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Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute to disease pathology in peripheral tissues1-4. Outside the marrow, these clones are potentially exposed to a variety of tissue-specific mutational processes, although the consequences of this are unclear. Here we investigate the development of blastic plasmacytoid dendritic cell neoplasm (BPDCN)-an unusual form of acute leukaemia that often presents with malignant cells isolated to the skin5. Using tumour phylogenomics and single-cell transcriptomics with genotyping, we find that BPDCN arises from clonal (premalignant) haematopoietic precursors in the bone marrow. We observe that BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet (UV) radiation. A reconstruction of tumour phylogenies reveals that UV damage can precede the acquisition of alterations associated with malignant transformation, implicating sun exposure of plasmacytoid dendritic cells or committed precursors during BPDCN pathogenesis. Functionally, we find that loss-of-function mutations in Tet2, the most common premalignant alteration in BPDCN, confer resistance to UV-induced cell death in plasmacytoid, but not conventional, dendritic cells, suggesting a context-dependent tumour-suppressive role for TET2. These findings demonstrate how tissue-specific environmental exposures at distant anatomical sites can shape the evolution of premalignant clones to disseminated cancer.
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Transformação Celular Neoplásica , Células Dendríticas , Leucemia Mieloide Aguda , Neoplasias Cutâneas , Pele , Raios Ultravioleta , Humanos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células da Medula Óssea/efeitos da radiação , Morte Celular/efeitos da radiação , Linhagem da Célula/genética , Linhagem da Célula/efeitos da radiação , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Transformação Celular Neoplásica/efeitos da radiação , Células Clonais/metabolismo , Células Clonais/patologia , Células Clonais/efeitos da radiação , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Células Dendríticas/efeitos da radiação , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Mutação/efeitos da radiação , Especificidade de Órgãos , Análise da Expressão Gênica de Célula Única , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Pele/patologia , Pele/efeitos da radiaçãoRESUMO
INTRODUCTION/AIMS: Redundant nerve roots (RNRs) are abnormally elongated and tortuous nerve roots that develop secondary to degenerative spinal stenosis. RNRs have been associated with poorer clinical outcomes after decompression surgery; however, studies on their clinical characteristics are limited. This study aimed to investigate the association between RNRs and denervation potentials, that is, abnormal spontaneous activity (ASA), on electromyography. METHODS: We retrospectively reviewed data of patients who underwent an electrodiagnostic study of the lower extremities between January 2020 and March 2023. Of these, patients with lumbar central spinal stenosis, as seen on magnetic resonance imaging, were included. We analyzed clinical and imaging data, including presence of ASA, and compared them according to the presence of RNRs. Multivariable logistic regression analysis was employed to identify factors associated with development of ASA. RESULTS: Among the 2003 patients screened, 193 were included in the study. RNRs were associated with advanced age (p < .001), longer symptom duration (p = .009), smaller cross-sectional area of the dural sac at the stenotic level (p < .001), and higher frequency of ASA (p < .001). Higher probability of ASA was correlated with greater RNR severity (p < .001). In the multivariable logistic regression analysis, ASA occurrence was associated with smaller cross-sectional area, multiple stenotic sites, and severe-grade RNRs. DISCUSSION: The presence of RNRs, particularly severe-grade RNRs, was identified as a significant risk factor for the development of ASA on electromyography. This finding may aid physicians in estimating the prognosis of patients with central spinal stenosis.
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Eletromiografia , Vértebras Lombares , Imageamento por Ressonância Magnética , Raízes Nervosas Espinhais , Estenose Espinal , Humanos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Feminino , Masculino , Raízes Nervosas Espinhais/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Denervação/métodos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). BACKGROUND: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. METHODS: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. RESULTS: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). CONCLUSION: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.
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Placa de Sangue Epidural , Hipotensão Intracraniana , Imageamento por Ressonância Magnética , Recidiva , Humanos , Hipotensão Intracraniana/terapia , Hipotensão Intracraniana/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Estudos de Casos e Controles , Aprendizado de MáquinaRESUMO
The Toba volcanic system in Indonesia has produced two of the largest eruptions (>2,000 km3 dense-rock equivalent [DRE] each) on Earth since the Quaternary. U-Pb crystallization ages of zircon span a period of â¼600 ky before each eruptive event, and in the run-up to each eruption, the mean and variance of the zircons' U content decrease. To quantify the process of accumulation of eruptible magma underneath the Toba caldera, we integrated these observations with thermal and geochemical modeling. We show that caldera-forming eruptions at Toba are the result of progressive thermal maturation of the upper crustal magma reservoir, which grows and chemically homogenizes, by sustained magma influx at average volumetric rates between 0.008 and 0.01 km3/y over the past 2.2 My. Protracted thermal pulses related to magma-recharge events prime the system for eruption without necessarily requiring an increased magma-recharge rate before the two supereruptions. If the rate of magma input was maintained since the last supereruption of Toba at 75 ka, eruptible magma is currently accumulating at a minimum rate of â¼4.2 km3 per millennium, and the current estimate of the total volume of potentially eruptible magma available today is a minimum of â¼315 km3 Our approach to evaluate magma flux and the rate of eruptible magma accumulation is applicable to other volcanic systems capable of producing supereruptions and thereby could help in assessing the potential of active volcanic systems to feed supereruptions.
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Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.
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Doença de Parkinson/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/fisiologia , Substância Negra/metabolismo , Animais , Comportamento Animal , Transplante de Células , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Células-Tronco Embrionárias/fisiologia , Edição de Genes , Predisposição Genética para Doença , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Células-Tronco Pluripotentes Induzidas/transplante , Camundongos , Camundongos Knockout , Mutação , Células-Tronco Neurais/fisiologia , Células-Tronco Neurais/transplante , Doença de Parkinson/genética , Ratos , Transplante de Células-TroncoRESUMO
Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Testes GenéticosRESUMO
BACKGROUND: There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct-to-consumer testing. OBJECTIVES: The aim is to determine the international landscape of genetic testing in PD to inform future worldwide recommendations. METHODS: A web-based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership. RESULTS: Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region-dependent differences in access to and availability of testing and counseling were most notable in Africa. High-income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan-American and Asian countries. CONCLUSIONS: This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Testes Genéticos , AconselhamentoRESUMO
OBJECTIVES: To develop and validate a nomogram based on MRI features for predicting iNPH. METHODS: Patients aged ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning-based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated. RESULTS: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample. CONCLUSION: A brain morphometry-based nomogram including high-convexity tightness, callosal angle < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH. KEY POINTS: ⢠The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. ⢠The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery.
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Doença de Alzheimer , Hidrocefalia de Pressão Normal , Masculino , Humanos , Idoso , Nomogramas , Estudos Retrospectivos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition. METHODS: This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences. RESULTS: Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls. CONCLUSIONS: Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed.
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Site-specific measurements of the crop yield during harvesting are essential for successfully implementing precision management techniques. This study aimed to estimate the mass of radish tubers using the impact principle under simulated vibration and sloped-field harvesting conditions with a laboratory test bench. These conditions included the conveyor speed (CS), impact plate layout (IP), falling height onto the impact plate (FH), the plate angle relative to the horizontal (PH), the field slope, and the vibration of the harvesting machine. Two layouts of impact-type sensors were fabricated and tested, one with a single load cell (SL) and the other with two load cells (DL). An adjustable slope platform and a vibration table equipped with vibration blades were utilized to simulate the slope and vibration effects, respectively. Calibrations were conducted to verify the accuracy of the sensor outputs, processed with the finite impulse response and moving average filters. Radish mass was estimated using an asymmetrically trimmed mean method. The relative percentage error (RE), standard error (SE), coefficient of determination (R²), and analysis of variance (ANOVA) were used to assess the impact plate performance. The results indicated that the SE for both impact plates was less than 4 g in the absence of vibration and slope conditions. The R2 for the single and double impact plates ranged from 0.58 to 0.89 and 0.69 to 0.81, respectively. The FH had no significant impact, while the PH significantly affected the mass measurements for both impact plates. On the other hand, the CS significantly affected the plate performance, except for the double-load-cell impact plate. Both vibration and slope affected the mass measurements, with RE values of 9.89% and 13.92%, respectively. The RE for filtered radish signals was reduced from 9.13% to 5.42%. The tests demonstrated the feasibility of utilizing the impact principle to assess the mass of radishes, opening up possibilities for the development of yield-monitoring systems for crops harvested in a similar manner.
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Raphanus , Vibração , Modalidades de Fisioterapia , Placas ÓsseasRESUMO
PURPOSE: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). DESIGN: A randomized-controlled design. METHODS: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. FINDINGS: Physical activity and non-motor symptoms improved more in the intervention group than in the control group. CONCLUSION: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. CLINICAL EVIDENCE: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.
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Doença de Parkinson , Autogestão , Humanos , Terapia por Exercício , Estudos de Viabilidade , Vida Independente , Doença de Parkinson/terapia , Doença de Parkinson/diagnósticoRESUMO
INTRODUCTION: We aimed to investigate the correlation between spinal sarcopenia, spinal sagittal balance (SSB), and spinal function in older women living in rural areas versus those of the older urban women in our previous study. METHODS: Twenty-five older rural-dwelling women aged more than 70 years were compared with 24 older urban-dwelling women from our previous study. Demographic variables, conventional and spinal sarcopenic indices, variable functional outcome parameters, occupational state, and exercise participation rate were evaluated. We also measured the isometric back extensor strength, radiological parameters for SSB on whole-spine radiography, and volumetric parameters of the lumbar extensor muscle on computed tomography. RESULTS: There were no significant intergroup differences in demographic variables or the prevalence of sarcopenia. Older women in rural areas had greater handgrip strength than those in urban areas (22.7±3.7 kg v 20.0±3.4 kg, p=0.010). However, their mean lumbar lordosis angle was lower (31.7±15.3° v 42.3±11.2°, p=0.012). Isometric back extensor strength was lower in rural women than in urban women. The vocational activity participation rate of rural women was significantly higher (84% v 12.5%, p<0.001), whereas their exercise participation rate was significantly lower (60% v 92%, p<0.001). CONCLUSION: Older women in rural areas had greater handgrip strength and vocational participation rates but lower back extensor strength and exercise participation rates. Therefore, more attention is needed for healthcare services to support their spinal health and exercise habits.
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Sarcopenia , Humanos , Feminino , Idoso , Sarcopenia/epidemiologia , Força da Mão/fisiologia , Região Lombossacral , Exercício FísicoRESUMO
BACKGROUND: Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. OBJECTIVE: The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). METHODS: We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). RESULTS: Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12-2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37-4.56], P = 0.003; P-difference with women = 0.029). CONCLUSIONS: Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Laticínios/efeitos adversos , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
BACKGROUND: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. OBJECTIVE: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction. METHODS: We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1. RESULTS: At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59-0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern. CONCLUSIONS: Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Humanos , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Fumar/genéticaRESUMO
Although digital image analysis methods that quantify histopathologic features have emerged, no validated quantitative methods are available to evaluate tendon injury. This study aimed to propose and validate a quantitative analysis method to identify the histopathologic features of tendon injuries. The histopathologic features of two Achilles tendon injury models (a partial full-thickness defect model and a collagenase injection model) using Sprague-Dawley rats were evaluated by semiquantitative grading and a quantitative analysis method using a digital pathology software at weeks 1 and 4 after tendon injury (six tendons per group at each time point). The outcome variables between tendon injury models and between time points were compared, and the correlation between semiquantitative scores and the results of the quantitative analysis was investigated. The proposed analysis method quantified the severity of the histopathological features after tendon injury. Quantitative analysis differentiated the cell morphology between tendon injury models and time points better than semiquantitative scoring. The results from quantitative measurements correlated significantly with the semiquantitative scores. The proposed quantitative method can be effective in evaluating the histopathology of tendon injuries.
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Tendão do Calcâneo , Traumatismos dos Tendões , Tendão do Calcâneo/patologia , Animais , Diferenciação Celular , Colagenases , Modelos Animais de Doenças , Ratos , Ratos Sprague-Dawley , Traumatismos dos Tendões/patologiaRESUMO
OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: ⢠Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. ⢠The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. ⢠Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.
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Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Imageamento por Ressonância Magnética/métodos , Transtornos Parkinsonianos/diagnóstico por imagem , Estudos Prospectivos , Substância Negra/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , TropanosRESUMO
BACKGROUND: Although deep brain stimulation (DBS) is a relatively safe and effective surgery compared with ablative surgeries, intracerebral hemorrhage (ICH) is a serious complication during DBS that could result in a fatal prognosis. We retrospectively investigated whether ICH incidence differed between patients who underwent DBS in the subthalamic nucleus (STN) and in the globus pallidus interna (GPi), together with previously identified risk factors for ICH. METHODS: We retrospectively reviewed the medical records of 275 patients (527 DBS targets) who received DBS for Parkinson's disease or dystonia from April 2001 to December 2020. In cases that developed intra- or postoperative ICH, patients were classified as asymptomatic, symptomatic with temporary neurological deficit or symptomatic with permanent neurological deficit, according to patient clinical status. RESULTS: ICH occurred in 12 procedures (2.3%) among the 527 DBS procedures (275 patients) evaluated. In multivariable logistic regression analysis, the risk factor for all cases of ICH was systolic blood pressure (BP) during surgery (cut-off value 129.4 mmHg) (OR = 1.05, 95% CI = 1.01-1.09, P = 0.023). In addition, for ICH with permanent neurological deficit, STN target site (P = 0.024) and systolic BP during surgery (cut-off value: 148.3 mmHg) (P = 0.004) were identified as risk factors in univariable analyses. CONCLUSION: Even though the risk factor for all ICH in DBS was BP during surgery, when focused on ICH evoking permanent neurological deficit, the target location as well as systolic BP during surgery proved to be related.
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Estimulação Encefálica Profunda , Núcleo Subtalâmico , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/terapia , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/métodos , Globo Pálido , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the effects of a mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease. METHODS: A randomized controlled design was used. The participants were randomly assigned to an intervention or a control group. The intervention group (n = 20) received mobile health intervention comprising mobile applications, smartwatches, smartphone-based short text messages and information, and telephone counselling; whereas the control group (n = 23) received short text messages and telephone counselling for 16 weeks. RESULTS: After 16 weeks, self-efficacy and non-motor symptom scores in the intervention group significantly improved compared to those in the control group. However, no significant differences were observed in the motor symptoms, self-management, and quality of life between the groups. CONCLUSIONS: The mobile health intervention for self-management is effective for self-efficacy and non-motor symptoms in people with Parkinson's disease.
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Doença de Parkinson , Autogestão , Telemedicina , Humanos , Doença de Parkinson/terapia , Qualidade de Vida , AutoeficáciaRESUMO
The ability to detect and correct errors is a critical aspect of human cognition. Neuronal dysfunction in error processing has been reported in addictive disorders. The aim of this study was to investigate neural systems underlying error processing using event-related potentials (ERPs) and current source localization as well as neurocognitive executive function tests in patients with Internet gaming disorder (IGD). A total of 68 individuals (34 patients with IGD and 34 healthy controls [HCs]) were included, and two ERP components, error-related negativity (ERN) and error positivity (Pe), were extracted during a GoNogo task. Patients with IGD exhibited significantly reduced ERN and Pe amplitudes compared with HCs. Standardized low-resolution brain electromagnetic tomography (sLORETA) in between-group comparisons revealed that patients with IGD had decreased source activations of the Pe component in the anterior cingulate cortex (ACC) under the Nogo condition. These ERP changes were associated with deficits in decision-making and response inhibition in IGD patients. The results suggest that IGD may be associated with functional abnormalities in the ACC and alterations in neural activity related to both the early unconscious and the later conscious stages of error processing, as well as deficits in area of decision-making.
Assuntos
Giro do Cíngulo/fisiopatologia , Transtorno de Adição à Internet/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Adulto JovemRESUMO
Stooped posture, which is usually aggravated during walking, is one of the typical postural deformities in patients with parkinsonism. However, the degree of stooped posture is difficult to quantitatively measure during walking. Furthermore, continuous feedback on posture is also difficult to provide. The purpose of this study is to measure the degree of stooped posture during gait and to investigate whether vibration feedback from sensor modules can improve a patient's posture. Parkinsonian patients with stooped posture were recruited for this study. Two wearable sensors with three-axis accelerometers were attached, one at the upper neck and the other just below the C7 spinous process of the patients. After being calibrated in the most upright posture, the sensors continuously recorded the sagittal angles at 20 Hz and averaged the data at every second during a 6 min walk test. In the control session, the patients walked with the sensors as usual. In the vibration session, sensory feedback was provided through vibrations from the neck sensor module when the sagittal angle exceeded a programmable threshold value. Data were collected and analyzed successfully in a total of 10 patients. The neck flexion and back flexion were slightly aggravated during gait, although the average change was <10° in most patients in both measurement sessions. Therefore, it was difficult to evaluate the effect of sensory feedback through vibration. However, some patients showed immediate response to the feedback and corrected their posture during gait. In conclusion, this preliminary study suggests that stooped posture could be quantitatively measured during gait by using wearable sensors in patients with parkinsonism. Sensory feedback through vibration from sensor modules may help in correcting posture during gait in selected patients.