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We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.
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Mapeamento Encefálico , Idioma , Lobo Temporal , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , População do Leste Asiático , Estimulação Elétrica , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Japão , Imageamento por Ressonância Magnética , Lobo Temporal/fisiologiaRESUMO
BACKGROUND: Patient-rated motor symptoms (PRMS) and clinician-rated motor symptoms (CRMS) often differ in Parkinson's disease (PD). OBJECTIVE: Our goal was to investigate the determinants and clinical implications of PRMS compared with CRMS in PD. METHODS: This retrospective, observational cohort study analyzed the cross-sectional associations and longitudinal impacts of PRMS as assessed by the Movement Disorders Society-sponsored Unified PD Rating Scale (MDS-UPDRS) part 2, while controlling for CRMS measured by MDS-UPDRS part 3. Longitudinal analyses used Cox proportional hazards models and multiple linear mixed-effects random intercepts/slope models, adjusting for many clinical predictors. We conducted propensity score matching (PSM) to reinforce our analyses' robustness and surface-based morphometry to investigate neural correlates. RESULTS: We enrolled 442 patients with early-stage PD. At baseline, regardless of CRMS, PRMS were associated with the severity of postural instability and gait disturbance (PIGD). Notably, PRMS independently and more accurately predicted faster long-term deterioration in motor function than CRMS (Hoehn and Yahr 4, adjusted hazard ratio per +1 point = 1.19 [95% confidence intervals, 1.08-1.32]), particularly in PIGD (PIGD subscore, ß-interaction = 0.052 [95% confidence intervals, 0.018-0.086]). PSM confirmed these findings' robustness. Surface-based morphometry suggested that enhanced sensory processing was distinctively associated with PRMS. CONCLUSIONS: In early-stage PD, PRMS weighed different aspects of symptoms and more effectively predicted motor deterioration compared to CRMS, with distinctive brain structural characteristics. The superior sensitivity of PRMS to subtle declines in drug-refractory symptoms like PIGD likely underlie our results, highlighting the importance of understanding the differential clinical implications of PRMS to prevent long-term motor deterioration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Basic Science is crucial for the advancement of clinical care for Movement Disorders. Here, we provide brief updates on how basic science is important for understanding disease mechanisms, disease prevention, disease diagnosis, development of novel therapies and to establish the basis for personalized medicine. We conclude the viewpoint by a call to action to further improve interactions between clinician and basic scientists. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Transtornos dos Movimentos , Humanos , Transtornos dos Movimentos/terapia , Pesquisa Translacional Biomédica/métodos , Medicina de Precisão/métodosRESUMO
OBJECTIVE: Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. METHODS: This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. RESULTS: A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8-8.9] vs. 4.9 [95% CI = 4.3-5.5] points; p < .001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2-9.3] vs. 6.4 [95% CI = 4.5-8.3] points; p = .008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3-9.2] vs. 5.4 [95% CI = 3.5-7.3] points; p = .004). Multivariate analysis revealed areas under the curve of .843, .825, and .881 for Parameters 1, 2, and 3, respectively. SIGNIFICANCE: SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy.
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Seleção de Pacientes , Humanos , Feminino , Masculino , Adulto , Estudos Retrospectivos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Eletroencefalografia/métodos , Epilepsia/cirurgia , Epilepsia/diagnóstico , Resultado do Tratamento , Criança , Estudos de Coortes , Procedimentos Neurocirúrgicos/métodos , Epilepsias Parciais/cirurgia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnósticoRESUMO
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and other brain regions. A key pathological feature of PD is the abnormal accumulation of α-synuclein protein within affected neurons, manifesting as Lewy bodies and Lewy neurites. Despite extensive research efforts spanning several decades, the underlying mechanisms of PD and disease-modifying therapies remain elusive. This review provides an overview of current trends in basic research on PD. Initially, it discusses the involvement of mitochondrial dysfunction in the pathogenesis of PD, followed by insights into the role of lysosomal dysfunction and disruptions in the vesicular transport system. Additionally, it delves into the pathological and physiological roles of α-synuclein, a crucial protein associated with PD pathophysiology. Overall, the purpose of this review is to comprehend the current state of elucidating the intricate mechanisms underlying PD and to outline future directions in understanding this disease.
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Lisossomos , Mitocôndrias , Doença de Parkinson , alfa-Sinucleína , alfa-Sinucleína/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , AnimaisRESUMO
PURPOSE: To assess whether early postoperative stiffness predicts long-term stiffness and its relationship with repair integrity in patients who undergo arthroscopic rotator cuff repair (ARCR). METHODS: This was a single-center retrospective study; 427 patients undergoing primary ARCR by a board-certified orthopaedic surgeon over 4 years were considered. Patients with at least 1 year of follow-up were categorized into stiff and non-stiff groups based on their range of motion (ROM) at 3 months' postoperatively. Stiffness was defined as passive forward flexion <120°, external rotation <30°, or internal rotation below L3. We evaluated clinical outcomes using demographics, ROM, Constant Shoulder (CS) score, University of California, Los Angeles (UCLA) score, and visual analog scale (VAS) for pain preoperatively and at 3, 6, and 12 months' postoperatively. Stiffness, retear rates, and tendon integrity were assessed via magnetic resonance imaging at 12 months. RESULTS: Of 155 patients meeting the inclusion criteria, 68 (43.9%) were stiff, and 87 (56.1%) were non-stiff. The stiff group had significantly lower preoperative CS and UCLA scores (P = .013/.014) and greater VAS score (P = .034). At 3 months, this group showed lower ROM and functional scores (P < .001), persisting at 6 and 12 months (except internal rotation) (P < .001). Their 12-month VAS score was greater (P = .024). Postoperative stiffness occurred in 10.3% of the stiff group and 2.3% of the non-stiff group (P = .035). The 12-month retear rate was 5.9% in the stiff group and 17.2% in the non-stiff group (P = .032). Minimal clinically important difference analysis indicated ROM changes but limited functional score changes in the 2 groups. CONCLUSIONS: This study showed that early postoperative shoulder stiffness correlates with lower preoperative functional scores and greater pain levels. Shoulder stiffness at 3 months' post-ARCR predicts 12-month shoulder stiffness but indicates better tendon integrity. While early stiffness is linked to lower functional scores and more pain, its long-term clinical impact seems limited. LEVEL OF EVIDENCE: Level III, retrospective comparison study.
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Artroscopia , Amplitude de Movimento Articular , Lesões do Manguito Rotador , Manguito Rotador , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Idoso , Cicatrização , Resultado do Tratamento , Período Pós-OperatórioRESUMO
BACKGROUND: Bone marrow edema (BME) in the acromioclavicular joint (ACj) may occur after arthroscopic rotator cuff repair (ARCR), resulting in persistent postoperative ACj pain. We investigated the incidence and clinical characteristics of BME in ACj after ARCR. METHODS: Patients exhibiting ACj-related symptoms prior to ARCR surgery, no BME in the ACj on MRI, and an ability to undergo 2-year postoperative physical and MRI examinations of the ACj were included. Patients who underwent distal clavicle resection or osteophyte resection below the ACj and those unable to achieve primary repair of the rotator cuff were excluded. MRI evaluation was performed preoperatively and at 3, 6, 12, and 24 months postoperatively. Patients who showed BME in ACj on fat-suppressed T2 MRI at 24 months postoperatively were classified into the BME + group, and those with no BME were classified into the BME- group. Patient background, operation time, Japanese Orthopedic Association (JOA) score, re-tear rate, ACj tenderness, and cross-body adduction test were compared between groups. In addition, we examined the time of occurrence of BME. RESULTS: A total of 345 ARCRs were performed during the study period. After the exclusion of 114 shoulders, the remaining 231 shoulders were included in this study. There were 208 cases in the BME- group and 23 cases in the BME + group. The incidence of BME was 9.96 %. Although the JOA scores of both groups showed a significant improvement postoperatively compared to preoperatively, there was no significant difference between the two groups. In terms of re-tear, there was 1 case in the BME + group and 7 in the BME- group. Positive ACj tenderness and cross-body adduction test were significantly higher in the BME + group (P < 0.001). BME occurred in 6 cases at 3 months, 9 cases at 6 months, and 8 cases at 1 year postoperatively. None of the patients developed BME at more than 1 year postoperatively. BME was observed on MRI in all cases at 2 years postoperatively. CONCLUSIONS: The rate of occurrence of BME in the ACj after ARCR was 9.96 %. Patients with BME were significantly more likely to have ACj tenderness and positive cross-body adduction test. BME in the ACj often occurs within 6 months to 1 year after ARCR of small-to-medium rotator cuff tears, suggesting a relationship with postoperative functional improvement of the shoulder joint. The ACj should be considered as a potential site of persistent pain after ARCR for small-to-medium rotator cuff tears.
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BACKGROUND: Carbon-ion radiotherapy(CIRT)has an advantage over conventional radiotherapy by its dose distribution and biological effect for locally advanced unresectable pancreatic cancer(UR-PC). Conversion surgery(CS)might be attempted for UR-PC with favorable response by chemotherapy and radiotherapy. CASE PRESENTATION: A 67-year-old female who have a history of distal gastrectomy. CT scan revealed locally advanced UR-PC with invasion to celiac artery, 60 mm in size. Systemic chemotherapy with gemcitabine and nab-paclitaxel was continued for 15 months, showing decrease of tumor markers and radiological shrinkage of the tumor. The patient was referred to our hospital for surgical consultation. Since there was no metastasis in staging laparoscopy, CIRT with gemcitabine was administered for 3 weeks. After completion of CIRT, distal pancreatectomy with celiac axis resection and total remnant gastrectomy for direct invasion of the tumor was performed as CS, resulting R0 resection. Her postoperative course was uneventful with 17 days of hospital stay. DISCUSSION: CS after CIRT was safely performed. Clinical trial of total neoadjuvant therapy with systemic chemotherapy, CIRT, followed by CS for locally advanced CIRT is ongoing in our hospital. CIRT could be an effective treatment in locally advanced UR-PC in the context of multi-modal treatment including CS.
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Gencitabina , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pâncreas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Carbono/uso terapêuticoRESUMO
There is an estimated 35-45% loss of striatal dopamine at the time of diagnosis of Parkinson's disease (PD), and cases clinically diagnosed in the early stages may already be pathologically in advanced stages. Recent large-scale clinical trials of disease-modifying therapies (DMT) also suggest the necessity of targeting patients at earlier stages of the disease. From this perspective, the prodromal phase of PD is currently the focus of attention, emphasizing the need for a prodromal mouse model that accurately reflects the pathophysiology, along with early biomarkers. To establish prodromal animal model of PD with high face validity that reflects the disease state, the model must possess high construct validity that accurately incorporates clinical and pathological features in the prodromal phase. Furthermore, as a preclinical model of DMT, the model must possess high predictive validity to accurately evaluate the response to intervention. This review provides an overview of animal models which reflect the characteristics of prodromal PD, including alpha-synuclein (aS) accumulation and associated early non-motor symptoms, with a focus on the aS propagation model and genetic model. In addition, we discuss the challenges associated with these models. The genetic model often fails to induce motor symptoms, while aS propagation models skip the crucial step of initial aS aggregate formation, thereby not fully replicating the entire natural course of the disease. Identifying factors that induce the transition from prodromal to symptomatic phase is important as a preclinical model for DMT to prevent or delay the onset of the disease.
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Background: This study aimed to investigate risk factors for recurrence of frozen shoulder after shoulder manipulation under ultrasound-guided cervical nerve root block (MUC). Methods: We retrospectively reviewed 135 frozen shoulders in 121 patients who underwent MUC. We defined frozen shoulder as a limited shoulder range of motion (ROM) (passive forward flexion <120°, external rotation <30°, or internal rotation lower than L3). Patients fulfilling any one criteria were considered to have frozen shoulder. If patients continued to have severe pain and limited ROM at 3 months after MUC, we defined as recurrence of frozen shoulder and they were offered a further MUC or arthroscopic capsular release (ACR). We compared the ROM, Constant Shoulder (CS) score, and University of California, Los Angeles score before and 3 months after MUC between patients with the successful of MUC group (Success group) with those recurrence of frozen shoulder who required a further MUC or ACR group (Recurrence group). Multiple logistic regression analysis was used to identify risk factors for recurrence of frozen shoulder after MUC. Results: Patients who underwent MUC were retrospectively enrolled and divided into: the successful of MUC group (Success group, n = 112) and required a further MUC or ACR group (Recurrence group, n = 9). The Recurrence group had significantly lower external rotation and CS score before MUC than those in the Success group (P < .05). The Recurrence group showed significantly inferior all ROM and functional scores 3 months after MUC (P < .05). The levels of blood glucose and hemoglobin A1c both before and 3 months after MUC in the Recurrence group showed inferior compared with those of Success group. The difference, although not statistically significant, trended towards significance (before MUC/3 months after MUC; the glucose levels P = .06/.06, the hemoglobin A1c levels P = .07/.09, respectively). The visual analog scale pain score (at rest, during activity, at night) both before and 3 months after MUC in the Recurrence group showed significantly higher scores compared with those of Success group (P < .05). Multiple logistic regression analysis revealed that lower CS score before MUC was independent risk factor for recurrence of frozen shoulder after MUC. Conclusion: The overall incidence of recurrence of frozen shoulder after MUC was 7.4%. The lower CS score before MUC was an independent risk factor for recurrence of frozen shoulder after MUC. Moreover, patients in the Recurrence group tended to have poorly controlled diabetes and higher visual analog scale pain score both before and 3 months after MUC.
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Controlling the ion velocity in an ion sheath by applying an alternating current (AC) voltage to an electrode and/or a substrate is critical in plasma material processes. To externally control the velocity distribution of incident ions on a substrate, the application of tailored-waveform AC voltages instead of sinusoidal voltages has garnered interest in recent years. In this study, to investigate temporal changes in ion-velocity distributions, we developed a time-resolved laser-induced fluorescence spectroscopy (LIF) system using a continuous-wave diode laser as an excitation-laser source. A time-resolved LIF system entails the capture of temporally continuous and spectrally discrete LIF spectra during an AC voltage cycle. By measuring temporal changes in the LIF signal intensity at various excitation-laser wavelengths, the argon-ion velocity distribution near the electrode following the AC voltage can be characterized. The results of applying sinusoidal, triangular, and rectangular bias waveforms indicate that the LIF measurement scheme proposed herein can be used to investigate the dynamic behavior of ion-velocity distributions controlled by tailored-waveform AC voltages.
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We aimed to investigate the relationship between superoxide dismutase 2-related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress. Patients were divided into two groups based on the superoxide dismutase 2 redox index. Spinal alignment, clinical skeletal muscle parameters, and succinic dehydrogenase (SDH) mean grayscale value were compared between the groups, with analyzes for both sexes. Multiple regression analyzes were used to adjust for the confounding effect of age on variables showing a significant difference between the two groups. Thirty-five patients with lumbar degenerative diseases were included. No significant differences were observed between the two groups for any of the parameters in males; however, females with a higher superoxide dismutase 2 redox index had greater lumbar lordosis, lower grip strength, and higher SDH mean grayscale value than those with a lower index. Multiple regression analyzes revealed that the superoxide dismutase 2 redox index was an independent explanatory variable for lumbar lordosis, grip strength, and SDH mean grayscale value in female patients. In conclusion, superoxide dismutase 2-related oxidative stress in the paraspinal muscles was associated with mitochondrial dysfunction and decreased grip strength in female lumbar degenerative disease patients.
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The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.
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Paraganglioma , Neoplasias Retroperitoneais , Humanos , Feminino , Adulto , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Paraganglioma/cirurgia , Paraganglioma Extrassuprarrenal/cirurgia , Paraganglioma Extrassuprarrenal/patologia , Normetanefrina/urina , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Doenças do Nervo Vago/cirurgia , Embolização Terapêutica , Norepinefrina/sangue , Nervo VagoRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that has been reported to be affected by inflammatory cells, such as microglia and macrophages, through the concept of non-cell autonomous neuronal death. Resident microglia in the human brain and monocyte-derived macrophages (MoDM) infiltrating in tissues are difficult to distinguish. Therefore, the effects of microglia and MoDMs in ALS remain poorly understood. This study aimed to investigate the role of resident microglia and MoDMs in the pathogenesis of ALS using postmortem brain and spinal cord samples. The samples used for immunohistochemical analysis included 11 cases of sporadic ALS and 11 age-matched controls. We stained the cells with TMEM119 to detect resident microglia and CCR2 to detect MoDMs. In ALS cases, TMEM119-immunopositive resident microglia were abundant in the motor cortex and subcortical white matter (SWM) of the motor area, whereas CCR2-immunopositive MoDM was similar to control cases. In addition, the mean density of CD68-immunopositive cells in the SWM significantly correlated with the mean density of pTDP-43-positive GCIs. These results suggest that resident microglial activation plays an important role in the cerebral pathogenesis of ALS and may provide novel therapeutic strategies to target excessive activation of resident microglia in ALS.
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Esclerose Lateral Amiotrófica , Encéfalo , Proteínas de Membrana , Microglia , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Microglia/metabolismo , Microglia/patologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Proteínas de Membrana/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Receptores CCR2/metabolismo , Substância Branca/patologia , Substância Branca/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Idoso de 80 Anos ou maisRESUMO
'No evidence of disease activity (NEDA)', judged by clinical and radiological findings, is a therapeutic goal in patients with multiple sclerosis (MS). It is, however, unclear if distinct biological mechanisms contribute to the maintenance of NEDA. To clarify the immunological background of long-term disease stability defined by NEDA, circulating immune cell subsets in patients with relapsing-remitting MS (RRMS) were analyzed using flow cytometry. Patients showing long-term NEDA (n = 31) had significantly higher frequencies of non-classical monocytes (NCMs) (6.1% vs 1.4%) and activated regulatory T cells (Tregs; 2.1% vs 1.6%) than those with evidence of disease activity (n = 8). The NCM frequency and NCMs to classical monocytes ratio (NCM/CM) positively correlated with activated Treg frequency and duration of NEDA. Co-culture assays demonstrated that NCMs could increase the frequency of activated Tregs and the expression of PD-L1, contributing to development of Tregs, was particularly high in NCMs from patients with NEDA. Collectively, NCMs contribute to stable remission in patients with RRMS, possibly by increasing activated Treg frequency. In addition, the NCM frequency and NCM/CM ratio had high predictive values for disease stability (AUC = 0.97 and 0.94, respectively), suggesting these markers are potential predictors of a long-term NEDA status in RRMS.
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Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.
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Síndrome HELLP , Sulfato de Magnésio , Adulto , Feminino , Humanos , Gravidez , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Síndrome HELLP/diagnóstico , Síndrome HELLP/terapia , Sulfato de Magnésio/uso terapêutico , Sulfato de Magnésio/administração & dosagem , Segundo Trimestre da GravidezRESUMO
Synucleinopathies refer to a group of disorders characterized by SNCA/α-synuclein (α-Syn)-containing cytoplasmic inclusions and neuronal cell loss in the nervous system including the cortex, a common feature being cognitive impairment. Still, the molecular pathogenesis of cognitive decline remains poorly understood, hampering the development of effective treatments. Here, we generated induced pluripotent stem cells (iPSCs) derived from familial Parkinson's disease (PD) patients carrying SNCA A53T mutation, differentiating them into cortical neurons by a direct conversion method. Patient iPSCs-derived cortical neurons harboring mutant α-Syn exhibited increased α-Syn-positive aggregates, shorter neurites, and time-dependent vulnerability. Furthermore, RNA-sequencing analysis, followed by biochemical validation, identified the activation of the ERK1/2 and JNK cascades in cortical neurons with SNCA A53T mutation. This result was consistent with a reverted phenotype of neuronal death in cortical neurons when treated with ERK1/2 and JNK inhibitors, respectively. Our findings emphasize the role of ERK1/2 and JNK cascades in the vulnerability of cortical neurons in synucleinopathies, and they could pave the way toward therapeutic advancements for synucleinopathies.
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Sinucleinopatias , alfa-Sinucleína , Humanos , Sistema de Sinalização das MAP Quinases , Neurônios , NeuritosRESUMO
Ono K, Takahashi R, Morita K, Ara Y, Abe S, Ito S, Uno S, Abe M, Shirasaka T. Can AI predict walking independence in patients with stroke upon admission to a recovery-phase rehabilitation ward? Jpn J Compr Rehabil Sci 2024; 15: 1-7. Objective: This study aimed to develop a prediction model for walking independence in patients with stroke in the recovery phase at the time of hospital discharge using Prediction One, an artificial intelligence (AI)-based predictive analysis tool, and to examine its utility. Methods: Prediction One was used to develop a prediction model for walking independence for 280 patients with stroke admitted to a rehabilitation ward-based on physical and mental function information at admission. In 134 patients with stroke hospitalized during different periods, accuracy was confirmed by calculating the correct response rate, sensitivity, specificity, and positive and negative predictive values based on the results of AI-based predictions and actual results. Results: The prediction accuracy (area under the curve, AUC) of the proposed model was 91.7%. The correct response rate was 79.9%, sensitivity was 95.7%, specificity was 62.5%, positive predictive value was 73.6%, and negative predictive value was 93.5%. Conclusion: The accuracy of the prediction model developed in this study is not inferior to that of previous studies, and the simplicity of the model makes it highly practical.
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OBJECTIVES: To investigate factors associated with symptomatic urinary tract infection (sUTI) in persons with chronic spinal cord lesion (SCL) who were using single-use catheters for intermittent self-catheterization (ISC). METHODS: Among respondents to an internet survey on the burden of illness on persons with SCL who were considered to be able to perform ISC, 111 persons using single-use catheters were included to examine factors associated with self-reported sUTI by univariate as well as multivariable analysis. RESULTS: The incidence of sUTI was significantly higher in males than in females (56.9% vs. 31.6%, p = .011), persons with stocks of antibiotics than those without it (82.9% vs. 28.6%, p < .011), and persons with more frequent bleeding during catheterization than those with less frequent bleeding (100% vs. 46.5%, p = .036). The incidence did not significantly differ between respective groups when various variables were evaluated by other characteristics of the participants, adherence to ISC procedures, and complications. On multivariable analysis, male gender and stocks of antibiotics were significant independent factors for sUTI. CONCLUSIONS: Male gender and stocks of antibiotics were associated with sUTI in persons with SCL who were performing ISC with single-use catheters.