Matairesinol blunts adverse cardiac remodeling and heart failure induced by pressure overload by regulating Prdx1 and PI3K/AKT/FOXO1 signaling.

BACKGROUND: Pathological cardiac remodeling is a critical process leading to heart failure, characterized primarily by inflammation and apoptosis. Matairesinol (Mat), a key chemical component of Podocarpus macrophyllus resin, exhibits a wide range of pharmacological activities, including anti-hydatid, antioxidant, antitumor, and anti-inflammatory effects. PURPOSE: This study aims to investigate whether Matairesinol alleviate cardiac hypertrophy and remodeling caused by pressure overload and to elucidate its mechanism of action. METHODS: An in vitro pressure loading model was established using neonatal rat cardiomyocytes treated with angiotensin Ⅱ, while an in vivo model was created using C57 mice subjected to transverse aortic constriction (TAC). To activate the PI3K/Akt/FoxO1 pathway, Ys-49 was employed. Moreover, small interfering RNA (siRNA) and short hairpin RNA (shRNA) were utilized to silence Prdx1 expression both in vitro and in vivo. Various techniques, including echocardiography, wheat germ agglutinin (WGA) staining, HE staining, PSR staining, and Masson trichrome staining, were used to assess cardiac function, cardiomyocyte cross-sectional area, and fibrosis levels in rats. Apoptosis in myocardial tissue and in vitro was detected by TUNEL assay, while reactive oxygen species (ROS) content in tissues and cells was measured using DHE staining. Furthermore, the affinity of Prdx1 with Mat and PI3K was analyzed using computer-simulated molecular docking. Western blotting and RT-PCR were utilized to evaluate Prdx1 levels and proteins related to apoptosis and oxidative stress, as well as the mRNA levels of cardiac hypertrophy and fibrosis-related indicators. RESULTS: Mat significantly alleviated cardiac hypertrophy and fibrosis induced by TAC, preserved cardiac function, and markedly reduced cardiomyocyte apoptosis and oxidative damage. In vitro, mat attenuated ang Ⅱ - induced hypertrophy of nrvms and activation of neonatal rat fibroblasts. Notably, activation of the PI3K/Akt/FoxO1 pathway and downregulation of Prdx1 expression were observed in TAC mice; however, these effects were reversed by Mat treatment. Furthermore, Prdx1 knockdown activated the PI3K/Akt/FoxO1 pathway, leading to exacerbation of the disease. Molecular docking indicated that Molecular docking indicated that Mat upregulated Prdx1 expression by binding to it, thereby inhibiting the PI3K/Akt/FoxO1 pathway and protecting the heart by restoring Prdx1 expression levels. CONCLUSION: Matairesinol alleviates pressure overload-induced cardiac remodeling both in vivo and in vitro by upregulating Prdx1 expression and inhibiting the PI3K/Akt/FoxO1 pathway. This study highlights the therapeutic potential of Matairesinol in the treatment of cardiac hypertrophy and remodeling, providing a promising avenue for future research and clinical application.

Moving beyond the mean: an analysis of faecal corticosterone metabolites shows substantial variability both within and across white-tailed deer populations.

Glucocorticoid (GC) levels have significant impacts on the health and behaviour of wildlife populations and are involved in many essential body functions including circadian rhythm, stress physiology and metabolism. However, studies of GCs in wildlife often focus on estimating mean hormone levels in populations, or a subset of a population, rather than on assessing the entire distribution of hormone levels within populations. Additionally, explorations of population GC data are limited due to the tradeoff between the number of individuals included in studies and the amount of data per individual that can be collected. In this study, we explore patterns of GC level distributions in three white-tailed deer (Odocoileus virginianus) populations using a non-invasive, opportunistic sampling approach. GC levels were assessed by measuring faecal corticosterone metabolite levels ('fCMs') from deer faecal samples throughout the year. We found both population and seasonal differences in fCMs but observed similarly shaped fCM distributions in all populations. Specifically, all population fCM cumulative distributions were found to be very heavy-tailed. We developed two toy models of acute corticosterone elevation in an effort to recreate the observed heavy-tailed distributions. We found that, in all three populations, cumulative fCM distributions were better described by an assumption of large, periodic spikes in corticosterone levels every few days, as opposed to an assumption of random spikes in corticosterone levels. The analyses presented in this study demonstrate the potential for exploring population-level patterns of GC levels from random, opportunistically sampled data. When taken together with individual-focused studies of GC levels, such analyses can improve our understanding of how individual hormone production scales up to population-level patterns.

Young People's Support for and Personal Interest in an Advance Provision Model for Medication Abortion.

PURPOSE: To assess young people's interest in advance provision (AP) of medication abortion-receiving mifepristone and misoprostol from a clinician in advance for their future use. METHODS: From November 2022-August 2023 we administered an electronic survey regarding advance provision to patients assigned female at birth at four Bay Area youth-serving clinics. RESULTS: Among 152 people ages 14-24 years (mean 17.9) surveyed, 73.7% (95% CI, 65.9%-80.5%) supported and 46.1% (95% CI, 37.9%-54.3%) were interested in the AP model. AP interest was higher among people who experienced three or more difficulties trying to access reproductive healthcare (70.6% [95% CI, 44.0%-89.7%]) and who experienced food or housing insecurity (60.3% [95% CI, 46.6%-73.0%]). Most youth (81.6%) had a safe place to store the pills for later use; this proportion was significantly higher among people ages 18-24 years (88.5%) than teens ages 14-17 years (74.3%, P = .025). The most common perceived advantages of AP included being able to have the abortion earlier in pregnancy (61.8%), privacy (57.9%) and convenience (50.7%). Common disadvantages noted included concern that people might take the pills incorrectly (50.0%) or lose the pills (40.1%). CONCLUSIONS: Young people have considerable interest in AP of medication abortion. Further research is needed to document the AP model's feasibility, clinical outcomes, and effect on access for adolescents.

Spiny dogfish, Squalus suckleyi, shows a good tolerance for hypoxia but need long recovery times.

Pacific spiny dogfish, Squalus suckleyi, move to shallow coastal waters during critical reproductive life stages and are thus at risk of encountering hypoxic events which occur more frequently in these areas. For effective conservation management, we need to fully understand the consequences of hypoxia on marine key species such as elasmobranchs. Because of their benthic life style, we hypothesized that S. suckleyi are hypoxia tolerant and able to efficiently regulate oxygen consumption, and that anaerobic metabolism is supported by a broad range of metabolites including ketones, fatty acids and amino acids. Therefore, we studied oxygen consumption rates, ventilation frequency and amplitude, blood gasses, acid-base regulation, and changes in plasma and tissue metabolites during progressive hypoxia. Our results show that critical oxygen levels (P crit) where oxyregulation is lost were indeed low (18.1% air saturation or 28.5 Torr at 13°C). However, many dogfish behaved as oxyconformers rather than oxyregulators. Arterial blood PO2 levels mostly decreased linearly with decreasing environmental PO2. Blood gases and acid-base status were dependent on open versus closed respirometry but in both set-ups ventilation frequency increased. Hypoxia below Pcrit resulted in an up-regulation of anaerobic glycolysis, as evidenced by increased lactate levels in all tissues except brain. Elasmobranchs typically rely on ketone bodies as oxidative substrates, and decreased concentrations of acetoacetate and ß-hydroxybutyrate were observed in white muscle of hypoxic and/or recovering fish. Furthermore, reductions in isoleucine, glutamate, glutamine and other amino acids were observed. After 6 hours of normoxic recovery, changes persisted and only lactate returned to normal in most tissues. This emphasizes the importance of using suitable bioindicators adjusted to preferred metabolic pathways of the target species in conservation physiology. We conclude that Pacific spiny dogfish can tolerate severe transient hypoxic events, but recovery is slow and negative impacts can be expected when hypoxia persists.

Adrenal and metabolic hormones demonstrate risk-reward trade-offs for African elephants foraging in human-dominated landscapes.

A key driver of the African savannah elephant population decline is the loss of habitat and associated human-elephant conflict. Elephant physiological responses to these pressures, however, are largely unknown. To address this knowledge gap, we evaluated faecal glucocorticoid metabolite (fGCM) concentrations as an indicator of adrenal activity and faecal thyroid metabolite (fT3) concentrations as an indicator of metabolic activity in relation to land use, livestock density, and human landscape modification, while controlling for the effects of seasonality and primary productivity (measured using the normalized difference vegetation index). Our best-fit model found that fGCM concentrations to be elevated during the dry season, in areas with higher human modification index values, and those with more agropastoral activities and livestock. There was also a negative relationship between primary productivity and fGCM concentrations. We found fT3 concentrations to be higher during the wet season, in agropastoral landscapes, in locations with higher human activity, and in areas with no livestock. This study highlights how elephants balance nutritional rewards and risks in foraging decisions when using human-dominated landscapes, results that can serve to better interpret elephant behaviour at the human-wildlife interface and contribute to more insightful conservation strategies.

Comparative plasma biochemistry analyte data in nesting leatherback (Dermochelys coriacea), foraging green (Chelonia mydas) and foraging and nesting hawksbill (Eretmochelys imbricata) sea turtles in Grenada, West Indies.

Blood biochemistry represents a minimally invasive tool for monitoring sea turtle health, assessing injured sea turtles and supporting conservation strategies. In Grenada, West Indies, plasma biochemical variables were examined in 33 nesting leatherback (Dermochelys coriacea), 49 foraging green (Chelonia mydas), 49 foraging hawksbill (Eretmochelys imbricata) and 12 nesting hawksbill sea turtles sampled between 2017 and 2022. Plasma biochemistry reference intervals are described herein except for nesting hawksbills, which are represented by descriptive statistics due to the low sample size. Select analyte concentrations were positively correlated with curved carapace length in leatherbacks (chloride), green turtles (total protein, albumin and globulin) and foraging hawksbills (total protein, albumin and phosphorus). Cholesterol (7.8 mmol/l ± 1.6 SD) and triglyceride (6.9 mmol/l ± 1.9 SD) concentrations were significantly higher in leatherbacks compared to foraging green turtles, foraging hawksbills and nesting hawksbills (P < 0.001 for all). Cholesterol was significantly higher in nesting hawksbills compared to foraging green turtles (P = 0.050) and foraging hawksbills (P = 0.050). Foraging hawksbills demonstrated significantly higher aspartate transaminase activities than leatherbacks (P = 0.002), green turtles (P = 0.009) and nesting hawksbills (P < 0.001). Biochemical results provide baseline population health data and support guidance for treatments during clinical sea turtle rehabilitation efforts. They also provide insight into species-specific physiologic differences and preludes further studies to better characterize the impacts of life-stage class on biochemistry reference intervals to better support wild sea turtle populations in Grenada.

Transperineal biopsy as a new technique versus well-established transrectal biopsy for diagnosis of prostate cancer - A comparative study.

Introduction: Transrectal (TR) prostate biopsy has been the gold standard for prostate cancer diagnosis for years. With the emergence of transperineal (TP) prostatic biopsy, there is a shift in practice across medical services to adopt TP biopsy as the primary method of prostatic biopsy. Objective: The objective of the study is to compare cancer detection rates and complications between TP and TR biopsies in our region providing single-center experience with introduction of TP biopsy. Patients and Methods: This is a retrospective study utilizing a prospectively designed database comparing consecutive 80 cases of TP biopsy to 80 cases of TR biopsy in a single center. Results: Prebiopsy PSA was 14.2 ± 24.9 ng/dl in the TP group versus 23.7 ± 71.3 ng/dl in the TR group with P = 0.108. Prostate Imaging-Reporting and Data System (PIRAD) 4 and 5 lesions were found in 47 (58.9%) cases of TP biopsy versus 44 (60.3%) of TR group cases and P = 0.131. Cancer was detected in 49 (61.25%) patients in the TP group versus 45 (56.25%) in the TR group with no statistically significant difference and P = 0.665. No cases of hematochezia was reported in TP group, vs 14 (17.5%) reported in TR group with P value <.001. There were no statistically significant differences regarding the incidence of febrile urinary tract infection (UTI), hematuria, and hematospermia in the TP group 0 (0%), 7 (8.75%), and 3 (3.75%) versus 2 (2.50%), 14 (17.50%), and 5 (6.25%) in the TR group with P = 0.497, 0.159, and 0.719 consecutively. Conclusion: TP and TR biopsy have comparable cancer detection rates. TP biopsy has a significantly lower rectal bleeding rate than TR biopsy. There is a trend toward lower febrile UTI in the TP group; however, it did not reach statistical significance.

Cardiac remodeling: novel pathophysiological mechanisms and therapeutic strategies.

Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered as a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and ß-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and aetiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulphide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling.

High-throughput mRNA sequencing of human placenta shows sex differences across gestation.

INTRODUCTION: Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. OBJECTIVES: We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. STUDY DESIGN: We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. RESULTS: Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. DISCUSSION: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.

The impact of COVID-19 vaccination prior to SARS-CoV-2 infection on prevalence of long COVID among a population-based probability sample of Michiganders, 2020-2022.

PURPOSE: To estimate the association between COVID-19 vaccination status at the time of COVID-19 onset and long COVID prevalence. METHODS: We used data from the Michigan COVID-19 Recovery Surveillance Study, a population-based probability sample of adults with COVID-19 (n = 4695). We considered 30-day and 90-day long COVID (illness duration ≥30 or ≥90 days, respectively), using Poisson regression to estimate prevalence ratios (PRs) comparing vaccinated (completed an initial series ≥14 days before COVID-19 onset) to unvaccinated individuals (received 0 doses before COVID-19 onset), accounting for differences in age, sex, race and ethnicity, education, employment, health insurance, and rurality/urbanicity. The full unvaccinated comparison group was further divided into historic and concurrent comparison groups based on timing of COVID-19 onset relative to vaccine availability. We used inverse probability of treatment weights to account for sociodemographic differences between groups. RESULTS: Compared to the full unvaccinated comparison group, the adjusted prevalence of 30-day and 90-day long COVID were lower among vaccinated individuals [PR30-day= 0.57(95%CI:0.49,0.66); PR90-day= 0.42(95%CI:0.34,0.53)]. Estimates were consistent across comparison groups (full, historic, and concurrent). CONCLUSIONS: Long COVID prevalence was 40-60% lower among adults vaccinated (vs. unvaccinated) prior to their COVID-19 onset. COVID-19 vaccination may be an important tool to reduce the burden of long COVID.

Tissue Pressure Changes and Implications on Dressing Selection when utilising Negative Pressure Wound Therapy on an Ex Vivo Porcine Model.

Negative Pressure Wound Therapy (NPWT) is broadly used in surgical wound management and more recently burn care; however, the tissue pressure changes and best dressing application technique remains unknown. This study was done to help understand the tissue pressure changes beneath negative pressure when varying the delivered pressures, dressing thickness and distribution of dressings. This study was done in 2021 at a quaternary paediatric burns hospital. Utilising a cadaveric porcine model, an intracranial pressure monitor and transducer were used to assess pressure. The transducer was placed on the epidermis or inserted under ultrasound guidance via cannulation to the dermis, subcutaneous or muscular layer. Mepitel™, ACTICOAT™, varying layers of Kerlix™ (10, 20 or 30 layers) and NPWT were then applied either circumferentially or non-circumferentially. Each set of results is indicative of the intracranial pressure probe reading when NPWT was delivered at -40, -60, -80, -100 and -120 mmHg. The median and interquartile pressure recordings were epidermis: -42 (-42.5 - -41), -60.5 (-62.5 - -60), -80.5 (-82 - -80), - 99 (-99 - -98)mmHg (p < 0.001); dermis: 1 (0 - 2), 2 (1 - 3.5), 3 (2 - 5.5), 4 (3 - 7), 5.5 (4 - 7.5)mmHg (p < 0.001) (the increase in pressure was less when circumferential dressings (p < 0.001) or more layers of Kerlix were applied (p < 0.001)); subcutis: 1.5 (-4.5-1), -2.5 (-7.5 - 1.5), -3.5 (-11 - 1.5), -5 (-14 - 1.5) and -6 (-16 - 2)mmHg (p = 006) (the decrease in pressure was less with increased layers of Kerlix (0.047) and muscular: 0 (-0.5 - 0), 0 (-1 - 0.5), 0 (-1 - 1), 0 0 (-1 - 1), 00 (-1.5 - 1)mmHg (p = 0.55). These data suggest negative pressure paradoxically exerts a positive pressure on the dermis. Circumferential and multi-layer dressings reduce this positive pressure. This knowledge has impacted our burn negative pressure wound therapy dressing selection. The limitation of this study is the cadaveric model, a live model is suggested for future studies.

Involvement of cardiac glycosides targeting Na/K-ATPase in their inhibitory effects on c-Myc expression via its transcription, translation and proteasomal degradation.

Cardiac glycosides (CGs) have been used for decades to treat heart failure and arrhythmic diseases. Recent non-clinical and epidemiological findings have suggested that CGs exhibit anti-tumor activities. Therefore, CGs may be repositioned as drugs for the treatment of cancer. A detailed understanding of the anti-cancer mechanisms of CGs is essential for their application to the treatment of targetable cancer types. To elucidate the factors associated with the anti-tumor effects of CGs, we performed transcriptome profiling on human multiple myeloma AMO1 cells treated with periplocin, one of the CGs. Periplocin significantly down-regulated the transcription of MYC (c-Myc), a well-established oncogene. Periplocin also suppressed c-Myc expression at the protein levels. This repression of c-Myc was also observed in several cell lines. To identify target proteins for the inhibition of c-Myc, we generated CG-resistant (C9) cells using a sustained treatment with digoxin. We confirmed that C9 cells acquired resistance to the inhibition of c-Myc expression and cell proliferation by CGs. Moreover, the sequencing of genomic DNA in C9 cells revealed the mutation of D128N in α1-Na/K-ATPase, indicating the target protein. These results suggest that CGs suppress c-Myc expression in cancer cells via α1-Na/K-ATPase, which provides further support for the anti-tumor activities of CGs.

Proline-rich transmembrane protein 2 knock-in mice present dopamine-dependent motor deficits.

Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions, including the basal ganglia, where dopaminergic neurons are most abundant in the brain. Here, we generated several types of Prrt2 knock-in (KI) mice harboring mutations, such as c.672dupG, that mimics the human pathological mutation c.649dupC and investigated the contribution of Prrt2 to dopaminergic regulation. Regardless of differences in the frameshift sites, all truncating mutations abolished Prrt2 expression within the striatum and cerebral cortex, consistent with previous reports of similar Prrt2 mutant rodents, confirming the loss-of-function nature of these mutations. Importantly, administration of l-dopa, a precursor of dopamine, exacerbated rotarod performance, especially in Prrt2-KI mice. These findings suggest that dopaminergic dysfunction in the brain by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders.

Mannose oligosaccharide recognition of CGL1, a mannose-specific lectin containing DM9 motifs from Crassostrea gigas, revealed by X-ray crystallographic analysis.

CGL1 is a mannose-specific lectin isolated from the Pacific oyster Crassostrea gigas, and it belongs to the DM9 domain protein family. Each subunit of the CGL1 dimer consists of a tandem repeat of DM9 motifs, which were originally found in the Drosophila melanogaster genome. The CGL1 protomer contains two carbohydrate-binding sites: a high-affinity site A and a low-affinity site B. An assay using dendrimers containing oligomannose from yeast (Saccharomyces cerevisiae) revealed that CGL1 exhibited significantly higher affinity for mannotetraose (Man4) compared to mannobiose (Man2) and mannotriose (Man3). To investigate its oligomannose-recognition mechanism, X-ray crystallographic analyses of CGL1/oligomannose complexes were performed. In the CGL1/Man2 and CGL1/Man3 complexes, Manα1-2Man and Manα1-2Manα1-2Man, respectively, were primarily bound to site A, interacting with the non-reducing mannose residue. On the other hand, in the CGL1/Man4 crystal, Man4 (Manα1-2Manα1-2Manα1-6Man) was bound at both site A and site B at the non-reducing and reducing ends, thus linking adjacent CGL1 molecules with crystallographic symmetry. These findings suggest that CGL1 can recognize both the non-reducing and reducing mannose residues of mannose oligosaccharides at its two distinct carbohydrate-binding sites. This enables efficient complex formation, making CGL1 a pattern-recognition molecule capable of recognizing diverse structures of mannose-containing carbohydrate chains.

Corrigendum: Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphys.2023.1216948.].

Characterization of recombinant photoconverting green fluorescent Akanes.

Akanes are fluorescent proteins that have several fluorescence maxima. In this report, Akane1 and Akane3 from Scleronephthya gracillima were selected, successfully overexpressed in Escherichia coli and purified by affinity chromatography. Fluorescence spectra of the recombinant Akanes matured in darkness, or ambient light were found to have several fluorescence peaks. SDS-PAGE analysis revealed that Akanes matured in ambient light have two fragments. MS/MS analysis of Akanes digested with trypsin showed that the cleavage site is the same as observed for the photoconvertible fluorescent protein Kaede. The differences between the calculated masses from the amino acid sequence of Akane1 and the measured masses of Akane1 fragments obtained under ambient light coincided with those of Kaede. In contrast, a mass difference between the measured N-terminal Akane3 fragment and the calculated mass indicated that Akane3 is modified in the N-terminal region. These results indicate that numerous peaks in the fluorescent spectra of Akanes partly arise from isoproteins of Akanes and photoconversion. Photoconversion of Akane1 caused a fluorescence change from green to red, which was also observed for Akane3; however, the fluorescent intensity decreased dramatically when compared with that of Akane3.

Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis.

Introduction: Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately. Methods: Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS. Results: A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis. Discussion: The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments. Systematic Review Registration: identifier: [CRD42021271001].

Evaluation of cardiac indices using M-mode echocardiography after administration of metoclopramide and ondansetron in donkeys (Equus asinus): an experimental study.

The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For this purpose, 10 apparently healthy Egyptian Baladi donkeys (Equus asinus) were used in a crossover prospective study. Two trials were conducted with the administration of metoclopramide hydrochloride anhydrous at a dose of 0.25 mg Kg-1 and ondansetron hydrochloride sodium at a dose of 0.15 mg Kg-1. The control group (placebo) received a total volume of 50 mL of isotonic saline at 0.9%. An echocardiographic examination was performed using a Digital Color Doppler Ultrasound System equipped with a 2-3.9 MHz phased array sector scanner transducer. In general, the fractional shortening (FS%) was significantly affected by the time for metoclopramide (p = 0.031) and ondansetron (p = 0.047) compared with those of placebo, with treatment with metoclopramide provoking significantly higher percentages of FS% at T60 (p = 0.009) and T90 (p = 0.028) compared with those for ondansetron and placebo. The interaction of time x treatment also showed a statistically significant alteration of FS% (p < 0.05), while the values returned to the basal line at T240. Metoclopramide induced a significant decrease in E-point to septal separation (EPSS) at T90 (p = 0.005), and T240 (p = 0.007) compared with ondansetron and placebo. The time x treatment interaction also showed a significant (p < 0.05) variation in EPSS, with values returning to the basal line at T300. Mitral valve opening velocity (DE SLP) values were significantly affected by time (p = 0.004) in the metoclopramide group compared with those of ondansetron and placebo. Administration of metoclopramide and ondansetron provoked significant alterations of DE SLP at T60 (p = 0.039), T120 (p = 0.036), and T300 (p = 0.005) compared with placebo. In conclusion, caution should be exercised when administering both treatments, especially to animals with suspected cardiac problems.

Phosphorylated SARM1 is involved in the pathological process of rotenone-induced neurodegeneration.

Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1) is a NAD+ hydrolase that plays a key role in axonal degeneration and neuronal cell death. We reported that c-Jun N-terminal kinase (JNK) activates SARM1 through phosphorylation at Ser-548. The importance of SARM1 phosphorylation in the pathological process of Parkinson's disease (PD) has not been determined. We thus conducted the present study by using rotenone (an inducer of PD-like pathology) and neurons derived from induced pluripotent stem cells (iPSCs) from healthy donors and a patient with familial PD PARK2 (FPD2). The results showed that compared to the healthy neurons, FPD2 neurons were more vulnerable to rotenone-induced stress and had higher levels of SARM1 phosphorylation. Similar cellular events were obtained when we used PARK2-knockdown neurons derived from healthy donor iPSCs. These events in both types of PD-model neurons were suppressed in neurons treated with JNK inhibitors, Ca2+-signal inhibitors, or by a SARM1-knockdown procedure. The degenerative events were enhanced in neurons overexpressing wild-type SARM1 and conversely suppressed in neurons overexpressing the SARM1-S548A mutant. We also detected elevated SARM1 phosphorylation in the midbrain of PD-model mice. The results indicate that phosphorylated SARM1 plays an important role in the pathological process of rotenone-induced neurodegeneration.

Interpretation and Misinterpretation of Medical Abbreviations Found in Patient Medical Records: A Cross-Sectional Survey.

Introduction  Medical abbreviations are used in patient medical records across all departments within the hospital setting and upon discharge. Abbreviations can have more than one contradictory or ambiguous definition, which can result in errors in communication due to misunderstanding or misinterpretation. Modern patient care is multidisciplinary, so there should be no room for ambiguity in patient medical records. Therefore, the aim of this survey was to assess individual interpretations and misinterpretations of a list of medical abbreviations found in patient medical records, and thereby increase awareness of the growing use of non-standard abbreviations.  Materials and methods  In this cross-sectional survey, anonymized questionnaires containing a list of 20 abbreviations were given to a convenience sample of consultant physicians, doctors-in-training, and nurses, all of whom are involved in the day-to-day use of patient medical records. Volunteers were asked to define each abbreviation in full. A provided definition was either the intended definition (given a score of one) or completely different in terms of text and meaning (alternative definition). The intended definitions, alternative definitions, and number of abbreviations that were defined by at least 50% of volunteers were collated. Abbreviations that had more than 50% of volunteers providing the intended definition, were regarded as "generally accepted" abbreviations. Volunteers were assured that this was not a test of knowledge and that questionnaires were completely anonymized.  Results  In total, 46 volunteers completed questionnaires. Volunteers consisted of 15 nurses, 15 doctors-in-training, and 16 consultant physicians. The number of volunteers who provided the intended definition for each abbreviation ranged from zero to 87%, depending on the abbreviation. Only four out of 20 abbreviations (20%) had more than 50% of volunteers providing the intended definition and thus regarded as "generally accepted". The maximum score achieved among the volunteers was 12 out of 20 (60%), and the minimum score achieved was 2 out of 20 (10%). The overall mean score achieved by the volunteers was 6.39 out of 20 (32%). Only one-quarter of the volunteers achieved a score above 50%. Additionally, 75% of the abbreviations had one or more (one to seven) alternative definitions.  Conclusions  This survey demonstrated that non-standard medical abbreviations used in patient medical records were being misunderstood or misinterpreted. A majority of abbreviations were not recognized among user groups. Additionally, three-quarters of abbreviations had one or more alternative definitions. Healthcare institutions should encourage the reporting of errors arising from the usage of abbreviations, and introduce initiatives to discourage the use of non-standard abbreviations in patient medical records.