Normalising participatory health research approaches in the WHO European region for refugee and migrant health: a paradigm shift.

While people's involvement in health research is increasingly the encouraged norm in many countries, the involvement of refugees and migrants in research about their health is rare. Here, we call for a paradigm shift in the field of refugee and migrant health to make participatory health research routine, i.e. normalised. To disrupt 'business as usual', we synthesise evidence about meaningful research partnerships and features of inclusive participatory spaces. We present examples of decolonial, culturally attuned methods that can be used to reimagine and reinvigorate research practice because they encourage critical reflexivity and power-sharing: arts-based research using music and singing, participatory learning and action research, Photovoice and co-design (ideas generation) workshops. We consider the consequences of not making this paradigm shift. We conclude with recommendations for specific structural and policy changes and empirical research questions that are needed to inform the normalisation of participatory health research in this field.

Efficient application of Pyrosin B for nano-gram level assay of antiparkinsonian medication, rasagiline: Evaluation of tablets and content uniformity.

Rasagiline (RAS) is a medication for Parkinson's disease that increases dopamine levels in the brain by inhibiting monoamine oxidase, helping to alleviate symptoms. The proposed study aims to develop an efficient, feasible, and sensitive method for RAS assay, utilizing Pyrosin B dye, a convenient fluorescent ligand. Combining the RAS analyte with Pyrosin B ligand in a mildly acidic buffered solution rapidly quenches the native fluorescence of the ligand. This quenching results from the formation of a specific ion-dipole association complex between the lone pair-bearing atoms of the ligand and the protonated amine moiety of RAS, highlighting their interactive chemistry under these conditions. The degree of this interaction demonstrated superior sensitivity compared with reported alternatives, exhibiting a linear range of 50.0 to 1000.0 ng/mL. The method is characterized by a limit of detection (LOD) of 16.0 ng/mL and a limit of quantification (LOQ) of 48.0 ng/mL. By optimizing the RAS-Pyrosin B system, the variable parameters were finely tuned, ensuring the assay method's reliability. The method's accuracy, precision, selectivity, and robustness were validated according to International Council for Harmonization (ICH) guidelines, enabling precise and efficient analysis of RAS in the nanogram range. This method streamlines the analysis procedure and reduces environmental impact, making it a promising approach for the quality control of ParkintreatR tablets (1 mg) and other analytical applications.

Stool Sampling as a Non-invasive Method to Confirm Miliary Tuberculosis in a Patient With a History of HIV Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge despite medical advancements. We present here a case of a 44-year-old male with a history of HIV infection and inconsistent treatment adherence. The patient exhibited weight loss and miliary lesions on a computed tomography (CT) scan, prompting suspicion of pulmonary TB. Due to his inability to expectorate sputum, stool samples were used for the acid-fast bacilli (AFB) smear and culture. His miliary TB diagnosis was confirmed through lung CT imaging and positive AFB smears from stool samples. This case underscores the utility of stool samples in diagnosing TB when sputum production is compromised, offering a minimally invasive diagnostic approach. It also underscores the importance of collaborative healthcare approaches in managing complex cases, ensuring comprehensive care tailored to individual patient needs.

Artificial Intelligence Application in a Case of Mandibular Third Molar Impaction: A Systematic Review of the Literature.

Objective: This systematic review aims to summarize the evidence on the use and applicability of AI in impacted mandibular third molars. Methods: Searches were performed in the following databases: PubMed, Scopus, and Google Scholar. The study protocol is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202460081). The retrieved articles were subjected to an exhaustive review based on the inclusion and exclusion criteria for the study. Articles on the use of AI for diagnosis, treatment, and treatment planning in patients with impacted mandibular third molars were included. Results: Twenty-one articles were selected and evaluated using the Scottish Intercollegiate Guidelines Network (SIGN) evidence quality scale. Most of the analyzed studies dealt with using AI to determine the relationship between the mandibular canal and the impacted mandibular third molar. The average quality of the articles included in this review was 2+, which indicated that the level of evidence, according to the SIGN protocol, was B. Conclusions: Compared to human observers, AI models have demonstrated decent performance in determining the morphology, anatomy, and relationship of the impaction with the inferior alveolar nerve canal. However, the prediction of eruptions and future horizons of AI models are still in the early developmental stages. Additional studies estimating the eruption in mixed and permanent dentition are warranted to establish a comprehensive model for identifying, diagnosing, and predicting third molar eruptions and determining the treatment outcomes in the case of impacted teeth. This will help clinicians make better decisions and achieve better treatment outcomes.

High rate of inadequate antenatal contacts among mothers in eastern Sudan: a cross-sectional study.

This study assesses the prevalence and determinants of inadequate (less than eight contacts) and late antenatal care (ANC) initiation (starting after 12 weeks) among mothers delivered at Gadarif Maternity Hospital in eastern Sudan. A hospital-based cross-sectional study was conducted at Gadarif Maternity Hospital. A questionnaire was used to collect sociodemographic, clinical, and obstetric data through face-to-face interviews. Seven hundred mothers were enrolled with the median (interquartile range) of mothers' age, and parity was 28(24-32) years and 3(2-5), respectively. Of these 700 mothers, 79.3 percent and 10.3 percent had inadequate and late ANC, respectively. In multivariable logistic regression analysis, being a housewife (adjusted odds ratio [AOR] 1.93, 95 percent CI 1.09, 3.43) was associated with inadequate ANC. High parity (AOR 1.27, 95 percent CI 1.07-1.52) was positively associated with late ANC initiation. There was no association between age, residence, education, preexisting medical disorder, and history of miscarriage) with inadequate or late ANC initiation In eastern Sudan, four out of five mothers did not comply with the World Health Organization's recommendation of a minimum of eight ANC contacts for positive pregnancy outcomes. This study is crucial for policy-makers to take further strategic actions to ensure adequate and early ANC initiation for all mothers in Sudan.

A study on value addition of cow dung-based anaerobic sludge for biomethane and bio-oil production via co-liquefaction with rice straw and clam shells as a catalyst.

The waste management sector is moving towards sustainable approaches for facilitating resource-recovery possibilities. Agriculture residue (rice straw), cow dung (cattle waste), and clam shells from the ocean are the primary waste materials possessing a huge value addition opportunity. In this study, the effective usage of rice straw and anaerobic sludge from cow dung for bio-energy production was studied. Cow dung was initially anaerobically processed for the generation of biomethane and sludge in a digester for a retention time of 40 days. The anaerobic sludge with rice straw was hydrothermally processed in varying proportions of 1 : 0, 0 : 1, 1 : 1,1 : 2, 2 : 1, 3 : 1, 1 : 3 and temperatures of 240-360 °C for 1 hour with varying biomass loads of 50, 75, 100, 125, and 150 g. Additionally, clam shells, one of the best bioresources, were used as a catalyst in the hydrothermal process at concentrations of 0.2-1 wt%. The maximum bio-oil produced was 36.23 wt% at a temperature of 320 °C, with a biomass load of 100 g, mixed proportion of 2 : 1 and catalyst loading of 0.6 wt%. The produced bio-oil comprised hydrocarbons, aldehydes, and carboxylic acids, as confirmed through GC-MS. In the anaerobic study, ≈0.018 m3 cumulative gas was produced at a retention time of 40 days. The biochar had a higher carbon content and its feasibility for further usage shows promise towards sustainability.

Acrylamide detection and reduction in meat products using organic acids, fruit extracts, and probiotics.

Grilled foods are an important source of acrylamide, which has neurotoxic, genotoxic, and carcinogenic properties. The current study aims to evaluate the level of acrylamide in beef, chicken, and fish products, especially those requiring high cooking temperatures, using High Performance Liquid Chromatography (HPLC). Reduction of acrylamide by organic acids i.e., (citric acid, malic acid, tartaric acid, and lactic acid) and fruit extracts of lemon, apple, and grape has also been investigated. The results revealed that the highest mean acrylamide concentration was found in chicken products (grilled chicken) which recorded 8.32 µg/100 g, followed by beef products (beef grilled) with a concentration of 7.91 µg/100 g, and fish products (pan-fried fish burgers) which recorded 6.77 µg/100 g). Furthermore, the mixture of organic acid has the highest effect on reducing the level of acrylamide in a chemical model system. Moreover, the fruit extract mixture was more effective in reducing the percentage of acrylamide in the grilled chicken than organic acids mixture. Finally, the addition of fruit extract improved the sensory properties of grilled chickens. In sum, this study offers novel and promising natural strategies to decrease acrylamide in meat products toward further future application in meat industry to deliver safe food to consumers.

Bioactivity of silverleaf nightshade (Solanum elaeagnifolium Cav.) berries parts against Galleria mellonella and Erwinia carotovora and LC-MS chemical profile of its potential extract.

Natural products received much attention as an environmentally beneficial solution for pest management. Therefore, the extracts of invasive silverleaf nightshade (Solanum elaeagnifolium Cav.) weeds using their berries parts (seeds, peels and mucilage) supported by bioassay-guided fractionation were tested against both the greater wax moth (Galleria mellonella) and Erwinia carotovora pv. carotovora causes of the blackleg of potatoes. The seeds and peels of S. elaeagnifolium were successively extracted by maceration using dichloromethane (DCM), ethyl acetate (EtOAc), and ethanol (EtOH), respectively. While, its mucilage was extracted using EtOAc. The successive EtOH extract of the plant seeds had promising inhibition efficacy and the best minimal inhibition concentration (MIC) of 50 µg/ml against E. Carotovora amongst other extracts (DCM and EtOAc of the plant berries parts). Depending on dose response activity, EtOH extract had G. mellonella larval mortality and pupal duration rates (LC50; 198.30 and LC95; 1294.73 µg/ml), respectively. Additionally, this EtOH extract of seeds was fractionated using preparative TLC to three characteristic bands. The insecticidal and bacterial activities of these isolated bands (SEA, SEB, and SEC) were evaluated at a dose of 100 µg/ml, causing mortality by 48.48, 62.63 and 92.93% (G. mellonella larvae) and inhibition by 15.22, 0.00 and 31.66 mm (E. carotovora), respectively. Moreover, the separated major three bands were tentatively identified using LC-ESI-MS analysis revealing the presence of two phenolic acids; chlorogenic acid (SEA) and dicaffeoyl quinic acid (SEB) in addition to one steroidal saponin (SEC) annotated as borassoside E or yamoscin. Finally, the plant seeds' successive EtOH extract as well as its active constituents, exhibited potential broad-spectrum activity and the ability to participate in future pest management initiatives. A field study is also recommended to validate its bio-efficacy against selected pests and to develop its formulations.

Comparative effectiveness of ultrathin vs. standard strut drug-eluting stents: insights from a large-scale meta-analysis with extended follow-up.

BACKGROUND: Newer generation ultrathin strut stents are associated with less incidence of target lesion failure (TLF) in patients undergoing percutaneous coronary intervention (PCI) in the short term. However, its long-term effect on different cardiovascular outcomes remains unknown. OBJECTIVES: We aim to identify the effects of newer-generation ultrathin-strut stents vs. standard thickness second-generation drug-eluting stents (DES) on long-term outcomes of revascularization in coronary artery disease. METHODS: We searched PubMed, Web of Science, Cochrane Library databases, and Scopus for randomized controlled trials (RCTs) and registries that compare newer-generation ultrathin-strut (< 70 mm) with thicker strut (> 70 mm) DES to evaluate cardioprotective effects over a period of up to 5 years. Primary outcome was TLF, a composite of cardiac death, target vessel myocardial infarction (TVMI) or target lesion revascularization (TLR). Secondary outcomes included the components of TLF, stent thrombosis (ST), and all-cause death were pooled as the standardized mean difference between the two groups from baseline to endpoint. RESULTS: We included 19 RCTs and two prospective registries (103,101 patients) in this analysis. The overall effect on the primary outcome was in favor of second-generation ultrathin struts stents in terms of TLF at ≥ 1 year, ≥ 2 years, and ≥ 3 years (P value = 0.01, 95% CI [0.75, 0.96]), P value = 0.003, 95% CI [0.77, 0.95]), P value = 0.007, 95% CI [0.76, 0.96]), respectively. However, there was no reported benefit in terms of TLF when we compared the two groups at ≥ 5 years (P value = 0.21), 95% CI [0.85, 1.04]). Some of the reported components of the primary and secondary outcomes, such as TLR, target vessel revascularization (TVR), and TVMI, showed the same pattern as the TLF outcome. CONCLUSION: Ultrathin-strut DES showed a beneficial effect over thicker strut stents for up to 3 years. However, at the 5-year follow-up, the ultrathin strut did not differ in terms of TLF, TLR, TVR, and TVMI compared with standard-thickness DES, with similar risks of patient-oriented composite endpoint (POCE), MI, ST, cardiac death, and all-cause mortality.

Serum 25-Hydroxyvitamin D Concentrations in Patients with Type 2 Diabetes Mellitus in Eastern Sudan: A Case-Control Study.

Introduction: Diabetes mellitus (DM) is one of the world's major public health problems. There are few published data on 25-hydroxyvitamin D (25[OH]D) concentrations and DM, and these studies showed different results. Objectives: The current study aimed to compare 25[OH]D concentrations between patients with type 2 DM (T2DM) and healthy controls in eastern Sudan. Methods: A case-control study of two groups matched for age and gender (88 in each group) was conducted in eastern Sudan from March to May 2022. The cases were patients with T2DM, and the controls were healthy participants. Sociodemographic data were collected, and serum 25(OH)D levels were assessed. A univariate analysis was performed. Results: Of the total 176, 82 (47%) were males, and 94 (53%) were females; the median (interquartile range [IQR]) of age, body mass index (BMI), and 25(OH)D concentration were 55 (50-61) years, 27 (23-31) kg/m2, and 13 (10-19) ng/mL, respectively. Of the 176, 137 (78%) were vitamin D deficiency cases. Compared with the controls, age, gender, educational level, marital status, or BMI were not different in the circumstances. Moreover, the median (IQR) for serum 25(OH)D concentrations showed no difference between patients with T2DM and the healthy controls (12 [10-18] ng/mL vs. 13 [10-20] ng/mL). The prevalence of vitamin D deficiency (25(OH)D level < 20 ng/mL) was not different between patients with T2DM and the healthy controls (66/88 [75%] vs. 71/88 [81%]). There was no association in the serum 25(OH)D levels between diabetic and nondiabetic participants (OR = 1.01, 95% CI 0.97-1.06) or in vitamin D deficiency between diabetic and nondiabetic participants (OR = 0.72, 95% CI 0.35-1.47). Conclusion: There was no significant difference in 25(OH)D levels between diabetic and nondiabetic participants in this study. Further studies investigating the mechanisms of association between 25(OH)D levels and DM are needed.

Marine fungal diversity unlocks potent antivirals against monkeypox through methyltransferase inhibition revealed by molecular dynamics and free energy landscape.

The escalating threat posed by the Monkeypox virus (MPXV) to global health necessitates the urgent discovery of effective antiviral agents, as there are currently no specific drugs available for its treatment, and existing inhibitors are hindered by toxicity and poor pharmacokinetic profiles. This study aimed to identify potent MPXV inhibitors by screening a diverse library of small molecule compounds derived from marine fungi, focusing on the viral protein VP39, a key methyltransferase involved in viral replication. An extensive virtual screening process identified four promising compounds-CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569-alongside a control molecule. Rigorous evaluations, including re-docking, molecular dynamics (MD) simulations, and hydrogen bond analysis, were conducted to assess their inhibitory potential against MPXV VP39. CMNPD15724 and CMNPD30883, in particular, demonstrated a superior binding affinity and stable interactions within the target protein's active site throughout the MD simulations, suggesting a capacity to overcome the limitations associated with sinefungin. The stability of these VP39-compound complexes, corroborated by MD simulations, provided crucial insights into the dynamic behavior of these interactions. Furthermore, Principal Component Analysis (PCA) based free energy landscape assessments offered a detailed understanding of the dynamic conformational changes and energetic profiles underlying these compounds' functional disruption of VP39. These findings establish CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569 as promising MPXV inhibitors and highlight marine fungi as a valuable source of novel antiviral agents. These compounds represent potential candidates for further experimental validation, advancing the development of safer and more effective therapeutic options to combat this emerging viral infection.

The role of alcohol control policies in the reversal of alcohol consumption levels and resulting attributable harms in China.

Yearly adult per capita consumption of alcohol in China between 2016 and 2019 decreased by 2.4 litres of pure alcohol, or 33%. According to the World Health Organization, this decrease in consumption was accompanied by reductions in alcohol-attributable mortality of 23% between 2015 and 2019. This paper examines the contribution of alcohol control policies in China to these public health gains. A systematic search of the literature was conducted on alcohol control policies and their effectiveness in China as part of a larger search of all countries in WHO Western Pacific Region. In addition to articles on empirical evidence on the impact of such alcohol control policies, we also searched for reviews. The plausibility of changes of traditional alcohol control policies (taxation increases, availability restrictions, restriction on advertisement and marketing, drink-driving laws, screening and brief interventions) in explaining reductions of consumption levels and attributable mortality rates was explored. There was some progress in the successful implementation of strict drink-driving policies, which could explain reductions in traffic injuries, including fatalities. Other traditional alcohol control policies seem to have played a minimal role in reducing alcohol consumption and attributable harms during the time period 2016-2019. However, an anti-corruption campaign was extensive enough to have substantially contributed to these reductions. The campaign prohibited the consumption of alcoholic beverages in everyday life of government officials and thus contributed to a de-normalization of alcohol. While this anti-corruption campaign was the only policy to potentially explain marked decreases in levels of alcohol consumption and attributable mortality, more detailed research is required to determine exactly how the campaign achieved these decreases.

A Case Report of an Acute Severe Tachyarrhythmia Presentation With Underlying Cardiomyopathy in a Patient With Anabolic Androgenic Steroid and Thyroxine Misuse.

A description of an acute hospital presentation with severe tachyarrhythmia requiring multiple direct current cardioversions in a 45-year-old male bodybuilder with underlying cardiomyopathy possibly caused by long-term anabolic steroid abuse and more recent thyroxine misuse is described. A review of the literature regarding the above associations was also done. This case report further adds to the literature regarding the harmful effect of androgenic anabolic steroid misuse (with the added effect of thyroxine misuse in this case) on the heart.

Dual benefits of NBD-Cl fluorogenic action and sample pretreatment (SALLE) technology in the assessment of anticoagulant medication: Dabigatran in pharmaceutical capsules and plasma samples.

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8 nm and by adjustment of a wavelength of 474.7 nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5 ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.

Exploring the sedative properties of natural molecules from hop cones (Humulus lupulus) as promising natural anxiolytics through GABA receptors and the human serotonin transporter.

This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbutanoyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds.

Association of IL-13 rs20541, FOXP3 rs3761548 genes polymorphisms and serum level of IL-13 with allergic asthma in Egyptian patients.

The interleukin 13 (IL-13) gene single nucleotide polymorphisms (SNPs) are frequently linked to increased vulnerability to allergic asthma. Forkhead box protein P3 (FOXP3) is an important molecule in the formation of regulatory T cells (Treg). The genetic variants that alter FOXP3 function may have a role in the development of asthma and other allergic disorders. We aimed to determine the association of IL-13 rs20541, FOXP3 rs3761548 genes SNPs and serum levels of IL-13 with allergic asthma patients. In this case-control study, 41 Egyptian patients with allergic asthma were included. Age and gender matched. 41 normal volunteers were considered the controls. All subjects were examined for IL-13 rs20541 and FOXP3 rs3761548 SNPs by the polymerase chain reaction /restriction fragment length polymorphism technique. The serum level of IL-13 was assessed by the enzyme linked immunosorbent assay (ELISA). AA genotype at IL-13 rs20541 SNP was statistically significantly different between the studied groups (p= 0.042). Also, a statistically significant difference was detected when compared AA genotype to GG genotype as AA genotype was three times at risk for asthma (p1=0.031) (OR=3.95) and A allele increased the risk of asthma by about 3 times (OR=3.2). AA genotype at FOXP3 rs3761548 SNP was statistically significantly different between the studied groups (p=0.013). Also, a statistically significant difference was detected when compared AA genotype to CC genotype as AA genotype was 7 times at risk for asthma (p1=0.003) (OR=7.04) and A allele increased the risk of asthma by about 3 times (p<0.001) (OR=3.07). The serum level of IL-13 was statistically significant different between both groups (p<0.001). We can conclude that IL-13 could be a useful tool for predicting allergic asthma. Patients with AA genotype of IL-13 rs20541 and AA genotype of FOXP3 rs3761548 have a higher risk for developing allergic asthma.

Cuticle Development And The Underlying Transcriptome-Metabolome Associations During Early Seedling Establishment.

The plant cuticle is a complex extracellular lipid barrier that has multiple protective functions. We investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by integrated statistical analyses identified three gene networks connected with the deposition of different elements of the cuticle: a) cuticular waxes; b) monomers of lipidized cell wall biopolymers, including cutin and suberin; and c) both of these elements. These gene networks reveal three metabolic programs that appear to support cuticle deposition, including processes of chloroplast biogenesis, lipid metabolism, and molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.

Synthesis and biological evaluation of O4'-benzyl-hispidol derivatives and analogs as dual monoamine oxidase-B inhibitors and anti-neuroinflammatory agents.

Design, synthesis, and biological evaluation of two series of O4'-benzyl-hispidol derivatives and the analogous corresponding O3'-benzyl derivatives aiming to develop selective monoamine oxidase-B inhibitors endowed with anti-neuroinflammatory activity is reported herein. The first O4'-benzyl-hispidol derivatives series afforded several more potentially active and MAO-B inhibitors than the O3'-benzyl derivatives series. The most potential compound 2e of O4'-benzyl derivatives elicited sub-micromolar MAO-B IC50 of 0.38 µM with a selectivity index >264 whereas most potential compound 3b of O3'-benzyl derivatives showed only 0.95 MAO-B IC50 and a selectivity index >105. Advancement of the most active compounds showing sub-micromolar activities to further cellular evaluations of viability and induced production of pro-neuroinflammatory mediators confirmed compound 2e as a potential lead compound inhibiting the production of the neuroinflammatory mediator nitric oxide significantly by microglial BV2 cells at 3 µM concentration without significant cytotoxicity up to 30 µM. In silico molecular docking study predicted plausible binding modes with MAO enzymes and provided insights at the molecular level. Overall, this report presents compound 2e as a potential lead compound to develop potential multifunctional compounds.

Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model.

Background: The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function. Methods: In 2 separate cohorts, 32 syngeneic orthotopic rat liver transplants were performed in Lewis rats. Livers were procured from donors with 45 min of warm ischemic injury. Liver grafts were flushed with histidine-tryptophan-ketoglutarate preservation solution mixed with either plasmin (experimental group) or albumin (control group). All investigators were blinded to treatment group. After preparing the liver for implant using a modified cuff technique, the liver was stored for 1 h by static cold storage at 4 °C. Immediately before implantation, the liver graft was flushed, and this effluent was analyzed for fibrin degradation products to determine graft clot burden. Twenty-four hours following transplantation, animals were euthanized, and samples were collected. Results: Recipient survival was significantly higher for DCD liver grafts treated with plasmin compared with control. Moreover, histology of liver graft tissue immediately before implant reflected significantly reduced congestion in plasmin-treated livers (score, mean ± SD: 0.73 ±â€…0.59 versus 1.12 ±â€…0.48; P = 0.0456). The concentration of fibrin degradation products in the final flush before implantation was significantly reduced in plasmin-treated livers (743 ±â€…136 versus 10 919 ±â€…4642 pg/mL; P = 0.0001), reflecting decreased clot burden in the graft. Conclusions: The present study demonstrates that plasmin improves survival and may reduce thrombotic burden in DCD liver grafts with prolonged warm ischemic injury, meriting further study.