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Jen-Ting Huang,1 Han-Yu Chen,2 Chang-Zern Hong,2 Ming-Ta Lin,3 Li-Wei Chou,4,5 Hsin-Shui Chen,6,7 Chien-Tsung Tsai,8 Wen-Dien Chang9 1Department of Orthopedic Surgery, Taichung Veterans General Hospital, 2Department of Physical Therapy, Hung-Kuang University, Sha Lu, 3Kuan-Ta Rehabilitation and Pain Clinic, Taichung, Taiwan; 4Department of Physical Medicine and Rehabilitation, China Medical University Hospital, 5School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 6Department of Rehabilitation Medicine, Bei-Gang Hospital, School of Medicine, China Medical University, Yun-Lin, Taiwan; 7School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 8Department of Rehabilitation Medicine, Da-Chien Hospital, Miao-Li City, Taiwan; 9Department of Sports Medicine, China Medical University, Taichung, Taiwan Background and aims: The aim of this study was to demonstrate the effectiveness of lumbar facet joint injection for piriformis myofascial pain syndrome. Methods: Fifty-two patients with chronic myofascial pain in the piriformis muscle each received a lumbar facet injection into the ipsilateral L5–S1 facet joint region, using the multiple insertion technique. Subjective pain intensity, trunk extension range, and lumbar facet signs were measured before, immediately after, and 2 weeks after injection. Thirty-six patients received follow-up for 6 months. Results: Immediately after the injection, 27 patients (51.9%) had complete pain subsidence, 19 patients (36.5%) had pain reduction to a tolerable level, and only 6 patients (11.5%) had no pain relief to a tolerable level. Mean pain intensity was reduced from 7.4±0.9 to 1.6±2.1 after injection (P

The quantum anomalous Hall effect (QAHE) in a magnetic topological insulator system without the need of an external magnetic field becomes of great interest because of its dissipationless spin currents. The proximity effect via a magnetic adlayer is a promising strategy to bring magnetism into a topological insulator (TI) due to its boosted Curie temperature for a realistic application. In this work, a proximity-induced magnetism above 90 K in a TI, (Bi 0.25 Sb 0.75 ) 2 Te 3 , on a ferrimagnetic adlayer with perpendicular magnetic anisotropy, thulium-iron-garnet (TIG), was evidenced directly by using magnetic circular dichroism. A competition between exchange couplings with different sublattice-sites was further revealed element-specifically in a temperature-driven spin-reorientation of TI, bringing an issue on magnetic inhomogeneity at the interface, which might cause difficulties in obtaining QAHE in such a TI/TIG bilayer system. Our results prove directly the robust magnetism of TI above liquid nitrogen temperatures and also give a deep insight into the mechanism of interfacial coupling in the proximity effect for the bilayer of TI and magnetic oxide, which could be essential for the design of a system with QAHE.

Background: Preoperative tumor aggressiveness biomarkers may help surgeons decide the extent of an operation. However, whether serum angiogenetic factors can be used to predict the prognosis of patients with differentiated thyroid cancer is still unclear. Methods: Seventy-six DTC patients were prospectively recruited. Preoperative serum samples were collected and measured for Tie-2, Ang-1, Ang-2, VEGF-A, and VEGF-D levels. The potential correlations between their serum levels and clinicopathologic features as well as their prognoses were analyzed. Results: Older age (>45 years old) and higher VEGF-A serum levels were independent predictors of extrathyroidal extension. The VEGF-D serum level was an independent factor for lymph node metastases and VEGF-A was an independent factor for distant metastases. None of these serum angiogenetic factors were significantly different between patients who were disease free and those with recurrences. The presence of lymph node metastases was the only independent factor for recurrence over the 2-year follow-up. Conclusion: Preoperative serum VEGF-A and VEGF-D levels were significantly elevated in DTC patients with distant and lymph node metastases. These findings, when combined with other clinicopathological factors, may help in surgical decisions.

Increased oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington's disease and Parkinson's disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD. [ABSTRACT FROM AUTHOR]

Oxidative stress and mitochondrial dysfunction are important features present in Alzheimer's disease (AD). They appear early and contribute to disease progression, both in human postmortem AD brains as well as in transgenic AD mouse brains. For this reason, targeting oxidative stress and mitochondria in AD may lead to the development of promising therapeutic strategies. Several exogenous antioxidant compounds have been tested and found beneficial in transgenic AD mice, such as vitamins and spices. However, their efficacy was much more modest in human trials. More recently, new strategies have been elaborated to promote endogenous antioxidant systems. Different pathways involved in oxidative stress response have been identified. Compounds able to upregulate these pathways are being generated and tested in animal models of AD and in human patients. Upregulation of antioxidant gene expression was beneficial in mice, giving hope for future avenues in the treatment of AD and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

RATIONALE: Acute respiratory distress syndrome (ARDS), a serious inflammatory reaction to acute lung injury, is associated with high mortality rates. Decoy receptor (DcR) 3 is a soluble protein with immunomodulatory effects. Biomarkers that reliably predict outcomes in ARDS are not currently available. OBJECTIVES: Comparing DcR3 with the Acute Physiology and Chronic Health Evaluation (APACHE) II scores and three other plasma markers to explore the association of DcR3 and the clinical outcome in ARDS. METHODS: Eighty-eight patients with ARDS were studied. Baseline APACHE II scores and clinical data were recorded. Plasma levels of DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, tumor necrosis factor (TNF)-alpha, and IL-6 were measured on Day 1 and later time points, and correlated with the survival status on Day 28 after the onset of ARDS. For validation, 59 patients with ARDS from another medical center were studied. MEASUREMENTS AND MAIN RESULTS: Among the biomarkers evaluated, only DcR3 discriminated the survivors and nonsurvivors at all time points in the first week of ARDS. DcR3 independently associated with and best predicted the 28-day mortality of patients with ARDS. Plasma DcR3 levels most correlated to multiple-organ dysfunction and ventilator dependence. Compared with survivors, the nonsurvivors had higher DcR3 levels regardless of the APACHE II scores. Kaplan-Meier survival analysis showed higher mortality in patients with ARDS with higher DcR3 levels. The outcome prediction of patients with ARDS by plasma DcR3 levels was recapitulated by the validation cohort. CONCLUSIONS: High plasma DcR3 levels correlate with development of multiple-organ dysfunction and independently predict the 28-day mortality in patients with ARDS. [ABSTRACT FROM AUTHOR]

Objectives: To find a noninvasive method to detect coarctation of the aorta (CoA) in the presence of a patent ductus arteriosus (PDA) in neonates. Study Design: From 1994 to 1998, 36 neonates with CoA and PDA confirmed by surgery or cardiac catheterization were studied; another 19 neonates with isolated PDA served as control patients. The prospective study was conducted from 2001 to 2002 on 162 neonates. Results: Among the 36 neonates in the CoA group, 14 patients (39%) had blood pressure discrepancy, 26 patients (72%) had a visualized posterior shelf by echocardiogram, and the ratio of isthmus/descending aorta diameters (I/D ratio) was below 0.64 in 32 patients (89%). None of the control patients had these features. A diagnostic approach was subsequently proposed, according to which a neonate with PDA who fulfilled any of the above features was diagnosed as CoA plus PDA. In the prospective study, the sensitivity and positive predictive values of this method were both 91.7%, whereas the specificity and negative predictive values were both 99.3%. Conclusions: Echocardiographic measurements of I/D ratio along with the delineation of posterior shelf and a BP discrepancy can satisfactorily identify CoA in the presence of PDA in neonates. [ABSTRACT FROM AUTHOR]

The molecular mechanism for the regression of pregnancy pyogenic granuloma after parturition remains unclear. It has been proposed that, in the absence of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) causes blood vessels to regress. Therefore, we investigated the roles of Ang-2 and VEGF in the regression of pregnancy pyogenic granuloma. The effects of tumor necrosis factor- α (TNF- α) on the transcription of Ang-2 were tested in endothelial cells by reverse transcriptase-polymerase chain reaction. A total of 15 specimens, including granulomas taken from five gravidas during pregnancy, five after parturition, and five from normal gingiva were compared by immunoblot assays for their relative expressions of Ang-1, Ang-2, Tie-2, VEGF, and β-actin. Double staining, immunohistochemistry for Ang-2, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling for apoptotic cells, were used to evaluate their regression. Finally, a fibrin gel culture system was used to investigate whether the withdrawal of VEGF and addition of Ang-2 could cause newly grown microvessels to regress. TNF- α upregulated the expression of Ang-2 in all endothelial cell types tested. The protein levels of Ang-2 and Tie-2 were highest in the granulomas in pregnancy, followed by those after parturition and normal gingiva, while Ang-1 and β-actin exhibited no significant differences. The amount of VEGF was high in the granulomas in pregnancy and almost undetectable after parturition. Double staining on granulomas after parturition revealed more apoptotic cells and less Ang-2 than did those in pregnancy. In the fibrin gel assay, VEGF alone or in combination with Ang-2 could protect microvessels from apoptosis, while Ang-2 alone had no effect. Our findings suggest that a lack of VEGF is associated with apoptosis of endothelial cells and regression of granuloma. The roles of Ang-2 require additional study. [ABSTRACT FROM AUTHOR]

Grey mullet (Mugil cephalus) aquaculture is economically vital due to the high value of its roe. However, it faces significant risks from disease outbreaks, particularly from Nocardia seriolae. Current reliance on antibiotics has drawbacks, highlighting the potential of probiotics as a promising alternative. Despite this, no studies have focused on the effects and mechanisms of probiotics in disease prevention and treatment in grey mullet. This study, therefore, investigates the efficacy of probiotics in enhancing disease resistance and promoting growth in grey mullet. Three strains of probiotics, Lacticaseibacillus rhamnosus FS3051, Limosilactobacillus reuteri FS3052, and Bacillus subtilis natto NTU-18, were selected to evaluate their anti-N. seriolae activity and hydrolytic enzyme secretion in vitro. Then, 144 grey mullet were randomly divided into four groups: control, L. rhamnosus FS3051, L. reuteri FS3052, and B. subtilis natto NTU-18. After being fed the corresponding diet for 28 days, fish were measured for immune gene expression and short-term growth followed by challenge of N. seriolae. Survival rates were recorded for 35 days post challenge. Additionally, the gut microbiota of the control and probiotic groups with effects on both growth and protection against N. seriolae were analyzed to investigate the potential role of gut microbiota. Results demonstrated that L. rhamnosus FS3051 and L. reuteri FS3052 inhibited N. seriolae, while B. subtilis natto NTU-18 did not inhibited N. seriolae. Probiotics also had the ability to secrete hydrolytic enzymes. Probiotic-fed grey mullet showed significant improvements in weight gain ratio, feed efficiency, and specific growth rate, particularly in the B. subtilis natto NTU-18 group. Immune gene expression was enhanced by probiotics, especially L. rhamnosus, FS3051, which induced IL-8, IL-1β, TNF-α, IFN-γ, and MHCI. Survival rates post-N. seriolae challenge improved significantly for L. rhamnosus FS3051-fed fish. L. rhamnosus FS3051 also altered the gut microbiota, enriching beneficial genera like Lactobacillus, which correlated positively with immune responses and growth, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses. This study underscores the potential of probiotics in enhancing disease resistance and growth via regulating gut microbiota in grey mullet., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.

Background: Twin atrioventricular nodes (TWAVNs) are common in heterotaxy syndrome., Objective: To investigate the presence and implications of TWAVNs and accessory pathways in congenital heart diseases with abnormal AV connections., Methods: A retrospective study on a 1980-2022 cohort with sufficient ECG data for review., Results: We enrolled 136 patients with heterotaxy syndrome, 70 with congenitally corrected transposition of great arteries (ccTGA, 4 with Ebstein's anomaly), 47 with double inlet ventricle (DIV), and 63 with isolated AV canal defect. TWAVNs, detected in the same ECG (18%), in separate ECGs (70.8%), or after electrophysiological study (11.2%), were present in 43.4% of heterotaxy, 10.6% of DIV, 10% of ccTGA and 1.6% of AV canal defect cases. Accessory pathways were noted in 11.4% of ccTGA, and 4.4% of heterotaxy, but none of DIV and AV canal cases. Actuarial incidence of supraventricular tachycardia (SVT) by age 10 was 0.354, 0.121, 0.022, and 0 in heterotaxy, ccTGA, DIV, and AV canal, respectively. In patients with TWAVNs, the risk of SVT varies according to the rate of TWAVNs in each CHD type, with risks of 65.5%, 58.3%, and 0% for TWAVNs rates of >50%, 10-50%, and <10%, respectively. The onset age of tachycardia did not differ between those with TWAVNs and those with accessory pathways., Conclusions: In CHD with abnormal AV connections, evidence suggested a developmental hierarchy in the propensity to exhibit TWAVNs, but not for accessory pathways. The earlier cardiac developmental errors occur, the higher the likelihood of TWAVNs and the greater the chance of SVT., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This study aimed to assess the impact of pay-for-performance (P4P) programmes on healthcare in Taiwan., Study Design: This was a systematic review and meta-analysis., Methods: A systematic literature search was performed using the PubMed, Medline, Embase, Cochrane review, Scopus, Web of Science and PsycINFO databases up to July 2023. Meta-analysis of the available outcomes was conducted using a random-effects model., Results: The search yielded 85 studies, of which 58 investigated the programme for diabetes mellitus (DM), eight looked at the programme for chronic kidney disease (CKD), and the remaining studies examined programmes for breast cancer, tuberculosis, schizophrenia and chronic obstructive pulmonary disease. The DM P4P programme was a cost-effective strategy associated with reduced hospitalisation and subsequent complications. The CKD P4P was associated with a lower risk of dialysis initiation. The P4P programme also improved outcomes in breast cancer, cure rates in tuberculosis, reduced admissions for schizophrenia and reduced acute exacerbation in chronic obstructive pulmonary disease. The meta-analysis revealed that the P4P programme for DM (odds ratio [OR] = 0.59; 95% confidence interval [CI] = 0.48-0.73) and CKD (OR = 0.73; 95% CI = 0.67-0.81) significantly reduced mortality risk. However, participation rate in the DM P4P programme was only 19% in 2014., Conclusions: P4P programmes in Taiwan improve quality of care. However, participation was voluntary and the participation rate was very low, raising the concern of selective enrolment of participants (i.e. 'cherry-picking' behaviour) by physicians. Future programme reforms should focus on well-designed features with the aim of reducing healthcare disparities., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Preserving parathyroid function during thyroidectomy is crucial, but remains challenging. Real-time near-infrared autofluorescence (NIRAF) aids surgeons in intraoperative parathyroid gland (PTG) identification. However, its role in detecting PTGs unintentionally removed during surgery is unclear., Study Design: This prospective study included adult patients undergoing endoscopic thyroidectomy. Surgeons identified and documented PTGs visually. Excised specimens underwent visual inspection and NIRAF imaging (PDE-Neo II). All fluorescent tissues were dissected and pathologically evaluated (reference standard). One scanned image per lobe was chosen to quantify autofluorescence (AF) intensity., Results: Overall, 95 patients underwent endoscopic thyroidectomies, with NIRAF imaging applied to 152 excised lobes. Of these, 19 lobes displayed a total of 23 spots with increased intensity. 175 specimens were sent for pathological evaluation, and 7 were confirmed to be parathyroid tissue. NIRAF demonstrated 100.0 % sensitivity and 90.5 % specificity for predicting parathyroid tissue, with 30.4 % positive predictive value, 100.0 % negative predictive value of and 90.9 % accuracy. Quantitatively normalized, the AF signal intensity was significantly higher in NIRAF-positive tissues than negative (4.3 vs 1.2 times, p < 0.0001). Additionally, the AF signal intensity in regions pathologically confirmed of parathyroid tissue was higher than non-parathyroid tissue (9.1 vs 2.1 times, p < 0.0001)., Conclusion: This study suggests that NIRAF has high sensitivity and specificity for detecting inadvertently resected PTGs after endoscopic thyroidectomy, contributing to preservation efforts. However, NIRAF-positive tissues still require additional confirmation through multiple methods, emphasizing other examinations to verify that they are indeed parathyroid tissues. Further research is warranted to refine NIRAF imaging parameters., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Objectives: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C., Methods: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset., Results: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors., Conclusion: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency., Competing Interests: Declaration of interests W.-J.C., Z.-Q.X., X.C., M.Z., Y.-H.Z., and L.C. have filed patents (CN2023113708968) to protect the application of CRACE therapy for the treatment of brain calcification., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polyclonal convergent evolution to PARPi resistance in a patient with metastatic breast cancer with gPALB2.

Background: Extracorporeal shockwave therapy (ESWT) has been proven beneficial for post-stroke spasticity (PSS) of ankle plantar flexor muscles. This study aims to investigate the dose-response effectiveness of focused-ESWT and the duration of its effect on the treatment of ankle PSS in stroke patients., Methods: In this double-blinded randomized controlled trial, stroke patients diagnosed with PSS in the ankle plantar flexor muscles were randomly assigned to two groups. The experimental group received double-dose ESWT (4000 pulses per session) targeting spastic calf muscles, while the control group received half the dose (2000 pulses per session). Both groups underwent four sessions over two weeks. The outcomes, including modified Ashworth Scale (MAS), modified Tardieu Scale (MTS), passive range of motion (PROM) of the ankle, Timed Up and Go (TUG) Test, Barthel index and strain elastography were evaluated at baseline, 1st, 4th, 12th, and 24th week after ESWT., Results: Within-group analysis revealed significant improvements in MAS, PROM, TUG Test, and Barthel index for the double-dose ESWT group and improvements in Barthel index for the control group. Between-group analysis revealed greater improvements in TUG Test, Barthel Index and strain elastography for the double-dose ESWT group. Generalized estimating equations analysis indicated that the double-dose ESWT group achieved superior outcomes in the TUG Test, Barthel Index, and strain elastography across various time points and groups., Conclusions: Double-dose ESWT showed better functional improvement and elastography compared to the control group. ESWT demonstrated dose-response effectiveness for PSS of ankle-equinus., Trial Registration: NCT05878223., (© 2024. The Author(s).)

Aims: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies., Methods: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy., Results: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays., Conclusions: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Purpose: To identify the predictive variables for post-stroke dysphagia (PSD) among anterior circulation large vessel occlusion (LVO) stroke patients who underwent endovascular thrombectomy (EVT)., Methods: This retrospective cohort study enrolled hospitalized patients with anterior LVO stroke who underwent EVT between January 1, 2018 and October 31, 2022. PSD was defined as the unsuccessful removal of the nasogastric (NG) tube. Factors, such as premorbid characteristics, laboratory results, EVT, rehabilitation-related parameters, and neuro-imaging, were analyzed for correlations to PSD at 4 and 12 weeks., Results: The study enrolled 136 patients, with a mean age of 72.9 ± 13.0 years, and 59 patients (43.4%) were male. At 4 weeks, 47.1% of the patients needed an NG tube, and at 12 weeks, 16.2% still required an NG tube. We found that lower albumin, lower body mass index (BMI), higher initial and 24-h post-EVT National Institute of Health Stroke Scale (NIHSS) scores, stroke-associated pneumonia, poor initial sitting balance and ability to sit up, insula or frontal operculum lesions, and bilateral hemisphere involvement were all associated with PSD at both 4 and 12 weeks in the univariate logistic regression. Multivariate analysis revealed that significant predictors of unsuccessful NG tube removal at 4 weeks included lower BMI (adjusted OR [aOR] 0.73, p = 0.005), hemorrhagic transformation (aOR 4.01, p = 0.0335), higher NIHSS scores at 24 h post-EVT (aOR 1.13, p = 0.0288), poor initial sitting ability (aOR 0.52, p = 0.0231), insular cortex ischemia (aOR 7.26, p = 0.0056), and bilateral hemisphere involvement (aOR 41.19, p < 0.0001). At 12 weeks, lower BMI (aOR 0.78, p = 0.0098), poor initial sitting balance (aOR 0.57, p = 0.0287), insular cortex lesions (aOR 4.83, p = 0.0092), and bilateral hemisphere involvement (aOR 4.07, p = 0.0139) remained significant predictors., Conclusions: In patients with anterior LVO following EVT, PSD was associated with lower BMI, higher NIHSS scores, poor initial sitting balance and sitting ability, insular lesions, and bilateral hemisphere involvement., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Left ventricular outflow tract obstruction (LVOTO) re-intervention is a significant cause of morbidity and mortality in patients with coarctation of the aorta (CoA) or interrupted aortic arch (IAA) after aortoplasty., Methods: This retrospective study analyzed data from neonates with IAA/CoA who underwent biventricular repair between 2012 and 2022. LVOTO events were defined by the detection of color Doppler flow acceleration ≥3.0 m/s at the valvular, subvalvular, or supravalvular regions via transthoracic echocardiography, and the necessity for surgical or catheter intervention to relieve the obstruction., Results: Among 121 neonates with CoA/IAA, 16 (13.7%) primary aortoplasty patients developed LVOTO. Additionally, one patient (25%) who underwent a staged Yasui operation developed LVOTO due to a narrowed ventricular septal defect-pulmonary atresia tunnel. During follow-up, 58% of patients with a bicuspid valve and 25% of patients with a subaortic ridge developed LVOTO. The combination of either a bicuspid valve, subaortic ridge, or an aortic valve annulus Z-score < -3.0 predicted a high re-intervention rate (7/8 [87.5%])., Conclusions: In patients with IAA/CoA, the presence of multiple risk factors, including a bicuspid valve, subaortic ridge, and an aortic valve annulus Z-score < -3.0, is associated with a significantly increased rate of re-intervention for LVOTO., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)