S-Methyl Cysteine Sulfoxide Does Not Ameliorate Weight Gain or Hyperlipidemia in Mice Fed a High-Fat Diet.

SCOPE: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed. METHODS AND RESULTS: Fifty C57BL/6 male mice are randomly assigned to standard-chow, high-fat, or high-fat supplemented with low-SMCSO (43 mg kg-1 body weight [BW] day-1), medium-SMCSO (153 mg kg-1 BW day-1), or high-SMCSO (256 mg kg-1 BW day-1) for 12-weeks. High-fat with SMCSO did not prevent diet-induced obesity, glucose intolerance, or hypercholesterolemia. Mice fed high-fat with SMCSO has higher hepatic lipids than mice fed standard-chow or high-fat alone. Urinary SMCSO increases at 6- and 12-weeks in the low-SMCSO group, before reducing 46% and 28% in the medium- and high-SMCSO groups, respectively, at 12-weeks, suggesting possible tissue saturation. Interestingly, two SMCSO-fed groups consume significantly more feed, without significant weight gain. Due to limitations in measuring consumed feed, caution should be taken interpreting these results. CONCLUSION: SMCSO (43-256 mg kg-1 BW day-1) does not ameliorate metabolic syndrome features in high-fat fed mice. Substantial knowledge gaps remain. Further studies should administer SMCSO separately (i.e., gavage), with metabolic studies exploring tissue levels to better understand its physiological action.

Evaluative judgement in practice education: How does the ability to judge the quality of work impact placement performance?

INTRODUCTION: Occupational therapy students need to be ready to work autonomously in a range of environments as soon as they complete their degree. Practice education experiences are considered key to students developing the competencies that autonomous work requires. To function autonomously in practice environments, it is argued that practitioners need to be able to judge the quality of their own work and the work of others. This is referred to as evaluative judgement. However, there is limited empirical literature relating to evaluative judgement and even less exploring the concept within occupational therapy. METHODS: This study used qualitative methods, seeking to understand the evaluative judgements of clinical practice made by third- and fourth-year occupational therapy students during practice education. RESULTS: Twenty-one interviews were conducted with third- (n = 10) and fourth-year occupational therapy students (n = 1), university support staff supporting practice education (n = 4), and practice education supervisors (n = 5) at one Australian university. Practice education grades and documentation were also used as data. Data were analysed thematically, and two themes, each with three sub-themes, were identified: students coming to understand expected standards, with the following sub-themes: students attuning to cues, cues that inform supervisors about students' meeting the standards, and barriers and frustrations to understanding standards; and practising and developing evaluative judgement, with the following sub-themes: making comparisons, acting on feedback, and reflective practice. CONCLUSIONS: Practice education experiences provide many context-specific opportunities for students to develop their evaluative judgement. Students may be supported to come to know what quality work looks like by offering scaffolded opportunities to develop evaluative judgement in university and practice education settings.

An Analysis of the Gut Microbiota and Related Metabolites following PCSK9 Inhibition in Statin-Treated Patients with Elevated Levels of Lipoprotein(a).

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, often associated with high blood levels of LDL cholesterol (LDL-c). Medications like statins and PCSK9 inhibitors, are used to manage LDL-c levels and reduce ASCVD risk. Recent findings connect the gut microbiota and its metabolites to ASCVD development. We showed that statins modulate the gut microbiota including the production of microbial metabolites involved in the regulation of cholesterol metabolism such as short chain fatty acids (SCFAs) and bile acids (BAs). Whether this pleiotropic effect of statins is associated with their antimicrobial properties or it is secondary to the modulation of cholesterol metabolism in the host is unknown. In this observational study, we evaluated whether alirocumab, a PCSK9 inhibitor administered subcutaneously, alters the stool-associated microbiota and the profiles of SCFAs and BAs. METHODS: We used stool and plasma collected from patients enrolled in a single-sequence study using alirocumab. Microbial DNA was extracted from stool, and the bacterial component of the gut microbiota profiled following an amplicon sequencing strategy targeting the V3-V4 region of the 16S rRNA gene. Bile acids and SCFAs were profiled and quantified in stool and plasma using mass spectrometry. RESULTS: Treatment with alirocumab did not alter bacterial alpha (Shannon index, p = 0.74) or beta diversity (PERMANOVA, p = 0.89) in feces. Similarly, circulating levels of SCFAs (mean difference (95% confidence interval (CI)), 8.12 [-7.15-23.36] µM, p = 0.25) and BAs (mean difference (95% CI), 0.04 [-0.11-0.19] log10(nmol mg-1 feces), p = 0.56) were equivalent regardless of PCSK9 inhibition. Alirocumab therapy was associated with increased concentration of BAs in feces (mean difference (95% CI), 0.20 [0.05-0.34] log10(nmol mg-1 feces), p = 0.01). CONCLUSION: In statin-treated patients, the use of alirocumab to inhibit PCSK9 leads to elevated levels of fecal BAs without altering the bacterial population of the gut microbiota. The association of alirocumab with increased fecal BA concentration suggests an additional mechanism for the cholesterol-lowering effect of PCSK9 inhibition.

Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia.

Elevated plasma lipoprotein(a) [Lp(a)] is a common, inherited condition independently causing cardiovascular disease. Recent expert recommendations suggest opportunistically testing for elevated Lp(a) during cascade testing for familial hypercholesterolaemia (FH). We investigated the effectiveness of detecting elevated Lp(a) in 103 children and adolescents who were first-degree relatives of 66 adult index FH cases as part of an established FH cascade screening program. The yield of detection of elevated Lp(a) using a threshold of ≥30 mg/dL in children and adolescents was assessed. Cascade testing from FH index cases with elevated Lp(a) ≥50 mg/dL identified 1 case of Lp(a) ≥30 mg/dL for every 2 children or adolescents tested. In contrast, opportunistic screening from index cases with FH but normal Lp(a) levels demonstrated 1 case of Lp(a) ≥30 mg/dL for every 7.5 children or adolescents tested (p < 0.001). In conclusion, cascade testing for elevated Lp(a) from index cases with FH and elevated Lp(a) is effective in identifying new cases of elevated Lp(a).

Gut microbiota and metabolomics profiles in patients with chronic stable angina and acute coronary syndrome.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).

Insights into the associations between the gut microbiome, its metabolites, and heart failure.

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome profile and production of associated metabolites when compared with a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of patients with HF. This single center, observational study, recruited 73 patients with HF and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-mo follow-up, along with anthropometric and clinical data. When compared with healthy controls, patients with HF had reduced gut bacterial alpha diversity at follow-up (P = 0.004) but not at baseline. The stool microbiota of patients with HF was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had significantly elevated baseline plasma acetate (P = 0.007), plasma trimethylamine-N-oxide (TMAO) (P = 0.003), serum soluble CD14 (sCD14; P = 0.005), and soluble CD163 (sCD163; P = 0.004) levels compared with healthy controls. Furthermore, patients with HF had a distinct metabolomic and lipidomic profile at baseline when compared with healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared with a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF.NEW & NOTEWORTHY We found a reduction in gut bacterial alpha diversity in patients with heart failure (HF) and that the stool microbiota of patients with HF was characterized by depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. Patients with HF also had altered bacterial metabolites and increased inflammatory profiles compared with healthy controls. A distinct metabolomic and lipidomic profile was present in patients with HF at baseline when compared with healthy controls.

Improved arterial inflammation with high dose omega-3 fatty acids in patients with elevated lipoprotein(a): Selective effect of eicosapentaenoic acid?

Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease. However, there are no approved and effective treatments for lowering Lp(a) and the associated cardiovascular risks. Omega-3 fatty acids (ω-3FAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have both triglyceride-lowering and anti-inflammatory properties. This pilot study investigated the effect of high dose ω-3FAs (3.6 g/day) on arterial inflammation in 12 patients with elevated Lp(a) (> 0.5 g/L) and stable coronary artery disease (CAD) receiving cholesterol-lowering treatment. Arterial inflammation was determined using 18F-fluorodexoyglucose positron emission tomography/computed tomography before and after 12-weeks intervention. ω-3FAs significantly lowered plasma concentrations of triglycerides (-17%, p < 0.01), Lp(a) (-5%, p < 0.01) as well as aortic maximum standardized uptake value (SUVmax) (-4%, p < 0.05). The reduction in SUVmax was significantly inversely associated with average on-treatment EPA (r = -0.750, p < 0.01), but not DHA and triglyceride, concentrations. In conclusion, high dose ω-3FAs decrease arterial inflammation in patients with elevated Lp(a) and stable CAD, which may involve a direct arterial effect of EPA.

A sex-based analysis of 5-year outcomes following stenting for the treatment of aorto-iliac occlusive disease.

OBJECTIVES: The aim of this study was to evaluate the impact of sex on mid-term outcomes following stenting for aorto-iliac occlusive disease (AIOD). METHODS: The Covered versus Balloon Expandable Stent Trial (COBEST) compared the safety and efficacy of the covered stent (CS) with those of the bare metal stent (BMS) in the treatment of hemodynamically significant AIOD. It was identified that CS provided a significant benefit. The primary endpoint of our analysis was the rate of primary patency 5 years following stenting for AIOD (inclusive of both CS and BMS) in both sexes. RESULTS: Of the 168 lesions treated, 103 (61%) were present in men and 65 (39%) were present in women. Of the concomitant comorbidities, diabetes mellitus was significantly more common in women (17.5% vs 41.5%, p = .006). Although chronic limb threatening ischemia (CLTI) at the time of intervention was more common in women, the difference was not significant (16.5% vs 24.6%, p = .395). Sex was not associated with the primary patency rate (male; 0.70, 95% confidence interval [CI]: 0.23-2.19, p = .543). When considering both male sex and the utilization of BMS, no significant impact was found on the primary patency rate (hazard ratio [HR]: 3.43, 95% CI: 0.69-17.10, p = .133). All-cause mortality at 60 months was 22.6% in men compared to 19.4% in women (p = .695). CONCLUSIONS: No significant difference was identified in the primary patency rate between the sexes. Further investigation is warranted to ascertain whether sex-specific interventional guidelines are required in this regard.

The Evolution of Telepsychiatry for Substance Use Disorders During COVID-19: a Narrative Review.

Purpose of Review: This article aims to review and synthesize the current research evidence regarding the efficacy of telepsychiatry-delivered substance use disorder treatment using a narrative review with a focus on the effects of remote healthcare delivery within the substance abuse treatment space. Recent Findings: The COVID-19 pandemic exerted substantial pressures on all levels of society. Social isolation, loss of employment, stress, physical illness, overburdened health services, unmet medical needs, and rapidly changing pandemic restrictions had particularly severe consequences for people with mental health issues and substance use disorders. Since the start of the pandemic, addiction treatment (and medical treatment overall) using remote health platforms has significantly expanded to different platforms and delivery systems. The USA, in particular, reported transformational policy developments to enable the delivery of telehealth during the COVID-19 pandemic. However, systemic barriers such as a widespread lack of internet access and insufficient patient and provider digital skills remain. Summary: Overall, telepsychiatry is a promising approach for the treatment of substance use disorders, but more randomized controlled trials are needed in the future to assess the evidence base of available interventions.

Gut Microbiome and Associated Metabolites Following Bariatric Surgery and Comparison to Healthy Controls.

The gut microbiome plays a significant role in regulating the host's ability to store fat, which impacts the development of obesity. This observational cohort study recruited obese adult men and women scheduled to undergo sleeve gastrectomy and followed up with them 6 months post-surgery to analyse their microbial taxonomic profiles and associated metabolites in comparison to a healthy control group. There were no significant differences in the gut bacterial diversity between the bariatric patients at baseline and at follow-up or between the bariatric patients and the cohort of healthy controls. However, there were differential abundances in specific bacterial groups between the two cohorts. The bariatric patients were observed to have significant enrichment in Granulicatella at baseline and Streptococcus and Actinomyces at follow-up compared to the healthy controls. Several operational taxonomic units assigned to commensal Clostridia were significantly reduced in the stool of bariatric patients both at baseline and follow-up. When compared to a healthy cohort, the plasma levels of the short chain fatty acid acetate were significantly higher in the bariatric surgery group at baseline. This remained significant when adjusted for age and sex (p = 0.013). The levels of soluble CD14 and CD163 were significantly higher (p = 0.0432 and p = 0.0067, respectively) in the bariatric surgery patients compared to the healthy controls at baseline. The present study demonstrated that there are alterations in the abundance of certain bacterial groups in the gut microbiome of obese patients prior to bariatric surgery compared to healthy individuals, which persist post-sleeve gastrectomy.

Update on advanced interventional neuromodulatory approaches to lower blood pressure.

Herein, we review interventional peripheral neuromodulatory approaches to reduce blood pressure (BP), specifically focusing on catheter-based renal denervation (RDN), as well as the latest data from recent clinical trials underpinning its clinical use. Given the apparent failure of established lifestyle measures and pharmacologic BP-lowering approaches to improve hypertension (HTN) control rates, the past decade has seen remarkable scientific efforts to explore the utility of interventional strategies for BP management. Experimental studies and human clinical trials have demonstrated the crucial role of the sympathetic nervous system in the development and mainenance of HTN - consequently, most recent interventional technologies aimed primarily at modulating neural pathways. Advanced approaches that were rigorously tested in human studies include RDN, endovascular baroreflex amplification, baroreflex activation therapy and cardiac neuromodulation stimulation.Amongst these, RDN is by far the most established technology. With recent robust evidence from clinical trials and real-world data showing the safety and efficacy of both ultrasound and radiofrequency-based approaches, a recent clinical consensus statement of the European Society of Cardiology Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions concludes that RDN represents an ancillary therapeutic option in patients with uncontrolled resistant HTN confirmed by ambulatory blood pressure measurement and in spite of attention to lifestyle changes and optimised pharmacological treatment. Furthermore, RDN could alos be considered for patienst unlikley to adhere to or tolerate long-term antihypertensive drug treatment. Very recent data indicate long-term safety and efficacy up to 10 years. Appropriate implementation of RDN into clinical practice is now warranted.For all other interventions additional data from adequately designed human studies are required to establish their safety and clinical utility for potential future use in routine practice.

Meaning making about performance: A comparison of two specialty feedback cultures.

INTRODUCTION: Specialty trainees often struggle to understand how well they are performing, and feedback is commonly seen as a solution to this problem. However, medical education tends to approach feedback as acontextual rather than located in a specialty-specific cultural world. This study therefore compares how specialty trainees in surgery and intensive care medicine (ICM) make meaning about the quality of their performance and the role of feedback conversations in this process. METHODS: We conducted a qualitative interview study in the constructivist grounded theory tradition. We interviewed 17 trainees from across Australia in 2020, eight from ICM and nine from surgery, and iterated between data collection and analytic discussions. We employed open, focused, axial and theoretical coding. FINDINGS: There were significant divergences between specialties. Surgical trainees had more opportunity to work directly with supervisors, and there was a strong link between patient outcome and quality of care, with a focus on performance information about operative skills. ICM was a highly uncertain practice environment, where patient outcome could not be relied upon as a source of performance information; valued performance information was diffuse and included tacit emotional support. These different 'specialty feedback cultures' strongly influenced how trainees orchestrated opportunities for feedback, made meaning of their performance in their day-to-day patient care tasks and 'patched together' experiences and inputs into an evolving sense of overall progress. DISCUSSION: We identified two types of meaning-making about performance: first, trainees' understanding of an immediate performance in a patient-care task and, second, a 'patched together' sense of overall progress from incomplete performance information. This study suggests approaches to feedback should attend to both, but also take account of the cultural worlds of specialty practice, with their attendant complexities. In particular, feedback conversations could better acknowledge the variable quality of performance information and specialty specific levels of uncertainty.

Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE-/- mice fed a high fat diet.

BACKGROUND AND AIMS: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE-/- mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. METHODS: 60 apoE-/- mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE-/- mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. RESULTS: Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. CONCLUSION: Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE-/- mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.

Anti-inflammatory effect of biologic therapy in patients with psoriatic disease: A prospective cohort FDG PET study.

AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

Promoting oral mucosal wound healing using a DCS-RuB2A2 hydrogel based on a photoreactive antibacterial and sustained release of BMSCs.

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB2A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB2A2-BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.

Phosphatidylserine in the Nervous System: Cytoplasmic Regulator of the AKT and PKC Signaling Pathways and Extracellular "Eat-Me" Signal in Microglial Phagocytosis.

Phosphatidylserine (PtdSer) is an important anionic phospholipid found in eukaryotic cells and has been proven to serve as a beneficial factor in the treatment of neurodegenerative diseases. PtdSer resides in the inner leaflet of the plasma membrane, where it is involved in regulating the AKT and PKC signaling pathways; however, it becomes exposed to the extracellular leaflet during neurodevelopmental processes and neurodegenerative diseases, participating in microglia-mediated synaptic and neuronal phagocytosis. In this paper, we review several characteristics of PtdSer, including the synthesis and translocation of PtdSer, the functions of cytoplasmic and exposed PtdSer, and different PtdSer-detection materials used to further understand the role of PtdSer in the nervous system.

Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.

Synaptic plasticity enhances or reduces connections between neurons, affecting learning and memory. Postsynaptic AMPARs mediate greater than 90% of the rapid excitatory synaptic transmission in glutamatergic neurons. The number and subunit composition of AMPARs are fundamental to synaptic plasticity and the formation of entire neural networks. Accordingly, the insertion and functionalization of AMPARs at the postsynaptic membrane have become a core issue related to neural circuit formation and information processing in the central nervous system. In this review, we summarize current knowledge regarding the related mechanisms of AMPAR expression and trafficking. The proteins related to AMPAR trafficking are discussed in detail, including vesicle-related proteins, cytoskeletal proteins, synaptic proteins, and protein kinases. Furthermore, significant emphasis was placed on the pivotal role of the actin cytoskeleton, which spans throughout the entire transport process in AMPAR transport, indicating that the actin cytoskeleton may serve as a fundamental basis for AMPAR trafficking. Additionally, we summarize the proteases involved in AMPAR post-translational modifications. Moreover, we provide an overview of AMPAR transport and localization to the postsynaptic membrane. Understanding the assembly, trafficking, and dynamic synaptic expression mechanisms of AMPAR may provide valuable insights into the cognitive decline associated with neurodegenerative diseases.

Low-density lipoprotein-cholesterol lowering effect of a nutraceutical regimen with or without ezetimibe in hypercholesterolaemic patients with statin intolerance.

Background: Statins are the most widely prescribed medication to lower low-density lipoprotein cholesterol (LDL-c). However, a significant portion of patients are unable to tolerate them due to side effects, most commonly muscle related. Nutraceuticals, natural plant derivatives with lipid-lowering properties, may provide an alternative to lower LDL-c in these patients. Aims: To investigate whether a nutraceutical regimen, either alone or in combination with ezetimibe, can lower LDL-c in patients with hypercholesterolemia who are intolerant to statins. Methods: Participants were recruited into a double-blind, randomized, placebo-controlled intervention study. Treatments were (i) placebo, (ii) nutraceutical (500 mg berberine, 200 mg red yeast rice (RYR), 2 g plant sterols)/daily, (iii) ezetimibe (10 mg)/daily, or (iv) the combination of nutraceutical and ezetimibe/daily. At baseline and week 8, all participants provide a fasting blood sample for assessment of lipid profile and safety bloods. Results: Fifty participants were randomized, with 44 completing the treatment period. Following adjustment for baseline levels and compared with placebo, LDL-c was significantly reduced (all p < 0.0001) with ezetimibe (-1.02 mmol/L), nutraceutical (-1.15 mmol/L) and the nutraceutical and ezetimibe combination (-1.92 mmol/L). Non-HDL cholesterol was significantly reduced (all p < 0.0001) with ezetimibe (-1.29 mmol/L), nutraceutical (-1.37 mmol/L) and the nutraceutical and ezetimibe combination (-2.18 mmol/L). Remnant cholesterol and triglycerides was significantly reduced with the nutraceutical and ezetimibe combination (p = 0.018). Conclusion: A nutraceutical regimen (berberine, RYR and plant sterols) and ezetimibe independently and additively lower LDL-c in patients with hypercholesterolemia who are intolerant to statins.