Plasma Markers of Alzheimer's Disease Pathology, Neuronal Injury, and Astrocytic Activation and MRI Load of Vascular Pathology and Neurodegeneration: The SMART-MR Study

BACKGROUND: Two of the main causes for dementia are Alzheimer's disease (AD) and vascular pathology, with most patients showing mixed pathology. Plasma biomarkers for Alzheimer's disease-related pathology have recently emerged, including Aβ (amyloid-beta), p-tau (phosphorylated tau), NfL (neurofilament light), and GFAP (glial fibrillary acidic protein). There is a current gap in the literature regarding whether there is an association between these plasma biomarkers with vascular pathology and neurodegeneration. METHODS AND RESULTS: Cross-sectional data from 594 individuals (mean [SD] age: 64 [8] years; 17% female) were included from the SMART-MR (Second Manifestations of Arterial Disease-Magnetic Resonance) study, a prospective cohort study of individuals with a history of arterial disease. Plasma markers were assessed using single molecular array assays (Quanterix). Magnetic resonance imaging markers included white matter hyperintensity volume, presence of infarcts (yes/no), total brain volume, and hippocampal volume assessed on 1.5T magnetic resonance imaging. Linear regressions were performed for each standardized plasma marker with white matter hyperintensity volume, total brain volume, and hippocampal volume as separate outcomes, correcting for age, sex, education, and intracranial volume. Logistic regressions were performed for the presence of lacunar and cortical infarcts. Higher p-tau181 was associated with larger white matter hyperintensity volume ( b per SD increase=0.16 [95% CI, 0.06-0.26], P=0.015). Higher NfL ( b=-5.63, [95% CI, -8.95 to -2.31], P=0.015) was associated with lower total brain volume and the presence of infarcts (odds ratio [OR], 1.42 [95% CI, 1.13-1.78], P=0.039). Higher GFAP levels were associated with cortical infarcts (OR, 1.45 [95% CI, 1.09-1.92], P=0.010). CONCLUSIONS: Plasma biomarkers that have been associated with tau pathology, axonal injury, and astrocytic activation are related to magnetic resonance imagingmarkers of vascular pathology and neurodegeneration in patients with manifest arterial disease

A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia

Metabolic reprogramming has emerged as a crucial regulator of immune cell activation, but how systemic metabolism influences immune cell metabolism and function remains to be investigated. To investigate the effect of dyslipidemia on immune cell metabolism, we performed in-depth transcriptional, metabolic, and functional characterization of macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage metabolism and attenuate inflammatory macrophage responses. In addition to diminished maximal mitochondrial respiration, hypercholesterolemia reduces the LPS-mediated induction of the pentose phosphate pathway (PPP) and the Nrf2-mediated oxidative stress response. Our observation that suppression of the PPP diminishes LPS-induced cytokine secretion supports the notion that this pathway contributes to inflammatory macrophage responses. Overall, this study reveals that systemic and cellular metabolism are strongly interconnected, together dictating macrophage phenotype and function

Self-monitoring of blood pressure in patients with hypertension related multi-morbidity: Systematic review and individual patient data meta-analysis

BACKGROUND Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (−3.12 mm Hg, [95% confidence intervals −4.78, −1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.</div

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Thermal acclimation increases the stability of a predator-prey interaction in warmer environments.

Global warming over the next century is likely to alter the energy demands of consumers and thus the strengths of their interactions with their resources. The subsequent cascading effects on population biomasses could have profound effects on food web stability. One key mechanism by which organisms can cope with a changing environment is phenotypic plasticity, such as acclimation to warmer conditions through reversible changes in their physiology. Here, we measured metabolic rates and functional responses in laboratory experiments for a widespread predator-prey pair of freshwater invertebrates, sampled from across a natural stream temperature gradient in Iceland (4-18℃). This enabled us to parameterize a Rosenzweig-MacArthur population dynamical model to study the effect of thermal acclimation on the persistence of the predator-prey pairs in response to warming. Acclimation to higher temperatures either had neutral effects or reduced the thermal sensitivity of both metabolic and feeding rates for the predator, increasing its energetic efficiency. This resulted in greater stability of population dynamics, as acclimation to higher temperatures increased the biomass of both predator and prey populations with warming. These findings indicate that phenotypic plasticity can act as a buffer against the impacts of environmental warming. As a consequence, predator-prey interactions between ectotherms may be less sensitive to future warming than previously expected, but this requires further investigation across a broader range of interacting species

Influence of habitat configuration on connectivity between fish assemblages of Caribbean seagrass beds, mangroves and coral reefs

The importance of seagrass beds and mangroves as juvenile habitats for coral reef fishes is still debatable. We hypothesised that the configuration of these habitats in the marine landscape in relation to the coral reef would influence accessibility from the reef (both for fishes that use these habitats for shelter or feeding, and their predators). In combination with differences in habitat complexity (related to habitat type) this could influence the utilisation of these habitats by juvenile reef fishes, and connectivity with the coral reef. Using underwater visual census, we studied the use by juvenile reef fishes of various seagrass and mangrove habitats situated differently in relation to the coral reef, on the Caribbean island of Aruba. Additionally, we studied fish assemblages on various coral reefs differing in proximity to seagrass Thalassia testudinum and mangrove Rhizophora mangle habitats at the scale of the whole island. In the seagrass and mangrove habitats, habitat configuration in relation to the reef was related to the composition of the fish assemblage, species richness, fish density and fish size. This was consistent with our expectations related to accessibility of these habitats from the reef, and habitat complexity. Most fish species that use seagrasses and mangroves as juvenile habitats were absent from or showed reduced densities on coral reefs located far (>9 km) from seagrass–mangrove habitats. At a smaller spatial scale, this effect was less clear. For some species, this lack of an effect at smaller spatial scales may be explained by local recruitment to the reef, whereas for other species (i.e. Haemulon sciurus, Lutjanus apodus, L. mahogoni and Scarus guacamaia) migration along the coast offers a more likely explanation. We suggest that the value of seagrass and mangrove habitats as a juvenile habitat should not be generalised a priori, since habitat configuration may interact with the degree of connectivity between seagrasses, mangroves and coral reefs.M. Dorenbosch, W. C. E. P. Verberk, I. Nagelkerken, G. van der Veld

Variations in consecutive serum neurofilament light levels in healthy controls and multiple sclerosis patients

Background Neurofilament light is a neuronal protein detectable in serum (sNfL), with high potential as disease activity biomarker in multiple sclerosis (MS). To date, little is known about sNfL fluctuations between 2 consecutive measurements in healthy controls (HC) and MS patients. Yet this information is critical, as it will help define a clinically significant variation. Methods sNfL was measured at 2 consecutive time points in a cohort of 90 MS patients (untreated relapsing remitting MS (uRRMS), n=35; treated relapsing remitting MS (tRRMS), n= 21; secondary progressive MS, SPMS, n=21; primary progressive MS, PPMS, n=13), and 90 age-matched HC, using the Simoa NfL light® assay. Results Mean sNfL was elevated in all MS subtypes compared to HC (p&lt;0.0001), and positively associated with age in HC (r=0.70, p&lt;0.001), confirming previous reports. Mean sNfL was higher at follow-up compared to baseline in HC (p&lt;0.001), and lower in uRRMS(p=0.036) and tRRMS (p=0.008). At follow-up, a similar proportion of HC (50.0%), untreated RRMS (51.4%), treated RRMS (33.3%), SPMS (45.0%) and PPMS (46.2%) had variations in sNfL levels exceeding 20% of baseline levels. Conclusions Our data suggest variations in sNfL occur both in HC and MS populations to a similar extent and magnitude. Variations between two consecutive sNfL measurements may reflect natural variations and not necessarily variations in inflammatory disease activity

Habitat selection during settlement of three Caribbean coral reef fishes: Indications for directed settlement to seagrasses and mangroves

We studied the settlement patterns of three Caribbean coral reef fishes in three different habitat types: mangroves, seagrass beds, and coral reefs. The settlement patterns of the three species were not random and could best be explained by active habitat selection during settlement. Acanthurus bahianus preferentially settled on the shallow reef flat and in adjacent seagrass beds, Lutjanus apodus settled exclusively into mangroves, and Ocyurus chrysurus, settled into both mangroves and seagrass beds. The settlement patterns of these three species reflect their habitat utilization during later juvenile stages. This study, therefore, suggests that the higher juvenile densities in mangroves and seagrass beds are determined by habitat selection during settlement rather than by post-settlement processes. This habitat selection during settlement is in accordance with the assumed importance of mangroves and seagrass beds as juvenile habitats of coral reef fishes and underlines the pressing need for their conservation.B. J. A. Pollux, W. C. E. P. Verberk, M. Dorenbosch, E. Cocheret de la Morinière, I. Nagelkerken, G. van der Veld

Erratum: Semiautomated surveillance of deep surgical site infections after colorectal surgeries: A multicenter external validation of two surveillance algorithms (Infection Control & Hospital Epidemiology (2023) 44: 4 (616-623) DOI: 10.1017/ice.2022.147)

In the above article1, table 2 was incorrect; below is the corrected table: 'Table Presented'