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Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin1,2. However, the mechanism leading to TDP-43 proteinopathy remains unclear. Here we use single-nucleus RNA sequencing to show that progranulin deficiency promotes microglial transition from a homeostatic to a disease-specific state that causes endolysosomal dysfunction and neurodegeneration in mice. These defects persist even when Grn-/- microglia are cultured ex vivo. In addition, single-nucleus RNA sequencing reveals selective loss of excitatory neurons at disease end-stage, which is characterized by prominent nuclear and cytoplasmic TDP-43 granules and nuclear pore defects. Remarkably, conditioned media from Grn-/- microglia are sufficient to promote TDP-43 granule formation, nuclear pore defects and cell death in excitatory neurons via the complement activation pathway. Consistent with these results, deletion of the genes encoding C1qa and C3 mitigates microglial toxicity and rescues TDP-43 proteinopathy and neurodegeneration. These results uncover previously unappreciated contributions of chronic microglial toxicity to TDP-43 proteinopathy during neurodegeneration.
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Microglía/metabolismo , Microglía/patología , Neuronas/metabolismo , Neuronas/patología , Progranulinas/deficiencia , Proteinopatías TDP-43/metabolismo , Proteinopatías TDP-43/patología , Envejecimiento/genética , Envejecimiento/patología , Animales , Núcleo Celular/genética , Núcleo Celular/patología , Activación de Complemento/efectos de los fármacos , Activación de Complemento/inmunología , Complemento C1q/antagonistas & inhibidores , Complemento C1q/inmunología , Complemento C3b/antagonistas & inhibidores , Complemento C3b/inmunología , Medios de Cultivo Condicionados/química , Medios de Cultivo Condicionados/farmacología , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Poro Nuclear/metabolismo , Poro Nuclear/patología , Progranulinas/genética , RNA-Seq , Análisis de la Célula Individual , Proteinopatías TDP-43/tratamiento farmacológico , Proteinopatías TDP-43/genética , Tálamo/metabolismo , Tálamo/patología , TranscriptomaRESUMEN
Field-free switching (FFS) and spin-orbit torque (SOT)-based neuromorphic characteristics were realized in a W/Pt/Co/NiO/Pt heterostructure with a perpendicular exchange bias (HEB) for brain-inspired neuromorphic computing (NC). Experimental results using NiO-based SOT devices guided the development of fully spin-based artificial synapses and sigmoidal neurons for implementation in a three-layer artificial neural network. This system achieved impressive accuracies of 91-96% when applied to the Modified National Institute of Standards and Technology (MNIST) image data set and 78.85-81.25% when applied to Fashion MNIST images, due presumably to the emergence of robust NiO antiferromagnetic (AFM) ordering. The emergence of AFM ordering favored the FFS with an enhanced HEB, which suppressed the memristivity and reduced the recognition accuracy. This indicates a trade-off between the requirements for solid-state memory and those required for brain-inspired NC devices. Nonetheless, our findings revealed opportunities by which the two technologies could be aligned via controllable exchange coupling.
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BACKGROUND: Data on self-harm (SH) repetition in non-Western adolescents are limited; this study is to survey the predictors. METHODS: A total of 5879 adolescents (mean age 16.02 years) in Northern Taiwan were recruited. The participants filled in online questionnaires about their sociodemographic data, suicidality, depressive symptoms, self-esteem, social support, family discord, impulsivity, and alcohol and tobacco use at baseline (T1) and at the 1 year follow-up (T2). We used logistic regression analysis to examine the predictors of SH continuation. Generalized structural equation modeling (GSEM) was then estimated to analyze the treatable variables for both years and to investigate their relationships and mediating effects. RESULTS: A total of 125 students were identified as being in the SH continuation group; while 470 students were identified as being in the SH stop group. The SH continuation rate was 21%; no significant gender difference was found. Logistic regression analysis showed that the predictors of SH continuation were low school ranking, poor quality of listening from relatives, use of the cutting method for SH, and a suicide plan in the past year at T1, and more depressed mood, use of the cutting method for SH, more suicide ideation and plans at T2. Similar predictors were found by GSEM; self-esteem at T1 and depressed mood at T2 were found to be mediators in the pathways. CONCLUSION: The continuation rate of SH was similar to that reported in Western countries. These predictors should be included in the treatment plan to prevent SH continuation.
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Conducta Autodestructiva , Adolescente , Humanos , Factores de Riesgo , Conducta Autodestructiva/epidemiología , Ideación Suicida , Encuestas y Cuestionarios , EstudiantesRESUMEN
Sunlight/UV (ultraviolet)-induced degradation is still a critical issue for outdoor applications of organic light-emitting diode (OLED) displays. Therefore, effective UV-blocking structures that can prevent OLED displays from sunlight/UV degradation and still keep the OLED panels' display performance is necessary. In this report, modified distributed Bragg reflector (DBR) structures having UV-absorbing dielectric materials and adjusted layer/pair thicknesses were developed to realize effective UV blocking properties (nearly 0% transmittance below 400â nm), constantly high transmittance like glass in the visible range (â¼92%) required for display applications, and sharp transition in transmission between the UV and the visible ranges. Furthermore, under the rigorous IEC 60068-2-5 solar test condition, it was verified that the developed modified, UV-blocking DBR can effectively enhance the OLED panel's resistance against UV/solar-induced degradation, effectively reducing voltage shifts of OLED devices after repeated solar test cycles.
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BACKGROUND: Cigarette smoking and alcohol drinking are the most common types of substance use and misuse (SUM) among adolescents. This study aimed to estimate the prevalence and psychosocial factors associated with current cigarette smoking and hazardous alcohol drinking among adolescents in Taiwan. METHODS: Data were collected via self-administered questionnaires on computers from students at 14 senior high schools in Taipei, Taiwan. Hierarchical multiple regression strategies were used to determine the risk factors for SUM. RESULTS: A total of 5879 participants were recruited, the majority of whom were female (56.7%). The prevalence rates of current smoking and hazardous alcohol drinking were 3.84% and 7.38%, respectively. Risk factors associated with current smoking were similar to those for hazardous alcohol drinking, including male gender, low school ranking, and depression. In addition, current smoking was associated with increasing age, hazardous alcohol drinking, and fewer parents with whom they can talk, whereas hazardous alcohol drinking was associated with current smoking, not living with both biological parents, and more peers with whom they can talk. CONCLUSION: The potential coexistence of adolescent SUM and common psychosocial correlates demands an integrated approach. Health professionals should provide corresponding intervention programs and coordinate with parents and teachers to develop an anti-SUM environment, especially for males and high-risk schools. Preventive psychiatric services as an integral part of anti-SUM strategies for adolescents targeting to depression may be useful in reducing the risk.
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Fumar Cigarrillos , Adolescente , Consumo de Bebidas Alcohólicas/epidemiología , Femenino , Humanos , Masculino , Prevalencia , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
BACKGROUND/PURPOSE: The restoration longevity depends on a high dentin-composite bond quality. This study investigated learning outcomes when using etch-and-rinse and self-etch adhesives among general practitioners in a hands-on bonding test course. METHODS: We recruited 30 general practitioners to perform shear bond strength (SBS) tests using five adhesives: one Peak® Universal Bond (PUB) etch-and-rinse and four Futurabond DC, Single Bond universal (SBU), Versa Optibond (VOB), and Tetric-N Bond Self-Etch (TNS) self-etch adhesives. SBS tests were conducted at pre-demonstration (pre-demo), post-demonstration (post-demo), and 24-h storage (delayed bonding) stages. SBS data were analyzed with paired Student's t-tests. We defined 17 MPa as "qualified bond strength (QBS)". The percentages of samples with SBS achieving QBS were analyzed using Mantel-Haenszel chi-square tests. The fracture surfaces of the samples were examined by scanning electron microscopy (SEM). RESULTS: Using PUB caused no significant differences in SBS between pre- and post-demo samples, whereas the SBS of the two self-etch adhesives (SBU and VOB) improved in post-demo samples (p < 0.05). SBU showed the highest percentage of samples with SBS achieving QBS in all three groups (pre-demo = 70%, post-demo = 83%, and delayed bonding = 76.5%). The QBS percentages of VOB and TNS notably improved from 0% (pre-demo) to 71.4% and 23.5% (post-demo), respectively. SEM indicated bubble-like defects at the dentin-resin interfaces in cases of low SBS. CONCLUSION: Bonding performance is both operator- and product-dependent. The continuing education hands-on course does help dentists to improve the bond strength especially when the self-etch system is used.
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Resinas Compuestas , Recubrimiento Dental Adhesivo/métodos , Recubrimientos Dentinarios , Odontólogos/educación , Resistencia al Corte , Grabado Ácido Dental , Adhesivos , Competencia Clínica , Análisis del Estrés Dental , Dentina , Humanos , Aprendizaje , Ensayo de MaterialesRESUMEN
Parents of children with attention deficit hyperactivity disorder (ADHD) have been found to prefer sensory integration (SI) training rather than guideline-recommended ADHD treatment. This study investigated whether SI intervention for children with ADHD was associated with a reduced risk of subsequent mental disorders. From children < 8-years-old newly diagnosed with ADHD in a nationwide population-based dataset, we established a SI cohort and a non-SI cohort (N = 1945) matched by propensity score. Incidence and hazard ratios of subsequent psychiatric disorders were compared after a maximum follow-up of 9 years. The incidence of psychiatric disorders was 1.4-fold greater in the SI cohort, with an adjusted hazard ratio of 1.41 (95% confidence interval 1.20-1.67), comparing to the non-SI cohort. Risks were elevated for emotional disturbances, conduct disorders, and adjustment disorders independent of age, gender, or comorbidity. Among children with only psychosocial intervention, the incidence of psychiatric disorders was 3.5-fold greater in the SI cohort than in the non-SI cohort. To our knowledge, this is the first study to report an increased risk of developing psychiatric disorders for children with ADHD who received SI compared to those who did not. Potential adverse effects of SI for ADHD children should be carefully examined and discussed before practice.
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Trastorno por Déficit de Atención con Hiperactividad/terapia , Terapia Conductista , Trastorno de la Conducta/epidemiología , Trastornos Mentales/epidemiología , Trastornos del Humor/epidemiología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Padres , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
This study examines the reliability, factor structure, convergent, and construct validities of the Mandarin Chinese version of the Reasons For Living Inventory (RFL) among Taiwanese psychiatric patients. Demographical characteristics of patients who hold these adaptive cognitions and differences on the level of endorsement between suicidal and non-suicidal individuals were also investigated. All adult patients that had visited the psychiatric ambulatory clinic or had been admitted to the psychiatric ward in a general hospital in Taiwan over a 3-month period were consecutively invited to complete an inventory that included background information, the Mandarin Chinese versions of the RFL, the Suicidal Behaviors Questionnaire-Revised (SBQ-R), and the Beck Hopeless Scale (BHS). Of the 254 respondents aged 19 to 65 years, 47.2% had suicidal ideations or attempts within the past year. The original six-factor structure of the American version was confirmed to be acceptable. The Cronbach α was 0.964.Total scores on RFL were inversely and significantly correlated with that from BHS. Multivariate analysis with demographic data and items from SBQ-R revealed that higher scores on the RFL have been associated with married, have children or religious beliefs, fewer past and current suicidal ideations and attempts, fewer histories of suicidal threats, and a less self-reported likelihood of future suicide in our sample. The Mandarin version of the RFL inventory showed acceptable psychometric properties and could distinguish suicidal patients from non-suicidal ones.
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Escalas de Valoración Psiquiátrica/normas , Psicometría/normas , Reproducibilidad de los Resultados , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Ideación Suicida , Suicidio/psicología , Intento de Suicidio/psicología , Encuestas y Cuestionarios , TaiwánRESUMEN
Kinesin-3 UNC-104(KIF1A) is the major axonal transporter of synaptic vesicles. Employing yeast two-hybrid and co-immunoprecipitation (Co-IP) assays, we characterized a LIN-2(CASK) binding site overlapping with that of reported UNC-104 activator protein SYD-2(Liprin-α) on the motor's stalk domain. We identified the L27 and GUK domains of LIN-2 to be the most critical interaction domains for UNC-104. Further, we demonstrated that the L27 domain interacts with the sterile alpha motifs (SAM) domains of SYD-2, while the GUK domain is able to interact with both the coiled coils and SAM domains of SYD-2. LIN-2 and SYD-2 colocalize in Caenorhabditis elegans neurons and display interactions in bimolecular fluorescence complementation (BiFC) assays. UNC-104 motor motility and Synaptobrevin-1 (SNB-1) cargo transport are largely diminished in neurons of LIN-2 knockout worms, which cannot be compensated by overexpressing SYD-2. The absence of the motor-activating function of LIN-2 results in increased motor clustering along axons, thus retaining SNB-1 cargo in cell bodies. LIN-2 and SYD-2 both positively affect the velocity of UNC-104, however, only LIN-2 is able to efficiently elevate the motor's run lengths. From our study, we conclude that LIN-2 and SYD-2 act in a functional complex to regulate the motor with LIN-2 being the more prominent activator.
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Transporte Axonal/fisiología , Axones/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Movimiento Celular/fisiología , Proteínas del Helminto/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Vesículas Sinápticas/metabolismo , Animales , Animales Modificados Genéticamente/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas del Tejido Nervioso/genética , Fosfoproteínas/metabolismoRESUMEN
Leafy flowers are the major symptoms of peanut witches' broom (PnWB) phytoplasma infection in Catharanthus roseus. The orthologs of the phyllody symptoms1 (PHYL1) effector of PnWB from other species of phytoplasma can trigger the proteasomal degradation of several MADS box transcription factors, resulting in leafy flower formation. In contrast, the flowering negative regulator gene SHORT VEGETATIVE PHASE (SVP) was up-regulated in PnWB-infected C. roseus plants, but most microRNA (miRNA) genes had repressed expression. Coincidentally, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing the PHYL1 gene of PnWB (PHYL1 plants), which show leafy flower phenotypes, up-regulate SVP of Arabidopsis (AtSVP) but repress a putative regulatory miRNA of AtSVP, miR396. However, the mechanism by which PHYL1 regulates AtSVP and miR396 is unknown, and the evidence of miR396-mediated AtSVP degradation is lacking. Here, we show that miR396 triggers AtSVP messenger RNA (mRNA) decay using genetic approaches, a reporter assay, and high-throughput degradome profiles. Genetic evidence indicates that PHYL1 plants and atmir396a-1 mutants have higher AtSVP accumulation, whereas the transgenic plants overexpressing MIR396 display lower AtSVP expression. The reporter assay indicated that target-site mutation results in decreasing the miR396-mediated repression efficiency. Moreover, degradome profiles revealed that miR396 triggers AtSVP mRNA decay rather than miRNA-mediated cleavage, implying that AtSVP caused miR396-mediated translation inhibition. We hypothesize that PHYL1 directly or indirectly interferes with miR396-mediated AtSVP mRNA decay and synergizes with other effects (e.g. MADS box transcription factor degradation), resulting in abnormal flower formation. We anticipate our findings to be a starting point for studying the posttranscriptional regulation of PHYL1 effectors in symptom development.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Flores/genética , MicroARNs/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Arabidopsis/crecimiento & desarrollo , Secuencia de Bases , Catharanthus/genética , Catharanthus/microbiología , Flores/crecimiento & desarrollo , Flores/microbiología , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Datos de Secuencia Molecular , Mutación , Fenotipo , Phytoplasma/fisiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
BACKGROUND: Pulsed radiofrequency (PRF) has been used to treat chronic pain for years, but its effectiveness and mechanism in treating diabetic neuropathic pain are still unexplored. The aim of this study was to elucidate the modulation of diabetic neuropathic pain induced by streptozotocin and the release of spinal excitatory amino acids by PRF. METHODS: Diabetes was induced by intraperitoneal administration of streptozotocin. Pulsed radiofrequency was applied to L5 and L6 dorsal roots at 42 °C for 2 min. The responses of all of the groups to thermal, mechanical and cold stimuli were measured for a period of 6 d after this process. Seven days after PRF treatment, intrathecal microdialysis was used to examine the effect of pulsed radiofrequency on the formalin-evoked spinal release of excitatory amino acids and concurrent behaviour responses from diabetic rats. RESULTS: Three weeks after intraperitoneal streptozotocin treatment and before PRF application, mechanical, thermal and cold hypersensitivity occurred. Application of PRF significantly alleviated hyperglycaemia-induced mechanical, thermal and cold hypersensitivity and also attenuated the increase in formalin-evoked CSF glutamate concentration, compared with sham treated diabetic rats. CONCLUSION: It may be concluded that PRF has an analgesic effect on neuropathic pain by suppressing the nociception-induced release of excitatory neurotransmitters. PRF may provide a novel promising therapeutic approach for managing diabetic neuropathic pain.
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Diabetes Mellitus Experimental/complicaciones , Neuropatías Diabéticas/terapia , Ácido Glutámico/metabolismo , Neuralgia/terapia , Tratamiento de Radiofrecuencia Pulsada , Animales , Diabetes Mellitus Experimental/terapia , Neuropatías Diabéticas/fisiopatología , Formaldehído/farmacología , Masculino , Neuralgia/etiología , Ratas , Ratas Sprague-Dawley , Vías Secretoras/efectos de los fármacosRESUMEN
The Prp19-associated complex is required for spliceosome activation by stabilizing the binding of U5 and U6 on the spliceosome after the release of U4. The complex comprises at least eight proteins, among which Ntc90 and Ntc77 contain multiple tetratricopeptide repeat (TPR) elements. We have previously shown that Ntc90 is not involved in spliceosome activation, but is required for the recruitment of essential first-step factor Yju2 to the spliceosome. We demonstrate here that Ntc77 has dual functions in both spliceosome activation and the first catalytic step in recruiting Yju2. We have identified an amino-terminal region of Ntc77, which encompasses the N-terminal domain and the first three TPR motifs, dispensable for spliceosome activation but required for stable interaction of Yju2 with the spliceosome. Deletion of this region had no severe effect on the integrity of the NTC, binding of NTC to the spliceosome or spliceosome activation, but impaired splicing and exhibited a dominant-negative growth phenotype. Our data reveal functional roles of Ntc77 in both spliceosome activation and the first catalytic step, and distinct structural domains of Ntc77 required for these two steps.
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Proteínas de Ciclo Celular/química , Proteínas de Saccharomyces cerevisiae/química , Empalmosomas/metabolismo , Biocatálisis , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/fisiología , ARN Helicasas DEAD-box/metabolismo , Proteínas Nucleares/metabolismo , Estructura Terciaria de Proteína , Factores de Empalme de ARN , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologíaRESUMEN
AIM: To identify the favorable factors in rectovaginal fistula (RVF) management. METHODS: After Institutional Review Board approval (99-0793B), we retrospectively studied all patients diagnosed, treated and followed up with RVF at Chang Gung Memorial Hospital, Taiwan between January 1990 and December 2009. All female patients with International Classification of Diseases RVF were included. We reviewed demographic data, socioeconomic status, clinical presentation, comorbidities, method of treatment, duration of hospitalization and clinical outcome at 12 months postoperatively. RESULTS: A total of 397 patients were included in the study. Fifty-six patients (14.1%) had conservative treatment and 341 patients (85.9%) underwent surgical intervention. A total of 125 patients underwent simple repair while 216 patients underwent reconstruction. Three hundred and forty-four patients (86.7%) had improved outcome at 12-month follow up. Age (P = 0.003), education level (P = 0.033), ability to pay insurance (P < 0.001), and choice of treatment (P < 0.0001) were identified as significant favorable factors. An etiological factor associated with favorable outcome was RVF from obstetric complication, while that resulting from malignancy had a less favorable outcome. CONCLUSIONS: Age, education level and ability to pay insurance significantly affect 12-month outcome of RVF. Surgery is the preferred option, while medical treatment should be used only for small rectovaginal fistulas or for patients not suitable for surgery and anesthesia. More support and assistance should be offered to those patients with unfavorable factors, such as old age, low education level and inability to afford insurance. All RVF secondary to obstetrical injury had a 100% favorable outcome compared with those secondary to surgery or malignancy. Women with suspected RVF should receive prompt and extensive evaluation to ensure immediate effective management and prevention of further serious complications.
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Fístula Rectovaginal/epidemiología , Fístula Rectovaginal/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán , Resultado del TratamientoRESUMEN
BACKGROUND/PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) often have problems in social interactions. We investigated the social and behavioral effects of providing both social skill training and parent training to school-aged children with ADHD in Taiwan. METHODS: Seven consecutive 8-week behavioral-based social skill training (SST) group sessions were held for 48 children with ADHD; parallel 8-week parent group sessions were provided simultaneously. Fifty-five children with ADHD were recruited as a control group. All children took medication as prescribed by their doctors. The effects were assessed using the teacher and parent version of the Chinese version of Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), the Chinese version of the Child Behavior Check List (CBCL-C), child and teacher version of the modified Social Skill Rating System (SSRS-C and SSRS-T), at baseline, post-treatment, and 4 months from baseline. The doses of methylphenidate and drug compliance were controlled during the analysis. RESULTS: The mixed-effects model demonstrated the main effect of group sessions on the Oppositional subscale of SNAP-P, the Anxious/Depressed subscale of CBCL-C, the Self Control subscale of SSRS-C, and the Active Participation subscale of SSRS-T, all in favor of the experimental group. However, the improvement on the Oppositional subscale of SNAP-P and the Self Control subscale of SSRS-C were noted only between baseline and post-treatment period and were not sustained at the end of the follow-up period. CONCLUSION: Our study demonstrated that children with ADHD could benefit from this low intensity psychosocial program, although some improvements were not maintained at follow-up assessment.
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Trastorno por Déficit de Atención con Hiperactividad/terapia , Terapia Conductista/métodos , Padres/educación , Psicoterapia de Grupo/métodos , Habilidades Sociales , Escala de Evaluación de la Conducta , Niño , Terapia Combinada , Femenino , Humanos , Modelos Lineales , Masculino , Escalas de Valoración Psiquiátrica , Clase Social , Taiwán , Resultado del TratamientoRESUMEN
Cross-protection triggered by a mild strain of virus acts as a prophylaxis to prevent subsequent infections by related viruses in plants; however, the underling mechanisms are not fully understood. Through mutagenesis, we isolated a mutant strain of Turnip mosaic virus (TuMV), named Tu-GK, that contains an Arg182Lys substitution in helper component-proteinase (HC-Pro(K)) that confers complete cross-protection against infection by a severe strain of TuMV in Nicotiana benthamiana, Arabidopsis thaliana Col-0, and the Arabidopsis dcl2-4/dcl4-1 double mutant defective in DICER-like ribonuclease (DCL)2/DCL4-mediated silencing. Our analyses showed that HC-Pro(K) loses the ability to interfere with microRNA pathways, although it retains a partial capability for RNA silencing suppression triggered by DCL. We further showed that Tu-GK infection triggers strong salicylic acid (SA)-dependent and SA-independent innate immunity responses. Our data suggest that DCL2/4-dependent and -independent RNA silencing pathways are involved, and may crosstalk with basal innate immunity pathways, in host defense and in cross-protection.
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Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular/genética , Protección Cruzada , Cisteína Endopeptidasas/genética , Enfermedades de las Plantas/inmunología , Potyvirus/genética , Ribonucleasa III/genética , Proteínas Virales/genética , Secuencias de Aminoácidos , Sustitución de Aminoácidos , Arabidopsis/inmunología , Arabidopsis/virología , Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cisteína Endopeptidasas/metabolismo , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , MicroARNs/genética , Modelos Biológicos , Mutación , Enfermedades de las Plantas/virología , Hojas de la Planta/inmunología , Hojas de la Planta/virología , Plantas Modificadas Genéticamente , Potyvirus/fisiología , Interferencia de ARN , Ribonucleasa III/metabolismo , Ácido Salicílico/metabolismo , Plantones/inmunología , Plantones/virología , Análisis de Secuencia de ARN , Nicotiana/inmunología , Nicotiana/virología , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: Gabapentin (GBP) is known to suppress neuropathic hypersensitivity of primary afferents and the spinal cord dorsal horn. However, its supra-spinal action sites are unclear. We identify the brain regions where GBP changes the brain glucose metabolic rate at the effective dose that alleviates mechanical allodynia using 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning. RESULTS: Comparing the PET imaging data before and after the GBP treatment, the spared nerve injury-induced increases of glucose metabolism in the thalamus and cerebellar vermis were reversed, and a significant decrease occurred in glucose metabolism in the medial prefrontal cortex (mPFC), including the anterior cingulate cortex. GBP treatment also reversed post-SNI connectivity increases between limbic cortices and thalamus. CONCLUSIONS: Our results indicate that GBP analgesic effect may be mediated by reversing central hypersensitivity, and suppressing mPFC, a crucial part of the cortical representation of pain, in the brain.
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Aminas/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Glucosa/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/patología , Corteza Prefrontal/metabolismo , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Ácidos Ciclohexanocarboxílicos/farmacología , Modelos Animales de Enfermedad , Fluorodesoxiglucosa F18 , Gabapentina , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Masculino , Dimensión del Dolor , Tomografía de Emisión de Positrones , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/efectos de los fármacos , Radiografía , Ratas , Ratas Sprague-Dawley , Tomógrafos Computarizados por Rayos X , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
BACKGROUND: Marginally low birth weight (MLBW) is defined as a birth weight of 2000 ~ 2499 g. Inconsistent findings have been reported on whether children with low birth weight had higher rates of neurological, attention, or cognitive symptoms. No studies have explored the occurrence of clinically diagnosed psychiatric disorders in term- born MLBW infants. We aimed to investigate the risk of subsequent psychiatric disorders in term-born children with MLBW. METHODS: This is a nationwide retrospective cohort study, by analysing the data from Taiwan's National Health Insurance Research Database from 2008 to 2018. The study population includes propensity-score-matched term-born infants with MLBW and those without MLBW (birth weight ≥ 2500 g). Cox proportional hazard analysis was used after adjustment for potential demographic and perinatal comorbidity confounders. Incidence rates and hazard ratios (HR) of 11 psychiatric clinical diagnoses were evaluated. RESULTS: A total of 53,276 term-born MLBW infants and 1,323,930 term-born infants without MLBW were included in the study. After propensity score matching for demographic variables and perinatal comorbidities, we determined that the term-born MLBW infants (n = 50,060) were more likely to have attention deficit and hyperactivity disorder (HR = 1.26, 95% confidence interval (CI) [1.20, 1.33]), autism spectrum disorder (HR = 1.26, 95% CI [1.14, 1.40]), conduct disorder (HR = 1.25, 95% CI [1.03, 1.51]), emotional disturbance (HR: = 1.13, 95% CI [1.02, 1.26]), or specific developmental delays (HR = 1.38, 95% CI [1.33, 1.43]) than term-born infants without MLBW (n = 50,060). CONCLUSION: MLBW was significantly associated with the risk of subsequent psychiatric disorder development among term-born infants. The study findings demonstrate that further attention to mental health and neurodevelopment issues may be necessary in term-born children with MLBW. However, possibilities of misclassification in exposures or outcomes, and risks of residual and unmeasured confounding should be concerned when interpreting our data.
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Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.
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Background: Some risk/protective factors of adolescent depression have been proposed but have not been comprehensively studied. Recent advances in neuroimaging techniques have provided greater insight into the underlying neuropsychiatric mechanisms of depression-related factors such as impulsivity, substance use, gender difference and social support. However, how these factors are interconnected and how they affect depression in the real world is poorly understood. This study aimed to explore the relationships between adolescent depression with trait impulsivity, substance use and gender. We also tested the hypothesis that social support may play a buffering role in preventing depression. By expanding the diathesis-stress model. Methods: The adolescents enrolled in this study were grade 1 senior high school students from northern Taiwan (N = 5879), and they were assessed for depression, trait impulsivity, and tobacco/alcohol use. Hierarchical multiple linear regression was performed to control possible confounders, including other depression-related diathesis and sociodemographic variables. Gender differences were also analyzed by separately examining variables significantly associated with depression. Results: A higher level of depression was associated with female gender, trait impulsivity, low self-esteem, negative attitude towards the future, tobacco use, alcohol use, family discord and difficulty in basic family needs. Good parental health, living with their biological family and social support were protective factors. Trait impulsivity was significantly associated with depression after controlling for the confounding factors. Gender-specific analysis showed that trait impulsivity and tobacco use had a significant synergistic interaction on female depression. Social support from parents/peers was significantly associated with depression, but social support from other family members/teachers was not. Conclusion: The current study advances the understanding of adolescent depression and highlights that trait impulsivity, addictive substance use, social support and their interaction may play an influential role in the emergence of adolescent depression. Gender-specific research and treatment approach are also crucial, and more investigations are necessary.
RESUMEN
BACKGROUND: The short form of the Borderline Symptom List (BSL-23) is a self-rated instrument developed from the initial 95-item German version of the Borderline Symptom List (BSL-95). It is widely used among Chinese adults, but its applicability, factor structure and validity remain uncertain in adolescents. This study aimed to evaluate the psychometric properties of the Chinese Mandarin version of the BSL-23 in a sample of suicidal adolescents. METHODS: The Chinese Mandarin BSL-23 was given to 279 outpatient adolescents with self-injurious thoughts or behaviors. The factor structure, reliability, convergent validity, criterion-related validity and cut-off value were investigated. RESULTS: The Chinese Mandarin version of the BSL-23 demonstrated a one-factor structure and replicated the original version. The scale had high reliability and good test-retest stability. The Chinese Mandarin BSL-23 was correlated with depression, hopelessness, impulsivity, emotional dysregulation, self-esteem, loneliness, childhood trauma and parental bonding patterns evaluated with a variety of scales. The measure showed good criterion-related validity and predictive accuracy (AUC = 0.87) for self-injurious and suicidal adolescents with borderline personality disorder (BPD) at a cut-off point of 60/61 (mean score 2.60/2.65), with a sensitivity of 0.76 and specificity of 0.83. CONCLUSIONS: The Chinese Mandarin version of the BSL-23 is a reliable and valid self-reported instrument to assess BPD symptomatology among suicidal adolescents.