Exploring the Functionality of Technology-driven CPR Training Methodologies Among Healthcare Practitioners: A Randomized Control Pilot Study.

Introduction: Cardiopulmonary resuscitation training in Malaysia has evolved from traditional to modern approaches, embracing technology for better outcomes. Smartphone-based training apps offer interactive learning with simulations and real-time feedback, improving cardiopulmonary resuscitation skills anytime, anywhere. This study evaluates the effectiveness of the smart-cardiopulmonary resuscitation application for healthcare practitioners. Methods: This randomized controlled pilot study was conducted with 30 healthcare practitioners at the University of Malaysia Sabah. Participants underwent a Cardiopulmonary Resuscitation Practical formal educational training program, and data were collected using a Basic Life Support questionnaire and skills assessment checklist sourced from the American Heart Association (2020). Data analysis was conducted utilizing repeated analysis of variance and the Cochran 'Q' test supported by Statistical Package for the Social Sciences statistical software. Result: The control and intervention groups showed improved knowledge and skills from pre-to post-cardiopulmonary resuscitation courses; a significant increase was observed in the intervention group compared to the control group. The F-test indicated a significant time-group effect (F-stat (df) = 16.14 (2), p = 0.01). Cochran's 'Q' test also revealed significant changes in the proportion of healthcare practitioners passing their skills assessments over time (2 = 14.90, control 01). Conclusion: The smart-cardiopulmonary resuscitation application is convenient for refreshing cardiopulmonary resuscitation skills and maintaining proficiency. While it doesn't replace formal cardiopulmonary resuscitation courses, it saves healthcare practitioners and the community time and money. Both groups showed improved cardiopulmonary resuscitation knowledge and skills, with the intervention group using the smart-cardiopulmonary resuscitation application showing higher success rates after two months. Adopting smartphone-based cardiopulmonary resuscitation training with comprehensive content is recommended.

Intratympanic injections of emulsion-like dispersions to augment cinnarizine amount in a healthy rabbit inner ear model.

Aim: To investigate eutectic liquid-based emulsion-like dispersions for intratympanic injections to augment cinnarizine permeability across round window membrane in a healthy rabbit inner ear model. Methods: Two-tier systematic optimization was used to get the injection formula. The drug concentrations in perilymph and plasma were analyzed via. Ultra-performance liquid chromatography-tandem mass spectrometry method after 30-, 60-, 90- and 120-min post intratympanic injection time points in rabbits. Results: A shear-thinning behavior, immediate drug release (∼98.80%, 10 min) and higher cell viability (>97.86%, 24 h) were observed in dispersions. The cinnarizine level of 8168.57 ± 1236.79 ng/ml was observed in perilymph at 30 min post intratympanic injection in rabbits. Conclusion: The emulsion-like dispersions can augment drug permeability through round window membrane.

[Box: see text].

Cochlear Implantation by Veria Technique in Abnormal Cochlea: Our Experience.

This study describes the clinical profile, operative findings, surgical technique, type of implant and complications encountered in implantation of abnormal cochlea by the transcanal (veria) technique in a tertiary care centre. This is a retrospective study done amongst 337 patients who underwent cochlear implantation by veria technique between January 2013 to August 2023. Based on pre-operative imaging with high-resolution computed tomography and magnetic resonance imaging the cochleovestibular malformations in this study were classified according to Sennaroglu classification and the cochlear ossification was graded from I to IV. Amongst the 337 patients who underwent cochlear implantation during the study period there were 79 cases (23.4%) with abnormalities of cochlea. This included 45 patients (13.4%) with congenital malformations, 20 patients (5.9%) with cochlear fibrosis and 14 patients (4.2%) with cochlear ossification. The commonest cochlear malformation was Incomplete Partition 2 which was present in 21 patients (46.7%). The other common malformations were cochlear hypoplasia (31.1%), Incomplete Partition 1(13.3%) and common cavity (8.9%). Out of the 20 patients with cochlear fibrosis, 17 patients had fibrosis only in the basal turn. Out of the 14 patients with cochlear ossification 8 patients (57.1%) had a grade 1 ossification, 2 patients (14.3%) had a grade 2 ossification and 4 patients (28.6%) had a grade 3 ossification. One of the patients required re-exploration for correcting the placement of electrode. The type of implant were chosen depending on individual malformation or length of ossification and fibrosis. In the past, inner ear anomalies were considered as a contraindication for cochlear implantation however it is now possible to implant most of these abnormal cochlea by careful planning, a modification of the surgical technique and the type of electrode used.

3D Reconstruction and Virtual Reality Is an Acceptable and Feasible Method for Addressing Body Image in Bariatric Metabolic Surgery.

BACKGROUND: Patients living with obesity continue to experience body image dissatisfaction following bariatric metabolic surgery. The underlying reasons are poorly understood but may be due to unmet expectations. Negative body image perception following metabolic surgery leads to poorer psychological and clinical outcomes. This study aims to establish the acceptability and feasibility of three-dimensional (3D) reconstruction and virtual reality (VR) as a method of providing psychological support to bariatric patients to improve body image satisfaction and interventional outcomes. METHODS: Seven participants were recruited from the Imperial Weight Centre. 3D photographs were captured and processed to produce two 3D reconstructed images with 15% and 25% total weight loss. Participants were shown their images using VR and participated in peer group workshops. RESULTS: Six participants were retained until the end of the study. Five out of six participants agreed the images provided them with a more accurate representation of their body changes and overall appearance following bariatric metabolic surgery. All participants strongly agreed with the group setting and felt VR facilitated discussions on body image. Overall, all participants felt that the use of VR and 3D reconstruction is beneficial in supporting patients to adjust to changes in their body image after bariatric metabolic surgery. CONCLUSIONS: This is the first study to explore and demonstrate that 3D reconstruction and VR is an acceptable and feasible method providing patients with a realistic expectation of how their body will change following significant weight loss, potentially improving body image satisfaction after surgery, as well as psychological and interventional outcomes.

Studies on cationic ocular emulsions containing bipartitioned oil droplets to codeliver cyclosporin A and etodolac.

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.

[Box: see text].

The Effect of a Combined Intermittent Fasting Healthy Plate Intervention on Anthropometric Outcomes and Body Composition Among Adults With Overweight and Obesity: Nonrandomized Controlled Trial.

BACKGROUND: Adult obesity and overweight pose a substantial risk to global public health and are associated with various noncommunicable diseases. Although intermittent fasting (IF) is increasingly used as a relatively new dietary strategy for weight loss, the effectiveness of 2 days per week of dry fasting remains unknown. OBJECTIVE: This study aims to evaluate the effectiveness of a combined dry IF and healthy plate (IFHP) and healthy plate (HP) intervention in improving anthropometric outcomes and body composition. METHODS: This nonrandomized controlled trial involved 177 adults who were overweight and obese. Among them, 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) were allocated to the HP group. The overall study duration was 6 months (October 2020 to March 2021). The intervention was divided into 2 phases: supervised (3 months) and unsupervised (3 months). The data were collected at baseline, after the supervised phase (month 3), and after the unsupervised phase (month 6). Anthropometric (weight, height, waist circumference, and hip circumference) and body composition (body fat percentage, body fat mass, skeletal muscle mass, and visceral fat area) data were measured at all 3 data collection points. Sociodemographic data were obtained using a questionnaire at baseline. RESULTS: Most participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). After 3 months, there were significant reductions in weight (difference -1.68; P<.001), BMI (difference -0.62; P<.001), body fat percentage (difference -0.921; P<.001), body fat mass (difference -1.28; P<.001), and visceral fat area (difference -4.227; P=.008) in the IFHP group, whereas no significant changes were observed in the HP group. Compared to baseline, participants in the IFHP group showed a significant decrease in weight (difference -1.428; P=.003), BMI (difference -0.522; P=.005), body fat percentage (difference -1.591; P<.001), body fat mass (difference -1.501; P<.001), visceral fat area (difference -7.130; P<.001), waist circumference (difference -2.304; P=.001), and hip circumference (difference -1.908; P=.002) at month 6. During the unsupervised phase, waist (IFHP difference -3.206; P<.001, HP difference -2.675; P=.004) and hip (IFHP difference -2.443; P<.001; HP difference -2.896; P<.001) circumferences were significantly reduced in both groups (P<.01), whereas skeletal muscle mass (difference 0.208; P=.04) and visceral fat area (difference -2.903; P=.003) were significantly improved in the IFHP group only. No significant difference in the between-group comparison was detected throughout the intervention (all P>.05). CONCLUSIONS: A combined IFHP intervention was effective in improving anthropometric outcomes and body composition in adults with overweight and obesity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/33801.

Surgical Management of Pulsatile Tinnitus due to Sigmoid Sinus Diverticulum and Dehiscence - A Technical Note.

Pulsatile tinnitus (PT) is the perception of an auditory sensation without an external source and in synchrony with the heartbeat. One of the most common cases of PT is bony anomalies of the sigmoid sinus, including dehiscence or diverticula. This case report describes a 26-year-old female patient who presented with pulsatile tinnitus caused by sigmoid sinus diverticula and dehiscence, which was successfully treated with cortical mastoidectomy with diverticula closure using pedicled temporalis fascia and resurfacing of the dehiscence with autogenous bone pate along with bone cement. We recommend thorough clinical and radiological workup to rule out other possible causes of PT before surgical intervention. In addition, we would like to highlight the surgical technique using pedicled temporalis fascia that we have used in our patient, which is easily reproducible and offers successful outcomes.

Pivotal relationship between heavy metal, PM2.5 exposures and tuberculosis in Bangladeshi children: protocol paper of a case-control study.

INTRODUCTION: Air pollution is a global issue that poses a significant threat to public health. Children, due to their developing physiology, are particularly susceptible to the inhalation of environmental pollutants. Exposure can trigger immune modulation and organ damage, increasing susceptibility to respiratory diseases. Therefore, we aim to examine the association between heavy metal and particulate matter exposure with tuberculosis in children. METHODS AND ANALYSIS: As a case-control study, we will include children diagnosed with pulmonary tuberculosis (n=60) and matched healthy controls (n=80) recruited from the same communities in Dhaka, Bangladesh. Exposure data for both cases and controls will be collected by a trained field team conducting home visits. They will administer an exposure questionnaire, measure child anthropometry, collect blood and household dust samples and instal 48-hour air quality monitors. The blood samples will be analysed by inductively coupled plasma mass spectrometry for serum heavy metal concentrations (lead, cadmium, arsenic, mercury and chromium), as a representative marker of exposure, and the presence of inflammatory biomarkers. Descriptive and inferential statistics, including independent samples t-tests, analysis of variance and conditional regression analysis, will be used to quantify heavy metal and particulate matter exposure status in tuberculosis cases compared with healthy controls, while accounting for potential confounders. Dust samples and air quality results will be analysed to understand household sources of heavy metal and particulate matter exposure. To test the study hypothesis, there is a positive association between exposure and tuberculosis diseases, we will also measure the accumulated effect of simultaneous exposures using Bayesian statistical modelling. ETHICS AND DISSEMINATION: This study has been approved by International Centre for Diarrhoeal Disease Research, Bangladesh's Institutional Review Board (PR-22030). The study findings will be disseminated at conferences and published in peer-reviewed journals.

High frequency neuronavigated repetitive transcranial magnetic stimulation in post-stroke shoulder pain: A double-blinded, randomized controlled study.

OBJECTIVE: This study aimed to determine the effect of 5Hz neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the affected primary motor cortex (M1) on pain, the effect of pain on activities of daily living, disability, mood, neurophysiological parameters and passive shoulder joint range of motion in patients with post-stroke shoulder pain. DESIGN: Twenty two patients were randomized into an experimental group (rTMS, n=7) who received daily rTMS 5Hz 1000 pulses, five times/week for three weeks (15 sessions) to the affected M1 and a control group (n=11) who received sham stimulation. Outcome measures were Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Disabilities of the arm, shoulder, and hand questionnaire (Quick DASH), Hospital Depression Anxiety Scale (HADS), joint range of motion (ROM) measurements, neurophysiological parameters. Selected outcome measures were performed before treatment (T0), after the 5th session (T1) of rTMS treatment, after the 10th session (T2), after the 15th session (T3), and four weeks after the end of the treatment (T4). In the analysis of the outcomes, within-group comparisons were performed by using the Wilcoxon or Friedman test and between-group comparisons were performed by using the Mann-Whitney U test. RESULTS: There was no statistically significant difference between and within groups in terms of change- and followup scores in the NRS measurements (p>0.05). BPI scale was found to be lower in rTMS group at T0 and T3 (p= 0.010). Quick-DASH scores at T4 were found to be significantly lower in rTMS group (p= 0.032). However, no difference was found within each group over time (p>0.05) and there was no statistical difference between the groups in terms of change scores (T3-T0 and T4-T0) (p>0.05) for BPI and Quick-DASH. In rTMS group, there was a statistically significant difference in shoulder external rotation at T3 compared to the baseline (T0) (p=0.039). However, the magnitude of external rotation change (T3-T0) with the treatment was comparable in the groups. No statistically significant change occurred in both treatment groups in other range of motion measurements. CONCLUSION: High frequency neuronavigated rTMS to the affected M1 did not show any significant beneficial effect on pain, activities of daily living, disability, anxiety and depression, neurophysiological measurements and passive ROM over sham stimulation.

Aspergillus infections of lateral skull base: a case series.

PURPOSE: While extensive research with accurate classification has been done in mycoses of the paranasal sinuses and anterior skull base, a similar understanding of lateral skull base fungal pathologies is lacking due to relative rarity and diagnostic difficulties. We introduce a series of eleven cases and two different invasive entities of Aspergillus temporal bone diseases-fungal skull base osteomyelitis (SBO)/malignant otitis externa (MOE) and chronic invasive granulomatous fungal disease (CIGFD). METHODOLOGY: A retrospective observational study was conducted at the neuro-otology unit of a tertiary care referral center between July 2017 and November 2022. Diagnosed cases of lateral skull base osteomyelitis with atypical symptoms and lack of response to culture-directed antibiotics were evaluated for fungal origin. Patient data, including history, laboratory findings, serum galactomannan assay, CT and MRI imaging findings, clinical examination findings, and co-morbidities, were analyzed. The treatment course and response were assessed. RESULTS: A total of 11 cases were included in the study. Of these, 9 were cases of Aspergillus-induced skull base osteomyelitis (SBO) and 2 of Aspergillus-induced chronic invasive granulomatous fungal disease (CIGFD). CIGFD presented with persistent ear discharge and slowly progressive post-aural swelling, while all patients of fungal SBO had lower cranial nerve palsies. CIGFD responded to excision and antifungals, while SBO responded well to conservative anti-fungal treatment. CONCLUSION: In cases of lateral SBO not responding to antibiotic therapy, the possibility of fungal etiology should be considered. Aspergillus spp. seems to be the major fungal pathogen.

From co-delivery to synergistic anti-inflammatory effect: Studies on chitosan-stabilized Janus emulsions having chloroquine phosphate and flavopiridol in Complete Freund's Adjuvant induced arthritis rat model.

For the first time, the co-delivery of chloroquine phosphate and flavopiridol by intra-articular route was achieved to provide local joint targeting in Complete Freund's Adjuvant-induced arthritis rat model. The presence of paired-bean structure onto the dispersed oil droplets of o/w nanosized emulsions allows efficient entrapment of two drugs (85.86-96.22 %). The dual drug-loaded emulsions displayed a differential in vitro drug release behavior, near normal cell viability in MTT assay, better cell uptake (internalization) and better reducing effect of mean immunofluorescence intensity of inflammatory proteins such as NF-κB and iNOS at in vitro RAW264.7 macrophage cell line. The radiographical study, ELISA test, RT-PCR study and H & E staining also indicated a reduction in joint tissue swelling, IL-6 and TNF-α levels diminution, fold change diminution in the mRNA expressions for NF-κB, IL-1ß, IL-6 and PGE2 and maintenance of near normal histology at bone cartilage interface respectively. The results of metabolomic pathway analysis performed by LC-MS/MS method using the rat blood (plasma) collected from disease control and dual drug-loaded emulsions treatment groups revealed a new follow-up study to understand not only the disease progression but also the formulation therapeutic efficacy assessment.

Single cell transcriptional changes across the blood stages of artemisinin resistant K13C580Y mutant Plasmodium falciparum upon dihydroartemisinin exposure.

Artemisinins have been a cornerstone of malaria control, but resistance in Plasmodium falciparum, due to mutations in the Kelch 13 gene, threaten these advances. Artemisinin exposure results in a dynamic transcriptional response across multiple pathways, but most work has focused on ring stages and ex vivo transcriptional analysis, limiting evaluation of all life cycle stages. We applied single cell RNAseq to two unsynchronized isogenic parasite lines (K13C580 and K13580Y) over 6 hrs after a pulse exposure to dihydroartemisinin (DHA). Transcription was altered across all stages, with the greatest occurring at the early trophozoite and mid ring stage in both lines. This response involved the arrest of metabolic processes and the enhancement of protein trafficking and the unfolded protein response. While similar, the response was enhanced in the K13580Y mutant, which may lead to the dormancy phenomenon upon treatment. Increased surface protein expression was seen in mutant parasites at baseline and upon drug exposure, highlighted by the increased expression of PfEMP1 and GARP, a potential therapeutic target. Antibody targeting GARP maintained anti-parasitic efficacy in mutant parasites. This work provides single cell insight of gene transcription across all life cycle stages revealing transcriptional changes that could initiate dormancy state and mediate survival.

Association of dietary behaviour and depression among adolescents in Malaysia: a cross-sectional study.

BACKGROUND: Depression is on the rise and has become a significant concern for public health. Limited research has explored the connection between dietary patterns and depression. This investigation aimed to examine how dietary behaviours relate to depression among adolescents attending school in Malaysia. METHODS: The study utilized data from the National School-Based Health Survey 2022, a nationwide survey involving school-going adolescents aged 13-17, with a total of 33,523 participants from 239 schools. To assess depression, the study employed the Patient Health Questionnaire (PHQ-9), considering a score of 10 or higher as indicative of depression. Dietary behaviours were assessed using a validated self-administered questionnaire adapted from the World Health Organization's Global School-based Student Health Survey. Descriptive analysis and complex sample logistic regression were carried out using SPSS version 26.0. RESULTS: The study revealed a 26.9% overall prevalence of depression, with higher risks among female adolescents (AOR 2.71, 95% CI 2.51, 2.92) and those in higher grades. Malays (AOR 1.71, 95% CI 1.41, 2.07), Other Bumiputeras (AOR 1.69, 95% CI 1.32, 2.17), and Others (AOR 1.63, 95% CI 1.16, 2.30) had elevated odds of depression compared to Indians. Healthy dietary habits, like consuming less than two servings of fruits daily, correlated with depression (AOR 1.44 95% CI 1.35, 1.54). Additionally, unhealthy dietary behaviours such as fast food consumption (AOR 1.73 [95% CI 1.55, 1.93]) and carbonated soft drink intake (AOR 1.59 [95% CI 1.48, 1.70]) were positively associated with depression. CONCLUSIONS: One out of every four Malaysian adolescents was identified to experience depression. Depression was linked to several factors, such as being female, belonging to higher grade levels, identifying as Malays, Other Bumiputeras, or belonging to other ethnicities, and participating in the consumption of fast food, carbonated soft drinks, and fruits. To address these observations, it is crucial to formulate effective public health programmes that prioritize adolescent mental health and encourage the adoption of healthy eating habits.

The Outcomes and Surgical Nuances of Minimally Invasive Parotid Surgery for Pleomorphic Adenoma.

Benign parotid tumors follow an indolent course and present as slow-growing painless swelling in the pre-and-infra-auricular areas. The treatment of choice is surgery. Though the gold standard technique is Superficial Parotidectomy, Extracapsular Dissection (ECD) is an alternative option with the same outcome and decreased complications. This study discusses our experience with extracapsular dissection and the surgical nuances for better results. A retrospective study of histologically confirmed cases of pleomorphic adenoma of the parotid gland, who underwent Extracapsular dissection between September 2019 and March 2023, was done. The demographic details, clinical characteristics, and outcomes were evaluated. There were 33 patients, including 16 females and 17 males, with a mean age of 32.75 years. All cases presented as slow-growing painless swelling for a mean duration of 5 years. Most of the tumors (94%) were of size between 2 and 4 cm, with few tumors more than 4 cm. All underwent extracapsular dissection with complete excision. There was only one complication (seroma) and no incidence of facial palsy in our experience with ECD. The goal of a benign parotid surgery is the complete removal of the tumor with minimum complications, which could be achieved with ECD, which has good tumor clearance and lesser rates of complications with good cosmesis. Thus, this minimally invasive parotid surgery could be a worthwhile option in properly selected cases.

A qualitative exploration of the facility-based trauma care for Road Traffic Crash patients in Bangladesh: When only numbers do not tell the whole story.

OBJECTIVE: Bangladesh is currently undergoing an epidemic of road traffic crashes (RTCs). In addition to morbidity and mortality, the economic loss from RTC as per cent of gross domestic product is comparatively higher than in countries with similar socioeconomic conditions. However, trauma care remained poorly developed as a specialty and service delivery mechanism. This study aimed to examine the current situation of in-hospital trauma care after RTCs to inform the design of a comprehensive service for Bangladesh. DESIGN, SETTING AND PARTICIPANTS: This qualitative study attempted to elicit stakeholders' perceptions and experiences of managing RTCs through in-depth interviews and focus group discussions. Three districts and Dhaka city were selected based on the frequency of occurrence of RTCs. Fifteen in-depth interviews and 5 focus group discussions were conducted with 38 RTC patients, their relatives and community members in the catchment areas of 11 facilities managing trauma patients. Key informant interviews were conducted with 21 service providers and 17 key stakeholders/policy-makers. RESULTS: Hospital-based trauma care was generally poor in primary and secondary-level facilities. There was no triage area or triage protocol in the emergency rooms, no trained staff for trauma care, no dedicated RTC patient register and scarce life-saving equipment. Only in Dhaka-based tertiary hospitals was trauma care prioritised. These hospitals follow Advanced Trauma Life Support guidelines and maintain an RTC logbook. Emergency diagnostic services were not always available in the hospitals. Most RTC patients were males; the female participants were additionally vulnerable to physical and mental trauma. Affected people avoided taking legal action considering it a lengthy, complicated and ultimately ineffective process. CONCLUSION: The trauma care services currently available in the studied health facilities are very rudimentary and without the necessary human and financial resources. This needs urgent attention from policymakers, programmers and practitioners to reduce morbidity and mortality from the current epidemic of RTCs in Bangladesh.

Reconstructive cranial surgery for invasive and non-responsive mucormycosis.

The incidence of mucormycosis showed a sharp rise during the COVID-19 pandemic in vulnerable populations like people with diabetes. Here, we report a case of mucormycosis of the frontal and ethmoid sinuses in a man in his mid-50s with a background of diabetes mellitus and COVID-19 infection requiring steroids and oxygen support. The infection had remained persistent despite initial debridement by functional endoscopic sinus surgery of the anterior frontal sinus wall and re-exploration, followed by debridement using the brow incision. The patient had received an entire course of systemic antifungal therapy during the postoperative period. A bifrontal craniotomy, excision of the supraorbital ridge and complete removal of bilateral frontal sinuses managed the persistent fungal infection. The defect was reconstructed with a custom-made three-dimensional-printed MRI-compatible titanium cranioplasty mesh. The patient had no signs of infection on the 9-month follow-up.

Recombinant VEGF-C (Cys156Ser) improves mesenteric lymphatic drainage and gut immune surveillance in experimental cirrhosis.

Background & Aims: Lymphatic vessels (LVs) are crucial for maintaining abdominal fluid homoeostasis and immunity. In cirrhosis, mesenteric LVs (mLVs) are dilated and dysfunctional. Given the established role of vascular endothelial growth factor-C (VEGF-C) in improving LVs, we hypothesised that VEGF-C treatment could ameliorate the functions of mLVs in cirrhosis. Methods: In this study, we developed a nanoformulation comprising LV-specific growth factor, recombinant human VEGF-C (Cys156Ser) protein (E-VEGF-C) and delivered it orally in different models of rat cirrhosis to target mLVs. Cirrhotic rats were given nanoformulation without VEGF-C served as vehicles. Drainage of mLVs was analysed using tracer dye. Portal and systemic physiological assessments and computed tomography were performed to measure portal pressures and ascites. Gene expression and permeability of primary mesenteric lymphatic endothelial cells (LyECs) was studied. Immune cells in mesenteric lymph nodes (MLNs) were quantified by flow cytometry. Endogenous and exogenous gut bacterial translocation to MLNs was examined. Results: In cirrhotic rats, mLVs were dilated and leaky with impaired drainage. Treatment with E-VEGF-C induced proliferation of mLVs, reduced their diameter, and improved functional drainage. Ascites and portal pressures were significantly reduced in E-VEGF-C rats compared with vehicle rats. In MLNs of E-VEGF-C animals, CD8+CD134+ T cells were increased, whereas CD25+ regulatory T cells were decreased. Both endogenous and exogenous bacterial translocation were limited to MLNs in E-VEGF-C rats with reduced levels of endotoxins in ascites and blood in comparison with those in vehicle rats. E-VEGF-C treatment upregulated the expression of vascular endothelial-cadherin in LyECs and functionally improved the permeability of these cells. Conclusions: E-VEGF-C treatment ameliorates mesenteric lymph drainage and portal pressure and strengthens cytotoxic T-cell immunity in MLNs in experimental cirrhosis. It may thus serve as a promising therapy to manage ascites and reduce pathogenic gut bacterial translocation in cirrhosis. Impact and Implications: A human recombinant pro-lymphangiogenic growth factor, VEGF-C, was encapsulated in nanolipocarriers (E-VEGF-C) and orally delivered in different models of rat liver cirrhosis to facilitate its gut lymphatic vessel uptake. E-VEGF-C administration significantly increased mesenteric lymphatic vessel proliferation and improved lymph drainage, attenuating abdominal ascites and portal pressures in the animal models. E-VEGF-C treatment limited bacterial translocation to MLNs only with reduced gut bacterial load and ascitic endotoxins. E-VEGF-C therapy thus holds the potential to manage ascites and portal pressure and reduce gut bacterial translocation in patients with cirrhosis.

EPR investigation of gamma-irradiated FAMOSER drug for DOSIMETRIC purposes.

Exposure to ionizing radiation can also lead to the formation of stable or unstable radicals in the structures of drugs, as in many materials. The concentrations of these radicals may show a linear dependence on the radiation dose exposed. Since drugs are materials that can be found next to or on radiation victims during a possible nuclear or radiological accident, it is very meaningful to determine the Electron Paramagnetic Resonance (EPR) dosimetric properties of stable radicals in their structures. In this study, the dosimetric properties of Famoser, which is one of the stomach-relieving drugs that people often have with them in their daily life, in the dose range of 10-800 Gy were investigated by EPR technique.

Development, systematic optimisation and biofilm disruption activity of eugenol-based nanosized emulsions stabilised with Tween 80.

The aims of this study were to systematically optimise a formula for eugenol emulsions via face-centered central composite design and to assess the activity against two-different bacterial strains (Staphylococcus aureus and Propionibacterium acnes) present at planktonic and biofilm forms. The molecular interaction of excipients, mean particle size (MPS) including zeta potential (ZP), drug entrapment efficiency (DEE) and in vitro drug release of optimised emulsions was done using FT-IR, Malvern Zetasizer, ultracentrifugation technique and membrane-free dissolution model, respectively. The emulsions consisted of 151.3 ± 1.45 nm MPS, -21.3 ± 1.25 mV ZP and 93.98 ± 1.41% DEE values. On storage of emulsions at 25 °C for 3 months, the value of DEE was found to be 72.12 ± 2.82%. The Tween 80 emulsifier film coverage onto the dispersed eugenol droplets of emulsions delayed significantly the drug release (12%-19%) compared to the drug release occurred from pure eugenol. The treatment of planktonic S. aureus and P. acnes with diluted eugenol emulsions showed the minimum inhibitory concentration and minimum bactericidal concentration values at 1.25-2.5 mg/ml whereas it occurred at 10 mg/ml for pure eugenol. Treating the biofilms with eugenol emulsions (1-2 mg/ml) yielded 59-70% minimum biofilm eradication concentration but 10 mg/ml pure eugenol showed 60%. Hence, the eugenol emulsions displayed antibacterial activity and could be projected as an antibiofilm or biofilm disruption agent.