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.

Hand Infections in End-Stage Renal Disease-Consider Tumoral Calcinosis.

Tumoral calcinosis (TC) is a rare condition defined by the accumulation of calcium salts in soft tissues surrounding joints, most commonly large joints. Chronic joint inflammation in the setting of local hyperphosphatemia leads to interruption and dysfunction of tissue repair and generates breakdown products that subsequently calcify and accumulate. We present a case of a 42-year-old man with a history of end-stage renal disease on dialysis presenting to the clinic with a painless digital mass of his right long finger at the proximal interphalangeal joint. Our initial impression was a splinter abscess based on presentation and patient history. Although our patient's presentation of traumatic, painless TC of the hand secondary to end-stage renal disease is rare, the pathogenic mechanisms behind TC support this presentation. The authors recommend including TC within the differential of presentations similar to that of chronic abscess or giant cell tumor, especially when their medical history includes end-stage renal disease.

Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm.

BACKGROUND: Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. METHODS: In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. CONCLUSIONS: Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.

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.

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.

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.

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.

Implementation of an Enhanced Recovery After Surgery Protocol for Cranial Vault Remodeling Procedures.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been implemented across surgical disciplines, including cranial vault remodeling for craniosynostosis. The authors aim to describe the implementation of an ERAS protocol for cranial vault remodeling procedures performed for patients with craniosynostosis at a tertiary care hospital. DESCRIPTION: Institutional review board approval was received. All patients undergoing a cranial remodeling procedure for craniosynostosis at the authors' institution over a 10-year period were collected (n = 168). Patient and craniosynostosis demographics were collected as well as operative details. Primary outcome measures were intensive care unit length of stay (ICU LOS) and narcotic usage. Chi squared and independent t-tests were employed to determine significance. A significance value of 0.05 was utilized. RESULTS: During the time examined, there were 168 primary cranial vault remodeling procedures performed at the authors' institution - all of which were included in the analysis. Use of the ERAS protocol was associated with decreased initial 24-hour morphine equivalent usage (p < 0.01) and decreased total morphine equivalent usage (p < 0.01). Patients using the ERAS protocol experienced a shorter ICU LOS (p < 0.01), but the total hospital length of stay was unchanged. CONCLUSION: This study reiterates the benefit of developing and implementing an ERAS protocol for patients undergoing cranial vault remodeling procedures. The protocol resulted in an overall decreased ICU LOS and a decrease in narcotic use. This has implications for ways to maximize hospital reimbursement for these procedures, as well as potentially improve outcomes.

Rhizobial secretion of truncated exopolysaccharides severely impairs the Mesorhizobium-Lotus symbiosis.

The symbiosis between Mesorhizobium japonicum R7A and Lotus japonicus Gifu is an important model system for investigating the role of bacterial exopolysaccharides (EPS) in plant-microbe interactions. Previously we showed that R7A exoB mutants that are affected at an early stage of EPS synthesis and in lipopolysaccharide (LPS) synthesis induce effective nodules on L. japonicus Gifu after a delay, whereas exoU mutants affected in the biosynthesis of the EPS side chain induce small uninfected nodule primordia and are impaired in infection. The presence of a halo around the exoU mutant when grown on Calcofluor-containing media suggested the mutant secreted a truncated version of R7A EPS. A non-polar ΔexoA mutant defective in the addition of the first glucose residue to the EPS backbone was also severely impaired symbiotically. Here we used a suppressor screen to show that the severe symbiotic phenotype of the exoU mutant was due to secretion of an acetylated pentasaccharide, as both monomers and oligomers, by the same Wzx/Wzy system that transports wild-type exopolysaccharide. We also present evidence that the ΔexoA mutant secretes an oligosaccharide by the same transport system, contributing to its symbiotic phenotype. In contrast, ΔexoYF, and polar exoA and exoL mutants have a similar phenotype to exoB mutants, forming effective nodules after a delay. These studies provide substantial evidence that secreted incompatible EPS is perceived by the plant leading to abrogation of the infection process.

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.

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.

Tixagevimab/Cilgavimab does not prevent COVID-19 in patients with multiple sclerosis and related disorders on B-cell depleting therapies.

BACKGROUND: Patients with MS and related disorders (pwMSARD) on B-cell depleting treatments have attenuated immune responses to vaccination and were eligible to receive tixagevimab/cilgavimab. OBJECTIVES: Understand incidence and severity of COVID-19 in pwMSARD on B-cell depleting therapies who received tixagevimab/cilgavimab compared to an untreated group. METHODS: We conducted a retrospective medical records review of adult pwMSARD on B-cell depleting treatments who received tixagevimab/cilgavimab between 1/2022-1/2023. PwMSARD on B-cell depleting treatments who did not served as a control group (CG). We compared COVID-19 incidence and severity within 6 months of tixagevimab/cilgavimab or rituximab/ocrelizumab infusion for the CG. RESULTS: 210 patients were identified, 135 in the treatment group (TG) and 75 in the CG. In the TG, 24 (17.8 %) developed COVID-19 compared to 12 (16 %) in the CG. There was no difference in the odds of developing COVID-19 in an unadjusted logistic regression model (OR=1.14; 95 % CI: 0.53, 2.42; p = 0.74) or after adjusting for age and disease duration (OR=1.05; 95 % CI: 0.47, 2.37; p = 0.91). There was also no difference in COVID-19 severity between groups. CONCLUSIONS: There was no difference in COVID-19 infection rates or severity in pwMSARD on B-cell depleting treatments who received tixagevimab/cilgavimab compared to those who remained untreated.

The Complete Genome Sequences of 12 Species of Enteromius (Cyprinidae, Cypriniformes, Actinopteri).

We present the complete genome sequences of 12 species of Enteromius. Illumina sequencing was performed on genetic material from museum specimens. The reads were assembled using a de novo method followed by a finishing step. The raw and assembled data are publicly available via Genbank.

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.

Bacterial proximity effects on the transfer of antibiotic resistance genes within the alimentary tract of yellow mealworm larvae.

The arthropod intestinal tract and other anatomical parts naturally carry microorganisms. Some of which are pathogens, secrete toxins, or carry transferable antibiotic-resistance genes. The risks associated with the production and consumption of edible arthropods are dependent on indigenous microbes, as well as microbes introduced during the processes of rearing. This mass arthropod production puts individual arthropods in close proximity, which increases the possibility of their exposure to antibiotic-resistant bacteria carried by bacteria from fellow insects, industry workers, or rearing hardware and substrates. The purpose of this study was to determine if the alimentary tract of the yellow mealworm provided an environment permitting horizontal gene transfer between bacteria. The effect of the concentration of bacterial exposure was also assessed. Antibiotic resistance gene transfer between marker Salmonella Lignières (Enterobacterales: Enterobacteriaceae) and Escherichia coli (Migula) (Enterobacterales: Enterobacteriaceae) introduced into the larval gut demonstrated that the nutrient-rich environment of the yellow mealworm gut provided favorable conditions for the transfer of antibiotic resistance genes. Conjugation frequencies were similar across inoculum concentrations; however, transconjugant production correlated positively to increased exposure concentration. The lowest concentration of bacterial exposure required enrichment to detect and thus may have been approaching a threshold level for the 2 bacteria to colocate within the expanse of the larval gut. While many factors can affect this transfer, the simple factor of the proximity of donor and recipient bacteria, as defined by the concentration of bacteria within the volume of the insect gut, likely primarily contributed to the efficiency of antibiotic gene transfer.

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.

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 .