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Abstract Background Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)42 and Aβ40 present a circadian rhythm. However sustained sampling of large volumes of CSF with indwelling intrathecal catheters used in most of these studies might have affected CSF dynamics and thereby confounded the observed fluctuations in the biomarker levels. Methods We included 38 individuals with either normal (N = 20) or abnormal (N = 18) CSF Aβ42/Aβ40 levels at baseline. CSF and plasma were collected at two visits separated by an average of 53 days with lumbar punctures and venipunctures performed either in the morning or evening. At the first visit, sample collection was performed in the morning for 17 participants and the order was reversed for the remaining 21 participants. CSF and plasma samples were analyzed for Alzheimer’ disease (AD) biomarkers, including Aβ42, Aβ40, GFAP, NfL p-tau181, p-tau217, p-tau231 and t-tau. CSF samples were also tested using mass spectrometry for 22 synaptic and endo-lysosomal proteins. Results CSF Aβ42 (mean difference [MD], 0.21 ng/mL; p = 0.038), CSF Aβ40 (MD, 1.85 ng/mL; p

Abstract Blood-based biomarkers for screening may guide tau positrion emissition tomography (PET) scan referrals to optimize prognostic evaluation in Alzheimer’s disease. Plasma Aβ42/Aβ40, pTau181, pTau217, pTau231, NfL, and GFAP were measured along with tau-PET in memory clinic patients with subjective cognitive decline, mild cognitive impairment or dementia, in the Swedish BioFINDER-2 study (n = 548) and in the TRIAD study (n = 179). For each plasma biomarker, cutoffs were determined for 90%, 95%, or 97.5% sensitivity to detect tau-PET-positivity. We calculated the percentage of patients below the cutoffs (who would not undergo tau-PET; “saved scans”) and the tau-PET-positivity rate among participants above the cutoffs (who would undergo tau-PET; “positive predictive value”). Generally, plasma pTau217 performed best. At the 95% sensitivity cutoff in both cohorts, pTau217 resulted in avoiding nearly half tau-PET scans, with a tau-PET-positivity rate among those who would be referred for a scan around 70%. And although tau-PET was strongly associated with subsequent cognitive decline, in BioFINDER-2 it predicted cognitive decline only among individuals above the referral cutoff on plasma pTau217, supporting that this workflow could reduce prognostically uninformative tau-PET scans. In conclusion, plasma pTau217 may guide selection of patients for tau-PET, when accurate prognostic information is of clinical value.

Abstract Background Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain. Methods NTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline. Results We demonstrate that plasma NTA-tau increases across the AD continuum¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p

This article addresses the challenges of selecting robust classifiers with increasing noise levels in real-world scenarios. We propose the WB Score methodology, which enables the identification of reliable classifiers for deployment in noisy environments. The methodology addresses four significant challenges that are commonly encountered: (i) Ensuring classifiers possess robustness to noise; (ii) Overcoming the difficulty of obtaining representative data that captures real-world noise; (iii) Addressing the complexity of detecting noise, making it challenging to differentiate it from natural variations in the data; and (iv) Meeting the requirement for classifiers capable of efficiently handling noise, allowing prompt responses for decision-making. WB Score provides a comprehensive approach for classifier assessment and selection to address these challenges. We analyze five classic datasets and one customized flooding dataset in São Paulo. The results demonstrate the practical effect of using the WB Score methodology is the enhanced ability to select robust classifiers for datasets in noisy real-world scenarios. Compared with similar techniques, the improvement centers around providing a visual and intuitive output, enhancing the understanding of classifier resilience against noise, and streamlining the decision-making process.

Abstract Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2) and moderate‐to‐severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = 8) treatment in a double‐blind parallel‐group design. Whole body glucose metabolism was determined by oral glucose tolerance test. A skeletal muscle biopsy was obtained to evaluate mitochondrial respiratory capacity and expression of proteins related to mitochondrial dynamics and energy metabolism. Whole body insulin‐sensitivity (Matsuda index) did not change in metformin or placebo treated groups. However, metformin treatment prevented increases in insulin release relative to placebo during follow‐up. Insulin area under the curve (AUC) and insulin to glucose AUC ratio increased in placebo but remained unchanged with metformin. Furthermore, metformin treatment improved skeletal muscle mitochondrial respiratory capacity and dynamics relative to placebo. Metformin treatment prevented the decline in whole body glucose homeostasis and skeletal muscle mitochondrial function in patients with moderate to severe OSA. Patients with OSA may benefit from the addition of metformin to prevent diabetes.

Abstract Background Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer’s disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231. Methods CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n=212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n=175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ $$-$$ - ). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ1–42/40 ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231). Results High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ− groups (Paris cohort: P ˂0.0001 for all; BIODEGMAR cohort: P ˂0.05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A−T− and A+T− groups (P ˂0.0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0.86 to 0.96) and discriminating AT groups (AUCs=0.79 to 0.98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts. Conclusions CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings.

Abstract As the leading cause of dementia, Alzheimer's disease (AD) is a major burden on affected individuals, their families and caregivers, and healthcare systems. Although AD can be identified and diagnosed by cerebrospinal fluid or neuroimaging biomarkers that concord with neuropathological evidence and clinical symptoms, challenges regarding practicality and accessibility hinder their widespread availability and implementation. Consequently, many people with suspected cognitive impairment due to AD do not receive a biomarker-supported diagnosis. Blood biomarkers have the capacity to help expand access to AD diagnostics worldwide. One such promising biomarker is plasma phosphorylated tau (p-tau), which has demonstrated specificity to AD versus non-AD neurodegenerative diseases, and will be extremely important to inform on clinical diagnosis and eligibility for therapies that have recently been approved. This review provides an update on the diagnostic and prognostic performances of plasma p-tau181, p-tau217 and p-tau231, and their associations with in vivo and autopsy-verified diagnosis and pathological hallmarks. Additionally, we discuss potential applications and unanswered questions of plasma p-tau for therapeutic trials, given their recent addition to the biomarker toolbox for participant screening, recruitment and during-trial monitoring. Outstanding questions include assay standardization, threshold generation and biomarker verification in diverse cohorts reflective of the wider community attending memory clinics and included in clinical trials.

In the course of climate change, natural regeneration of oaks (Quercus spp.) is gaining in importance for forest conversion to climate-adapted mixed forests. In order to predict areas in which natural oak regeneration could establish, variables influencing the occurrence and density of oak regeneration were identified using geostatistical zero-altered negative binomial generalized linear models (ZANB). For this purpose, large-scale inventory data from the state forest of Saxony were analysed. The dataset was derived from 6060 permanent plots. The results show that the occurrence of oak regeneration depends on a number of environmental variables. In addition to seed availability, the establishment environment, especially with regard to the light ecology of oak regeneration, was important. High basal area of pine increased the probability for oak regeneration occurrence. The most important variables for the regeneration density of oak have similarly been found to be those describing the seed availability. The highest regeneration densities are predicted within oak stands, with an optimum relationship at 25 m2 ha-1 of oak basal area. The results further show that a high regeneration density was achieved on sites with low fertility and favourable light conditions. Oak regeneration density increased with increasing browsing percent on rowan, indicating that browsing on oak can be reduced if other palatable species are available. Using the identified variables, the occurrence and density of oak regeneration can be predicted in space with high accuracy. The statistical tool developed can be used for planning forest conversion incorporating natural regeneration.

Abstract Introduction Cerebrospinal fluid (CSF) tau biomarkers are reliable diagnostic markers for Alzheimer’s disease (AD). However, their strong association with amyloid pathology may limit their reliability as specific markers of tau neurofibrillary tangles. A recent study showed evidence that a ratio of CSF C-terminally truncated tau (tau368, a tangle-enriched tau species), especially in ratio with total tau (t-tau), correlates strongly with tau PET tracer uptake. In this study, we set to evaluate the performance of the tau368/t-tau ratio in capturing tangle pathology, as indexed by a high-affinity tau PET tracer, as well as its association with severity of clinical symptoms. Methods In total, 125 participants were evaluated cross-sectionally from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort (21 young, 60 cognitively unimpaired [CU] elderly [15 Aβ+], 10 Aβ+ with mild cognitive impairment [MCI], 14 AD dementia patients, and 20 Aβ− individuals with non-AD cognitive disorders). All participants underwent amyloid and tau PET scanning, with [18F]-AZD4694 and [18F]-MK6240, respectively, and had CSF measurements of p-tau181, p-tau217, and t-tau. CSF concentrations of tau368 were quantified in all individuals with an in-house single molecule array assay. Results CSF tau368 concentration was not significantly different across the diagnostic groups, although a modest increase was observed in all groups as compared with healthy young individuals (all P < 0.01). In contrast, the CSF tau368/t-tau ratio was the lowest in AD dementia, being significantly lower than in CU individuals (Aβ−, P < 0.001; Aβ+, P < 0.01), as well as compared to those with non-AD cognitive disorders (P < 0.001). Notably, in individuals with symptomatic AD, tau368/t-tau correlated more strongly with [18F]-MK6240 PET SUVR as compared to the other CSF tau biomarkers, with increasing associations being seen in brain regions associated with more advanced disease (isocortical regions > limbic regions > transentorhinal regions). Importantly, linear regression models indicated that these associations were not confounded by Aβ PET SUVr. CSF tau368/t-tau also tended to continue to become more abnormal with higher tau burden, whereas the other biomarkers plateaued after the limbic stage. Finally, the tau368/t-tau ratio correlated more strongly with cognitive performance in individuals with symptomatic AD as compared to t-tau, p-tau217 and p-tau181. Conclusion The tau368/t-tau ratio captures novel aspects of AD pathophysiology and disease severity in comparison to established CSF tau biomarkers, as it is more closely related to tau PET SUVR and cognitive performance in the symptomatic phase of the disease.

Abstract Background Sarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified that a mitochondrial‐targeted furazano[3,4‐b]pyrazine named BAM15 is orally available and selectively lowers respiratory coupling efficiency and protects against diet‐induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity. Methods Eighty‐week‐old male C57BL/6J mice with obesity were randomized to 10 weeks of high fat diet (CTRL) or BAM15 (BAM15; 0.1% w/w in high fat diet) treatment. Body weight and food intake were measured weekly. Body composition, muscle function, energy expenditure, locomotor activity, and glucose tolerance were determined after treatment. Skeletal muscle was harvested and evaluated for histology, gene expression, protein signalling, and mitochondrial structure and function. Results BAM15 decreased body weight (54.0 ± 2.0 vs. 42.3 ± 1.3 g, P

Summary: Background: The diagnosis of symptomatic Alzheimer's disease is a clinical challenge in adults with Down syndrome. Blood biomarkers would be of particular clinical importance in this population. The astrocytic Glial Fibrillary Acidic Protein (GFAP) is a marker of astrogliosis associated with amyloid pathology, but its longitudinal changes, association with other biomarkers and cognitive performance have not been studied in individuals with Down syndrome. Methods: We performed a three-centre study of adults with Down syndrome, autosomal dominant Alzheimer's disease and euploid individuals enrolled in Hospital Sant Pau, Barcelona (Spain), Hospital Clinic, Barcelona (Spain) and Ludwig-Maximilians-Universität, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET 18F-fluorodeoxyglucose, amyloid tracers and MRI measurements. Findings: This study included 997 individuals, 585 participants with Down syndrome, 61 Familial Alzheimer's disease mutation carriers and 351 euploid individuals along the Alzheimer's disease continuum, recruited between November 2008 and May 2022. Participants with Down syndrome were clinically classified at baseline as asymptomatic, prodromal Alzheimer's disease and Alzheimer's disease dementia. Plasma GFAP levels were significantly increased in prodromal and Alzheimer's disease dementia compared to asymptomatic individuals and increased in parallel to CSF Aβ changes, ten years prior to amyloid PET positivity. Plasma GFAP presented the highest diagnostic performance to discriminate symptomatic from asymptomatic groups (AUC = 0.93, 95% CI 0.9−0.95) and its concentrations were significantly higher in progressors vs non-progressors (p

Abstract Information on the altitudinal distribution of the hard ticks Amblyomma aureolatum and Amblyomma ovale in Brazil is scarce and mainly limited to occasional records. In this study we report our evaluation of records on the altitudinal distribution of A. aureolatum and A. ovale collected from dogs and humans and directly from the environment (host-questing ticks), based on active or passive procedures. The collections were conducted in rural areas of municipalities in the state of Rio de Janeiro, Brazil between 2013 and 2017. Active procedures consisted of dragging or flagging, visual examination of vegetation and removal of ticks present on the authors’ clothing or on infested dogs. Overall, 222 ticks were collected. The altitudes at the collection sites ranged from 98 to 1220 m a.s.l. We noted a significant difference in the altitudinal distribution of A. aureolatum and A. ovale (Mann–Whitney U-test, U = 518.5, P

Abstract Background Plasma biomarkers for Alzheimer’s disease (AD) have broad potential as screening tools in primary care and disease-modifying trials. Detecting elevated amyloid-β (Aβ) pathology to support trial recruitment or initiating Aβ-targeting treatments would be of critical value. In this study, we aimed to examine the robustness of plasma biomarkers to detect elevated Aβ pathology at different stages of the AD continuum. Beyond determining the best biomarker—or biomarker combination—for detecting this outcome, we also simulated increases in inter-assay coefficient of variability (CV) to account for external factors not considered by intra-assay variability. With this, we aimed to determine whether plasma biomarkers would maintain their accuracy if applied in a setting which anticipates higher variability (i.e., clinical routine). Methods We included 118 participants (cognitively unimpaired [CU, n = 50], cognitively impaired [CI, n = 68]) from the ADNI study with a full plasma biomarker profile (Aβ42/40, GFAP, p-tau181, NfL) and matched amyloid imaging. Initially, we investigated how simulated CV variations impacted single-biomarker discriminative performance of amyloid status. Then, we evaluated the predictive performance of models containing different biomarker combinations, based both on original and simulated measurements. Plasma Aβ42/40 was represented by both immunoprecipitation mass spectrometry (IP-MS) and single molecule array (Simoa) methods in separate analyses. Model selection was based on a decision tree which incorporated Akaike information criterion value, likelihood ratio tests between the best-fitting models and, finally, and Schwartz’s Bayesian information criterion. Results Increasing variation greatly impacted the performance of plasma Aβ42/40 in discriminating Aβ status. In contrast, the performance of plasma GFAP and p-tau181 remained stable with variations >20%. When biomarker models were compared, the models “AG” (Aβ42/40 + GFAP; AUC = 86.5), “A” (Aβ42/40; AUC = 82.3), and “AGP” (Aβ42/40 + GFAP + p-tau181; AUC = 93.5) were superior in determining Aβ burden in all participants, within-CU, and within-CI groups, respectively. In the robustness analyses, when repeating model selection based on simulated measurements, models including IP-MS Aβ42/40 were also most often selected. Simoa Aβ42/40 did not contribute to any selected model when used as an immunoanalytical alternative to IP-MS Aβ42/40. Conclusions Plasma Aβ42/40, as quantified by IP-MS, shows high performance in determining Aβ positivity at all stages of the AD continuum, with GFAP and p-tau181 further contributing at CI stage. However, between-assay variations greatly impacted the performance of Aβ42/40 but not that of GFAP and p-tau181. Therefore, when dealing with between-assay CVs that exceed 5%, plasma GFAP and p-tau181 should be considered for a more robust determination of Aβ burden in CU and CI participants, respectively.

Abstract Background Changes in soluble amyloid-beta (Aβ) levels in cerebrospinal fluid (CSF) are detectable at early preclinical stages of Alzheimer’s disease (AD). However, whether Aβ levels can predict downstream AD pathological features in cognitively unimpaired (CU) individuals remains unclear. With this in mind, we aimed at investigating whether a combination of soluble Aβ isoforms can predict tau pathology (T+) and neurodegeneration (N+) positivity. Methods We used CSF measurements of three soluble Aβ peptides (Aβ1 –38, Aβ1 –40 and Aβ1 –42) in CU individuals (n = 318) as input features in machine learning (ML) models aiming at predicting T+ and N+. Input data was used for building 2046 tuned predictive ML models with a nested cross-validation technique. Additionally, proteomics data was employed to investigate the functional enrichment of biological processes altered in T+ and N+ individuals. Results Our findings indicate that Aβ isoforms can predict T+ and N+ with an area under the curve (AUC) of 0.929 and 0.936, respectively. Additionally, proteomics analysis identified 17 differentially expressed proteins (DEPs) in individuals wrongly classified by our ML model. More specifically, enrichment analysis of gene ontology biological processes revealed an upregulation in myelinization and glucose metabolism-related processes in CU individuals wrongly predicted as T+. A significant enrichment of DEPs in pathways including biosynthesis of amino acids, glycolysis/gluconeogenesis, carbon metabolism, cell adhesion molecules and prion disease was also observed. Conclusions Our results demonstrate that, by applying a refined ML analysis, a combination of Aβ isoforms can predict T+ and N+ with a high AUC. CSF proteomics analysis highlighted a promising group of proteins that can be further explored for improving T+ and N+ prediction.

Abstract Background Muscle atrophy and strength loss are common adverse outcomes following bariatric surgery. This randomized, controlled trial investigated the effects of exercise training on bariatric surgery‐induced loss of muscle mass and function. Additionally, we investigated the effects of the intervention on molecular and histological mediators of muscle remodelling. Methods Eighty women with obesity were randomly assigned to a Roux‐en‐Y gastric bypass (RYGB: n = 40, age = 42 ± 8 years) or RYGB plus exercise training group (RYGB + ET: n = 40, age = 38 ± 7 years). Clinical and laboratory parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6 month, three‐times‐a‐week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post‐surgery (for RYGB + ET). A healthy, lean, age‐matched control group was recruited to provide reference values for selected variables. Results Surgery resulted in a similar (P = 0.66) reduction in lower‐limb muscle strength in RYGB and RYGB+ET (−26% vs. −31%), which was rescued to baseline values in RYGB + ET (P = 0.21 vs. baseline) but not in RYGB (P 0.05 vs. baseline) but not RYGB (P > 0.01 vs. baseline). RYGB + ET showed greater Type I (5187 vs. 3898 μm2, P

Abstract Background Enhanced metabolic plasticity and diversification of energy production is a hallmark of highly proliferative breast cancers. This contributes to poor pharmacotherapy efficacy, recurrence, and metastases. We have previously identified a mitochondrial-targeted furazano[3,4-b]pyrazine named BAM15 that selectively reduces bioenergetic coupling efficiency and is orally available. Here, we evaluated the antineoplastic properties of uncoupling oxidative phosphorylation from ATP production in breast cancer using BAM15. Methods The anticancer effects of BAM15 were evaluated in human triple-negative MDA-MB-231 and murine luminal B, ERα-negative EO771 cells as well as in an orthotopic allograft model of highly proliferative mammary cancer in mice fed a standard or high fat diet (HFD). Untargeted transcriptomic profiling of MDA-MB-231 cells was conducted after 16-h exposure to BAM15. Additionally, oxidative phosphorylation and electron transfer capacity was determined in permeabilized cells and excised tumor homogenates after treatment with BAM15. Results BAM15 increased proton leak and over time, diminished cell proliferation, migration, and ATP production in both MDA-MB-231 and EO771 cells. Additionally, BAM15 decreased mitochondrial membrane potential, while inducing apoptosis and reactive oxygen species accumulation in MDA-MB-231 and EO771 cells. Untargeted transcriptomic profiling of MDA-MB-231 cells further revealed inhibition of signatures associated with cell survival and energy production by BAM15. In lean mice, BAM15 lowered body weight independent of food intake and slowed tumor progression compared to vehicle-treated controls. In HFD mice, BAM15 reduced tumor growth relative to vehicle and calorie-restricted weight-matched controls mediated in part by impaired cell proliferation, mitochondrial respiratory function, and ATP production. LC-MS/MS profiling of plasma and tissues from BAM15-treated animals revealed distribution of BAM15 in adipose, liver, and tumor tissue with low abundance in skeletal muscle. Conclusions Collectively, these data indicate that mitochondrial uncoupling may be an effective strategy to limit proliferation of aggressive forms of breast cancer. More broadly, these findings highlight the metabolic vulnerabilities of highly proliferative breast cancers which may be leveraged in overcoming poor responsiveness to existing therapies.

Felix Angst,1 Thomas Benz,1,2 Susanne Lehmann,1 Peter Sandor,1 Stephan Wagner3 1Research Department, Rehaklinik Bad Zurzach, Bad Zurzach, Switzerland; 2ZHAW Zurich University of Applied Sciences, School of Health Professions, Institute of Physiotherapy, Winterthur, Switzerland; 3Department of Angiology, Rehaklinik Bad Zurzach, Bad Zurzach, SwitzerlandCorrespondence: Felix AngstRehaklinik Bad Zurzach, Zurzach Care Group, Quellenstrasse 34, Bad Zurzach, 5330, SwitzerlandTel +41 56 269 51 51Fax +41 56 269 51 70Email fangst@vtxmail.ch; felix.angst@zurzachcare.chObjective: To examine the common and specific characteristics of fibromyalgia and lipedema, two chronic soft-tissue pain syndromes without curative therapy options.Methods: Diseases’ characteristics were compared using the findings of extensive literature and the empiric data from two cohorts, both fulfilling standardized diagnostic criteria. Outcome was measured by various socio-demographics, the generic Short Form 36 (SF-36), the Fibromyalgia Severity Questionnaire (FSQ), and the 6-minute walk distance (6MWD). Empiric SF-36 data were compared to specific population-based norms and between the diagnostic groups, using standardized mean differences (SMD).Results: Female participants with fibromyalgia (n = 77) and lipedema (n = 112) showed comparable education levels and living situations. Lipedema cases were, on average, 3.9 years younger and BMI 6.3kg/m2 more obese. Women with fibromyalgia smoked more, did less sport, had more comorbidities, and worked less. Compared to the norms, health in fibromyalgia was worse than expected by SMD = – 1.60 to – 2.35 and in lipedema by – 0.44 to – 0.82 on the SF-36. The score differences between the two conditions ranged from SMD = – 0.96 to – 1.34 (all p < 0.001) on the SF-36 and the FSQ. For the inpatients (n = 77 fibromyalgia, n = 38 lipedema), the 6MWD was comparable (SMD = – 0.09, p = 0.640). These findings were consistent with detailed data from the literature reviewed.Discussion: Fibromyalgia and lipedema share characteristics of clinical phenomenology and comorbid conditions. Disease perception is more pronounced in fibromyalgia than in lipedema, especially in social and role dysfunction, whereas the walking distance was similar for both syndromes. This difference may be explicable by limited coping skills in fibromyalgia.Keywords: fibromyalgia, lipedema, diagnosis, outcome measures, SF-36

Sorbus aucuparia L. (rowan) and Betula spp. (birch) are the most common of the early successional pioneer tree species in central Europe with the ability to form a soil seed bank. Little is known about the reasons for the high variations observed in the persistence in the soil of rowan and birch seeds. The objective of this study was to assess the ability of buried birch and rowan seeds to form short-term persistent soil seed banks and to analyse the influence of burial depth on seed persistence. An artificial seed burial experiment was initiated to study the persistence of birch seeds and rowan seeds, with and without pulp, stored at depths of 2, 5 and 10 cm in mineral soil over 2.5 years. The predicted maximum storability periods for buried birch seeds was 13 years, compared to 4.5 years for rowan seeds with pulp and 3.5 years without pulp. The lower storage capacity of rowan seeds was demonstrated by germinations in the darkness within soil of 3-22% of seeds without pulp and 4-48% of seeds with pulp. Germination percentages of birch and rowan with and without pulp did not differ between depths. Only burial duration had an effect for either tree species. Birch and rowan seeds are able to form short-term persistent soil seed banks. Birch accumulates a seed reserve in the soil over time, until a change in conditions conducive to germination occurs, while rowan seeds germinate promptly after overcoming seed dormancy. The pulp provides no benefits in relation to the persistence of rowan seeds; rather, it appears to act as a physical inhibitor of germination. Therefore, annual input of fresh seeds is required for the success of rowan. Seed input every few years seems sufficient to guarantee a minimum number of viable birch seeds.

Abstract Background The emergence and spread of antimicrobial resistance and infectious agents have challenged hospitals in recent decades. Our aim was to investigate the circulation of target infectious agents using Geographic Information System (GIS) and spatial–temporal statistics to improve surveillance and control of healthcare-associated infection and of antimicrobial resistance (AMR), using Klebsiella pneumoniae complex as a model. Methods A retrospective study carried out in a 450-bed federal, tertiary hospital, located in Rio de Janeiro. All isolates of K. pneumoniae complex from clinical and surveillance cultures of hospitalized patients between 2014 and 2016, identified by the use of Vitek-2 system (BioMérieux), were extracted from the hospital's microbiology laboratory database. A basic scaled map of the hospital’s physical structure was created in AutoCAD and converted to QGis software (version 2.18). Thereafter, bacteria according to resistance profiles and patients with carbapenem-resistant K. pneumoniae (CRKp) complex were georeferenced by intensive and nonintensive care wards. Space–time permutation probability scan tests were used for cluster signals detection. Results Of the total 759 studied isolates, a significant increase in the resistance profile of K. pneumoniae complex was detected during the studied years. We also identified two space–time clusters affecting adult and paediatric patients harbouring CRKp complex on different floors, unnoticed by regular antimicrobial resistance surveillance. Conclusions In-hospital GIS with space–time statistical analysis can be applied in hospitals. This spatial methodology has the potential to expand and facilitate early detection of hospital outbreaks and may become a new tool in combating AMR or hospital-acquired infection.

BackgroundChikungunya is a widely distributed, re-emerging tropical disease caused by the chikungunya virus (CHIKV). Little is known about the duration for which CHIK RNA are detectable in bodily fluids, especially genital secretions, and current evidence is based on small series or case reports. An understanding of viral dynamics across different body compartments can inform diagnostic testing algorithms and public health prevention interventions.MethodologyA prospective cohort study was conducted to assess the presence and duration of detectable levels of CHIKV RNA in blood, urine, saliva, semen, and vaginal secretions. Men and women (≥ 18 years) with a positive reverse transcriptase-polymerase chain reaction (RT-PCR) test for CHIKV in the acute phase (1-14 days) of the disease were included. After enrollment, clinical data and samples were collected every 15 days over the first 2 months, and a final collection was performed 3 months after recruitment. The Kaplan-Meier interval-censoring method and the parametric Weibull model were fitted to estimate the median time of viral persistence until the lack of CHIKV RNA detection among all body fluids. Punctual estimates of the median time of CHIKV RNA persistence for each fluid were estimated using a 95% confidence interval (CI).ResultsFrom April to December 2019, 170 participants were screened. Of these, 152 (100 women) were enrolled in the study. The median and interquartile range (IQR) ages for men and women were 39.3 (IQR: 26.9, 50.7) and 43.5 (IQR: 33.8, 53.6) years, respectively. CHIKV RNA was detected in 80.3% (122/152) of serum samples, 23.0% (35/152) of urine samples, 30.3% (46/152) of saliva samples, 14.3% (6/42) of semen samples, and 20.2% (20/99) of vaginal secretion samples. The median time until the loss of CHIKV RNA detection was 19.6 days (95% CI, 17.5-21.7) in serum, 25.3 days (95% CI, 17.8-32.8) in urine, 23.1 days (95% CI, 17.9-28.4) in saliva, and 25.8 days (95% CI, 20.6-31.1) in vaginal secretion. The number of semen samples available was too small to make statistical estimates, but a last positive sample was obtained from a participant 56 days after the onset of symptoms.ConclusionsCHIKV RNA could be detected in all bodily fluids studied, including genital secretions during the acute and convalescent phases and additional studies on viral infectivity in semen and vaginal secretions are warranted.

Abstract Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long‐term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet‐induced obesity. Exposure to BAM15 in vitro enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15‐treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid‐rich tissues. We provide the first phenotypic characterization and demonstration of pre‐clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases.

Qualea grandiflora Mart. (Vochysiaceae) is one of the most widespread species within the cerrado formation, which counts amongst the most threatened ecosystems worldwide. Understanding the regeneration ecology of Q. grandiflora is a central requirement for the success of conservation measures and silvicultural management strategies. Exhaustive investigation was carried out into each of the development stages, and the connected processes within the regeneration cycle, to provide a better understanding of the main factors influencing the regeneration ecology and the recruitment dynamics of the species. For this purpose, we analysed 92 different sources of information in this review, divided into two groups (n = 41 with “basic species information” and n = 51 with “specific information about regeneration stages and processes”) relevant for regeneration and silviculture. Our literature review showed the high proportion of studies addressing the processes flowering, pollination and fruiting, whereas the subsequent processes like seed dispersal, seed storage, germination and seedling development are almost entirely lacking. This also applies for spatial information about environmental conditions and the related regeneration processes in Q. grandiflora. This knowledge is important for management, for example, knowledge of the critical distances between flowering and seed producing trees to ensure genetically diverse regeneration and the identification of safe sites for seedling establishment. Most of the practical suggestions in relation to increasing densities or growth of Q. grandiflora seedlings and saplings made in the literature are linked to less intensive fire management strategies adopted at certain times. The use of selective herbivory to reduce the increasing competition pressure exerted by invasive grasses and hampering Q. grandiflora seedlings is also cited. In this study we highlight the need for more complex species-specific information following the development stages and processes of the regeneration cycle so as to prepare a continuous strategy with a range of management approaches.

Rameshwar Patil,1 Anna Galstyan,1 Zachary B Grodzinski,1 Ekaterina S Shatalova,1 Shawn Wagner,2 Liron L Israel,1 Hui Ding,1 Keith L Black,1 Julia Y Ljubimova,1,3 Eggehard Holler1 1Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Oncology Translational Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USACorrespondence: Eggehard HollerNanomedicine Research Center, Department of Neurosurgery, Cedars Sinai Medical Center, 127 S. San Vicente Boulevard, Suite A8304, Los Angeles, CA 90048 Tel +1 310 423-6630Email eggehard.holler@cshs.orgBackground: Position of gadolinium atom(s) plays a key role in contrast enhancement of gadolinium-based contrast agents. To gain a better understanding of effects of distance of gadolinium in relation to the nanoconjugate platform, we designed and synthesized single- and multi-arm (“star”) gadolinium conjugates equipped with antibody and peptides for targeting. The contrast agents were studied for their tumor imaging performance in a glioma mouse model.Materials and Methods: Antibody- and peptide-targeted nano contrast agents (NCAs) were synthesized using polymalic acid platforms of different sizes. Gadolinium-DOTA and intermediates were attached as amides and targeting agents such as antibodies and peptides as thioethers. For in vivo experiments, we used human U87MG xenografts as glioma models. Magnetic resonance imaging (MRI) was performed on a Bruker BioSpec 94/20USR 9.4 T small-animal scanner. Delivery of contrast agents across the blood–brain barrier was studied by fluorescent microscopy.Results: All contrast agents accumulated into tumor and showed composition-dependent imaging performance. Peptide-targeted mini-NCAs had hydrodynamic diameters in the range 5.2– 9.4 nm and antibody-targeted NCAs had diameters in the range 15.8– 20.5 nm. Zeta potentials were in the range of – 5.4–− 8.2 mV and − 4.6–− 8.8 mV, respectively. NCAs showed superior relaxivities compared to MultiHance at 9.4 T. The signal enhancement indicated maximum accumulation in tumor 30– 60 minutes after intravenous injection of the mouse tail vein. Only targeted NCAs were retained in tumor for up to 3 hours and displayed contrast enhancement.Conclusion: The novel targeted NCAs with star-PEG features displayed improved relaxivity and greater contrast compared with commercial MultiHance contrast agent. The enhancement by mini-NCAs showed clearance of tumor contrast after 3 hours providing a suitable time window for tumor diagnosis in clinics. The technology provides a great tool with the promise of differential MRI diagnosis of brain tumors.Keywords: magnetic resonance imaging, Gd-DOTA, structure variation, blood–brain barrier, tumor targeting, accelerated diagnosis

Summary: Background: Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (Aβ) positivity as determined by position emission tomography (PET), and if an ordinal sequence of p-tau epitopes occurs at this incipient phase Methods: We measured CSF concentrations of p-tau181, p-tau217 and p-tau231 in 171 participants across the AD continuum who had undergone Aβ ([18F]AZD4694) and tau ([18F]MK6240) position emission tomography (PET) and clinical assessment Findings: All CSF p-tau biomarkers were accurate predictors of cognitive impairment but CSF p-tau217 demonstrated the largest fold-changes in AD patients in comparison to non-AD dementias and cognitively unimpaired individuals. CSF p-tau231 and p-tau217 predicted Aβ and tau to a similar degree but p-tau231 attained abnormal levels first. P-tau231 was sensitive to the earliest changes of Aβ in the medial orbitofrontal, precuneus and posterior cingulate before global Aβ PET positivity was reached Interpretation: We demonstrate that CSF p-tau231 increases early in development of AD pathology and is a principal candidate for detecting incipient Aβ pathology for therapeutic trial application Funding: Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Weston Brain Institute, Brain Canada Foundation, the Fonds de Recherche du Québec.

IntroductionThe World Health Organization recognizes dementia as a public health priority and highlights research as an action to respond to the consequences, with early career dementia researchers (ECDRs) representing the key driving force. Due to the COVID-19 pandemic, however, biomedical and psychosocial dementia research was strained worldwide. The aim of this study was to understand the impact of the pandemic on ECDRs.MethodsIn autumn 2021, the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Professional Interest Area to Elevate Early Career Researchers (PEERs) and University College London conducted an online survey querying ECDRs' experiences during the COVID-19 pandemic. The survey was shared through the ISTAART network, social media, podcasts, and emailing lists. Data were analyzed using descriptive and inferential statistics.ResultsSurvey data from n = 321 ECDRs from 34 countries were analyzed (67.6% women; 78.8% working in academia). Overall, 77.8% of ECDRs surveyed indicated research delays, 53.9% made project adjustments, 37.9% required additional or extended funding, and 41.8% reported a negative impact on career progression. Moreover, 19.9% felt unsupported by their institutions and employers (33% felt well supported, 42.7% somewhat supported). ECDR's conference attendance remained the same (26.5%) or increased (More: 28.6%; a lot more: 5.6%) since the start of the pandemic. Continental differences were visible, while the impact of the pandemic did not differ greatly based on ECDRs' sociodemographic characteristics.ConclusionsThe COVID-19 pandemic had a substantial impact on ECDRs worldwide and institutions, employers, and funding bodies are urged to consider the implications and lessons-learned when working with, managing, and promoting ECDRs. Strategies related to the pandemic and general career support to improve ECDRs career progression are discussed, including social media training, digital networking, and benefits of hybrid events. Global resources specific for ECDRs are highlighted.

Abstract Background Young people can receive mental health care from many sources, from formal and informal sectors. Caregiver characteristics/experiences/beliefs may influence whether young people get help and the type of care or support used by their child. We investigate facilitators/barriers to receiving formal and/or informal care, particularly those related to the caregiver’s profile. Methods We interviewed 1,400 Brazilian primary caregivers of young people (aged 10–19), participants of a high-risk cohort. Caregivers reported on young people’s formal/informal mental health care utilization, and associated barriers and facilitators to care. Data were also collected on youth mental health and its impact on everyday life; and caregiver characteristics—education, socioeconomics, ethnicity, mental health, and stigma. Logistic regression models were used to examine the relationship between caregiver and young people characteristics with formal/informal care utilization. Results Persistence and greater impact of youth mental health conditions were associated with a higher likelihood of care, more clearly for formal care. Caregiver characteristics, however, also played a key role in whether young people received any care: lower parental stigma was associated with greater formal service use, and lower socioeconomic class showed higher odds of informal care (mainly from religious leaders). Conclusions This study highlights the key role of the caregivers as gatekeepers to child treatment access, particularly parental stigma influencing whether young people received any mental health care, even in a low resource setting. These results help to map barriers for treatment access and delivery for young people, aiming to improve intervention efforts and mental health support.

Abstract Introduction Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well‐described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three‐range approach and its prognostic impact remains under‐explored for cerebrospinal fluid (CSF) biomarkers . Methods With two‐graph receiver‐operating characteristics based on different reference schemes, we derived three‐range cut‐points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid–beta (Aβ) positron emission tomography (PET) accumulation in non‐demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n = 1246). In all analyses, we compared herein‐derived three‐range CSF cut‐points to previously described binary ones. Results In our main longitudinal analyses, we highlight CSF p‐tau181/Aβ1‐42 three‐range cut‐points derived based on the cognitively normal Aβ‐PET negative versus dementia Aβ‐PET positive reference scheme for best depicting a prognostically relevant biomarker abnormality range. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization and a clearly abnormal group at higher risk for cognitive decline, with power analyses suggesting the latter group as potential trial enrichment candidates. Furthermore, we demonstrate that individuals with intermediate‐range CSF status have similar rates of Aβ deposition to those in the clearly abnormal group. Discussion The proposed approach can refine clinico‐biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker‐related cognitive decline in comparison to binary cut‐points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.

The electrical power system is susceptible to several faults, which can cause the system to malfunction. Among these, the ones that occur in the busbars of substations stand out. The main bus of a substation can concentrate a large amount of power and many derivations to service electrical loads, making it an element of high importance for the reliability of the system. Although the buses have a low incidence of faults, they are considered critical elements of the electrical power system, as their operating output can cause a large number of forced outages. This situation makes the protection of this component of paramount importance. There are currently two widely used bus differential protection techniques: high-impedance and low-impedance bus differential protection. The second technique is more commonly used due to the possibility of sharing current transformers (CTs). However, the high cost and greater requirements for maintenance makes the differential protection of busbars in distribution or sub-transmission substations unfeasible. With the advent and implementation of the IEC 61850 standard, modern protection systems based on this standard offer significant advantages, such as lower expenses with installation, wiring, commissioning and maintenance; adaptable bus configuration; use of different CT ratios; considerably minimized susceptibility to CT saturation; lower risks of open secondary CT circuits and viability of implantation in distribution substations. The objective of this review is to present an overview of the works found in the literature on substation busbar differential protection, considering classical methods and those based on the IEC 61850 standard.

Abstract The use of biopesticides based on Bacillus thuringiensis (Berliner 1915) in agriculture has been considered harmless for non-target organisms such as fish. The present study aimed to investigate the effects of a biopesticide based on B. thuringiensis on the physiology and histology of the liver, kidney and intestine of Arapaima gigas (Schinz, 1822), via exposure to water (0.13 g/L) and in the diet (0.13 g), after 24 and 48 h. Fish subjected to B. thuringiensis in the water of their breeding and feeding tanks exhibited mortality due to changes in erythrogram (hematocrit, hemoglobin, erythrocytes), thrombogram and leucogram blood parameters, and plasma (sodium, chloride, potassium, cholesterol, glucose, triglycerides, cortisol and total proteins) and enzymatic (Aspartate Amino Transferase and Alanine Amino Transferase) biochemistry. Histopathological alterations in the liver and kidney ranged from mild to severe and were characterized by the presence of cytoplasmic vacuolization, nuclear hypertrophy and atrophy, melanomacrophage centers and necrosis, and in the intestine by changes to the number of villi and goblet cells. Therefore, these physiological and histopathological alterations indicate that care should be taken with the dispersion of biopesticides based on agricultural B. thuringiensis in fish farming.

This work proposes a facile methodology for producing porous biochar material (ABC) from açaí kernel residue, produced by chemical impregnation with ZnCl2 (1:1) and pyrolysis at 650.0 °C. The characterization was achieved using several techniques, and the biochar material was employed as an adsorbent to remove catechol. The results show that ABC carbon has hydrophilic properties. The specific surface area and total pore volume are 1315 m2·g−1 and 0.7038 cm3·g−1, respectively. FTIR revealed the presence of oxygenated groups, which can influence catechol adsorption. The TGA/DTG indicated that the sample is thermally stable even at 580 °C. Adsorption studies showed that equilibrium was achieved in Qmax is 339.5 mg·g−1 (40 °C) with 98.36% removal of simulated effluent, showing that açaí kernel is excellent biomass to prepare good biochar that can be efficiently used to treat real industrial effluents.

PurposeThe aim of this exploratory study was to investigate whether the degree of weight loss properly reflects improvements in cardiometabolic health among patients who underwent Roux-en-Y gastric bypass.MethodsIn this ancillary analysis from a clinical trial, patients were clustered into tertiles according to the magnitude of the percentage weight loss (1st tertile: “higher weight loss”: −37.1 ± 5.8%; 2nd tertile: “moderate weight loss”: −29.7 ± 1.4%; 3rd tertile: “lower weight loss”: −24.2 ± 2.3%). Delta changes (9 months after surgery-baseline) in clustered cardiometabolic risk (i.e., blood pressure index, fasting glucose, high-density lipoprotein [HDL] and triglycerides [TG]), glycated hemoglobin (HbA1c), homeostasis model assessment (HOMA-IR), and C-reactive protein (CRP) were calculated.ResultsA total of 42 patients who had complete bodyweight data (age = 40 ± 8 year; BMI = 47.8 ± 7.1 kg/m2) were included. Surgery led to substantial weight loss (−37.9 ± 11.3 kg, P < 0,001), and clinically significant improvements in blood pressure index (−17.7 ± 8.2 mmHg, P < 0.001), fasting glucose (−36.6 ± 52.5 mg/dL, P < 0.001), HDL (9.4 ± 7.1 mg/dL, P < 0.001), TG (−35.8 ± 44.1 mg/dL P < 0,001), HbA1c (−1.2 ± 1.6%, P < 0.001), HOMA-IR (−4.7 ± 3.9 mg/dL, P < 0.001) and CRP (−8.5 ± 6.7 μg/mL P < 0.001). Comparisons across tertiles revealed no differences for cardiometabolic risk score, fasting glucose, HbAc1, HOMA-IR, blood pressure index, CRP, HDL, and TG (P > 0.05 for all). Individual variable analysis confirmed cardiometabolic improvements across the spectrum on weight-loss. There were no associations between weight loss and any dependent variable.ConclusionWeight loss following bariatric surgery does not correlate with improvements in cardiovascular risk factors. These findings suggest that weight loss alone may be insufficient to assess the cardiometabolic success of bariatric surgery, and the search for alternate proxies that better predict surgery success are needed.

The ability of short-lived tree species such as birch, alder, willow, poplar and rowan to form even a short-term soil seed bank is discussed controversially in the literature. Soil seed banks are an important component of succession and regeneration in ecosystems. Following disturbance, buried viable seeds germinate and the seedlings that establish cover the disturbed, exposed soil surfaces. The objective of this study was to undertake a literature review of soil seed bank research carried out in central and north-west European temperate forests to provide an overview of the ability of pioneer tree species to form a viable seed bank. The review of 33 publications revealed that birch is the only pioneer tree species of temperate forests with longer-lived seeds, persisting in the soil for 1 - 5 years. Birch seeds remain viable in deeper soil layers (5 - 10 cm), so birch may be assigned to the short-term persistent soil seed bank type. The seeds of alder, willow and poplar would appear to be short-lived. Maximum seed densities of all tree species were found in the upper soil layers. With increasing soil depth, seed density declined. Viable seeds of rowan were not detected in any of the soil seed bank studies, although seed trees were present. We found that in spite of the capacity for long seed dispersal distances, high densities of birch, alder and willow seeds were only observed in close proximity to seed trees. The higher the numbers of seed trees, the higher the seed densities in soils. Maximum seed densities were recorded during and shortly after seed rains had occurred. Our results reveal that a birch seed bank may compensate for years with lower levels of seed production. However, as the seed bank is only short-term persistent, it must be supplemented by fresh seeds from surrounding seed trees as often as possible to guarantee a continuous capacity for regeneration.

Jimmy Pruitt III,1 Carolina Moracho-Vilrriales,1,2 Tiffaney Threatt,3 Sarah Wagner,3 Jun Wu,1 E Alfonso Romero-Sandoval1 1Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Biochemistry and Biotechnology, University of Alcalá de Henares, Madrid, Spain; 3Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Diabetic peripheral neuropathy (DPN) represents significant burdens to many patients and the public health-care system. Patients with diabetes in rural areas have higher risk of developing complications and having less access to proper treatment. We studied a rural population of patients with diabetes who attended a pharmacist-led free clinic for a diabetic education program. Our objectives were to 1) determine the prevalence of DPN and painful diabetic neuropathy (p-DN) in patients with type 2 diabetes; 2) assess the proportion of patients with DPN and p-DN left undocumented upon physician referral to a pharmacist-led free clinic; and 3) determine the appropriateness of pain medication regimen. We performed a retrospective analysis of clinical records of patients from the Presbyterian College School of Pharmacy (PCSP) Wellness Center located in Clinton, SC. Diagnoses of DPN and/or p-DN were obtained from referral notes in the clinical records and compared with results from foot examinations performed in the free clinic and clinical features. Medication regimens were also obtained and compared using American Academy of Neurology (AAN) treatment guidelines. Within our study population (n=111), the prevalence of DPN was 62.2% (national average of 28%–45%) and that of p-DN was 23.4% (national average of 11%–24%). In p-DN patients (n=26), 53.8% (n=14) had a documented diagnosis of p-DN by the referring physician, and 46.2% (n=12) were identified by the pharmacists. A total of 95% (19 of 20) of the patients treated for p-DN received adequate pharmacological agents, though suboptimal as per clinical guidelines. More than 50% of the patients used subtherapeutic doses of their medications. Gabapentin was the most frequently used medication in our population (65.4%). Patients in rural South Carolina had a higher prevalence of DPN and p-DN with >60% undocumented cases of p-DN. More than 95% of treated patients did not receive optimum therapy according to AAN guidelines. Keywords: polysensory neuropathy, pharmacist-led diabetes clinic, diabetes educator, gabapentin, chronic pain free clinic, pain, gabapentin

Thermal comfort of wheelchairs still requires improvements, since users remain on the chair for as long as 12 h a day. Increased sweating makes the skin more susceptible to colonization by fungi and bacteria, and may cause pressure ulcers. In this sense, the microencapsulation of Phase-Change Materials (PCMs) may help to enhance wheelchair cushion comfort by regulating heat exchange. This study describes the production of PCM microcapsules and their application in flexible polyurethane foams after expansion, and assesses improvements in heat exchange. Microcapsules with eicosane core coated with melamine-formaldehyde were produced. Eicosane is a thermoregulation agent whose phase-change temperature is near that of the human body’s. Microcapsules were characterized by thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy. Then, microcapsules were applied on polyurethane foams by vacuum filtration and high-pressure air gun. Samples were exposed to a heat source and analysed by infrared thermography. The results indicate that thermal load increased in samples treated with microcapsules, especially by pressure air gun, and show that it is possible to enhance thermal comfort in wheelchair seats. Thereby, this study contributes to enhance quality of life for wheelchair users, focusing on thermal comfort provided by cushion seats made from PU foam.

The literature lacks studies investigating the performance of supplemented replacement heifers grazing on intensively managed warm-season pasture. Our objective was to evaluate the effects of supplement composition (energetic or protein) on the performance, muscle development, thermogenisis, nutrient intake, and digestibility of replacement Holstein heifers grazing Mombaça grass. Eighteen Holstein heifers with an average age and initial body weight (BW) of 12.57 ± 2.54 mo and 218.76 ±47.6 kg, respectively, were submitted to a randomized block design, with six replicates on a rotational grazing system of Panicum maximum cv. Mombaça pasture. Treatments were: control (CON; mineral salt ad libitum); energy supplement (ENE; corn meal as supplement, 8% CP and 3.78 Mcal/kg DE); and protein supplement (PRO; corn and soybean meal, 25% CP and 3.66 Mcal/kg DE). Supplements were individually fed at 0.5% BW. The experiment lasted 120 days, subdivided into three periods. Titanium dioxide and indigestible neutral detergent fiber (iNDF) were used to estimate the intakes and digestibility of the nutrients. BW, wither height, thoracic circumference, body length, and ultrasound of ribeye fat thickness measurements were taken once per period. Body condition score (BCS) was assessed twice during the experiment. The MIXED procedure of SAS, including period as a repeated measure, was used and significance was declared at P ≤ 0.05. Dry matter intake (DMI), CP intake (CPI) and DE intake were greater in heifers fed PRO compared to CON and ENE. Heifers supplemented with ENE had the lowest DMI. Treatment affected pasture intake/BW; it was similar between PRO and CON heifers, and lower for the ENE treatment. A treatment × period interaction was observed for NDF intake (%BW), in which heifers fed PRO and CON had the greatest NDF intake and ENE had the lowest. The digestibility of DM was the greatest in PRO-supplemented heifers and the lowest in CON heifers. Heifers fed ENE had decreased CP digestibility compared to PRO and CON heifers. Average daily gain (ADG) and thoracic circumference gain were greatest in the PRO treatment. BCS was greater in PRO compared to CON and ENE heifers. Supplementing Holstein heifers at 0.5% BW using PRO supplementation resulted in better animal performance, primarily greater ADG, than feeding ENE or not supplementing (CON). In conclusion, our results indicate that dairy heifers should be fed a protein supplement when grazing intensively managed Mombaça grass pasture.