Parental developmental experience affects vocal learning in offspring.

Cultural and genetic inheritance combine to enable rapid changes in trait expression, but their relative importance in determining trait expression across generations is not clear. Birdsong is a socially learned cognitive trait that is subject to both cultural and genetic inheritance, as well as being affected by early developmental conditions. We sought to test whether early-life conditions in one generation can affect song acquisition in the next generation. We exposed one generation (F1) of nestlings to elevated corticosterone (CORT) levels, allowed them to breed freely as adults, and quantified their son's (F2) ability to copy the song of their social father. We also quantified the neurogenetic response to song playback through immediate early gene (IEG) expression in the auditory forebrain. F2 males with only one corticosterone-treated parent copied their social father's song less accurately than males with two control parents. Expression of ARC in caudomedial nidopallium (NCM) correlated with father-son song similarity, and patterns of expression levels of several IEGs in caudomedial mesopallium (CMM) in response to father song playback differed between control F2 sons and those with a CORT-treated father only. This is the first study to demonstrate that developmental conditions can affect social learning and neurogenetic responses in a subsequent generation.

"Like another human being in the room": a community case study of smart speakers to reduce loneliness in the oldest-old.

This community case study examined the potential benefits of smart speakers to tackle loneliness in the oldest old adults living in supported accommodation. The program was established as a collaboration between the supported accommodation provider and a technology company to explore the feasibility of smart speakers to alleviate resident loneliness. Loneliness in later life often accompanies a shrinking social circle, loss of a spouse or increased disability. People aged 85 years of age and over are increasingly likely to experience these life events, leading to an increased risk of social isolation and loneliness. Five older people, mean age 90 years of age, who resided in supported accommodation, were given a smart speaker for 8 weeks to examine their experience with the voice assistant. The experiences of the five older adults are explored as case studies, with each person interviewed both before and after receiving the smart speaker. All five valued their smart speaker, recognised its potential for tackling loneliness, and wanted to keep it. The three most lonely individuals reported that their smart speaker made them feel less lonely and isolated through two mechanisms: (i) creating a presence and (ii) having some control over their situation. Although only a small study, these experiences suggest providing smart speakers for lonely and isolated oldest-old people, could be one way to help combat loneliness in community settings.

Characterising 24-h skeletal muscle gene expression alongside metabolic & endocrine responses under diurnal conditions.

CONTEXT: Skeletal muscle plays a central role in the storage, synthesis, and breakdown of nutrients, yet little research has explored temporal responses of this human tissue, especially with concurrent measures of systemic biomarkers of metabolism. OBJECTIVE: To characterise temporal profiles in skeletal muscle expression of genes involved in carbohydrate metabolism, lipid metabolism, circadian clocks, and autophagy and descriptively relate them to systemic metabolites and hormones during a controlled laboratory protocol. METHODS: Ten healthy adults (9M/1F, mean ± SD: age: 30 ± 10 y; BMI: 24.1 ± 2.7 kg·m-2) rested in the laboratory for 37 hours with all data collected during the final 24 hours of this period (i.e., 0800-0800 h). Participants ingested hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200-0700 h. Blood samples were collected hourly for endocrine and metabolite analyses, with muscle biopsies occurring every 4 h from 1200 h to 0800 h the following day to quantify gene expression. RESULTS: Plasma insulin displayed diurnal rhythmicity peaking at 1804 h. Expression of skeletal muscle genes involved in carbohydrate metabolism (Name - Acrophase; GLUT4 - 1440 h; PPARGC1A -1613 h; HK2 - 1824 h) and lipid metabolism (FABP3 - 1237 h; PDK4 - 0530 h; CPT1B - 1258 h) displayed 24 h rhythmicity that reflected the temporal rhythm of insulin. Equally, circulating glucose (0019 h), NEFA (0456 h), glycerol (0432 h), triglyceride (2314 h), urea (0046 h), CTX (0507 h) and cortisol concentrations (2250 h) also all displayed diurnal rhythmicity. CONCLUSION: Diurnal rhythms were present in human skeletal muscle gene expression as well systemic metabolites and hormones under controlled diurnal conditions. The temporal patterns of genes relating to carbohydrate and lipid metabolism alongside circulating insulin are consistent with diurnal rhythms being driven in part by the diurnal influence of cyclic feeding and fasting.

Substituting carbohydrate at lunch for added protein increases fat oxidation during subsequent exercise in healthy males.

CONTEXT: How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear. OBJECTIVE: Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake. METHODS: Twelve healthy males completed three trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 h (∼16:15) and post-exercise ad-libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and acylated ghrelin (AG) were measured for 5 h post-lunch. RESULTS: Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (p < 0.001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; p < 0.05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all p < 0.01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all p < 0.01). AG was lower during HI-CARB and LO-CARB versus FAST (p < 0.01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; p < 0.001) and HI-CARB (-313 ± 284 kcal; p < 0.001). CONCLUSION: Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake.

Combined Turmeric, Vitamin C, and Vitamin D Ready-to-Drink Supplements Reduce Upper Respiratory Illness Symptoms and Gastrointestinal Discomfort in Elite Male Football Players.

Elite football is associated with the increased risk of illness, although targeted supplementation can reduce illness risk. This study assessed the effects of a supplement containing turmeric root within a black pepper and fat-soluble blend, vitamin C and vitamin D, on upper respiratory symptoms (URS), gastrointestinal symptoms (GIS), muscle soreness, and markers of inflammation and gut permeability in elite male footballers. Twenty-three footballers completed 3 weeks of no intervention (CON), followed by 16 weeks of daily consuming 60 mL of a commercially available supplement containing raw turmeric root (17.5 g, estimated to contain 700 mg of curcumin), vitamin C (1000 mg), and vitamin D3 (3000 IU/75 mcg) (SUP). URS and GIS were measured daily. Immediately (0 h), 40, and 64 h after six competitive matches (two in CON, four in SUP), the subjective soreness and plasma concentrations of creatine kinase [CK], c-reactive protein [CRP], and intestinal fatty-acid binding protein [I-FABP] were assessed. URS incidence (p < 0.001), GIS (p < 0.05), and plasma [I-FABP] at 0 h (p < 0.05) were greater during CON versus SUP. At 40 h, [CRP] was greater than 0 h during CON (p < 0.01) but not SUP (p = 0.204). There were no differences in soreness or [CK]. This study indicates that turmeric root, vitamin C, and vitamin D supplementation over 16 weeks can reduce URS, GIS, and post-match [I-FABP] in elite footballers.

Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study.

BACKGROUND: Atrophied T2-lesion volume (aT2-LV) is an exploratory imaging marker in multiple sclerosis (MS) reflecting the volume of lesions subsumed into cerebrospinal fluid (CSF). OBJECTIVE: To investigate the effect of ocrelizumab (OCR) versus placebo (PBO) over 120 weeks on the accumulation of aT2-LV in a double-blind placebo-controlled (DBP) phase 3, primary-progressive (PP) MS study (ORATORIO; NCT01194570). METHODS: This post-hoc, MRI-blinded analysis evaluated 732 PPMS randomised to OCR (488) or PBO (244). Atrophied T2-LV was calculated by overlaying baseline T2-lesion masks on follow-up CSF maps. Clinical data from DBP and open-label extension (OLE) periods were available. Treatment effect was evaluated by a mixed-effect model with repeated measures, while logistic regression explored the association of aT2-LV at week 120 and clinical outcomes in the OLE period. RESULTS: OCR treatment significantly reduced accumulation of aT2-LV compared with PBO (319.4 mm3 vs 366.1 mm3, p=0.015) at 120 weeks. OCR showed superiority over PBO in reducing aT2-LV in patients who developed confirmed disability progression (CDP) during the DBP period at 12 (CDP12) and 24 (CDP24) weeks for the composite of Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test and Timed 25-Foot Walk test. Accumulation of aT2-LV at week 120 was related to CDP12-EDSS (p=0.018) and CDP24-EDSS (p=0.022) in the OLE for the patients who were treated by PBO in the DBP only. CONCLUSIONS: OCR showed a significant effect of reducing the accumulation of aT2-LV in PPMS in the DBP period and was related to CDP-EDSS in OLE only in the PBO arm.

Concurrent invasions of European starlings in Australia and North America reveal population-specific differentiation in shared genomic regions.

A species' success during the invasion of new areas hinges on an interplay between the demographic processes common to invasions and the specific ecological context of the novel environment. Evolutionary genetic studies of invasive species can investigate how genetic bottlenecks and ecological conditions shape genetic variation in invasions, and our study pairs two invasive populations that are hypothesized to be from the same source population to compare how each population evolved during and after introduction. Invasive European starlings (Sturnus vulgaris) established populations in both Australia and North America in the 19th century. Here, we compare whole-genome sequences among native and independently introduced European starling populations to determine how demographic processes interact with rapid evolution to generate similar genetic patterns in these recent and replicated invasions. Demographic models indicate that both invasive populations experienced genetic bottlenecks as expected based on invasion history, and we find that specific genomic regions have differentiated even on this short evolutionary timescale. Despite genetic bottlenecks, we suggest that genetic drift alone cannot explain differentiation in at least two of these regions. The demographic boom intrinsic to many invasions as well as potential inversions may have led to high population-specific differentiation, although the patterns of genetic variation are also consistent with the hypothesis that this infamous and highly mobile invader adapted to novel selection (e.g., extrinsic factors). We use targeted sampling of replicated invasions to identify and evaluate support for multiple, interacting evolutionary mechanisms that lead to differentiation during the invasion process.

Turmeric supplementation improves markers of recovery in elite male footballers: a pilot study.

Football match-play causes muscle damage and provokes an inflammatory response. Rapid recovery is paramount to optimising subsequent performance and reducing injury risk. Turmeric contains high concentrations of curcumin, a polyphenol that has been shown to reduce muscle damage and soreness post-exercise in recreational exercisers. However, it is unknown whether a curcumin-containing supplement can support elite footballers recovery between matches. This applied study explored whether a turmeric supplement could improve performance, subjective and physiological markers of recovery, in elite male footballers. Twenty-four elite male footballers divided into a turmeric group, who consumed 60 mL of a turmeric drink twice per day, or a control group who did not. After 96 h of rest, baseline measurements of subjective soreness (leg and whole-body), plasma creatine kinase ([CK]), plasma C-reactive protein ([CRP]), isometric mid-thigh pull (IMTP) and counter movement jump (CMJ), were collected. Following eight competitive matches, subjective leg and whole-body soreness and plasma concentrations of inflammation markers ([CK] and [CRP]) were assessed immediately (0 h), 40 and 64 h post-match. Performance markers (IMTP and CMJ) were also assessed at 40 and 64 h post-match. Percentage change from baseline showed a main effect of group (p = 0.035, p = 0.005) and time (p = 0.002, p = 0.002) for both leg and whole-body soreness, respectively. There was a group by time interaction effect (p = 0.049) for [CRP]. There were no effects of turmeric on [CK], CMJ or IMTP. This applied study is the first in elite footballers to show that a curcumin-containing supplementation may attenuate a biomarker of inflammation [CRP] and soreness post-match play.

Intermittent fasting and bone health: a bone of contention?

Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarise and critically evaluate the preclinical and clinical evidence on IF regimens (the 5:2 diet, alternate-day fasting (ADF) and time-restricted eating (TRE)/time-restricted feeding and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions; thus, findings from these studies are difficult to apply to humans. While limited in scope, observational studies suggest a link between some IF practices (e.g. breakfast omission) and compromised bone health, although lack of control for confounding factors makes these data difficult to interpret. Interventional studies suggest that TRE regimens practised up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (< 5 % of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the '5­2' diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by dual-energy X-ray absorptiometry) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes and designed to include clinically relevant bone assessments.

Multi-arm U-Net with dense input and skip connectivity for T2 lesion segmentation in clinical trials of multiple sclerosis.

T2 lesion quantification plays a crucial role in monitoring disease progression and evaluating treatment response in multiple sclerosis (MS). We developed a 3D, multi-arm U-Net for T2 lesion segmentation, which was trained on a large, multicenter clinical trial dataset of relapsing MS. We investigated its generalization to other relapsing and primary progressive MS clinical trial datasets, and to an external dataset from the MICCAI 2016 MS lesion segmentation challenge. Additionally, we assessed the model's ability to reproduce the separation of T2 lesion volumes between treatment and control arms; and the association of baseline T2 lesion volumes with clinical disability scores compared with manual lesion annotations. The trained model achieved a mean dice coefficient of ≥ 0.66 and a lesion detection sensitivity of ≥ 0.72 across the internal test datasets. On the external test dataset, the model achieved a mean dice coefficient of 0.62, which is comparable to 0.59 from the best model in the challenge, and a lesion detection sensitivity of 0.68. Lesion detection performance was reduced for smaller lesions (≤ 30 µL, 3-10 voxels). The model successfully maintained the separation of the longitudinal changes in T2 lesion volumes between the treatment and control arms. Such tools could facilitate semi-automated MS lesion quantification; and reduce rater burden in clinical trials.

Effects of Morning Vs. Evening exercise on appetite, energy intake, performance and metabolism, in lean males and females.

Exercise is an important component of a weight management strategy. However, little is known about whether circadian variations in physiological and behavioural processes can influence the appetite and energy balance responses to exercise performed at different times of the day. This study compared the effects of morning and evening exercise on appetite, post-exercise energy intake, and voluntary performance. In randomised, counterbalanced order, 16 healthy males and females (n = 8 each) completed two trials, performing morning exercise at 10:30 (AMEx) or evening exercise at 18:30 (PMEx). Exercise consisted of 30 min steady-state cycling (60% V˙ O2peak), and a 15-min performance test. A standardised meal (543 ± 86 kcal) was consumed 2-h before exercise and ad-libitum energy intake was assessed 15 min after exercise, with subjective appetite measured throughout. Absolute ad-libitum energy intake was 152 ± 126 kcal greater during PMEx (P < 0.001), but there was no differences in subjective appetite between trials immediately pre-exercise, or immediately before the post-exercise meal (P ≥ 0.060). Resting energy expenditure (P < 0.01) and carbohydrate oxidation (P < 0.05) were greater during AMEx, but there were no differences in substrate oxidation or energy expenditure during exercise (P ≥ 0.155). Exercise performance was not different between trials (P = 0.628). In conclusion, acute morning and evening exercise prompt similar appetite responses, but post-exercise ad-libitum energy intake is greater following evening exercise. These findings demonstrate discordant responses between subjective appetite and ad-libitum energy intake but suggest that exercise might offset circadian variations in appetite. Longer-term studies are required to determine how exercise timing affects adherence and weight management outcomes to exercise interventions. TRIAL REGISTRATION: NCT04742530, February 8, 2021.

Fasting Before Evening Exercise Reduces Net Energy Intake and Increases Fat Oxidation, but Impairs Performance in Healthy Males and Females.

Acute morning fasted exercise may create a greater negative 24-hr energy balance than the same exercise performed after a meal, but research exploring fasted evening exercise is limited. This study assessed the effects of 7-hr fasting before evening exercise on energy intake, metabolism, and performance. Sixteen healthy males and females (n = 8 each) completed two randomized, counterbalanced trials. Participants consumed a standardized breakfast (08:30) and lunch (11:30). Two hours before exercise (16:30), participants consumed a meal (543 ± 86 kcal; FED) or remained fasted (FAST). Exercise involved 30-min cycling (∼60% VO2peak) and a 15-min performance test (∼85% VO2peak; 18:30). Ad libitum energy intake was assessed 15 min postexercise. Subjective appetite was measured throughout. Energy intake was 99 ± 162 kcal greater postexercise (p < .05), but 443 ± 128 kcal lower over the day (p < .001) in FAST. Appetite was elevated between the preexercise meal and ad libitum meal in FAST (p < .001), with no further differences (p ≥ .458). Fat oxidation was greater (+3.25 ± 1.99 g), and carbohydrate oxidation was lower (-9.16 ± 5.80 g) during exercise in FAST (p < .001). Exercise performance was 3.8% lower in FAST (153 ± 57 kJ vs. 159 ± 58 kJ, p < .05), with preexercise motivation, energy, readiness, and postexercise enjoyment also lower in FAST (p < .01). Fasted evening exercise reduced net energy intake and increased fat oxidation compared to exercise performed 2 hr after a meal. However, fasting also reduced voluntary performance, motivation, and exercise enjoyment. Future studies are needed to examine the long-term effects of this intervention as a weight management strategy.

Evaluating the Safety and Efficacy of Crenezumab vs Placebo in Adults With Early Alzheimer Disease: Two Phase 3 Randomized Placebo-Controlled Trials.

Importance: Alzheimer disease (AD), a neurodegenerative disease characterized by ß-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression. Objective: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting ß-amyloid oligomers, in participants with prodromal to mild (early) AD. Design, Setting, and Participants: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD. CREAD (194 sites in 30 countries) and CREAD2 (209 sites in 27 countries) were global multicenter studies. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. Both trials enrolled individuals aged 50 to 85 years with early AD. Participants with some comorbidities and evidence of cerebral infarction or more than 4 microbleeds or areas of leptomeningeal hemosiderosis on magnetic resonance imaging were excluded. After 2923 and 2858 were excluded, respectively, 813 participants in CREAD and 806 in CREAD2 were randomly assigned in a 1:1 ratio to either placebo or crenezumab. In the final analysis, there were 409 participants in the placebo group and 404 in the crenezumab group in CREAD and 399 in the placebo group and 407 in the crenezumab group in CREAD2. Data were analyzed up until January 2019 and August 2019, respectively. Interventions: Participants received placebo or 60 mg/kg crenezumab intravenously every 4 weeks for up to 100 weeks. Main Outcomes and Measures: The primary outcome was change from baseline to week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Results: There were 813 participants in CREAD (mean [SD] age, 70.7 [8.2] years; 483 female and 330 male) and 806 in CREAD2 (mean [SD] age, 70.9 [7.7] years; 456 female and 350 male). Baseline characteristics were balanced between both groups. The between-group difference in mean change from baseline in CDR-SB score (placebo minus crenezumab) was -0.17 (95% CI, -0.86 to 0.53; P = .63) at week 105 in the CREAD study (88 placebo; 86 crenezumab). Compared with previous trials, no new safety signals were identified, and amyloid-related imaging abnormalities with edema were rare, mild, and transient. No meaningful changes in AD biomarkers were observed. Both studies were discontinued following a preplanned interim analysis indicating that CREAD was unlikely to meet the primary end point. Conclusions and Relevance: Crenezumab was well tolerated but did not reduce clinical decline in participants with early AD. Trial Registration: ClinicalTrials.gov Identifiers: CREAD, NCT02670083; CREAD2, NCT03114657.

Social isolation and the role of AgeTech in a post-COVID world.

The COVID-19 pandemic particularly affected social connection through enforced social isolation and loss of regular activities. For healthcare systems, various initiatives have sprung up, leveraging existing technologies to connect people with services, activities, and loved ones. Here we review some AgeTech offerings to address social isolation for healthcare leadership and management to consider.

Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a.

BACKGROUND: Myelin water imaging is a magnetic resonance imaging (MRI) technique that quantifies myelin damage and repair in multiple sclerosis (MS) via the myelin water fraction (MWF). OBJECTIVE: In this substudy of a phase 3 therapeutic trial, OPERA II, MWF was assessed in relapsing MS participants assigned to interferon beta-1a (IFNb-1a) or ocrelizumab (OCR) during a two-year double-blind period (DBP) followed by a two-year open label extension (OLE) with ocrelizumab treatment. METHODS: MWF in normal appearing white matter (NAWM), including both whole brain NAWM and 5 white matter structures, and chronic lesions, was assessed in 29 OCR and 26 IFNb-1a treated participants at weeks 0, 24, 48 and 96 (DBP), and weeks 144 and 192 (OLE), and in white matter for 23 healthy control participants at weeks 0, 48 and 96. RESULTS: Linear mixed-effects models of data from baseline to week 96 showed a difference in the change in MWF over time favouring ocrelizumab in all NAWM regions. At week 192, lesion MWF was lower for participants originally randomised to IFNb-1a compared to those originally randomised to OCR. Controls showed no change in MWF over 96 weeks in any region. CONCLUSION: Ocrelizumab appears to protect against demyelination in MS NAWM and chronic lesions and may allow for a more permissive micro environment for remyelination to occur in focal and diffusely damaged tissue.

Transcript- and annotation-guided genome assembly of the European starling.

The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgaris vAU), and a second, North American, short-read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species-specific transcript mapping and gene annotation revealed good gene-level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counterintuitive behaviour in traditional busco metrics, and present buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base-calling quality. This work expands our knowledge of avian genomes and the available toolkit for assessing and improving genome quality. The new genomic resources presented will facilitate further global genomic and transcriptomic analysis on this ecologically important species.

One week of high-fat overfeeding alters bone metabolism in healthy males: A pilot study.

OBJECTIVES: Short periods of excessive consumption of indulgent high-fat foods are common in Western society, but the effect this has on bone is unknown. The aim of this pilot study was to explore how a 7-d hyperenergetic, high-fat diet affects candidate biomarkers of bone metabolism. METHODS: The study included 12 healthy men with a mean age of 24 y (SD = 4 y) and body mass index (BMI) of 24.1 kg/m2 (SD = 1.5). The men consumed a 7-d hyperenergetic, high-fat diet (HE-HFD; 20.9 [SD = 0.8] MJ; 65% total energy as fat) and a control (CON) diet (10.9 [SD = 2] MJ; 36% total energy as fat), in randomized, crossover order, with each trial separated by 3 wk. Markers of bone formation (P1NP) and bone resorption (CTx) were measured at baseline and after 1, 3, and 7 d of each diet. Bone metabolic responses were analyzed using two-factor repeated-measures analysis of variance and subsequent pairwise comparisons. RESULTS: There was a main effect of time (P < 0.05), but no trial (P = 0.270) or time- × -trial interaction (P = 0.693) effects for plasma concentrations of CTx. Mean CTx concentrations did not differ between trials (CON: 0.97 ng/mL [SD = 0.39]; HE-HFD: 1.03 ng/mL [SD = 0.22]; P = 0.225). There was a main effect of trial (P < 0.01), but no time (P = 0.138) or trial- × -interaction (P = 0.179) effects for plasma concentrations of P1NP. Mean P1NP concentrations were lower during the HE-HFD (61.79 ng/mL [SD = 26.54]) than during the CON diet (77.89 ng/mL [SD = 28.71]; P < 0.01). CONCLUSIONS: A 7-d hyperenergetic, high-fat diet reduces a marker of bone formation but does not affect a marker of bone resorption. This pilot study suggested that short periods of excessive energy and fat consumption may detrimentally affect bone health.

Deformation-based morphometry identifies deep brain structures protected by ocrelizumab.

BACKGROUND: Despite advancements in treatments for multiple sclerosis, insidious disease progression remains an area of unmet medical need, for which atrophy-based biomarkers may help better characterize the progressive biology. METHODS: We developed and applied a method of longitudinal deformation-based morphometry to provide voxel-level assessments of brain volume changes and identified brain regions that were significantly impacted by disease-modifying therapy. RESULTS: Using brain MRI data from two identically designed pivotal trials of relapsing multiple sclerosis (total N = 1483), we identified multiple deep brain regions, including the thalamus and brainstem, where volume loss over time was reduced by ocrelizumab (p < 0.05), a humanized anti-CD20 + monoclonal antibody approved for the treatment of multiple sclerosis. Additionally, identified brainstem shrinkage, as well as brain ventricle expansion, was associated with a greater risk for confirmed disability progression (p < 0.05). CONCLUSIONS: The identification of deep brain structures has a strong implication for developing new biomarkers of brain atrophy reduction to advance drug development for multiple sclerosis, which has an increasing focus on targeting the progressive biology.

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.