Widespread Neuroanatomical Integration and Distinct Electrophysiological Properties of Glioma-Innervating Neurons.

Gliomas are the most common malignant primary brain tumors and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation. Yet, the locations and properties of neurons that innervate gliomas have remained elusive. In this study, we utilized transsynaptic tracing with a pseudotyped, glycoprotein-deleted rabies virus to specifically infect TVA and glycoprotein-expressing human glioblastoma cells in an orthotopic xenograft mouse model, allowing us to identify the neurons that form synapses onto the gliomas. Comprehensive whole-brain mapping revealed that these glioma-innervating neurons (GINs) consistently arise at brain regions, including diverse neuromodulatory centers and specific cortical layers, known to project to the glioma locations. Molecular profiling revealed that these long-range cortical GINs are predominantly glutamatergic, and subsets express both glutamatergic and GABAergic markers, whereas local striatal GINs are largely GABAergic. Electrophysiological studies demonstrated that while GINs share passive intrinsic properties with cortex-innervating neurons, their action potential waveforms are altered. Our study introduces a novel method for identifying and mapping GINs and reveals their consistent integration into existing location-dependent neuronal network involving diverse neurotransmitters and neuromodulators. The observed intrinsic electrophysiological differences in GINs lay the groundwork for future investigations into how these alterations may correspond with the postsynaptic characteristics of glioma cells. Significance: We have developed a novel system utilizing rabies virus-based monosynaptic tracing to directly visualize neurons that synapse onto human glioma cells implanted in mouse brain. This approach enables the mapping and quantitative analysis of these glioma-innervating neurons (GINs) in the entire mouse brain and overcomes previous barriers of molecular and electrophysiological analysis of these neurons due to the inability to identify them. Our findings indicate that GINs integrate into existing neural networks in a location-specific manner. Long-range GINs are mostly glutamatergic, with a subset expressing both glutamatergic and GABAergic markers and local striatal GINs are GABAergic, highlighting a complex neuromodulatory profile. Additionally, GINs exhibit unique action potential characteristics, distinct from similarly selected neurons in non-tumor-bearing brains. This study provides new insights into neuronal adaptations in response to forming putative synapses onto glioma, elucidating the intricate synaptic relationship between GINs and gliomas.

Age-Related Topological Organization of Phase-Amplitude Coupling Between Postural Fluctuations and Scalp EEG During Unsteady Stance.

Through phase-amplitude analysis, this study investigated how low-frequency postural fluctuations interact with high-frequency scalp electroencephalography (EEG) amplitudes, shedding light on age-related mechanic differences in balance control during uneven surface navigation. Twenty young ( 24.1 ± 1.9 years) and twenty older adults ( 66.2 ± 2.7 years) stood on a training stabilometer with visual guidance, while their scalp EEG and stabilometer plate movements were monitored. In addition to analyzing the dynamics of the postural fluctuation phase, phase-amplitude coupling (PAC) for postural fluctuations below 2 Hz and within EEG sub-bands (theta: 4-7 Hz, alpha: 8-12 Hz, beta: 13-35 Hz) was calculated. The results indicated that older adults exhibited significantly larger postural fluctuation amplitudes(p <0.001) and lower mean frequencies of the postural fluctuation phase ( p = 0.005 ) than young adults. The PAC between postural fluctuation and theta EEG (FCz and bilateral temporal-parietal-occipital area), as well as that between postural fluctuation and alpha EEG oscillation, was lower in older adults than in young adults (p <0.05). In contrast, the PAC between the phase of postural fluctuation and beta EEG oscillation, particularly in C3 ( p=0.006 ), was higher in older adults than in young adults. In summary, the postural fluctuation phase and phase-amplitude coupling between postural fluctuation and EEG are sensitive indicators of the age-related decline in postural adjustments, reflecting less flexible motor state transitions and adaptive changes in error monitoring and visuospatial attention.

Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives.

The coronavirus disease 2019 (COVID-19) pandemic has sparked widespread concern globally, particularly with the Omicron variant and its sub-lineages emerging as the predominant cause of infection for nearly two years. Taiwan's successful containment of COVID-19, underscored by broad vaccine coverage, the utilization of anti-viral therapeutics, and timely response strategies, has resulted in reduced excess mortality. Moreover, there is a crucial need for a phased exit strategy, balancing efforts to curtail disease transmission with the mitigation of socioeconomic impacts from rigorous measures. In this review, we examined the evolution and the epidemiological landscape of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sub-variants in Taiwan as well as other countries of the world. We also critically evaluated the effectiveness of COVID-19 vaccines against various SARS-CoV-2 variants. Additionally, we addressed the advantages of heterologous immunization strategies, fluctuations in neutralizing antibody titers, and complexities in establishing protective correlates among swiftly mutating viral variants.

Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.

Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.

Differential training benefits and motor unit remodeling in wrist force precision tasks following high and low load blood flow restriction exercises under volume-matched conditions.

BACKGROUND: Blood flow restriction (BFR) resistance training has demonstrated efficacy in promoting strength gains beneficial for rehabilitation. Yet, the distinct functional advantages of BFR strength training using high-load and low-load protocols remain unclear. This study explored the behavioral and neurophysiological mechanisms that explain the differing effects after volume-matched high-load and low-load BFR training. METHODS: Twenty-eight healthy participants were randomly assigned to the high-load blood flow restriction (BFR-HL, n = 14) and low-load blood flow restriction (BFR-LL, n = 14) groups. They underwent 3 weeks of BFR training for isometric wrist extension at intensities of 25% or 75% of maximal voluntary contraction (MVC) with matched training volume. Pre- and post-tests included MVC and trapezoidal force-tracking tests (0-75%-0% MVC) with multi-channel surface electromyography (EMG) from the extensor digitorum. RESULTS: The BFR-HL group exhibited a greater strength gain than that of the BFR-LL group after training (BFR_HL: 26.96 ± 16.33% vs. BFR_LL: 11.16 ± 15.34%)(p = 0.020). However, only the BFR-LL group showed improvement in force steadiness for tracking performance in the post-test (p = 0.004), indicated by a smaller normalized change in force fluctuations compared to the BFR-HL group (p = 0.048). After training, the BFR-HL group activated motor units (MUs) with higher recruitment thresholds (p < 0.001) and longer inter-spike intervals (p = 0.002), contrary to the BFR-LL group, who activated MUs with lower recruitment thresholds (p < 0.001) and shorter inter-spike intervals (p < 0.001) during force-tracking. The discharge variability (p < 0.003) and common drive index (p < 0.002) of MUs were consistently reduced with training for the two groups. CONCLUSIONS: BFR-HL training led to greater strength gains, while BFR-LL training better improved force precision control due to activation of MUs with lower recruitment thresholds and higher discharge rates.

Distinct functional and molecular profiles between physiological and pathological atrial enlargement offer potential new therapeutic opportunities for atrial fibrillation.

Atrial fibrillation (AF) remains challenging to prevent and treat. A key feature of AF is atrial enlargement. However, not all atrial enlargement progresses to AF. Atrial enlargement in response to physiological stimuli such as exercise is typically benign and reversible. Understanding the differences in atrial function and molecular profile underpinning pathological and physiological atrial remodelling will be critical for identifying new strategies for AF. The discovery of molecular mechanisms responsible for pathological and physiological ventricular hypertrophy has uncovered new drug targets for heart failure. Studies in the atria have been limited in comparison. Here, we characterised mouse atria from (1) a pathological model (cardiomyocyte-specific transgenic (Tg) that develops dilated cardiomyopathy [DCM] and AF due to reduced protective signalling [PI3K]; DCM-dnPI3K), and (2) a physiological model (cardiomyocyte-specific Tg with an enlarged heart due to increased insulin-like growth factor 1 receptor; IGF1R). Both models presented with an increase in atrial mass, but displayed distinct functional, cellular, histological and molecular phenotypes. Atrial enlargement in the DCM-dnPI3K Tg, but not IGF1R Tg, was associated with atrial dysfunction, fibrosis and a heart failure gene expression pattern. Atrial proteomics identified protein networks related to cardiac contractility, sarcomere assembly, metabolism, mitochondria, and extracellular matrix which were differentially regulated in the models; many co-identified in atrial proteomics data sets from human AF. In summary, physiological and pathological atrial enlargement are associated with distinct features, and the proteomic dataset provides a resource to study potential new regulators of atrial biology and function, drug targets and biomarkers for AF.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

Cross-frequency modulation of postural fluctuations and scalp EEG in older adults: error amplification feedback for rapid balance adjustments.

Virtual error amplification (VEA) in visual feedback enhances attentive control over postural stability, although the neural mechanisms are still debated. This study investigated the distinct cortical control of unsteady stance in older adults using VEA through cross-frequency modulation of postural fluctuations and scalp EEG. Thirty-seven community-dwelling older adults (68.1 ± 3.6 years) maintained an upright stance on a stabilometer while receiving either VEA or real error feedback. Along with postural fluctuation dynamics, phase-amplitude coupling (PAC) and amplitude-amplitude coupling (AAC) were analyzed for postural fluctuations under 2 Hz and EEG sub-bands (theta, alpha, and beta). The results revealed a higher mean frequency of the postural fluctuation phase (p = .005) and a greater root mean square of the postural fluctuation amplitude (p = .003) with VEA compared to the control condition. VEA also reduced PAC between the postural fluctuation phase and beta-band EEG in the left frontal (p = .009), sensorimotor (p = .002), and occipital (p = .018) areas. Conversely, VEA increased the AAC of posture fluctuation amplitude and beta-band EEG in FP2 (p = .027). Neither theta nor alpha band PAC or AAC were affected by VEA. VEA optimizes postural strategies in older adults during stabilometer stance by enhancing visuospatial attentive control of postural responses and facilitating the transition of motor states against postural perturbations through a disinhibitory process. Incorporating VEA into virtual reality technology is advocated as a valuable strategy for optimizing therapeutic interventions in postural therapy, particularly to mitigate the risk of falls among older adults.

Fatigue Alleviation by Low-Level Laser Preexposure in Ischemic Neuromuscular Electrical Stimulation.

PURPOSE: Despite its susceptibility to muscle fatigue, combined neuromuscular electrical stimulation (NMES) and blood flow restriction (BFR) are effective regimens for managing muscle atrophy when traditional resistance exercises are not feasible. This study investigated the potential of low-level laser therapy (LLLT) in reducing muscle fatigue after the application of combined NMES and BFR. METHODS: Thirty-six healthy adults were divided into control and LLLT groups. The LLLT group received 60 J of 850-nm wavelength LLLT before a training program of combined NMES and BFR of the nondominant extensor carpi radialis longus (ECRL). The control group followed the same protocol but received sham laser therapy. Assessments included maximal voluntary contraction, ECRL mechanical properties, and isometric force tracking for wrist extension. RESULTS: The LLLT group exhibited a smaller normalized difference in maximal voluntary contraction decrement (-4.01 ± 4.88%) than the control group (-23.85 ± 7.12%) ( P < 0.001). The LLLT group demonstrated a smaller decrease in muscle stiffness of the ECRL compared with the control group, characterized by the smaller normalized changes in frequency ( P = 0.002), stiffness ( P = 0.002), and relaxation measures ( P = 0.011) of mechanical oscillation waves. Unlike the control group, the LLLT group exhibited a smaller posttest increase in force fluctuations during force tracking ( P = 0.014), linked to the predominant recruitment of low-threshold MU ( P < 0.001) without fatigue-related increases in the discharge variability of high-threshold MU ( P > 0.05). CONCLUSIONS: LLLT preexposure reduces fatigue after combined NMES and BFR, preserving force generation, muscle stiffness, and force scaling. The functional benefits are achieved through fatigue-resistant activation strategies of motor unit recruitment and rate coding.

The use of multicomponent reactions in the development of bis-boronic acids for the detection of ß-sialic acid.

Sialic acid (SA) is a naturally occurring monosaccharide found in glycoproteins and glycolipids. Changes in the expression of SA are associated with several diseases; thus, the detection of SA is of great significance for biological research, cancer diagnosis, and treatment. Boronic acid analogs have emerged as a promising tool for detecting sugars such as SA due to its reversible covalent bonding ability. In this study, 11 bis-boronic acid compounds and 2 mono-boronic acid compounds were synthesized via a highly efficient Ugi-4CR strategy. The synthesized compounds were subjected to affinity fluorescence binding experiments to evaluate their binding capability to SA. Compound A1 was shown to have a promising binding constant of 2602 ± 100 M-1 at pH = 6.0. Density Functional Theory (DFT) calculations examining the binding modes between A1 and SA indicated that the position of the boronic acid functional group was strongly correlated with its interaction with SA's α-hydroxy acid unit. The DFT calculations were consistent with the observations from the fluorescence experiments, demonstrating that the number and relative positions of the boronic acid functional groups are critical factors in enhancing the binding affinity to SA. DFT calculations of both S and R configuration of A1 indicated that the effect of the S/R configuration of A1 on its binding with ß-sialic acid was insignificant as the Ugi-4CR generated racemic products. A fluorine atom was incorporated into the R2 substituent of A1 as an electron-withdrawing group to produce A5, which possessed a significantly higher capability to bind to SA (Keq = 7015 ± 5 M-1 at pH = 6.0). Finally, A1 and A5 were shown to possess exceptional binding selectivity toward ß-sialic acid under pH of 6.0 and 6.5 while preferring to bind with glucose, fructose, and galactose under pH of 7.0 and 7.5.

Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Cardiovascular magnetic resonance imaging for sequential assessment of cardiac fibrosis in mice: technical advancements and reverse translation.

Cardiovascular magnetic resonance (CMR) imaging has become an essential technique for the assessment of cardiac function and morphology, and is now routinely used to monitor disease progression and intervention efficacy in the clinic. Cardiac fibrosis is a common characteristic of numerous cardiovascular diseases and often precedes cardiac dysfunction and heart failure. Hence, the detection of cardiac fibrosis is important for both early diagnosis and the provision of guidance for interventions/therapies. Experimental mouse models with genetically and/or surgically induced disease have been widely used to understand mechanisms underlying cardiac fibrosis and to assess new treatment strategies. Improving the appropriate applications of CMR to mouse studies of cardiac fibrosis has the potential to generate new knowledge, and more accurately examine the safety and efficacy of antifibrotic therapies. In this review, we provide 1) a brief overview of different types of cardiac fibrosis, 2) general background on magnetic resonance imaging (MRI), 3) a summary of different CMR techniques used in mice for the assessment of cardiac fibrosis including experimental and technical considerations (contrast agents and pulse sequences), and 4) provide an overview of mouse studies that have serially monitored cardiac fibrosis during disease progression and/or therapeutic interventions. Clinically established CMR protocols have advanced mouse CMR for the detection of cardiac fibrosis, and there is hope that discovery studies in mice will identify new antifibrotic therapies for patients, highlighting the value of both reverse translation and bench-to-bedside research.

Invasive lactobacillus infection in pediatric patients in a tertiary center in Taiwan - 16 years' experience and literature review.

BACKGROUND: Lactobacilli are common microorganisms in the human body. Some species were used as probiotics supplement for many purposes such as preventing necrotizing enterocolitis, or improving allergic diseases or diarrhea. Previously, Lactobacillus infection was thought of as contamination due to its low pathogenicity. However, there have been reports of invasive Lactobacillus infection in immunocompromised patients or patients with comorbidities. The purpose of this study was to analyze the clinical characteristics, antibiotic treatment and outcomes of pediatric patients with invasive Lactobacillus infection. METHODS: We retrospectively reviewed pediatric patients diagnosed with invasive Lactobacillus infection between 2004 and 2020. Invasive Lactobacillus infection was diagnosed if sterile sites yielded Lactobacillus spp. Clinical manifestations, chronic diseases, potential predisposing factors, medical treatments, antimicrobial susceptibility tests and outcomes were recorded. RESULTS: Fifteen pediatric patients were diagnosed with invasive Lactobacillus infection, accounting for 2.4% of total invasive Lactobacillus infections during the 16-year period. Eleven infections were bacteremia, two were intra-abdominal infections, and two were biliary tract infections. Fever was the most common symptom. Potential predisposing factors were immunocompromised status, central venous device, prolonged antibiotics use and receiving supplemented probiotics for at least one week. All patients survived with favorable outcomes. Most pathogens were identified as Lactobacillus spp, and two were Lactobacillus rhamnosus, which were related to supplemented probiotics. The antimicrobial susceptibility tests showed that Lactobacilli were all sensitive to ampicillin but resistant to glycopeptides. CONCLUSION: Invasive Lactobacillus infections in pediatric patients were rare. Despite its low pathogenicity, Lactobacillus could cause invasive infection in those immunocompromised patients.

Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.

Background: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD. Methods: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan. Results: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI. Conclusion: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.

Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children.

BACKGROUND: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. METHODS: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. RESULTS: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/µL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy. CONCLUSIONS: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.

Effectiveness of Mix-and-Match Vaccination in Preventing SARS-CoV-2 Omicron Variant Infection in Taiwan: A Test-Negative Control Study.

This study aimed to evaluate the effectiveness (VE) of mix-and-match vaccination against SARS-CoV-2 Omicron variant infection and severe outcomes. An SARS-CoV-2 PCR-confirmed retrospective cohort from Chang Gung Medical System in Taiwan was constructed. Vaccination records were tracked from the National Immunization Information System and categorized by different regimens or unvaccinated status. The main outcomes are VE against PCR-confirmed infection and COVID-19-associated moderate to severe disease. Participants were observed during the Omicron wave from March to August 2022. Of 298,737 PCR testing results available, 162,219 were eligible for analysis. VE against infection was modest, ranging from 38.3% to 49.0%, while mRNA-based vaccine regimens revealed better protection against moderate to severe disease, ranging from 80.8% to 90.3%. Subgroup analysis revealed lower VE among persons with major illness in preventing moderate to severe disease. For young adults, the VE of protein-based vaccine regimens showed a comparable protection with other mixed vaccine regimens. The mix-and-match vaccination strategy provided modest clinical effectiveness in preventing Omicron variant infection. mRNA vaccine-based regimens were superior to other regimens against moderate to severe disease especially in older adults. The mix-and-match vaccination strategy could be an alternative to prevent COVID-19 in unstable vaccine supply regions.

Deficits in neuromuscular control of increasing force in patients with chronic lateral epicondylitis.

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE). Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3 years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5 years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%-75%-0% MVC) were assessed. Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors (p = 0.007) and force fluctuations (p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release (p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts (p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group (p < 0.005). Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force. Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units.

Risk reduction analysis of mix-and-match vaccination strategy in healthcare workers during SARS-CoV-2 Omicron variant predominant period: A multi-center cohort study in Taiwan.

This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P < .001) of acquiring infection, respectively. Our study demonstrated that mix-and-match vaccination strategy may be associated with different level of risk reduction in acquiring infection, and sizable, prospective studies are encouraged to further elucidate our observation.

Low-Level Laser Therapy Facilitates Postcontraction Recovery with Ischemic Preconditioning.

PURPOSE: Despite early development of muscle fatigue, ischemic preconditioning is gaining popularity for strength training combined with low-load resistance exercise. This study investigated the effect of low-level laser (LLL) on postcontraction recovery with ischemic preconditioning. METHODS: Forty healthy adults (22.9 ± 3.5 yr) were allocated into sham (11 men, 9 women) and LLL (11 men, 9 women) groups. With ischemic preconditioning, they were trained with three bouts of intermittent wrist extension of 40% maximal voluntary contraction (MVC). During the recovery period, the LLL group received LLL (wavelength of 808 nm, 60 J) on the working muscle, whereas the sham group received no sham therapy. MVC, force fluctuations, and discharge variables of motor units (MU) for a trapezoidal contraction were compared between groups at baseline (T0), postcontraction (T1), and after-recovery (T2). RESULTS: At T2, the LLL group exhibited a higher normalized MVC (T2/T0; 86.22% ± 12.59%) than that of the sham group (71.70% ± 13.56%; P = 0.001). The LLL group had smaller normalized force fluctuations (LLL, 94.76% ± 21.95%; sham, 121.37% ± 29.02%; P = 0.002) with greater normalized electromyography amplitude (LLL, 94.33% ± 14.69%; sham, 73.57% ± 14.94%; P < 0.001) during trapezoidal contraction. In the LLL group, the smaller force fluctuations were associated with lower coefficients of variation of interspike intervals of MUs (LLL, 0.202 ± 0.053; sham, 0.208 ± 0.048; P = 0.004) with higher recruitment thresholds (LLL, 11.61 ± 12.68 %MVC; sham, 10.27 ± 12.73 %MVC; P = 0.003). CONCLUSIONS: LLL expedites postcontraction recovery with ischemic preconditioning, manifesting as superior force generation capacity and force precision control for activation of MU with a higher recruitment threshold and lower discharge variability.