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 biopsychosocialprofiles 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.

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.

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.

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.

Factors influencing older adults' participation in telehealth interventions for primary prevention and health promotion: A rapid review.

OBJECTIVE: To identify facilitators and barriers to older adults' participation in telehealth interventions for primary prevention and health promotion. METHODS: Relevant articles were searched using keywords in Embase and MEDLINE. Study characteristics, type of telehealth interventions and technology involved, as well as facilitators and barriers to their use, were extracted from selected articles. The Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) model was used to organise data. RESULTS: A total of 24 articles (pertaining to 20 studies) were included. Nine facilitators and 11 barriers influencing the participation in telehealth interventions for primary prevention and health promotion among older adults were identified. The most recurrent facilitators were related to the individual's performance expectancy and effort expectancy, as well as the presence of a social dimension associated with the intervention (i.e. having a good relationship with the other participants in the program). The two most prevalent barriers were also related to effort expectancy and performance expectancy, followed by barriers related to the inherent characteristics of the technology and older adults' health condition. Experience, age and gender were also found to moderate technology use and acceptance. CONCLUSIONS: This rapid review highlights the importance of adopting a holistic perspective when designing telehealth interventions aimed at preventive and health promotion purposes among older adults.

Efficacy and Safety of Risperidone in Patients With Delirium: The RIDDLE Pilot Study.

BACKGROUND: The cornerstone treatment of delirium is to assess and treat its underlying causes and prevent further complications. Drug therapy may be necessary to control agitation and behavioral symptoms associated with delirium. The aim of this pilot study was to evaluate the feasibility of a randomized placebo controlled trial to evaluate the efficacy and safety of risperidone in the treatment of delirium. METHODS: This was a randomized double-blinded placebo-controlled trial. Patients were enrolled in the study if they were hospitalized and 65 years or older and had a diagnosis of delirium. Delirium Rating Scale revised 98 was used to determine delirium and motor agitation. RESULTS: A total of 14 participants with 57% being men and having a mean age of 86 years were included. There were no statistically significant differences between the risperidone and placebo group for the Delirium Rating Scale revised 98 score. There were no severe adverse reactions reported in the study, and no patients discontinued the study for adverse reactions. CONCLUSIONS: Risperidone at low doses (1 mg daily or less) was well tolerated for the treatment of delirium. Future large-scale trials are needed to evaluate the safety and efficacy of risperidone in the treatment of delirium. This pilot study taught us that the phase 2 RIsperDone DELirium trial will need a multicenter design with more research personnel to increase the number of participants enrolled.

The effects of acute exercise and a nap on heart rate variability and memory in young sedentary adults.

Recent evidence suggests that the autonomic nervous system can contribute to memory consolidation during sleep. Whether fluctuations in cardiac autonomic activity during sleep following physical exercise contribute to the process of memory consolidation has not been studied. We assessed the effects of a non-rapid eye movement (NREM) nap following acute exercise on cardiac autonomic regulation assessed with heart rate variability (HRV) to examine if HRV influences memory processes. Fifty-six (59% female) healthy young adults (23.14 ± 3.74 years) were randomly allocated to either the exercise plus nap (ExNap, n = 27) or nap alone (NoExNap, n = 29) groups. The ExNap group performed a 40-minute moderate-intensity cycling, while the NoExNap group was sedentary prior to learning 45 neutral pictures for a later test. Subsequently, participants underwent a 60-minute NREM nap while measuring EKG, followed by a visual recognition test. Our results indicated that heart rate did not significantly differ between the groups (p = .243), whereas vagally mediated HRV indices were lower in the ExNap group compared to the NoExNap group (p < .05). There were no significant differences in sleep variables between the groups (p > .05). Recognition accuracy was significantly higher in the ExNap group than in the NoExNap group (p = .027). In addition, the recognition accuracy of the ExNap group was negatively associated with vagally mediated HRV (p < .05). Pre-nap acute exercise appears to attenuate parasympathetic activity and to alter the relationship between memory and cardiac autonomic activity.

Standardized ileal amino acid digestibility of high-oleic full-fat soybean meal in broilers.

High-oleic (HO) soybean may serve as a value-added feed ingredient to enrich poultry meat due to its fatty acid content. However, the amino acid (AA) nutrient digestibility of soybean meal (SBM) made from these soybeans has yet to be determined. The objective of this study was to determine apparent ileal AA digestibility (AID) and standardized ileal AA digestibility (SID) of high-oleic full-fat (HO-FF) SBM compared to normal oleic full-fat (NO-FF), normal oleic extruded expeller (NO-EE), and solvent-extracted SBM (SE-SBM) in broilers. A nitrogen-free basal diet (NFD) was fed to 1 treatment group with 10 chicks/cage to determine basal endogenous losses (BEL). Titanium dioxide was used as an inert marker. The test diets contained 57.5% of the basal NFD and 42.5% of 1 of the 4 soybean sources. A total of 272 Ross-708 male broilers were placed in 40 battery cages with 5 treatments and 8 replicates per treatment. A common starter diet was provided to all the chickens for 14 d. Experimental diets were provided as a mash for 9 d before sample collection. Chickens were euthanized with CO2 on d 23, and contents of the distal ileum were collected, frozen, and freeze-dried. The BEL were similar to the values found in the literature. At d 23, broilers fed the SE-SBM had the highest body weight gain and best FCR compared to chickens fed the HO-FF and NO-FF treatments (P < 0.001). Broilers fed the SE-SBM and NO-EE experimental diets had (P < 0.001) higher apparent ileal AA digestibility and AA SID than broilers fed the HO-FF and NO-FF treatments. In conclusion, the SID of AA from HO-FF is similar to the digestibilities of other full-fat soybeans found in the literature and is lower than that of NO-EE and SE-SBM.

Simultaneous spectral differentiation of multiple fluorophores in super-resolution imaging using a glass phase plate.

By engineering the point-spread function (PSF) of single molecules, different fluorophore species can be imaged simultaneously and distinguished by their unique PSF patterns. Here, we insert a silicon-dioxide phase plate at the Fourier plane of the detection path of a wide-field fluorescence microscope to produce distinguishable PSFs (X-PSFs) at different wavelengths. We demonstrate that the resulting PSFs can be localized spatially and spectrally using a maximum-likelihood estimation algorithm and can be utilized for hyper-spectral super-resolution microscopy of biological samples. We produced superresolution images of fixed U2OS cells using X-PSFs for dSTORM imaging with simultaneous illumination of up to three fluorophore species. The species were distinguished only by the PSF pattern. We achieved ∼21-nm lateral localization precision (FWHM) and ∼17-nm axial precision (FWHM) with an average of 1,800 - 3,500 photons per PSF and a background as high as 130 - 400 photons per pixel. The modified PSF distinguished fluorescent probes with ∼80 nm separation between spectral peaks.

Age- and sex-specific associations between obstructive sleep apnea risk and cognitive decline in middle-aged and older adults: A 3-year longitudinal analysis of the Canadian longitudinal study on aging.

BACKGROUND: Whether obstructive sleep apnea (OSA) increases the risk of cognitive decline and how sex and age influence this association is not clear. Here, we characterized the sex- and age-specific associations between OSA risk and 3-year cognitive change in middle-aged and older adults. METHODS: We included 24,819 participants aged 45-85 (52% women) from the Canadian Longitudinal Study on Aging. OSA risk was measured at baseline using the STOP combined to body mass index (STOP-B). Neuropsychological tests assessed memory, executive functioning, and psychomotor speed at baseline and at 3-year follow-up. We conducted age- and sex-specific linear mixed models to estimate the predictive role of baseline STOP-B score on 3-year cognitive change. RESULTS: Men at high-risk for OSA aged 45-59 years showed a steeper decline in psychomotor speed (+13.2 [95% CI: -1.6, 27.9]) compared to men at low-risk. Men at high-risk for OSA aged 60-69 showed a steeper decline in mental flexibility (-1.2 [-1.9, -0.5]) and processing speed (+0.6 [0.3, 0.9]) than those at low-risk. Women at high-risk for OSA aged 45-59 showed a steeper decline in processing speed (+0.1 [-0.2, 0.4]) than women at low-risk, while women at high-risk ≥70 years had a steeper decline in memory (-0.2 [-0.6, 0.1]) and processing speed (+1.0 [0.4, 1.5]). CONCLUSIONS: Associations between OSA risk and cognitive decline over 3 years depend on age and sex. Being at high-risk for OSA is associated with a generalized cognitive decline in attention and processing speed, while a memory decline is specific to older women (≥70 years).

Enzyme-responsive macrocyclic metal complexes for biomedical imaging.

Metal chelator-based contrast agents are used as tumor navigators for cancer diagnosis. Although approved metal chelators show excellent contrast performance in magnetic resonance imaging (MRI), large doses are required for cancer diagnoses due to rapid clearance and nonspecific accumulation throughout the body, which can compromise safety. The present study describes an enzyme-responsive metal delivery system, in which enzyme overexpressed in the tumor microenvironment selectively activates the tumor uptake of gadolinium (Gd). Gd was loaded into enzyme-responsive macrocyclam (ErMC) modified with a PEGylated enzyme-cleavable peptide resulting in Gd@ErMC. The PEGylated shell layer protected Gd@ErMC from nonspecific binding in the blood, increasing the half-life of the contrast agent. Specific cleavage of the PEGylated shell layer by the enzyme selectively liberated Gd from Gd@ErMC at the tumor site. Evaluation of the in vivo distribution of Gd@ErMC in tumor-bearing mice by MRI and positron emission tomography (PET) showed that Gd@ErMC had an extended half-life and was highly specific. Histological and serological analysis of Gd@ErMC-treated mice showed that this agent was safe. This novel enzyme-responsive contrast agent delivery system shows promise as specific theranostic agent for MR-guided radiotherapy.