Depressive Symptoms and Sleep Quality Mediate the Relationship Between Race and Quality of Life Among Patients With Heart Failure: A Serial Multiple Mediator Model.

BACKGROUND: Black patients with heart failure (HF) report worse quality of life (QoL) than White patients. Few investigators have examined mediators of the association between race and QoL, but depressive symptoms and sleep quality are associated with QoL. OBJECTIVE: The aim of this study was to determine whether depressive symptoms and sleep quality are mediators of the relationship between race and QoL among patients with HF. METHODS: This was a cross-sectional study. We included 271 outpatients with HF. Self-reported race (White/Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected at baseline. A serial multiple mediator analysis was conducted using the PROCESS macro for SPSS. RESULTS: Ninety-six patients (35.4%) were Black. Black participants reported higher levels of depressive symptoms and poorer sleep quality than White participants. Race was not directly associated with QoL but indirectly associated with QoL through depressive symptoms and poorer sleep quality. Because of higher levels of depressive symptoms and poorer sleep quality, Black participants reported poorer QoL than White participants. CONCLUSIONS: Depressive symptoms and sleep quality together mediated the relationship between race and QoL. These findings suggest that screening for depressive symptoms and sleep quality could identify patients at risk for poor QoL, especially in Black patients.

Comparison of ultrasonography, progesterone assay, ballottement, and non-return-to-heat with digital rectal palpation technique for early pregnancy diagnosis in Red Sokoto goat.

The objective of the study was to evaluate the effectiveness of the digital rectal palpation (DRP) technique for early pregnancy diagnosis and to compare the results of experiments I and II in the Red Sokoto goat. Experiment I had 68 goats with 52 does and 16 bucks. Does were divided into prostaglandin F2 -alpha (PGF2 α; n = 18), progesterone pessaries (P4 P; n = 18), and Control (n = 16) groups as oestrus synchronizaton methods. Bucks were used for oestrus detection (n = 6) and breeding (n = 10). Comparative pregnancy diagnosis was carried out on day 21 post-breeding using ultrasonography (US), DRP, progesterone assay (PA), ballottement (BL), and non-return-to-heat (NRH). Experiment II was a repeat but had 51 animals with 42 does and nine bucks; three bucks for oestrus detection and six for breeding. Does were divided into recto-vaginal artificial insemination (AI) by DRP (n = 14), vaginal speculum AI (n = 14), and Control-natural service (n = 14) groups, indicating breeding methods. Oestrus was synchronized with PGF2 α and pregnancy diagnosis was carried out on day 21 using US, DRP, PA, and NRH. The results for both experiments were similar. Pregnancy rates for PGF2 α group were 66.2%, 66.7%, 64.8%, 62.1%, and 63.0% for US, DRP, PA, BL, and NRH, respectively; P4 P had 81.5%, 81.5%, 42.6%, 20.3%, and 42.6% for US, DRP, PA, BL, and NRH, respectively; while Control was 73.6%, 79.2%, 70.9%, 73.6%, and 73.6% for US, DRP, PA, BL, and NRH, respectively. Proportions are significantly (p < .000) different in the P4 P group. It was concluded that the DRP technique was effective and consistent in early pregnancy diagnosis on day 21 and comparable to US, PA, BL, and non-return-to-oestrus in both experiments in Red Sokoto goat does.

In search of a better CPAP interface: A network meta-analysis comparing nasal masks, nasal pillows and oronasal masks.

Until now, no study has directly network meta-analysed the impact of nasal masks, nasal pillows and oronasal masks on continuous positive airway pressure therapy in patients with obstructive sleep apnea. This study aimed to meta-analyse the impact of three kinds of nasal interfaces with both network meta-analysis and pairwise comparison. PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to December 2020 for studies that compared the three types of nasal interfaces for treating obstructive sleep apnea with continuous positive airway pressure. The outcomes were residual apnea-hypopnea index, continuous positive airway pressure, and nightly average usage. The network meta-analysis was conducted using multivariate random-effects in a frequentist framework where three interfaces were ranked with the surface under the cumulative ranking probabilities. The pairwise comparison was conducted using random-effects meta-analysis. Twenty-nine articles comprising 6378 participants were included. The pairwise comparison showed both nasal masks and nasal pillows were associated with lower residual apnea-hypopnea index, lower continuous positive airway pressure, and higher continuous positive airway pressure adherence compared with oronasal masks. The surface under the cumulative ranking confirmed that nasal masks were associated with the lowest residual apnea-hypopnea index and highest adherence, while pillows were associated with the lowest continuous positive airway pressure. The meta-regression identified that lower pretreatment apnea-hypopnea index and continuous positive airway pressure determined during continuous positive airway pressure titration (versus determined during continuous positive airway pressure therapy) was associated with lower continuous positive airway pressure with nasal masks and nasal pillows. In conclusion, compared with oronasal masks, nasal masks and nasal pillows are better interfaces, especially in patients with lower pretreatment apnea-hypopnea index and those with the therapeutic pressure determined during continuous positive airway pressure titration.

Spatially Controlled CO2 Conversion Kinetics in Natural Leaves for Motion Generation.

Living systems that can spontaneously exhibit directional motion belong to diverse classes such as bacteria, sperm and plankton. They have fascinated scientists in recent years to design completely artificial or biohybrid mobile objects. Natural ingredients, like parts of plants, have been used to elaborate miniaturized dynamic objects, which can move when they are combined with other, non-natural, building blocks. Herein, we report that the precise structural tailoring of natural plant leaves allows generating a spatially predefined and confined release of oxygen gas, due to the conversion of carbon dioxide. This constitutes the driving force for generating motion, which is solely due to the respiration of leaves by photosynthesis. The rate of gas evolution can be fine-tuned by changing the light intensity and the leaf size, allowing ultimately to control the motility of objects with dimensions ranging from the millimeter to the micrometer scale.

Light and electric field induced unusual large-scale charge separation in hybrid semiconductor objects.

Separation of electric charges is the most crucial phenomenon in natural photosynthesis, and is also extremely important for many artificial energy conversion systems based on semiconductors. The usual roadblock in this context is the fast recombination of electrons and holes. Here we demonstrate that the synergy of light and electric fields allows separating very efficiently electric charges over an unusually large distance in TiO2. The generated internal electric field can also be used to shuttle electrons simultaneously to the two opposite sides of a hybrid TiO2-polyaniline object. This counterintuitive behavior is based on the combination of the principles of bipolar electrochemistry and semi-conductor physics.

The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

IL-6 ameliorates defective leptin sensitivity in DIO ventromedial hypothalamic nucleus neurons.

Rats selectively bred to develop diet-induced obesity (DIO) have an early onset reduction in the sensitivity of their ventromedial hypothalamic nucleus (VMN) neurons to leptin compared with diet-resistant (DR) rats. This reduced sensitivity includes decreased leptin receptor (Lepr-b) mRNA expression, leptin receptor binding, leptin-induced phosphorylation of STAT3 (pSTAT3), and impaired leptin excitation (LepE) of VMN neurons. When administered exogenously, the pancreatic peptide, amylin, acts synergistically to reduce food intake and body weight in obese, leptin-resistant DIO rats by increasing VMN leptin signaling, likely by stimulation of microglia IL-6, which acts on its receptor to increase leptin-induced pSTAT3. Here, we demonstrate that incubation of cultured VMN neurons of outbred rats with IL-6 increases their leptin sensitivity. Control, dissociated DIO VMN neurons express 66% less Lepr-b and 75% less Bardet Biedl Syndrome-6 (BBS6) mRNA and have reduced leptin-induced activation of LepE neurons compared with DR neurons. Incubation for 4 days with IL-6 increased DIO neuron Lepr-b expression by 77% and BBS6 by 290% and corrected their defective leptin activation of LepE neurons to DR levels. Since BBS6 enhances trafficking of Lepr-b to the cell membrane, the increases in Lepr-b and BBS6 expression appear to account for correction of the reduced leptin excitation of DIO LepE neurons to that of control DR rats. These data support prior findings suggesting that IL-6 mediates the leptin-sensitizing effects of amylin on VMN neurons and that the inherent leptin resistance of DIO rats can be effectively reversed at a cellular level by IL-6.

Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity.

Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80-90% in 4-wk-old male DR rats reduced their ARC and VMN (125)I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.

Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.

Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.

Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats.

The objective of this study was to determine the potential role of astrocyte-derived ketone bodies in regulating the early changes in caloric intake of diet induced-obese (DIO) versus diet-resistant (DR) rats fed a 31.5% fat high-energy (HE) diet. After 3 days on chow or HE diet, DR and DIO rats were assessed for their ventromedial hypothalamic (VMH) ketone bodies levels and neuronal ventromedial hypothalamic nucleus (VMN) sensing using microdialysis coupled to continuous food intake monitoring and calcium imaging in dissociated neurons, respectively. DIO rats ate more than DR rats over 3 days of HE diet intake. On day 3 of HE diet intake, DR rats reduced their caloric intake while DIO rats remained hyperphagic. Local VMH astrocyte ketone bodies production was similar between DR and DIO rats during the first 6 h after dark onset feeding but inhibiting VMH ketone body production in DR rats on day 3 transiently returned their intake of HE diet to the level of DIO rats consuming HE diet. In addition, dissociated VMN neurons from DIO and DR rats were equally sensitive to the largely excitatory effects of ß-hydroxybutyrate. Thus while DR rats respond to increased VMH ketone levels by decreasing their intake after 3 days of HE diet, this is not the case of DIO rats. These data suggest that DIO inherent leptin resistance prevents ketone bodies inhibitory action on food intake.

Interim estimates of 2013/14 influenza clinical severity and vaccine effectiveness in the prevention of laboratory-confirmed influenza-related hospitalisation, Canada, February 2014.

During the 2013/14 influenza season in Canada, 631 of 654 hospitalisations for laboratory-confirmed influenza enrolled in sentinel hospitals were due to Influenza A. Of the 375 with known subtype, influenza A(H1N1) accounted for 357. Interim unmatched vaccine effectiveness adjusted for age and presence of one or more medical comorbidities was determined by test-negative case-control design to be 58.5% (90% confidence interval (CI): 43.9-69.3%) overall and 57.9% (90% CI: 37.7-71.5) for confirmed influenza A(H1N1).

OSA diagnosis goes wearable: are the latest devices ready to shine?

STUDY OBJECTIVES: Since 2019, the FDA has cleared nine novel obstructive sleep apnea (OSA)-detecting wearables for home sleep apnea testing, with many now commercially available for sleep clinicians to integrate into their clinical practices. To help clinicians comprehend these devices and their functionalities, we meticulously reviewed their operating mechanisms, sensors, algorithms, data output, and related performance evaluation literature. METHODS: We collected information from PubMed, FDA clearance documents, ClinicalTrial.gov, and web sources, with direct industry input whenever feasible. RESULTS: In this "device-centered" review, we broadly categorized these wearables into two main groups: those that primarily harness Photoplethysmography (PPG) data and those that do not. The former include the peripheral arterial tonometry (PAT)-based devices. The latter was further broken down into two key subgroups: acoustic-based and respiratory effort-based devices. We provided a performance evaluation literature review and objectively compared device-derived metrics and specifications pertinent to sleep clinicians. Detailed demographics of study populations, exclusion criteria, and pivotal statistical analyses of the key validation studies are summarized. CONCLUSIONS: In the foreseeable future, these novel OSA-detecting wearables may emerge as primary diagnostic tools for patients at risk for moderate-to-severe OSA without significant comorbidities. While more devices are anticipated to join this category, there remains a critical need for cross-device comparison studies as well as independent performance evaluation and outcome research in diverse populations. Now is the moment for sleep clinicians to immerse themselves in understanding these emerging tools to ensure our patient-centered care is improved through the appropriate implementation and utilization of these novel sleep technologies.

Correction: Detection of obstructive sleep apnea using Belun Sleep Platform wearable with neural network-based algorithm and its combined use with STOP-Bang questionnaire.

[This corrects the article DOI: 10.1371/journal.pone.0258040.].

Consumer Wearable Sleep Trackers: Are They Ready for Clinical Use?

As the importance of good sleep continues to gain public recognition, the market for sleep-monitoring devices continues to grow. Modern technology has shifted from simple sleep tracking to a more granular sleep health assessment. We examine the available functionalities of consumer wearable sleep trackers (CWSTs) and how they perform in healthy individuals and disease states. Additionally, the continuum of sleep technology from consumer-grade to medical-grade is detailed. As this trend invariably grows, we urge professional societies to develop guidelines encompassing the practical clinical use of CWSTs and how best to incorporate them into patient care plans.

Evaluation of local oxygen flux produced by photoelectrochemical hydroxide oxidation by scanning electrochemical microscopy.

Several in-situ electrochemical approaches have been developed for performing a localized photoelectrochemical investigation of the photoanode. One of the techniques is scanning electrochemical microscopy (SECM), which probes local heterogeneous reaction kinetics and fluxes of generated species. In traditional SECM analysis of photocatalysts, evaluation of the influence of radiation on the rate of studied reaction requires an additional dark background experiment. Here, using SECM and an inverted optical microscope, we demonstrate the determination of O2 flux caused by light-driven photoelectrocatalytic water splitting. Photocatalytic signal and dark background are recorded in a single SECM image. We used an indium tin oxide electrode modified with hematite (α-Fe2O3) by electrodeposition as a model sample. The light-driven flux of oxygen is calculated by analysis of SECM image recorded in substrate generation/tip collection mode. In photoelectrochemistry, the qualitative and quantitative knowledge of oxygen evolution will open new doors for understanding the local effects of dopants and hole scavengers in a straightforward and conventional manner.

Belun Ring (Belun Sleep System BLS-100): Deep learning-facilitated wearable enables obstructive sleep apnea detection, apnea severity categorization, and sleep stage classification in patients suspected of obstructive sleep apnea.

GOAL AND AIMS: Our objective was to evaluate the performance of Belun Ring with second-generation deep learning algorithms in obstructive sleep apnea (OSA) detection, OSA severity categorization, and sleep stage classification. FOCUS TECHNOLOGY: Belun Ring with second-generation deep learning algorithms REFERENCE TECHNOLOGY: In-lab polysomnography (PSG) SAMPLE: Eighty-four subjects (M: F = 1:1) referred for an overnight sleep study were eligible. Of these, 26% had PSG-AHI<5; 24% had PSG-AHI 5-15; 23% had PSG-AHI 15-30; 27% had PSG-AHI ≥ 30. DESIGN: Rigorous performance evaluation by comparing Belun Ring to concurrent in-lab PSG using the 4% rule. CORE ANALYTICS: Pearson's correlation coefficient, Student's paired t-test, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Cohen's kappa coefficient (kappa), Bland-Altman plots with bias and limits of agreement, receiver operating characteristics curves with area under the curve, and confusion matrix. CORE OUTCOMES: The accuracy, sensitivity, specificity, and kappa in categorizing AHI ≥ 5 were 0.85, 0.92, 0.64, and 0.58, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 15 were 0.89, 0.91, 0.88, and 0.79, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 30 were 0.91, 0.83, 0.93, and 0.76, respectively. BSP2 also achieved an accuracy of 0.88 in detecting wake, 0.82 in detecting NREM, and 0.90 in detecting REM sleep. CORE CONCLUSION: Belun Ring with second-generation algorithms detected OSA with good accuracy and demonstrated a moderate-to-substantial agreement in categorizing OSA severity and classifying sleep stages.

Morbidity indicators of urogenital schistosomosis and risk factors in school children in three Senatorial Districts of Cross River State, Nigeria.

The morbidity indicators and risk factors of urinary schistosomosis in school-age children were ascertained in three Senatorial Districts of Cross River State (CRS). A cross-sectional study conducted between April 2015 and March 2016. Seven hundred and seventy-seven (777) urine samples were randomly collected from selected children and examined for ova of Schistosoma haematobium, using a modified filtration system. Commercial reagent strips were employed for the detection of haematuria and proteinuria. Chi-square test was used to determine the statistical differences between the data in subgroups and the results from specimen examinations. S. haematobium ova was observed in 13 (1.7%) of the 777 participants examined. Ninety (11.6%) children showed haematuria, and 137 (17.6%) showed proteinuria. Infection varied significantly across the age-groups (P<0.05). Males 11 (2.4%) were more infected than females 2 (0.6%) (P<0.05). The age group 9-12 years accounted for the highest mean ova count (7.33±2.1) in urine samples analysed. Female participants had a higher mean ova count (7.50±0.71) than male participants (6.18±1.66). Age, gender and the habit of fetching water from streams were significant risk factors for urinary schistosomiasis. It is evident from this study that S. haematobium infection is still endemic in the three Senatorial Districts of CRS, despite periodic chemotherapy.

Comparison of expiratory pressures generated by four different EPAP devices in a laboratory bench setting.

OBJECTIVE/BACKGROUND: Expiratory positive airway pressure (EPAP) has been a treatment option for patients with obstructive sleep apnea (OSA). ULTepap is a new FDA-cleared EPAP device that seals the nares with a nasal pillow interface. Comparisons of expiratory pressures generated by ULTepap and other EPAP devices like Provent, Bongo Rx, and Theravent are not available. We aimed to compare the backpressures created by these devices in an in vitro laboratory bench setting. METHODS: A test rig was designed and fabricated to test the expiratory pressures generated by ULTepap, Provent, Bongo Rx, and Theravent. Airflow was generated by a linear actuator-driven piston in a syringe, and a range of flow rates was provided by varying the voltage input to the actuator. The resulting expiratory and inspiratory pressures were measured and resistances were calculated. RESULTS: The backpressures generated by ULTepap and Provent were comparable at all flow rates. For flow rates at 99/142/212 ml/s, the expiratory pressures were 3.5/7.5/13.8 cmH2O for ULTepap and 4.5/8.5/14.5 cmH2O for Provent. Bongo Rx and Theravent devices produced substantially lower backpressures compared to ULTepap devices (0.8/1.8/3.5 cmH2O for Bongo Rx and 0.9/2.2/5.3 cmH2O for Theravent at flow rates of 99/142/212 ml/s). All four devices presented very low inspiratory flow resistance, with all generating 0.5 cmH2O or less at all flow rates. CONCLUSION: Not all FDA-cleared EPAP devices produce similar expiratory pressure profiles. ULTepap generated backpressures closest to that of Provent. Clinical trials comparing the efficacy, tolerance, and adherence of these EPAP devices in patients with OSA are warranted.

Erythropoietin-derived peptide treatment reduced neurological deficit and neuropathological changes in a mouse model of tauopathy.

BACKGROUND: Prominent activation of microglial immune/inflammatory processes is a characteristic feature of brains of patients with tauopathies including Alzheimer's disease (AD), suggesting that neuroinflammation may be a critical factor in their pathogenesis. Strategies aimed at developing new therapeutics for tauopathies based on anti-inflammation or immunomodulation are likely to be promising avenues of research. We previously developed JM4-a 19'mer cyclic peptide derived from the first loop of human erythropoietin. This peptide possesses beneficial immune modulatory and tissue protective effects while lacking the undesirable side effects of full-length erythropoietin. In this preclinical study, we investigated the effect of chronic JM4 treatment on the PS19 mouse that carries the P301S mutant human tau gene, linked to a form of frontotemporal dementia. This transgenic mouse has been widely used as a model of tauopathies including AD and related dementias. METHODS: Daily subcutaneous treatment of female PS19 mice with JM4 was initiated before disease onset and continued on for the animals' lifespan. The progression of neurological deficit and the lifespan of these mice were assessed. To evaluate the effect of JM4 treatment on cognition of these animals, the PS19 mice underwent Barnes maze test and elevated plus maze test. In addition, neuronal loss, phosphorylated tau aggregation, and microglial activation were assessed using immunohistochemistry of PS19 mouse brain sections. RESULTS: JM4 treatment of PS19 mice initiated before disease onset reduced neurological deficit, prolonged lifespan, and rescued memory impairment. The beneficial effects of JM4 were accompanied by reductions in neuronal loss, phosphorylated tau aggregation, and microglial activation in the PS19 mouse brain. LIMITATIONS: Use of a single dose of JM4 and female mice only. CONCLUSION: JM4 is a potential novel therapeutic agent for the treatment of tauopathies including AD and related dementias.