Forecasting Atrial Fibrillation: The Predictive Power of N-terminal Prohormone of Brain Natriuretic Peptide in a Five-Year Study.

Introduction Atrial fibrillation (AF) is a major global health concern, and early prediction is essential for managing high-risk individuals. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) has emerged as a crucial biomarker for predicting AF. While most studies have concentrated on cohorts already diagnosed with AF or other cardiac diseases, this research investigates the predictive value of NT-proBNP for AF development in a population without prior AF diagnosis. Methods and materials A five-year prospective observational study was conducted on 4090 individuals aged 45 to 75 with no previous diagnosis of AF. Baseline demographic characteristics, comorbid conditions, cardiac-specific measures, and NT-proBNP levels were systematically recorded. The primary endpoint was the onset of AF, confirmed through annual 12-lead ECG or 24-hour Holter monitoring. Univariate and multivariate analyses identified factors associated with AF onset. Results Out of the total population, 16.6% (679 individuals) developed AF. Notably, increased NT-proBNP levels (P=0.001), older age (P=0.001), and hypertension (P=0.001) were significantly associated with the onset of AF. The mean NT-proBNP levels in the AF group were significantly higher than in the non-AF group (P<0.001). The AF group also showed a higher mean age and a greater prevalence of hypertension (P<0.001 for both). Conclusion This study confirms the predictive value of NT-proBNP for AF onset in a non-AF population, highlighting older age and hypertension as significant risk factors for AF development. The findings underscore the potential of NT-proBNP not only as a predictive biomarker but also as a therapeutic target. These insights emphasize the potential role of NT-proBNP in early intervention and management strategies for AF, suggesting that future research should include additional variables, such as lifestyle factors and genetic predisposition, in assessing AF risk.

Access to and utilisation of antimicrobials among forcibly displaced persons in Uganda, Yemen and Colombia: a pilot cross-sectional survey.

OBJECTIVES: Identifying key barriers to accessing quality-assured and affordable antimicrobials among forcibly displaced persons in Uganda, Yemen and Colombia and investigating their (1) utilisation patterns of antibiotics, (2) knowledge about antimicrobial resistance (AMR) and (3) perception of the quality of antimicrobials received. DESIGN: Pilot cross-sectional survey. SETTING: Data were collected from five health facilities in the Kiryandongo refugee settlement (Bweyale, Uganda), three camps for internally displaced persons (IDPs) in the Dar Sad district (Aden, Yemen) and a district with a high population of Venezuelan migrants (Kennedy district, Bogotá, Colombia). Data collection took place between February and May 2021. The three countries were selected due to their high number of displaced people in their respective continents. PARTICIPANTS: South Sudanese refugees in Uganda, IDPs in Yemen and Venezuelan migrants in Colombia. OUTCOME MEASURE: The most common barriers to access to quality-assured and affordable antimicrobials. RESULTS: A total of 136 participants were enrolled in this study. Obtaining antimicrobials through informal pathways, either without a doctor's prescription or through family and friends, was common in Yemen (27/50, 54.0%) and Colombia (34/50, 68.0%). In Yemen and Uganda, respondents used antibiotics to treat (58/86, 67.4%) and prevent (39/86, 45.3%) a cold. Knowledge of AMR was generally low (24/136, 17.6%). Barriers to access included financial constraints in Colombia and Uganda, prescription requirements in Yemen and Colombia, and non-availability of drugs in Uganda and Yemen. CONCLUSION: Our multicentred research identified common barriers to accessing quality antimicrobials among refugees/IDPs/migrants and common use of informal pathways. The results suggest that knowledge gaps about AMR may lead to potential misuse of antimicrobials. Due to the study's small sample size and use of non-probability sampling, the results should be interpreted with caution, and larger-scale assessments on this topic are needed. Future interventions designed for similar humanitarian settings should consider the interlinked barriers identified.

Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic.

Exposure to inorganic arsenic (As) is recognized as a risk factor for non-melanoma skin cancer (NMSC). We followed up with 7000 adults for 6 years who were exposed to As. During follow-up, 2.2% of the males and 1.3% of the females developed basal cell carcinoma (BCC), while 0.4% of the male and 0.2% of the female participants developed squamous cell carcinoma (SCC). Using a panel of more than 400 cancer-related genes, we detected somatic mutations (SMs) in the first 32 NMSC samples (BCC = 26 and SCC = 6) by comparing paired (tissue-blood) samples from the same individual and then comparing them to the SM in healthy skin tissue from 16 participants. We identified (a) a list of NMSC-associated SMs, (b) SMs present in both NMSC and healthy skin, and (c) SMs found only in healthy skin. We also demonstrate that the presence of non-synonymous SMs in the top mutated genes (like PTCH1, NOTCH1, SYNE1, PKHD1 in BCC and TP53 in SCC) significantly affects the magnitude of differential expressions of major genes and gene pathways (basal cell carcinoma pathways, NOTCH signaling, IL-17 signaling, p53 signaling, Wnt signaling pathway). These findings may help select groups of patients for targeted therapy, like hedgehog signaling inhibitors, IL17 inhibitors, etc., in the future.

Evaluation of Surveillance Strategies of Antimicrobial Consumption in Animals.

The aim of this paper is to explore and assess various strategies for monitoring antimicrobial consumption (AMC) in animals, within the context of the One Health approach. Recent studies have shed light on the limited surveillance and data collection for AMC in animals. Using the United States Center for Disease Control and Prevention Policy Analytical Framework, we assess global, national, and farm-level surveillance strategies on public health impact and feasibility using evidence from primary, secondary, and grey literature. From this, we identify key policy mechanisms that support the adoption of surveillance while providing specific recommendations. We find that a global strategy, though valuable for benchmarking and policy guidance, faces participation and data visibility challenges. National-level surveillance offers direct inputs into national action plans but struggles with data uniformity and comparability. Farm-level surveillance, while resource-intensive, provides the most granular data for informing specific interventions. We advocate for a multi-faceted approach to AMC surveillance, emphasizing that legal mandates and financial incentives are crucial for encouraging surveillance participation, along with international cooperation for enhancing participation and data quality. Drawing parallels with public reporting challenges in other sectors can provide valuable lessons on how to address data collection, analysis, and reporting barriers.

Comprehensive insights on treatment modalities with conventional and herbal drugs for the treatment of duodenal ulcers.

Areas of the body accessible to gastric secretions, such as the stomach and duodenum, are most commonly damaged by circumscribed lesions of the upper gastrointestinal tract mucosa. Peptic ulcer disease is the term for this illness (PUD). About 80% of peptic ulcers are duodenal ulcers, with stomach ulcers accounting for the remaining 20%. Duodenal ulcers are linked to the two primary results about Helicobacter pylori infection and COX inhibitor users. Additional causes might include drinking, smoking, stress, and coffee consumption. The indications and symptoms of a duodenal ulcer depend on the patient's age and the lesion's location. For duodenal ulcers, proton pump inhibitors (PPIs) are the usual course of treatment. This comprehensive study included an in-depth literature search in the literature and methods section using electronic databases such as PubMed, ScienceDirect, and Google Scholar. The search method included publications published from the inception of the relevant database to the present. Inclusion criteria included studies investigating different treatment options for duodenal ulcer disease, including traditional pharmacotherapy and naturopathic treatments. Data mining includes information on treatment techniques, treatment outcomes, and possible synergies between conventional and herbal treatments. In addition, this review critically examines the available information on the effectiveness, safety, and possible side effects of different treatments. The inclusion of conventional and herbal treatments is intended to provide a comprehensive overview of the many treatment options available for duodenal ulcer disease. A more comprehensive and personalized treatment plan can be achieved by incorporating dietary changes, lifestyle modifications, and, if necessary, herbal therapies to complement other treatments normally.

Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.

Objective: This study investigated the significance of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) in esophageal cancer (ESCA) and its underlying mechanism in ESCA regulation through the induction of RAC1 ubiquitination and degradation. Methods: Characterization studies of HACE1 in ESCA clinical tissues and cell lines were performed. Next, the effects of HACE1 on the biological behavior of ESCA cells were examined by silencing and overexpressing HACE1. Protein-protein interactions (PPIs) involving HACE1 were analyzed using data from the String website. The function of HACE1 in RAC1 protein ubiquitination was validated using the proteasome inhibitor MG132. The effects of HACE1 on ESCA cells through RAC1 were elucidated by applying the RAC1 inhibitor EHop-016 in a tumor-bearing nude mouse model. To establish the relationship between HACE1 and TRIP12, rescue experiments were conducted, mainly to evaluate the effect of TRIP12 silencing on HACE1-mediated RAC1 regulation in vitro and in vivo. The PPI between HACE1 and TRIP12 and their subcellular localization were further characterized through co-immunoprecipitation and immunofluorescence staining assays, respectively. Results: HACE1 protein expression was notably diminished in ESCA cells but upregulated in normal tissues. HACE1 overexpression inhibited the malignant biological behavior of ESCA cells, leading to restrained tumor growth in mice. This effect was coupled with the promotion of RAC1 protein ubiquitination and subsequent degradation. Conversely, silencing HACE1 exhibited contrasting results. PPI existed between HACE1 and TRIP12, compounded by their similar subcellular localization. Intriguingly, TRIP12 inhibition blocked HACE1-driven RAC1 ubiquitination and mitigated the inhibitory effects of HACE1 on ESCA cells, alleviating tumor growth in the tumor-bearing nude mouse model. Conclusion: HACE1 expression was downregulated in ESCA cells, suggesting that it curbs ESCA progression by inducing RAC1 protein degradation through TRIP12-mediated ubiquitination.

Development and characterization of semi-refined iota carrageenan/fish gelatin-based biocomposite film incorporated with SiO2/ZnO nanoparticles.

Food packaging based on natural polymers from polysaccharides and proteins can be an alternative to replace conventional plastics. In the present study, semi-refined iota carrageenan (SRIC) and fish gelatin (FG) were used as polymer matrix film with different concentration ratios (0.5:1.5 %, 1.0:1.0 % and 1.5:0.5 % w/w) and SiO2-ZnO nanoparticles were incorporated as fillers with the same concentration in all formulas (0.5:1.5 % w/w carrageenan-fish gelatin). This study aimed to develop films for food packaging applications with desirable physical, mechanical, optical, chemical, and microbiological properties. The results showed that incorporating SiO2-ZnO nanoparticles significantly (p < 0.05) improved the films' elongation at break, UV-screening properties, and antimicrobial activity. Also, the films' thickness, degradability, and transparency significantly (p < 0.05) increased with the higher concentration of fish gelatin addition in the SRIC matrix polymer. The best formula was obtained on the SRIC-FG film at the ratio of 1.5:0.5 % w/w, which performed excellent antimicrobial activity. Thus, semi-refined iota carrageenan/fish gelatin-based biocomposite film incorporated with SiO2-ZnO nanoparticles can be potentially developed as eco-friendly and intelligent food packaging materials to resolve traditional plastic-related issues and prevent food waste.

Correction: Zaman et al. Synthesis and Evaluation of Thiol-Conjugated Poloxamer and Its Pharmaceutical Applications. Pharmaceutics 2021, 13, 693.

In the original publication, there was a mistake in one author name, Mohammed Alasmari should be Mohammed S [...].

Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis.

Background and Aim: Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF. Methods: The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Results: Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81). Conclusion: Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Navigating the tumor microenvironment: mesenchymal stem cell-mediated delivery of anticancer agents.

Scientific knowledge of cancer has advanced greatly throughout the years, with most recent studies findings includes many hallmarks that capture disease's multifaceted character. One of the novel approach utilised for the delivery of anti-cancer agents includes mesenchymal stem cell mediated drug delivery. Mesenchymal stem cells (MSCs) are non-haematopoietic progenitor cells that may be extracted from bone marrow, tooth pulp, adipose tissue and placenta/umbilical cord blood dealing with adult stem cells. MSCs are mostly involved in regeneration of tissue, they have also been shown to preferentially migrate to location of several types of tumour in-vivo. Usage of MSCs ought to improve both effectiveness and safety of anti-cancer drugs by enhancing delivery efficiency of anti-cancer therapies to tumour site. Numerous researches has demonstrated that various drugs, when delivered via mesenchymal stem cell mediated delivery can elicit anti-tumour effect of cells in cancers of breast cells and thyroid cells. MSCs have minimal immunogenicity because to lack of co-stimulatory molecule expression, which means there is no requirement for immunosuppression after allogenic transplantation. This current review elaborates recent advancements of mesenchyma stem cell mediated drug delivery of anti-cancer agents along with its mechanism and previously reported studies of drugs manufactured via this drug delivery system.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200mg/kg extract dose exhibited %age pain inhibition of 55.12% and reduced body temperature from 39.78±0.03°C to 37.22±0.02°C in hyperthermic rats. A decrease in blood glucose levels up to 57.88% was observed on the 21st day of the treatment with 500mg/kg ethanolic extract.

Mapping a Way to Displaced Persons' Access to Quality Medicines.

Reliable, adequate supply of essential items, including quality-assured medicines, is hard to maintain in refugee camps in low- and middle-income countries. Disruption of medicine supply chains delays treatment for displaced persons and drives procurement of poor-quality products, often from unauthorized or unlicensed sellers. This article explains how current strategies and policies disrupt reliable flow of safe medicines to refugee camps and calls on stakeholders to rigorously map medicine supply chains to refugee camps, which would help identify strategies to improve displaced persons' access to quality-assured medicines.

Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel.

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.

From field to table: Ensuring food safety by reducing pesticide residues in food.

The present review addresses the significance of lowering pesticide residue levels in food items because of their harmful impacts on human health, wildlife populations, and the environment. It draws attention to the possible health risks-acute and chronic poisoning, cancer, unfavorable effects on reproduction, and harm to the brain or immunological systems-that come with pesticide exposure. Numerous traditional and cutting-edge methods, such as washing, blanching, peeling, thermal treatments, alkaline electrolyzed water washing, cold plasma, ultrasonic cleaning, ozone treatment, and enzymatic treatment, have been proposed to reduce pesticide residues in food products. It highlights the necessity of a paradigm change in crop protection and agri-food production on a global scale. It offers opportunities to guarantee food safety through the mitigation of pesticide residues in food. The review concludes that the first step in reducing worries about the negative effects of pesticides is to implement regulatory measures to regulate their use. In order to lower the exposure to dietary pesticides, the present review also emphasizes the significance of precision agricultural practices and integrated pest management techniques. The advanced approaches covered in this review present viable options along with traditional methods and possess the potential to lower pesticide residues in food items without sacrificing quality. It can be concluded from the present review that a paradigm shift towards sustainable agriculture and food production is essential to minimize pesticide residues in food, safeguarding human health, wildlife populations, and the environment. Furthermore, there is a need to refine the conventional methods of pesticide removal from food items along with the development of modern techniques.

Preparation, In Vitro Characterization, and Evaluation of Polymeric pH-Responsive Hydrogels for Controlled Drug Release.

The purpose of the current research is to formulate a smart drug delivery system for solubility enhancement and sustained release of hydrophobic drugs. Drug solubility-related challenges constitute a significant concern for formulation scientists. To address this issue, a recent study focused on developing PEG-g-poly(MAA) copolymeric nanogels to enhance the solubility of olmesartan, a poorly soluble drug. The researchers employed a free radical polymerization technique to formulate these nanogels. Nine formulations were formulated. The newly formulated nanogels underwent comprehensive tests, including physicochemical assessments, dissolution studies, solubility evaluations, toxicity investigations, and stability examinations. Fourier transform infrared (FTIR) investigations confirmed the successful encapsulation of olmesartan within the nanogels, while thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies verified their thermal stability. Scanning electron microscopy (SEM) images revealed the presence of pores on the surface of the nanogels, facilitating water penetration and promoting rapid drug release. Moreover, powder X-ray diffraction (PXRD) studies indicated that the prepared nanogels exhibited an amorphous structure. The nanogel carrier system led to a significant enhancement in olmesartan's solubility, achieving a remarkable 12.3-fold increase at pH 1.2 and 13.29-fold rise in phosphate buffer of pH 6.8 (NGP3). Significant swelling was observed at pH 6.8 compared to pH 1.2. Moreover, the formulated nexus is nontoxic and biocompatible and depicts considerable potential for delivery of drugs and protein as well as heat-sensitive active moieties.

Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.