RESUMEN
In recent years, there has been a growing trend in the use of immune checkpoint inhibitors (ICIs) for treating a larger patient population. However, it is important to note that immune-related adverse events (irAEs) frequently arise as a result. Therefore, precise patient monitoring becomes essential. We present the findings of a retrospective study conducted at the International University of Health and Welfare Narita Hospital (referred to as "our hospital") that aimed to identify risk factors linked to the occurrence of irAEs. The study focused on analyzing various factors, including therapeutic and lifestyle backgrounds, as well as laboratory values of patients who received ICI treatment and were subsequently diagnosed with irAE. The study included patients who met the eligibility criteria for ICIs (both single agent and combination therapy) as well as ICI in combination with anticancer drugs. The inclusion period for the study encompassed April 2020 to May 2022 at our hospital. The fifty patients were divided into two groups based on the severity of irAEs: the first group consisted of patients with irAE Grade 2 or lower (referred to as irAE Grade under 2), while the second group included patients with irAE Grade 3 or higher (referred to as irAE Grade over 3). Statistical analysis revealed significant differences in age (p=0.027) and CRP (C-reactive protein) levels (p=0.008) among the background factors when comparing the two groups. Additionally, statistically significant differences were observed among different ICI treatment groups in the occurrence of irAEs (p=0.035). however, it was indicated to be a relatively weak correlation. Moving forward, we shifted our focus to examine the frequency of irAEs in relation to exposure. However, we did not observe any significant correlation between exposure and irAE grade. Additionally, even when exposure was doubled through the use of ipilimumab in combination with ICIs (referred to as "Mod exposure"), no correlation was found. Exposure was further categorized into three groups: the PD-1 group, PD-L1 group, and PD-1 + CTLA-4 group. However, no significant correlation was observed between exposure in any of these groups and the grade of irAEs. Similarly, no significant correlation was observed between the dosage of ICI in the fixed-dose group and the weight-based dosage group with exposure and irAE Grade. Based on our study findings, there is a suggestive relationship between age and CRP levels and the occurrence of irAEs of Grade 3 or higher. These factors may play a role in contributing to the development of more severe irAEs.
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Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Neoplasias/tratamiento farmacológico , Adulto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiologíaRESUMEN
BACKGROUND: Non-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. METHODS: In 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. RESULTS: We found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LIMITATIONS: Limited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). CONCLUSIONS: These data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.
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Trastorno Obsesivo Compulsivo , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Red en Modo Predeterminado , Resultado del Tratamiento , Encéfalo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/terapia , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: There were no formal regulatory approvals for antivirals for the COVID-19 pandemic as of June 2020. AREAS COVERED: We compare the first regulatory approvals for remdesivir, through emergency pathways available to three of the main regulators in the world, the U.S., Japan, and the EU. We look at the data supporting the decisions and how authorities exchanged information and collaborated to speed up approvals. Based only on topline data available as of 29 April 2020, regulators granted approvals to remdesivir based on very limited but robust data and waiting for more safety and efficacy data. This included the Emergency Use Authorization in the U.S. on 1 May, the Special Approval for Emergency in Japan on 7 May, and Compassionate Use (3 April) followed by a Conditional Marketing Authorization in Europe (Opinion 25th June, Decision (3 July)). EXPERT OPINION: While the regulatory approvals were clearly based on evidence, regulators used agile methods to speed up approval, and make the first antiviral with reliable data available to patients in their constituencies in a very short time frame. More data and wider patient access are still necessary for this product, and more treatments are needed for patients affected by COVID-19.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Aprobación de Drogas , Neumonía Viral/tratamiento farmacológico , Adenosina Monofosfato/uso terapéutico , Alanina/uso terapéutico , Betacoronavirus , COVID-19 , Ensayos de Uso Compasivo , Servicios Médicos de Urgencia , Unión Europea , Humanos , Japón , Pandemias , SARS-CoV-2 , Estados Unidos , Tratamiento Farmacológico de COVID-19RESUMEN
AIMS: To study the mechanism of the antibacterial action of tea polyphenols such as catechins and theaflavins against Bacillus coagulans, and the interaction of epigallocatechin gallate (EGCg) or theaflavin 3,3'-di-O-gallate (TFDG) with the surface of B. coagulans cells was investigated. METHODS AND RESULTS: The antibacterial activities of EGCg and TFDG against B. coagulans cells were measured by counting of the viable cells after the mixing with each polyphenol. Bactericidal effect of TFDG was shown at the concentration of greater than or equal to 62·5 mg l-1 ; however, at the same concentration, EGCg did not. According to the results of two dimensional (2D)-electrophoresis analysis, TFDG seemed to interact with cytoplasmic membrane proteins. The activity of the glucose transporters of the cells decreased 40% following the treatment with TFDG of 62·5 mg l-1 ; however, this decrease was only slight in case of EGCg. This result was in accordance with the strength of their bactericidal activities. CONCLUSION: Our results suggest that the direct interaction between membrane proteins and TFDG is an important factor in the antibacterial activity of polymerized catechins, affecting their functions and leading to cell death. SIGNIFICANCE AND IMPACT OF THE STUDY: Tea polyphenols can effectively use the prevention of product spoilage in the food and beverage industry.
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Antibacterianos/farmacología , Bacillus coagulans/efectos de los fármacos , Biflavonoides/farmacología , Catequina/análogos & derivados , Bacillus coagulans/metabolismo , Biflavonoides/metabolismo , Catequina/metabolismo , Catequina/farmacología , Membrana Celular/efectos de los fármacos , Glucosa/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Viabilidad Microbiana/efectos de los fármacos , Polifenoles/química , Polifenoles/farmacología , Té/químicaRESUMEN
Corynebacterium simulans was first reported in 2000. Although it is a member of the normal skin flora, some cases of C. simulans infection have been reported. Other Corynebacterium spp. rarely cause chronic pyogenic spondylitis, and pyogenic spondylitis caused by C. simulans has not been reported at all. Here we report a case of acute pyogenic spondylitis due to C. simulans. A 78-year-old man with diabetes mellitus visited our hospital with a 3-day history of lower back pain and fever. Blood culture revealed C. simulans and magnetic resonance images of lumbar vertebrae showed pyogenic spondylitis. He recovered after treatment by vancomycin for 9 weeks and was discharged home. No recurrence has been observed for half a year. This is likely the first reported case of pyogenic spondylitis by C. simulans. In general, Corynebacterium spp. cause chronic pyogenic spondylitis, but this case showed an acute course.
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Infecciones por Corynebacterium , Corynebacterium , Espondilitis , Enfermedad Aguda , Anciano , Antibacterianos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Vancomicina/uso terapéuticoRESUMEN
Eye tracking (ET) studies are becoming increasingly popular due to rapid methodological and technological advances as well as the development of cost efficient and portable eye trackers. Although historically ET has been mostly employed in psychophysics or developmental cognition studies, there is also promising scope to use ET for movement disorders and measuring cognitive processes in neurodegeneration. Particularly, ET can be a powerful tool for cognitive and neuropsychological assessments of patients with pathologies affecting motor and verbal abilities, as tasks can be adapted without requiring motor (except eye movements) or verbal responses. In this review, we will examine the existing evidence of ET methods in neurodegenerative conditions and its potential clinical impact for cognitive assessment. We highlight that current evidence for ET is mostly focused on diagnostics of cognitive impairments in neurodegenerative disorders, where it is debatable whether it has any more sensitivity or specificity than existing cognitive assessments. By contrast, there is currently a lack of ET studies in more advanced disease stages, when patients' motor and verbal functions can be significantly affected, and standard cognitive assessments are challenging or often not possible. We conclude that ET is a promising method not only for cognitive diagnostics but more importantly, for potential cognitive disease tracking in progressive neurodegenerative conditions.
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Disfunción Cognitiva/diagnóstico , Medidas del Movimiento Ocular , Enfermedades Neurodegenerativas/fisiopatología , Pruebas Neuropsicológicas , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/psicología , Cognición , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Movimientos Oculares , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/psicología , Humanos , Enfermedades Neurodegenerativas/psicología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Sensibilidad y EspecificidadRESUMEN
AIM: The purpose of this study was to clarify the mechanism of the antibacterial action of two high potential and natural food additives, epigallocatechin gallate (EGCg) and theaflavin-3,3'-digallate (TF3), on Clostridium perfringens. METHODS AND RESULTS: Minimal inhibitory concentrations were determined by the serial dilution method. Afterwards, the cells were treated with 250 or 1000 mg l-1 of EGCg and 125 or 500 mg l-1 of TF3 and morphological changes were observed and cell sizes were also measured under fluorescence microscopy. Our results showed that TF3 had a twice stronger antibacterial activity than EGCg against C. perfringens. Phase-contrast and fluorescence microscopy confirmed that the bacterial cells elongated without DNA segregation and septum formation in the presence of 250 mg l-1 EGCg. While in the higher concentration of EGCg and TF3, cell growth was suppressed. Bacterial cells reached to around 12 µm after the 24 h incubation with 250 mg l-1 EGCg, but the cells were shorter than the control at 1000 mg l-1 of EGCg. After washing and incubating the elongated cells in fresh medium, DNA segregated at 2 h of incubation. The average cell length decreased gradually and reached the normal size at 8 h. CONCLUSION: It seems that EGCg at a low concentration affected the proteins involved in the septum formation, DNA segregation and cell division. Furthermore, the high concentration of EGCg and TF3 seemed to cause stronger cellular damage to C. perfringens. SIGNIFICANCE AND IMPACT OF THE STUDY: These polyphenols are widely distributed in all higher plants especially in tea plants, and people tend to use natural food additives rather than synthetic ones. EGCg and TF3, as natural food additives, can prevent C. perfringens food poisoning along with other potential health benefits.
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Antibacterianos/farmacología , Biflavonoides/farmacología , Catequina/análogos & derivados , Clostridium perfringens/efectos de los fármacos , Catequina/farmacologíaRESUMEN
AIM: Here, we have extensively investigated the relationship between thermoregulation and neurodegeneration-induced dementia of the Alzheimer's type using intracerebroventricular injections of streptozotocin (icv-STZ). METHODS: Male Wistar rats were treated with bilateral injections of icv-STZ, and their thermoregulatory profiles (core body temperature, tail-skin temperature, cold and heat defence responses and thermal place preference) were evaluated. Spatial memory, locomotor activity, social interaction, brain ventricular volume, and Aß1-42 and tau protein levels in the brain were analysed to characterize the effects of STZ on the brain and behaviour. RESULTS: In addition to deficits in spatial memory, reduced social interaction and an increased brain ventricular volume, icv-STZ rats presented a pattern of hyperthermia, as demonstrated by an increased core body temperature. Hyperthermia was due to the activation of both autonomic heat conservation and behavioural cold avoidance, as STZ-treated rats presented tail-cutaneous vasoconstriction and an altered thermal preference. They also showed a distinct cold defence response when exposed to cold. CONCLUSION: Our data bring evidence that icv-STZ in rats causes hyperthermia, with activation of both autonomic and behavioural thermoregulatory defence responses when challenged at colder temperatures, leading us to hypothesize that they are more efficient in preventing hypothermia. These data are relevant for a better understanding of neurodegenerative disease mechanisms.
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Enfermedad de Alzheimer/inducido químicamente , Regulación de la Temperatura Corporal/efectos de los fármacos , Fiebre/inducido químicamente , Estreptozocina/administración & dosificación , Enfermedad de Alzheimer/fisiopatología , Animales , Encéfalo/metabolismo , Infusiones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratas , Ratas Wistar , Proteína Amiloide A Sérica/metabolismo , Estreptozocina/toxicidad , Proteínas tau/metabolismoRESUMEN
Gordon H. Sato, an innovator in mammalian tissue culture and integrated cellular physiology, passed away in 2017. In tribute to Dr. Sato, In Vitro Cellular and Developmental Biology-Animal presents a collection of invited remembrances from six colleagues whose associations with Dr. Sato spanned more than 40 years. Dr. Sato was a past president of the Tissue Culture Association (now the Society for In Vitro Biology), editor-in-chief of In Vitro Cellular and Developmental Biology (1987-1991), and the recipient of the lifetime achievement award from the Society for In Vitro Biology (2002). He was elected to the US National Academy of Sciences in 1984.
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Técnicas de Cultivo de Célula/historia , Mamíferos/crecimiento & desarrollo , Animales , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Estados UnidosRESUMEN
OBJECTIVE: An increase in coronal laxity is recognized as a risk factor for progression of knee osteoarthritis (OA). The purpose of this study was to evaluate coronal laxity, which was defined as the angular motion from the neutral, unloaded (baseline) position to the loaded position, in patients with advanced medial knee OA. METHOD: Preoperative coronal laxity was assessed using radiographs in patients with medial knee OA undergoing total knee arthroplasty by applying a force of 150 N with an arthrometer. A consecutive series of 211 knees with OA and 40 normal control knees were examined. A knee with OA was defined as clinically "balanced" when the difference between medial and lateral laxity was 3° or less. Values are expressed as median [25th, 75th percentile]. RESULTS: The laxity was 4° [3, 5] from the baseline on the medial side and 3° [2, 4] on the lateral side. The distribution of medial and lateral laxity indicated that 90% (189/211) of patients fell within 3°. The equivalence test showed that the medial and lateral laxity was similar, with an equivalence margin of 3° (P < 0.001). In the control knees, the laxity was 3° [2, 4] from the baseline on the medial side and 2° [2, 4] on the lateral side. The differences between the knees with advanced OA and the controls were significant (P = 0.005, medial; P = 0.006, lateral). CONCLUSION: This study showed that a clinically balanced knee was maintained even in patients with advanced medial knee OA.
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Inestabilidad de la Articulación/complicaciones , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/etiología , Radiografía/métodos , Rango del Movimiento Articular/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inestabilidad de la Articulación/diagnóstico , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/cirugía , Periodo Preoperatorio , Factores de RiesgoRESUMEN
Tumour hypoxia can be detected by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). Few studies have assessed the relationships of new PET parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), with 5-year survival of patients treated surgically for oral squamous cell carcinoma (OSCC). This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42-84 years; 15 male, eight female) with OSCC underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery. All of them underwent radical surgery and were followed up for more than 5 years. The FDG-PET maximum standardized uptake value (SUVmax), HV, MTV, and TLG were measured. The ability of PET parameters to predict disease-free survival (DFS) and loco-regional recurrence (LR) was evaluated using receiver operating characteristic curve analysis. During the follow-up period, five of the 23 patients (22%) died and six (26%) experienced LR. Although FDG-PET SUVmax was not significantly associated with DFS or LR, HV correlated significantly with both DFS and LR. TLG, but not MTV, was significantly associated with DFS; however neither MTV nor TLG was related significantly to LR. In conclusion, tumour HV may predict outcomes in patients with OSCC.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/cirugía , Tomografía de Emisión de Positrones/métodos , Hipoxia Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Misonidazol/análogos & derivados , Neoplasias de la Boca/patología , Disección del Cuello , Clasificación del Tumor , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A six-month-old female cat suffered aspiration of an abundant amount of barium sulfate during a radiographic procedure for the diagnosis of megaesophagus. Latero-lateral contrast radiography revealed severe dilation of the thoracic esophagus cranial to the base of the heart. Persistence of the right aortic arch was suspected and later confirmed during corrective surgery. Accumulation of barium sulfate, used as a contrast agent, was clearly observed in the lumen of the bronchi, bronchioles, and alveoli in the radiographic image. Days after the surgery, the animal developed severe respiratory distress, which resulted in death. Cytology results and histology analysis using polarized light demonstrated that the lumen of bronchi, bronchioles, and alveoli exhibited evident histiocytic infiltration with cytoplasm filled by abundant amorphous refractive granular material consistent with barium sulfate. In this report, we describe the anatomical, cytological, histopathological (using polarized light), and x-ray findings of a case of barium sulfate aspiration pneumonia in a cat resulting from the use of this contrast medium for the diagnosis of megaesophagus secondary to persistent right aortic arch.(AU)
Uma gata de seis meses aspirou grande quantidade de sulfato de bário durante procedimento radiográfico para diagnóstico de megaesôfago. Contraste radiográfico látero-lateral revelou dilatação de esôfago torácico até a base do coração. Persistência do arco aórtico direito foi confirmada durante cirurgia corretiva. Acúmulo de sulfato de bário, utilizado como agente de contraste, foi observado no lúmen de brônquios, bronquíolos e alvéolos à imagem radiográfica. Dias após a cirurgia o animal desenvolveu insuficiência respiratória grave e evoluiu para óbito. Resultado de citologia e histologia utilizado luz polarizada demonstrou que lúmen de brônquios, bronquíolos e alvéolos mostraram infiltração histológica com citoplasma cheio de material refratário granular amorfo compatível com sulfato de bário. Nesse relatório, descrevemos achados anatômicos, citológicos, histopatológicos e radiográficos de um caso de pneumonia aspirativa em gata resultante do uso desse meio de contraste para diagnóstico de megaesôfago secundário a persistência do arco aórtico direito.(AU)
Asunto(s)
Animales , Gatos , Sulfato de Bario/análisis , Acalasia del Esófago/veterinaria , Neumonía por Aspiración/veterinaria , Aorta TorácicaRESUMEN
OBJECTIVE: In many decision support systems, some input features can be marginal or irrelevant to the diagnosis, while others can be redundant among each other. Thus, feature selection (FS) algorithms are often considered to find relevant/non-redundant features. This study aimed to evaluate the relevance of FS approaches applied to Alzheimer's Disease (AD) EEG-based diagnosis and compare the selected features with previous clinical findings. METHODS: Eight different FS algorithms were applied to EEG spectral measures from 22 AD patients and 12 healthy age-matched controls. The FS contribution was evaluated by considering the leave-one-subject-out accuracy of Support Vector Machine classifiers built in the datasets described by the selected features. RESULTS: The Filtered Subset Evaluator technique achieved the best performance improvement both on a per-patient basis (91.18% of accuracy) and on a per-epoch basis (85.29±21.62%), after removing 88.76±1.12% of the original features. All algorithms found out that alpha and beta bands are relevant features, which is in agreement with previous findings from the literature. CONCLUSION: Biologically plausible EEG datasets could achieve improved accuracies with pre-processing FS steps. SIGNIFICANCE: The results suggest that the FS and classification techniques are an attractive complementary tool in order to reveal potential biomarkers aiding the AD clinical diagnosis.
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Algoritmos , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Electroencefalografía/clasificación , Aprendizaje Automático/clasificación , Anciano , Anciano de 80 o más Años , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.
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Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Adolescente , Niño , Estudios Transversales , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Tamaño de los ÓrganosRESUMEN
Purpose: Thiamazole (MMI) is frequently used for the treatment of Graves' disease, but it occasionally induces agranulocytosis at the beginning of the treatment. To date, the predictive factors of recovery from MMI-induced agranulocytosis remain unclear. The primary aim of this study was to evaluate the predictive factor of the recovery time from MMI-induced agranulocytosis. Method: This was a retrospective cohort study performed in a university hospital and a thyroid hospital. We included 27 Japanese patients with Graves' disease with MMI-induced agranulocytosis diagnosed during follow-up. All patients were administrated recombinant human granulocyte colony-stimulating factor daily until they had a neutrophil count>1 000/µL, which was defined as recovery. The predictive factors associated with recovery time were estimated using multivariable regression analysis. Results: At the onset of agranulocytosis, the median administration period of MMI was 33 days, the average white blood cell count was 1 896/µL, and the median neutrophil count was 22/µL. The median recovery time was 4 days. Stepwise multivariate regression analysis identified the monocyte and basophil counts to be significant predictors of MMI-induced agranulocytosis. Conclusion: Patients with agranulocytosis and decreased monocyte and basophil counts at onset may recover late and require careful treatment.
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Agranulocitosis , Basófilos , Enfermedad de Graves , Metimazol , Monocitos , Neutrófilos , Recuperación de la Función/efectos de los fármacos , Adulto , Agranulocitosis/sangre , Agranulocitosis/inducido químicamente , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Metimazol/administración & dosificación , Metimazol/efectos adversos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.
RESUMEN
Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.
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Trastorno Bipolar/genética , Regulación de la Expresión Génica/genética , Trastornos Psicóticos/genética , Esquizofrenia/genética , Psicología del Esquizofrénico , Adulto , Proteínas Portadoras/genética , Estudios de Casos y Controles , ARN Helicasas DEAD-box/genética , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Proteína Básica de Mielina/genética , Proteínas Proto-Oncogénicas c-akt/genética , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Psicometría , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/psicología , Valores de Referencia , Ribonucleasa III/genética , Esquizofrenia/diagnóstico , Estadística como Asunto , Adulto JovenRESUMEN
Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( rs > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.
Asunto(s)
Lupus Eritematoso Sistémico/diagnóstico , Adolescente , Niño , Consenso , Conducta Cooperativa , Humanos , Lupus Eritematoso Sistémico/epidemiología , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
OBJECTIVES AND BACKGROUND: The involvement of DNA methylation in periodontal disease is not clear. Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis is involved in the progression of periodontal disease. We recently developed an in vitro model of LPS infection in human periodontal fibroblast cells (HPdLFs) for a prolonged period. In this study, we examined genome-wide analysis of DNA methylation in HPdLFs stimulated with LPS derived from P. gingivalis for a prolonged period. We noted the hypermethylation of extracellular matrix (ECM)-related genes and examined whether hypermethylation affected their transcription levels. MATERIAL AND METHODS: HPdLFs were grown in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. The culture was repeated, alternating 3 d with LPS derived from P. gingivalis and 3 d without LPS for 1 mo. Untreated samples were used as controls. DNA was analyzed using the human CpG island microarray. Quantitative methylation-specific polymerase chain reaction was carried out to confirm reproducibility of the microarray data. The expression levels of mRNA of the selected ECM-related genes from the data were analyzed by quantitative reverse transcription-polymerase chain reaction. RESULTS: We found 25 ECM-related genes with hypermethylation at the CpG island of the promoter region, which exhibited a fourfold greater hypermethylation than controls. Among these genes, hypermethylation of nine ECM-related genes, FANK1, COL4A1-A2, 12A1 and 15A1, LAMA5 and B1, MMP25, POMT1 and EMILIN3, induced a significantly downregulated expression of their mRNA. CONCLUSION: These results indicate that LPS derived from P. gingivalis may cause DNA hypermethylation of some ECM-related genes followed by downregulated expression of their transcriptional levels.
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Metilación de ADN , Matriz Extracelular/genética , Fibroblastos/metabolismo , Lipopolisacáridos/farmacología , Porphyromonas gingivalis , Células Cultivadas , Regulación hacia Abajo , Matriz Extracelular/metabolismo , Humanos , Transcripción GenéticaRESUMEN
UNLABELLED: We investigated the demographic characteristics of patients who were diagnosed with intersection syndrome and also investigated the dominance of the affected hand, duration of symptoms and any precipitating factor for pain of the wrist. These features were compared with patients who had de Quervain's disease. Ultrasonography was used to confirm the clinical diagnosis. Intersection syndrome occurred more frequently in men and in the dominant hand than de Quervain's disease when all the patients were compared and when peripartum women were excluded. It occurred at a younger age than de Quervain's disease only when the comparison excluded peripartum women. Patients with intersection syndrome presented with a much shorter duration of symptoms. These results were consistent with previous reports about occupational factors in intersection syndrome, and might be helpful in the understanding of epidemiological difference between the two conditions. LEVEL OF EVIDENCE: Level 3.