Sustained Increase in Pediatric Inflammatory Bowel Disease Incidence Across the South West United Kingdom Over the Last 10 Years.

BACKGROUND: Pediatric inflammatory bowel disease (pIBD) incidence has increased over the last 25 years. We aim to report contemporaneous trends across the South West United Kingdom. METHODS: Data were provided from centers covering the South West United Kingdom (Bristol, Oxford, Cardiff, Exeter, and Southampton), with a total area at-risk population (<18 years of age) of 2 947 534. Cases were retrieved from 2013 to 2022. Incident rates were reported per 100 000 at-risk population, with temporal trends analyzed through correlation. Subgroup analysis was undertaken for age groups (0-6, 6-11, and 12-17 years of age), sex, and disease subtype. Choropleth maps were created for local districts. RESULTS: In total, 2497 pIBD cases were diagnosed between 2013 and 2022, with a mean age of 12.6 years (38.7% female). Diagnosis numbers increased from 187 to 376, with corresponding incidence rates of 6.0 per 100 000 population per year (2013) to 12.4 per 100 000 population per year (2022) (b = 0.918, P < .01). Female rates increased from 5.1 per 100 000 population per year in 2013 to 11.0 per 100 000 population per year in 2022 (b = 0.865, P = .01). Male rates increased from 5.7 per 100 000 population per year to 14.4 per 100 000 population per year (b = 0.832, P = .03). Crohn's disease incidence increased from 3.1 per 100 000 population per year to 6.3 per 100 000 population per year (b = 0.897, P < .01). Ulcerative colitis increased from 2.3 per 100 000 population per year to 4.3 per 100 000 population per year (b = 0.813, P = .04). Inflammatory bowel disease unclassified also increased, from 0.6 per 100 000 population per year to 1.8 per 100 000 population per year (b = 0.851, P = .02). Statistically significant increases were seen in those ≥12 to 17 years of age, from 11.2 per 100 000 population per year to 24.6 per 100 000 population per year (b = 0.912, P < .01), and the 7- to 11-year-old age group, with incidence rising from 4.4 per 100 000 population per year to 7.6 per 100 000 population per year (b = 0.878, P = .01). There was no statistically significant increase in very early onset inflammatory bowel disease (≤6 years of age) (b = 0.417, P = .231). CONCLUSIONS: We demonstrate significant increases in pIBD incidence across a large geographical area including multiple referral centers. Increasing incidence has implications for service provision for services managing pIBD.

Incidence of inflammatory bowel disease continues to increase in childhood, particularly in older children. This is demonstrated in a contemporary dataset collected over a 10-year period, and covering an at-risk population of nearly 3 000 000. These data have significant implications for service provision.

Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow.

BACKGROUND: There is evidence that aerobic exercise is beneficial for brain health, but these effects are variable between individuals and the underlying mechanisms that modulate these benefits remain unclear. OBJECTIVE: We sought to characterize the acute physiological response of bioenergetic and neurotrophic blood biomarkers to exercise in cognitively healthy older adults, as well as relationships with brain blood flow. METHODS: We measured exercise-induced changes in lactate, which has been linked to brain blood flow, as well brain-derived neurotrophic factor (BDNF), a neurotrophin related to brain health. We further quantified changes in brain blood flow using arterial spin labeling. RESULTS: As expected, lactate and BDNF both changed with time post exercise. Intriguingly, there was a negative relationship between lactate response (area under the curve) and brain blood flow measured acutely following exercise. Finally, the BDNF response tracked strongly with change in platelet activation, providing evidence that platelet activation is an important mechanism for trophic-related exercise responses. CONCLUSIONS: Lactate and BDNF respond acutely to exercise, and the lactate response tracks with changes in brain blood flow. Further investigation into how these factors relate to brain health-related outcomes in exercise trials is warranted.

Blood Biomarkers Discriminate Cerebral Amyloid Status and Cognitive Diagnosis when Collected with ACD-A Anticoagulant.

BACKGROUND: The development of biomarkers that are easy to collect, process, and store is a major goal of research on current Alzheimer's Disease (AD) and underlies the growing interest in plasma biomarkers. Biomarkers with these qualities will improve diagnosis and allow for better monitoring of therapeutic interventions. However, blood collection strategies have historically differed between studies. We examined the ability of various ultrasensitive plasma biomarkers to predict cerebral amyloid status in cognitively unimpaired individuals when collected using acid citrate dextrose (ACD). We then examined the ability of these biomarkers to predict cognitive impairment independent of amyloid status. METHODS: Using a cross-sectional study design, we measured amyloid beta 42/40 ratio, pTau-181, neurofilament-light, and glial fibrillary acidic protein using the Quanterix Simoa® HD-X platform. To evaluate the discriminative accuracy of these biomarkers in determining cerebral amyloid status, we used both banked plasma and 18F-AV45 PET cerebral amyloid neuroimaging data from 140 cognitively unimpaired participants. We further examined their ability to discriminate cognitive status by leveraging data from 42 cognitively impaired older adults. This study is the first, as per our knowledge, to examine these specific tests using plasma collected using acid citrate dextrose (ACD), as well as the relationship with amyloid PET status. RESULTS: Plasma AB42/40 had the highest AUC (0.833, 95% C.I. 0.767-0.899) at a cut-point of 0.0706 for discriminating between the two cerebral amyloid groups (sensitivity 76%, specificity 78.5%). Plasma NFL at a cut-point of 20.58pg/mL had the highest AUC (0.908, 95% CI 0.851- 0.966) for discriminating cognitive impairment (sensitivity 84.8%, specificity 89.9%). The addition of age and apolipoprotein e4 status did not improve the discriminative accuracy of these biomarkers. CONCLUSION: Our results suggest that the Aß42/40 ratio is useful in discriminating clinician-rated elevated cerebral amyloid status and that NFL is useful for discriminating cognitive impairment status. These findings reinforce the growing body of evidence regarding the general utility of these biomarkers and extend their utility to plasma collected in a non-traditional anticoagulant.

NIMBUS study protocol: a single-centre feasibility study of non-invasive monitoring with bowel ultrasound in paediatric inflammatory bowel disease.

INTRODUCTION: Incidence of inflammatory bowel disease (IBD) is increasing in childhood and treatment increasingly targets mucosal healing. Monitoring bowel inflammation requires endoscopy or MRI enterography which are invasive, expensive and have long waiting lists.We aim to examine the feasibility of a non-invasive monitoring tool-bowel ultrasound (BUS)-in children with IBD and explore correlations with inflammatory markers and disease activity measures. Some BUS criteria have been found to correlate with these markers; however, this has not been validated in children.We aim to examine the feasibility of BUS for monitoring inflammation in this population; highlighting useful parameters for this purpose. We aim to inform a larger scale randomised controlled trial using BUS. METHODS AND ANALYSIS: This prospective observational feasibility study will be carried out over 24 months at the Noah's Ark Children's Hospital for Wales, Cardiff; with the endpoint recruitment of 50 participants. Children aged 2-18 years with a modified Porto criteria diagnosis of IBD will be included.Patients without IBD or who have previously undergone IBD-related surgery will be excluded; as will families unable to give informed consent.Ultrasound scan images and reports will be collected, as well as laboratory results and clinical outcomes.The primary aim will assess the feasibility of targeted BUS for disease monitoring; including recruitment statistics. The secondary aims will involve data collection and correlation analysis for targeted ultrasound parameters, biomarkers, disease activity scores and prediction of changes in treatment. The statistical methods will include: feasibility metrics, descriptive statistics, cross-tabulation and χ2 analysis, correlation analysis, regression analysis. ETHICS AND DISSEMINATION: Ethical approval is granted by NHS Research Ethics Committee. The sponsor is Cardiff and Vale University Health Board. We will publish the results in a peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT05673278.

Recent developments in the assessment and management of inflammatory bowel disease in childhood: a narrative review.

Background and Objective: The landscape of paediatric inflammatory bowel disease (pIBD) continues to evolve in an era of increasing incidence. There have been rapid developments in understanding, as we begin to perceive IBD as a spectrum of conditions, alongside advancements in monitoring and treatment. The objective of this article was to provide an overview of recent advances and challenges in the management of pIBD, with a focus on sustainable healthcare, personalised therapy, genomics, new drugs and avenues for future optimisation. Methods: We present a narrative review that synthesises and summarises recent research (2017-2022) related to pIBD. We undertook a structured search of the literature (PubMed and Medline) and additional articles were identified through manual searches of reference lists. Evidence tables were compiled for disease outcomes. Key Content and Findings: In this review we outline current practice, integrating clinical guidelines and contemporary research. We discuss initial investigations (including suggested threshold for paediatric faecal calprotectin), specialist investigations for disease monitoring [with reference to video capsule endoscopy (VCE) and therapeutic drug levels] and outline new and established treatment options. Biomarkers and genomic testing are examined as important tools for individualising care and identifying potential therapeutic targets, including for top-down therapy. Despite these advances, significant challenges remain, including the need for further research to understand the mechanisms of disease and the translation of these advances into real-world improvements in practice. Conclusions: Recent advances in understanding of the pathogenesis of pIBD, alongside genomic and pharmacological developments have added more tools to the armamentarium for the treatment of these conditions and highlighted ongoing areas of research need.

Increased Functional Connectivity of the Precuneus in Individuals with a Family History of Alzheimer's Disease.

BACKGROUND: First-degree relatives of individuals with late-onset Alzheimer's disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. OBJECTIVE: We aimed to investigate default mode network connectivity, medial temporal cortex volume, and cognition in cognitively healthy (CH) individuals with (FH+) and without (FH-) a family history of AD, alongside amnestic mild cognitive impairment (aMCI) and AD individuals, to determine the context and directionality of dysfunction in at-risk individuals. Our primary hypothesis was that there would be a linear decline (CH FH- > CH FH+ > aMCI > AD) within the risk groups on all measures of AD risk. METHODS: We used MRI and fMRI to study cognitively healthy individuals (n = 28) with and without AD family history (FH+ and FH-, respectively), those with aMCI (n = 31) and early-stage AD (n = 25). We tested connectivity within the default mode network, as well as measures of volume and thickness within the medial temporal cortex and selected seed regions. RESULTS: As expected, we identified decreased medial temporal cortex volumes in the aMCI and AD groups compared to cognitively healthy groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH- and AD groups (CH FH+ > CH FH- > aMCI > AD). This pattern emerged primarily in connectivity between the precuneus and frontal regions. CONCLUSION: These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.

Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15 minutes of moderate-intensity aerobic exercise in older adults (≥65 years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6 min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12 minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers.

INTRODUCTION: Fasting glucose increases with age and is linked to modifiable Alzheimer's disease risk factors such as cardiovascular disease and Type 2 diabetes (T2D). METHODS: We leveraged available biospecimens and neuroimaging measures collected during the Alzheimer's Prevention Through Exercise (APEx) trial (n = 105) to examine the longitudinal relationship between change in blood glucose metabolism and change in regional cerebral amyloid deposition and gray and white matter (WM) neurodegeneration in older adults over 1 year of follow-up. RESULTS: Individuals with improving fasting glucose (n = 61) exhibited less atrophy and regional amyloid accumulation compared to those whose fasting glucose worsened over 1 year (n = 44). Specifically, while individuals with increasing fasting glucose did not yet show cognitive decline, they did have regional atrophy in the hippocampus and inferior parietal cortex, and increased amyloid accumulation in the precuneus cortex. Signs of early dementia pathology occurred in the absence of significant group differences in insulin or body composition, and was not modified by apolipoprotein E ε4 carrier status. DISCUSSION: Dysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine whether treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.

Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle.

Alzheimer's Disease (ad) associates with insulin resistance and low aerobic capacity, suggestive of impaired skeletal muscle mitochondrial function. However, this has not been directly measured in AD. This study ( n  = 50) compared muscle mitochondrial respiratory function and gene expression profiling in cognitively healthy older adults (CH; n = 24) to 26 individuals in the earliest phase of ad-related cognitive decline, mild cognitive impairment (MCI; n  = 11) or MCI taking the ad medication donepezil (MCI + med; n  = 15). Mitochondrial respiratory kinetics were measured in permeabilized muscle fibers from muscle biopsies of the vastus lateralis. Untreated MCI exhibited lower lipid-stimulated skeletal muscle mitochondrial respiration (State 3, ADP-stimulated) than both CH ( P = .043) and MCI + med (P = .007) groups. MCI also exhibited poorer mitochondrial coupling control compared to CH (P = .014). RNA sequencing of skeletal muscle revealed unique differences in mitochondrial function and metabolism genes based on both MCI status (CH vs MCI) and medication treatment (MCI vs MCI + med). MCI + med modified over 600 skeletal muscle genes compared to MCI suggesting donepezil powerfully impacts the transcriptional profile of muscle. Overall, skeletal muscle mitochondrial respiration is altered in untreated MCI but normalized in donepezil-treated MCI participants while leak control is impaired regardless of medication status. These results provide evidence that mitochondrial changes occur in the early stages of AD, but are influenced by a common ad medicine. Further study of mitochondrial bioenergetics and the influence of transcriptional regulation in early ad is warranted.

Variation and appropriateness of antipsychotic use in long-term care facilities across Newfoundland and Labrador.

OBJECTIVE: The use of antipsychotics to treat seniors in long-term care facilities (LTCFs) has raised concern because of health consequences (i.e., increased risk of falls, stroke, death) in this vulnerable population. This study measured geographic patterns of antipsychotic utilization among seniors living in LTCFs in Newfoundland and Labrador (NL) and assessed potential inappropriateness. METHOD: We analyzed prescription records among adults 66 years and older with provincial prescription drug coverage admitted to LTCFs in NL between April 1, 2011, and March 31, 2014. Patterns of use were analyzed across the 4 regional health authorities (RHAs) in NL and LTCFs. Logistic, Poisson and linear regression models were used to test variations in prevalence, rate and volume of antipsychotic utilization. To assess potential inappropriateness of antipsychotic use, we analyzed data from Resident Assessment Instrument-Minimum Data Set (RAI-MDS) 2.0 forms from NL LTCFs between January 1, 2016, and December 31, 2018. Pearson chi-squared analysis was performed at the RHA and LTCF levels to determine changes in percentage of total prescriptions or antipsychotic prescriptions without psychosis. RESULTS: Between 2011 and 2014, 2843 seniors were admitted to LTCFs across NL; of these, 1323 residents were prescribed 1 or more antipsychotics. Within the 3-year period, the percentage of antipsychotic use across facilities ranged from 35% to 78%. Using data from 27,260 RAI-MDS 2.0 assessments between 2016 and 2018, 71% (6995/9851) of antipsychotic prescriptions were potentially inappropriate. DISCUSSION: There is substantial variation across NL regions concerning the utilization of antipsychotics for senior in LTCFs. Facility size and management styles may be reasons for this. CONCLUSION: With nearly three-quarters of antipsychotic prescriptions shown to be potentially inappropriate, systematic interventions to assess indications for antipsychotic use are warranted. Can Pharm J (Ott) 2021;154:xx-xx.

Rationale and methods to characterize the acute exercise response in aging and Alzheimer's Disease: the AEROBIC pilot study.

There is evidence that exercise benefits the brain, but the mechanisms for this benefit are unclear. The chronic benefits of exercise are likely a product of discreet, acute responses in exercise-related blood biomarkers and brain metabolism. This acute exercise response has not been compared in aging and Alzheimer's Disease (AD). It is known that acute exercise elicits a powerful peripheral response in young individuals, and exercise-related biomarkers such as glucose and lactate readily penetrate the brain. How this changes with aging and neurodegenerative disease is less clear. It is critical to characterize and understand the acute effects of exercise, including different exercise intensities, in terms of the peripheral metabolic response and relationship with brain metabolism. This will help determine potential mechanisms for brain benefits of exercise and better inform the design of future clinical trials. The primary goal of the AEROBIC study is to characterize the acute exercise response of brain glucose metabolism and exercise-related blood biomarkers. We will measure how cerebral metabolism is affected by an acute bout of moderate and higher intensity exercise and characterize the extent to which this differs between cognitively healthy older adults and individuals with AD. Related to this primary goal, we will quantify the peripheral biomarker response to moderate and higher intensity exercise and how this relates to brain metabolic change in both groups.

Routine abdominal magnetic resonance imaging can determine psoas muscle area in paediatric Crohn's disease and correlates with bioelectrical impedance spectroscopy measures of lean mass.

BACKGROUND: Paediatric Crohn's disease (CD) has been associated with undernutrition. Accurate and accessible measures of body composition would provide data to personalise nutritional therapy. We assessed feasibility of MRI-derived measures of psoas cross-sectional area (PCSA) in paediatric CD and correlated with anthropometric and bioelectrical impedance spectroscopy (BIS) measures. METHODS: MRI small bowel/pelvis images of patients with CD, aged <18 years, were retrieved. Patients with concurrent anthropometric and BIS measurements were eligible for inclusion. The PCSA at L3 was calculated by two assessors and combined. To assess reproducibility of measures we calculated the coefficient of variation (CoV). Age, height-Z-scores, weight-Z-scores and BIS measures were correlated with PCSA. Using normal paediatric data from CT-scans we derived psoas area Z-scores for our cohort. RESULTS: 10 patients were included. Mean age at MRI scan was 14.6 years (11.7-16.3). PCSA was calculated for all MRI scans. There was high reproducibility between measurers, mean CoV 0.099. There was a significant positive correlation between PCSA and BIA-derived fat free mass, Pearson correlation coefficient (PCC) 0.831, p = 0.003. Correlation coefficients for PCSA and Height-for-age Z-score, weight-for-age -Z-score and age were PCC 0.343- p = 0.33, PCC = 0.222- p = 0.54, and PCC 0.6034- p = 0.065, respectively. The mean PCSA Z-score was -1.81, with 70% of the patients having a Z-score < -2.0. CONCLUSIONS: These data demonstrate the feasibility of deriving measures of body composition from routine MRI imagine. There was significant positive correlation between PCSA and BIS-derived lean mass. Further studies are required to confirm applicability of normal ranges prior to routine clinical implementation.

Growth failure is rare in a contemporary cohort of paediatric inflammatory bowel disease patients.

AIM: We assessed growth in a paediatric inflammatory bowel disease (PIBD) cohort. METHODS: Paediatric inflammatory bowel disease patients were eligible if they were diagnosed at Southampton Children's Hospital from 2011 to 2018. Weight and height standard deviation scores (SDS) were retrieved. Mean SDS values, SDS change and anti-TNF status were analysed at diagnosis and during follow-up. RESULTS: Four hundred and ninety patients were included, 313 with Crohn's disease (CD). CD patients presented with mean height SDS -0.13, -0.1 at 1-year, -0.11 at 2-years and -0.03 at 5 years, reflecting preserved linear growth. There was no significant height-SDS change from diagnosis to 5-year follow-up, +0.12, 95%-CI: 0.48 to -0.24. Mean weight-SDS at diagnosis was -0.39, driven by CD patients (-0.65). Mean weight-SDS approached 0 after 1 year and remained at the 50th centile throughout follow-up. Growth in ulcerative colitis was maintained. In multivariable regression males had worse height growth from diagnosis to transition (P = .036). Anti-TNF treatment (P = .013) and surgical resection (P = .005) were also associated with poorer linear growth. Patients treated with anti-TNF therapy had lower height-SDS compared to those never treated with anti-TNF at 1 year (-0.2 vs -0.01, P = .22), 2-years (-0.27 vs -0.01, P = .07) and 5 years (-0.21 vs 0.25, P = .051). CONCLUSION: Height was generally maintained in Crohn's disease, and impaired linear growth was rare in this cohort.

Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

BACKGROUND: Individuals with Alzheimer's Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear. METHODS: Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging. RESULTS: The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions. CONCLUSION: Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.

Inflammatory bowel disease: long-term therapeutic challenges.

Introduction: Long-term, sustained, remission is the ultimate goal of contemporary inflammatory bowel disease (IBD) therapy. Avoiding complications, surgery and malignancy, alongside minimizing the side effects of medications are vital. However, the reality of treatment involves patients losing response to therapy, or developing complications requiring cessation of medication. The reasons underlying this are numerous and include medication and host-related influences. Underpinning the response to medication, long-term outcomes and loss of response are individual etiological factors including the molecular cause of disease and individual pharmacogenomic influences.Areas covered: In this review, we discuss the long-term outcome of IBD, with a focus on pediatric-onset illness and discuss the factors leading to loss of treatment response whilst briefly considering the future of personalized therapy as a strategy to improve long-term outcomes.Expert opinion: Research findings are now moving toward clinical translation, including application of novel medications targeting new pathways. The integration of biological and multiomic data to predict disease outcome will provide personalized therapeutic management.

Oxylipin Profiling of Alzheimer's Disease in Nondiabetic and Type 2 Diabetic Elderly.

Oxygenated lipids, called "oxylipins," serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer's disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD.

What's New in Rezum: a Transurethral Water Vapour Therapy for BPH.

PURPOSE OF REVIEW: Rezum is a new minimally invasive treatment for benign prostate enlargement using thermal transurethral water vapour therapy. We review the evidence with advantages and disadvantages of this technique. RECENT FINDINGS: There are five studies reported including a randomised control trial looking at the outcomes of Rezum. The outcomes show an IPSS reduction by 45-60%, QoL improvement with a score reduction of 37-59%, the Qmax improvement by 44-72% and the PVR reduction by 20-38%. Convective water vapour therapy using the Rezum system has been shown to have successful outcomes in the treatment of LUTS resulting from BPH. The reported complications are infrequent and often minor, and it seems to be relatively cost-effective.

Health-Related Quality of Life of Older Adults in Costa Rica as Measured by the Short-Form-36 Health Survey.

Objective: To test the validity of a common measure of health-related quality of life (Short-Form-36 [SF-36]) in cognitively healthy older adults living in rural and urban Costa Rica. Method: Confirmatory factor analysis was applied to SF-36 data collected in 250 older adults from San Jose and Guanacaste, Costa Rica. Results: The best fitting model for the SF-36 was an eight first-order factor structure. A high correlation between the Mental Component Summary and Physical Component Summary scores was found. Region differences indicated that rural dwellers perceive a poorer health-related quality of life compared with the urban group. Discussion: Costa Rican older adults perceived health as a unidimensional construct. Age and urbanity of older adult Costa Ricans should be appreciated when trying to measure self-reported physical and mental health. Cultural context of the individuals should be considered when studying health-related quality of life.

Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.

Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.