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1.
Sensors (Basel) ; 23(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37420587

RESUMO

A design for a millimeter wave RF probe card that removes resonance is proposed. The designed probe card optimizes the position of the ground surface and the signal pogo pins to resolve the resonance and signal loss issues that occur when connecting a dielectric socket and a PCB. At millimeter wave frequencies, the height of the dielectric socket and pogo pin matches the length of half a wavelength, allowing the socket to act as a resonator. When the leakage signal from the PCB line is coupled to the 2.9 mm high socket with pogo pins, resonance at a frequency of 28 GHz is generated. The probe card uses the ground plane as a shielding structure to minimize this resonance and radiation loss. The importance of the signal pin location is verified via measurements in order to address the discontinuity caused by field polarity switching. A probe card fabricated using the proposed technique exhibits an insertion loss performance of -8 dB up to 50 GHz and eliminates resonance. A signal with an insertion loss of -3.1 dB can be transmitted to a system-on-chip in a practical chip test.


Assuntos
Utensílios Domésticos , Fixadores Internos , Imagem de Difusão por Ressonância Magnética , Publicações , Registros
4.
Toxicol In Vitro ; 82: 105352, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35341918

RESUMO

Air-liquid-interface (ALI) exposure systems deliver aerosol to the apical surface of cells which mimics the in vivo inhalation exposure conditions. It is necessary, however, to quantify the delivered amount of aerosol for ALI-based in vitro toxicity assessment. In this study, we evaluated two commercially available ALI exposure systems, a Vitrocell® Ames 48 (Ames 48) and a Vitrocell® 24/48 (VC 24/48), and the Vitrocell® VC1/7 smoking machine using a cig-a-like cartridge-based e-vapor device with a prototype formulation (containing 4% nicotine by weight). We characterized aerosol particle-size distribution, aerosol mass, and major chemical components (nicotine, propylene glycol, and glycerol) at the generation source and verified the repeatability of the aerosol generation. We determined aerosol delivery at the ALI by gravimetric analysis of mass collected on Cambridge filter pads and analytical quantitation of the buffer medium which showed that both aerosol mass and nicotine to an exposure insert linearly increased up to 400 puffs. The delivered aerosol mass covered a wide range of 0.8-3.4 mg per insert in the Ames 48 with variability (relative standard deviation, RSD) up to 12% and 1.1-6.4 mg per insert in the VC 24/48 with variability up to 15%. The delivered nicotine ranged approximately up to 200 µg per insert in both exposure systems. These results provided operation and aerosol delivery information of these ALI exposure systems for subsequent in vitro testing of e-vapor aerosols.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Aerossóis , Exposição por Inalação , Nicotina/toxicidade , Fumar
5.
BJOG ; 128(4): 738-744, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32946626

RESUMO

OBJECTIVE: To determine whether postpartum haemorrhage (PPH) is associated with cardiovascular disease (CVD), including cerebrovascular and ischaemic heart disease beyond the peripartum period. DESIGN: Population-based cohort study. SETTING: Merged databases of the Korea National Health Insurance (KNHI) claims, National Health Screening Examination and National Health Screening Program for Infants and Children. POPULATION: Women who gave birth in 2007 in the Republic of Korea and who were tracked through to 2015 for the occurrence of CVD. METHODS: Patients were identified and the occurrences of PPH and transfusion were determined using the KNHI claims database. The occurrence of CVD was tracked through 2015 using codes from the International Classification of Diseases, tenth revision (ICD-10). MAIN OUTCOME MEASURES: The risk of CVD after PPH. RESULTS: Among 150 381 women who gave birth during the study period, 9107 were diagnosed with PPH and 899 were treated with transfusion. The risk of CVD in women with PPH was no different than in women without PPH, after adjustment (HR 1.03, 95% CI 0.93-1.13). The risk of CVD in women with PPH requiring transfusion was significantly increased compared with women without PPH, after adjustment (HR 1.60, 95% CI 1.25-2.06). The risk of CVD in women with PPH without transfusion was not significantly different compared with women without PPH (HR 0.96, 95% CI 0.86-1.07). CONCLUSIONS: Postpartum haemorrhage (PPH) requiring transfusion is associated with an increased risk of CVD. Guidelines for management should be established, and further studies on the mechanisms involved should be conducted. TWEETABLE ABSTRACT: PPH requiring transfusion is associated with an increased risk of CVD.


Assuntos
Transfusão de Sangue , Doenças Cardiovasculares/etiologia , Hemorragia Pós-Parto/terapia , Adulto , Doenças Cardiovasculares/epidemiologia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gravidez , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
6.
Osteoarthritis Cartilage ; 28(4): 486-491, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32028021

RESUMO

OBJECTIVES: Pharmacological options for treating osteoarthritis (OA) are limited and alternative treatments are required. Given the clinical data indicating that granulocyte macrophage-colony stimulating factor (GM-CSF) may be a therapeutic target in human OA, we evaluated different treatment regimens with a neutralizing anti-GM-CSF monoclonal antibody (mAb) in an experimental OA model to determine their effectiveness on amelioration of pain and disease. METHODS: The collagenase-induced osteoarthritis (CiOA) model was induced in C57BL/6 mice, followed by different treatment regimens of anti-GM-CSF mAb or isotype control. Anti-CCL17 mAb treatment was also administered continually during the late stage of CiOA. Pain-related behavior (change in weight distribution of hind limbs), and disease (cartilage damage and osteophyte size) were assessed. RESULTS: Blocking GM-CSF only during early synovitis in CiOA prevented pain and disease development. Once OA pain was established, regardless of the treatment regimen, anti-GM-CSF mAb treatment rapidly and efficiently ameliorated it; however, unless the treatment was continued, pain returned and disease progressed. Continual late stage blockade of GM-CSF was able to ameliorate pain (between-group difference: -6.567; 95% confidence interval (CI): -10.12, -3.011) and suppress cartilage damage (P = 0.0317, 95% CI: -1.75, -0.0556). Continual late stage blockade of CCL17 showed similar effects on pain and disease development. CONCLUSIONS: Early and short-term GM-CSF neutralization is effective at preventing CiOA pain and disease development but, once pain is evident, continual GM-CSF blockade is required to prevent pain from returning and to suppress disease progression in mice. These data reinforce the potential benefits of anti-GM-CSF (and anti-CCL17) mAb therapy in OA and should inform further clinical trials.


Assuntos
Anticorpos Neutralizantes/farmacologia , Cartilagem Articular/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Osteoartrite do Joelho/patologia , Joelho de Quadrúpedes/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Cartilagem Articular/patologia , Quimiocina CCL17/antagonistas & inibidores , Colagenases/toxicidade , Progressão da Doença , Intervenção Médica Precoce , Injeções Intra-Articulares , Camundongos , Osteoartrite do Joelho/induzido quimicamente , Osteófito/patologia , Medição da Dor , Joelho de Quadrúpedes/patologia , Membrana Sinovial/patologia , Sinovite/patologia
7.
Mol Psychiatry ; 25(2): 368-378, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31455859

RESUMO

Cellular models of neurodevelopmental disorders provide a valuable experimental system to uncover disease mechanisms and novel therapeutic strategies. The ability of induced pluripotent stem cells (iPSCs) to generate diverse brain cell types offers great potential to model several neurodevelopmental disorders. Further patient-derived iPSCs have the unique genetic and molecular signature of the affected individuals, which allows researchers to address limitations of transgenic behavioural models, as well as generate hypothesis-driven models to study disorder-relevant phenotypes at a cellular level. In this article, we review the extant literature that has used iPSC-based modelling to understand the neuronal and glial contributions to neurodevelopmental disorders including autism spectrum disorder (ASD), Rett syndrome, bipolar disorder (BP), and schizophrenia. For instance, several molecular candidates have been shown to influence cellular phenotypes in three-dimensional iPSC-based models of ASD patients. Delays in differentiation of astrocytes and morphological changes of neurons are associated with Rett syndrome. In the case of bipolar disorders and schizophrenia, patient-derived models helped to identify cellular phenotypes associated with neuronal deficits (e.g., excitability) and mutation-specific abnormalities in oligodendrocytes (e.g., CSPG4). Further we provide a critical review of the current limitations of this field and provide methodological suggestions to enhance future modelling efforts of neurodevelopmental disorders. Future developments in experimental design and methodology of disease modelling represent an exciting new avenue relevant to neurodevelopmental disorders.


Assuntos
Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/fisiopatologia , Células-Tronco Pluripotentes/metabolismo , Astrócitos/metabolismo , Diferenciação Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Modelos Biológicos , Neuroglia/metabolismo , Neurônios/metabolismo , Fenótipo
8.
Opt Express ; 27(12): 16571-16577, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31252881

RESUMO

We demonstrate the generation of spectrally tunable phase-dependent wavefronts, using the 2D Airy as the primary test case, via a polymer-stabilized cholesteric liquid crystal (PSCLC) element. Specifically, we use a novel spatial light modulator (SLM) based projection system to photo-align the initial helix angle landscape of the PSCLC so that it imparts the appropriate cubic phase profile to the reflected beam. This element is spectrally selective, with a reflection bandwidth of ≈ 100 nm, and electrically tunable from λ = 530 nm to 760 nm. Under both green and red laser illumination, the element is shown to conditionally form an Airy beam depending on the position of the electrically tailored reflection band. We briefly demonstrate the generality of this approach by producing PSCLC elements which form a computer-generated hologram and a higher-order Mathieu beam.

9.
Lupus ; 28(7): 898-902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31042127

RESUMO

Headaches are common in patients with systemic lupus erythematosus (SLE). It is important to identify the exact cause of headaches in SLE to avoid unnecessary steroid or immunosuppressive therapy like in neuropsychiatric SLE. A 35-year-old woman with SLE suddenly developed severe headache. Magnetic resonance angiography showed multifocal segmental narrowing of cerebral arteries, suggestive of central nervous system vasculitis. However, lack of abnormal enhancement in vessel wall imaging indicated reversible cerebral vasoconstriction syndrome (RCVS) rather than central nervous system vasculitis. The patient was treated with oral nimodipine and she recovered over a period of two months. Following magnetic resonance angiography on day 90 was normal. Herein we report a case of reversible cerebral vasoconstriction syndrome in an SLE patient with literature review.


Assuntos
Transtornos da Cefaleia Primários/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasoconstrição , Vasoespasmo Intracraniano/complicações , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/patologia , Diagnóstico Diferencial , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Angiografia por Ressonância Magnética , Síndrome , Vasoespasmo Intracraniano/diagnóstico por imagem
10.
BJOG ; 126(7): 901-905, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30758126

RESUMO

OBJECTIVES: To evaluate the association of a history of threatened preterm labour (TPL) followed by term delivery with the risk of spontaneous preterm delivery (PTD) in subsequent pregnancy. DESIGN: Population-based cohort study. SETTING: Data of the National Health Insurance Claims Database and a national health-screening programme for infants and children in South Korea. POPULATION: Women who had their first singleton delivery in 2010 and a subsequent second singleton delivery between 2011 and 2015. METHODS: Multivariable analysis adjusting for maternal age and interval between first and second deliveries was used to assess the risk of PTD based on PTD, TPL followed by term delivery, and term delivery in the first pregnancy. MAIN OUTCOME MEASURES: The risk of PTD during the second pregnancy. RESULTS: This study included 115 629 women with two consecutive deliveries during the study period. Spontaneous PTD rates in the second pregnancy were 7.71, 2.22 and 1.02% in women with PTD, TPL followed by term delivery, and term delivery in the first pregnancy, respectively. Threatened preterm labour followed by term delivery in the first pregnancy was associated with increased risk of PTD in the subsequent pregnancy after adjustment for potential confounding factors (adjusted odds ratio 2.21; 95% CI 1.76-2.78). CONCLUSION: Although women with a history of TPL followed by term delivery had a lower risk of PTD during a subsequent pregnancy compared with those with history of previous PTD, they still had a significantly increased risk of PTD compared with those who delivered at term without TPL. TWEETABLE ABSTRACT: The history of threatened preterm labour followed by term delivery is related to increased risk of subsequent spontaneous preterm delivery.


Assuntos
Ameaça de Aborto/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento a Termo/fisiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Idade Materna , Gravidez , Recidiva , República da Coreia/epidemiologia , Fatores de Risco
11.
J Intellect Disabil Res ; 62(12): 1008-1017, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30450801

RESUMO

BACKGROUND: Self-injurious behaviour (SIB) can be classified as intentional, direct injuring of body tissue usually without suicidal intent. In its non-suicidal form it is commonly seen as a clinical sign of borderline personality disorder, autism, PTSD, depression, and anxiety affecting a wide range of ages and conditions. In rhesus macaques SIB is most commonly manifested through hair plucking, self-biting, self-hitting, and head banging. SIB in the form of self-biting is observed in approximately 5-15% of individually housed monkeys. Recently, glial cells are becoming recognised as key players in regulating behaviours. METHOD: The goal of this study was to determine the role of glial activation, including astrocytes, in macaques that had displayed SIB. To this end, we performed immunohistochemistry and next generation sequence of brain tissues from rhesus macaques with SIB. RESULTS: Our studies showed increased vimentin, but not nestin, expression on astrocytes of macaques displaying SIB. Initial RNA Seq analyses indicate activation of pathways involved in tissue remodelling, neuroinflammation and cAMP signalling. CONCLUSIONS: Glia are most probably activated in primates with self-injury, and are therefore potential novel targets for therapeutics.


Assuntos
Encéfalo/patologia , Neuroglia/patologia , Comportamento Autodestrutivo/patologia , Animais , Comportamento Animal , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Imuno-Histoquímica , Macaca mulatta , Comportamento Autodestrutivo/fisiopatologia
12.
Transplant Proc ; 50(8): 2496-2501, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30316385

RESUMO

BACKGROUND: Low levels of natriuretic peptide may activate the renin-angiotensin-aldosterone system, which may contribute to the development of obesity. Therefore, in study we aim to evaluate the relationship between metabolic syndrome (MetS) and serum N-terminal pro‒B-type natriuretic peptide (NT-proBNP) concentration in kidney transplant recipients. METHODS: Fasting blood samples were obtained from 66 kidney transplant recipients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS: A total of 20 patients (30.3%) had MetS. Hypertension, prevalence of diabetes, use of statin or fibrate, body weight, body mass index, waist circumference, body fat mass, and levels of systolic blood pressure, total cholesterol, triglyceride, blood urea nitrogen, insulin, and HOMA-IR were higher, whereas the levels of high-density lipoprotein cholesterol and NT-proBNP were lower in patients with MetS. Logarithmically transformed creatinine and log-HOMA-IR were associated with NT-proBNP levels in a multivariable linear regression analysis. Multivariate logistic regression analysis revealed that NT-proBNP was an independent predictor of MetS in kidney transplant recipients. CONCLUSION: Our study has revealed that fasting level of NT-proBNP was negatively associated with MetS and that serum creatinine and HOMA-IR were independent predictors of serum NT-proBNP level in kidney transplant recipients.


Assuntos
Transplante de Rim , Síndrome Metabólica/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Índice de Massa Corporal , Creatinina/sangue , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Circunferência da Cintura
13.
Bone Joint Res ; 7(8): 501-507, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30258568

RESUMO

OBJECTIVES: The objective of this study was to quantify the relative movement between the articular surfaces in the tibiotalar and subtalar joints during normal walking in asymptomatic individuals. METHODS: 3D movement data of the ankle joint complex were acquired from 18 subjects using a biplanar fluoroscopic system and 3D-to-2D registration of bone models obtained from CT images. Surface relative velocity vectors (SRVVs) of the articular surfaces of the tibiotalar and subtalar joints were calculated. The relative movement of the articulating surfaces was quantified as the mean relative speed (RS) and synchronization index (SIENT) of the SRVVs. RESULTS: SIENT and mean RS data showed that the tibiotalar joint exhibited translational movement throughout the stance, with a mean SIENT of 0.54 (sd 0.21). The mean RS of the tibiotalar joint during the 0% to 20% post heel-strike phase was 36.0 mm/s (sd 14.2), which was higher than for the rest of the stance period. The subtalar joint had a mean SIENT value of 0.43 (sd 0.21) during the stance phase and exhibited a greater degree of rotational movement than the tibiotalar joint. The mean relative speeds of the subtalar joint in early (0% to 10%) and late (80% to 90%) stance were 23.9 mm/s (sd 11.3) and 25.1 mm/s (sd 9.5), respectively, which were significantly higher than the mean RS during mid-stance (10% to 80%). CONCLUSION: The tibiotalar and subtalar joints exhibited significant translational and rotational movement in the initial stance, whereas only the subtalar joint exhibited significant rotational movement during the late stance. The relative movement on the articular surfaces provided deeper insight into the interactions between articular surfaces, which are unobtainable using the joint coordinate system.Cite this article: C-B. Phan, D-P. Nguyen, K. M. Lee, S. Koo. Relative movement on the articular surfaces of the tibiotalar and subtalar joints during walking. Bone Joint Res 2018;7:501-507. DOI: 10.1302/2046-3758.78.BJR-2018-0014.R1.

14.
Aliment Pharmacol Ther ; 48(2): 196-205, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29869804

RESUMO

BACKGROUND: There are increasing reports of paradoxical psoriasiform diseases secondary to anti-tumour necrosis factor (TNF) agents. AIMS: To determine the risks of paradoxical psoriasiform diseases secondary to anti-TNF agents in patients with inflammatory bowel disease (IBD). METHODS: A nationwide population study was performed using the Korea National Health Insurance Claim Data. A total of 50 502 patients with IBD were identified between 2007 and 2016. We compared 5428 patients who were treated with any anti-TNF agent for more than 6 months (anti-TNF group) and 10 856 matched controls who had never taken anti-TNF agents (control group). RESULTS: Incidence of psoriasis was significantly higher in the anti-TNF group (36.8 per 10 000 person-years) compared to the control group (14.5 per 10 000 person-years) (hazard ratio [HR] 2.357, 95% confidence interval [CI] 1.668-3.331). Palmoplantar pustulosis (HR 9.355, 95% CI 2.754-31.780) and psoriatic arthritis (HR 2.926, 95% CI 1.640-5.218) also showed higher risks in the anti-TNF group. In subgroup analyses, HRs for psoriasis by IBD subtype were 2.549 (95% CI 1.658-3.920) in Crohn's disease and 2.105 (95% CI 1.155-3.836) in ulcerative colitis. Interestingly, men and younger (10-39 years) patients have significantly higher risks of palmoplantar pustulosis (HR 19.682 [95% CI 3.867-100.169] and HR 14.318 [95% CI 2.915-70.315], respectively), whereas women and older (≥40 years) patients showed similar rates between the two groups. CONCLUSIONS: The risks of psoriasiform diseases are increased by anti-TNF agents in patients with IBD. Among psoriasiform diseases, the risk of palmoplantar pustulosis shows the biggest increase particularly in male and younger patients.


Assuntos
Anti-Inflamatórios/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Psoríase/induzido quimicamente , Psoríase/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Estudos de Casos e Controles , Criança , Estudos de Coortes , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Humanos , Incidência , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
15.
Neurogastroenterol Motil ; 30(7): e13323, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29532576

RESUMO

BACKGROUND: The purpose of this study was to investigate the association between mylohyoid motor-evoked potentials (MH-MEP) and swallowing function and determine the value of MH-MEP for predicting aspiration 3 months poststroke. METHODS: Subacute patients within a month of their first stroke were enrolled up for 2 consecutive years. Videofluoroscopic swallowing studies (VFSS) were performed twice. Patients were evaluated during VFSS using the penetration aspiration scale (PAS) and videofluoroscopic dysphagia scale (VDS). MH-MEP was recorded in the mylohyoid muscles. The active electrode was positioned submentally, 2 cm lateral to midline. Magnetic stimulation was performed on the contralateral motor cortex, 2-4 cm anterior and 4-6 cm lateral to the cranial vertex. The resting motor threshold (rMT), latency, and amplitude stimulation at 120% (amp120) and 150% (amp150) of the rMT were assessed. The ratio of each parameter was also estimated. The relationship between MH-MEP and VFSS findings was analyzed. KEY RESULTS: Sixty-eight patients completed the study. On VFSS at 3 months poststroke, 24 (35.3%) patients showed aspiration. The rMT, rMT ratio, amp120 and amp120 ratio were significantly correlated with the PAS and VDS (P < .05). The rMT ratio (OR = 1.208, P = .001) and amp120 ratio (OR = 0.821, P = .002) were independent predictors of aspiration at 3 months. The optimal cut-off value of the rMT ratio was 126.1 (AUC = 0.94, sensitivity = 0.92, specificity = 0.89); that of the amp120 ratio was 66.5 (AUC = 0.89, sensitivity = 0.88, specificity = 0.86). CONCLUSIONS AND INFERENCES: MH-MEP was well-correlated with dysphagia severity assessed by VFSS. The rMT ratio and amplitude ratio of MH-MEP can effectively predict persistent dysphagia 3 months poststroke.


Assuntos
Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/fisiopatologia , Potencial Evocado Motor/fisiologia , Mandíbula/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
16.
Neuropathol Appl Neurobiol ; 44(6): 590-605, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29380402

RESUMO

AIMS: Degeneration of the distal neuromuscular circuitry is a hallmark pathology of Amyotrophic Lateral Sclerosis (ALS). The potential for microtubule dysfunction to be a critical pathophysiological mechanism in the destruction of this circuitry is increasingly being appreciated. Stabilization of microtubules to improve neuronal integrity and pathology has been shown to be a particularly favourable approach in other neurodegenerative diseases. We present evidence here that treatment with the microtubule-targeting compound Epothilone D (EpoD) both positively and negatively affects the spinal neuromuscular circuitry in the SOD1G93A mouse model of ALS. METHODS: SOD1G93A mice were treated every 5 days with 2 mg/kg EpoD. Evaluation of motor behaviour, neurological phenotype and survival was completed, with age-dependent histological characterization also conducted, using the thy1-YFP mouse. Motor neuron degeneration, axonal integrity, neuromuscular junction (NMJ) health and gliosis were also assessed. RESULTS: EpoD treatment prevented loss of the spinal motor neuron soma, and distal axon degeneration, early in the disease course. This, however, was not associated with protection of the NMJ synapse and did not improve motor phenotype or clinical progression. EpoD administration was also found to be neurotoxic at later disease stages. This was evidenced by accelerated motor neuron cell body loss, increasing gliosis, and was associated with detrimental outcomes to motor behaviour, clinical assessment and survival. CONCLUSIONS: The results suggest that EpoD accelerates disease progression in the SOD1G93A mouse model of ALS, and highlights that the pathophysiological involvement of microtubules in ALS is an evolving and underappreciated phenomenon.


Assuntos
Esclerose Lateral Amiotrófica/patologia , Epotilonas/farmacologia , Neurônios Motores/patologia , Junção Neuromuscular/patologia , Superóxido Dismutase-1/genética , Esclerose Lateral Amiotrófica/genética , Animais , Axônios/patologia , Modelos Animais de Doenças , Progressão da Doença , Força da Mão , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/efeitos dos fármacos , Destreza Motora/efeitos dos fármacos
17.
Int Nurs Rev ; 65(2): 254-261, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28542894

RESUMO

AIM: To investigate the risk factors and predictors of falls according to the general characteristics, conscious state, physical condition and treatment of hospitalized patients with cancer. BACKGROUND: Inpatients with cancer experience falls more frequently than those without cancer, and the degree of injuries is more severe among inpatients with cancer. A specific fall prevention strategy is needed for each patient. Prevention of falls in patients with cancer is very important for improving the quality of nursing care. METHODS: This retrospective study included matched case-control patients. We evaluated patients between January 1, 2013, and December 31, 2014. A total of 356 patients (fall group, 178; non-fall group, 178) were included. For fall prediction, logistic regression was performed on the variables that were statistically significant in the univariate analysis. RESULTS: The variables that were significant predictors of falls were the use of an assistive device, history of falls and fatigue. DISCUSSION: The predictors of falls in patients with cancer include physical conditions and general characteristics. Fall prevention strategies in patients with cancer should be planned individually with multifaceted aspects, including physical symptom management. LIMITATIONS: The study was conducted at a single cancer center in Korea; thus, our results cannot be generalized. Additionally, in Korea, it is common to have family members or private caregivers for patient care, and this might have influenced the results. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The predictive factors for falls reflect the nature of the patient's environment, culture and disease. Falls have a negative effect on patient safety and can significantly influence quality of life. Policies for patient safety need more specialized and customized approaches.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Marcha/fisiologia , Neoplasias/complicações , Qualidade de Vida , Medição de Risco , Acidentes por Quedas/prevenção & controle , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Neoplasias/terapia , República da Coreia , Estudos Retrospectivos , Fatores de Risco
18.
Neuropharmacology ; 128: 448-459, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29109058

RESUMO

A history of binge-drinking decreases protein expression of the glutamate-related scaffolding protein Homer2 within the central nucleus of the amygdala (CEA), coinciding with behavioral signs of negative affect. To assess the functional relevance of this protein change for withdrawal-induced hyper-anxiety, adult (PND 56) and adolescent (PND 28) male C57BL/6J mice were administered an intra-CEA infusion of an adeno-associated viral vector (AAV) carrying either cDNA to express Homer2 (H2-cDNA) or GFP as control. Mice underwent 14 days of binge-drinking under multi-bottle, limited-access conditions and were assayed for behavioral signs of negative affect during withdrawal using the light-dark box, marble burying, and forced swim tests (FST). Following behavioral testing, all animals experienced 5 days of drinking to evaluate the effects of prior alcohol experience and Homer2 manipulation on subsequent alcohol consumption. During protracted (4 weeks) withdrawal, adolescent alcohol-experienced GFP controls showed increased signs of negative affect across all 3 assays, compared to water-drinking GFP animals, and also showed elevated alcohol consumption during the subsequent drinking period. Homer2-cDNA infusion in adolescent-onset alcohol-drinking animals was anxiolytic and reduced subsequent alcohol consumption. Conversely, Homer2-cDNA was anxiogenic and increased drinking in water-drinking adolescents. Unfortunately, the data from adult-onset alcohol-drinking animals were confounded by low alcohol consumption and negligible behavioral signs of anxiety. Nevertheless, the present results provide novel cause-effect evidence supporting a role for CEA Homer2 in the regulation of both basal anxiety and the time-dependent intensification of negative affective states in individuals with a history of binge-drinking during adolescence.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Ansiedade/etiologia , Ansiedade/patologia , Núcleo Central da Amígdala/metabolismo , Proteínas de Arcabouço Homer/metabolismo , Síndrome de Abstinência a Substâncias/complicações , Fatores Etários , Consumo de Bebidas Alcoólicas/psicologia , Animais , Núcleo Central da Amígdala/patologia , Comportamento de Escolha/fisiologia , Adaptação à Escuridão/efeitos dos fármacos , Adaptação à Escuridão/fisiologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Arcabouço Homer/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Transdução Genética
19.
Oncogene ; 36(34): 4951, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28604745

RESUMO

This corrects the article DOI: 10.1038/onc.2011.331.

20.
Am J Transplant ; 17(6): 1656-1662, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28296255

RESUMO

Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models by using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B cells (Bregs). To elucidate further the mechanism by which Bregs induce tolerance, we investigated the requirement of natural killer (NK) and NKT cells in this model. To do so, hyperglycemic B6, µMT, Beige, or CD1d-/- mice received BALB/c islet grafts and treatment with the tolerance-inducing regimen consisting of anti-CD45RB and anti-TIM1. B6 mice depleted of both NK and NKT cells by anti-NK1.1 antibody and mice deficient in NK activity (Beige) did not develop tolerance after dual-antibody treatment. In contrast, transplant tolerance induction was successful in CD1d-/- recipients (deficient in NKT cells), indicating that NK, but not NKT, cells are essential in B cell-dependent tolerance. In addition, reconstitution of Beige host with NK cells restored the ability to induce transplant tolerance with dual-antibody treatment. Transfer of tolerance by B cells from tolerant mice was also dependent on host Nk1.1+ cells. In conclusion, these results show that regulatory function of B cells is dependent on NK cells in this model of transplantation tolerance.


Assuntos
Linfócitos B Reguladores/imunologia , Transplante das Ilhotas Pancreáticas/imunologia , Células Matadoras Naturais/imunologia , Células T Matadoras Naturais/imunologia , Tolerância ao Transplante/imunologia , Animais , Anticorpos Monoclonais/imunologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
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