the age of fast digital transformation, Docker containers have become one of the central technologies for flexible and scalable application deployment. However, this has opened a new dimension of challenges in security, which are skyrocketing with increased technology adoption. This paper discerns these challenges through a manifold approach: first, comprehensive static analysis by Trivy, and second, real-time dynamic analysis by Falco in order to uncover vulnerabilities in Docker environments pre-deployment and during runtime. One can also find similar challenges in security within the Internet of Things (IoT) sector, due to the huge number of devices connected to WiFi networks, from simple data breaches such as brute force attacks and unauthorized access to large-scale cyber attacks against critical infrastructure, which represent only a portion of the problems. In connection with this, this paper is calling for the execution of robust AWS cloud security solutions: IoT Core, CloudWatch, and GuardDuty. IoT Core provides a secure channel of communication for IoT devices, and CloudWatch offers detailed monitoring and logging. Additional security is provided by GuardDuty’s automatized threat detection system, which continuously seeks out potential threats across network traffic. Armed with these technologies, we try to build a more resilient and privacy-oriented IoT while ensuring the security of our digital existence. The result is, therefore, an all-inclusive work on security in both Docker and IoT domains, which might be considered one of the most important efforts so far to strengthen the digital infrastructure against fast-evolving cyber threats, combining state-of-the-art methods of static and dynamic analyses for Docker security with advanced, cloud-based protection for IoT devices.

Liver diseases cause nearly 2 million deaths worldwide each year, with approximately 1 million deaths from cirrhosis complications and another 1 million from viral hepatitis and liver cancer, according to WHO estimates. Liver transplantation (LT) remains the primary curative option, boasting success rates of 85% in the first year and 75% at five years post-transplant. Despite high costs, LT is considered cost-effective, especially for younger patients with active work years remaining. However, post-transplant complications, particularly intrahepatic cholestasis, present notable challenges. This complication arises from factors such as ischemia-reperfusion injury, infections, immunological rejection, and surgical complications, all contributing to impaired bile flow and liver damage. Current medical therapies for post-LT cholestasis are limited, with ursodeoxycholic acid (UDCA) frequently used, despite questionable efficacy. Obeticholic acid (OCA), a potent Farnesoid X Receptor (FXR) agonist approved by the FDA for treating primary biliary cholangitis (PBC), has shown potential benefits in reducing elevated cholestatic liver enzymes. Given its significant effects on liver health, OCA may offer therapeutic value in managing post-transplant cholestasis and improving graft survival. This randomized controlled trial (RCT) aims to evaluate OCA’s efficacy compared to UDCA in reducing cholestatic injury and enhancing graft function post-LT. The primary outcomes will focus on a 15% reduction in alkaline phosphatase and gamma-glutamyl transferase levels at 3, 6, and 12 months from baseline one month. Secondary outcomes include molecular markers, biliary complications, graft rejection, quality of life, and cost-effectiveness. Results are anticipated to demonstrate that OCA could improve graft survival, reduce complications, and enhance quality of life, potentially setting a new standard in post-LT care if found beneficial.

Background: Acute variceal bleeding (AVB), a life-threatening complication of liver cirrhosis, can be effectively treated by endoscopy, but there is a risk of early rebleeding after endoscopic variceal treatment (EVT). Thrombocytopenia is the most common hemostatic abnormality in liver cirrhosis. However, it is still unclear about whether thrombocytopenia increases the failure of EVT in cirrhotic patients with AVB. Objectives: We investigated the association between thrombocytopenia and the failure of EVT in cirrhotic patients with AVB. Design: International multicenter, retrospective study. Methods: Overall, 2467 cirrhotic patients with acute gastrointestinal bleeding who were enrolled into an international multicenter study between September 30, 2020 and June 30, 2023 were retrospectively screened. Thrombocytopenia was defined as platelet count below 150 × 10 9 /L and further classified as mild (100 × 10 9 /L–150 × 10 9 /L), moderate (50 × 10 9 /L–100 × 10 9 /L), and severe (

Menopause marks a significant transition in a woman’s life, typically occurring between the ages of 46 and 55 years, characterized by the cessation of menstruation and a decline in ovarian function. This article provides a comprehensive overview of menopause, examining its physiological, psychological, and social dimensions. It explores the hormonal changes, including decreased levels of estrogen and progesterone, and how these changes contribute to common symptoms such as hot flashes, sleep disturbances, and mood fluctuations. Additionally, it highlights contemporary approaches to management, including lifestyle modifications and hormonal and non-hormonal therapies. By synthesizing current research and clinical insights, this overview aims to enhance understanding and support for women navigating menopause and the healthcare professionals assisting them.

Alterations in normal metabolic processes are defining features of cancer. Glutamine, an abundant amino acid in the human blood, plays a critical role in regulating several biosynthetic and bioenergetic pathways that support tumour growth. Glutaminolysis is a metabolic pathway that converts glutamine into various metabolites involved in the tricarboxylic acid (TCA) cycle and generates antioxidants that are vital for tumour cell survival. As glutaminase catalyses the initial step of this metabolic pathway, it is of great significance in cancer metabolism and tumour progression. Inhibition of glutaminase and targeting of glutaminolysis have emerged as promising strategies for cancer therapy. This review explores the role of glutaminases in cancer metabolism and discusses various glutaminase inhibitors developed as potential therapies for tumour regression.

Air heaters have poor thermal efficiency. Flow obstructions improve the efficiency of the air heater by enhancing heat transfer and disrupting the formation of the laminar sub-layer. In the present study, a rectangular channel of aspect ratio 6 and obstructions of various geometry (triangular, rectangular, and arc (or semi-circular)) are used with a longitudinal pitch (Pl/e) of 4, transverse pitch (Pt/b) of 2 ratios for Reynolds Number (Re) from 5000 to 20000. Various performance parameters such as Nusselt Number (Nu), Friction factor (f), and Thermal Enhancement Factor (TEF) were analyzed for the above conditions using Computational Fluid Dynamics (CFD) to compare the thermohydraulic performance of air heaters with various obstruction geometries. Maximum TEF of 1.27, 1.08, and 1.05 are obtained at Re = 5000 for delta, rectangular, and arc flow obstructions, respectively. Delta flow obstructions are superior to arc and rectangular shapes for the investigated range of Reynolds numbers.

PURPOSEBreast conservation after systemic therapy requires accurate localization of the lesion and its margins, especially in nonpalpable tumors. The present study aims to describe a cost-effective technique of tumor localization using the combination of surgical clips and methylene blue.METHODSA minimum of three or four clips were inserted into the tumor to allow easy visualization of the clip mass. After insertion, measurements of the clips from the nipple and pectoral muscles were recorded to assess for clip migration. After chemotherapy, the disease and clip mass were localized intra-operatively using blue dye. A single-center review of breast conservations performed after neoadjuvant chemotherapy that used the above-described localization technique was undertaken. The primary aim was to assess successful detection and margin-negative resection rates.RESULTSThe study included 65 patients, and the clip mass was detected on ultrasound following chemotherapy in all patients without clip migration. This detection was accurate even in cases of complete pathological and radiological response. Importantly, there were no procedure-related complications. Postchemotherapy disease localization was successfully achieved in all patients using the readily available and cost-effective methylene blue dye. No patient had an invasive margin positive at resection.CONCLUSIONThe combination of using multiple surgical clips and methylene blue is not only an extremely cheap and accurate technique for tumor site localization but also ensures precise surgical removal. The technique allows tumor localization even in low-income economies.

This exhaustive review, explored the multifaceted symptoms and their management in patients with cirrhosis. Patients frequently endure pain, muscle cramps, sleep disturbances, psychological distress, and gastrointestinal issues, significantly impairing their quality of life. Pain is prevalent, often requiring analgesics, while muscle cramps affect up to 68% of patients, treated with supplements like zinc and taurine despite limited evidence. Sleep disturbances, including insomnia and excessive daytime sleepiness, afflict up to 80% of patients, managed through lactulose, melatonin, and cognitive behavioral therapies. Gastrointestinal symptoms, affecting 80%, include abdominal pain and bloating, necessitating lifestyle and dietary adjustments. Mental health disorders, such as depression and anxiety, are common, managed with a combination of pharmacotherapy and psychotherapy. Sexual dysfunction, often overlooked, profoundly impacts both men and women, requiring holistic treatment approaches. Pruritus, another distressing symptom, is managed with moisturizers and antihistamines, though many treatments show limited success. Hair loss and skin changes add to the psychological burden, highlighting the need for a comprehensive, multidisciplinary approach. The review underscores the imperative for tailored, compassionate care to enhance patient outcomes and quality of life in cirrhosis.

Alcohol-associated hepatitis is an extreme form of alcohol-related liver disease associated with high short-term mortality. Currently, there are no authorized therapies for the treatment of severe alcohol-associated hepatitis. Important diagnostic steps for alcohol-associated hepatitis include recognizing the presence of an alcohol use disorder, distinguishing alcohol-related liver disease from metabolic-dysfunction-associated steatotic liver disease, ruling out alternative causes of acute hepatitis, confirming the diagnosis with validated criteria or a liver biopsy, and using the model for end-stage liver disease score to predict clinical outcome and initiate therapy. Due to the lack of other effective therapy options, corticosteroids continue to be used as initial treatment for patients with severe alcohol-associated hepatitis. Patients who do not improve while on steroid treatment and are ideal candidates should be considered for curative liver transplantation as soon as possible. Avoiding unnecessary and ineffective pharmacological and interventional therapy can help to keep costs down. If a patient is not a good candidate for a transplant or is rapidly deteriorating in health due to a condition such as acute or chronic liver failure, a salvage/bridge to transplant should be pursued through enrolment in a clinical trial program. The role of healthy donor stool transplant and targeted bacteriophage therapy seems promising, pending prospective controlled trials.

Introduction. The well-being of nurses in the field of oncology is paramount, both for the individuals themselves, also for the healthcare system. The purpose of this study was to comprehend and investigate nurses' experiences in the field of oncology, to understand the factors influencing their well-being. Methods. Between January 1, 2023, and April 5, 2023, a descriptive qualitative design was employed to gather data from individual in-depth interviews with eleven nurses working in the oncology department of a tertiary care hospital in Central Kerala, South India. Participants were selected and recruited based on inclusion criteria and purposive sampling techniques. A semi-structured in-depth face-to-face interview was conducted to obtain the data. Codes were identified, patterns analyzed, and themes were recorded using the Colaizzi approach, steps of thematic analysis. Results. The mean experience of the participants in the oncology department was 6.2 years and all were females. Two main themes that emerged from the analysis were Roadblocks to well-being and Concerns with satisfaction. Additionally, four sub-themes under the first theme and six under the second were identified, providing a nuanced understanding of the challenges faced by these nurses. Conclusion.The study's nurses battled occupational stress as well as physical and psychological issues, which can even reduce their quality of life. The results of this investigation provide valuable primary data for developing bio-psycho-social skill interventions for health professionals’ well-being in the oncology department.