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The present work describes a biocomposite with thermal and acoustic insulating properties from agricultural or forestry residues using a steam injection molding technique. The biocomposites showed reasonable thermal insulation properties as judged based on their thermal conductivity, thermal diffusivity, and thermal stability data. The biocomposites had also good sound absorption properties. The dimensional stability of the biocomposites under accelerated weathering conditions was almost ideal. Although the flame retardancy of the biocomposites had rating acceptable to building products, it was yet concluded that for the biocomposites to have a wider market share, their flame-retardant capacity should be improved. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between sagittal spinal alignment and musculoskeletal health in older women, particularly those exhibiting diminished bone density without apparent symptoms. The study assessed the impact of global tilt (GT) and the presence of coronal malalignment on spinal health. The research involved 165 asymptomatic older women with an average age of 68.91 ± 7.25 years and average body mass index of 24.26 ± 3.66 kg/m². Comprehensive standing anteroposterior and lateral spine radiographs were used for assessment. Through multivariate linear regression analysis, the study identified significant correlations between increased GT angles and various factors, including coronal malalignment, the C7 slope, and pelvic incidence. This led to the formulation of a predictive GT model: GT = -9.79 + 0.06 × menopausal period + 0.19 × body mass index (BMI)- 0.81 × average T score - 0.11 × grip strength + 3.03 × (presence of coronal malalignment) + 0.08 × sagittal vertical axis (SVA) + 0.12 × C7 slope - 0.35 × upper lumbar lordosis (ULL) - 0.43 × lower lumbar lordosis (LLL) + 0.70 × pelvic incidence (PI), with an adjusted R² of 0.816. The study findings highlight the prevalence of coronal malalignment in this demographic and its significant associations with critical spinal parameters. The proposed GT predictive model may enable development of personalized treatment plans for older women with low bone mass., (© 2024. The Author(s).)

Current vertebral augmentation procedures (VAPs) often involve devices associated with bone cement leakage. Tripod-Fix is designed to mitigate the risk of bone cement leakage by expanding in three dimensions to fit a narrower vertebral space. This study enrolled 12 patients diagnosed with osteoprorotic vertebral compression fractures (VCFs) for 12 month follow up. The primary outcomes assessed were changes in the Visual Analog Score (VAS) and Oswestry Disability Index (ODI) before and after treatment. Our results demonstrated significant pain relief with VAS decreasing from 8.58 ± 1.83 to 2.75 ± 1.54 cm and improved mobility with ODI decreasing from 73.67 ± 16.29 to 31.83 ± 23.33% post-treatment and sustained for 12 months. Follow-up radiographs revealed no device-related adverse events such as cement leakage, vertebral body collapse, or adjacent vertebral fractures (AVFs). In addition, the mean anterior height restoration ratio after treatment was 15.87 ± 5.13%. Our preliminary findings suggest that Tripod-Fix exhibits safety and efficacy comparable to the third-generation devices currently utilized for treating osteoporotic VCFs., (© 2024. The Author(s).)

Gynecologic surgery with minimally invasive method using robotic or laparoscopic techniques has gained popularity for reducing perioperative discomfort and length of hospital stay. However, the debate over postoperative pain superiority between traditional laparoscopy and robotic surgery persist. This study compared the postoperative pain of patients within 24 h of robotic (RM) and laparoscopic myomectomy (LM). This retrospective cohort study included 24 and 53 patients who underwent RM and LM, respectively, between January 2019 and July 2023. The primary outcomes were the postoperative pain levels of patients within 24 h and the use and dosage of postoperative analgesia. Additional perioperative analgesia, including long-acting non-steroidal anti-inflammatory drugs (Dynastat) and abdominal nerve block, was also recorded. The secondary outcomes were blood loss and hospitalization duration. The patient characteristics were similar between the groups. Factors that could potentially increase pain, such as the number of ports (p < 0.0001), additional procedures (p = 0.0195), operative time (p < 0.0001), number of myomas (p = 0.0057), and the largest myoma size (p = 0.0086), were significantly higher in the RM group than in the LM group. However, there were no significantly different in the postoperative visual analog scale pain scores, use and dosage of ketorolac and opioid, and use of Dynastat and nerve block between the groups. Hospitalization duration and intraoperative blood loss were similar between the groups. RM and LM offer comparable postoperative pain outcomes, emphasizing the importance of patient-specific factors in decision-making regarding myomectomy techniques., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Existing data on maternal dietary patterns and birth weight remains limited and inconsistent, especially in non-Western populations. We aimed to examine the relationship between maternal dietary patterns and birth weight among a cohort of Chinese., Methods: In this study, 4,184 mother-child pairs were included from the Iodine Status in Pregnancy and Offspring Health Cohort. Maternal diet during pregnancy was evaluated using a self-administered food frequency questionnaire with 69 food items. Principal component analysis was used to identify dietary patterns. Information on birth weight and gestational age was obtained through medical records. Adverse outcomes of birth weight were defined according to standard clinical cutoffs, including low birth weight, macrosomia, small for gestational age, and large for gestational age., Results: Three maternal dietary patterns were identified: plant-based, animal-based, and processed food and beverage dietary patterns, which explained 23.7% variance in the diet. In the multivariate-adjusted model, women with higher adherence to the plant-based dietary patten had a significantly higher risk of macrosomia (middle tertile vs. low tertile: odds ratio (OR) 1.45, 95% CI 1.00-2.10; high tertile vs. low tertile: OR 1.55, 95% CI 1.03-2.34; P-trend = 0.039). For individual food groups, potato intake showed positive association with macrosomia (high tertile vs. low tertile: OR 1.72, 95% CI 1.20-2.47; P-trend = 0.002). Excluding potatoes from the plant-based dietary pattern attenuated its association with macrosomia risk. No significant associations was observed for the animal-based or processed food and beverage dietary pattern with birth weight outcomes., Conclusions: Adherence to a plant-based diet high in carbohydrate intake was associated with higher macrosomia risk among Chinese women. Future studies are required to replicate these findings and explore the potential mechanisms involved., (© 2024. The Author(s).)

Botrytis cinerea is an important fungal pathogen that causes gray mold disease in plants. Previously, Bacillus velezensis TCS001 live culture presented broad-spectrum antifungal activity against various plant pathogenic fungi and oomycetes, particularly B. cinerea . Here, the bioactivity of lipopeptides produced by TCS001 against B. cinerea was investigated. The IC 50 values of the crude lipopeptide extract (CLE) from TCS001 to suppress mycelial growth and conidial germination were 14.20 and 49.39 mg/L, respectively. SEM and TEM imaging revealed that CLE caused morphological deformities and ultrastructural changes in the mycelium. Transcriptomic analyses combined with Δ Bcpsd mutant construction demonstrated that the CLE could confer antifungal activity via suppressing Bcpsd expression in the pathogen. In addition, the CLE activated the plant immune system by increasing the content of defense-related enzymes and the expression of marker genes in immunity signaling pathways in cucumber plants. Therefore, TCS001 CLE could be potentially developed into biopesticides for the biocontrol of gray mold disease.

Measurement of infrared spectroscopy has emerged as a significant challenge for carbon materials due to the sampling problem. To overcome this issue, in this work, we performed measurements of IR spectra for carbon materials including C 60 , C 70 , diamond powders, graphene, and carbon nanotubes (CNTs) using the photoacoustic spectroscopy (PAS) technique; for comparison, the vibrational patterns of these materials were also studied with a conventional transmission method, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, or Raman spectroscopy. We found that the IR photoacoustic spectroscopy (IR-PAS) scheme worked successfully for these carbon materials, offering advantages in sampling. Interestingly, the profiles of IR-PAS spectra for graphene and CNTs exhibit negative bands using carbon black as the reference; the negative spectral information may provide valuable knowledge about the storage energy, production, structure, defect, or impurity of graphene and CNTs. Thus, this approach may open a new avenue for analyzing carbon materials.

A patient-friendly and efficient treatment method for patients with spinocerebellar ataxia type 3 (SCA3) was provided through a nose-to-brain liposomal system. Initially, PGK1 was overexpressed in HEK 293-84Q-GFP diseased cells (HEK 293-84Q-GFP-PGK1 cells) to confirm its effect on the diseased protein polyQ. A decrease in polyQ expression was demonstrated in HEK 293-84Q-GFP-PGK1 cells compared to HEK 293-84Q-GFP parental cells. Subsequently, PGK1 was encapsulated in a liposomal system to evaluate its therapeutic efficiency in SCA3. The optimized liposomes exhibited a significantly enhanced positive charge, facilitating efficient intracellular protein delivery to the cells. The proteins were encapsulated within the liposomes using an optimized method involving a combination of heat shock and sonication. The liposomal system was further demonstrated to be deliverable to the brain via intranasal administration. PGK1/liposomes were intranasally delivered to SCA3 mice, which subsequently exhibited an amelioration of motor impairment, as assessed via the accelerated rotarod test. Additionally, fewer shrunken morphology Purkinje cells and a reduction in polyQ expression were observed in SCA3 mice that received PGK1/liposomes but not in the untreated, liposome-only, or PGK1-only groups. This study provides a non-invasive route for protein delivery and greater delivery efficiency via the liposomal system for treating neurodegenerative diseases., (© 2023. Controlled Release Society.)

The aim of this work is to explore the effects of herbal medicine on secondary metabolites of microorganisms during fermentation. Clonostachys rogersoniana was found to metabolize only small amounts of polyketide glycosides rogerson B and C on fresh potatoes, but after replacing the medium to the medicinal plant Rubus delavayi Franch., the type and content of the metabolized polyketones showed significant changes. The sugars and glycosides in R. delavayi are probably responsible for the changes in secondary metabolites. Six polyketide glycosides including a new metabolite, rogerson F, and two potential antitumor compounds, TMC-151C and TMC-151D, were isolated from the extract of R. delavayi fermented by C. rogersoniana. In addition, 13 C labeling experiments were used to trace the biosynthesis process of these compounds. TMC-151C and TMC-151D showed significant cytotoxic activity against PANC-1, K562 and HCT116 cancer cells but had no obvious cytotoxic activity against BEAS-2B human normal lung epithelial cells. The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 g/kg and 1.98 ± 0.43 g/kg, respectively, after fermentation at 28 °C for 30 days. This is the first study to confirm that herbal medicine can induce microbes to metabolize active compounds. And the technology of fermenting medicinal materials can bring more economic value to medicinal plants., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Evidence on the effects of plantar intrinsic foot muscle exercise in older adults remains limited. This study aimed to evaluate the effect of an integrated intrinsic foot muscle exercise program with a novel three-dimensional printing foot core training device on balance and body composition in community-dwelling adults aged 60 and above., Methods: A total of 40 participants aged ≥ 60 years were enrolled in this quasi-experimental, single-group, pretest-posttest design; participants were categorized into two groups, those with balance impairment and those without balance impairment. The participants performed a 4-week integrated intrinsic foot muscle exercise program with a three-dimensional printing foot core training device. The short physical performance battery (SPPB) and timed up and go test were employed to evaluate mobility and balance. A foot pressure distribution analysis was conducted to assess static postural control. The appendicular skeletal muscle mass index and fat mass were measured by a segmental body composition monitor with bioelectrical impedance analysis. The Wilcoxon signed rank test was used to determine the difference before and after the exercise program., Results: Among the 40 enrolled participants (median age, 78.0 years; female, 80.0%; balance-impaired group, 27.5%), the 95% confidence ellipse area of the center of pressure under the eyes-closed condition was significantly decreased (median pretest: 217.3, interquartile range: 238.4; median posttest: 131.7, interquartile range: 199.5; P = 0.001) after the exercise. Female participants without balance impairment demonstrated a significant increase in appendicular skeletal muscle mass index and a decrease in fat mass. Participants in the balance-impaired group exhibited a significant increase in SPPB., Conclusions: Integrated intrinsic foot muscle exercise with a three-dimensional printing foot core training device may improve balance and body composition in adults aged 60 and above., Trial Registration: ClinicalTrials.gov ID: NCT05750888 (retrospectively registered 02/03/2023)., (© 2024. The Author(s).)

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93-1.42 or aOR 1.23; 95% CI 0.96-1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90-1.58 or aOR 1.24; 95% CI 0.90-1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions., (© 2024. The Author(s).)

Background: The effects of integrated care with case management and nutritional counselling for frail patients with nutritional risk are unclear., Objectives: To assess the impact of the integrated care model for frail patients with nutritional risk in the primary care setting., Methods: This was a retrospective observational study. We enrolled 100 prefrail or frail patients according to Clinical Frailty Scale (CFS) aged ≥ 60 years with nutritional risk from the geriatric clinic. We implemented the frailty intervention model, including integrated care with comprehensive geriatric assessments (CGA), case management, and nutritional counselling by the dietitian. We obtained measures of CGA components, physical performance, body mass index (BMI), and daily caloric intake before and after the 2-month care program. We used the Wilcoxon signed-rank test to analyse differences after the care program and applied multiple linear regression to determine the predictive factors for CFS improvement., Results: Among the 100 patients (mean age, 75.0 ± 7.2 years; females, 71.0%; frail patients, 26%), 93% improved their CFS status, and 91% achieved > 80% of recommended daily caloric intake after the care program. The Mini Nutritional Assessment Short-Form significantly improved after the program. BMI and daily caloric intake increased significantly after nutritional counselling. The post-test short physical performance battery (SPPB) significantly increased with a faster 4 m gait speed. Baseline poor CFS was a significant predictor for CFS improvement., Conclusions: Integrated care with case management and nutritional counselling for prefrail and frail patients with nutritional risk in the primary care setting may improve physical performance and nutritional status., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-β) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles. The conformations of the peptide pair exhibited inverted chirality according to CD and NMR spectroscopic analyses. Both heterochiral peptides displayed enhanced stability and low hemolysis activities. Irrespective of their different d-enantiomer contents, both heterochiral peptides exhibited bactericidal activities in the presence of human serum or physiological enzymes. However, the peptide with higher d-amino acid content (TP4-β) caused better bacterial clearance when tested in mice infected with NDM-1 K. pneumoniae. In addition, we observed a relatively higher hydrogen bonding affinity in a simulation of the interaction between TP4-β and a model bacterial membrane. In sum, our results demonstrate that the current design strategy may be applicable for development of new molecules with enhanced stability and in vivo antimicrobial activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Antimicrobial peptides (AMPs) are natural molecules that function within the innate immune system to counteract pathogenic invasion and minimize the detrimental consequences of infection. However, utilizing these molecules for medical applications has been challenging. In this study, we selected a model AMP with poor stability, Tilapia Piscidin 4 (TP4), and modified its sequence and chirality (TP4-γ) to improve its potential for clinical application. The strategy of chirality inversion was inspired by the cereulide peptide, which has a DDLL enantiomer pattern and exhibits exceptional stability. Sequential substitution of key residues and selective chirality inversion yielded a less toxic peptide with enhanced stability and notable antimicrobial activity. In addition to its superior stability profile and antimicrobial activity, TP4-γ treatment reduced the level of LPS-induced nitric oxide (NO) release in a macrophage cell line. This reduction in NO release may reflect anti-inflammatory properties, as NO is widely known to promote inflammatory processes. Hence, our heterochiral peptide construct shows a more suitable pharmacokinetic profile than its parental compound, and further studies are warranted to develop the molecule for potential clinical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

As an innovative technique, laser-GMAW hybrid welding manifests significant superiority in enhancing welding productivity and quality, albeit the optimization of process parameters poses a challenge for practical application. The present manuscript elucidates the influence of process parameters on the dimensional characteristics of the welding seam and the distortion of 8 mm T-joints in the context of laser-GMAW hybrid welding, and channels both simulation and experimentation. The outcomes denote that the dual conical model serves as an efficacious aid for the numerical simulation of T-joint laser-GMAW hybrid welding. Furthermore, the repercussions of process parameters on welding seam dimensional characteristics remain consistently similar in both the simulation and experimental results. From the simulation outcomes, it becomes apparent that the distortion of the base material can be efficiently managed by implementing anti-distortion measures. This inquiry offers both a theoretical and experimental foundation for optimizing process parameters of T-joint laser-GMAW hybrid welding, presenting certain engineering applicability.

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780-5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780-5p, wherein hsa-miRNA-6780-5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780-5p were further applied to HEK-293-84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780-5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780-5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780-5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells., (Copyright © 2023. Published by Elsevier B.V.)

A new benzophenone derivative, 8'-hydroxymonomethylsulochrin ( 1 ), together with eighteen known compounds ( 2-19 ) were produced by the endophytic fungus Aspergillus fumigatus WJ-131, isolated from the stem of Gardenia jasminoides . The structure of 1 was determined by extensive spectroscopic analysis and X-ray crystallography. Under the condition of concentration of 20.0  μ M, the splenic lymphocytes proliferation rates of compounds 1 and 7 induced by LPS were 39.4% and 38.1% (LPS, the splenic lymphocytes cell proliferation rates of 21.3%), and the splenic lymphocytes proliferation rate of compounds 7 induced by ConA is 44.6% (ConA, the splenic lymphocytes proliferation rates of 28.9%). Therefore, compounds 1 and 7 promoted the proliferation of ConA/LPS-stimulated splenic lymphocytes at 20.0  μ M in vitro . In addition, compound 1 showed weak antibacterial activity against Fusarium oxysporum .

Objective: To understand the performance of public health risk assessment in emergencies of institutions for disease control and prevention at different levels in China, and provide suggestions for the improvement of public health risk assessment. Methods: A self-administered survey was conducted in professionals involved in public health risk assessment in emergencies from national institution, provincial institutions and some prefectural institutions for disease control and prevention (1-2 prefectural institutions were selected using convenience sampling in each province) between March and April in 2021. Results: A total of 79 institutions for disease control and prevention were investigated, including 1 national institution, 32 provincial institutions and 46 prefectural institutions. By April 2021, all the 79 institutions surveyed had conducted risk assessment of public health emergencies, in which 61 (77.2%) had established departments responsible for the public health risk assessment, i.e. emergency management office or communicable disease prevention and control office (section), and regular risk assessment mechanisms. The main sources of information for public health risk assessment were public health surveillance systems, including the National Notifiable Diseases Reporting System (100.0%) and Public Health Emergencies Management Information System (97.5%). Compared with the provincial institutions, the prefectural institutions were more likely to use specific disease surveillance systems (84.8% vs . 62.5%; χ 2 =5.09, P =0.024). The risk management recommendations made by 43 institutions for disease control and prevention (54.4%) after the risk assessment were accepted by the superior health administrative departments and used in epidemic prevention and control. Conclusions: Public health risk assessment in emergencies has been widely carried out by national, provincial and prefectural institutions for disease control and prevention in China. Specialized departments and mechanisms have been established, but the information sources are still confined to public health surveillance systems and the application of the risk assessment results still needs to be further improved.

Two previous unreported fusicoccane diterpenoids macrostines A and B, together with seven known compounds were isolated from an extract of the fungus Periconia macrospinosa WTG-10. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Macrostines A and B showed no cytotoxicity, antimicrobial activity and inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. Compound 9 showed moderate activity against Bacillus subtilis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Previous evidence suggests that bisphosphonates may improve glycemic control. The present meta-analysis, comprising seven studies with 1,233,844 participants, demonstrated that bisphosphonate use was significantly associated with a lower risk of diabetes. However, in the randomized controlled trial subgroup, a non-significant association was found. Further studies are needed to determine causality., Purpose: This study aimed to evaluate the impact of bisphosphonates on glycemic control and the risk of incident diabetes., Methods: MEDLINE, Embase, and Cochrane Library were searched from inception to February 15, 2022. Experimental or observational studies that compared fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and the diabetes risk with and without bisphosphonates were included. Studies without relevant outcomes, only providing crude estimates, or the absence of a control group were excluded. Two reviewers independently screened the articles, extracted data, and appraised studies. The pooled relative risk (RR) and weighted mean difference (WMD) were calculated using random effects models., Results: Seven studies (n = 1,233,844) on diabetes risk were included, including two post hoc analyses of randomized controlled trials (RCTs) and five observational studies. Compared with controls, bisphosphonates (BPs) were associated with a significant decrease in the risk of diabetes (RR = 0.77; 95% CI, 0.65 to 0.90; P = 0.002). However, in the subgroup of post hoc analyses of RCTs, the association was non-significant (RR = 0.93; 95% CI, 0.74 to 1.18; P = 0.576). Moreover, three studies (n = 4906) on FBG and one (n = 60) on HbA1c were included. We observed non-significant association between BPs and changes in FBG (WMD =  - 0.61 mg/dL; 95% CI, - 2.72 to 1.49; P = 0.567) and HbA1c (WMD =  - 0.11%; 95% CI, - 0.23 to 0.01; P = 0.083)., Conclusion: Patients taking BPs may have a lower risk of incident diabetes than those without BPs. However, due to the high between-study heterogeneity and inconsistent findings between post hoc analyses of RCTs and observational studies, further rigorous RCTs are required to determine whether the findings are causal., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Spinal cord injuries (SCI) have a profound impact on autonomic systems, sometimes resulting in multi-organ dysfunction, including of the neurogenic bladder. Autonomic dysreflexia (AD) is commonly seen in patients with SCI above T6 when the injured cord develops a deregulated sympathetic reflex, which can be induced by bladder sensation and can cause hypertensive crisis. While intravesical injection of botulinum toxin A (Botox) is a standard therapy for neurogenic detrusor overactivity, the role of Botox for AD has rarely been described. This study reviewed the medical records of SCI patients who reported AD and received either detrusor or urethral sphincter injection with Botox. The primary endpoint is the subjective improvement of AD. The secondary endpoint is a change in videourodynamic parameters before and after Botox injection. A total of 200 patients were enrolled for analysis. There were 125 (62.5%) patients in the detrusor injection group, and 75 (37.5%) in the urethral sphincter injection group. There were 79 (63.2%) patients in the detrusor injection group and 43 (57.3%) in the urethral sphincter injection group reporting moderate or marked improvement. Detrusor injection leads to a greater improvement in AD, probably because of decreased detrusor pressure and increased compliance after Botox injection. Urethral sphincter injection appears to have a modest effect on AD, despite general improvements in the voiding parameters of videourodynamic study.

Background: Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin., Methods: A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models., Results: The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings., Conclusions: This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms., (© 2023. The Author(s).)

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo . In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Si-Qi Jia et al.)

Purpose: Dysfunctional voiding (DV) in women is a common disorder that causes bladder outlet obstruction (BOO) and may aggravate overactive bladder (OAB) symptoms. The diagnosis of DV relies on clinical alertness and videourodynamic study (VUDS). In this pilot study, we aimed to explore the diagnostic potential of urinary biomarkers in women with DV., Methods: Women who visited our institute for the management of OAB were enrolled in this prospective study. Urine samples were collected before treatment and urinary proteins were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Patients with DV and patients with normal tracings were included in the study and control group, respectively. The patients with DV were further divided into two subgroups: those with and those without detrusor overactivity (DO). VUDS parameters and urinary protein levels were compared between each subgroup., Results: A total of 67 women were enrolled. There were 47 patients with VUDS-diagnosed DV and 20 patients in the control group. Urinary 8-OHdG level (32.65 vs. 15.59, p < 0.001) and urinary TNF-α level (1.43 vs. 0.83, p = 0.031) were significantly higher in the DV group, and urinary IL-2 level (0.29 vs. 0.83, p < 0.001) was significantly lower in the DV group. Among the DV patients, urinary PGE2 level was higher in the DO group (240.4 vs 149.6, p = 0.049)., Conclusions: In women with DV, urinary 8-OHdG level is elevated compared to women with normal VUDS. Urinary PGE2 level is elevated in patients with DV and DO. These finding suggests increased reactive-oxidative stress response and detrusor hyperactivity in DV patients. Urinary biomarkers can serve as potential non-invasive diagnostic tools in women with OAB., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The objective of this study was to conduct a 2-year follow-up of individuals having unsatisfactory reports of Pap smears and to analyze the contributing factors. This was a retrospective study at a medical center that performed about 5000-6000 Pap smears annually in Eastern Taiwan. Women who had unsatisfactory results due to scant cellularity between January 1, 2015-December 31, 2016, were included in this study. The control group comprised age-matched women with normal Pap smears at a 1:4 ratio, during the same period. The clinical characteristics and the 2-year outcomes were followed. Patients who were unavailable for follow-up assessments or who had insufficient clinical information were excluded. Student's t-test and chi-square test were used for continuous and categorical variables, respectively. Statistical significance was defined as a p-value &lt; 0.05. A total of 887 Pap smears were included. A total of 717 and 170 women had normal Pap and unsatisfactory Pap tests, respectively. After excluding women who were unavailable for follow-up, the final analysis included 248 and 67 women with normal and unsatisfactory Pap tests, respectively. The mean age was not significantly different between the two groups (49.97 ± 10.69 and 51.61 ± 11.28 years in the unsatisfactory Pap and control groups, respectively [p &gt; 0.05]). The percentage of menopause and vaginal discharge were significantly different between the two groups. Multivariate analysis revealed that premenopausal status, increased discharge were associated with the risk of unsatisfactory Pap tests. Of the 67 women with unsatisfactory Pap tests, all tested negative for any malignancies at a 2-year follow-up assessment. Women with increased vaginal discharge and without menopause were at an increased risk of having an unsatisfactory Pap test. Our results indicate that an unsatisfactory Pap smear due to scant cellularity might not increase the risk of intraepithelial neoplasia or cancer after 2 years. Further, large-scale studies with longer follow-up periods are required., (© 2022. The Author(s).)

Purpose: There is limited and inconsistent evidence about the relationships of erythrocyte polyunsaturated fatty acids (PUFAs) with stroke and stroke types, particularly in China where the stroke rates are high. We aimed to investigate the associations of different erythrocyte PUFAs with incidence of total stroke, ischemic stroke (IS), and intracerebral hemorrhage (ICH) in Chinese adults., Methods: In the prospective China Kadoorie Biobank, erythrocyte PUFAs were measured using gas chromatography in 10,563 participants who attended 2013-14 resurvey. After a mean follow-up of 3.8 years, 412 incident stroke cases (342 IS, 53 ICH) were recorded among 8,159 participants without prior vascular diseases or diabetes. Cox regression yielded adjusted hazard ratios (HRs) for stroke associated with 13 PUFAs., Results: Overall, the mean body mass index was 24.0 (3.4) kg/m 2 and the mean age was 58.1 (9.9) years. In multivariable analyses, 18:2n-6 was positively associated with ICH (HR = 2.33 [95% CIs 1.41, 3.82] for top versus bottom quintile, P trend  = 0.007), but inversely associated with IS (0.69 [0.53,0.90], P trend  = 0.027), while 20:3n-6 was positively associated with risk of IS (1.64 [1.32,2.04], P trend  < 0.001), but not with ICH. Inverted-U shape curve associations were observed of 20:5n-3 with IS (P nonlinear  = 0.002) and total stroke (P nonlinear  = 0.008), with a threshold at 0.70%. After further adjustment for conventional CVD risk factors and dietary factors, these associations remained similar., Conclusion: Among relatively lean Chinese adults, erythrocyte PUFAs 18:2n-6, 20:3n-6 and 20:5n-3 showed different associations with risks of IS and ICH. These results would improve the understanding of stroke etiology., (© 2022. The Author(s).)

Background: Evidence on the effects of Acute Care for Elders (ACE) units in frail older adults remains limited. Therefore, we aimed to evaluate the effects of the ACE unit on functional outcomes in frail older adults., Methods: In this prospective observational study, we enrolled 114 consecutive patients aged 65 years and older admitted to the ACE unit for acute medical conditions between October 2019 and September 2020. The FRAIL scale (5-question assessment of fatigue, resistance, aerobic capacity, illnesses, and loss of weight) was used to classify the patients into three groups: robust (score = 0, n = 28), prefrail (score = 1-2, n = 57), and frail (score = 3-5, n = 29). The primary outcome was the activities of daily living (ADL) measured by the Barthel Index at admission and before discharge. Paired sample t-test was employed to determine the difference in ADL. Multiple linear regression analysis, with adjustment for covariates, was conducted to examine the association between frailty status and change in ADL., Results: Among 114 patients enrolled (mean age, 79.8 ± 8.1 years; mean length of stay, 6.4 ± 5.6 days), 77 (67.5%) were female. ADL at admission (60.3 ± 31.9) and before discharge (83.7 ± 21.6) were significantly different (P < 0.001). After covariates adjustment, a significant association between frailty status and change in ADL was found (prefrail vs. robust: β = 9.0, 95% confidence interval [CI] 0.3-17.6, P = 0.04; frail vs. robust: β = 13.4, 95% CI 2.7-24.0, P = 0.01)., Conclusions: Older adults with frailty experienced functional improvement after admission to the ACE unit. Prefrail and frail groups were associated with a more significant change in ADL between admission and discharge compared to the robust group., (© 2022. The Author(s).)

While disrupted lipid metabolism is a well-established risk factor for hypertension in animal models, the links between various lipidomic signatures and hypertension in human studies remain unclear. We aimed to examine associations between plasma lipidomic profiles and prevalence of hypertension among 2248 community-living Chinese aged 50-70 years. Hypertension was defined according to 2020 International Society of Hypertension global hypertension practice guidelines and 2018 Chinese guidelines. In total, 728 plasma lipidomic species were profiled using high-coverage targeted lipidomics. After multivariate adjustment, including lifestyle, body mass index, blood lipids, and sodium intake, 110 metabolites from nine lipidomic subclasses showed significant associations with hypertension, among which phosphatidylethanolamines (PEs) had the strongest association. Eleven lipidomic signals for hypertension risk were further identified from the nine subclasses, including PE(18:0/18:2) (OR per SD, 1.49; 95% confidence intervals, 1.30-1.69), phosphatidylcholine (PC) (18:0/18:2) (1.27; 1.13-1.43), phosphatidylserine (18:0/18:0) (1.24; 1.09-1.41), lysophosphatidylinositol (18:1) (1.17; 1.06-1.29), triacylglycerol (52:5) (1.38; 1.18-1.61), diacylglycerol (16:0/18:2) (1.42; 1.19-1.69), dihydroceramide (24:0) (1.25; 1.09-1.43), hydroxyl-sphingomyelins (SM[2OH])C34:1 (1.19; 1.07-1.33), lysophosphatidylcholine (20:1) (0.86; 0.78-0.95), SM(OH)C38:1 (0.87; 0.79-0.96), and PC (18:2/20:1) (0.84; 0.75-0.94). Principal component analysis also showed that a factor mainly containing specific PEs was positively associated with hypertension (1.20; 1.09-1.33). Collectively, our study revealed that disturbances in multiple circulating lipidomic subclasses and signatures, especially PEs, were significantly associated with the prevalence of hypertension in middle-aged and elderly Chinese. Future studies are warranted to confirm our findings and determine the mechanisms underlying these associations., Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00057-y., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Human Phenome Institutes (Shanghai) 2022.)

Urinary tract infections (UTIs) are a leading hospital-acquired infection. Although timely detection of causative pathogens of UTIs is important, rapid and accurate measures assisting UTI diagnosis and bacterial determination are poorly developed. By reading infrared spectra of urine samples, Fourier-transform infrared spectroscopy (FTIR) may help detect urine compounds, but its role in UTI diagnosis remains uncertain. In this pilot study, we proposed a characterization method in attenuated total reflection (ATR)-FTIR spectra to evaluate urine samples and assessed the correlation between ATR-FTIR patterns, UTI diagnosis, and causative pathogens. We enrolled patients with a catheter-associated UTI in a subacute-care unit and non-UTI controls (total n = 18), and used urine culture to confirm the causative pathogens of the UTIs. In the ATR-FTIR analysis, the spectral variation between the UTI group and non-UTI, as well as that between various pathogens, was found in a range of 1800-900 cm -1 , referring to the presence of specific constituents of the bacterial cell wall. The results indicated that the relative ratios between different area zones of vibration, as well as multivariate analysis, can be used as a clue to discriminate between UTI and non-UTI, as well as different causative pathogens of UTIs. This warrants a further large-scale study to validate the findings of this pilot research.

This study aims to investigate the role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). 18 F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD 3mo ), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD 3mo ( p = 0.009), dCt ( p = 0.014) and bsumMTV ( p = 0.014) were independent predictors of PFS, and dCt ( p = 0.014) and ΔsumMTV ( p = 0.005) were independent predictors of OS. 18 F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.

Retinal ganglion cell (RGC) axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain. RGC axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision. OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that, in response to stress, exogenous OTX2 increases the in vitro and in vivo survival of RGCs. Here we examined and quantified the effects of OTX2 on adult RGC axon regeneration in vitro and in vivo. The results show that exogenous OTX2 stimulates the regrowth of axons from RGCs in cultures of dissociated adult retinal cells and from explants of adult retinal tissue and that RGCs respond directly to OTX2 as regrowth is observed in cultures of purified adult rat RGCs. Importantly, after nerve crush in vivo, we observed a positive effect of OTX2 on the number of regenerating axons up to the optic chiasm within 14 days post crush and a very modest level of acuity absent in control mice. The effect of OTX2 on RGC survival and regeneration is of potential interest for degenerative diseases affecting this cell type. All animal procedures were approved by the local "Comié d'éιthique en expérimentation animale n°59" and authorization n° 00702.01 delivered March 28, 2014 by the French "Ministére de l'enseignement supérieur et de la recherche"., Competing Interests: None

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling., (© 2022. The Author(s).)

Studying heart rate dynamics would help understand the effects caused by a hyperkinetic heart in patients with hyperthyroidism. By using a multiscale entropy (MSE) analysis of heart rate dynamics derived from one-channel electrocardiogram recording, we aimed to compare the system complexity of heart rate dynamics between hyperthyroid patients and control subjects. A decreased MSE complexity index (CI) computed from MSE analysis reflects reduced system complexity. Compared with the control subjects ( n = 37), the hyperthyroid patients ( n = 37) revealed a significant decrease ( p < 0.001) in MSE CI (hyperthyroid patients 10.21 ± 0.37 versus control subjects 14.08 ± 0.21), sample entropy for each scale factor (from 1 to 9), and high frequency power (HF) as well as a significant increase ( p < 0.001) in low frequency power (LF) in normalized units (LF%) and ratio of LF to HF (LF/HF). In conclusion, besides cardiac autonomic dysfunction, the system complexity of heart rate dynamics is reduced in hyperthyroidism. This finding implies that the adaptability of the heart rate regulating system is impaired in hyperthyroid patients. Additionally, it might explain the exercise intolerance experienced by hyperthyroid patients. In addition, hyperthyroid patients and control subjects could be distinguished by the MSE CI computed from MSE analysis of heart rate dynamics.

Background: Tear film instability plays an important role in the course of Sjögren's Syndrome dry eye (SSDE) even though it is generally classified as aqueous-deficient dry eye. The measurement of the first tear film break-up point (FTBUP) helps to evaluate the most unstable position of the tear film on ocular surface. We aim to investigate FTBUP in Sjögren's Syndrome dry eye (SSDE) and non-Sjögren's Syndrome dry eye (NSSDE) patients, and explore its correlation with dry eye indices., Methods: Twenty-two SSDE patients (44 eyes) and 22 NSSDE patients (44 eyes) were enrolled in the study. Oculus Keratograph K5M was used to measure FTBUP, the first and average non-invasive keratographic breakup time (f-NIKBUT and av-NIKBUT), the tear meniscus height, and meibomian gland dropout. Other tests of tear film were also performed including Ocular Surface Dryness Index (OSDI), Schirmer I test, fluorescein break-up time and corneal fluorescein staining. Dry eye indices and the locations of the FTBUP were compared between SSDE and NSSDE patients. Generalized estimating equation (GEE) was used to ajusted the correlations between right and left eyes. The correlations between the FTBUP and ocular symptoms and signs were investigated using Pearson's correlation coefficient test., Results: The FTBUP occurred at the supranasal quadrant in 12/88 eyes, supratemporal quadrant in 8/88 eyes, inferonasal quadrant in 34/88 eyes, and inferotemporal quadrant in 34/88 eyes. The percentage eyes with inferior FTBUP was significantly higher in the SSDE than in the NSSDE subjects (86.3% vs 68.1%, P = .049). Moreover, in SSDE subjects, temporal breakup point was seen more often in those who presented corneal fluorescein staining in any location, while nasal breakup point was more frequent in those who did not present any corneal fluorescein staining (P = .045)., Conclusion: The location of the FTBUP in SSDE patients had specific characteristics. However, the diagnostic potential of FTBUP in early recognition of SSDE needs further validation., (© 2021. The Author(s).)

Voiding dysfunction can result from detrusor underactivity (DU), bladder outlet obstruction (BOO), or both. Conceptually, women with high-pressure low-flow urodynamic profiles are diagnosed with BOO without DU. However, the possibility of BOO is often neglected in women with DU-like (low-pressure low-flow) urodynamic (UDS) profiles. By reviewing the videourodynamic studies (VUDS) of 1678 women, our study identified the key factors suggesting urodynamic BOO (determined by radiographic evidence of obstruction) in women with DU-like UDS profiles (Pdet.Qmax < 20 cmH2O and Qmax < 15 mL/s). In 355 women with DU-like UDS profiles, there were 70 (19.7%) with BOO and 285 (80.3%) without BOO. The BOO group had predominantly obstructive symptoms. The BOO group showed significantly decreased bladder sensation, lower detrusor pressure (Pdet.Qmax), lower flow rate (Qmax), smaller voided volume, and larger post-voiding residual (PVR) compared to the non-BOO group. In multivariate analysis, volume at first sensation, Qmax, PVR, and detrusor overactivity (DO) remained independent factors for BOO. The receiver operating characteristic (ROC) areas for the parameters were largest for PVR (area = 0.786) and Qmax (area = 0.742). The best cut-off points were 220 mL for PVR and 4 mL/s for Qmax. Our findings provide simple indicators for BOO in women with DU., (© 2021. The Author(s).)

Cognitive impairment is a serious side effect of post-myocardial infarction (MI) course. We have recently demonstrated that human adipose-derived stem cells (hADSCs) ameliorated myocardial injury after MI by attenuating reactive oxygen species (ROS) levels. Here, we studied whether the beneficial effects of intramyocardial hADSC transplantation can extend to the brain and how they may attenuate cognitive dysfunction via modulating ROS after MI. After coronary ligation, male Wistar rats were randomized via an intramyocardial route to receive either vehicle, hADSC transplantation (1 × 10 6 cells), or the combination of hADSCs and 3-Morpholinosydnonimine (SIN-1, a peroxynitrite donor). Whether hADSCs migrated into the hippocampus was assessed by using human-specific primers in qPCR reactions. Passive avoidance test was used to assess cognitive performance. Postinfarction was associated with increased oxidative stress in the myocardium, circulation, and hippocampus. This was coupled with decreased numbers of dendritic spines as well as a significant downregulation of synaptic plasticity consisting of synaptophysin and PSD95. Step-through latency during passive avoidance test was impaired in vehicle-treated rats after MI. Intramyocardial hADSC injection exerted therapeutic benefits in improving cardiac function and cognitive impairment. None of hADSCs was detected in rat's hippocampus at the 3rd day after intramyocardial injection. The beneficial effects of hADSCs on MI-induced histological and cognitive changes were abolished after adding SIN-1. MI-induced ROS attacked the hippocampus to induce neurodegeneration, resulting in cognitive deficit. The remotely intramyocardial administration of hADSCs has the capacity of improved synaptic neuroplasticity in the hippocampus mediated by ROS, not the cell engraftment, after MI. KEY MESSAGES: Human adipose-derived stem cells (hADSCs) ameliorated injury after myocardial infarction by attenuating reactive oxygen species (ROS) levels. Intramyocardial administration of hADSCs remotely exerted therapeutic benefits in improving cognitive impairment after myocardial infarction. The improved synaptic neuroplasticity in the hippocampus was mediated by hADSC-inhibiting ROS, not by the stem cell engraftment., (© 2021. The Author(s).)

Multiple N-methyl-D-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105-0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer's Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076-0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145-0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia., (© 2021. The Author(s).)

Background: This study aimed to evaluate fetal adverse outcomes of laparoscopy and laparotomy in pregnant women to determine the safety of these surgical approaches., Methods: This was a retrospective nationwide case-control study of women who became pregnant for the first time between 2000 and 2012 in Taiwan. The case (with adverse fetal outcomes) and control groups comprised 208,604 and 417,124 participants, respectively. Participants who underwent appendectomy, cholecystectomy, ovarian cystectomy, or myomectomy were treated with either laparoscopy or laparotomy. A conditional logistic regression model was used to calculate the odds ratios (ORs) for adverse fetal outcomes., Results: The laparotomy and laparoscopy groups comprised 632 and 536 patients, respectively. Women who underwent laparoscopy had a significantly higher risk of adverse fetal outcomes (adjusted OR [AOR] = 2.33; 95% CI 1.66-2.99) than those who underwent laparotomy. Adverse fetal outcomes were found to be significantly associated with laparoscopy among women aged 20-39 years (AOR = 2.30; 95% CI 1.70-3.31). Regarding surgical indication, unlike laparotomy, laparoscopic cholecystectomy and appendectomy were not associated with adverse fetal outcomes. However, laparoscopic myomectomy and ovarian surgeries were associated with a higher incidence of adverse fetal outcomes than the laparotomy group (AOR = 2.29 [95% CI 1.57-3.35, p < 0.0001] and AOR = 2.52 [95% CI 1.58-4.04, p = 0.0001], respectively)., Conclusions: Pregnant women who underwent laparoscopic surgery experienced significantly more adverse fetal outcomes than those who underwent laparotomy. Therefore, pregnant women undergoing either laparotomy or laparoscopy should be informed of the risk of adverse fetal outcomes., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15-2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05-1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality., (© 2021. The Author(s).)

Dysfunctional voiding (DV), a voiding dysfunction due to hyperactivity of the external urethral sphincter or pelvic floor muscles leading involuntary intermittent contractions during voiding, is not uncommon in neurologically normal women with lower urinary tract symptoms (LUTS). We aimed to investigate the therapeutic efficacy of biofeedback pelvic floor muscle training (PFMT) in female patients with DV and to identify the therapeutic efficacy. Thirty-one patients diagnosed with DV. All participates completed the 3-month biofeedback PFMT program, which was conducted by one experienced physiotherapist. At 3 months after treatment, the assessment of treatment outcomes included global response assessment (GRA), and the changes of clinical symptoms, quality of life index, and uroflowmetry parameters. 25 (80.6%) patients had successful outcomes (GRA ≥ 2), and clinical symptoms and quality of life index significantly improved after PFMT. Additionally, uroflowmetry parameters including maximum flow rate, voided volume, voiding efficiency, total bladder capacity, voiding time, and time to maximum flow rate significantly improved after PFMT treatment. Patients with the history of recurrent urinary tract infection in recent 1 year were found to have unsatisfied therapeutic outcomes. In conclusion, biofeedback PFMT is effective in female patients with DV with significant improvements in clinical symptoms, quality of life, and uroflowmetry parameters. The history of urinary tract infection in recent 1 year is a negative predictor of successful outcome.

Background: The short-term effect of ambient air pollution on atopic dermatitis (AD), along with its effect modifiers, has not been fully addressed., Objectives: To examine the short-term associations between air pollution and AD, and to identify effect modifications by age and season., Methods: We used the generalized additive model to evaluate the short-term effect of ambient air pollution on daily hospital visits for AD, adjusting for potential confounders. Subgroup analyses were performed to identify potential effect modifications by season and age (< 18 years and ≥ 18 years)., Results: A total of 29 972 hospital visits for AD were recorded in Guangzhou, China, from 19 January 2013 to 31 December 2017. Among them, 72·8% were visits by children and 51·4% occurred in the cool season. Acute and delayed effects on AD hospital visits were significant for all air pollutants. Stronger effects were seen in the cool season (approximately 1·7-3·0 times higher than effects in the warm season). Stronger effects were also observed in children (approximately 1·3-1·8 times higher than effects in adults). Sensitivity analyses indicated the results were robust., Conclusions: Air pollution might be an important trigger for AD in subtropical Guangzhou, China. Children are more vulnerable than adults, and the effects are stronger in the cool season., (© 2020 British Association of Dermatologists.)

This study aimed to evaluate the risk of ischemic stroke (IS) in hormone therapy (HT) with oral conjugated equine estrogen (CEE) and estradiol (E2) in postmenopausal women in Taiwan. A retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women, aged 40-65 years, who received HT with E2 and CEE orally were enrolled. The primary outcome was IS. Propensity score matching with menopausal age and comorbidities was used. Cox proportional hazard regression models were used to calculate the incidence and hazard ratios (HRs) for IS. The mean menopausal ages of the E2 and CEE groups were 50.31 ± 4.99 and 50.45 ± 5.31 years, respectively. After adjusting for age and comorbidities, the incidence of IS was 1.17-fold higher in the women treated with CEE than in those treated with E2 (4.24 vs. 3.61/1000 person-years), with an adjusted HR (aHR) of 1.23 (95% confidence interval [CI] 1.05-1.44). Moreover, HT with CEE initiated within 5 years of menopause had a higher HR than E2 (aHR = 1.20; 95% CI 1.02-1.42). In conclusion, HT with oral CEE might be associated with a higher risk of IS than E2 in postmenopausal Taiwanese women. The use of HT with CEE should be cautioned with the risk of IS.

Patients with hepatocellular carcinoma (HCC) might be more vulnerable to develop stroke than other cancer patients because of HCC-associated coagulation dysfunction. However, limited studies have investigated the relationship between HCC and stroke. This nationwide population-based cohort study enrolled all patients with HCC diagnosed between 2011 and 2015 from the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database; an age- and sex-matched cohort without cancer was included. The primary outcome was the 1-year risk for first-ever stroke after the index date. The Fine and Gray competing risk regression model was used to estimate the 1-year stroke risk with adjusted hazard ratios (aHRs). After propensity score matching, each cohort has 18,506 patients with similar baseline characteristics. Compared with the cancer-free cohort, the aHRs in the HCC cohort for overall, ischemic, and hemorrhagic strokes were 1.59 [95% confidence interval (CI), 1.35-1.88], 1.38 [95% CI, 1.15-1.65], and 2.62 [95% CI, 1.79-3.84], respectively. On subgroup analysis, HCC patients without cirrhosis, those with stage 3 or 4 cancer had a higher stroke risk than cancer-free cohort. Therefore, stroke prevention should be considered in patients with HCC, especially in those without cirrhosis and with stage 3 or 4 cancer.

The aim of this study was to compare the clinical outcomes of transvaginal mesh (TVM) surgery with and without midline fascial plication for anterior prolapse repair. This is a prospective randomized trial in a teaching hospital. This study compared patients with anterior vaginal wall prolapse (POP-Q Ba > -1) who were randomly assigned to either transvaginal mesh (TVM, Avaulta Solo TM , CR Bard. Inc., Covington, GA, USA polypropylene mesh delivery system) (group A, n = 32) or TVM with concomitant midline fascial plication (group B, n = 32). The outcomes of anatomy correction and life quality were evaluated using a pelvic organ prolapse quantification system and questionnaires. Sixty-four patients were included from January 2011 through April 2014 in this study. Group A had a mean age of 63.7 years and a body mass index (BMI) of 25.4 kg/m 2 . Group B had a mean age of 62.9 years and a BMI of 25.4. The mean follow-up duration was 18.6 months (range 12-50). At the 12-month follow-up, anatomic recurrence was higher in Group A (5/31, 16.1%) than in Group B (1/30, 3.3%) but without statistical significance ( p = 0.19). Improvements in symptoms and quality of life were not significantly different between the two groups. Mesh extrusion was detected in three of 61 patients (4.9%): two from group A (6.7%) and one from Group B (3.2%). TVM with concomitant midline fascia repair for anterior vaginal prolapse had a comparable anterior support and mesh exposure rate compared with TVM alone. Trial Registration: IRB-B09904021.