A sequential, multiple-assignment, randomized trial of analgesic strategies for acute musculoskeletal Pain.

BACKGROUND: Most methodologically rigorous, ED-based, comparative effectiveness analgesic studies completed in the last two decades failed to find a clinically important difference between the comparators. We believe that many of these comparative effectiveness studies were biased towards the null hypothesis because some ED patients with intense pain will respond to relatively mild interventions. We hypothesized that including a run-in period would alter the results of an acute pain RCT. METHODS: We conducted a sequential, multiple-assignment, randomized study. Adults with acute moderate/severe musculoskeletal pain were randomized (3:1 ratio) to run-in period or no run-in. We administered 650 mg acetaminophen to run-in participants. Those run-in patients who reported insufficient relief one-hour later were randomized (1:1 ratio) to ibuprofen 800mg PO or ketorolac 20mg PO as were all participants randomized to no run-in. The primary outcome was achieving a clinically important improvement, defined as improvement ≥1.3 on a 0-10 scale. We built a logistic regression model including run-in/no run-in, ketorolac/ibuprofen, age and sex. RESULTS: Of 307 participants who received acetaminophen, 100 (32.6%) reported inadequate relief and were randomized to an NSAID. Of the 100 patients randomized to no run-in, 84/100 (84%) achieved the primary outcome versus 246/287 (86%) run-in participants (95% CI for difference = 2%:-7,10%). Among run-in participants who received an NSAID, 82/99(83%) achieved the primary outcome versus 84/100(84%) no run-in participants (p = 0.82). Among all ibuprofen participants, 44/49(90%) randomized to run-in and 42/50(84%) randomized to no run-in achieved the primary outcome. Among all ketorolac participants, 38/50(76%) randomized to run-in and 42/50 (84%) randomized to no run-in achieved the primary outcome. We observed the following results in a multivariable analysis: OR for ketorolac versus ibuprofen:0.60 (95% CI: 0.28, 1.28); OR for run-in versus no run-in:0.91(95% CI: 0.43, 1.93). CONCLUSIONS: Among patients with acute musculoskeletal pain, using an acetaminophen first strategy did not alter pain outcomes.

Discovery of a long half-life AURKA inhibitor to treat MYC-amplified solid tumors as a monotherapy and in combination with everolimus.

Aurora kinase inhibitors such as alisertib can destabilize MYC-family oncoproteins and have demonstrated compelling anti-tumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A (AURKA) inhibitor that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer (BC) cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC- overexpressing xenografts including SCLC, triple-negative breast cancer (TNBC), hepatocellular carcinoma and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC- driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC- and/or N-MYC.

Dermoscopic features of pigmented basal cell carcinoma according to size.

BACKGROUND: Basal cell carcinoma (BCC), the most common skin cancer in humans, requires early detection. Dermoscopy enhances diagnostic accuracy through a noninvasive approach. Pigmented BCC (pBCC) is characterized by distinctive dermoscopic features, including the presence of pigmented globules or nests. While dermoscopic features of large pBCC (size >6 mm) have been extensively studied, limited data are available on small pBCC (size ≤6 mm) and its relationship with tumor progression. METHODS: Dermoscopic images of histologically proven pBCCs were collected between 2014 and 2022 at Hualien Tzu Chi Hospital. Each image was analyzed for patterns of pigmentation, vasculature, and epidermal and dermal structures. Statistical analysis was performed to compare the differences according to the size and the trend during tumor progression. RESULTS: In total, 135 pBCCs (48 small and 87 large) were included. Pigment structures were present in all cases. Short fine telangiectasia and small erosions constituted over 85% of the cases, showing no significant distinction between small and large pBCCs, nor any specific pattern correlating with tumor enlargement. The number of arborizing vessels, ulcerations, and shiny white structures showed an increasing trend associated with size progression. Arborizing vessels appeared when tumor size exceeded 6 mm. CONCLUSIONS: This study provides a dynamic interpretation of the dermoscopic features of pBCC according to size enlargement. Short fine telangiectasia and small erosions are highly important features for the early diagnosis of small pBCCs. Arborizing vessels, ulceration, and shiny white structures are more frequent in large pBCCs, and they increase in association with tumor progression.

The clinical application of traditional Chinese medicine NRICM101 in hospitalized patients with COVID-19.

BACKGROUND: The aim of this study was to assess the efficacy and safety of NRICM101 in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We conducted a retrospective study from 20 April 2021 to 8 July 2021, and evaluated the safety and outcomes (mortality, hospital stay, mechanical ventilation, oxygen support, diarrhea, serum potassium) in COVID-19 patients. Propensity score matching at a 1:2 ratio was performed to reduce confounding factors. RESULTS: A total of 201 patients were analyzed. The experimental group (n = 67) received NRICM101 and standard care, while the control group (n = 134) received standard care alone. No significant differences were observed in mortality (10.4% vs. 14.2%), intubation (13.8% vs. 11%), time to intubation (10 vs. 11 days), mechanical ventilation days (0 vs. 9 days), or oxygen support duration (6 vs. 5 days). However, the experimental group had a shorter length of hospitalization (odds ratio = 0.12, p = 0.043) and fewer mechanical ventilation days (odds ratio = 0.068, p = 0.008) in initially severe cases, along with an increased diarrhea risk (p = 0.035). CONCLUSION: NRICM101 did not reduce in-hospital mortality. However, it shortened the length of hospitalization and reduced mechanical ventilation days in initially severe cases. Further investigation is needed.

Overexpressing plant ferredoxin-like protein enhances photosynthetic efficiency and carbohydrates accumulation in Phalaenopsis.

Crassulacean acid metabolism (CAM) is one of three major models of carbon dioxide assimilation pathway with better water-use efficiency and slower photosynthetic efficiency in photosynthesis. Previous studies indicated that the gene of sweet pepper plant ferredoxin-like protein (PFLP) shows high homology to the ferredoxin-1(Fd-1) family that belongs to photosynthetic type Fd and involves in photosystem I. It is speculated that overexpressing pflp in the transgenic plant may enhance photosynthetic efficiency through the electron transport chain (ETC). To reveal the function of PFLP in photosynthetic efficiency, pflp transgenic Phalaenopsis, a CAM plant, was generated to analyze photosynthetic markers. Transgenic plants exhibited 1.2-folds of electron transport rate than that of wild type (WT), and higher CO2 assimilation rates up to 1.6 and 1.5-folds samples at 4 pm and 10 pm respectively. Enzyme activity of phosphoenolpyruvate carboxylase (PEPC) was increased to 5.9-folds in Phase III, and NAD+-linked malic enzyme (NAD+-ME) activity increased 1.4-folds in Phase IV in transgenic plants. The photosynthesis products were analyzed between transgenic plants and WT. Soluble sugars contents such as glucose, fructose, and sucrose were found to significantly increase to 1.2, 1.8, and 1.3-folds higher in transgenic plants. The starch grains were also accumulated up to 1.4-folds in transgenic plants than that of WT. These results indicated that overexpressing pflp in transgenic plants increases carbohydrates accumulation by enhancing electron transport flow during photosynthesis. This is the first evidence for the PFLP function in CAM plants. Taken altogether, we suggest that pflp is an applicable gene for agriculture application that enhances electron transport chain efficiency during photosynthesis.

Intelligent Performance Evaluation in Rowing Sport Using a Graph-Matching Network.

Rowing competitions require consistent rowing strokes among crew members to achieve optimal performance. However, existing motion analysis techniques often rely on wearable sensors, leading to challenges in sporter inconvenience. The aim of our work is to use a graph-matching network to analyze the similarity in rowers' rowing posture and further pair rowers to improve the performance of their rowing team. This study proposed a novel video-based performance analysis system to analyze paired rowers using a graph-matching network. The proposed system first detected human joint points, as acquired from the OpenPose system, and then the graph embedding model and graph-matching network model were applied to analyze similarities in rowing postures between paired rowers. When analyzing the postures of the paired rowers, the proposed system detected the same starting point of their rowing postures to achieve more accurate pairing results. Finally, variations in the similarities were displayed using the proposed time-period similarity processing. The experimental results show that the proposed time-period similarity processing of the 2D graph-embedding model (GEM) had the best pairing results.

Perovskite-Based X-ray Detectors.

X-ray detection has widespread applications in medical diagnosis, non-destructive industrial radiography and safety inspection, and especially, medical diagnosis realized by medical X-ray detectors is presenting an increasing demand. Perovskite materials are excellent candidates for high-energy radiation detection based on their promising material properties such as excellent carrier transport capability and high effective atomic number. In this review paper, we introduce X-ray detectors using all kinds of halide perovskite materials along with various crystal structures and discuss their device performance in detail. Single-crystal perovskite was first fabricated as an active material for X-ray detectors, having excellent performance under X-ray illumination due to its superior photoelectric properties of X-ray attenuation with µm thickness. The X-ray detector based on inorganic perovskite shows good environmental stability and high X-ray sensitivity. Owing to anisotropic carrier transport capability, two-dimensional layered perovskites with a preferred orientation parallel to the substrate can effectively suppress the dark current of the device despite poor light response to X-rays, resulting in lower sensitivity for the device. Double perovskite applied for X-ray detectors shows better attenuation of X-rays due to the introduction of high-atomic-numbered elements. Additionally, its stable crystal structure can effectively lower the dark current of X-ray detectors. Environmentally friendly lead-free perovskite exhibits potential application in X-ray detectors by virtue of its high attenuation of X-rays. In the last section, we specifically introduce the up-scaling process technology for fabricating large-area and thick perovskite films for X-ray detectors, which is critical for the commercialization and mass production of perovskite-based X-ray detectors.

Unified real-time environmental-epidemiological data for multiscale modeling of the COVID-19 pandemic.

An impressive number of COVID-19 data catalogs exist. However, none are fully optimized for data science applications. Inconsistent naming and data conventions, uneven quality control, and lack of alignment between disease data and potential predictors pose barriers to robust modeling and analysis. To address this gap, we generated a unified dataset that integrates and implements quality checks of the data from numerous leading sources of COVID-19 epidemiological and environmental data. We use a globally consistent hierarchy of administrative units to facilitate analysis within and across countries. The dataset applies this unified hierarchy to align COVID-19 epidemiological data with a number of other data types relevant to understanding and predicting COVID-19 risk, including hydrometeorological data, air quality, information on COVID-19 control policies, vaccine data, and key demographic characteristics.

Predicting the successful application of high-flow nasal oxygen cannula in patients with COVID-19 respiratory failure: a retrospective analysis.

BACKGROUND: The right time of high-flow nasal cannulas (HFNCs) application in COVID-19 patients with acute respiratory failure remains uncertain. RESEARCH DESIGN AND METHODS: In this retrospective study, COVID-19-infected adult patients with hypoxemic respiratory failure were enrolled. Their baseline epidemiological data and respiratory failure related parameters, including the Ventilation in COVID-19 Estimation (VICE), and the ratio of oxygen saturation (ROX index), were recorded. The primary outcome measured was the 28-day mortality. RESULTS: A total of 69 patients were enrolled. Fifty-four (78%) patients who intubated and received invasive mechanical ventilatory (MV) support on day 1 were enrolled in the MV group. The remaining fifteen (22%) patients received HFNC initially (HFNC group), in which, ten (66%) patients were not intubated during hospitalization were belong to HFNC-success group and five (33%) of these patients were intubated later due to disease progression were attributed to HFNC-failure group. Compared with those in the MV group, those in the HFNC group had a lower mortality rate (6.7% vs. 40.7%, p = 0.0138). There were no differences in baseline characteristics among the two groups; however, the HFNC group had a lower VICE score (0.105 [0.049-0.269] vs. 0.260 [0.126-0.693], p = 0.0092) and higher ROX index (5.3 [5.1-10.7] vs. 4.3 [3.9-4.9], p = 0.0007) than the MV group. The ROX index was higher in the HFNC success group immediately before (p = 0.0136) and up to 12 hours of HFNC therapy than in the HFNC failure group. CONCLUSIONS: Early intubation may be considered in patients with a higher VICE score or a lower ROX index. The ROX score during HFNCs use can provide an early warning sign of treatment failure. Further investigations are warranted to confirm these results.

High flow nasal cannulas (HFNCs) were widely used in patients with COVID-19 infection related hypoxemic respiratory failure. However, there were concerns about its failure and related delayed intubation may be associated with a higher mortality rate. This retrospective study revealed patients with higher baseline disease severity and higher VICE scores may be treated with primary invasive mechanical ventilation. On the contrary, if their baseline VICE score is low and ROX index is high, HFNCs treatment might be safely applied initially. The trends of serial ROX index values during HFNC use could be a reliable periscope to predict the HFNC therapy outcome, therefore avoided delayed intubation.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Outcome prediction in hospitalized COVID-19 patients: Comparison of the performance of five severity scores.

Background: The aim of our study was to externally validate the predictive capability of five developed coronavirus disease 2019 (COVID-19)-specific prognostic tools, including the COVID-19 Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), Shang COVID severity score, COVID-intubation risk score-neutrophil/lymphocyte ratio (IRS-NLR), inflammation-based score, and ventilation in COVID estimator (VICE) score. Methods: The medical records of all patients hospitalized for a laboratory-confirmed COVID-19 diagnosis between May 2021 and June 2021 were retrospectively analyzed. Data were extracted within the first 24 h of admission, and five different scores were calculated. The primary and secondary outcomes were 30-day mortality and mechanical ventilation, respectively. Results: A total of 285 patients were enrolled in our cohort. Sixty-five patients (22.8%) were intubated with ventilator support, and the 30-day mortality rate was 8.8%. The Shang COVID severity score had the highest numerical area under the receiver operator characteristic (AUC-ROC) (AUC 0.836) curve to predict 30-day mortality, followed by the SEIMC score (AUC 0.807) and VICE score (AUC 0.804). For intubation, both the VICE and COVID-IRS-NLR scores had the highest AUC (AUC 0.82) compared to the inflammation-based score (AUC 0.69). The 30-day mortality increased steadily according to higher Shang COVID severity scores and SEIMC scores. The intubation rate exceeded 50% in the patients stratified by higher VICE scores and COVID-IRS-NLR score quintiles. Conclusion: The discriminative performances of the SEIMC score and Shang COVID severity score are good for predicting the 30-day mortality of hospitalized COVID-19 patients. The COVID-IRS-NLR and VICE showed good performance for predicting invasive mechanical ventilation (IMV).

Development of Furanopyrimidine-Based Orally Active Third-Generation EGFR Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is described. First, selectivity for mutant EGFR was accomplished by replacing the (S)-2-phenylglycinol moiety of 12 with either an ethanol or an alkyl substituent. Then, the cellular potency and physicochemical properties were optimized through insights from molecular modeling studies by implanting various solubilizing groups in phenyl rings A and B. Optimized lead 52 shows 8-fold selective inhibition of H1975 (EGFRL858R/T790M overexpressing) cancer cells over A431 (EGFRWT overexpressing) cancer cells; western blot analysis further confirmed EGFR mutant-selective target modulation inside the cancer cells by 52. Notably, 52 displayed in vivo antitumor effects in two different mouse xenograft models (BaF3 transfected with mutant EGFR and H1975 tumors) with TGI = 74.9 and 97.5% after oral administration (F = 27%), respectively. With an extraordinary kinome selectivity (S(10) score of 0.017), 52 undergoes detailed preclinical development.

Scalable Synthesis of Multi-Metal Electrocatalyst Powders and Electrodes and their Application for Oxygen Evolution and Water Splitting.

Multi-metal electrocatalysts provide nearly unlimited catalytic possibilities arising from synergistic element interactions. We propose a polymer/metal precursor spraying technique that can easily be adapted to produce a large variety of compositional different multi-metal catalyst materials. To demonstrate this, 11 catalysts were synthesized, characterized, and investigated for the oxygen evolution reaction (OER). Further investigation of the most active OER catalyst, namely CoNiFeMoCr, revealed a polycrystalline structure, and operando Raman measurements indicate that multiple active sites are participating in the reaction. Moreover, Ni foam-supported CoNiFeMoCr electrodes were developed and applied for water splitting in flow-through electrolysis cells with electrolyte gaps and in zero-gap membrane electrode assembly (MEA) configurations. The proposed alkaline MEA-type electrolyzers reached up to 3 A cm-2 , and 24 h measurements demonstrated no loss of current density of 1 A cm-2 .

Startling Acoustic Stimulation Has Task-Specific Effects on Intracortical Facilitation and Inhibition at Rest and During Visually Guided Isometric Elbow Flexion in Healthy Individuals.

Startling acoustic stimulation (SAS) causes a transient effect on the primary motor cortex (M1) nonreflexively. It reduces the cortical excitability at rest, but not during voluntary contraction. However, the effect of SAS on intracortical activity is not clear. The purpose of this study was to investigate the SAS effect on short-interval intracortical inhibition and intracortical facilitation using transcranial magnetic stimulation (TMS). Eleven healthy individuals performed isometric elbow flexion at 10% of maximum voluntary contraction on the dominant side with a real-time visual target (i.e., M1 preactivation) or at rest. TMS was delivered to the M1 ipsilateral to elbow flexion without or with SAS delivered 90 ms prior to TMS. There were three TMS delivery conditions: (a) single pulse, (b) short-interval intracortical inhibition, and (c) intracortical facilitation. TMS-induced motor-evoked potential (MEP) was compared between predetermined TMS and SAS conditions at rest and during ipsilateral voluntary contraction. We confirmed that SAS decreased the MEP amplitude at rest, but not during M1 preactivation. SAS caused task-specific effects on intracortical excitability. Specifically, SAS increased intracortical facilitation at rest and during voluntary contraction. However, SAS decreased short-interval intracortical inhibition only during M1 preactivation. Collectively, our results suggest that SAS transiently influences the motor cortex excitability, possibly via its activation of higher centers, to achieve a visually guided goal-directed task.

Neurodevelopmental Outcomes for Retinopathy of Prematurity: A Taiwan Premature Infant Follow-up Network Database Study.

PURPOSE: To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. RESULTS: A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. CONCLUSIONS: Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.

Effects of hydrometeorological and other factors on SARS-CoV-2 reproduction number in three contiguous countries of tropical Andean South America: a spatiotemporally disaggregated time series analysis.

Background: The COVID-19 pandemic has caused societal disruption globally, and South America has been hit harder than other lower-income regions. This study modeled the effects of six weather variables on district-level SARS-CoV-2 reproduction numbers (Rt ) in three contiguous countries of tropical Andean South America (Colombia, Ecuador, and Peru), adjusting for environmental, policy, healthcare infrastructural and other factors. Methods: Daily time-series data on SARS-CoV-2 infections were sourced from the health authorities of the three countries at the smallest available administrative level. Rt values were calculated and merged by date and unit ID with variables from a unified COVID-19 dataset and other publicly available sources for May-December, 2020. Generalized additive models were fitted. Findings: Relative humidity and solar radiation were inversely associated with SARS-CoV-2 Rt . Days with radiation above 1000 kJ/m2 saw a 1.3% reduction in Rt , and those with humidity above 50% recorded a 0.9% reduction in Rt . Transmission was highest in densely populated districts, and lowest in districts with poor healthcare access and on days with lowest population mobility. Wind speed, temperature, region, aggregate government policy response, and population age structure had little impact. The fully adjusted model explained 4.3% of Rt variance. Interpretation: Dry atmospheric conditions of low humidity increase district-level SARS-CoV-2 reproduction numbers, while higher levels of solar radiation decrease district-level SARS-CoV-2 reproduction numbers - effects that are comparable in magnitude to population factors like lockdown compliance. Weather monitoring could be incorporated into disease surveillance and early warning systems in conjunction with more established risk indicators and surveillance measures. Funding: NASA's Group on Earth Observations Work Programme (16-GEO16-0047).

Motor Unit Number Estimation in Spastic Biceps Brachii Muscles of Chronic Stroke Survivors Before and After BoNT Injection.

OBJECTIVE: The study aims to characterize the motor unit (MU) loss in spastic biceps brachii muscle (BBM) of chronic stroke survivors before and after botulinum neurotoxin (BoNT) injection. METHODS: High-density weighted average (HDWA) motor unit number estimation (MUNE) was employed to estimate the number of functioning motor units of BBMs of eight chronic stroke survivors 1-week before (1st visit) and 3-week after (2nd visit) BoNT injection based on the surface electromyography (sEMG) signals recorded during voluntary contraction and supramaximal electrical stimulation. RESULT: Significant lower MUNE was estimated from the spastic BBMs compared to the non-spastic MUNEs during two visits. A surprisingly higher MUNE was obtained from the spastic side during the 2nd visit after BoNT injection. CONCLUSIONS: The HDWA MUNE technique can be employed to characterize the motor unit loss in spastic muscle caused by upper motor neuro lesions at contraction level up to 30% MVC, but may fail to detect the MU loss caused by the chemodenervation effect of BoNT due to the non-uniform denervation of small and large size MUs. SIGNIFICANCE: This study presents the first effort to evaluate the applicability of HDWA MUNE technique to characterize the MU loss in the spastic muscle following stroke and the subsequent BoNT injection for the treatment of post-stroke spasticity. The finding of this study suggests that HDWA MUNE can be a sensitive approach to detect the MU loss in spastic muscles after stroke, but the large inter-subject MUNE variability after the BoNT injection should be interpreted with caution.

Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention.

CXCR4 antagonists have been claimed to reduce mortality after myocardial infarction in myocardial infarction (MI) animals, presumably due to suppressing inflammatory responses caused by myocardial ischemia-reperfusion injury, thus, subsequently facilitating tissue repair and cardiac function recovery. This study aims to determine whether a newly designed CXCR4 antagonist DBPR807 could exert better vascular-protective effects than other clinical counterparts (e.g., AMD3100) to alleviate cardiac damage further exacerbated by reperfusion. Consequently, we find that instead of traditional continuous treatment or multiple-dose treatment at different intervals of time, a single-dose treatment of DBPR807 before reperfusion in MI animals could attenuate inflammation via protecting oxidative stress damage and preserve vascular/capillary density and integrity via mobilizing endothelial progenitor cells, leading to a desirable fibrosis reduction and recovery of cardiac function, as evaluated with the LVEF (left ventricular ejection fraction) in infarcted hearts in rats and mini-pigs, respectively. Thus, it is highly suggested that CXCR4 antagonists should be given at a single high dose prior to reperfusion to provide the maximal cardiac functional improvement. Based on its favorable efficacy and safety profiles indicated in tested animals, DBPR807 has a great potential to serve as an adjunctive medicine for percutaneous coronary intervention (PCI) therapies in acute MI patients.