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.].

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.

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.

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.

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.

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.

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.

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.

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

Many wearables allow physiological data acquisition in sleep and enable clinicians to assess sleep outside of sleep labs. Belun Sleep Platform (BSP) is a novel neural network-based home sleep apnea testing system utilizing a wearable ring device to detect obstructive sleep apnea (OSA). The objective of the study is to assess the performance of BSP for the evaluation of OSA. Subjects who take heart rate-affecting medications and those with non-arrhythmic comorbidities were included in this cohort. Polysomnography (PSG) studies were performed simultaneously with the Belun Ring in individuals who were referred to the sleep lab for an overnight sleep study. The sleep studies were manually scored using the American Academy of Sleep Medicine Scoring Manual (version 2.4) with 4% desaturation hypopnea criteria. A total of 78 subjects were recruited. Of these, 45% had AHI < 5; 18% had AHI 5-15; 19% had AHI 15-30; 18% had AHI ≥ 30. The Belun apnea-hypopnea index (bAHI) correlated well with the PSG-AHI (r = 0.888, P < 0.001). The Belun total sleep time (bTST) and PSG-TST had a high correlation coefficient (r = 0.967, P < 0.001). The accuracy, sensitivity, specificity in categorizing AHI ≥ 15 were 0.808 [95% CI, 0.703-0.888], 0.931 [95% CI, 0.772-0.992], and 0.735 [95% CI, 0.589-0.850], respectively. The use of beta-blocker/calcium-receptor antagonist and the presence of comorbidities did not negatively affect the sensitivity and specificity of BSP in predicting OSA. A diagnostic algorithm combining STOP-Bang cutoff of 5 and bAHI cutoff of 15 events/h demonstrated an accuracy, sensitivity, specificity of 0.938 [95% CI, 0.828-0.987], 0.944 [95% CI, 0.727-0.999], and 0.933 [95% CI, 0.779-0.992], respectively, for the diagnosis of moderate to severe OSA. BSP is a promising testing tool for OSA assessment and can potentially be incorporated into clinical practices for the identification of OSA. Trial registration: ClinicalTrial.org NCT03997916 https://clinicaltrials.gov/ct2/show/NCT03997916?term=belun+ring&draw=2&rank=1.

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.

Growth of sillenite Bi12FeO20 single crystals: structural, thermal, optical, photocatalytic features and first principle calculations.

Ideal sillenite type Bi12FeO20 (BFO) micron sized single crystals have been successfully grown via inexpensive hydrothermal method. The refined single crystal X-ray diffraction data reveals cubic Bi12FeO20 structure with single crystal parameters. Occurrence of rare Fe4+ state is identified via X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS). The lattice parameter (a) and corresponding molar volume (Vm) of Bi12FeO20 have been measured in the temperature range of 30-700 °C by the X-ray diffraction method. The thermal expansion coefficient (α) 3.93 × 10-5 K-1 was calculated from the measured values of the parameters. Electronic structure and density of states are investigated by first principle calculations. Photoelectrochemical measurements on single crystals with bandgap of 2 eV reveal significant photo response. The photoactivity of as grown crystals were further investigated by degrading organic effluents such as Methylene blue (MB) and Congo red (CR) under natural sunlight. BFO showed photodegradation efficiency about 74.23% and 32.10% for degrading MB and CR respectively. Interesting morphology and microstructure of pointed spearhead like BFO crystals provide a new insight in designing and synthesizing multifunctional single crystals.

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.

Belun Ring Platform: a novel home sleep apnea testing system for assessment of obstructive sleep apnea.

STUDY OBJECTIVES: The objective of the study is to validate the performance of Belun Ring Platform, a novel home sleep apnea testing system using a patented pulse oximeter sensor and a proprietary cloud-based neural networks algorithm. METHODS: The Belun Ring captures oxygen saturation, photoplethysmography, and accelerometer signals. The Belun Ring total sleep time is derived from features extracted from accelerometer, oxygen saturation, and photoplethysmography signals. The Belun Ring respiratory event index is derived from Belun Ring total sleep time and features extracted from heart rate variability and oxygen saturation changes. A total of 50 adults without significant cardiopulmonary or neuromuscular comorbidities and heart rate affecting medications were evaluated. In-lab sleep studies were performed simultaneously with the Ring and the studies were manually scored using the American Academy of Sleep Medicine Scoring Manual 4% desaturation criteria. RESULTS: The Belun Ring respiratory event index correlated well with the polysomnography-apnea-hypopnea index (AHI; r = .894, P < .001). The sensitivity and specificity in categorizing AHI ≥ 15 events/h were 0.85 and 0.87, respectively, and the positive predictive value and negative predictive value were 0.88 and 0.83, respectively. The Belun Ring total sleep time also correlated well with the polysomnography-total sleep time (r = .945, P < .001). Although the Belun Ring Platform has a good overall performance, it tends to overestimate AHI in individuals with AHI under 15 events/h and underestimate AHI in those with AHI over 15 events/h. Conclusions: In this proof-of-concept study, the Belun Ring Platform demonstrated a reasonable accuracy in predicting AHI and total sleep time in patients without significant comorbidities and heart rate-affecting medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Validation of a Novel Device for Screening Patients With Symptoms of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04121923; Identifier: NCT04121923.

Support vector machine prediction of obstructive sleep apnea in a large-scale Chinese clinical sample.

STUDY OBJECTIVES: Polysomnography is the gold standard for diagnosis of obstructive sleep apnea (OSA) but it is costly and access is often limited. The aim of this study is to develop a clinically useful support vector machine (SVM)-based prediction model to identify patients with high probability of OSA for nonsleep specialist physician in clinical practice. METHODS: The SVM model was developed using the features routinely collected at the clinical evaluation from 6,875 Chinese patients referred to sleep clinics for suspected OSA. Three apnea-hypopnea index (AHI) cutoffs, ≥5/h, ≥15/h, and ≥30/h were used to define the severity of OSA. The continuous and categorized features were selected separately and were further selected through stepwise forward feature selection. The modeling was achieved through fivefold cross-validation. The model discriminative ability was evaluated for the whole data set and four subgroups categorized with gender and age (<65 versus ≥65 years old [y/o]). RESULTS: Two features were selected to predict AHI cutoff ≥5/h with six features selected for ≥15/h, and six features selected for ≥30/h, respectively, to reach Area under the Receiver Operating Characteristic (AUROC) 0.82, 0.80, and 0.78, respectively. The sensitivity was 74.14%, 75.18%, and 70.26%, while the specificity was 74.71%, 68.73%, and 70.30%, respectively. Compared to logistic regression, Berlin questionnaire, NoSAS Score, and Supersparse Linear Integer Model (SLIM) scoring system, the SVM model performs better with a more balanced sensitivity and specificity. The discriminative ability was best for male <65 y/o and modest for female ≥65 y/o. CONCLUSION: Our model provides a simple and accurate modality for early identification of patients with OSA and may potentially help prioritize them for sleep study.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

In vivo Bioluminescence Imaging Used to Monitor Disease Activity and Therapeutic Response in a Mouse Model of Tauopathy.

Many studies of tauopathy use transgenic mice that overexpress the P301S mutant form of tau. Neuronal damage in these mice is associated with astrogliosis and induction of glial fibrillary acidic protein (GFAP) expression. GFAP-luc transgenic mice express firefly luciferase under the GFAP promoter, allowing bioluminescence to be measured non-invasively as a surrogate biomarker for astrogliosis. We bred double transgenic mice possessing both P301S and GFAP-luc cassettes and compared them to control mice bearing only the GFAP-luc transgene. We used serial bioluminescent images to define the onset and the time course of astrogliosis in these mice and this was correlated with the development of clinical deficit. Mice containing both GFAP-luc and P301S transgenes showed increased luminescence indicative of astroglial activation in the brain and spinal cord. Starting at 5 months old, the onset of clinical deterioration in these mice corresponded closely to the initial rise in the luminescent signal. Post mortem analysis showed the elevated luminescence was correlated with hyperphosphorylated tau deposition in the hippocampus of double transgenic mice. We used this method to determine the therapeutic effect of JM4 peptide [a small peptide immunomodulatory agent derived from human erythropoietin (EPO)] on double transgenic mice. JM4 treatment significantly decreased the intensity of luminescence, neurological deficit and hyperphosphorylated tau in mice with both the P301S and GFAP-luc transgenes. These findings indicate that bioluminescence imaging (BLI) is a powerful tool for quantifying GFAP expression in living P301S mice and can be used as a noninvasive biomarker of tau-induced neurodegeneration in preclinical therapeutic trials.