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

PURPOSE: Despite its susceptibility to muscle fatigue, combined neuromuscular electrical stimulation (NMES) and blood flow restriction (BFR) is an effective regimen 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 non-dominant extensor carpi radialis longus (ECRL). The control group followed the same protocol but received sham laser therapy. Assessments included maximal voluntary contraction (MVC), ECRL mechanical properties, and isometric force-tracking for wrist extension. RESULTS: The LLLT group exhibited a smaller normalized difference in MVC decrement (-4.01 ± 4.88%) than the control group (-23.85 ± 7.12%) (P < .001). The LLLT group demonstrated a smaller decrease in muscle stiffness of the ECRL compared to the control group, characterized by the smaller normalized changes in frequency (P = .002), stiffness (P = .002), and relaxation measures (P = .011) of mechanical oscillation waves. Unlike the control group, the LLLT group exhibited a smaller post-test increase in force fluctuations during force-tracking (P = .014), linked to the predominant recruitment of low-threshold MUs (P < .001) without fatigue-related increases in the discharge variability of high-threshold MUs (P > .05). CONCLUSIONS: LLLT pre-exposure 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.

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.

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.

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.

Failure to improve task performance after visuomotor training with error reduction feedback for young adults.

Visual feedback that reinforces accurate movements may motivate skill acquisition by promoting self-confidence. This study investigated neuromuscular adaptations to visuomotor training with visual feedback with virtual error reduction. Twenty-eight young adults (24.6 ± 1.6 years) were assigned to error reduction (ER) (n = 14) and control (n = 14) groups to train on a bi-rhythmic force task. The ER group received visual feedback and the displayed errors were 50% of the real errors in size. The control group was trained with visual feedback with no reduction in errors. Training-related differences in task accuracy, force behaviors, and motor unit discharge were contrasted between the two groups. The tracking error of the control group progressively declined, whereas the tracking error of the ER group was not evidently reduced in the practice sessions. In the post-test, only the control group exhibited significant task improvements with smaller error size (p = .015) and force enhancement at the target frequencies (p = .001). The motor unit discharge of the control group was training-modulated, as indicated by a reduction of the mean inter-spike interval (p = .018) and smaller low-frequency discharge fluctuations (p = .017) with enhanced firing at the target frequencies of the force task (p = .002). In contrast, the ER group showed no training-related modulation of motor unit behaviors. In conclusion, for young adults, ER feedback does not induce neuromuscular adaptations to the trained visuomotor task, which is conceptually attributable to intrinsic error dead-zones.

Quick balance skill improvement after short-term training with error amplification feedback for older adults.

This study investigated behavioral and cortical mechanisms for short-term postural training with error amplification (EA) feedback in the elderly. Thirty-six elderly subjects (65.7 ± 2.2 years) were grouped (control and EA, n = 18) for training in stabilometer balance under visual guidance. During the training session (8 training rounds of 60 s in Day 2), the EA group received visual feedback that magnified errors to twice the real size, whereas the control group received visual feedback that displayed real errors. Scalp EEG and kinematic data of the stabilometer plate and ankle joint were recorded in the pre-test (Day 1) and post-test (Day 3). The EA group (-46.5 ± 4.7%) exhibited greater post-training error reduction than that of the control group (-27.1 ± 4.0%)(p = 0.020), together with a greater decline in kinematic coupling between the stabilometer plate and ankle joint (EA: -26.6 ± 4.8%, control: 2.3 ± 8.6%, p = 0.023). In contrast to the control group, the EA group manifested greater reductions in mean phase-lag index (PLI) connectivity in the theta (4-7 Hz)(p = 0.011) and alpha (8-12 Hz) (p = 0.027) bands. Only the EA group showed post-training declines in the mean PLI in the theta and alpha bands. Minimal spanning tree analysis revealed that EA-based training led to increases in the diameter (p = 0.002) and average eccentricity (p = 0.004) of the theta band for enhanced performance monitoring and reduction in the leaf fraction (p = 0.030) of the alpha band for postural response with enhanced automaticity. In conclusion, short-term EA training optimizes balance skill, favoring multi-segment coordination for the elderly, which is linked to more sophisticated error monitoring with less attentive control over the stabilometer stance.

Impact of multiplex polymerase chain reaction syndromic panel on antibiotic use among hospitalized children with respiratory tract illness during COVID-19 pandemic.

BACKGROUND/PURPOSE: Precise detection of respiratory pathogens by molecular method potentially may shorten the time to diagnose and reduce unnecessary antibiotic use. METHODS: Medical records of hospitalized children from January 2020 to June 2021 with acute respiratory illness who received a FilmArray RP for respiratory pathogens were reviewed and compared with data from diagnosis-matched patients without receiving the test. RESULTS: In total, 283 patients and 150 diagnosis-matched controls were included. Single pathogen was detected in 84.3% (193/229) of the patients. The most common pathogen was human rhinovirus/enterovirus (31.6%, 84/266), followed by respiratory syncytial virus (18.8%, 50/266) and adenovirus (15%, 40/266). Although antimicrobial days of therapy (DOT) was significantly longer in FilmArray group than the control [7.1 ± 4.9 days vs 5.7 ± 2.7 days, P = 0.002], the former showed a higher intensive care unit (ICU) admission rate (3.9% vs 0%; P = 0.010). All ICU admissions were in FilmArray RP-positive group. There was no difference in antimicrobial DOT between FilmArray RP-positive and the negative groups, in all admissions, even after excluding ICU admissions. Antimicrobial DOT was shorter in the positive than negative group in patients with lower respiratory tract infections without admission to ICU [median (IQR): 6 (4-9) days vs 9 (4-12) days, P = 0.047]. CONCLUSIONS: Shorter antimicrobial DOTs were identified in children with lower respiratory tract infection admitted to general pediatric ward and with an identifiable respiratory pathogen, indicating a role of the multiplex PCR in reducing antimicrobial use for children with respiratory tract infection.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

COVID-19 associated mold infections: Review of COVID-19 associated pulmonary aspergillosis and mucormycosis.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

Factors influencing loneliness among older people using homecare services during the COVID-19 pandemic.

BACKGROUND: Elderly homecare service users may reduce their level of social participation and interpersonal interactions due to physiological loss, which may lead to loneliness and depression over the years. However, there is a lack of research on loneliness among older people who use homecare services. The purpose of this study was to examine the factors influencing loneliness among older people using homecare services. METHODS: This is a longitudinal study conducted in communities in Central Taiwan, and data were collected using a structured questionnaire. The questionnaire was first administered as a pre-test to obtain baseline information about the participants, and the same questionnaire was administered as a post-test after 6 months to follow-up. The pre- and post-test questionnaires included five sections, that is, participant demographics, Brief Symptom Rating Scale, Interpersonal Interaction Scale (IIS), Frenchay Activities Index, and UCLA Loneliness Scale (UCLA). RESULTS: A total of 178 participants were recruited in this study. Results indicated that gender, whether participants eat alone or with others at dinner, social media use, perceived economic status, and IIS score were significantly correlated with the loneliness score on the UCLA. Furthermore, there was a significant increase in the loneliness score among male participants in the low loneliness group from baseline to 6 months follow-up. CONCLUSIONS: Gender, presence of others at dinner, social media use, perceived economic status, and interpersonal interaction skills are significant factors that influence loneliness among older people using homecare services. Men tend to experience higher levels of loneliness over time.

Using Response Surface for Searching the Nearly Optimal Parameters Combination of the Foam Concrete Muffler.

A car muffler is a device to improve car noise emission. Some conventional mufflers use layers of glass fiber as a material to absorb noise. However, filling glass fiber is an environmentally unfriendly work, mainly manually filling with chop strand fiber. This research selected a composite material of glass fiber and foam concrete to replace chop strand fiber to avoid this hazard and maintain the muffler's good noise reduction performance. A response surface methodology with a two-way factorial experimental design repeated the center point twice is performed. The density of the foamed concrete and the weight of the glass fiber is being considered in order to determine the nearly optimal combination of the values in two factors. The response variable is the loudness sensation in Sone of the noise generated from the muffler. At present, the lowest loudness sensation from the two-way factorial design is 16.6494 Sones, which occurred for a muffler with a formula combination of a density of 0.2 g/cm3 and 40 g of glass fiber. The significance of this paper is the presentation of a new application of foam concrete to the green muffler design. To the best of our knowledge, this unique area has never been tackled in the material application of concrete. We have discovered that foam concrete indeed does an excellent job in terms of noise reduction as compared with that of a market muffler.