Search

Background: Fertility is one of the three main components which determines the size, structure, and composition of a population, and fertility preferences are important measures for forecasting fertility levels of a population. Therefore, this study aims to assess the impacts of the inequalities in the utilization of key maternal health services on fertility preference among high parity women in four selected regions (i.e., Afar, Beninshangul-Gumuz, Gambella and Somali) of Ethiopia. Methods: The study used data collected for the 2016 Ethiopian Demographic and Health Surveys (EDHS) survey. It includes a total of 977 high parity women (104 urban and 873 rural) residing in the four regions of the study. Bivariate logistic regression was used to select the potential variables by using a cut off p-value < 0.2 and then the multivariable logistic regression analyses were performed to assess the association between the selected explanatory variables (i.e., control and exposure variables) and the outcome variable (i.e. fertility preference). Further, the study employed a Population Attributable Fractions (PAFs) to examine the population level impacts of the inequalities in maternal and child health service variables on fertility preference. Results: The results showed that religion, household wealth index, place of delivery and contraceptive use were significantly associated with fertility preference. The results of the PAFs analysis indicated that contraceptive use had the biggest impact (80%), meaning that non-use of contraceptive increased fertility preference among women in the four regions. Similarly, out of health facility delivery increased fertility preference by 37%. Conclusion: The study findings underscore the critical factors influencing women's fertility preferences in the studied regions. Low utilization of maternal health services had an impact on fertility preference, accounting for more than half of the observed variations in fertility preferences. To address this issue, targeted interventions are recommended: enhancing access to maternal health services, strengthening fertility control programs, promoting the benefits of using these services, and actively addressing inequalities. [ABSTRACT FROM AUTHOR]

Background: Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. Methods: In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. Results: The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06–2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05–2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% − 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% − 24.1%) had the highest population attributable fraction for intussusception. Conclusion: Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception. [ABSTRACT FROM AUTHOR]

Abstract Background Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens. Methods In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception. Results The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06–2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05–2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% − 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% − 24.1%) had the highest population attributable fraction for intussusception. Conclusion Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.

Background: The study of tactile perception during a childhood is extremely important for understanding the social and communicative aspects of the child's development. Tactile perception of stimuli with different valence can have different normative stages of development. Methods: In the present study, we examined changes in linear and nonlinear electroencephalogram (EEG) parameters during the presentation of pleasant (C-tactile optimal stroking), unpleasant (ice stroking), and neutral tactile stimuli in three groups of healthy volunteers: preschoolers 4 and 5 years, school-age children from 8 to 10 years, and adults from 20 to 40 years. Results: According to our findings, child maturation plays a significant role in the perception of pleasant and neutral tactile stimuli. Patterns of EEG dynamics related to tactile perception showed greater similarity between adult volunteers and school-aged children than preschoolers. Conclusions: Non-linear EEG parameters such as fractal dimension (FD), envelope mean frequency (EMF), and power spectral density (PSD) dynamics of the theta-rhythm were particularly sensitive to developmental changes in tactile perception. Hjorth complexity and peak alpha frequency (PAF) scores may serve as indicators of mature perception of C-tactile (CT)-stimuli. [ABSTRACT FROM AUTHOR]

Background & aims: Accumulating studies have demonstrated associations between single lifestyle exposures and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the joint effects of lifestyle exposures remain unclear, hindering the development of targeted prevention and control strategies. We aimed to investigate the joint associations between lifestyle exposomes and MAFLD. Methods: This study included 5,002 participants from NHANES 2017-2020. Lifestyle exposomes, including sleep duration, metabolic equivalent of task (MET), Healthy Eating Index (HEI)-2015 score, alcohol consumption, and smoke exposure, were identified from questionnaire data. MAFLD was diagnosed by vibration-controlled transient elastography measurements and laboratory data. A logistic regression model and the weighted quantile sum method were used to evaluate the associations of single and joint lifestyle exposomes, respectively, with MAFLD. The population attributable fractions (PAFs) were calculated to assess the population benefits of different intervention strategies. Results: Per-quartile range increases in sleep duration (OR=0.883, 95% CI: 0.826-0.944), MET (0.916, 0.871-0.963), and HEI-2015 score (0.827, 0.756-0.904) were significantly associated with MAFLD. The joint exposure of sleep duration, MET, and HEI-2015 score was associated with MAFLD (0.772, 0.688-0.865), with the highest weight (importance) for MET (0.526). PAFs revealed greater intervention benefits for sleep and the HEI-2015 when the majority of the population (>5%) had a low MAFLD risk (weak intervention targets), whereas MET was the most efficient intervention strategy when minority populations (=5%) had a low MAFLD risk (strong intervention targets). Conclusion: This study demonstrated significant associations between MAFLD and single and joint exposures to sleep duration, MET, and HEI-2015 and identified physical activity as the most important lifestyle factor. Further population benefit analyses may provide evidence and suggestions for population-level interventions. [ABSTRACT FROM AUTHOR]

The fourth universal definition of MI defines requires presence of j point elevation in two contiguous leads except v2–3 where the elevation should be equal to or >2 mm in men (2.5 mm in <40 years) and 1.5 mm in women.(1) We present two cases of patients who presented with electrocardiographic manifestations of occlusion of septal perforator of left anterior descending artery and discuss the salient feature of ECG in such patients. We also present the limitations of STEMI criteria given the dynamic nature of acute coronary occlusion and stress on early recognition of this MI. [ABSTRACT FROM AUTHOR]

Inflammation and thrombosis are implicated in several chronic disorders. Recent studies have outlined the way in which several compounds can offer protection against inflammation. Within this comprehensive review the so-far reported anti-inflammatory health-promoting effects of several metal-based complexes, both in vitro and in vivo, are thoroughly presented. These metal-based compounds usually interfere with various biochemical processes associated with the inflammatory response and thrombus formation and become capable of inhibiting these biochemical pathways with proposed health benefits. Emphasis is given to the multifaceted actions of metal-based complexes that have exhibited potent anti-inflammatory and antithrombotic activities against the inflammatory mediator, platelet-activating factor (PAF), and its thrombo-inflammatory signaling, as well as on their anti-platelet and antitumor health promoting properties. Furthermore, the enhancement of the anti-inflammatory potency of well-established bioactive compounds by their incorporation as ligands in several metal-based complexes is discussed. Metal-based complexes bearing natural anti-inflammatory bioactives are also outlined. Characteristic examples of both free and metal-based porphyrins are explored. These compounds are recognized to have anti-inflammatory and antithrombotic assets, in addition to other pleiotropic advantages including antibacterial or anticancer actions. Additionally, applications of metal complexes in various models of inflammatory and thrombotic complications are demonstrated. The combined results of this study show that further research is required towards the preparation of several metal-based complexes with improved pharmacological profiles. Finally, restrictions on the application of these metal-based compounds are also covered, along with their prospects for the future and the need for additional study in order to improve their efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: End‐stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). Aims: We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet‐activating factor (PAF), and P‐selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function. Methods: The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF. Results and Discussion: The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP‐1, respectively (p <.001). Serum TM was positively correlated with the levels of PAF and CD62P (p <.001), and PAF was positively correlated with the levels of CD62P (p <.001), respectively. Serum levels of TM, PAF and CD62P were risk factors for vascular access failure in AVF patients (p <.05). The area under the curve of serum TM, PAF and CD62P levels in predicting vascular access failure in AVF patients was 0.879. Conclusion: The serum levels of TM, PAF, and CD62P in AVF patients were correlated with the vascular access function of AVF patients, which was very important for maintaining the stability of vascular access function, and had certain value in predicting vascular access failure/disorder in AVF patients, and could be popularized and applied. [ABSTRACT FROM AUTHOR]

Acid mine drainage poses a significant challenge in open-pit coal mining, particularly in Indonesia, necessitating the development of effective prevention and control methods. This research aimed to assess the impact of fly ash (FA) and bottom ash (BA) coating on the mixing ratio of potentially acid-forming (PAF) and non-acid-forming (NAF) materials using a leaching column over an 8-week period. The results revealed a trend of increasing pH values and decreasing sulfate and metal concentrations in the leachate. Mixing 25% FABA in both PAF scenarios produced leachate with total concentrations of S, Fe, and Mn at 0.026 mg/L, 0.117 mg/L, and 0.677 mg/L, respectively, with a pH close to neutral (6.28). Kinetic tests indicate TDS and EC values in the resulting leachate at 1221 ppm and 2442 µs/m. This study demonstrated that PAF coating using NAF and the fly ash bottom ash (FABA) is an effective method for preventing or minimizing the generation of acid mine drainage. [ABSTRACT FROM AUTHOR]

Acid mine drainage poses a significant challenge in open-pit coal mining, particularly in Indonesia, necessitating the development of effective prevention and control methods. This research aims to assess the impact of fly ash (FA) and bottom ash (BA) coating on the mixing ratio of potential acid-forming (PAF) and non-acid-forming (NAF) materials using a leaching column over an 8-week period. The results revealed a trend of increasing pH values and decreasing sulfate and metal concentrations in the leachate. Mixing 25% FABA in both PAF scenarios produced leachate with total concentrations of S, Fe, and Mn at 0.026 mg/L, 0.117 mg/L, and 0.677 mg/L, respectively, with a pH close to neutral (6.28). Kinetic tests indicate TDS and EC values in the resulting leachate at 1221 ppm and 2442 µs/m. This study demonstrates that PAF coating using NAF and FABA is an effective method for preventing or minimizing the generation of acid mine drainage.

Since 2000s, we have outlined the multifaceted role of inflammation in several aspects of cancer, via specific inflammatory mediators, including the platelet activating factor (PAF) and PAF-receptor (PAFR) related signaling, which affect important inflammatory junctions and cellular interactions that are associated with tumor-related inflammatory manifestations. It is now well established that disease-related unresolved chronic inflammatory responses can promote carcinogenesis. At the same time, tumors themselves are able to promote their progression and metastasis, by triggering an inflammation-related vicious cycle, in which PAF and its signaling play crucial role(s), which usually conclude in tumor growth and angiogenesis. In parallel, new evidence suggests that PAF and its signaling also interact with several inflammation-related cancer treatments by inducing an antitumor immune response or, conversely, promoting tumor recurrence. Within this review article, the current knowledge and future perspectives of the implication of PAF and its signaling in all these important aspects of cancer are thoroughly re-assessed. The potential beneficial role of PAF-inhibitors and natural or synthetic modulators of PAF-metabolism against tumors, tumor progression and metastasis are evaluated. Emphasis is given to natural and synthetic molecules with dual anti-PAF and anti-cancer activities (Bio-DAPAC-tives), with proven evidence of their antitumor potency through clinical trials, as well as on metal-based anti-inflammatory mediators that constitute a new class of potent inhibitors. The way these compounds may promote anti-tumor effects and modulate the inflammatory cellular actions and immune responses is also discussed. Limitations and future perspectives on targeting of PAF, its metabolism and receptor, including PAF-related inflammatory signaling, as part(s) of anti-tumor strategies that involve inflammation and immune response(s) for an improved outcome, are also evaluated.

Apple pomace (AP) is a bio-waste product of apples that is co-produced as a by-product during apples' processing for making apple-based products, mainly apple juice, cider and vinegar. AP is a rich source of several bioactives that can be valorized as ingredients for developing novel functional foods, supplements and nutraceuticals. Within the present study, food-grade extracts from AP with different tannin contents were found to contain bioactive polar lipids (PLs), phenolics and carotenoids with strong anti-oxidant, antithrombotic and anti-inflammatory properties. The extract from the low-in-tannins AP showed stronger anti-inflammatory potency in human platelets against the potent thrombo-inflammatory mediator platelet-activating factor (PAF), while it also exhibited considerable anti-platelet effects against the standard platelet agonist, adenosine diphosphate (ADP). The infusion of 0.5–1.0 g of this bioactive AP extract as functional ingredients for whole-grain bread-making resulted in the production of novel bio-functional bread products with stronger anti-oxidant, antithrombotic and anti-inflammatory potency against both PAF and ADP in human platelets, compared to the standard non-infused control breads. Structural analysis by LCMS showed that the PL-bioactives from all these sources (AP and the bio-functional breads) are rich in bioactive unsaturated fatty acids (UFA), especially in the omega-9 oleic acid (OA; 18:1n9), the omega-3 alpha linolenic acid (ALA; 18:n3) and the omega-6 linoleic acid (LA; 18:2n6), which further supports their strong anti-inflammatory and antithrombotic properties. All food-grade extracted AP including that infused with AP-bioactives novel functional breads showed higher hydrophilic, lipophilic and total phenolic content, as well as total carotenoid content, and subsequently stronger antioxidant capacity. These results showed the potential of appropriately valorizing AP-extracts in developing novel bio-functional bakery products, as well as in other health-promoting applications. Nevertheless, more studies are needed to fully elucidate and/or validate the anti-inflammatory, antithrombotic and antioxidant potential of novel bio-functional products across the food and cosmetic sectors when infused with these AP bioactives. [ABSTRACT FROM AUTHOR]

Abstract Background End‐stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). Aims We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet‐activating factor (PAF), and P‐selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function. Methods The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF. Results and Discussion The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP‐1, respectively (p

Background: The study of tactile perception during a childhood is extremely important for understanding the social and communicative aspects of the child’s development. Tactile perception of stimuli with different valence can have different normative stages of development. Methods: In the present study, we examined changes in linear and nonlinear electroencephalogram (EEG) parameters during the presentation of pleasant (C-tactile optimal stroking), unpleasant (ice stroking), and neutral tactile stimuli in three groups of healthy volunteers: preschoolers 4 and 5 years, school-age children from 8 to 10 years, and adults from 20 to 40 years. Results: According to our findings, child maturation plays a significant role in the perception of pleasant and neutral tactile stimuli. Patterns of EEG dynamics related to tactile perception showed greater similarity between adult volunteers and school-aged children than preschoolers. Conclusions: Non-linear EEG parameters such as fractal dimension (FD), envelope mean frequency (EMF), and power spectral density (PSD) dynamics of the theta-rhythm were particularly sensitive to developmental changes in tactile perception. Hjorth complexity and peak alpha frequency (PAF) scores may serve as indicators of mature perception of С-tactile (CT)-stimuli.

G-coupled protein receptors (GPCRs) comprise the largest class of druggable targets. Signaling by GPCRs is initiated from subcellular hot spots including the plasma membrane, signalosomes, and endosomes to contribute to vascular inflammation. GPCR-G protein signaling at the plasma membrane causes endothelial barrier disruption and also cross-talks with growth factor receptors to promote proinflammatory signaling. A second surge of GPCR signaling is initiated by cytoplasmic NFκB activation mediated by β-arrestins and CARMA-BCL10-MALT1 signalosomes. Once internalized, ubiquitinated GPCRs initiate signaling from endosomes via assembly of the transforming growth factor-β-activated kinase binding protein-1 (TAB1)-TAB2-p38 MAPK complex to promote vascular inflammation. Understanding the complexities of GPCR signaling is critical for development of new strategies to treat vascular inflammation such as that associated with COVID-19.

Objective: The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects. Methods: A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention. Results: Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels. Conclusion: Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects. Clinical Trial Registration: ClinicalTrials.gov (NCT02259205).

Atherosclerosis is a progressive vascular multifactorial process. The mechanisms underlining the initiating event of atheromatous plaque formation are inflammation and oxidation. Among the modifiable risk factors for cardiovascular diseases, diet and especially the Mediterranean diet (MedDiet), has been widely recognized as one of the healthiest dietary patterns. Olive oil (OO), the main source of the fatty components of the MedDiet is superior to the other "Mono-unsaturated fatty acids containing oils" due to the existence of specific microconstituents. In this review, the effects of OO microconstituents in atherosclerosis, based on data from in vitro and in vivo studies with special attention on their inhibitory activity against PAF (Platelet-Activating Factor) actions, are presented and critically discussed. In conclusion, we propose that the anti-atherogenic effect of OO is attributed to the synergistic action of its microconstituents, mainly polar lipids that act as PAF inhibitors, specific polyphenols and α-tocopherol that also exert anti-PAF activity. This beneficial effect, also mediated through anti-PAF action, can occur from microconstituents extracted from olive pomace, a toxic by-product of the OO production process that constitutes a significant ecological problem. Daily intake of moderate amounts of OO consumed in the context of a balanced diet is significant for healthy adults. [ABSTRACT FROM AUTHOR]

Traditionally cardiovascular disease (CVD) risk has been assessed through blood lipids and inflammatory marker C‐reactive protein (hsCRP). Recent clinical interest in novel pro‐inflammatory markers platelet‐activating factor (PAF) and lipoprotein‐associated phospholipase A2 (Lp‐PLA2) recognizes that vascular damage can exist in the absence of traditional risk factors. This cross‐sectional study investigated the potential relationship between circulating PAF, Lp‐PLA2, hsCRP, and traditional risk factors for CVD. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting inflammatory markers PAF, Lp‐PLA2 and hsCRP and total, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL) cholesterol, and triglycerides were measured. Blood pressure, body mass index, and waist circumference were measured. Medical and physical activity data were self‐reported. Linear and multiple regressions were performed. PAF, Lp‐PLA2, and hsCRP independently correlated with several CVD risk factors. PAF was correlated significantly with risk factors in an unexpected way; there was a medium positive correlation between PAF and HDL cholesterol (r = 0.394, p < 0.001) and medium negative correlations with Total:HDL cholesterol; (r = −0.436, p < 0.001) systolic blood pressure; (r = −0.307, p = 0.001); BMI (r = −0.381, p < 0.001); and waist circumference (r = −0.404, p < 0.001). There were large positive correlations between Lp‐PLA2 and LDL (r = 0.525, p < 0.001) and non‐HDL cholesterol (r = 0.508, p < 0.001). There were large positive correlations between hsCRP and Total:HDL cholesterol (r = 0.524, p < 0.001); BMI (r = 0.668, p < 0.001); and waist circumference (r = 0.676, p < 0.001). PAF, Lp‐PLA2, and hsCRP are implicated in the pathophysiology of inflammation in CVD; however, the relationships between each marker and traditional risk factors were different suggesting they may be involved in different atherogenic pathways. [ABSTRACT FROM AUTHOR]

Summary: Background: Quantifying the proportion of dementia attributable to highly prevalent modifiable risk factors, such as hypertension, is important in informing effective dementia prevention strategies. We aim to quantify the population attributable fraction (PAF) of hypertension for dementia (the proportion of dementia cases that would not occur if hypertension was eliminated) at global, regional, and national levels. Methods: In this study, we searched international and governmental websites for global, regional, and national data reporting population hypertension (according to 10-year age categories) and dementia prevalence. MEDLINE was searched for studies reporting the risk of dementia from age at hypertension diagnosis from database inception to December 31, 2022. Longitudinal observational studies with >500 participants reporting hazard ratios by age at hypertension diagnosis for risk of future all-cause dementia were eligible for inclusion. Studies excluded had cross-sectional methodology, specific vascular dementia or ‘cognitive impairment’ outcomes, and no age-specific metrics of association reported. The PAF of hypertension for dementia was calculated globally and for each country and region worldwide. Findings: Data from the Global Burden of Disease, United Nations Population Prospectus, NCD Risk Factor Collaboration, UK Biobank, and Atherosclerosis Risk in Communities Study were obtained. 186 countries reported dementia and hypertension prevalence data. The global PAF of hypertension for dementia was 15.8% [95% Credible Interval (CI), 8.8%–22.7%]. Latin America and the Caribbean (18.0% [95% CI, 9.4%–26.6%]), and Europe (17.2% [95% CI, 9.6%–24.7%]) had the highest PAF of hypertension for dementia. Hypertension diagnosed between the ages of 30–44 had the highest age-specific global attributable fraction for dementia (8.4% [95% CI, 3.4%–13.5%]), followed by ages 45–54 (2.92% [ 95% CI, 0.96%–4.88%]), 55–64 (2.59% [95% CI, 1.15%–4.03%]) and 65–74 (1.82% [95% CI, −2.31%–5.96%]). Interpretation: The population attributable risk of hypertension for dementia is 15.8%, suggesting that optimal detection and treatment, particularly at midlife, has the potential to markedly reduce the global burden of dementia. Funding: Wellcome Trust; Health Research Board of Ireland; Alzheimer's Association.

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAFD19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated 15N-1H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H2O mixtures were more similar in the mixed solvents then they were in water. The 15N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the Tm melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAFD19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF. [ABSTRACT FROM AUTHOR]

Platelet‐activating factor (PAF) is a phospholipid‐derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso‐PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood–brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions. [ABSTRACT FROM AUTHOR]

Ocular allergies are becoming more prevalent as more airborne pollutants, irritants and microbes pervade our environment. Inflammatory and allergic mediators released by dendritic and mast cells within the conjunctiva cause allergic conjunctivitis (AC), a prevalent ocular surface disorder that affects >40% of the world's human population on a seasonal or perennial basis. Even though histamine is a major culprit, platelet‐activating factor (PAF) also contributes to AC, acting either directly or synergistically with histamine and other mediators. PAF receptor‐meditated inflammatory reactions, via cell‐membrane‐bound and nuclear‐membrane‐bound and nuclear PAF receptors, are also implicated in the etiology of other eye diseases such as uveitis, diabetic retinopathy, corneal and choroidal neovascularization, and age‐related macular degeneration which cause serious visual impairment and can lead to blindness. This review highlights the various deleterious elements implicated in the pathological aspects of ocular allergic reactions and inflammation and provides concepts and treatment options to mitigate these eye disorders with a special focus on PAF and PAF receptor antagonists. [ABSTRACT FROM AUTHOR]

According to previous studies, during Drosophila embryogenesis, the recruitment of RNA polymerase II precedes active gene transcription. This work is aimed at exploring whether this mechanism is used during Drosophila metamorphosis. In addition, the composition of the RNA polymerase II "paused" complexes associated with promoters at different developmental stages are described in detail. For this purpose, we performed ChIP-Seq analysis using antibodies for various modifications of RNA polymerase II (total, Pol II CTD Ser5P, and Pol II CTD Ser2P) as well as for subunits of the NELF, DSIF, and PAF complexes and Brd4/Fs(1)h that control transcription elongation. We found that during metamorphosis, similar to mid-embryogenesis, the promoters were bound by RNA polymerase II in the "paused" state, preparing for activation at later stages of development. During mid-embryogenesis, RNA polymerase II in a "pause" state was phosphorylated at Ser5 and Ser2 of Pol II CTD and bound the NELF, DSIF, and PAF complexes, but not Brd4/Fs(1)h. During metamorphosis, the "paused" RNA polymerase II complex included Brd4/Fs(1)h in addition to NELF, DSIF, and PAF. The RNA polymerase II in this complex was phosphorylated at Ser5 of Pol II CTD, but not at Ser2. These results indicate that, during mid-embryogenesis, RNA polymerase II stalls in the "post-pause" state, being phosphorylated at Ser2 of Pol II CTD (after the stage of p-TEFb action). During metamorphosis, the "pause" mechanism is closer to classical promoter-proximal pausing and is characterized by a low level of Pol II CTD Ser2P. [ABSTRACT FROM AUTHOR]

The anti-oxidant properties of vitamin C and of phenolic compounds of citrus fruits are well established. However, the evaluation of the anti-inflammatory and antithrombotic potential of both vitamin C and of the more amphiphilic and lipophilic components of citrus fruits needs further attention. In this study, the anti-inflammatory and antithrombotic properties of vitamin C and of freshly squeezed juices and their lipid bioactives from the Navalina and Sanguine orange varieties and the Clementine variety of mandarins, as well as from their remaining by-products, were evaluated against the inflammatory and thrombotic pathways of the platelet-activating factor (PAF) and thrombin in platelets, as well as against PAF-biosynthesis in leukocytes. The non-oxidized juices of these citrus fruits and a vitamin C supplement showed stronger anti-PAF and antithrombin effects than their oxidized versions through their general anti-oxidant effect in platelets. The total lipids (TLs) and the HPLC-derived fractions of phenolic compounds and of polar lipid bioactives from both juices and their peels' by-products showed a more specific stronger inhibitory effect against the inflammatory and thrombotic pathways of PAF and thrombin in platelets, while these bioactives strongly inhibited also the specific enzyme activities of the main biosynthetic enzymes of PAF in leukocytes. The stronger bioactivity of the dietary bioactives found in the juices of these citrus fruits against specific biochemical pathways of inflammation and thrombosis seems to act with synergy with the anti-oxidant potential of their vitamin C content, which further supports the notion that these juices are functional foods with anti-inflammatory protective health benefits. In addition, the presence of these dietary bioactive phenolic compounds and polar lipid bioactives in the remaining peels' wastes further enhance the valorization of such food industry by-products as potential sources of anti-inflammatory bioactives to be used as ingredients for novel functional products. [ABSTRACT FROM AUTHOR]

Since 2000s, we have outlined the multifaceted role of inflammation in several aspects of cancer, via specific inflammatory mediators, including the platelet activating factor (PAF) and PAF-receptor (PAFR) related signaling, which affect important inflammatory junctions and cellular interactions that are associated with tumor-related inflammatory manifestations. It is now well established that disease-related unresolved chronic inflammatory responses can promote carcinogenesis. At the same time, tumors themselves are able to promote their progression and metastasis, by triggering an inflammation-related vicious cycle, in which PAF and its signaling play crucial role(s), which usually conclude in tumor growth and angiogenesis. In parallel, new evidence suggests that PAF and its signaling also interact with several inflammation-related cancer treatments by inducing an antitumor immune response or, conversely, promoting tumor recurrence. Within this review article, the current knowledge and future perspectives of the implication of PAF and its signaling in all these important aspects of cancer are thoroughly re-assessed. The potential beneficial role of PAF-inhibitors and natural or synthetic modulators of PAF-metabolism against tumors, tumor progression and metastasis are evaluated. Emphasis is given to natural and synthetic molecules with dual anti-PAF and anti-cancer activities (Bio-DAPAC-tives), with proven evidence of their antitumor potency through clinical trials, as well as on metal-based anti-inflammatory mediators that constitute a new class of potent inhibitors. The way these compounds may promote anti-tumor effects and modulate the inflammatory cellular actions and immune responses is also discussed. Limitations and future perspectives on targeting of PAF, its metabolism and receptor, including PAF-related inflammatory signaling, as part(s) of anti-tumor strategies that involve inflammation and immune response(s) for an improved outcome, are also evaluated., (© 2024 The Author(s). Published by IMR Press.)

Within the present study, the effects of fermentation on the anti-inflammatory and anti-platelet properties of both homemade and commercially purchased bovine dairy and almond, coconut, and rice-based dairy alternatives were evaluated. The extracted total lipids (TL) from homemade and commercially purchased fermented and unfermented bovine, almond, coconut, and rice-based products were further separated into their neutral lipids (NL) and polar lipids (PL) fractions by counter current distribution. The TL, PL, and NL of each sample were assessed in human platelets against the inflammatory and thrombotic mediator, platelet-activating factor (PAF), and the well-established platelet agonist, adenosine 5′ diphosphate (ADP). In all samples, the PL fractions showed significantly stronger inhibitory effects against human platelet aggregation induced by PAF or ADP, in comparison to the TL and NL, with higher specificity against PAF. PL of all fermented products (bovine yogurt and fermented dairy alternatives from almond, rice, and coconut), exhibited the strongest anti-inflammatory and anti-platelet potency, in comparison to PL from their initial pasteurized materials (bovine milk and rice, almond, and coconut-based dairy alternative drinks). PL of the pasteurized rice-based drink and, especially PL from the novel homemade rice-based fermented product (HMFRD), showed the strongest anti-PAF and anti-ADP potency compared to all samples, with anti-PAF activity being most potent overall. The unfermented pasteurized coconut-based drink showed the lowest anti-inflammatory and anti-platelet potency, and the bovine and almond-based fermented products showed an intermediate effect. Further lipidomics with LC-MS analysis of all these PL fractions revealed that fermentation altered their fatty acid content in a way that decreased their degree of saturation and increased the content of unsaturated fatty acids, thus providing a rationale for the stronger anti-inflammatory and anti-platelet potency of the more unsaturated PL fractions of the fermented products. This study has shown that fermentation alters the fatty acid content and the bio-functionality of the PL bioactives in both fermented bovine dairy and plant-based dairy alternatives, and subsequently improved their anti-inflammatory and anti-platelet functional properties. [ABSTRACT FROM AUTHOR]

Context Atherosclerosis is a disease of chronic inflammation. Recent research has identified 2 novel inflammatory biomarkers: platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Diet has been proposed as a mediator of inflammation, but to date, the focus for these novel biomarkers has been on individual foods and nutrients rather than overall dietary patterns. Objective To systematically review the literature on the association between dietary patterns and PAF and Lp-PLA2. Data Sources The PubMed, Embase, CINAHL, and Cochrane CENTRAL literature databases were searched. Data Analysis Study quality was evaluated using the Quality Criteria Checklist. Sixteen studies (n = 4 observational and n = 12 interventional) were included and assessed for associations between dietary patterns and PAF and Lp-PLA2. Conclusion Study quality varied from neutral (n = 10) to positive (n = 6). Mediterranean, heart healthy, and vegetarian dietary patterns were associated with improved levels of PAF and Lp-PLA2. Conversely, Western dietary patterns were less favorable. A range of well-established, healthier dietary patterns may lower inflammation and the risk of atherosclerosis. More well-designed studies are needed to confirm these findings and identify other dietary patterns that improve inflammation. [ABSTRACT FROM AUTHOR]

The characterization of cardio-protective lipid bioactives from cyanobacteria, such as Spirulina spp., has rarely been investigated. In this study, neutral lipids, glycolipids, and phospholipids of Irish marine cyanobacterium Spirulina subsalsa, were tested for anti-inflammatory and antithrombotic activities in vitro in human platelets. Glycolipids and phospholipids inhibited strongly platelet aggregation induced by platelet-activating factor (PAF) or thrombin, with IC50 (half maximal inhibitory concentration) values ranging ∼60–110 µg of polar lipids. The characterisation of the glycolipids revealed the presence of sulfoquinovosyl diacylglycerols (SQDG), monogalactosylodiglycerides (MGDG) and glycosphingolipids (cerebrosides and ceramides). Phospholipids contained mostly bioactive phosphatidylcholines (PC) and phosphatidylethanolamines (PE) molecules such as, diacyl-PC, diacyl-PE, alkyl-acyl PC, and alkyl-acyl-PE, as well as considerable amounts of phosphatidylglycerols (PG), phosphatidylinositols (PI), phosphatidylserines (PS), and phosphatidic acids (PA). The total presence of such lipid bioactives with cardio-protective properties makes marine Spirulina subsalsa a candidate as a sustainable source for health supplements with cardiovascular health benefits.

OBJECTIVES: This study aimed to investigate the influence of chronic diseases and multimorbidity on entering paid employment among unemployed persons. A secondary objective was to estimate the proportion of persons not entering paid employment that can be attributed to specific chronic diseases across different age groups. METHODS: Data linkage of longitudinal nationwide registries on employment status, medication use and socio­demographic characteristics was applied. Unemployed Dutch persons (N=619 968) were selected for a three-year prospective study. Cox proportional hazards analyses with hazard ratios (HR) were used to investigate the influence of six common chronic diseases on entering paid employment, stratified by age. The population attributable fraction (PAF) was calculated as the proportion of all persons who did not enter paid employment that can be attributed to a chronic disease. RESULTS: Persons with chronic diseases were less likely to enter paid employment among all age groups. The impact of a chronic disease on maintaining unemployment at population level was largest for common mental disorders (PAF 0.20), due to a high prevalence of common mental disorders (6%), and for psychotic disorders (PAF 0.19), due to a high likelihood of not entering paid employment (HR 0.21), among persons aged 45–55 years. Multimorbidity increased with age, and the impact of having multiple chronic diseases on remaining unemployed increased especially among persons aged ≥45 years. CONCLUSION: Chronic diseases and multimorbidity are important factors that reduce employment chances among all age groups. Our results provide directions for policy measures to target specific age and disease groups of unemployed persons in order to improve employment opportunities.

This study explores Neutrophil Extracellular Trap (NET) formation in equine neutrophils, which is crucial for eliminating infections and is implicated in various equine inflammatory diseases. We investigated the molecular pathways involved in NET release by equine neutrophils in response to stimuli. We use PMA, A23187, LPS, PAF, OZ, and cytokines, observing NET release in response to PMA, PAF, and A23187. In contrast, LPS, OZ, and the cytokines tested did not induce DNA release or did not consistently induce citrullination of histone 4. Peptidyl-arginine deiminase inhibition completely halted NET release, while NADPH oxidase and mitochondrial reactive oxygen species only played a role in PMA-induced NETs. Neutrophil elastase inhibition modestly affected PAF-induced NET liberation but not in PMA or A23187-induced NET, while myeloperoxidase did not contribute to NET release. We expect to provide a foundation for future investigations into the role of NETs in equine health and disease and the search for potential therapeutic targets. • PMA, A23187, and PAF induce extracellular trap release in equine neutrophils. • Reactive oxygen species are only necessary for extracellular traps induced by PMA. • Neutrophil elastase is only relevant for PAF-induced extracellular traps. • Myeloperoxidase is not required for neutrophil extracellular trap release. • Peptidyl-arginine deiminase inhibition halted neutrophil extracellular trap release. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a progressive vascular multifactorial process. The mechanisms underlining the initiating event of atheromatous plaque formation are inflammation and oxidation. Among the modifiable risk factors for cardiovascular diseases, diet and especially the Mediterranean diet (MedDiet), has been widely recognized as one of the healthiest dietary patterns. Olive oil (OO), the main source of the fatty components of the MedDiet is superior to the other “Mono-unsaturated fatty acids containing oils” due to the existence of specific microconstituents. In this review, the effects of OO microconstituents in atherosclerosis, based on data from in vitro and in vivo studies with special attention on their inhibitory activity against PAF (Platelet-Activating Factor) actions, are presented and critically discussed. In conclusion, we propose that the anti-atherogenic effect of OO is attributed to the synergistic action of its microconstituents, mainly polar lipids that act as PAF inhibitors, specific polyphenols and α-tocopherol that also exert anti-PAF activity. This beneficial effect, also mediated through anti-PAF action, can occur from microconstituents extracted from olive pomace, a toxic by-product of the OO production process that constitutes a significant ecological problem. Daily intake of moderate amounts of OO consumed in the context of a balanced diet is significant for healthy adults.

The natural product Ginkgolide B was used as a raw material and modified by etherification on C10–OH to obtain 10 derivatives (1 to 10), which were structurally characterized with nuclear magnetic resonance spectroscopy. An test of rabbit platelet aggregation induced by platelet activating factor showed that All ginkgolide compounds and ginkgolide B derivatives inhibited platelet aggregation in rabbits induced by platelet activating factor and compounds 1, 2, 9, and 10 exhibited strong inhibitory activity against Rabbit platelet aggregation, with IC50 values of 127.5 ± 5.9 μM, 86.9 ± 5.4 μM, 111.1 ± 13.6 μM, and 100.9 ± 8.0 μM. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are distributed in tissues throughout the body and are highly involved in many physiological and pathophysiological processes. The potential and involvement of different MC phenotypes are still not well understood. MCs are present in blood vessel walls, but their specific phenotypic features are unknown. We aimed at characterizing MCs from human saphenous veins for localization, mediator content, and receptor expression. This was done in MCs from both healthy and varicose human saphenous veins (hSV and vSV, respectively). For both vSV and hSV, we found that vein MCs are mainly present in the tunica adventitia (99% MCs in adventitia) and that the population consists of both MCT and MCTC phenotypes (vSV: 55% MCT, hSV: 64% MCT). The vein MCs contained high levels of histamine (vSV: 27 pg/MC, hSV: 55 pg/MC) and tryptase (vSV: 98 pg/MC, hSV: 111 pg/MC), indicating a strong potential for regulatory effects on blood vessels. The receptor expression of FcεRI, MRGPRX2, PTAFR, C3aR, and C5aR was found, even though the percentage of positive cells differed between vSV and hSV MCs. We conclude that vein MCs from the blood vessel wall have a high potential to affect the tissue around them. [ABSTRACT FROM AUTHOR]

To investigate the influencing factors of spontaneous preterm birth, and to analyze the value of maternal fetal fibronectin(fFN), monocyte chemotactic protein 1(MCP-1) and platelet activating factor(PAF) in predicting spontaneous preterm birth. Methods: 300 pregnant women who underwent obstetric examination in the obstetric clinic of our hospital from June 2019 to June 2020 were selected as the research object, including 45 cases of spontaneous preterm birth (preterm birth group), 255 cases without spontaneous preterm birth (control group). Venous blood of both groups was collected at 30 weeks of gestation, the levels of serum fFN, MCP-1and PAF were detected. The related data were collected, and multivariate Logistic regression was used to analyze the factors affecting the occurrence of spontaneous preterm birth. Receiver operating characteristic curve(ROC) was used to analyze the value of fFN, MCP-1 and PAF in predicting spontaneous preterm birth. Results: Univariate analysis showed that the body mass index < 19 kg/m2, assisted reproductive technology assisted pregnancy, history of preterm birth, history of cervical surgery, pregnancy interval time < 18 months, pregnancy complicated with premature rupture of membranes, pregnancy complicated with cervical shortening, the proportion of smoking during pregnancy, and the levels of serum fFN, MCP-1 and PAF in the preterm birth group were higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that pregnancy complicated with premature rupture of membranes, cervical shortening, history of preterm birth, high level of fFN, high level of MCP-1 and high level of PAF were the risk factors of spontaneous preterm birth(OR＞1, P＜0.05). The area under the curve (AUC) (0.95CI) of fFN, MCP-1, PAF and their combined application in predicting spontaneous preterm birth were 0.736 (0.480~0.990), 0.713 (0.488~0.935), 0.735 (0.495~0.967) and 0.866 (0.782~0.940), respectively, the pre-diction efficiency of combined application was higher than that of single index. Conclusion: Pregnancy complicated with premature rupture of membranes, cervical shortening, history of preterm birth, elevated serum levels of fFN, MCP-1 and PAF are the risk factors of spontaneous preterm birth. Combined with the levels of FN, MCP-1 and PAF can predict the risk of spontaneous preterm birth. [ABSTRACT FROM AUTHOR]

To investigate the changes of serum levels of PLA2 and PAF in pregnant rats with amniotic fluid embolism. Methods The 30 healthy pregnant rats were divided into normal saline group (group A), amniotic fluid group (group B) and amniotic fluid meconium mixture group (group C). Healthy pregnant rats were anesthetized. After the anesthesia effect was generated, the left com-mon carotid artery was isolated from the posterior closure of the uterus, and the two channels of physiological recorder were connected with it to continuously monitor the hemodynamic indicators. The rats were then intravenously injected with saline, amniotic fluid and a mixture of amniotic fluid and meconium. The rat lung tissue was taken 1 hour later. HE and APK staining and CK16 immunohistochemistry were used to detect the success of the model. At two blood points 1 hour before and after the experiment, 1mL of blood was taken from the left carotid artery cannula of the prepared amniotic fluid embolization model rats. The contents of PLA2 and PAF in serum, amniotic fluid and amniotic fluid meconium mixture were determined by enzyme-linked immunoassay. The obtained data were processed by SPSS 20.0 software, and serum PLA2 and PAF concentrations were analysed by paired t test, covariance analysis and correlation regression analysis. Results The 3 hemodynamic indexes (systolic, diastolic and mean arterial pressure) of group B and group C were significantly lower than that of group A (P<0.05), while the 4 hemodynamic indexes of group B and group C were not significantly different(P>0.05). Meanwhile, there was no significant difference in heart rate between group A, group B and group C (P>0.05). In HE staining, the lung interstitium of the rats in group B and C was significantly widened, with hyperemia, edema and inflammatory cell infiltration, while that of group A was not observed. In AMP staining, the lung tubules of group B and C showed blue amorphous material and pink keratinized squamous epithelium, while those of group A did not. In CK16 staining, yellow particles and squamous epithelium could be seen in the lung tubules of rats in group B and C, but not in group A. After 1 hour of experiment, the PLA2 and PAF content in group Band C was significantly higher than that in group A (P<0.05), and the elevation was greater in group C. PLA2 and PAF were detected in both the amniotic fluid and the amniotic fluid meconium mixture of pregnant rats, and both were high in the amniotic fluid meconium mixture. There was no correlation between PLA2 and PAF concentrations in the blood taken 1 hour before the experiment (P=0.762,R=0.012), while there was a positive correlation between PLA2 and PAF concentrations in the blood taken 1 hour after the experiment(P=0.002, R=0.437). The results of HE and APK combined with CK16 staining showed that the model of amniotic fluid embolization was successfully made. Both PLA2 and PAF were present in the amniotic fluid and meconium of the rats, and the levels ofPLA2 and PAF in the blood taken 1 hour after the experiment were significantly higher in group B combination C than in group A. This suggests that amniotic fluid and meconium contain stimulants that increase PLA2 and PAF levels. [ABSTRACT FROM AUTHOR]

The beneficial effects of fish-derived lipid bioactives have come to prominence over the last few decades, especially for their utilization in fish oils, supplements, and nutraceuticals. Omega-3 (n-3) polyunsaturated fatty acids (PUFA), lipid vitamins, carotenoids, and polar lipid bioactives from fish have shown to possess a vast range of beneficial effects against a multitude of chronic disorders and especially against inflammation-and cardiovascular disorders (CVD). The observed cardio-protective effects and health benefits are believed to be attributed to the synergy of these fish-derived lipid bioactives. Within the present article the recent findings in the literature on the lipid content of the mainly consumed fish species, their bio-functionality, and cardio-protective benefits is thoroughly reviewed. Moreover, the recovery and valorization of such lipid bioactives from fish by-products and fishing by-catch, in order to reduce waste, while developing useful products containing cardio-protective lipids from the leftover materials of fisheries and aquaculture industries, are also of industrial and environmental interest. Emphasis is also given to the effects of heat treatments during fish processing on the structures and bio-functionality of these marine lipid bioactives, based on the paradigm of different cooking methodologies and thermal processing, while the compounds produced during such treatment(s) with detrimental changes in the fish lipid profile, which can reduce its cardio-protective efficacy, are also reviewed. Novel green extraction technologies and low temperature processing and cooking of fish and fishery by-products are needed to reduce these undesirable effects in a sustainable and environmentally friendly way. [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy is considered beneficial in acute ischemic stroke (AIS) patients with intracranial artery stenosis (ICAS), with more bleeding events. Ginkgolide is shown to reduce platelet activation after infarction, which might be of benefit in AIS. We aimed to explore the effect of Ginkgolide in AIS patients with ICAS. Methods: This was a randomized, double‐blinded, placebo‐controlled trial conducted at 61 centers in China. Within 72 h after onset, consecutive patients diagnosed as AIS with ICAS were randomized to either Ginkgolide or placebo treatment. The primary outcome was the composite of mortality and recurrent stroke (ischemic or hemorrhagic) during first 4 weeks in an intention‐to‐treat analysis. Secondary functional outcome was assessed by modified Rankin Scale and improvement of stroke severity was assessed by National Institution of Health Stroke Scale at day 28. Safety outcome was measured by the rate of severe adverse event (SAE). Results: There were 936 patients randomized to either Ginkgolide or placebo treatment. Their average age was 64.2 ± 10.4 years old and 36.0% of the patients were female. The composite index event occurred in six patients in placebo group, and none occurred in Ginkgolide group (risk ratio 1.01; 95% CI 1.00–1.02). There were more patients who achieved favorable outcome in Ginkgolide group, compared with that of the placebo group (OR 2.16, 95%CI 1.37–3.41). SAE occurred in five (1.1%) patients in the Ginkgolide group and three (0.6%) in the placebo group (OR0.60, 95CI% 0.14–2.53). Intracranial hemorrhage occurred in 1/473 (0.2%) in the placebo group. Conclusions: Ginkgolide, working as PAF antagonist, may reduce recurrent stroke in AIS with ICAS patients within 72 hours after onset. It might be an optional treatment in moderate‐to‐severe AIS patients with ICAS. (http://www.chictr.org.cn Number as ChiCTR‐IPR‐17012310). [ABSTRACT FROM AUTHOR]

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAFD19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated 15N-1H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H2O mixtures were more similar in the mixed solvents then they were in water. The 15N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the Tm melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAFD19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF.

Background & Aims: Accumulating studies have demonstrated associations between single lifestyle exposures and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the joint effects of lifestyle exposures remain unclear, hindering the development of targeted prevention and control strategies. We aimed to investigate the joint associations between lifestyle exposomes and MAFLD., Methods: This study included 5,002 participants from NHANES 2017-2020. Lifestyle exposomes, including sleep duration, metabolic equivalent of task (MET), Healthy Eating Index (HEI)-2015 score, alcohol consumption, and smoke exposure, were identified from questionnaire data. MAFLD was diagnosed by vibration-controlled transient elastography measurements and laboratory data. A logistic regression model and the weighted quantile sum method were used to evaluate the associations of single and joint lifestyle exposomes, respectively, with MAFLD. The population attributable fractions (PAFs) were calculated to assess the population benefits of different intervention strategies., Results: Per-quartile range increases in sleep duration (OR=0.883, 95% CI: 0.826-0.944), MET (0.916, 0.871-0.963), and HEI-2015 score (0.827, 0.756-0.904) were significantly associated with MAFLD. The joint exposure of sleep duration, MET, and HEI-2015 score was associated with MAFLD (0.772, 0.688-0.865), with the highest weight (importance) for MET (0.526). PAFs revealed greater intervention benefits for sleep and the HEI-2015 when the majority of the population (>5%) had a low MAFLD risk (weak intervention targets), whereas MET was the most efficient intervention strategy when minority populations (≤5%) had a low MAFLD risk (strong intervention targets)., Conclusion: This study demonstrated significant associations between MAFLD and single and joint exposures to sleep duration, MET, and HEI-2015 and identified physical activity as the most important lifestyle factor. Further population benefit analyses may provide evidence and suggestions for population-level interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Zhang, Huang, Pan, Tang, Lan, Bu and Wang.)

Aqueous zinc-iodine batteries (AZIBs) are attracting increasing attention because of their high safety and abundance of resources. However, the performance of AZIBs is compromised by inadequate confinement of soluble polyiodides, the undesired shuttle effect, and slow reaction kinetics. In this study, a porous aromatic framework (PAF) with abundant benzene motifs and a well-organized pore structure is adopted as the iodine host, which exhibits high iodine adsorption capacity and robust polyiodide confinement. Both experimental characterizations and theoretical simulations indicate that the interactions between iodine species and the PAF-1 facilitate the redox reaction by coupling the electronic structures of the active species in the framework. A comparison of PAF-1, PAF-5, and PAF-11 also emphasizes the structural advantages of the high surface area and interconnected three-dimensional channels of PAF-1. Consequently, the I 2 @PAF-1 cathode can deliver a high capacity of 328 mAh g -1 at 0.5 C, outstanding rate performance, and a stable cycling life of 20 000 cycles (86 % retention at 10 C). The robust polyiodide confinement and superb electrochemical performance of Zn-I 2 @PAF-1 provide insights into the practical application of PAFs as excellent electrode materials for AZIBs., (© 2024 Wiley‐VCH GmbH.)

The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Ursodeoxycholic acid (UDCA) has been used as an anti-inflammatory, antioxidant, and anti-apoptotic agent. We investigated the possible protective effects of UDCA in a neonatal rat pup model of NEC. We randomly divided rat pups into three groups: a control group, a non-treated NEC group, and a UDCA-treated NEC group. We induced NEC by feeding formula enterally and via hypoxia/reoxygenation. Intestinal samples were collected for histopathological and immunohistochemical evaluation. Blood samples were taken for biochemical analyses. UDCA significantly reduced the extents of terminal ileal and jejunal injuries compared to the NEC group (p <.01), reduced Bax and caspase-3 immunoreactivities (both p <.01), and lowered serum levels of platelet-activating factor and intestinal fatty acid-binding protein (p <.01, p =.023, respectively). In a rat model of NEC, UDCA protects against adverse intestinal histological, immunohistochemical, and biochemical changes. UDCA significantly reduces the effects of NEC on the rat pup intestine. [ABSTRACT FROM AUTHOR]