Sirtuin 1 in regulating the p53/glutathione peroxidase 4/gasdermin D axis in acute liver failure.

In this editorial, we comment on the article by Zhou et al. The study reveals the connection between ferroptosis and pyroptosis and the effect of silent information regulator sirtuin 1 (SIRT1) activation in acute liver failure (ALF). ALF is characterized by a sudden and severe liver injury resulting in significant hepatocyte damage, often posing a high risk of mortality. The predominant form of hepatic cell death in ALF involves apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis. Glutathione peroxidase 4 (GPX4) inhibition sensitizes the cell to ferroptosis and triggers cell death, while Gasdermin D (GSDMD) is a mediator of pyroptosis. The study showed that ferroptosis and pyroptosis in ALF are regulated by blocking the p53/GPX4/GSDMD pathway, bridging the gap between the two processes. The inhibition of p53 elevates the levels of GPX4, reducing the levels of inflammatory and liver injury markers, ferroptotic events, and GSDMD-N protein levels. Reduced p53 expression and increased GPX4 on deletion of GSDMD indicated ferroptosis and pyroptosis interaction. SIRT1 is a NAD-dependent deacetylase, and its activation attenuates liver injury and inflammation, accompanied by reduced ferroptosis and pyroptosis-related proteins in ALF. SIRT1 activation also inhibits the p53/GPX4/GSDMD axis by inducing p53 acetylation, attenuating LPS/D-GalN-induced ALF.

The translation and validation of the MES for an Austrian sample.

INTRODUCTION: Empathy plays an important role in midwifery care, not only for the women but also for midwives. The Midwifery Empathy Scale (MES) was developed to assess the empathy levels of midwives and midwifery students. The purpose of this study was the translation and validation of the MES for an Austrian sample. METHODS: A total of 277 midwives working in Austria completed the questionnaire of the MES. The psychometric measurements that were performed included explanatory factor analysis using a varimax rotation and principal components analysis. Moreover, the internal consistency of the MES was assessed with reliability coefficients. The Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy and a Bartlett's test of sphericity were carried out. RESULTS: Principal components analysis showed seven orthogonal factors. KMO measure of sample adequacy = 0.724 and Bartlett's test of sphericity = 1058.904 (df=231, p<0.0001). The MES showed an acceptable overall internal consistency: Cronbach's alpha was found to be 0.721 and the Guttman split-half coefficient was 0.611. The findings of our study confirm the multidimensionality of MES, demonstrating a seven-factor structure which contained subscales reflecting empathy and emotional connection. The mean total score of Austrian midwives' responses to the MES was 44.80 with scores ranging from 24 to 81. CONCLUSIONS: This study shows that the German version of the Midwifery Empathy Scale is a reliable instrument for evaluating the empathy levels of midwives and midwifery students in Austria. The German MES could be used in the selection and education of future midwives as well as in connection with empathy trainings of midwives.

Targeting both ferroptosis and pyroptosis may represent potential therapies for acute liver failure.

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.

Ischaemic Cardiomyopathy Secondary to Asymptomatic Coronary Artery Disease: A Case Report.

Ischaemic cardiomyopathy (ICM) represents a common complication of coronary artery disease (CAD). Ischaemia causes ventricular remodelling, leading to an irreversible loss of myocardial tissue and adequate contractility, primarily affecting the left ventricular ejection fraction (LVEF). We present the case of a 46-year-old male known as hypertensive presented to the hospital with a five-week history of progressive exertional dyspnoea, bilateral lower limb oedema subsequently involving his scrotum and penis. He reported reduced oral intake and occasional palpitations but denied chest pain, cough, fever, or haemoptysis. He had no personal history of cardiac disease, recent travels, or recreational drug use. Notably, he consumed approximately 12 units of alcohol weekly and was a non-smoker. On admission, he was treated for new-onset heart failure, and initial investigations showed acute kidney injury, raised troponin, and brain natriuretic peptide (BNP), and chest X-ray showed an enlarged heart size (cardiothoracic ratio (CTR), 0.56) with moderate right pleural effusion. Echocardiography revealed a severely dilated left ventricle with severely impaired systolic function (LVEF 16%), bi-atrial dilatation, borderline dilated right ventricle with impaired systolic function, and moderate tricuspid regurgitation. Cardiac MRI showed that the left ventricle was severely dilated with severely impaired systolic function with nonviable mid to apical inferior and inferoseptal transmural post-ischaemic scar with associated hypokinesia. Ischaemic cardiomyopathy may vary from asymptomatic to severely symptomatic, commonly when symptomatic patients will present with anginal chest pain and dyspnoea on exertion. In contrast, asymptomatic patients can sometimes have up to 80% of transient ischaemic events with no chest pain or associated symptoms. This case underscores the importance of considering asymptomatic coronary artery disease in clinical practice and highlights the need for novel interventions and markers for early ischemia detection.

Wutou Decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Wutou Decoction (WTD) has long been used to alleviate arthritis. Emerging studies have reported that WTD could improve the symptoms of rheumatoid arthritis (RA). However, the mechanism by which WTD is involved in the treatment of RA remains elusive, posing a challenge to the worldwide acceptance of WTD as an efficient RA therapy. AIM OF THE STUDY: This study investigated the antiarthritic efficacy of WTD in a collagen-induced arthritis (CIA) rat model and explored silent information regulator 1 (SIRT1)-mediated deacetylation of the high mobility group box 1 (HMGB1)/NF-κB pathway. MATERIALS AND METHODS: A rat CIA model was used to evaluate the antiarthritic activity of WTD. Clinical arthritis score assessment, left ankle thickness assessment, micro-CT, histopathological staining, immunofluorescence staining, and ELISA were conducted to elucidate the anti-inflammatory effects of WTD. The M1 macrophage polarization state, cell viability, and invasion were also determined to assess the effects of WTD on macrophage proliferation and invasion in vitro. Additionally, in vivo and in vitro HMGB1 nuclear translocation and NF-κB activation were analysed. Finally, deacetylase activity was assessed by Western blot, NAD+/NADH analysis, and co-immunoprecipitaion. RESULTS: WTD significantly alleviated arthritis in CIA rats and inhibited pathological changes in joint lesions while concurrently suppressing TNF-α, IL-6, and IL-1ß release. Mechanistically, WTD suppressed M1 infiltration in ankle tissues and their invasion in vitro. Furthermore, WTD downregulated HMGB1/p65 nuclear translocation and acetylation, which may be associated with SIRT1 upregulation. CONCLUSIONS: Overall, WTD potentially alleviates RA through SIRT1-mediated downregulation of HMGB1 and NF-κB acetylation.

Blunt Chest Wall Trauma Leading to Sudden Cardiac Arrest.

A 54-year-old hockey player survived sudden cardiac arrest after a chest slapshot, receiving immediate resuscitation and defibrillation of ventricular fibrillation. Examinations revealed chest trauma and subclinical single-vessel disease; a coronary dissection could not be ruled out. The patient recovered without complications, underscoring the importance of rescue equipment in sports facilities.

Downregulation of microRNA­221­3p promotes angiogenesis of lipoprotein(a)­injured endothelial progenitor cells by targeting silent information regulator 1 to activate the RAF/MEK/ERK signaling pathway.

The present study aimed to investigate the role of microRNA (miR)­221­3p in endothelial progenitor cells (EPCs) treated with lipoprotein(a) [LP(a)]. EPCs were identified using immunofluorescence assays and miR­221­3p levels were measured using reverse transcription­quantitative PCR. EPC migration was detected using Transwell assays, proliferation was measured by staining with 5­ethynyl­2'­deoxyuridine and adhesion was assessed by microscopy. Flow cytometry was used to measure apoptosis and protein expression was detected using western blotting. A dual­luciferase reporter assay was used to confirm the target interactions. The proliferation, migration, adhesion and angiogenesis of EPCs were decreased, and apoptosis was increased after treatment with LP(a). These effects were weakened by transfection with miR­221­3p inhibitor. The negative effects of LP(a) on EPCs were also weakened by overexpression of silent information regulator 1 (SIRT1). Inhibition of the RAF/MEK/ERK signaling pathway blocked the effects of SIRT1 overexpression. In conclusion, miR­221­3p inhibitor transfection activated the RAF/MEK/ERK signaling pathway through SIRT1, promoted the proliferation, migration, adhesion and angiogenesis of EPCs, and reduced apoptosis.

Lithium-induced cognitive dysfunction assessed over 1-year hospitalisation: A case report.

Introduction: Lithium-induced neurotoxicity is almost always reversible but can cause irreversible neurological sequelae, namely the syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). As there is no definitive treatment for SILENT, caution is required when administering lithium. Reports on the effect of lithium-effectuated neurotoxicity on cognitive function are limited. We report a case in which high cognitive function was lost after lithium overdose and hardly recovered, as evaluated using multiple neuropsychological tests during a 1-year hospitalisation period. Patient presentation: A 52-year-old man on lithium medication with bipolar disorder was admitted to the intensive care unit because of lithium overdose. The patient achieved lucid consciousness after continuous haemodiafiltration. However, he could not move his body as desired or produce appropriate verbal expressions; thus, he was moved to our psychiatric ward, where his treatment continued. Management and outcome: After several months, the patient was diagnosed with SILENT owing to persistent motor and cognitive dysfunctions. Multiple neuropsychological tests were performed, and cognitive function was evaluated. The Neurobehavioural Cognitive Status Examination showed a worsening trend, and the full intelligence quotient of the Wechsler Adult Intelligence Scale-Third Edition was in the mild intellectual disability range. Conclusion: This is a clear case of cognitive dysfunction due to SILENT and is difficult to treat. Thus, it is crucial to prevent the onset of SILENT. Contribution: This report is valuable because it is one of the few to track changes in cognitive function over time in a patient with SILENT using objective measures over 1 year of hospitalisation.

Does the standard proteinuria cut-off for renal biopsy in lupus nephritis as per the current guidelines hold good for Asian population? A single-centre study from South India.

INTRODUCTION: Current rheumatology and nephrology society guidelines in lupus nephritis do not recommend renal biopsy for proteinuria of less than 500 mg/24 h. This might lead to a significant delay in the early diagnosis of lupus nephritis. AIM: The main aim of this study is to determine the nature of renal lesions in patients with low-grade proteinuria and to analyze the predictors for clinically significant lupus nephritis. METHODS: This was a single-center, retrospective study. All consecutive patients of lupus nephritis, with low-grade proteinuria (200 mg to 500 mg/24 h) undergoing renal biopsy were enrolled in this study. The renal biopsies were classified into significant lesions (Class III/IV/V) and non-significant lesions (Class I and II). Treatment naïve groups and treatment-modified groups were analyzed separately. Predictive factors for significant renal lesions were determined by univariate and multivariate analysis. RESULTS: We identified 183 patients of lupus with proteinuria between 200 and 500 mg / 24 h. Mean (SD) age was 30.2 (11.39) years with 167 (91.2%) of them being females. The mean (SD) baseline proteinuria was 351.03 (98.1) mg/24 h 85 patients (46.5%) had proliferative lupus nephritis where whereas 17 patients (9.3%) had membranous nephropathy. Crescents and fibrinoid necrosis were seen in 10 (5.46%) and 24 (13.11 %) patients respectively. Isolated proteinuria without any other sediments was seen in 95 patients (51.9%) of which 29 patients had proliferative lupus nephritis. Elevated Anti-double stranded DNA (anti-dsDNA), low C3, low C4 and the presence of urinary sediments were significantly associated with significant renal lesions in biopsy. CONCLUSION: Significant renal lesions were seen in around half of the patients with low-grade proteinuria underscoring the importance of performing a renal biopsy in this set of patients. Low C3 and C4, urinary sediments, and elevated anti-dsDNA were predictors for significant renal lesions.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.

OBJECTIVE: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates. METHODS: The demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups. RESULTS: 54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables. INTERPRETATION: We found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.

Effect of Intensive Blood Pressure Lowering on the Risk of Incident Silent Myocardial Infarction: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. METHODS: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). RESULTS: During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23). CONCLUSIONS: This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

Silent inactivation of asparaginase in Japan: results of the prospective ALL-ASP19 trial.

Silent inactivation (SI) of L-asparaginase (ASP) is a phenomenon by which a neutralizing antibody for ASP (AAA) decreases ASP activity (ASA) in patients without a clinical allergy to ASP. Acute lymphoblastic leukemia (ALL) has a poor prognosis in patients with SI. Therefore, measurement of ASA levels, not AAA levels, is needed to identify patients with SI. We herein report the results of the prospective clinical trial ALL-ASP19, the first study in Japan to measure ASA and AAA to identify patients with SI. A total of 110 newly diagnosed ALL patients were enrolled, and ASA levels were measured three times during ALL treatment. Besides the 12 patients who discontinued the study, 32 were excluded due to inappropriate frequency and timing of ASA measurements and inappropriate ASP dosing. The remaining 66 patients were analyzed, and 3 patients with SI (4.5%) were identified. The incidence of SI is lower in Japan than in other countries. AAA was detected in all patients with SI, but four of the seven patients with AAA did not develop SI. Clinical characteristics did not significantly differ between patients with and without SI. Therefore, ASA levels must be measured to identify patients receiving insufficient ASP treatment.

Variant-specific antibody profiling for tracking SARS-CoV-2 variant infections in children and adolescents.

Monitoring the seroprevalence of SARS-CoV-2 in children and adolescents can provide valuable information for effective SARS-CoV-2 surveillance, and thus guide vaccination strategies. In this study, we quantified antibodies against the spike S1 domains of several SARS-CoV-2 variants (wild-type, Alpha, Delta, and Omicron variants) as well as endemic human coronaviruses (HCoVs) in 1,309 children and adolescents screened between December 2020 and March 2023. Their antibody binding profiles were compared with those of 22 pre-pandemic samples from children and adolescents using an in-house Luminex®-based Corona Array (CA). The primary objectives of this study were to (i) monitor SARS-CoV-2-specific antibodies in children and adolescents, (ii) evaluate whether the S1-specific antibody response can identify the infecting variant of concern (VoC), (iii) estimate the prevalence of silent infections, and (iv) test whether vaccination or infection with SARS-CoV-2 induce HCoV cross-reactive antibodies. Both SARS-CoV-2 infection and vaccination induced a robust antibody response against the S1 domain of WT and VoCs in children and adolescents. Antibodies specific for the S1 domain were able to distinguish between SARS-CoV-2 VoCs in infected children. The serologically identified VoC was typically the predominant VoC at the time of infection. Furthermore, our highly sensitive CA identified more silent SARS-CoV-2 infections than a commercial ELISA (12.1% vs. 6.3%, respectively), and provided insights into the infecting VoC. Seroconversion to endemic HCoVs occurred in early childhood, and vaccination or infection with SARS-CoV-2 did not induce HCoV S1 cross-reactive antibodies. In conclusion, the antibody response to the S1 domain of the spike protein of SARS-CoV-2 is highly specific, providing information about the infecting VoC and revealing clinically silent infections.

Impact of different energy sources on coagulation biomarkers and silent cerebral events in balloon-based ablation for atrial fibrillation.

Background: Different energy sources of balloon-based ablation for pulmonary vein isolation cause different kinds of endothelial damage and coagulation responses associated with thromboembolic risk. Objectives: The study sought to compare the impact of different balloon-based ablation, cryoballoon ablation (CBA) and laser balloon ablation (LBA), on coagulation/fibrinolysis biomarkers and silent cerebral events (SCEs) in paroxysmal atrial fibrillation. Methods: Paroxysmal atrial fibrillation patients who underwent pulmonary vein isolation using either CBA (n = 52) or LBA (n = 53) without radiofrequency touch-up ablation were eligible. Time course (day 0 [before ablation], day 1, day 2, and day 28) of myocardial enzymes and inflammatory and coagulation/fibrinolysis biomarkers was evaluated during the perioperative period. Brain magnetic resonance imaging was performed within 2 days after the procedure to evaluate SCEs. Results: There was no difference in patient characteristics between CBA and LBA.CBA had greater myocardial injury (troponin I and creatine kinase-MB) and lower inflammatory reaction (white blood cell count and neutrophil/lymphocyte ratio) than LBA. The coagulation biomarkers maximally increased by day 2 and then decreased in both groups. In day 28, the serum prothrombin fragment 1+2 and D-dimer levels in LBA were significantly higher than the values in CBA. The fibrinolysis biomarker (plasmin-α2 plasmin inhibitor complex) did not increase after the procedure in either group. The incidence of SCEs was comparable between CBA and LBA (11% vs 15%; P = .591). No thromboembolic event was observed. Conclusion: CBA and LBA had different effects on myocardial injury, inflammatory reaction, and coagulation activity but did not affect the incidence of thromboembolic events. LBA had significantly higher coagulation activity in day 28 and may require more careful postprocedural anticoagulation than CBA.

Development of an Innovative Pupillometer Able to Selectively Stimulate the Eye's Fundus Photoreceptor Cells.

Recent advancements in clinical research have identified the need to combine pupillometry with a selective stimulation of the eye's photoreceptor cell types to broaden retinal and neuroretinal health assessment opportunities. Our thorough analysis of the literature revealed the technological gaps that currently restrict and hinder the effective utilization of a method acknowledged to hold great potential. The available devices do not adequately stimulate the photoreceptor types with enough contrast and do not guarantee seamless device function integration, which would enable advanced data analysis. RetinaWISE is an advanced silencing pupillometry device that addresses these deficiencies. It combines a Maxwellian optical arrangement with advanced retinal stimulation, allowing for calibrated standard measurements to generate advanced and consistent results across multiple sites. The device holds a Class 1 CE marking under EU regulation 2017/745, thus facilitating clinical research progress.

Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors.

Elimination of the binding of immunoglobulin Fc to Fc gamma receptors is highly desirable for the avoidance of unwanted inflammatory responses to therapeutic antibodies and fusion proteins. Many different approaches have been used in the clinic, but they have not been systematically compared. We have now produced a matched set of anti-CD20 antibodies with different Fc subclasses and variants and compared their activity for binding to C1q, Fc-gamma receptors and in cell-based assays. Most of the variants still have significant levels of activity in one or more of these assays and many of them have impaired temperature stability compared with the corresponding wild-type antibody.

Angiographically silent macular retinoschisis and vitreomacular traction in a patient with same - side Duane retraction syndrome.

Introduction: To report the unusual fundus features of a case with unilateral Duane retraction syndrome (DRS) with same-side extensive macular retinoschisis. Methods: A 75-year-old woman was diagnosed to have DRS type 3 and several multimodal fundus imaging modalities were performed. Results: There was limited abduction and adduction, globe retraction, and narrowing of the palpebral fissure on the adduction of the left eye without a compensatory face turn. Concurrently, spectral domain optical coherence tomography revealed marked macular retinoschisis and severe vitreoretinal traction without any evidence of dye leakage or pooling on fluorescein angiography in the left eye. Discussion: Various ocular abnormalities may rarely accompany DRS and the present case is the first reported case of most likely coincidental macular retinoschisis in association with DRS.

Clinical characterization of the silent chronic pancreatitis patient: a single-center retrospective cohort study.

Background: Silent chronic pancreatitis (SCP) is a poorly understood subtype of chronic pancreatitis (CP) in which individuals describe little to no abdominal pain. The risk factors for SCP are unclear, and it is unknown whether there are differences in the clinical outcomes of SCP and painful CP. We set out to investigate the clinical features of SCP and the risk factors associated with this condition. Methods: This was a retrospective cohort study using data from the Penn State Milton S. Hershey Medical Center from 2019-2022. Two patient groups, the SCP cohort (23 patients) and the painful CP cohort (94 patients), were identified from consecutive clinics. Descriptive statistics and bivariate and logistic regression analyses (including variables with a P-value <0.1 on bivariate analysis) were performed to characterize the study cohort and to evaluate for independent associations with SCP. Results: SCP was independently associated with older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.01-1.11; P=0.03) and male sex (OR 5.38, 95%CI 1.38-20.96; P=0.02), and inversely associated with current opioid use (OR 0.18, 95%CI 0.03-0.96; P=0.04). There was no association between SCP and current pain medication or diabetes mellitus. Conclusions: Our study adds to the growing body of literature describing SCP as a condition associated with older age and male sex, and inversely associated with opioid use. We found no greater association of diabetes with SCP. Future larger longitudinal studies are needed to gain a better understanding of SCP.

Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study.

BACKGROUND: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue. METHODS: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume. RESULTS: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume). CONCLUSIONS: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

Satisfaction of patients with frozen shoulder following silent manipulation: a prospective observation study.

Silent manipulation is a procedure for frozen shoulders that involves manipulating the shoulder while the patient is awake by performing C5, C6, and C7 cervical nerve root block under ultrasound guidance. This retrospective study, conducted at Yokohama City University Hospital, aimed to evaluate the clinical outcomes of silent manipulation and assess whether the experience level of the practitioner influenced treatment efficacy. Between October 2020 and January 2022, 53 patients who met the inclusion criteria underwent silent manipulation for frozen shoulder. The procedure was performed by either an experienced or a less experienced practitioner, and the patients were followed-up for up to 1 year post-treatment. Silent manipulation resulted in significant improvements in shoulder range of motion, as measured by forward flexion, abduction, external rotation, and hand-behind-back, as well as in patient-reported outcomes, including disabilities of the arm, shoulder, and hand and Shoulder 36 scores. These improvements were observed 1 week, 3 months, and 1 year after silent manipulation, indicating the short-term efficacy of the procedure. Furthermore, this study revealed that the practitioners' level of experience played a significant role in the outcomes. The experienced doctor achieved better 1st external rotation and belt tying outcomes, as well as Shoulder 36 pain, muscle strength, and activities of daily living domain scores. This suggests that technical expertise in silent manipulation is crucial to achieve optimal outcomes. Silent manipulation offers an effective therapeutic approach for frozen shoulder, leading to significant improvements in range of motion and patient satisfaction. Practitioner expertise is a vital factor in treatment success, emphasizing the importance of skilled professionals in the performance of this procedure.