Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

BACKGROUND: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. METHODS: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. RESULTS: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. CONCLUSIONS: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. TRIAL REGISTRATION NUMBERS AND DATES OF REGISTRATION: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017.

The prevalence of insomnia increases with age; however, some hypnotics used for treating insomnia do not adequately resolve sleep problems in older adults and may be associated with adverse residual effects. Specifically, some hypnotics pose safety concerns in this population of patients who are generally more vulnerable to treatment-related effects, including increasing the risk of falls, risks of cognitive impairment, automobile accidents, and unresponsiveness to auditory stimuli. Safer and more effective insomnia medications are needed to reduce sleep problems with improved side-effect profiles. This analysis of lemborexant clinical studies conducted in adult subjects at least 65 years old found the drug to be effective without impairing memory, attention or balance the following day compared with placebo. These subjects were normal sleepers (for age) or had insomnia disorder. Furthermore, lemborexant was not associated with impaired ability to drive the next morning or awaken to loud middle-of-the-night sounds. Lemborexant was well tolerated in these older adults, similar to findings for adults aged at least 18 years. These findings indicate that lemborexant may be an appropriate treatment option for insomnia in older adults.

The effect of peanut skins as a natural antimicrobial feed additive on ileal and cecal microbiota in broiler chickens inoculated with Salmonella enterica Enteritidis.

The consumption of poultry products contaminated with Salmonella species is one of the most common causes of Salmonella infections. In vivo studies demonstrated the potential application of peanut skins (PS) as an antimicrobial poultry feed additive to help mitigate the proliferation of Salmonella in poultry environments. Tons of PS, a waste by-product of the peanut industry, are generated and disposed in U.S. landfills annually. Peanut skins and extracts have been shown to possess antimicrobial and antioxidant properties. Hence, we aimed to determine the effect of PS as a feed additive on the gut microbiota of broilers fed a control or PS supplemented (4% inclusion) diet and inoculated with or without Salmonella enterica Enteritidis (SE). At hatch 160 male broilers were randomly assigned to 4 treatments: 1) CON-control diet without SE, 2) PS-PS diet without SE, 3) CONSE-control diet with SE, 4) PSSE-PS diet with SE. On d 3, birds from CONSE and PSSE treatments were inoculated with 4.2 × 109 CFU/mL SE. At termination (4 wk), 10 birds/treatment were euthanized and ileal and cecal contents were collected for 16S rRNA analysis using standard methodologies. Sequencing data were analyzed using QIIME2. No effect of PS or SE was observed on ileal alpha and beta diversity, while evenness, richness, number of amplicon sequence variants (ASV) and Shannon, as well as beta diversity were significantly (P < 0.05) affected in ceca. Similarly, more differentially abundant taxa between treatment groups were identified in ceca than in ileum. However, more microbiota functional changes, based on the PICRUST2 prediction, were observed in ileum. Overall, relatively minor changes in microbiota were observed during SE infection and PS treatment, suggesting that PS addition may not attenuate the SE proliferation, as shown previously, through modulation of microbiota in gastrointestinal tract. However, while further studies are warranted, these results suggest that PS may potentially serve as a functional feed additive for poultry for improvement of animal health.

Effects of full-fat high-oleic soybean meal in layer diets on performance, egg quality and chemical composition.

The utilization of full-fat high-oleic soybean meal in layer diets could lead to value-added poultry products. To test this idea, 336 hens were randomly assigned to 4 isonitrogenous (18.5% CP) and isocaloric (2,927 kcal/kg) formulated diets and fed the following diets for eight weeks: conventional control solvent-extracted defatted soybean meal (CON); extruded-expelled defatted soybean meal (EENO); full fat normal-oleic soybean meal (FFNO); or full fat high-oleic soybean meal (FFHO). Body weights (BW) were collected at week 0 and week 8. Eggs were collected daily, and the totals counted each week. Feed consumption was measured weekly, and egg quality was measured bi-weekly. Eggs were collected at wk 0 and wk 8 for fatty acid analysis. There were no significant treatment differences in any of the production parameters measured, BW, feed consumption, feed conversion ratio or egg production (P > 0.05). Eggshell strength was significantly greater in eggs produced from the EENO group as compared to the control (P < 0.01), while egg yolk color was significantly darker in eggs of the control and EENO treatment groups relative to the FFNO and FFHO treatments (P < 0.0001). Eggs produced by hens fed the FFHO diet had a 52% increase in monounsaturated n-9 oleic acid content (P < 0.0001) and reduced palmitic (P < 0.01) and stearic (P < 0.0001) saturated fatty acid levels as compared to the conventional controls. These results validate the utilization of FFHO as a value-added poultry feed ingredient to enrich the eggs and/or poultry meat produced.

Full-Fat Soybean Meals as an Alternative Poultry Feed Ingredient-Feed Processing Methods and Utilization-Review and Perspective.

On a global scale, the poultry industry expands its wings in terms of meat and egg production to the masses. However, this industry itself requires a sustainable and permanent supply of different inputs, one of which is poultry feed and nutrition. Soybean is a versatile protein that is offered to poultry in different inclusion rates in commercial diets after being processed using various thermal and mechanical processing methods. Conventional commercial soybean meal is usually prepared by the extraction of oil from whole soybeans using solvents, producing a meal that has approximately 1% crude fat. Without oil extraction, full-fat soybean (FFSBM) is produced, and it is an excellent source of dietary energy and protein for poultry with a nutritional profile of 38-40% protein and 18-20% crude fat, on average. FFSBM has less crude protein (CP) than solvent-extracted soybean meal (SE SBM) but higher metabolizable energy due to higher fat content. Alternatively, extruded expeller processing produces defatted soybean meal containing approximately 6-7% crude fat. Studies have demonstrated that FFSBM can be used in poultry diets to improve poultry nutrition, performance, and quality of the poultry meat and eggs produced. This review aims to evaluate the nutrition and use of meals prepared from conventional and high-oleic soybeans using various feed processing methods.

NREM sleep brain networks modulate cognitive recovery from sleep deprivation.

Decrease in cognitive performance after sleep deprivation followed by recovery after sleep suggests its key role, and especially non-rapid eye movement (NREM) sleep, in the maintenance of cognition. It remains unknown whether brain network reorganization in NREM sleep stages N2 and N3 can uniquely be mapped onto individual differences in cognitive performance after a recovery nap following sleep deprivation. Using resting state functional magnetic resonance imaging (fMRI), we quantified the integration and segregation of brain networks during NREM sleep stages N2 and N3 while participants took a 1-hour nap following 24-hour sleep deprivation, compared to well-rested wakefulness. Here, we advance a new analytic framework called the hierarchical segregation index (HSI) to quantify network segregation across spatial scales, from whole-brain to the voxel level, by identifying spatio-temporally overlapping large-scale networks and the corresponding voxel-to-region hierarchy. Our results show that network segregation increased in the default mode, dorsal attention and somatomotor networks during NREM sleep compared to wakefulness. Segregation within the visual, limbic, and executive control networks exhibited N2 versus N3 sleep-specific voxel-level patterns. More segregation during N3 was associated with worse recovery of working memory, executive attention, and psychomotor vigilance after the nap. The level of spatial resolution of network segregation varied among brain regions and was associated with the recovery of performance in distinct cognitive tasks. We demonstrated the sensitivity and reliability of voxel-level HSI to provide key insights into within-region variation, suggesting a mechanistic understanding of how NREM sleep replenishes cognition after sleep deprivation.

Machine Learning Approaches for Stroke Risk Prediction: Findings from the Suita Study.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7389 participants and 53 variables. Initially, unsupervised k-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (LightGBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised k-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF, was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

Predicting response to stepped-care cognitive behavioral therapy for insomnia using pre-treatment heart rate variability in cancer patients.

OBJECTIVE: This study examined whether high frequency heart-rate variability (HF-HRV) and HF-HRV reactivity to worry moderate response to cognitive behavioural therapy for insomnia (CBT-I) within both a standard and stepped-care framework among cancer patients with comorbid insomnia. Biomarkers such as HF-HRV may predict response to CBT-I, a finding which could potentially inform patient allocation to different treatment intensities within a stepped-care framework. METHODS: 177 participants (86.3 % female; Mage = 55.3, SD = 10.4) were randomized to receive either stepped-care or standard CBT-I. 145 participants had their HRV assessed at pre-treatment during a rest and worry period. Insomnia symptoms were assessed using the Insomnia Severity Index (ISI) and daily sleep diary across five timepoints from pre-treatment to a 12-month post-treatment follow-up. RESULTS: Resting HF-HRV was significantly associated with pre-treatment sleep efficiency and sleep onset latency but not ISI score. However, resting HF-HRV did not predict overall changes in insomnia across treatment and follow-up. Similarly, resting HF-HRV did not differentially predict changes in sleep diary parameters across standard or stepped-care groups. HRV reactivity was not related to any of the assessed outcome measures in both cross-sectional and longitudinal analyses. CONCLUSION: Although resting HF-HRV was related to initial daily sleep parameters, HF-HRV measures did not significantly predict longitudinal responses to CBT-I. These findings suggest that HF-HRV does not predict treatment responsiveness to CBT-I interventions of different intensity in cancer patients.

Low-density lipoprotein particle profiles compared with standard lipids measurements in the association with asymptomatic intracranial artery stenosis.

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance "low LDL-c-high LDL-p" group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55-5.00) in the reference of the concordance "low LDL-c-low LDL-p" group. This was followed by the concordance "high LDL-c-high LDL-p" group of 2.56 (1.69-3.85) and the discordance "high LDL-c-low LDL-p" group of 2.40 (1.29-4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS.

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

BACKGROUND: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. METHOD: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. RESULTS: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. CONCLUSIONS: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

Insomnia is a common sleep disorder associated with significant difficulties, particularly in older adults. Although there are many drug treatments available, some are associated with the important risk of side effects and may not adequately treat sleep maintenance (ability to stay asleep), which is a frequent sleep complaint in older people. Lemborexant has been approved in multiple countries for the treatment of adults with insomnia based on studies that show lemborexant improved adults' ability to fall asleep and stay asleep and is well tolerated. To examine the long-term benefit of lemborexant, we investigated subject-reported benefits and safety of lemborexant in older (≥ 65 years) adults who participated in a 1-year study. The results showed that within the first few days of taking lemborexant, and lasting through 12 months of treatment, nightly lemborexant improved nighttime sleep (that is, it reduced the time it took to fall asleep, reduced the time awake during the night, and increased total sleep time) more than placebo. Morning alertness improved more in older adults who took lemborexant compared with placebo. In addition, those who took lemborexant also reported that their insomnia symptoms were less severe and they had less fatigue compared with placebo. Lemborexant was well tolerated in older adults. These results suggest that lemborexant may be a good option for older adults with insomnia disorder.

A multidimensional investigation of sleep and biopsychosocial profiles with associated neural signatures.

Sleep is essential for optimal functioning and health. Interconnected to multiple biological, psychological and socio-environmental factors (i.e., biopsychosocial factors), the multidimensional nature of sleep is rarely capitalized on in research. Here, we deployed a data-driven approach to identify sleep-biopsychosocial profiles that linked self-reported sleep patterns to inter-individual variability in health, cognition, and lifestyle factors in 770 healthy young adults. We uncovered five profiles, including two profiles reflecting general psychopathology associated with either reports of general poor sleep or an absence of sleep complaints (i.e., sleep resilience) respectively. The three other profiles were driven by sedative-hypnotics-use and social satisfaction, sleep duration and cognitive performance, and sleep disturbance linked to cognition and mental health. Furthermore, identified sleep-biopsychosocial profiles displayed unique patterns of brain network organization. In particular, somatomotor network connectivity alterations were involved in the relationships between sleep and biopsychosocial factors. These profiles can potentially untangle the interplay between individuals' variability in sleep, health, cognition and lifestyle - equipping research and clinical settings to better support individual's well-being.

A Pilot Randomized Trial of Combined Cognitive-Behavioral Therapy and Exercise Training Versus Exercise Training Alone for the Management of Chronic Insomnia in Obstructive Sleep Apnea.

Insomnia treatment among individuals with comorbid insomnia and obstructive sleep apnea is suboptimal. In a pilot randomized controlled trial, 19 individuals with comorbid insomnia and obstructive sleep apnea were allocated to one of two arms: EX + EX, consisting of two 8-week phases of exercise training (EX), or RE + CBTiEX, encompassing 8 weeks of relaxation training (RE) followed by 8 weeks of combined cognitive-behavioral therapy and exercise (CBTiEX). Outcomes included Insomnia Severity Index (ISI), polysomnography, and cardiorespiratory fitness measures. A mixed-model analysis of variance revealed a Group × Time interaction on peak oxygen consumption change, F(1, 14) = 10.1, p = .007, and EX increased peak oxygen consumption (p = .03, g' = -0.41) and reduced ISI (p = .001, g' = 0.82) compared with RE (p = .49, g = 0.16) post-8 weeks. Post-16 weeks, there was a significant Group × Time interaction (p = .014) driven by RE + CBTiEX yielding a larger improvement in ISI (p = .023, g' = 1.48) than EX + EX (p = .88, g' < 0.1). Objective sleep was unchanged. This study showed promising effects of regular EX alone and combined with cognitive-behavioral therapy for insomnia on ISI in comorbid insomnia and obstructive sleep apnea.

A multidimensional investigation of sleep and biopsychosocial profiles with associated neural signatures.

Sleep is essential for optimal functioning and health. Interconnected to multiple biological, psychological and socio-environmental factors (i.e., biopsychosocial factors), the multidimensional nature of sleep is rarely capitalized on in research. Here, we deployed a data-driven approach to identify sleep-biopsychosocial profiles that linked self-reported sleep patterns to inter-individual variability in health, cognition, and lifestyle factors in 770 healthy young adults. We uncovered five profiles, including two profiles reflecting general psychopathology associated with either reports of general poor sleep or an absence of sleep complaints (i.e., sleep resilience) respectively. The three other profiles were driven by the use of sleep aids and social satisfaction, sleep duration and cognitive performance, and sleep disturbance linked to cognition and mental health. Furthermore, identified sleep-biopsychosocial profiles displayed unique patterns of brain network organization. In particular, somatomotor network connectivity alterations were involved in the relationships between sleep and biopsychosocial factors. These profiles can potentially untangle the interplay between individuals' variability in sleep, health, cognition and lifestyle - equipping research and clinical settings to better support individual's well-being.

Precise cuts for tailoring chromene-phenyl COX inhibitors with Ligand Designer.

Cyclooxygenases 1 and 2 (COX-1/2) are enzymes renowned for inducing inflammatory responses through the production of prostaglandins. Thus, the development of COX inhibitors has been a promising approach for identifying compounds with anti-inflammatory potential. In this study, we designed 27 new compounds (1-27) based on the structure of a previously known COX inhibitor, using the Ligand Designer tool. Our aim was to improve the affinity of the compounds with COX enzymes by inducing interactions with residue Arg120 while retaining the good π-π stacking interactions of the chromene-phenyl scaffold. Through screening based on ligand-binding free energy defined by molecular docking simulations and MM/GBSA technique, compounds 9 and 10 were identified as having the highest ability to inhibit COX proteins. The binding affinities of the two compounds with COX-1/2 were superior to those of the original NAI10 compound and the reference drug indomethacin. Our virtual screening suggests that compounds 9 and 10 have a strong ability to inhibit COX-1/2 and thus could be promising candidates for further anti-inflammatory drug studies. In essence, our study underscores the pivotal role of the N-aryl iminocoumarin scaffold in shaping the future landscape of novel anti-inflammatory drug development.

The effectiveness of exercise interventions targeting sleep in older adults with cognitive impairment or Alzheimer's disease and related dementias (AD/ADRD): A systematic review and meta-analysis.

Sleep loss is associated with reduced health and quality of life, and increased risk of Alzheimer's disease and related dementias. Up to 66% of persons with Alzheimer's disease and related dementias experience poor sleep, which can predict or accelerate the progression of cognitive decline. Exercise is a widely accessible intervention for poor sleep that can protect against functional and cognitive decline. No previous systematic reviews have investigated the effectiveness of exercise for sleep in older adults with mild cognitive impairment or Alzheimer's disease and related dementias. We systematically reviewed controlled interventional studies of exercise targeting subjectively or objectively (polysomnography/actigraphy) assessed sleep in persons with mild cognitive impairment or Alzheimer's disease and related dementias. We conducted searches in PubMed, Embase, Scopus and Cochrane-Library (n = 6745). Nineteen randomised and one non-randomised controlled interventional trials were included, representing the experiences of 3278 persons with mild cognitive impairment or Alzheimer's disease and related dementias. Ten had low-risk, nine moderate-risk, and one high-risk of bias. Six studies with subjective and eight with objective sleep outcomes were meta-analysed (random-effects model). We found moderate- to high-quality evidence for the beneficial effects of exercise on self-reported and objectively-measured sleep outcomes in persons with mild cognitive impairment or Alzheimer's disease and related dementias. However, no studies examined key potential moderators of these effects, such as sex, napping or medication use. Our results have important implications for clinical practice. Sleep may be one of the most important modifiable risk factors for a range of health conditions, including cognitive decline and the progression of Alzheimer's disease and related dementias. Given our findings, clinicians may consider adding exercise as an effective intervention or adjuvant strategy for improving sleep in older persons with mild cognitive impairment or Alzheimer's disease and related dementias.

Methodological approach to sleep state misperception in insomnia disorder: Comparison between multiple nights of actigraphy recordings and a single night of polysomnography recording.

STUDY OBJECTIVE: To provide a comprehensive assessment of sleep state misperception in insomnia disorder (INS) and good sleepers (GS) by comparing recordings performed for one night in-lab (PSG and night review) and during several nights at-home (actigraphy and sleep diaries). METHODS: Fifty-seven INS and 29 GS wore an actigraphy device and filled a sleep diary for two weeks at-home. They subsequently completed a PSG recording and filled a night review in-lab. Sleep perception index (subjective/objective × 100) of sleep onset latency (SOL), sleep duration (TST) and wake duration (TST) were computed and compared between methods and groups. RESULTS: GS displayed a tendency to overestimate TST and WASO but correctly perceived SOL. The degree of misperception was similar across methods within the GS group. In contrast, INS underestimated their TST and overestimated their SOL both in-lab and at-home, yet the severity of misperception of SOL was larger at-home than in-lab. Finally, INS overestimated WASO only in-lab while correctly perceiving it at-home. While only the degree of TST misperception was stable across methods in INS, misperception of SOL and WASO were dependent on the method used. CONCLUSIONS: We found that GS and INS exhibit opposite patterns and severity of sleep misperception. While the degree of misperception in GS was similar across methods, only sleep duration misperception was reliably detected by both in-lab and at-home methods in INS. Our results highlight that, when assessing sleep misperception in insomnia disorder, the environment and method of data collection should be carefully considered.

Influence of extruded soybean meal with varying fat and oleic acid content on nitrogen-corrected apparent metabolizable energy in broilers.

High oleic (HO) soybeans may serve as a value-added feed ingredient; providing amino acids and estimating their dietary energy value for broilers is essential. In this study, we determined the apparent metabolizable energy (AME), AME corrected for zero nitrogen retention (AMEn), digestibility, and nitrogen (N) retention of HO full-fat (HO-FF) soybean as compared to solvent-extracted soybean meal (SE-SBM), normal oleic full-fat (NO-FF) and extruded expeller (NO-EE) soybean. A total of 240 Ross-708 male broilers were selected, with 8 replicates per treatment and 6 chicks per cage. The AME and AMEn were estimated using the difference method with a 30% inclusion of test ingredients using a corn-soy reference diet with partial and total excreta collection. The index method with partial excreta collection used titanium dioxide as an inert marker. The same starter diet was provided for all birds for 14 d, followed by the reference and assay diets for the next 6 adaptation days. Total excreta were collected twice a day for 3 d. The AME and AMEn values determined for the HO-FF and NO-FF were higher (P < 0.001) than the NO-EE and SE-SBM. The AME of SE-SBM and NO-EE were similar with both methods, but the AMEn of SE-SBM was lower than the NO-EE only with the partial collection method. The agreement between AME and AMEn values determined by partial and total excreta collection analysis was 98%. Data from the total excreta collection method yielded higher AME and AMEn values (P < 0.001) than those from the partial collection method. In summary, HO-FF and NO-FF soybean meals had similar AME and AMEn values. The HO-FF soybean had 39 and 24% higher AME and AMEn than SE-SBM. Hence, high oleic full-fat soybean meal could serve as a valuable alternative feed ingredient to conventional SE-SBM meals in broiler diets, providing additional energy while providing amino acids and more oleic acid to enrich poultry meat products.

A close-up shot of protein-protein docking, from experiment to theory and reverse with the PROTAC performers.

PROTACs (Proteolysis Targeting Chimeras), heterobifunctional molecules, exhibit selectivity in degrading target proteins through E3 ubiquitin ligases. Designing effective PROTACs requires a deep understanding of the intricate binding interactions in the ternary complex (POI/PROTAC/E3 ligase), crucial for efficient target protein degradation. To address this challenge, we introduce a novel computational virtual screening method that considers essential amino acid interactions between the protein of interest and the chosen E3 ligase. This approach enhances accuracy and reliability, facilitating the strategic development of potent PROTACs. Utilizing a crystallized model of the VHL:PROTAC:SMARCA2BD ternary complex (PDB: 7Z6L), we assessed the effectiveness of our method. Our study reveals that increasing the number of essential restraints between the two proteins reduces the generated docking poses, leading to closer alignment with the experimental ternary complex. Specifically, utilizing three restraints showed the closest resemblance to the published complex, highlighting crucial interactions such as an H-bond between A:Gln 89 and B:Asn 67, along with two hydrophobic interactions: A:Gly 22 with B:Arg 69 and A:Glu 37 with B:Pro 99. This resulted in a significant decrease in the mean RMSD value from 31.8 and 31.0 Å to 24.4 Å, respectively. This underscores the importance of incorporating multiple essential restraints to enhance docking accuracy. Building on this progress, we introduce a systematic approach to design potential PROTACs between the Estrogen receptor and the E3 ligase, utilizing bridging intermediates with 4, 6, or 7 carbon atoms. By providing a more accurate and efficient means of identifying optimal PROTAC candidates, this approach has the potential to accelerate the development of targeted therapies and reduce the time and costs associated with drug discovery.Communicated by Ramaswamy H. Sarma.

Effects of high oleic full-fat soybean meal on broiler live performance, carcass and parts yield, and fatty acid composition of breast fillets.

The effects of high oleic oil full-fat (HO-FF) soybean meal (SBM) on broiler meat quality could lead to value-added food products. This experiment evaluated the effects of dietary normal oleic extruded expelled (NO-EE), normal oleic full-fat (NO-FF), or HO-FF SBM on live performance, carcass and parts yield, and breast fatty acid composition. Diets were formulated to be isoenergetic and isonitrogenous. A total of 540 Ross-708 male broilers were raised on floor pens with 18 broilers/pen and 10 replicates/treatment. Data were analyzed in a completely randomized design. Chickens were fed with a starter (0-14 d), grower (15-35 d), or a finisher diet (36-47 d) up to 47 d. Chickens were weighed at 7, 14, 35, and 47 d. At 48 d, 4 broilers per pen were processed. Breast samples were collected and evaluated for quality and fatty acid content. Broilers fed diets with NO-EE were heavier (P < 0.05) than chickens fed diets with full-fat SBM (NO-FF and HO-FF) at d 7, 14, 35 while feed conversion ratio (FCR) of NO-EE was best (P < 0.05) at 7 and 47 d. Carcass yield was also higher for broilers fed NO-EE than the other treatments. Diet did not affect parts yield, breast meat color, cooking, drip loss, white stripping, or SM quality parameters. More breast fillets without wooden breast (score 1) were observed (P < 0.05) for NO-FF than the other 2 treatments. The breast meat fatty acid profile (g fatty acid/100 g of all fatty acids) was significantly affected (P < 0.001) by diet. Broilers fed the HO-FF SBM diet had 54 to 86% more oleic acid, 72.5% to 2.2 times less linoleic acid, and reduced stearic and palmitic acid levels in the breast meat than NO-FF and NO-EE. In conclusion, feeding HO-FF to broilers enriched the oleic acid content of their breast meat while reducing the saturated fatty acid content relative to the NO-FF and NO-EE treatment groups.

Slow oscillation-spindle cross-frequency coupling predicts overnight declarative memory consolidation in older adults.

Cross-frequency coupling (CFC) between brain oscillations during non-rapid-eye-movement (NREM) sleep (e.g. slow oscillations [SO] and spindles) may be a neural mechanism of overnight memory consolidation. Declines in CFC across the lifespan might accompany coinciding memory problems with ageing. However, there are few reports of CFC changes during sleep after learning in older adults, controlling for baseline effects. Our objective was to examine NREM CFC in healthy older adults, with an emphasis on spindle activity and SOs from frontal electroencephalogram (EEG), during a learning night after a declarative learning task, as compared to a baseline night without learning. Twenty-five older adults (M [SD] age = 69.12 [5.53] years; 64% female) completed a two-night study, with a pre- and post-sleep word-pair associates task completed on the second night. SO-spindle coupling strength and a measure of coupling phase distance from the SO up-state were both examined for between-night differences and associations with memory consolidation. Coupling strength and phase distance from the up-state peak were both stable between nights. Change in coupling strength between nights was not associated with memory consolidation, but a shift in coupling phase towards (vs. away from) the up-state peak after learning predicted better memory consolidation. Also, an exploratory interaction model suggested that associations between coupling phase closer to the up-state peak and memory consolidation may be moderated by higher (vs. lower) coupling strength. This study supports a role for NREM CFC in sleep-related memory consolidation in older adults.