Effect of a 4-Week Telerehabilitation Program for People with Post-COVID Syndrome on Physical Function and Symptoms: Protocol for a Randomized Controlled Trial.

OBJECTIVE: COVID-19 has led to significant morbidity and mortality globally. Post-COVID sequelae can persist beyond the acute and subacute phases of infection, often termed Post-COVID Syndrome (PCS). There is limited evidence on the appropriate rehabilitation for people with PCS. The aim of this study is to evaluate the effect on exercise capacity, symptoms, cognition, anxiety, depression, health-related quality of life (HRQoL), and fatigue, of a 4-week, twice-weekly supervised pulmonary telerehabilitation program compared to usual medical care for people with PCS with persistent respiratory symptoms. METHODS: The study will be a multi-site randomized controlled trial (RCT) with assessor blinding. Participants with confirmed previous COVID-19 infection and persistent respiratory symptoms who attend a post-COVID respiratory clinic will be randomized 1:1 to either an intervention group (IG) of 4 weeks, twice-weekly pulmonary telerehabilitation or a control group (CG) of usual medical care. Participants in the CG will be invited to cross-over into the IG after the week 4 assessment. Primary outcome: exercise capacity measured by the 1-minute sit-to-stand test. Secondary outcomes: 5 repetition sit-to-stand test; Montreal Cognitive Assessment; COVID-19 Yorkshire Rehabilitation Scale; COPD Assessment Test; 36-Item Short-Form Health Survey; Hospital Anxiety and Depression Scale; Fatigue Severity Scale; and the Kessler Psychological Distress Scale. Outcomes will be collected at baseline, after 4-weeks intervention or control period, after intervention in the cross-over group, and at 12-month follow-up. IMPACT STATEMENT: Research into effective rehabilitation programs is crucial given the substantial morbidity associated with PCS and the lack of long-term data for COVID-19 recovery. A short duration pulmonary telerehabilitation program, if effective compared to usual care, could inform practice guidelines and direct future clinical trials for the benefit of individuals with persistent respiratory symptoms post-COVID.

Research progress on the regulation of oxidative stress by phenolics: the role of gut microbiota and Nrf2 signaling pathway.

In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body's oxidative stress. They can also improve the body's inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body. © 2023 Society of Chemical Industry.

Impact of Sarcopenia on Percutaneous Epidural Balloon Neuroplasty in Patients with Lumbar Spinal Stenosis: A Retrospective Analysis.

Background and Objectives: With the aging population, the incidence of degenerative lumbar spinal stenosis (LSS) is increasing. Sarcopenia is an age-related muscular decrease. Although epidural balloon neuroplasty is effective in patients with LSS refractory to conventional treatments, its effect has not been assessed in patients with sarcopenia. Therefore, this study evaluated the effect of epidural balloon neuroplasty in patients with LSS and sarcopenia. Materials and Methods: This retrospective study reviewed the following details from the electronic medical records: patient characteristics, including sex, age, body mass index, diabetes, hypertension, stenosis grading, pain duration, location, pain intensity, and medications. Back and leg pain intensity was evaluated before and after the procedure at one, three, and six months during the follow-up period. A generalized estimating equations model was used at six months follow-up. Patients were divided into sarcopenia and non-sarcopenia groups using the cross-sectional area of the psoas muscle at the level of L3 on magnetic resonance imaging. Results: A total of 477 patients were included (sarcopenia group: 314 patients, 65.8%; non-sarcopenia group: 163 patients, 34.2%). Age, sex, body mass index, and medication quantification scale III were statistically different between both groups. The generalized estimating equations analyses-with unadjusted and adjusted estimation-revealed a significantly reduced pain intensity after the procedure compared to the baseline in both groups. The difference in pain intensity between both groups was not statistically different. Conclusions: Percutaneous epidural balloon neuroplasty may be considered for patients with chronic lumbar LSS regardless of accompanying sarcopenia.

Development of albumin monitoring system with hepatic hypoxia-on-a-chip.

Hypoxia plays an essential role in the pathogenesis of various liver diseases, and albumin is one of the important biomarkers secreted by the liver. In this study, we developed an albumin monitoring system composed of hepatic hypoxia-on-a-chip and an albumin sensor to study liver function change due to hypoxia. In hepatic hypoxia-on-a-chip, we vertically stack an oxygen-scavenging channel on a liver on a chip with a thin gas-permeable membrane in the middle. This unique design of the hepatic hypoxia-on-a-chip can help to induce hypoxia quickly, attaining <5% within 10 min. An electrochemical albumin sensor was fabricated based on the covalent immobilization of antibodies on the Au electrode to monitor albumin secreting function on the hepatic hypoxia-on-a-chip. Standard albumin samples spiked in PBS, and culture media were measured by the electrochemical impedance spectroscopy using the fabricated immunosensor. The LOD was calculated to be 10 ag/mL in both cases. Using the electrochemical albumin sensor, we measured albumin secretion in normoxia and hypoxia in the chips. The albumin concentration decreased to 27% after 24 h in hypoxia compared to normoxia. This response was consistent with physiological studies. With technical refinements, the present albumin monitoring system can be a powerful tool in studying hepatic hypoxia with real-time liver function monitoring.

Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

Identification of priority management areas for non-point source pollution based on critical source areas in an agricultural watershed of Northeast China.

Identification of critical source areas (CSAs) for non-point source (NPS) pollution is of great significance for environment governance and prevention. However, the CSAs are generally characterized as great spatial dispersion, and spatially heterogeneous precipitation has a great influence on the spatial distribution of nutrient yields. Therefore, we identify the CSAs for nutrient yields in an agricultural watershed of Northeast China at hydrological response units (HRUs) scale based on the Soil and Water Assessment Tool (SWAT), assess the impacts of spatially heterogeneity of precipitation on the identification of the CSAs, analyze the sensitivity of nutrient yields to precipitation by scenarios analysis method, and further identify priority management areas (PMAs) that have poor ability to retain nutrients. The results showed that the CSAs for nutrient yields identified by uniform precipitation showed greater fluctuation range and coverage area than actual precipitation; the major prevention areas of total nitrogen (TN) yield were mainly distributed in regions nearby main stem of lower reaches, while that of total phosphorus (TP) yield were mostly located in urban area nearby outlet of the watershed; the identification of the PMAs significantly decreased the CSAs for TN yield, whereas that for TP yield was no significant difference with the CSAs. This study could provide scientific guidance for the NPS pollution governance and prevention.

Response of macroinvertebrate community to water quality factors and aquatic ecosystem health assessment in a typical river in Beijing, China.

Healthy aquatic ecosystems can offer basic ecological services for the sustainable development of humans and society. Water quality greatly influences the macroinvertebrate community in aquatic ecosystems and can alter the aquatic ecosystem's health status. However, the quantitative relationship between macroinvertebrate community and water quality factors in rivers remains unclear, particularly in urban rivers, which are strongly affected by human activities. Therefore, a new framework for the quantitative analysis between macroinvertebrate community and key water quality driving factors was developed in the study, meanwhile, the aquatic ecosystem health conditions were evaluated and validated by different methods. The framework was applied to a typical urban river, the North Canal River, which is regarded as the "mother river" of Beijing. Combined with the redundancy analysis (RDA) and the threshold indicator taxa analysis (TITAN), the water quality driving factors and their indicator species were identified and the corresponding response threshold was determined. Based on the benthic index of biotic integrity (B-IBI), the multi-metric rapid bioassessment method, and the biological monitoring working party (BMWP) score, the aquatic ecosystem health condition in the basin was comprehensively evaluated. The results show that fluoride, biochemical oxygen demand, ammonia-nitrogen and total phosphorus were the key water quality driving factors influencing the community structure of macroinvertebrates. Four indicator species of ammonia-nitrogen were identified by the TITAN method with a threshold range of 1.09-6.94 mg L-1, and three indicator species of total phosphorus were identified with a threshold range of 0.48-1.27 mg L-1. According to the results of the aquatic ecosystem health assessment, the river ecosystem was generally unhealthy and the upstream was better than downstream; the health condition in the mountainous areas of Changping district was the best, while that in Chaoyang district and the central city area was the worst. The framework could provide a strong basis for ecological restoration and pollution control of the urban rivers and become an important tool for the rehabilitation of aquatic ecosystems.

Mechanical and Biocompatibility Properties of Sintered Titanium Powder for Mimetic 3D-Printed Bone Scaffolds.

A composite comprising Ti and NaCl powders was sintered similar to a three-dimensional (3D)-printed patient-customized artificial bone scaffold. Additionally, a proper microstructure of the mimetic scaffold and the optimum processing parameters for its development were analyzed. The mechanical properties of the metal-based porous-structured framework used as an artificial bone scaffold were an optimum replacement for the human bone. Thus, it was confirmed that patient-customized scaffolds could be manufactured via 3D printing. The 3D-printed mimetic specimens were fabricated by a powder-sintering method using Ti for the metal parts, NaCl as the pore former, and polylactic acid as the biodegradable binder. Scanning electron microscopy (SEM) images showed that pores were formed homogeneously, while X-ray computed tomography confirmed that open pores were generated. The porosity and pore size distribution were measured using a mercury porosimeter, while the flexural strength and flexural elastic modulus were calculated using the three-point bending test. Based on these measurements, a pore-former content of 15 vol % optimized the density and flexural strength to 2.52 g cm-2 and 283 MPa, respectively, similar to those of the actual iliac bone. According to the 3D-printing production method, a selective laser-sintering process was applied for the fabrication of the mimetic specimen, and it was determined that the microstructure and properties similar to those of previous metal specimens could be achieved in the as-prepared specimen. Additionally, a decellularized extracellular matrix (dECM) was used to coat the surfaces and interiors of the specimens for evaluating their biocompatibilities. SEM image analysis indicated that the adipose-derived stem cells grew evenly inside the pores of the coated specimens, as compared with the bulky Ti specimens without the dECM coating. The doubling time at 65% was measured at 72, 75, and 83 h for specimens with pore-former contents of 5, 10, and 15 vol %, respectively. The doubling time without the pore former was 116 h. As compared with the specimens without the pore former (73 h), 15% of the dECM-coated specimens showed a doubling time of 64%, measured at 47 h.

Epidermal Growth Factor (EGF)-Like Repeats and Discoidin I-Like Domains 3 (EDIL3): A Potential New Therapeutic Tool for the Treatment of Keloid Scars.

In keloids, the mechanism underlying the excessive accumulation of extracellular matrix after injury of the skin is unclear, and there is no effective treatment because of the incomplete understanding of their pathogenesis; thus, a high recurrence rate is observed. We studied a new marker of keloids to determine a new treatment strategy. First, the keloid gene expression profile (GSE44270) was analyzed (downloaded from the Gene Expression Omnibus database) and the new keloid marker candidate, epidermal growth factor (EGF)-like repeats and discoidin I-like domains 3 (EDIL3) which were upregulated in keloid samples was identified. Knockdown of EDIL3 is known to suppresses angiogenesis by downregulating relevant inhibitory factors that can limit the supply of survival factors to tumor cells from the circulation via the vascular endothelial cells. In keloids, the mechanism of action of EDIL3 may be similar to that in tumors; the inhibition of apoptosis in tumor cells via a reduction in the apoptosis of blood vessels by upregulating an angiogenic factor. To determine whether EDIL3 is involved in keloid formation, we performed knockdown of EDIL3 in keloid fibroblasts in vitro by transfection with anti-EDIL3 small interfering RNA (via microporation). EDIL3 was upregulated in keloid fibroblasts compared with normal fibroblasts in collagen type I, II and III. Our results indicate the control of EDIL3 expression may be a new promising treatment of keloid disease also the molecular targeting of EDIL3 may improve the quality of treatment and reduce the formation of keloids.

Contrast-enhanced ultrasound for differentiation of benign and malignant thyroid lesions: meta-analysis.

OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is a new noninvasive modality for the diagnosis of thyroid nodules. However, the performance of CEUS in differentiating malignant and benign thyroid nodules has not been systematically evaluated. This meta-analysis was performed to assess the accuracy of CEUS in diagnosing thyroid nodules. DATA SOURCES: PubMed, Embase, and the references of included studies were examined. REVIEW METHODS: We recorded the characteristics of the included studies and assessed the quality of each study using the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. We also evaluated the publication bias. RESULTS: This meta-analysis included 7 studies with a total of 597 thyroid nodules. The pooled the sensitivity, specificity, and positive and negative LR were 0.853, 0.876, 5.822, and 0.195, respectively. The DOR and AUC were 34.730 and 0.9162, respectively. Heterogeneity existed between the included studies. The results of subgroup analyses indicated that the evaluation processes are likely the predominant source of heterogeneity. No significant publication bias was observed. CONCLUSION: Contrast-enhanced ultrasound is a promising noninvasive technique for the differential diagnosis of benign and malignant thyroid nodules and could be a valuable supplemental method to fine-needle aspiration.

Cardiac capillary hemangioma: a case report and brief review of the literature.

Among primary cardiac tumors, hemangiomas are relatively rare, with a reported incidence of 2.8%. To date, less than 100 cases have been reported in literature. We report the case of a 61-year-old woman who complained from chest discomfort since 3 years and in whom transthoracic echocardiography revealed a pedunculated tumor in the left ventricle. The tumor was successfully resected and its histopathological examination revealed a capillary hemangioma. The patient had an uneventful recovery without any complication.

Differences in lipid distribution and expression of peroxisome proliferator-activated receptor gamma and lipoprotein lipase genes in torafugu and red seabream.

Lipid content is one of the major determinants of the meat quality in fish. However, the mechanisms underlying the species-specific distribution of lipid are still poorly understood. The present study was undertaken to investigate the mechanisms associated with lipid accumulation in two species of fish: torafugu (a puffer fish) and red seabream. The lipid content of liver and carcass were 67.0% and 0.8% for torafugu, respectively, and 8.8% and 7.3% for red seabream, respectively. Visceral adipose tissue was only apparent in the red seabream and accounted for 73.3% of its total lipid content. Oil red O staining confirmed this species-specific lipid distribution, and further demonstrated that the lipid in the skeletal muscle of the red seabream was mainly localized in the myosepta. We subsequently cloned cDNAs from torafugu encoding lipoprotein lipase 1 (LPL1) and LPL2, important enzymes for the uptake of lipids from blood circulation system into various tissues. The relative mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) and the LPLs of torafugu were determined by quantitative real-time PCR together with their counterparts in red seabream previously reported. The relative mRNA levels of PPARγ and LPL1 correlated closely to the lipid distribution of both fish, being significantly higher in liver than skeletal muscle in torafugu, whereas the highest in the adipose tissue, followed by liver and skeletal muscle in red seabream. However, the relative mRNA levels of LPL2 were tenfold lower than LPL1 in both species and only correlated to lipid distribution in torafugu, suggesting that LPL2 has only a minor role in lipid accumulation. In situ hybridization revealed that the transcripts of LPL1 co-localized with lipids in the adipocytes located along the myosepta of the skeletal muscle of red seabream. These results suggest that the transcriptional regulation of PPARγ and LPL1 is responsible for the species-specific lipid distribution of torafugu and red seabream.

Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation.

Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the receptor level. It can interfere with binding to type I receptors and thus activation of receptor-regulated Smads or recruit the E3 ubiquitin ligase Smurf to receptors and thus target them for degradation. Here, we report that Smad7 is predominantly localized in the nucleus of Hep3B cells. The targeted expression of Smad7 in the nucleus conferred superior inhibitory activity on TGF-beta signaling, as determined by reporter assay in mammalian cells and by its effect on zebrafish embryogenesis. Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors. An oligonucleotide precipitation assay revealed that Smad7 can specifically bind to the Smad-responsive element via its MH2 domain, and DNA-binding activity was further confirmed in vivo with the promoter of PAI-1, a TGF-beta target gene, by chromatin immunoprecipitation. Finally, we provide evidence that Smad7 disrupts the formation of the TGF-beta-induced functional Smad-DNA complex. Our findings suggest that Smad7 inhibits TGF-beta signaling in the nucleus by a novel mechanism.