Novel Electrophysiological Signatures of Learning and Forgetting in Human Rapid Eye Movement Sleep.

Despite the known behavioral benefits of rapid eye movement (REM) sleep, discrete neural oscillatory events in human scalp electroencephalography (EEG) linked with behavior have not been discovered. This knowledge gap hinders mechanistic understanding of the function of sleep, as well as the development of biophysical models and REM-based causal interventions. We designed a detection algorithm to identify bursts of activity in high-density, scalp EEG within theta (4-8 Hz) and alpha (8-13 Hz) bands during REM sleep. Across 38 nights of sleep, we characterized the burst events (i.e., count, duration, density, peak frequency, amplitude) in healthy, young male and female human participants (38; 21F) and investigated burst activity in relation to sleep-dependent memory tasks: hippocampal-dependent episodic verbal memory and nonhippocampal visual perceptual learning. We found greater burst count during the more REM-intensive second half of the night (p < 0.05), longer burst duration during the first half of the night (p < 0.05), but no differences across the night in density or power (p > 0.05). Moreover, increased alpha burst power was associated with increased overnight forgetting for episodic memory (p < 0.05). Furthermore, we show that increased REM theta burst activity in retinotopically specific regions was associated with better visual perceptual performance. Our work provides a critical bridge between discrete REM sleep events in human scalp EEG that support cognitive processes and the identification of similar activity patterns in animal models that allow for further mechanistic characterization.

Understanding the roles of central and autonomic activity during sleep in the improvement of working memory and episodic memory.

The last decade has seen significant progress in identifying sleep mechanisms that support cognition. Most of these studies focus on the link between electrophysiological events of the central nervous system during sleep and improvements in different cognitive domains, while the dynamic shifts of the autonomic nervous system across sleep have been largely overlooked. Recent studies, however, have identified significant contributions of autonomic inputs during sleep to cognition. Yet, there remain considerable gaps in understanding how central and autonomic systems work together during sleep to facilitate cognitive improvement. In this article we examine the evidence for the independent and interactive roles of central and autonomic activities during sleep and wake in cognitive processing. We specifically focus on the prefrontal-subcortical structures supporting working memory and mechanisms underlying the formation of hippocampal-dependent episodic memory. Our Slow Oscillation Switch Model identifies separate and competing underlying mechanisms supporting the two memory domains at the synaptic, systems, and behavioral levels. We propose that sleep is a competitive arena in which both memory domains vie for limited resources, experimentally demonstrated when boosting one system leads to a functional trade-off in electrophysiological and behavioral outcomes. As these findings inevitably lead to further questions, we suggest areas of future research to better understand how the brain and body interact to support a wide range of cognitive domains during a single sleep episode.

Assessing risk of recurrent small bowel obstruction after non-operative management in patients with history of intra-abdominal surgery: a population-based comprehensive analysis in Taiwan.

BACKGROUND: Despite a significant 30% ten-year readmission rate for SBO patients, investigations into recurrent risk factors after non-operative management are scarce. The study aims to generate a risk factor scoring system, the 'Small Bowel Obstruction Recurrence Score' (SBORS), predicting 6-month recurrence of small bowel obstruction (SBO) after successful non-surgical management in patients who have history of intra-abdominal surgery. METHODS: We analyzed data from patients aged ≥ 18 with a history of intra-abdominal surgery and diagnosed with SBO (ICD-9 code: 560, 568) and were successful treated non-surgically between 2004 and 2008. Participants were divided into model-derivation (80%) and validation (20%) group. RESULTS: We analyzed 23,901 patients and developed the SBORS based on factors including the length of hospital stay > 4 days, previous operations > once, hemiplegia, extra-abdominal and intra-abdominal malignancy, esophagogastric surgery and intestino-colonic surgery. Scores > 2 indicated higher rates and risks of recurrence within 6 months (12.96% vs. 7.27%, OR 1.898, p < 0.001 in model-derivation group, 12.60% vs. 7.05%, OR 1.901, p < 0.001 in validation group) with a significantly increased risk of mortality and operative events for recurrent episodes. The SBORS model demonstrated good calibration and acceptable discrimination, with an area under curve values of 0.607 and 0.599 for the score generation and validation group, respectively. CONCLUSIONS: We established the effective 'SBORS' to predict 6-month SBO recurrence risk in patients who have history of intra-abdominal surgery and have been successfully managed non-surgically for the initial obstruction event. Those with scores > 2 face higher recurrence rates and operative risks after successful non-surgical management.

Competitive dynamics underlie cognitive improvements during sleep.

We provide evidence that human sleep is a competitive arena in which cognitive domains vie for limited resources. Using pharmacology and effective connectivity analysis, we demonstrate that long-term memory and working memory are served by distinct offline neural mechanisms that are mutually antagonistic. Specifically, we administered zolpidem to increase central sigma activity and demonstrated targeted suppression of autonomic vagal activity. With effective connectivity, we determined the central activity has greater causal influence over autonomic activity, and the magnitude of this influence during sleep produced a behavioral trade-off between offline long-term and working memory processing. These findings suggest a sleep switch mechanism that toggles between central sigma-dependent long-term memory and autonomic vagal-dependent working memory processing.

Laparoscopic training workshop to assess medical students' skill acquisition and interest in surgical careers.

BACKGROUND: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations. METHODS: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training. RESULTS: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants. CONCLUSION: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals.

The Phosphoprotein Synapsin Ia Regulates the Kinetics of Dense-Core Vesicle Release.

Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia.SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation.

Autonomic central coupling during daytime sleep differs between older and younger people.

Decreased functioning in the elderly is mirrored by independent changes in central and autonomic nervous systems. Additionally, recent work suggests that the coupling of these systems may also serve an important role. In young adults, Autonomic and Central Events (ACEs), measured in the temporal coincidence of heart rate bursts (HRBs) and increased slow-wave-activity (SWA, 0.5-1 Hz) and sigma activity (12-15 Hz), followed by parasympathetic surge (RRHF) during non-rapid eye movement (NREM) sleep, predicted cognitive improvements. However, ACEs have not been examined in the elderly. Thus, the current study compared ACEs during wake and daytime sleep in older and younger adults and examined associations with working memory improvement before and after a nap. Compared to youngers, older adults showed lower amplitude of ACEs during NREM sleep, but not during wake. Furthermore, while younger adults demonstrated a parasympathetic surge after HRBs, older adults showed an earlier rise and longer maintenance of the RRHF. Taken together, our results demonstrate that autonomic-central coupling declines with age. Pathological aging implicates independent roles for decreased autonomic and central nervous system functioning, the current findings suggest that the coupling of these systems may also deserve attention.

Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation.

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

Reconstruction of Distal Nasal Defects Using Free Cartilage Batten Grafting With Secondary Intention Healing: A Retrospective Case Series of 129 Patients.

BACKGROUND: Surgical defects of the distal nose can pose significant reconstructive challenges. Free cartilage batten graft (FCBG) with secondary intention healing is an underreported yet effective repair option with cosmetically and functionally satisfying outcomes. OBJECTIVE: To share the authors' experience using FCBG with secondary intention healing on multiple nasal subunits, including a detailed evaluation of wound/graft characteristics and design modifications to optimize success with this single-stage approach. METHODS: A retrospective study of 129 patients who underwent FCBG with secondary intention healing after Mohs surgery from 2011 to 2018, using statistical analysis of numerous outcome measures graded independently by 2 fellowship-trained Mohs surgeons. RESULTS: Overall, healed wounds were graded aesthetically as follows: excellent (24%), very good (31%), good (31%), or poor (14%). Excellent/very good outcomes were seen for superficial (p < .001), small-to-medium sized wounds (p < .0001) repaired with cartilage that closely approximated the defect size (p < .05). Consistently optimal outcomes were seen in the 19 repairs involving the alar lobule (mid-ala) alone, graded excellent (47%), very good (32%), and good (21%). A majority of patients (86%) experienced mild to no alar retraction. Although 67% of all patients had some skin surface contour irregularity, only 8% of patients sought dermabrasion. Neither hematoma, infection, ear deformity, chondritis, nor graft desiccation were reported. CONCLUSION: A modified approach to FCBG with secondary intention healing provides a reliable, minimalistic, low-risk reconstructive option for mid-alar defects.

Pediatric melanoma in the Hispanic population: An analysis of institutional and national data.

BACKGROUND/OBJECTIVES: Pediatric melanoma is rare and remains poorly characterized, especially in racial/ethnic minorities of whom Hispanics are the largest and fastest growing in the United States. The health care burden of melanoma in Hispanics, who often present with more advanced disease, is rising and has even been called an early epidemic in California. We sought to document key clinicopathologic features of melanoma in Hispanic pediatric patients and to compare these parameters to pediatric non-Hispanic whites (NHWs) under the a priori hypothesis that Spitzoid melanomas occur in greater proportions in Hispanics. METHODS: Single-institution cross-sectional study of pediatric melanoma cases (age < 20 years) with Hispanic stratification and comparison with matched Surveillance, Epidemiology, and End Results (SEER) data from the same time frame (1988-2016). RESULTS: Of our 61 institutional cases of pediatric melanoma, Hispanics (11), compared with NHWs (40), presented significantly younger (11.7 years, 95% CI: 2.77-8.00 years; P = .001), with lower limb predominance (46%; P < .05), mostly Spitzoid melanomas (82%; P < .05), and thicker tumors (2.34 mm, CI: 0.26-2.19 mm; P < .05). Similarly, SEER data (2499 cases) showed greater proportions of childhood/pre-pubertal adolescent melanomas (<15 years), lower limb involvement, Spitzoid subtype (36.5% vs 22.5% in NHWs; P = .001), and advanced (regional/distant) disease stages in Hispanics (212) compared with NHWs (2197). CONCLUSIONS: Pediatric melanomas may present differently in Hispanics, and heightened awareness/lower threshold to biopsy high-risk Spitzoid tumors on the lower limb may be warranted. Further investigations are needed to aid prevention and early detection in a vulnerable minority population less likely to seek outpatient dermatology specialty care.

Autonomic Activity during a Daytime Nap Facilitates Working Memory Improvement.

Recent investigations have implicated the parasympathetic branch of the autonomic nervous system in higher-order executive functions. These actions are purported to occur through autonomic nervous system's modulation of the pFC, with parasympathetic activity during wake associated with working memory (WM) ability. Compared with wake, sleep is a period with substantially greater parasympathetic tone. Recent work has reported that sleep may also contribute to improvement in WM. Here, we examined the role of cardiac parasympathetic activity during sleep on WM improvement in healthy young adults. Participants were tested in an operation span task in the morning and evening, and during the intertest period, participants experienced either a nap or wake. We measured high-frequency heart rate variability as an index of cardiac, parasympathetic activity during both wake and sleep. Participants showed the expected boost in parasympathetic activity during nap, compared with wake. Furthermore, parasympathetic activity during sleep, but not wake, was significantly correlated with WM improvement. Together, these results indicate that the natural boost in parasympathetic activity during sleep may benefit gains in prefrontal executive function in young adults. We present a conceptual model illustrating the interaction between sleep, autonomic activity, and prefrontal brain function and highlight open research questions that will facilitate understanding of the factors that contribute to executive abilities in young adults as well as in cognitive aging.

Autonomic/central coupling benefits working memory in healthy young adults.

Working memory (WM) is an executive function that can improve with training. However, the precise mechanism for this improvement is not known. Studies have shown greater WM gains after a period of sleep than a similar period of wake, and correlations between WM improvement and slow wave activity (SWA; 0.5-1 Hz) during slow wave sleep (SWS). A different body of literature has suggested an important role for autonomic activity during wake for WM. A recent study from our group reported that the temporal coupling of Autonomic/CentralEvents (ACEs) during sleep was associated with memory consolidation. We found that heart rate bursts (HR bursts) during non-rapid eye movement (NREM) sleep are accompanied by increases in SWA and sigma (12-15 Hz) power, as well as increases in the high-frequency (HF) component of the RR interval, reflecting vagal rebound. In addition, ACEs predict long-term, episodic memory improvement. Building on these previous results, we examined whether ACEs also contribute to gains in WM. We tested 104 young adults in an operation span task (OSPAN) in the morning and evening, with either a nap (n = 53; with electroencephalography (EEG) and electrocardiography (ECG)) or wake (n = 51) between testing sessions. We identified HR bursts in the ECG and replicated the increases in SWA and sigma prior to peak of the HR burst, as well as vagal rebound after the peak. Furthermore, we showed sleep-dependent WM improvement, which was predicted by ACE activity. Using regression analyses, we discovered that significantly more variance in WM improvement could be explained with ACE variables than with overall sleep activity not time-locked with ECG. These results provide the first evidence that coordinated autonomic and central events play a significant role in sleep-related WM improvement and implicate the potential of autonomic interventions during sleep for cognitive enhancement.

Establishment of an animal challenge model as a potency assay for an inactivated Enterovirus Type 71 vaccine.

Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2.62 ± 0.45). EV71 VP1 protein was identified in the brain tissues at histology. In the second phase of the model, 3-week-old female ICR mice received one primary and two boosting i.p. injections of formalin-inactivated EV71 B4 and C4 vaccine. Immunized serum was neutralized in vitro with EV71 C4 and applied to the murine challenge model. The C4 vaccine-immunized serum exhibited the highest protective titre (ED50 = 114.6), while the B4 immunized serum had the weakest protective titre (ED50 = 34.3). Additionally, human plasma and intravenous immunoglobulin displayed significant protection in the neutralization assay. Our results could facilitate candidate EV71 vaccine immunogenicity and efficacy evaluations, and may help establish reference EV71 antisera in the future.

Rat Pheochromocytoma PC12 Cells in Culture.

PC12 cells serve as a secretory cell model, especially suitable for studying the molecular mechanisms underlying fusion pore kinetics in regulated exocytosis of dense-core vesicles (DCVs). In this chapter, we describe a series of PC12 cell culture procedures optimized for real-time functional assays such as single-vesicle amperometry. In addition, these conditions have been widely used for single-cell biochemical assays such as the proximity ligation assay with immunostaining.

Gender and Age Differences in Anthropometric Characteristics of Taiwanese Older Adults Aged 65 Years and Older.

A previous study provided reference data on the age and gender distribution of anthropometric parameters in Taiwanese adults. However, there are very few large-scale analyses of anthropometric data of older adults in Taiwan. Therefore, the main purpose of this study was to describe gender- and age-specific distributions of anthropometric measurements and anthropometry assessments of Taiwanese older adults. This was a cross-sectional study conducted on 22,389 adults aged 65 years or older (8017 males and 14,372 females) who participated in Taiwan's National Physical Fitness Survey 2014-2015. All participants were recruited using stratified convenience sampling from 46 physical fitness test stations in 22 cities or counties in Taiwan. The anthropometric measurements and anthropometry assessments included in the present study were the assessments of height, weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). The results showed statistically significant differences in weight, height, WC, and WHR across all age groups among both male and female individuals aged 65 years and older in Taiwan. However, there was no significant difference in BMI and HC between males and females in all age groups. Anthropometric status provides an initial assessment of the overall health of the population. This study uses a representative population of Taiwanese older adults over the age of 65 for analysis and provides detailed information on anthropometric data distribution.

Does hepatectomy improve outcomes of breast cancer with liver metastasis? A nationwide analysis of real-world data in Taiwan.

BACKGROUND: Liver metastases from breast cancer are associated with poor prognosis, and treatment options are usually restricted to palliative systemic therapy. The impact of liver resection on metastasis remains controversial. The aim of this study is to investigate whether liver resection can offer better survival outcomes in cases of isolated liver metastases from breast cancer. METHODS: We conducted a nationwide cohort study using a claims dataset from Taiwan's National Health Insurance Research Database (NHIRD). We identified all patients with breast cancer (diagnostic code ICD-9: 174.x) from the Registry for Catastrophic Illness Patient Database (RCIPD) of the NHIRD who underwent mastectomy between January 1, 2000, and December 31, 2008. Patients with other malignancies (history, initially, or during follow-up), those with a history of metastasis prior to or at initial admission for mastectomy, and those without liver metastases were excluded. Patients with other metastases between mastectomy and liver metastasis and those who died at first admission for liver resection were also excluded. All patients were followed up until December 31, 2013, or withdraw from the database because of death. RESULTS: Data were analyzed for 1,116 patients who fulfilled the inclusion criteria (resection group: 89; non-resection group: 1,027). There were no differences in age, Charlson Comorbidity Index, or major coexisting diseases except renal disease between two groups. Kaplan-Meier analysis demonstrated that the liver resection group had significantly better overall survival (OS) than the non-resection group. (1-year: 96.6% vs. 52.3%, 2-year: 86.8% vs. 35.4%, 3-year: 72.3% vs. 25.2%, 5-year: 51.6% vs. 16.9%, respectively, p<0.001). Cox analysis revealed that the liver resection group exhibited a significant improvement in patient survival (hazard ratio [HR] = 0.321, 95% confidence interval [CI]: 0.234-0.440, p<0.001). CONCLUSION: These findings indicate that liver resection may offer better survival benefit in patients with breast cancer who develop new liver metastases post mastectomy.

Associations of Health-Related Physical Fitness with Waist Circumference and Abdominal Obesity Risk in Taiwanese Adults.

In this study, we aimed to determine the associations among health-related physical fitness measurements, waist circumference (WC), and abdominal obesity risk in Taiwanese adults. We conducted a cross-sectional study based on data from the 2017 Taiwan Scientific Physical Fitness Survey (the TSPFS). We collected the responses from 17,973 participants (7907 men and 10,066 women) aged 23-64 years for this study. The participants completed the study protocol with a standardized structural questionnaire and a series of health-related physical fitness measurements. The fitness measurements included cardiorespiratory fitness (measured by a 3-min progressive knee-up and step test), muscular fitness (measured by a hand grip strength test), and flexibility (measured by a sit-and-reach test). Our anthropometric measurements included height, weight, WC, hip circumference (HC), body mass index (BMI), and waist-to-hip ratio (WHR). We identified the quartiles of the health-related physical fitness results as the dependent variable in the multiple linear and multiple logistic regression analysis to determine the associations of the physical fitness measurements with WC distribution and abdominal obesity risk. We also considered the dose-response relationship. We found that cardiorespiratory fitness, relative grip strength, and flexibility were each significantly negatively associated with WC, but absolute grip strength was significantly positively associated with WC. We also found that higher levels of cardiorespiratory fitness, relative grip strength, and flexibility were each associated with a lower risk of abdominal obesity. Moreover, our secondary finding was of a dose-response relationship between physical fitness performance, WC, and abdominal obesity risk. In short, health-related physical fitness was an effective predictor of waist circumference for both sexes of Taiwanese adults, and higher levels of health-related physical fitness were associated with lower risks of abdominal obesity in Taiwanese adults.

Bio-Inspired Amphoteric Polymer for Triggered-Release Drug Delivery on Breast Cancer Cells Based on Metal Coordination.

Nanoscale coordination polymers are promising vehicles for anticancer drug delivery because their surface composition and particle size can be tuned to exploit the enhanced permeability and retention effect, and their reversible interaction with metal cations enables triggered drug release at the tumor site. Here, we develop a novel nanoscale coordination polymer using the diblock copolymer poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(serinyl acrylate) (PMPC-b-PserA) and demonstrate its use for encapsulation of a hydrophobic drug and triggered drug release to induce breast cancer cell apoptosis in vitro. The zwitterionic PMPC block was inspired by the antifouling structure of cell membranes, and the PserA block was inspired by the amphoteric amino acids of proteins. The polymer was synthesized by reversible addition-fragmentation chain transfer polymerization, and a mixture of the polymer and FeCl3 self-assembled into nanoparticles via complexation of Fe3+ with PserA, with the hydrophilic PMPC block at the particle surface. At a molar ratio of Fe3+ to serA of 3:1, the hydrodynamic diameter of the particles was 22.2 nm. Curcumin, a natural water-insoluble polyphenol used to enhance the effects of chemotherapeutics, was encapsulated in the particles as an oil-in-water emulsion, with an encapsulation efficiency of 99.6% and a particle loading capacity of 32%. Triggered release of curcumin was achieved by adding deferoxamine, an FDA-approved Fe3+ chelating agent; curcumin release efficiency increased at higher deferoxamine concentrations and lower pH. Triggered release of curcumin induced apoptosis in human triple-negative breast cancer cells; cell viability decreased to 34.3% after 24 h of treatment with the curcumin-loaded nanoparticles and deferoxamine, versus >80% viability without deferoxamine to trigger drug release. The biocompatibility, tunable composition and size, high hydrophobic drug loading, and triggered-release capability of this nanoscale coordination polymer make it well-suited for use in anticancer drug delivery.

Age-related losses in cardiac autonomic activity during a daytime nap.

In healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between young and older healthy adults during a daytime nap and a similar period of wakefulness (quiet wake; QW). For each condition, from the electrocardiogram (ECG), we obtained beat-to-beat HRV intervals (RR), root mean square of successive differences between adjacent heart-beat-intervals (RMSSD), high-frequency (HF), low-frequency (LF) power, and total power (TP), HF normalized units (HFnu ), and the LF/HF ratio. As previously reported, young subjects showed a parasympathetic dominance during NREM, compared with REM, prenap rest, and WASO. Moreover, older, compared to younger, adults showed significantly lower vagally mediated HRV (measured by RMSSD, HF, HFnu ) during NREM. Interestingly, however, no age-related differences were detected during prenap rest or QW. Altogether, our findings suggest a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.

Bio-inspired zwitterionic polymeric chelating assembly for treatment of copper-induced cytotoxicity and hemolysis.

We developed a hemocompatible, bio-inspired, multivalent, polymeric-chelating assembly based on the poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(serinyl acrylate) (PMPC-b-PserA) zwitterionic diblock copolymer. Functional PMPC-b-PserA was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization to catch and encapsulate free copper ions (Cu2+) in a solution. PMPC with an identical polar group to phospholipids exhibits high hydrophilicity and fouling resistance against non-specific adsorption, and inertness to the metal ions. On the other hand, PserA with pendant groups of amino acids possesses a strong capability to react with Cu2+ by coordination interaction. Therefore, when PMPC-b-PserA was brought into contact with Cu2+, a hydrophobic core with multiple coordination "bridges" between polymers and Cu2+ was formed, leading to self-assembly of core-shell polymer-metal nanoparticles. As a result, free Cu2+ ions can be removed from the solution to prevent damage to cells and tissues. The synthesis and chemical structure of PMPC-b-PserA were characterized, and the formation of self-assembled polymer-Cu2+ nanoparticles and colloidal stability were analyzed. More importantly, the detoxification of PMPC-b-PserA in presence of Cu2+ with fibroblast cells was demonstrated by increased cell viability >80%. In addition, the hemolysis, which occurred due to disruption of RBC membranes by free Cu2+, was effectively suppressed by adding PMPC-b-PserA. The bio-inspired and biocompatible chelating agent of PMPC-b-PserA provides a new treatment approach to encapsulate and detoxify heavy metals in complex media for chelation therapy.