Profiling people with Parkinson's disease at risk of cognitive decline: Insights from PPMI and ICICLE-PD data.

Introduction: A subset of people with Parkinson's disease (PD) develop dementia faster than others. We aimed to profile PD cognitive subtypes at risk of dementia based on their rate of cognitive decline. Method: Latent class mixed models stratified subtypes in Parkinson's Progression Markers Initiative (PPMI) (N = 770) and ICICLE-PD (N = 212) datasets based on their decline in the Montreal Cognitive Assessment over at least 4 years. Baseline demographic and cognitive data at diagnosis were compared between subtypes to determine their clinical profile. Results: Four subtypes were identified: two with stable cognition, one with steady decline, and one with rapid decline. Performance on Judgement of Line Orientation, but not category fluency, was associated with a steady decline in the PPMI dataset, and deficits in category fluency, but not visuospatial function, were associated with a steady decline in the ICICLE-PD dataset. Discussion: People with PD susceptible to cognitive decline demonstrate unique clinical profiles at diagnosis, although this differed between cohorts. Highlights: Four cognitive subtypes were revealed in two Parkinson's disease samples.Unique profiles of cognitive impairment were related to cognitive decline.Judgement of Line Orientation/category fluency predictive of steady decline.Global deficits related to rapid cognitive decline and increased dementia risk.

The Efficacy of Risk Factor Modification Compared to NAD+ Repletion in Diastolic Heart Failure.

Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD+) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD+ repletion as therapy. We quantified myocardial NAD+ and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR). Findings show significant NAD+ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD+ levels. In murine HF with preserved ejection fraction, NR as preventive and therapeutic intervention improved metabolic and antioxidant profiles. This study underscores NAD+ repletion's potential in diastolic HF management.

Preventing sheep carotid artery spasm for vascular graft surgery and computed tomography angiography.

The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is a paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols. In this study, four healthy Merino cross White Suffolk wethers (1-2 years, 52.1 ± 0.8 kg) underwent CT angiography and CA graft surgery. CT angiography using iodinated contrast agent was performed with innominate artery access via the CA or ascending aortic arch access via the femoral artery. Sheep were randomly allocated to then underwent right CA sham surgery or left CA vascular graft implantation. A variety of vasodilators, including papaverine, sodium nitroprusside, verapamil and their combination, were tested for preventing or treating CA spasms intraoperatively. Blood flow was reassessed immediately after CA surgery using CT angiography. The results showed that innominate artery access via the CA for CT angiography in sheep induced pre-surgical CA spasm with reduced arterial flow. Conversely, ascending aortic arch access via the femoral artery for CT angiography did not cause CA spasm and maintained arterial flow. During CA graft surgery, surgical trauma induced CA spasm, which was prevented by localised intraarterial administration of vasodilators papaverine hydrochloride and verapamil prior to significant surgical manipulation.

Rapid benefits in older age from transition to whole food diet regardless of protein source or fat to carbohydrate ratio: Arandomised control trial.

Plant-based diets reduces the risk of chronic conditions. The interaction between protein source and other macronutrients-fat (F) and carbohydrate (C)-has yet to be investigated. The aim was to assess the main and interactive effects of protein-source (plant vs. animal) and F:C (high or low) and the transition from an Australian diet to a whole food diet on various health markers in older individuals. This single-blinded, parallel, randomised experimental trial used a 2 × 2 factorial design to compare pro-vegetarian (70:30 plant to animal) versus omnivorous (50:50 plant to animal) diets at 14% protein and varying fat-to-carbohydrate ratios (high fat ~40% vs. low fat ~30%) over 4 weeks. Study foods were provided, alcohol consumption was discouraged, and dietary intake was determined through food records. Analysis included both RCT and observational data. Changes in appetite, palatability of diets, and dietary intake were assessed. Body composition, muscle strength, function, gut microbiome, and cardiometabolic health parameters were measured. Data from 113 (of the 128 randomised) individuals aged 65-75 years were analysed. Pro-vegetarian diets reduced diastolic blood pressure, total cholesterol and glucose levels. Moreover, the overall sample exhibited increased short-chain fatty acids and FGF21 levels, as well as improvements in body composition, function, and cardio-metabolic parameters irrespective of dietary treatment. Transitioning to a diet rich in fruit, vegetables, fibre, and moderate protein was associated with improved health markers in older age, with added benefits from pro-vegetarian diets. Further research on long-term effects is needed.

Quantitative source apportionment of faecal indicator bacteria from anthropogenic and zoogenic sources of faecal contamination.

Recreational bathing waters are complex systems with diverse inputs from multiple anthropogenic and zoogenic sources of faecal contamination. Faecal contamination is a substantial threat to water quality and public health. Here we present a comprehensive strategy to estimate the contribution of faecal indicator bacteria (FIB) from different biological sources on two at-risk beaches in Dublin, Ireland. The daily FIB loading rate was determined for three sources of contamination: a sewage-impacted urban stream, dog and wild bird fouling. This comparative analysis determined that the stream contributed the highest daily levels of FIB, followed by dog fouling. Dog fouling may be a significant source of FIB, contributing approximately 20 % of E. coli under certain conditions, whereas wild bird fouling contributed a negligible proportion of FIB (<3 %). This study demonstrates that source-specific quantitative microbial source apportionment (QMSA) strategies are vital to identify primary public health risks and target interventions to mitigate faecal contamination.

ChatGPT-4 Can Help Hand Surgeons Communicate Better With Patients.

The American Society for Surgery of the Hand and British Society for Surgery of the Hand produce patient-focused information above the sixth-grade readability recommended by the American Medical Association. To promote health equity, patient-focused content should be aimed at an appropriate level of health literacy. Artificial intelligence-driven large language models may be able to assist hand surgery societies in improving the readability of the information provided to patients. The readability was calculated for all the articles written in English on the American Society for Surgery of the Hand and British Society for Surgery of the Hand websites, in terms of seven of the commonest readability formulas. Chat Generative Pre-Trained Transformer version 4 (ChatGPT-4) was then asked to rewrite each article at a sixth-grade readability level. The readability for each response was calculated and compared with the unedited articles. Chat Generative Pre-Trained Transformer version 4 was able to improve the readability across all chosen readability formulas and was successful in achieving a mean sixth-grade readability level in terms of the Flesch Kincaid Grade Level and Simple Measure of Gobbledygook calculations. It increased the mean Flesch Reading Ease score, with higher scores representing more readable material. This study demonstrated that ChatGPT-4 can be used to improve the readability of patient-focused material in hand surgery. However, ChatGPT-4 is interested primarily in sounding natural, and not in seeking truth, and hence, each response must be evaluated by the surgeon to ensure that information accuracy is not being sacrificed for the sake of readability by this powerful tool.

Echocardiographic predictors of cardiovascular outcome in heart failure with preserved ejection fraction.

AIMS: The optimal echocardiographic predictors of cardiovascular outcome in heart failure (HF) with preserved ejection fraction (HFpEF) are unknown. We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF. METHODS AND RESULTS: Systematic literature search of three electronic databases was conducted from date of inception until November 2022. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for echocardiographic variables from multivariate prediction models for the composite primary endpoint of cardiovascular death and HF hospitalization were pooled using a random effects meta-analysis. Specific subgroup analyses were conducted for studies that enrolled patients with acute versus chronic HF, and for those studies that included E/e', pulmonary artery systolic pressure (PASP), renal function, natriuretic peptides and diuretic use in multivariate models. Forty-six studies totalling 20 056 patients with HFpEF were included. Three echocardiographic parameters emerged as independent predictors in all subgroup analyses: decreased left ventricular (LV) global longitudinal strain (HR 1.24, 95% CI 1.10-1.39 per 5% decrease), decreased left atrial (LA) reservoir strain (HR 1.30, 95% CI 1.13-1.1.50 per 5% decrease) and lower tricuspid annular plane systolic excursion (TAPSE) to PASP ratio (HR 1.17, 95% CI 1.07-1.25 per 0.1 unit decrease). Other independent echocardiographic predictors of the primary endpoint were a higher E/e', moderate to severe tricuspid regurgitation, LV mass index and LA ejection fraction, although these variables were less robust. CONCLUSIONS: Impaired LV global longitudinal strain, lower LA reservoir strain and lower TAPSE/PASP ratio predict cardiovascular death and HF hospitalization in HFpEF and are independent of filling pressures, clinical characteristics and natriuretic peptides. These echocardiographic parameters reflect key functional changes in HFpEF, and should be incorporated in future prospective risk prediction models.

Agricultural and urban practices are correlated to changes in the resistome of riverine systems.

The objective of this study was to comprehensively characterise the resistome, the collective set of antimicrobial resistance genes in a given environment, of two rivers, from their source to discharge into the sea, as these flow through areas of different land use. Our findings reveal significant differences in the riverine resistome composition in areas of different land uses, with increased abundance and diversity of AMR in downstream agricultural and urban locations, with the resistome in urban areas more similar to the resistome in wastewater. The changes in resistome were accompanied by changes in microbial communities, with a reduction in microbial diversity in downstream agricultural and urban affected areas, driven mostly by increased relative abundance in the phyla, Bacteroidetes and Proteobacteria. These results provide insight into how pollution associated with agricultural and urban activities affects microbial communities and influences AMR in aquatic water bodies. These results add valuable insights to form effective strategies for mitigating and preserving aquatic ecosystems. Overall, our study highlights the critical role of the environment in the development and dissemination of AMR and underscores the importance of adopting a One Health approach to address this global public health threat.

Cardiac Substrate Utilization and Relationship to Invasive Exercise Hemodynamic Parameters in HFpEF.

The authors conducted transcardiac blood sampling in healthy subjects and subjects with heart failure with preserved ejection fraction (HFpEF) to compare cardiac metabolite and lipid substrate use. We demonstrate that fatty acids are less used by HFpEF hearts and that lipid extraction is influenced by hemodynamic factors including pulmonary pressures and cardiac index. The release of many products of protein catabolism is apparent in HFpEF compared to healthy myocardium. In subgroup analyses, differences in energy substrate use between female and male hearts were identified.

Hippocampal resting-state connectivity is associated with posterior-cortical cognitive impairment in Parkinson's disease.

AIM: Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD. A subset of PD participants (N = 42) and 20 healthy controls (HCs) underwent rs-fMRI. Connectivity of bilateral hippocampi with regions of interest was compared between posterior-cortical, cognitively intact, and HC participants using seed-based analysis, controlling for age. Exploratory correlations were performed between areas of interest from the group analysis and a series of cognitive tests. RESULTS: The posterior-cortical subtype (N = 19) showed weaker connectivity between the left hippocampus and right anterior temporal fusiform cortex compared to the cognitively intact (N = 11) group, p-false discovery rate (FDR) = .01, and weaker connectivity between bilateral hippocampi and most fusiform regions compared to HCs (N = 20). No differences were found between HCs and cognitively intact PD. Exploratory analyses revealed strongest associations between connectivity of the right anterior temporal fusiform cortex and left hippocampus with category fluency (p-FDR = .01). CONCLUSION: Results suggest that weakened connectivity between the hippocampus and fusiform region is a unique characteristic of posterior-cortical cognitive deficits in PD. Further exploration of hippocampal and fusiform functional integrity as a marker of cognitive decline in PD is warranted.

Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult. METHODS: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts. RESULTS: The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated diastolic dysfunction, metabolic remodeling, oxidative stress, inflammation, gut microbiota dysbiosis, and intestinal epithelial barrier damage. In the heart, IPA suppressed the expression of NNMT (nicotinamide N-methyl transferase), restored nicotinamide, NAD+/NADH, and SIRT3 (sirtuin 3) levels. IPA mediates the protective effects on diastolic dysfunction, at least in part, by promoting the expression of SIRT3. SIRT3 regulation was mediated by IPA binding to the aryl hydrocarbon receptor, as Sirt3 knockdown diminished the effects of IPA on diastolic dysfunction in vivo. The role of the nicotinamide adenine dinucleotide circuit in HFpEF was further confirmed by nicotinamide supplementation, Nnmt knockdown, and Nnmt overexpression in vivo. IPA levels were significantly reduced in patients with HFpEF in 2 independent human cohorts, consistent with a protective function in humans, as well as mice. CONCLUSIONS: Our findings reveal that IPA protects against diastolic dysfunction in HFpEF by enhancing the nicotinamide adenine dinucleotide salvage pathway, suggesting the possibility of therapeutic management by either altering the gut microbiome composition or supplementing the diet with IPA.

A physiotherapy group exercise and self-management approach to improve physical activity in people with mild-moderate Parkinson's disease: a randomized controlled trial.

BACKGROUND: Physical activity levels are low in people with Parkinson's disease (PD) and have proved difficult to increase with exercise programs alone. Intervention approaches that address both the capacity to engage in physical activity and self-management strategies to change and maintain exercise behaviours are needed to address this intractable issue. METHODS: This will be an assessor-blinded, randomized controlled trial performed in Brisbane, Australia. Ninety-two people with mild-moderate PD will be randomly allocated to two groups: usual care, and a physiotherapy-led group exercise program combined with self-management strategies. In the intervention group, twelve, 80-min sessions will be conducted over 4 weeks in groups of up to 4 participants. The intervention will consist of circuit training including treadmill walking to target aerobic fitness, and activities targeting strength, balance, and gait performance. In addition, each session will also incorporate strategies focusing on self-management and behaviour change, augmented by the provision of a fitness activity tracker. Outcome measures will be collected at baseline (T1), immediately post intervention (T2) and at 6 months follow-up (T3). The primary outcome measure is free-living physical activity (average daily step count over 7 days) at pre (T1) and post (T2) intervention measured using an activPAL™ device. Secondary outcome measures captured at all time points include time spent walking, sedentary and in moderate intensity exercise over 7 days; spatiotemporal gait performance (step length, gait speed, endurance); health-related quality of life; and outcome expectations and self-efficacy for exercise. DISCUSSION: Sustainability of gains in physical activity following exercise interventions is a challenge for most populations. Our incorporation of a chronic disease self-management approach into the exercise program including fitness tracking extends previous trials and has potential to significantly improve free-living physical activity in people with PD. TRIAL REGISTRATION: This study has been prospectively registered in Australian and New Zealand Clinical Trial Registry (ACTRN12617001057370), registered on 19/07/2017. Available from www.anzctr.org.au/ACTRN12617001057370.aspx .

A biologging database of mobulid rays from the Gulf of California, Mexico.

We initiated a tagging program in 2004 to determine the large-scale and long-term movement patterns of three species of Mobulid Ray (Mobula mobular, M. munkiana, M. thurstoni). Between 2004 and 2014 we deployed 48 pop-up archival (PAT) tags that recorded temperature, pressure, and light level. Pressure and light level records were then used to calculate animal depth and geolocation. Transmitted and when available recovered raw data files from successful deployments (n = 45) were auto-ingested from the manufacturer into the United States Animal Telemetry Network's (ATN) Data Assembly Center (DAC). Through the ATN DAC, all necessary metadata were compiled, dataset was prepped for release, and derived geolocation trajectories (n = 43) were visualized within their public facing data portal. These data and the full metadata records are available for download from the ATN portal as well as permanently archived under the DataONE Research Workspace member node.

Feasibility and Acceptability of a Videoconferencing CBT Intervention for Anxiety in People with Parkinson's Disease.

OBJECTIVES: In people with Parkinson's disease (PwPD), non-motor symptoms such as anxiety are common and have negative impacts on their quality of life. There are currently few interventions that address anxiety in PwPD, and access to diagnosis and treatment is often limited for those living in rural areas. The aim of this study was to evaluate the feasibility and acceptability of a telehealth videoconferencing CBT intervention for anxiety in PwPD. METHODS: A pre- and post-test feasibility study (N = 10) was conducted and evaluated utilizing the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). RESULTS: Lack of access to the internet and videoconferencing technology were identified as barriers to participation. Physical health issues also impacted recruitment and retention. Non-completers were significantly older and less likely to have a carer involved in the intervention. Clinician adoption of the intervention was low while participant acceptability of videoconferencing technology varied and required carer support. CONCLUSIONS: Providing access to technology and support to overcome technological issues, as well as telehealth training for clinicians, are recommended in future studies to improve recruitment, retention, and implementation. CLINICAL IMPLICATIONS: Identification of barriers and facilitators provides future studies with the knowledge to tailorize their program to better suit PwPD.

The first human normative ranges and biomarker performance of dimethylguanidino valeric acid isoforms in fatty liver disease.

We have recently determined dimethylguanidino valeric acid (DMGV) to be a novel biomarker of liver injury in non-alcoholic fatty liver disease (NAFLD) and an independent predictor of incident diabetes over a decade in advance. DMGV consists of two stereo-isomers, asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV). Here we report, for the first time, the upper limits of normal of both isomers in humans at the accepted 5.56% liver fat threshold for NAFLD, determined using in vivo magnetic resonance spectroscopy. We performed independent and blinded comparative analyses of ADGV and SDGV levels using two different liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods in (A) our laboratory, and (B) the New South Wales Chemical Pathology state laboratory, using unique columns, LC-MS/MS equipment, extraction protocols and normalisation approaches. Despite these differences, each laboratory reported consistent absolute concentrations across a range of liver fat percentages. We next determined the diagnostic performance of SDGV compared to ADGV in a cohort of 268 individuals with liver fat measurements. In derivation-validation analyses we determined rule-in/rule-out thresholds and the concentration of SDGV that provides optimal performance across sensitivity and specificity for the identification of NAFLD. In conclusion, we have herein determined for the first time the true human plasma reference range of both isoforms of an emerging novel biomarker of NAFLD, at the accepted upper normal threshold of liver fat. We have also identified that SDGV is the isoform with the best diagnostic performance and determined the optimal cut-point for its detection of NAFLD.

Lessons learnt in the first year of an Australian pediatric cardio oncology clinic.

BACKGROUND: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management. OBJECTIVES: Our pediatric cardio-oncology clinic aimed to: (i) Document cardiovascular toxicities observed within a pediatric cardio-oncology clinic and. (ii) Evaluate the applicability of the Australian and New Zealand Pediatric Cardio-Oncology recommendations. METHODS: Monthly multidisciplinary cardio-oncology clinics were conducted in an Australian tertiary pediatric hospital. Structured standardised approaches to assessment were built into the electronic medical record (EMR). All patients underwent baseline echocardiogram and electrocardiogram assessment together with vital signs in conjunction with standard history and examination. RESULTS: Nineteen (54%) individuals had a documented cardiovascular toxicity or pre-existing risk factor prior to referral. The two most common cardiovascular toxicities documented during clinic review included Left Ventricular Dysfunction (LVD) and hypertension. Of note 3 (8.1%) patients had CTCAE grade III LVD. An additional 10 (27%) patients reviewed in clinic had CTCAE grade I hypertension. None of these patients had hypertension noted within their referral. Cascade testing for cardiac history was warranted in 2 (5.4%) of patients. CONCLUSIONS: Pediatric cardio-oncology clinics are likely beneficial to documenting previously unrecognised cardiotoxicity and relevant cardiac family histories, whilst providing an opportunity to address lifestyle risk factors.

Pareidolias are a function of visuoperceptual impairment.

Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH. This association could, however, be mediated by visuoperceptual impairment. To understand the drivers of performance on the NPT, we contrasted performances in patient groups that varied both in terms of visuoperceptual ability and rates of VH. N = 43 patients were studied of whom n = 13 had DLB or PD with Dementia (PDD); n = 13 had PD; n = 12 had typical, memory-onset Alzheimer's Disease (tAD); and n = 5 had Posterior Cortical Atrophy (PCA) due to Alzheimer's disease. All patient groups reported pareidolias. Within the Lewy body disorders (PD, DLB, PDD), there was no significant difference in pareidolic response rates between hallucinating and non-hallucinating patients. Visuoperceptual deficits and pareidolic responses were most frequent in the PCA group-none of whom reported VH. Regression analyses in the entire patient cohort indicated that pareidolias were strongly predicted by visuoperceptual impairment but not by the presence of VH. These findings suggest that pareidolias reflect the underlying visuoperceptual impairment of Lewy body disorders, rather than being a direct marker for VH.

Levetiracetam for the treatment of mild cognitive impairment in Parkinson's disease: a double-blind controlled proof-of-concept trial protocol.

BACKGROUND: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance. METHODS: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity. RESULTS: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes. CONCLUSIONS: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020.

Evaluation of probiotic growth stimulation using prebiotic ingredients to optimize compounds for in ovo delivery.

The use of probiotics, prebiotics and synbiotics in poultry diets beneficially stimulates the gut microbiome thus promoting the health and welfare of the animals. In this study, we analyzed 7 poultry probiotics (Lactobacillus plantarum - B1 and B4, Lactobacillus rhamnosus - B3, Bifidobacterium lactis - B2, Carnobacterium divergens - B5, Propionibacterium thoenii - B6, Clostridium butyricum - B7) and 12 prebiotics, differing in chemical composition and source of origin (fungi, algae, animal, etc.). The main goal of our research was to select the most promising candidates to develop synbiotic combinations. We determined the growth kinetics of all probiotics in the presence of prebiotics in a series of in vitro studies to select optimal combinations. Five out of seven investigated probiotics were significantly stimulated by astragalus polysaccharide, and this prebiotic was characterized in our work as the most effective. Moreover, in the case of three probiotics, B2, B3 and B4, significant growth stimulation has been found when beta-glucan, vegetable protein hydrolysate and liquid seaweed extract were supplied. Strain B1 (L. plantarum) was stimulated by 6 out of 12 prebiotics. The growth of B4 (L. plantarum) and B2 (B. lactis) was enhanced by prebiotics after 2 h of incubation. A high growth rate of 3.13% was observed in the case of L. plantarum (B4) and a 3.37% higher rate for B. lactis (B3), compared to the growth of probiotics in the control medium with glucose but no prebiotics. The best candidates for synbiotic combinations based on this in vitro work are the strains belonging to L. plantarum (B4), L. rhamnosus (B3) and B. lactis (B2), consistent with prebiotics such as astragalus polysaccharides and vegetable protein hydrolysate. These combinations will be subject to future in vivo poultry trials involving the in ovo microbiome modulation.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.