Targeting the prefrontal-supplementary motor network with online and offline tDCS to modulate disgust: A single-blind and sham-controlled study.

Combining transcranial direct current stimulation with a rhythm-based intervention to improve reading fluency in young adults with dyslexia.

Exercise ameliorates microglial activation and cognitive impairment induced by GFAT1 knockdown after traumatic brain injury.

EEG microstate beta-band abnormalities in obsessive-compulsive disorder: Associations with disease symptoms and sensitivity to repetitive transcranial magnetic stimulation.

Cerebellar magnetic stimulation increased beta power and phase synchronisation in spinocerebellar ataxia type 3.

Walking difficulties and fatigue severely limit daily life in persons with multiple sclerosis (pwMS). Sensory stimulation, such as transcutaneous electrical nerve stimulation (TENS), might offer a non-pharmacological strategy to enhance motor function through sensorimotor interactions in the central nervous system. This randomized, double-blinded, sham-controlled, parallel-group superiority trial investigated the effects of TENS applied to the knee extensors, with and without concurrent exercise, on walking and fatigue in pwMS. PwMS (n = 80) with fatigue (FSS>4 or MFIS>38) and walking difficulties (MSWS-12>30) were randomized to one of four groups: TENS only (TENS; n = 21), TENS+exercises (COMBINATION; n = 20), sham stimulation (SHAM; n = 20) or sham+exercises (EXERCISE; n = 19) using a computer-generated stratified randomization. Each group performed twelve 10-min sessions over 4 weeks. Participants and outcome assessors were blinded to the stimulation type. Primary outcomes were walking performance (6-minute walk test, 6-MWT), fatigue (FSS, MFIS), and self-reported walking limitations (MSWS-12). Secondary outcomes were knee extensor strength and force steadiness and the 30-second chair-stand test (30-CST). Outcomes were assessed at baseline, immediately post-intervention, and at 2-week follow-up. Intention-to-treat linear mixed-effect models showed a significant time*group interaction for the 6-MWT (p < .05). Relative to SHAM, within-group comparisons indicated significant improvements in the TENS group only (+35 m [95% CI: 23.1-46.5] post-intervention; +35 m [95% CI: 22.4-48.4] at follow-up). Clinically meaningful improvements (>21.6 m) in walking distance were achieved by 74% of the TENS group compared to 44%, 40% and 28% in the COMBINATION, SHAM and EXERCISE group. FSS, MFIS, MSWS-12 and secondary outcomes improved across all groups, with no between-group differences. No important harms were notified. TENS during rest, but not during exercise, improved walking performance in pwMS more than SHAM, but not subjective outcomes such as fatigue or perceived walking limitations. Future studies should investigate underlying neurophysiological mechanisms to optimize therapeutic outcomes. ClinicalTrials.gov (NCT05321927).

Effect of encephalomyosynangiosis procedure on post stroke recovery in a permanent model of ischemic stroke.

Heart failure (HF) is a common disease resulting in high morbidity, mortality, and healthcare costs. An important cause of HF is mitral valve regurgitation (MR), which induces left ventricular remodeling and volume overload. For HF research, a reproducible and reliable large animal model is crucial. Several MR models have been developed, but they often show high variability in MR severity and MR jet characteristics, as well as an underlying ischemic cardiomyopathy, which may increase the risk of complications during follow-up. We present a straightforward and uniform porcine model of primary MR-induced HF. A custom-made retractor was used to induce severe and uniform MR by chordal rupture. After four weeks, severe MR led to significant left ventricular remodeling compared to the sham group, with a significant increase in left ventricular end-diastolic (+34.5 ± 6.8ml vs. +8.4 ± 5.3ml, p = 0.023) and end-systolic volume (+29.9 ± 4.0ml vs. +4.2 ± 2.9ml, p = 0.001), a decrease in left ventricular ejection fraction (-11.9 ± 1.9% vs. -0.7 ± 0.9%, p < 0.001) and fractional shortening (-12.2 ± 1.3% vs. -2.2 ± 0.8%, p < 0.001), and a higher amount of left ventricular fibrosis (12.6 ± 1.0% vs. 6.4 ± 0.9%, p = 0.001). This porcine model allows a straightforward and reproducible induction of primary MR-induced HF, with a high success rate. It could be valuable in basic research to study the underlying pathophysiology and in translational research to develop novel diagnostics and therapeutics targeting volume-overload induced HF and/or primary MR.

Background Sensory recovery following digital nerve neurorrhaphy is often incomplete, and strategies to enhance regeneration remain under investigation. Low-frequency transcutaneous electrical stimulation has been proposed as a potential adjunctive therapy, but its efficacy in clinical settings is uncertain. Methods In this randomized controlled trial, 32 patients with isolated traumatic digital nerve injuries underwent surgical neurorrhaphy at a tertiary care hospital. Participants were randomly allocated to an intervention group (n = 16) or sham group (n = 16). The intervention consisted of a single postoperative session of square-pulsed, biphasic transcutaneous electrical stimulation at 20 Hz for 1 hour. The sham group received identical conditions without active stimulation. After stimulation, patients underwent physiotherapy sessions for three months. Sensory recovery was assessed using Semmes-Weinstein monofilament testing and two-point discrimination at baseline, 1 week, 1 month, and 3 months postoperatively. Results Both groups showed progressive sensory improvement throughout follow-up, approaching normal values at 3 months. No statistically significant differences were observed between groups in any outcome measure. Confidence intervals for group comparisons overlapped, and no clinically meaningful differences were detected. No adverse effects were reported. Conclusions In this model, a single postoperative session of low-frequency transcutaneous electrical stimulation did not significantly enhance sensory recovery after digital nerve repair. Further research with varied stimulation protocols, repeated sessions, or extended follow-up may be warranted to clarify its potential role in peripheral nerve regeneration. Level of Evidence Therapeutic Level I.

The objective of this study was to assess the efficacy of theta-burst stimulation (TBS) in treating late-life depression. A triple-blind, sham-controlled randomized clinical trial was performed. The study included participants age 60 and older with a diagnosis of moderate to severe major depressive disorder who were not using antidepressants. Exclusion criteria included other psychiatric disorders, neurological disorders, and contraindications to TBS. TBS was administered bilaterally, with intermittent TBS on the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS on the right DLPFC, with 1,800 pulses at each side. Participants underwent 20 daily sessions of active or sham TBS over 20 consecutive weekdays and one additional session during weeks 6, 8, and 12 (totaling 23 sessions). A total of 108 participants (mean age, 67 years) were enrolled and underwent either active or sham TBS. In an intention-to-treat analysis, there was no significant difference between groups at week 6 in mean reduction in Hamilton Depression Rating Scale (HAM-D) score (mean difference, -1.65, 95% CI=-3.38, 0.08). By week 12, active TBS was associated with a significantly greater reduction in HAM-D score compared to sham (mean difference, -1.89, 95% CI=-3.75, -0.03), with response rates of 52% in the active group and 33% in the sham group. Linear mixed models analyzing HAM-D score did not show a statistically significant greater reduction in the active TBS group compared to the sham group at week 6 (Cohen's d=-0.36, 95% CI=-0.74, 0.01). The active TBS group did not have a statistically significant greater reduction in HAM-D scores compared to the sham group at week 6. By week 12, however, active TBS was superior to sham stimulation in reducing depressive symptoms in patients with late-life depression, suggesting TBS as a possible treatment option for this population.

Exercise is the first-line treatment for knee osteoarthritis (KOA). Cryotherapy is used to control pain and inflammation, but robust evidence on its benefits is lacking. Analyze the additional effects of cryotherapy, when associated with an exercise protocol, on pain, function, and quality of life in people with KOA. A randomized controlled trial with sham and control groups, concealed allocation, blinded assessors, and intention-to-treat analysis. Individuals (n = 120) aged from 40 to 75, with knee pain ≥ 4 cm on 10 cm visual analog scale, and radiographic diagnosis of grade 2 or 3 (Kellgren and Lawrence) were included and divided into 3 groups (n = 40 per group): Exercise; Exercise + Cryotherapy; Exercise + Sham Cryotherapy Treatment was delivered 3 times per week for 8 weeks (24 sessions). Primary outcome was pain intensity (Visual Analog Scale). Secondary outcomes were physical function [Western Ontario and McMaster Universities (WOMAC)] and functional tests: 30-second sit-to-stand test, stair climbing test, 40-meter fast walking test, and quality of life [36-item Short Form Health Survey (SF-36)]. At post-intervention, for pain at rest, there were no between-group differences: Exercise vs. Exercise + Cryotherapy (mean difference, MD = -0.46 [confidence interval, 95 % CI: -1.97, 1.05]), Exercise vs. Exercise + Sham (MD = -1.27 [95 % CI: -2.78, 0.23]), Exercise + Cryotherapy vs. Exercise + Sham (MD = -0.82 [95 % CI: -2.32, 0.69]). At follow-up period, the results also did not show between-group differences (p > 0.05). Results showed the beneficial effects of exercise in the treatment of KOA, without additional effects of cryotherapy.

Postpartum pelvic floor dyssynergic defecation (PFDD) is a common and distressing condition. We hypothesized that transcutaneous tibial nerve stimulation (TTNS) combined with standard rehabilitation would be superior to rehabilitation alone for alleviating symptoms in primiparous women with PFDD. In this randomized controlled trial, 40 primiparous women with PFDD were allocated to an intervention group (TTNS + standard rehabilitation, n = 20) or a control group (sham stimulation + standard rehabilitation, n = 20). The intervention lasted 6weeks. Primary (constipation symptom score) and secondary outcomes (clinical efficacy, pelvic floor surface electromyography) were assessed at baseline and post-treatment. Both groups improved significantly after treatment (p < 0.05). However, the intervention group demonstrated a significantly greater reduction in constipation symptom scores (p < 0.05) and a higher overall clinical effectiveness rate (90% vs. 65%, p < 0.05). Pelvic floor surface electromyography showed significantly greater improvement in the intervention group for resting, fast, and slow contraction phases (p < 0.05), but not for endurance (p > 0.05). TTNS is an effective adjunct to standard rehabilitation for improving constipation symptoms and pelvic floor muscle function in primiparous women with PFDD. It represents a valuable, non-invasive therapeutic option for this condition.This study demonstrates positive effects of transcutaneous tibial nerve stimulation as an adjunctive therapy for primiparous women with postpartum pelvic floor dyssynergic defecation. It significantly improves constipation symptoms, clinical effectiveness rates, and key parameters of pelvic floor muscle function compared to standard rehabilitation alone. Given its non-invasive nature, favorable safety profile, and demonstrated clinical benefits,TTNS represents a valuable addition to the therapeutic options for this common postpartum condition.

Aim: Abdominal aortic aneurysm is a progressive enlargement of the abdominal aorta associated with high mortality risk. Despite advances in surgical and endovascular treatments, no pharmacological therapy has been established to prevent aneurysm growth. Dapagliflozin, a sodium–glucose cotransporter-2 inhibitor, has demonstrated cardiovascular benefits beyond glycemic control. The aim of this study was to investigate the effects of dapagliflozin in a calcium phosphate–induced rat model of abdominal aortic aneurysm. Material and Methods: Twenty male Wistar albino rats were randomly divided into three groups: sham operated rats (Sham, n=6), rats with abdominal aortic aneurysm induced by calcium phosphate (AAA, n=7), and rats with aneurysm treated with dapagliflozin (Dapagliflozin group, n=7). Aneurysm formation was induced by periaortic application of calcium phosphate. The Dapagliflozin group received daily oral dapagliflozin at a dose of 1 mg/kg for 28 days. Morphometric parameters including lumen area, lumen plus intima area, and lumen plus intima plus media area were evaluated using hematoxylin–eosin staining. Elastin degradation was assessed with Van Gieson staining, vascular calcification with Alizarin Red staining, and apoptosis with immunohistochemical detection of Caspase-3 and Caspase-9. Statistical analyses were performed using Student’s t-test and Mann–Whitney U test, with a significance threshold of p&lt;0.05. Results: Morphometric parameters were significantly increased in the AAA group compared with the Sham group (all p&lt;0.001). These parameters were reduced in the Dapagliflozin group compared with the AAA group (all p&lt;0.001). Elastin degradation and calcium deposition were higher in the AAA group compared with Sham (p=0.001 and p=0.002) and decreased with dapagliflozin treatment (p=0.001 and p=0.012). Caspase-3 and Caspase-9 expression was elevated in the AAA group (p=0.002 and p=0.003) and decreased in the Dapagliflozin group, although the reduction in Caspase-9 did not reach statistical significance (p=0.068). Conclusion: Dapagliflozin reduced aortic dilatation, elastin degradation, vascular calcification, and Caspase-3–mediated apoptosis in a calcium phosphate–induced rat model of abdominal aortic aneurysm. These findings suggest that dapagliflozin exerts protective effects on vascular integrity beyond glucose regulation and may represent a potential medical therapy for abdominal aortic aneurysm.

We aimed to evaluate the effectiveness of combining Low-Frequency (1 Hz) rTMS (LF-rTMS) over the unaffected hemisphere or Intermittent Theta Burst Stimulation (iTBS) over the affected hemisphere with conventional rehabilitation (CR) on lower extremity motor function, balance and gait. This single-center, randomized, sham-controlled study included patients with chronic stroke (>6mo) and unilateral hemiplegia (Brunnstrom stages 3-5), who were assigned to LF-rTMS+CR (n=21), iTBS+CR (n=21), or sham rTMS+CR (n=21) for 10 sessions using a figure-of-eight coil. All active participants completed treatment, and 18 sham participants were analyzed. The Fugl-Meyer Assessment, Berg Balance Scale (BBS), Timed-Up and Go (TUG) test, Functional Independence Measure, and 36-item Short Form Health Survey (SF-36) were performed during pretreatment, posttreatment, and 6-week follow-up, alongside assessments of the Hmax/Mmax amplitude at baseline and 6-week follow-up. Both real rTMS groups showed greater improvements in balance and mobility (BBS and TUG) versus sham group. Additionally, intragroup evaluation revealed that improvements in mental function and general health (SF-36) were more pronounced in the real rTMS groups. The combination of rTMS, including LF-rTMS or iTBS, with CR may serve as an effective neurorehabilitation strategy to improve balance and mobility in individuals with chronic stroke.

Emotional difficulties, such as low mood and worry, are more prevalent among female forces veterans compared to their male peers. However, female veterans are more reluctant to access mental health services available for armed force veterans. To enhance help seeking, the Iona female forces veterans (IonaFFV) research app has been developed and adapted for low mood and worry management among female veterans. This feasibility randomised controlled trial primarily seeks to explore the methodological uncertainties of conducting a definitive randomised controlled trial using IonaFFV. Secondary aims seek to explore acceptability and engagement with IonaFFV. Additionally, progression criteria will be assessed to determine feasibility of moving to a definitive trial. Participants were recruited online and asked to complete two screening assessments to assess eligibility. Eligible participants were randomised using block randomisation to use either the IonaFFV or Iona sham app for 6 weeks. Recruitment and randomisation are complete, and data collection is currently ongoing. At the end of the 6-week intervention period, participants will complete the Patient Health Questionnaire-9, the Generalised Anxiety Disorder-7 and Work and Social Adjustment Scale outcome measures. At 4 weeks postintervention (10 weeks postrandomisation), participants will complete the same outcome measures in addition to the mHealth App Usability Questionnaire (MAUQ) to assess acceptability of both IonaFFV and Iona sham. At the end of the study, the participants who were in the Iona sham group will be given an option to use the IonaFFV app for 6 weeks. Proportions will be reported for feasibility and demographic data with descriptive analysis conducted for the outcome measures. Median values with IQRs will be conducted for each subscale of MAUQ. This study received ethical approval from the University of Exeter Psychology Ethics Committee with consent obtained from all participants. Study findings will be published in peer-reviewed journals, presented at conferences, with a final report presented to the funders of the project. ISRCTN50744553.

Critical-sized bone defects require grafts with ideal spatial supporting. We upcycled eggshell waste sustainably into porous amorphous calcium phosphate (ACP) scaffolds and evaluated their early bone-regeneration performance alone and in combination with flexible and bioactive adjuncts in vivo. ACP scaffolds with ∼60% porosity were fabricated by pressure-densification, using ice microspheres as space holders. Before implantation, ACP scaffolds were vacuum-infiltrated with a hyaluronic acid (HA) hydrogel to minimize internal voids. Bilateral critical-size femoral and calvarial defects were created in New Zealand White rabbits and reconstructed with one of four treatments: (1) Sham, (2) ACP scaffold (ACP), (3) ACP infused with HA hydrogel containing a proline-rich peptide P2 (ACP + HA/P2), or (4) ACP infused with HA/P2 supplemented with soluble eggshell membrane proteins (prepared by our lab, ACP + HA/P2 + SEPs). After 6 weeks, micro-CT and histology were performed. All ACP-containing groups showed greater defect filling and mineralization than the Sham group. Micro-CT analysis demonstrated that ACP + HA/P2 + SEPs achieved the highest bone volume and trabecular number and the lowest trabecular separation. Histology confirmed more extensive mineralized collagenous deposition on ACP scaffolds and a more integrated bone-material fusion zone in this group. In femoral defects with graft displacement, ACP scaffolds induced cortical-scaffold bone bridging within the marrow, most evident with SEPs. Eggshell-derived ACP scaffolds, particularly when paired with SEP-enriched HA hydrogel, enhance early regeneration of critical-sized bone defects. Upcycling the inorganic and organic constituents of eggshell waste yields a complementary, single-origin biomaterials package for sustainable bone repair.

Chronic cerebral hypoperfusion (CCH) is a cerebral dysfunction caused by insufficient cerebral perfusion, and Huoluo Yinao (HLYN) formula is a traditional Chinese medicinal formula used for CCH treatment. We investigated the specific mechanism of HLYN formula on CCH through network pharmacological analysis and in vivo experiments. The active ingredients and drug targets of HLYN formula obtained through network pharmacological analysis were subjected to molecular docking with disease targets of CCH. Wistar male rats (six weeks) were used to establish a CCH rat model by the two-vessel occlusion (2VO) method. The rats were treated with HLYN alone or in combination with the HSP90AA1 overexpression vector before behavior tests. The groups were as follows: Sham group, CCH group, CCH+HLYN group, CCH+HLYN+oe-NC group, and CCH+HLYN+oe-HSP90AA1 group, with six rats in each group. The hippocampal tissues were assessed after Hematoxylin and eosin (H&amp;E) and Nissl stainings. Autophagosomes were observed using immunofluorescence and transmission electron microscopy. There were 83 active ingredients and 1339 potential pharmacological targets in HLYN formula, while 3175 genes were found associated with CCH. A total of 235 overlapped genes were obtained. Rats in the CCH+HLYN group showed shortened escaping latency, increased times in the target quadrant, and increased number of platform crossings, along with attenuated tissue injury, elevated Nissl-positive neurons and less apoptosis. In addition, inflammation and oxidative stress (OS) were decreased in the CCH+HLYN group, evidenced by reduced malondialdehyde (MDA), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6 and IL-1β, and increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and IL-10 expression. HLYN formula led to suppressed HSP90AA1 expression and autophagy, along with increased p-PI3K/p-AKT/p-mTOR protein expression. The phenotypes in the CCH+HLYN group can be reversed by further treatment with HSP90AA1 overexpression. HLYN formula can inhibit HSP90AA1 expression to inhibit autophagy, inflammation, and OS, which in turn contributes to attenuating cognitive impairment in CCH rats.

Acute myocardial infarction can lead to ventricular remodelling, which affects ventricular function and survival prognosis. Therefore, improving ventricular remodelling has become a focus of research. This study aims to investigate the effect of Acanthopanax senticosus leaf saponins (ASS) on cardiac function and left ventricular remodelling in a rat model of myocardial infarction, and explore its potential mechanism. Coronary artery ligation was used to establish a rat model of myocardial infarction, and ASS was administered orally for 28 days. After 28 days, cardiac function was evaluated by hemodynamic detection, and the levels of myocardial enzymes, inflammatory cytokines, oxidative stress and fibrosis-related factors were detected. The degree of fibrosis was evaluated by immunohistochemical detection of collagen I and collagen III deposition. The expression levels of MMP-2, MMP-9 and TIMP-1 were checked by Western blot. Compared with the Sham group, the cardiac function of the Model group was significantly impaired, and ASS administration could improve this change. In addition, compared with the Model group, ASS significantly alleviated myocardial injury, reduced the release of inflammatory cytokines TNF-α and IL-β, improved the oxidative stress state, reduced the release of NT-propBNP, Ang II, ET-1 and inhibited myocardial fibrosis. Moreover, ASS could reduce the expression of MMP-2 and MMP-9, and increase the expression level of TIMP-1. In conclusion, ASS may inhibit left ventricular remodelling by reducing the expression of MMP-2 and MMP-9.

Background/Objectives: Stroke frequently leads to balance deficits. Vestibular physical therapy (VPT) may enhance postural control through neuroplastic mechanisms. Virtual reality (VR) can provide ecologically valid environments for rehabilitation, increasing patient engagement. Methods: In this randomized feasibility study, nine individuals with chronic stroke were randomized to either a Real visuo-vestibular rehabilitation group (n = 6) or a Sham VR group (n = 3) to explore the feasibility of the protocol and randomization procedures rather than to compare clinical efficacy. Both groups were trained in immersive VR environments for 12 sessions. The Real group experienced visuo-vestibular stimuli requiring sensorimotor integration; the Sham group trained in the same environments without such stimuli. Feasibility was assessed through attendance, participation (Pittsburgh Rehabilitation Participation Scale, PRPS), and user satisfaction (USEQ). Safety and acceptability were monitored through adverse event reporting. Secondary exploratory outcomes included measures of balance-the Mini Balance Evaluation Systems Test (MiniBESTest), the Berg Balance Scale (BBS), and the Performance-Oriented Mobility Assessment (POMA)-as well as functional independence (Barthel Index), health-related quality of life (Stroke-Specific Quality of Life Scale, SSQoL), and a set of spatiotemporal and gait quality parameters derived from inertial measurement unit (IMU) data collected during the 10-Meter Walk Test and the Figure of 8 Walk Test. Results: All participants completed the protocol without adverse events. Participation, as measured by the PRPS, remained consistently high across sessions (mean ≥5.7/6), while USEQ scores indicated excellent user satisfaction (mean ≥28/30). Exploratory analyses revealed improvements in MiniBESTest and BBS scores for the Real group. Instrumental measures derived from IMUs demonstrated improvements across groups. Conclusions: Exploratory outcomes suggested positive trends in balance improvements, and the integration of clinical scales with wearable sensors proved feasible and informative.

Treating myocardial infarction combined with depression via regulating M1/TNF-α/TNFR1/NF-κB.