Timing Of Intervention Research Articles

Atherectomy Followed by Drug-Coated Balloon Angioplasty Versus Surgery for Symptomatic Deep Femoral Artery Arteriosclerotic Disease.

Limited data are available regarding endovascular therapy of arteriosclerotic lesions of the deep femoral artery (DFA). In this study, we compare the outcomes of atherectomy combined with drug-coated balloon (DCB) angioplasty and open repair of DFA lesions. This is a multicenter retrospective registry of patients with peripheral artery occlusive disease Rutherford categories 2 to 5 treated by surgical profundaplasty (SP) or atherectomy followed by DCB for DFA lesions (symptomatic DFA). The primary endpoint was clinically driven target lesion revascularization (CD-TLR). Overall mortality, target limb reinterventions, major amputation, and major adverse limb events (MALEs) were additionally analyzed. A total of 373 patients treated for an arteriosclerotic lesion of the DFA between February 2015 and August 2021 were included, 301 treated by SP and 72 with atherectomy and DCB. The rates of chronic limb threatening ischemia (CLTI) were 42.2% and 22.2% (p<0.002) for the surgical and endovascular groups, respectively. A previous DFA intervention was more frequent in the endovascular group (30.6% vs 15.3%; p<0.003). Patients who had an open repair were more likely to have an occlusion of the profunda (34.9% vs 19.7%, p=0.014), severe calcified lesions (26.5% vs 5.6%, p=0.001), and lesions longer than 20 mm (95.7% vs 88.7%, p=0.024). After propensity score matching, no significant differences were found with regard to technical and hemodynamic success. At 24 months, no difference was found in terms of freedom from CD-TLR (95.7% vs 96.8%), freedom from all-cause mortality (94.2% vs 98.5%), freedom from MALE (90.4% vs 93.9%), and amputation-free survival (93.8% vs 97%). Following endovascular therapy, length of stay was significantly lower (p<0.001) and any reintervention on the index limb was more frequent (p=0.039). Patients with CLTI, occlusion of profunda, severe calcified lesions, and longer lesions are more frequently treated by open surgery, while reinterventions are more commonly treated by atherectomy and DCB. In patients with comparable clinical and lesion characteristics after matching, endovascular and surgical reconstruction of DFA lesions showed similar mid-term clinical outcomes. However, the risk of reintervention at the index limb is higher after endovascular treatment. Randomized studies are now warranted to compare both techniques in terms of medical and financial aspects. Atherectomy followed by DCB of symptomatic DFA is safe and effective. In patients with comparable clinical and lesion characteristics, outcomes are comparable with surgery. However, the risk of reintervention at the index limb is higher after endovascular treatment. Therefore, whenever possible an additional outflow vessel revascularization should be performed by the time of the primary intervention. Randomized studies are warranted to compare endovascular techniques and open surgery also under economic aspects.

Effect of low-frequency alternating magnetic field on exopolysaccharide production and antioxidant capacity of Pleurotus citrinopileatus by submerged fermentation.

The objective of this study was to investigate the effect of low-frequency alternating magnetic field (LF-AMF) on the production of extracellular polysaccharide (EPS) by submerged fermentation of Pleurotus citrinopileatus. The fermentation conditions optimized by the central composite design method were as follows: fermentation time of 6.18days, temperature of 28.28°C, shaking speed of 149.04 r/min, and inoculum amount of 8.43%. Under these conditions, a LF-AMF was applied to the submerged fermentation of P. citrinopileatus. When the intensity of LF-AMF was 40 Gs, the initial intervention time was 24h after inoculation, and the treatment time was 6h at one time, the mycelial biomass of P. citrinopileatus increased by 11.30%, and the EPS yield increased by 23.09% compared with the fermentation without LF-AMF treatment. The morphology of mycelium after LF-AMF treatment was observed by scanning electron microscopy. It was found that the surface of mycelium was wrinkled, and the structure of mycelium was loose, which might be more conducive to the production of EPS. Mycelium diameter decreased, and ATPase activity increased, indicating that LF-AMF had a positive effect on the production of EPS by P. citrinopileatus fermentation. Moreover, LF-AMF could improve the permeability of the mycelial cell membrane, facilitate the exchange of intracellular and extracellular substances, and increase the metabolic capacity of P. citrinopileatus. In vitro antioxidant test of EPS showed that LF-AMF treatment also improved its antioxidant capacity.

Alteration of treatment choices and the visual prognosis for diabetic macular edema in the era of anti-VEGF drugs: Analysis of the STREAT-DME 2 study.

To assess the real-world outcome of best-corrected visual acuity (BCVA) following 2-year intervention for treatment-naïve diabetic macular edema (DME) since the approval of anti-vascular endothelial growth factor (VEGF) therapy. A total of 1,780 treatment-naïve eyes with DME for which intervention was initiated between 2015 and 2019, and which were followed for 2 years, were extracted from the longitudinal medical records of 37 retinal disease institutions in Japan. Interventions included anti-VEGF therapy, topical corticosteroid therapy, macular photocoagulation, and vitrectomy. The baseline and final BCVA, and the number and timing of interventions were recorded. Eyes were classified according to the year in which intervention was initiated. Over a 2-year period, BCVA improved annually, finally reaching 7 letters. The proportion of eyes in which good vision was maintained (BCVA >20/40) increased to 73.3% in the latest period. The administration of anti-VEGF therapy remained stable, accounting for approximately 90% of eyes. Notably, the proportion of eyes receiving anti-VEGF drugs as first-line treatment increased dramatically to approximately 80%. Anti-VEGF therapy has become the first-line treatment since the approval of anti-VEGF drugs for DME. These findings reflect the evolution of DME treatment and highlight the superiority of anti-VEGF therapy and its increased uptake over time.

Kinematic Changes throughout Childhood in Youth with Cerebral Palsy: Influence of Age and Orthopaedic Surgery.

Abnormal gait kinematics are common in youth with cerebral palsy (CP), but prior studies have not analyzed their longitudinal change throughout childhood. This study examines how age and orthopaedic surgery influence gait kinematics throughout childhood in those with ambulatory CP. In this institutional review board-approved prospective cohort study, children with spastic CP (GMFCS I-III) were recruited at age 17-40 months. Instrumented gait analysis was performed at 3-year intervals from age 4 to 21 years, collecting longitudinal kinematic data in bare feet at a self-selected speed. The change in Gait Profile Score (ΔGPS) between each pair of gait analyses (intervals) was analyzed by age distribution (<10, 10-15, ≥15 years) and by presence/absence of orthopaedic surgery. The study included 31 children (GMFCS: I [13], II [14], III [4]). A baseline instrumented gait analysis was performed at age 5.8 ± 1.6 years with subsequent analysis at 2.5 ± 1.3-year intervals. Examining ΔGPS from baseline to final outcome, 87% of limbs were improved/unchanged; 298 intervals of ΔGPS were analyzed and classified as nonsurgical or surgical. Analysis revealed greater GPS improvement in intervals with surgery versus intervals without (p = 0.0004). Surgical intervals had significantly greater GPS improvement in the <10- vs. >15-year-old groups, p = 0.0063. Improvement in gait kinematics in children with CP is significantly influenced by age and timing of orthopaedic surgical intervention for gait correction, and was most pronounced for children <10 years old. Although surgery was associated with improved outcomes in all age groups, these improvements were significantly less for children >10 years old. These results reinforce the importance of considering the timing of orthopaedic surgery.

Characterization of six clinical drugs and dietary intervention in the non-obese CDAA-HFD mouse model of MASH and progressive fibrosis.

The choline-deficient L-amino acid defined-high fat diet (CDAA-HFD) mouse model is widely used in preclinical metabolic dysfunction-associated steatohepatitis (MASH) research. To validate the CDAA-HFD mouse, we evaluated disease progression and responsiveness to dietary and pharmacological interventions with semaglutide, lanifibranor, elafibranor, obeticholic acid (OCA), firsocostat and resmetirom.Disease phenotyping was performed in C57BL/6J mice fed CDAA-HFD for 3-20 weeks and ranked using the MASLD Human Proximity Score (MHPS). Semaglutide, lanifibranor, elafibranor, OCA, firsocostat or resmetirom were profiled as treatment intervention for 8 weeks, starting after 6 weeks of CDAA-HFD feeding. Semaglutide and lanifibranor were further evaluated as early (preventive) therapy for 9 weeks, starting 3 weeks after CDAA-HFD diet feeding. Additionally, benefits of dietary intervention (chow reversal) for 8 weeks were characterized following 6 weeks of CDAA-HFD feeding. CDAA-HFD mice demonstrated a non-obese phenotype with fast onset and progression of MASH and fibrosis, high similarity to human MASH-fibrosis, and tumor development after 20 weeks of diet-induction. Semaglutide and lanifibranor partially reversed fibrosis when administered as prevention, but not as treatment intervention. Elafibranor was the only interventional drug to improve fibrosis. In comparison, chow-reversal resulted in complete steatosis regression with improved liver inflammation and fibrosis in CDAA-HFD mice. CDAA-HFD mice recapitulate histological hallmarks of advanced MASH with progressive severe fibrosis, however, in the absence of a clinical translational obese dysmetabolic phenotype. CDAA-HFD mice are suitable for profiling drug candidates directly targeting hepatic lipid metabolism, inflammation, and fibrosis. The timing of pharmacological intervention is critical for determining antifibrotic drug efficacy in the model.

Elevated Trans-mitral Pressure Gradient Predicts Surgery in Young People with Moderate-Severe Rheumatic Mitral Regurgitation.

Mitral regurgitation (MR) is the most common lesion in children with rheumatic heart disease (RHD). Progression of RHD results in the need for surgical intervention, the timing of which is dictated by left ventricular dilatation and the onset of heart failure symptoms. We sought to determine whether elevation in trans-mitral pressure gradient (TMPG) in those with moderate or severe rheumatic MR without significant mitral stenosis (MS) could predict the need for future surgical intervention. Echocardiographic studies were reviewed for 116 children and young people with moderate or severe rheumatic MR. Those with significant mitral stenosis or concurrent aortic valve disease were excluded. Trans-mitral pressure gradient was measured at baseline and details of mitral valve surgical intervention were retrieved from a registry database. Time to future surgery (up to six years) was compared between those with TMPG < 5mmHg and TMPG ≥ 5mmHg. Survival curves demonstrated an increased risk of surgery for those with TMPG ≥ 5mmHg with Cox proportional regression analysis providing a hazard ratio of 5.8. The proportion free from mitral valve surgery at one year for the TMPG < 5mmHg group was 0.94 (95% CI 0.86-0.97), compared to 0.62 (95% CI 0.42-0.77) in the ≥ 5mmHg group. Trans-mitral pressure gradient is a strong predictor of future mitral valve surgery in children and young people with significant rheumatic MR without MS. This non-invasive measure could be used to signal the need for more aggressive monitoring in order to optimize the timing of intervention.

EARLY SUCCESSFUL PRIMARY PERCUTANEOUS CORONARY INTERVENTION ON LEFT VENTRICULAR EJECTION FRACTION IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION

Early intervention in patients with ST-elevation myocardial infarction (STEMI) is crucial for preserving left ventricular function and improving patient outcomes. Primary percutaneous coronary intervention (PPCI) has become the standard of care, and the timing of intervention significantly influences recovery and long-term prognosis. Objective: This study aimed to evaluate the impact of early successful primary percutaneous coronary intervention (PPCI) on left ventricular ejection fraction (LVEF) in patients presenting with STEMI. Methods: A prospective cohort study was conducted on 116 STEMI patients undergoing PPCI at a tertiary care hospital. The patients were categorized into two cohorts: early presenters (n=67) who received PPCI within 6 hours of symptom onset and late presenters (n=49) who received PPCI after 6 hours. Baseline characteristics, procedural outcomes, Thrombolysis in Myocardial Infarction (TIMI) flow grades, and LVEF measurements were assessed at presentation and two months post-PPCI using transthoracic echocardiography. The primary outcome was the change in LVEF from baseline to follow-up, and the secondary outcome was the distribution of TIMI flow grades achieved during PPCI. Statistical analysis was performed using appropriate tests to compare outcomes between the two groups. Results: Early presenters demonstrated significantly better outcomes compared to late presenters. At presentation, the mean LVEF in the early group was higher (45.67 ± 1.73%) compared to the late group (36.94 ± 1.25%) (p = 0.0001). At the two-month follow-up, the LVEF improved significantly in both groups, with early presenters achieving an LVEF of 56.24 ± 1.73%, which was notably higher than the LVEF of late presenters (45.12 ± 1.42%) (p = 0.0001). In terms of coronary reperfusion, 62.7% of early presenters achieved TIMI grade 3 flow compared to 26.5% of late presenters (p = 0.0001), indicating better coronary artery perfusion in the early intervention group. Conclusion: Early successful PPCI in STEMI patients is associated with superior recovery of left ventricular function and improved coronary reperfusion compared to delayed intervention. Patients who received PPCI within 6 hours of symptom onset demonstrated significantly higher LVEF at follow-up and achieved better TIMI flow grades, highlighting the critical importance of minimizing treatment delays in STEMI management.

Low-intensity pulsed ultrasound regulates bone marrow mesenchymal stromal cells differentiation and inhibits bone loss by activating the IL-11-Wnt/β-catenin signaling pathway

BackgroundOsteoporosis (OP) is a common metabolic bone disease. Low-intensity pulsed ultrasound (LIPUS) can effectively promote bone formation and fracture healing. The Wnt/β-catenin signaling pathway is crucial for regulating bone homeostasis and bone diseases, and its downregulation is one of the main mechanisms of osteoporosis pathogenesis. Interleukin-11 (IL-11), which is regulated by mechanical stress, is a key factor in bone remodeling. Here, we investigated the optimal intervention parameters for LIPUS, the relationships among LIPUS, IL-11, and the Wnt/β-catenin signaling pathway, and the effects of LIPUS on bone loss and potential molecular mechanisms in ovariectomized (OVX) mice. MethodsBone marrow mesenchymal stromal cells (BMSCs) were subjected to LIPUS intervention for 0, 10, or 20 min to determine the optimal intervention time. The mediating role of IL-11 in LIPUS intervention was explored through IL-11 knockdown and overexpression. Finally, animal experiments were conducted to investigate the in vivo therapeutic effects of LIPUS. ResultsThe optimal intervention time for LIPUS was 20 min. LIPUS promoted IL-11 expression and upregulated the Wnt/β-catenin signaling pathway, thereby promoting osteogenic differentiation and inhibiting adipogenic differentiation of BMSCs. IL-11 mediates the regulation of the Wnt/β-catenin signaling pathway by LIPUS. Additionally, LIPUS effectively improved the bone microstructure in ovariectomized mice, inhibited bone loss, promoted IL-11 expression in bone tissue, and activated the Wnt/β-catenin signaling pathway in the femur. ConclusionLow-intensity pulsed ultrasound can regulate BMSCs differentiation and inhibit bone loss by promoting IL-11 expression and activating the Wnt/β-catenin signaling pathway.

Surgical Treatment of Primary Spinal Tumors

Primary spinal tumors appear to be much less common than metastatic lesions, but their surgical treatment comprises a complex and multifaceted task. Numerous factors influence indications and timing of surgical intervention, including neurological status of the patient, histological characteristics of the tumor, its localization, stability of the spinal column, and comorbidities. Significant spinal cord compression, rapid progression of neurologic deficits, or pronounced instability of the spinal column may require urgent surgical intervention. When the spinal canal is not affected, treatment should start with a biopsy to accurately determine the histology of the tumor. Some tumor types, such as giant cell tumors, osteoblastomas, chordomas, and chondrosarcomas, require complete removal of the tumor. However, performing a wide resection in a single block is often found difficult due to compression of vascular and nerve structures. Current approaches to surgical management of primary spinal tumors involve minimally invasive techniques that significantly improve postoperative recovery and reduce the risk of complications. These techniques were originally used to treat degenerative spinal diseases and trauma; however, they have also demonstrated their effectiveness in tumor surgery. Adapting surgical strategy based on histology and tumor location, as well as integrating minimally invasive techniques, can improve patient survival and quality of life. The present paper describes the latest advances in the surgical treatment of primary spinal tumors, discusses current techniques and strategies, and prospects for further research in this area.

The Impact of Anterior Pelvic Tilt on Return to Duty/Return to Run in Active Duty Personnel After Hip Arthroscopy for Femoroacetabular Impingement.

Annually, 300,000 soldiers are rendered medically nondeployable because of musculoskeletal injuries (MSKIs). Of this population, nearly 10,000 (3.3%) involve injuries to the hip. Factors related to these injuries impose significant healthcare, financial, and readiness burdens on the Army system, degrading overall mission readiness. The purpose of this retrospective study was to assess for correlation between increased anterior pelvic tilt and a lower likelihood for return to duty/return to run (RTD/RTR) in active duty personnel who underwent hip arthroscopy for femoroacetabular impingement (FAI), thus identifying increased anterior pelvic tilt as a potential prognostic indicator for RTD/RTR. Ninety-two active duty U.S. Army service members aged 18 years or older who underwent hip arthroscopy for FAI at the William Beaumont Army Medical Center from September 1, 2014, to September 1, 2019, were included. Utilizing a retrospective review of existing data, the amount of anterior pelvic tilt, as estimated on a presurgical weight-bearing anterior-posterior pelvis radiograph using the distance from the pubic symphysis to the transischial line, was measured and compared to postoperative RTD/RTR statuses, assessing for correlation. The overall RTD rate was 39.1% with a 22.8% RTR rate. Only 6.5% (6/92) of subjects returned to full, unrestricted duty and running. Logistic regression analyses showed that individuals with increased anterior pelvic tilt (≥7°) were 2.6 times less likely to RTD and 2.9 times less likely to RTR compared to those with minimal or no anterior pelvic tilt (<7°) (respectively, odds ratio (OR) 2.619; 95% CI, 1.107-6.195; P = .029 and OR 2.897; 95% CI, 1.041-8.059; P = .042). Results support the study teams' hypothesis that increased anterior pelvic tilt is associated with a lower odds of RTD/RTR. Statistical analysis confirmed the correlation between an increased amount of anterior pelvic tilt and a lower odds of RTD and RTR after hip arthroscopy for FAI in active duty U.S. Army personnel. This information can be used in patient counseling to better inform shared decision-making, provide more thorough informed consent, and help determine the optimal timing for surgical intervention, thus contributing to better stewardship of medical resources and decreasing the ever-growing financial healthcare burden. These findings will spur future research to consider the causes and optimal treatment of anterior pelvic tilt, positively impacting the culture of Army medicine by focusing on preventive and targeted treatments in order to preserve and grow the force.

Childbirth self-efficacy and birth related PTSD symptoms: an online childbirth education randomised controlled trial for mothers

BackgroundThis study evaluated an online childbirth education course on childbirth self-efficacy and, subsequent birth related posttraumatic stress disorder (PTSD) symptoms and mother-infant relationship quality.MethodThree group (intervention, passive control, active control) parallel randomised controlled trial. Groups were assigned using computer generated random allocation. For the passive control group participants were instructed to carry on with whatever they were currently undertaking with their pregnancy, while the active control group were asked to read a booklet comprised of twelve birth stories. The purpose of the active control was to check if the act of having an activity to complete would influence outcomes. For the online course group (intervention) participants were asked to complete the online version of a birthing course designed by She Births®. One hundred and twenty-five women residing in Australia between 12 and 24 weeks pregnant were recruited online. Participants were asked to complete their required activity between 24 and 36 weeks pregnant. Childbirth self-efficacy scores were tested pre and post intervention (time one and time 2), PTSD symptoms and mother-infant relationship quality were tested at six weeks and six months postnatal.ResultsThere was no significant interaction by group for childbirth self-efficacy scores. Mean difference scores at time one (pre-intervention) and time two (post-intervention) for each group indicated a trend in the online group towards higher childbirth self-efficacy compared with the two control groups. The main effect of group on birth related PTSD scores was not statically significant at six weeks postnatal or at six months postnatal. The main effect of group on mother-infant relationship scores was not statically significant at six weeks postnatal or six months postnatal.ConclusionsTrends showed childbirth self-efficacy scores to be higher in the intervention group compared with the two control groups, demonstrating effectiveness for the intervention. Paradoxically, PTSD scores were higher in the intervention group compared with the two control groups and therefore also reported poorer mother-infant relationship quality. External factors may be more important than childbirth self-efficacy highlighting the need for a holistic approach that addresses systemic and socio-political influences to improve communication, autonomy, and respectful maternity care.Trial RegistrationThis trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry number: ACTRN12624000241538 on March 11, 2024.

Endoscopic and microsurgical decompression for central lumbar spinal stenosis

Objective. To perform comparative analysis of the results of endoscopic and microsurgical decompression for lumbar spinal stenosis.Material and Methods. Design: Retrospective monocentric intra-cohort comparison of two groups of patients. The study included 99 patients aged 51–88 years with clinically significant lumbar spinal stenosis manifested by neurogenic intermittent claudication syndrome. Endoscopic decompression was performed in 51 patients, and microsurgical decompression – in 48 patients. To objectify and standardize clinical symptoms, walking distance in meters, pain syndrome and quality of life were assessed before and after surgery using standard scales and questionnaires (VAS, ODI). On the first day after surgery, back and lower limb pain were assessed, and during the observation period back and lower limb pain, quality of life and walking distance were assessed. Functional lumbar radiography was performed to exclude instability of the spinal motion segment. Using MRI, the cross-sectional area of the dural sac at the level of stenosis was measured before and after surgery. Clinical efficacy was assessed using the MCID (Minimal Clinical Important Difference) criterion. The results of the operation were followed-up for 12 months after the operation.Results. Blood loss in the endoscopic intervention group was less than in the microsurgical group. Pain in the lumbar spine and in the lower extremities decreased, and the cross-sectional area of the dural sac increased. In the first days after surgery, patients after endoscopic decompression had less severe back and lower extremity pain than patients after microsurgical decompression due to less soft tissue trauma. Pain syndrome in back 10–12 months after surgery was without statistically significant difference between the groups. Patients after endoscopic decompression had statistically significantly better quality of life according to ODI, lesser pain in the lower extremities according to VAS and longer walking distance than those in the microsurgical decompression group. Surgical treatment in both groups turned out to be effective, which is confirmed by MCID. The time of endoscopic intervention is significantly longer than that of microsurgical intervention. The length of the incision during endoscopic decompression is shorter than that of microsurgical decompression.Conclusion. A comparative analysis of the results of endoscopic and microsurgical decompression for degenerative central lumbar stenosis showed comparable effectiveness of both methods, including an increase in the spinal canal dimension and ensuring regression of clinical symptoms. The results of the comparison do not allow making a sufficiently substantiated judgment on the advantages of one of the methods, which dictates the need for further research.

Early prediction of sudden cardiac death using multimodal fusion of ECG Features extracted from Hilbert–Huang and wavelet transforms with explainable vision transformer and CNN models

Background and Objective:Sudden cardiac death (SCD) is a critical health issue characterized by the sudden failure of heart function, often caused by ventricular fibrillation (VF). Early prediction of SCD is crucial to enable timely interventions. However, current methods predict SCD only a few minutes before its onset, limiting intervention time. This study aims to develop a deep learning-based model for the early prediction of SCD using electrocardiography (ECG) signals. Methods:A multimodal explainable deep learning-based model is developed to analyze ECG signals at discrete intervals ranging from 5 to 30 min before SCD onset. The raw ECG signals, 2D scalograms generated through wavelet transform and 2D Hilbert spectrum generated through Hilbert–Huang transform (HHT) of ECG signals were applied to multiple deep learning algorithms. For raw ECG, a combination of 1D-convolutional neural networks (1D-CNN) and long short-term memory networks were employed for feature extraction and temporal pattern recognition. Besides, to extract and analyze features from scalograms and Hilbert spectra, Vision Transformer (ViT) and 2D-CNN have been used. Results:The developed model achieved high performance, with accuracy, precision, recall and F1-score of 98.81%, 98.83%, 98.81%, and 98.81% respectively to predict SCD onset 30 min in advance. Further, the proposed model can accurately classify SCD patients and normal controls with 100% accuracy. Thus, the proposed method outperforms the existing state-of-the-art methods. Conclusions:The developed model is capable of capturing diverse patterns on ECG signals recorded at multiple discrete time intervals (at 5-minute increments from 5 min to 30 min) prior to SCD onset that could discriminate for SCD. The proposed model significantly improves early SCD prediction, providing a valuable tool for continuous ECG monitoring in high-risk patients.

Incorporating online writing resources into self‐regulated learning strategy‐based instruction: An intervention study

AbstractBackgroundWhile self‐regulated learning (SRL) strategy‐based writing instruction has been proposed in English as a foreign language (EFL) classrooms, there is insufficient evidence with Japanese EFL learners and little discussion on incorporating online resources into SRL strategy‐based writing instruction, despite the availability of various online platforms.ObjectivesThis study proposed an SRL strategy‐based instruction for technology‐assisted writing and explored its immediate and sustained impacts on Japanese tertiary EFL learners' writing performance, reported use of SRL strategies, self‐efficacy beliefs and perceived acceptance of technology.MethodsThe research design used was a pre‐experimental pre‐test, post‐test and delayed post‐test design with a quantitative approach using convenience sampling. Participants were 44 students enrolled in an academic writing course at a Japanese university. Over an 8‐week period, these students received SRL strategy‐based writing instruction supported by online writing resources. The research instruments included writing tests and questionnaires assessing SRL strategies, self‐efficacy and technology acceptance at the beginning of the intervention (Time 1), immediately after the intervention (Time 2) and 1 month after the intervention (Time 3). The data analysis techniques involved ANOVA, post‐hoc tests, and examination of the effect sizes.Results and ConclusionThe results showed statistically significant improvements in students' writing performance, SRL strategy use, self‐efficacy and technology acceptance from Time 1 to Time 2 and persistent impacts at Time 3, suggesting the intervention's potential to improve EFL writing. This study contributes to EFL writing pedagogy by exploring the immediate and sustained impacts of teaching SRL strategies in a technology‐enhanced writing environment.

In Supracondylar Humerus Fractures With Nerve Injury, Does Time to Surgery Impact Recovery?

Background: Supracondylar humerus (SCH) fractures are common and present with associated nerve injuries in 11% to 42% of cases. Historically, SCH fractures with neurological compromise warranted urgent surgical intervention. A recent study showed that treatment delay is acceptable in patients with isolated anterior interosseous nerve (AIN) injury. Though indications for urgent treatment are relaxing, no studies have evaluated the need for urgent surgical treatment for other nerve injuries associated with SCH fractures. The aim of this study was to determine if the timing of surgical intervention is related to the timing of neurological recovery in SCH fractures associated with any nerve injury. Methods: A retrospective review of 64 patients with surgically managed SCH fractures and concomitant neurological deficit on presentation was conducted at a single level 1 pediatric trauma hospital from 1997 to 2022. The relationship between the time to surgical intervention and the time to partial and complete nerve recovery was analyzed using linear regression. Results: Sixty-four patients with an average age of 6.9±2.0 years and an average time to surgery of 9.8±5.6 hours were analyzed. Sixty-two patients (97%) were followed to partial neurological recovery and 36 (56%) were followed to full neurological recovery. Neurological deficit included median [n=41 (64%)], radial [n=22 (34%)], and ulnar [n=15 (23%)]. Ten patients (16%) had isolated AIN injury. The average time to partial neurological recovery was 20±23 days and the time to full recovery was 93±83 days. There was a statistically significant relationship between time to partial neurological recovery and time to surgical intervention (P=0.02). There was no relationship between time to full neurological recovery and time to surgery (P=0.8). Conclusion: Earlier time to surgical intervention in pediatric SCH fractures with isolated nerve injury was associated with earlier partial recovery but not full neurological recovery. Prioritizing urgent surgery in these patients did not improve their ultimate neurological recovery. Level of Evidence: Therapeutic level III.

A Complex Meta-Regression Model to Identify Effective Features of Interventions From Multi-Arm, Multi-Follow-Up Trials.

Network meta-analysis (NMA) combines evidence from multiple trials to compare the effectiveness of a set of interventions. In many areas of research, interventions are often complex, made up of multiple components or features. This makes it difficult to define a common set of interventions on which to perform the analysis. One approach to this problem is component network meta-analysis (CNMA) which uses a meta-regression framework to define each intervention as a subset of components whose individual effects combine additively. In this article, we are motivated by a systematic review of complex interventions to prevent obesity in children. Due to considerable heterogeneity across the trials, these interventions cannot be expressed as a subset of components but instead are coded against a framework of characteristic features. To analyse these data, we develop a bespoke CNMA-inspired model that allows us to identify the most important features of interventions. We define a meta-regression model with covariates on three levels: intervention, study, and follow-up time, as well as flexible interaction terms. By specifying different regression structures for trials with and without a control arm, we relax the assumption from previous CNMA models that a control arm is the absence of intervention components. Furthermore, we derive a correlation structure that accounts for trials with multiple intervention arms and multiple follow-up times. Although, our model was developed for the specifics of the obesity data set, it has wider applicability to any set of complex interventions that can be coded according to a set of shared features.

Photobiomodulation using red and infrared spectrum light emitting-diode (LED) for the healing of diabetic foot ulcers: a controlled randomized clinical trial.

Assessing the responses to the application of photobiomodulation using red and infrared spectrum light-emitting diodes (LED) on diabetic foot ulcers. Diabetic volunteers, of both genders, aged between 30 and 65 years, with grade I or II ulcers, were randomized into the groups: red LED, infrared LED, LED associated, and control. Home-based interventions took place on a daily basis for 12 weeks. Assessments of sample characterization were performed on day 1 and 90, and the variables wound healing index, mean skin temperature, sensitivity and pain in the wound area were measured at the pre-intervention time on days 1, 30, 60 and 90, with subsequent follow-up 30 days after the end of treatment. For statistical analysis, the software SPSS, version 17.0, intention-to-treat analysis, data normality was tested, and the linear mixed effects model, with a significance level of 5%. Magnitudes of clinical effect by Cohen's d. At the pre vs post intervention time of 90 days, we found a large clinical effect of G-LED V (d=1.7) and G -LED IV (d=1.6) in relation to G-C, where these intervention groups showed a tendency for faster wound healing compared to G-C. We also observed small clinical effect of G-LED IV, which showed greater reduction in the area in relation to G-LED V (d=0.4) and G-LED A (d=0.3). Conclusion: The use of individually applied red and infrared LED phototherapy clinically tended to be more effective for the reduction of diabetic foot ulcer areas, and infrared LED was the most effective. Trial registration: NCT03250533 (clinicaltrials.gov).

Dietary modulation of human milk bioactives is associated with maternal FUT2 secretor phenotype: an exploratory analysis of carotenoids and polyphenol metabolites.

Maternal diet modifies profiles of human milk oligosaccharides (HMOs), carotenoids, and polyphenols in human milk (HM). However, substantial variability in profiles exists between women, highlighting the complexity of non-dietary factors modulating these profiles. The objective of this study was to carry out a secondary analysis exploring the effect of maternal diet on HM carotenoids and polyphenols and relationships between dietary modulation of HM bioactives (carotenoids, polyphenols, and oligosaccharides) and maternal α1,2-fucosyltransferase 2 (FUT2) secretor phenotype. In this pilot study, 16 exclusively breastfeeding women with obesity were enrolled between 4 and 5 months postpartum. The women were provided a 4-week meal plan consistent with the 2020 Dietary Guidelines for Americans (DGA). HM was collected for 24 h at baseline and post-intervention. Maternal FUT2 secretor phenotype was determined by 2'-fucosyllactose concentration in HM (non-secretor: < 100 nmol/ml; secretor: ≥100 nmol/ml). Concentrations of carotenoids and HMOs were determined by LC and polyphenol metabolites by UPLC-MS/MS. Thirteen women completed the study (6 secretors, 7 non-secretors). The change in HM concentrations of the HMOs lacto-N-tetraose (LNT, p = 0.007), lacto-N-fucopentaose II (LNFP II, p = 0.02), difucosyllacto-N-tetraose (DFLNT, p = 0.003), and disialyllacto-N-tetraose (DSLNT, p = 0.003) and polyphenol metabolites 4-hydroxybenzoic acid (4-HBA, p = 0.08) and ferulic acid (p = 0.02) over the intervention time frame was differentially associated with maternal secretor status. 4-HBA and ferulic acid positively correlated with HMOs LNT and DSLNT (rrm = 0.82-0.90, p = 0.03-0.06) for secretors but not for non-secretors. Only secretors demonstrated a negative correlation between 4-HBA and DFLNT (rrm = -0.94, p = 0.001). The influence of maternal diet on composition of HMOs and polyphenol metabolites in HM differs based on maternal secretor status. Consideration of non-dietary factors is needed to evaluate differences in response of HM bioactives to dietary modulation.

Crafting the Future of Community-Based Medical Rehabilitation: Exploring Optimal Models for Non-Inpatient Rehabilitation Services through a Narrative Review.

Community-based medical rehabilitation encompasses diverse programs that cater to patients outside of inpatient settings, such as home rehabilitation, day rehabilitation centers, and ambulatory clinics. While inpatient rehabilitation principles are widely standardized, outpatient programs display significant variability influenced by healthcare models, local environments, economic constraints, and available resources. This narrative review aims to explore and synthesize the various models of non-inpatient rehabilitation services, evaluating their effectiveness, cost-efficiency, and patient satisfaction. The review also seeks to identify optimal practices and strategies to enhance community-based rehabilitation, alleviate the burden on inpatient facilities, and improve patient outcomes through multidisciplinary and patient-centered approaches. Additionally, the study examines the critical role of a professional program coordinator and the importance of effective clinical communication in outpatient rehabilitation. A comprehensive search of peer-reviewed literature was conducted across multiple databases, focusing on studies that examined community-based rehabilitation models. The findings suggest that community-based rehabilitation programs are generally more cost-effective than inpatient programs, with their success being heavily dependent on the intensity and timing of interventions. Multidisciplinary approaches and high-intensity rehabilitation have shown promise in improving patient quality of life, though their effectiveness varies by condition. Despite limited research, the involvement of a Physical and Rehabilitation Medicine (PRM) physician as a program coordinator appears vital for ensuring continuity of care. Moreover, effective clinical communication is essential, impacting all aspects of patient care and interprofessional collaboration, with continuous adaptation required to meet the evolving needs of diverse patient populations.

Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington’s disease mice

BackgroundTherapeutic approaches aimed at lowering toxic mutant huntingtin (mHTT) levels in the brain can reverse disease phenotypes in animal models of Huntington's disease (HD) and are currently being evaluated in clinical trials. Sensitive and dynamic response biomarkers are needed to assess the efficacy of such candidate therapies. Neurofilament light chain (NfL) is a biomarker of neurodegeneration that increases in cerebrospinal fluid (CSF) and blood with progression of HD. However, it remains unknown whether NfL in biofluids could serve as a response biomarker for assessing the efficacy of disease-modifying therapies for HD.MethodsLongitudinal plasma and cross-sectional CSF samples were collected from the YAC128 transgenic mouse model of HD and wild-type (WT) littermate control mice throughout the natural history of disease. Additionally, biofluids were collected from YAC128 mice following intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting the mutant HTT transgene (HTT ASO), at ages both before and after the onset of disease phenotypes. NfL concentrations in plasma and CSF were quantified using ultrasensitive single-molecule array technology.ResultsPlasma and CSF NfL concentrations were significantly elevated in YAC128 compared to WT littermate control mice from 9 months of age. Treatment of YAC128 mice with either 15 or 50 µg HTT ASO resulted in a dose-dependent, allele-selective reduction of mHTT throughout the brain at a 3-month interval, which was sustained with high-dose HTT ASO treatment for up to 6 months. Lowering of brain mHTT prior to the onset of regional brain atrophy and HD-like motor deficits in this model had minimal effect on plasma NfL at either dose, but led to a dose-dependent reduction of CSF NfL. In contrast, initiating mHTT lowering in the brain after the onset of neuropathological and behavioural phenotypes in YAC128 mice resulted in a dose-dependent stabilization of NfL increases in both plasma and CSF.ConclusionsOur data provide evidence that the response of NfL in biofluids is influenced by the magnitude of mHTT lowering in the brain and the timing of intervention, suggesting that NfL may serve as a promising exploratory response biomarker for HD.