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1.
Cell ; 163(6): 1348-59, 2015 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-26627734

RESUMO

Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl(-) efflux and osmotic cell shrinkage by opening TMEM16A Ca(2+)-activated Cl(-) channels. Release of Cl(-) from ISCs also forces K(+) efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea and prevents ATP-dependent shrinkage of supporting cells. These results indicate that supporting cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells.


Assuntos
Orelha Interna/crescimento & desenvolvimento , Células Ciliadas Auditivas/citologia , Trifosfato de Adenosina/metabolismo , Animais , Anoctamina-1 , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Orelha Interna/citologia , Orelha Interna/metabolismo , Células Ciliadas Auditivas/metabolismo , Células Labirínticas de Suporte/citologia , Células Labirínticas de Suporte/metabolismo , Camundongos , Camundongos Knockout , Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Gânglio Espiral da Cóclea/citologia , Gânglio Espiral da Cóclea/metabolismo
2.
J Immunol ; 213(5): 588-599, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38975728

RESUMO

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) in vivo. Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.


Assuntos
Antígenos CD , Apirase , Linfócitos T CD8-Positivos , Diferenciação Celular , Células T de Memória , Animais , Apirase/imunologia , Apirase/metabolismo , Camundongos , Linfócitos T CD8-Positivos/imunologia , Antígenos CD/metabolismo , Antígenos CD/imunologia , Humanos , Células T de Memória/imunologia , Diferenciação Celular/imunologia , Memória Imunológica/imunologia , Camundongos Endogâmicos C57BL , 5'-Nucleotidase/metabolismo , 5'-Nucleotidase/imunologia
3.
J Immunol ; 206(3): 554-565, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361206

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS that is characterized by demyelination, axonal loss, gliosis, and inflammation. The murine model of MS is the experimental autoimmune encephalopathy (EAE) induced by immunization of mice with myelin oligodendrocyte glycoprotein (MOG)35-55 Ig-like transcript 3 (ILT3) is an inhibitory cell surface receptor expressed by tolerogenic human dendritic cells. In this study, we show that the recombinant human ILT3.Fc protein binds to murine immune cells and inhibits the release of proinflammatory cytokines that cause the neuroinflammatory process that result in paralysis. Administration of ILT3.Fc prevents the rapid evolution of the disease in C57BL/6 mice and is associated with a profound reduction of proliferation of MOG35-55-specific Th1 and Th17 cells. Inhibition of IFN-γ and IL-17A in mice treated with ILT3.Fc is associated with delayed time of onset of the disease and its evolution to a peak clinical score. Neuropathological analysis shows a reduction in inflammatory infiltrates and demyelinated areas in the brains and spinal cords of treated mice. These results indicate that inhibition of Th1 and Th17 development provides effective suppression of EAE and suggests the feasibility of a clinical approach based on the use of ILT3.Fc for treatment of MS. Furthermore, our results open the way to further studies on the effect of the human ILT3.Fc protein in murine experimental models of autoimmunity and cancer.


Assuntos
Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/imunologia , Glicoproteínas de Membrana/metabolismo , Esclerose Múltipla/imunologia , Receptores Imunológicos/metabolismo , Proteínas Recombinantes/metabolismo , Células Th1/imunologia , Células Th17/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Terapia de Imunossupressão , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/imunologia , Receptores Imunológicos/genética , Proteínas Recombinantes/genética
4.
Ophthalmology ; 129(6): 679-693, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35085662

RESUMO

PURPOSE: To evaluate targetable mutations and molecular genetic pathways in conjunctival melanoma with clinical correlation. DESIGN: Observational case series. PARTICIPANTS: Patients with conjunctival melanoma. MAIN OUTCOME MEASURES: Mutational profile of the tumor by next-generation sequencing (NGS), alternative lengthening of telomeres (ALT) by fluorescence in situ hybridization (FISH), and ATRX immunohistochemistry. Outcomes at 2 years and 5 years of tumor-related metastasis and death were recorded. RESULTS: Of the 101 patients, mean age at presentation was 60 years, 52% were male, and 88% were White. The NGS panels initially targeted BRAF only (n = 6, 6%), BRAF/NRAS (n = 17, 17%), and BRAF/NRAS/NF1 (n = 10, 10%). Sixty-eight tumors were tested with the expanded 592-gene panel. Next-generation sequencing identified high-frequency mutations in NF1 (29/74, 39%), BRAF (31/101, 31%), NRAS (25/95, 26%), and ATRX (17/68, 25%). Of those with an ATRX mutation, 12 (71%) had an additional NF1 mutation. A subset analysis of 21 melanomas showed that the ATRX mutation was associated with loss of ATRX protein expression and ALT. Loss of ATRX expression and ALT were present in both intraepithelial and invasive tumors, suggesting that an ATRX mutation is an early event in conjunctival melanoma progression. The NF1 and ATRX mutations were associated with tarsal (vs. nontarsal) tumors (NF1: 28% vs. 9%, P = 0.035, ATRX: 41% vs. 14%, P = 0.021) and orbital (vs. nonorbital) tumors (ATRX: 24% vs. 2%, P = 0.007). ATRXMUT (vs. ATRXWT) tumors were associated with a lower 2-year rate of metastasis (0% vs. 24%, P = 0.005). NRASMUT (vs. NRASWT) tumors were associated with a greater 2-year rate of metastasis (28% vs. 14%, P = 0.07) and death (16% vs. 4%, P = 0.04), with a 5-fold increased risk of death (relative risk, 5.45 [95% confidence interval, 1.11-26.71], P = 0.039). CONCLUSIONS: This study confirms the high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma. An NRAS mutation implied increased risk for metastasis and death. Loss of ATRX and ALT may be early events in conjunctival melanoma development.


Assuntos
Neoplasias da Túnica Conjuntiva , Melanoma , Neoplasias Cutâneas , Neoplasias da Túnica Conjuntiva/genética , Neoplasias da Túnica Conjuntiva/patologia , Análise Mutacional de DNA , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Melanoma/genética , Melanoma/patologia , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia
5.
J Vasc Surg ; 76(6): 1704-1709, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35709855

RESUMO

OBJECTIVE: A surgical temporal artery biopsy (TAB) is the gold standard for diagnosis of giant cell arteritis (GCA). The necessity of performing a bilateral biopsy remains under debate. The primary objective of this study was to assess the rate of discordance between pathology results in patients who underwent bilateral TAB for suspected GCA. METHODS: We performed a retrospective review of patients who underwent bilateral TAB for the diagnosis of GCA between 2011 and 2020. The primary end point was the rate of discordance between specimens for patients with pathology positive GCA. Secondary end points included assessments of the sensitivity of preoperative temporal artery duplex and the effects of specimen length and specialty of referring provider on the diagnostic yield of the biopsy. RESULTS: During the study period, 310 patients underwent bilateral TAB for the diagnosis of GCA. These patients were primarily female (73.9%), elderly (mean age, 70.8 years), and Caucasian (95.8%). Preoperative symptoms for patients were typically bilateral (59%) and included headache (81%), vision changes (45.2%), and temporal tenderness (32.6%). Most patients (85.2%) were on preoperative steroid therapy at the time of surgical biopsy with a mean preoperative duration of steroid therapy of 15.1 days. Overall, 91 patients (29.4%) had a positive pathologic diagnosis after bilateral TAB. Of these patients, 11 had a positive pathology result in only a single specimen, resulting in a discordance rate of 12.1%. Preoperative temporal artery duplex demonstrated a low sensitivity (27.3%) for identifying patients with pathologic positive disease. There were no significant differences between the pathology-positive and -negative patients in terms of mean surgical specimen length (1.67 cm vs 1.64 cm; P = .67) or the specialty of the referring provider (P = .73). CONCLUSIONS: At our institution, we observed a 12.1% discordance rate between pathology results in patients who underwent bilateral TAB for diagnosis of GCA. A preoperative temporal artery duplex provided little value in identifying patients with biopsy-proven GCA.


Assuntos
Arterite de Células Gigantes , Humanos , Feminino , Idoso , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/patologia , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/cirurgia , Artérias Temporais/patologia , Biópsia/métodos , Estudos Retrospectivos , Terapia Neoadjuvante
6.
Brain ; 144(9): 2696-2708, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33856027

RESUMO

Many patients with SARS-CoV-2 infection develop neurological signs and symptoms; although, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological and molecular findings of 41 consecutive patients with SARS-CoV-2 infections who died and underwent autopsy in our medical centre. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit. Hospital-associated complications were common, including eight patients (20%) with deep vein thrombosis/pulmonary embolism, seven (17%) with acute kidney injury requiring dialysis and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 h of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischaemic changes in all brains, both global and focal; large and small infarcts, many of which appeared haemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis of large arteries and arteriolosclerosis, although none showed evidence of vasculitis. Eighteen patients (44%) exhibited pathologies of neurodegenerative diseases, which was not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR, RNAscope® and immunocytochemistry with primers, probes and antibodies directed against the spike and nucleocapsid regions. The PCR analysis revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in the nasal epithelia. RNAscope® and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in coronavirus disease 2019 brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but more likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischaemia. Further studies are needed to define whether these pathologies, if present in patients who survive coronavirus disease 2019, might contribute to chronic neurological problems.


Assuntos
Infarto Encefálico/patologia , Encéfalo/patologia , COVID-19/patologia , Hipóxia-Isquemia Encefálica/patologia , Hemorragias Intracranianas/patologia , Injúria Renal Aguda/complicações , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/complicações , Encéfalo/metabolismo , Infarto Encefálico/complicações , COVID-19/complicações , COVID-19/fisiopatologia , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Inflamação , Unidades de Terapia Intensiva , Hemorragias Intracranianas/complicações , Masculino , Microglia/patologia , Pessoa de Meia-Idade , Neurônios/patologia , Fagocitose , Fosfoproteínas/metabolismo , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , RNA Viral/metabolismo , Diálise Renal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Taxa de Sobrevida , Linfócitos T/patologia , Trombose Venosa/complicações , Trombose Venosa/fisiopatologia
7.
Chemistry ; 25(1): 367-372, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30379367

RESUMO

A simple aqueous-phase synthesis of PbSe nanocubes with tunable sizes has been developed by first preparing a Na2 SeSO3 stock solution through dissolution of selenium powder in a solution of Na2 SO3 at 90-100 °C for 30 min, and adding part of this solution to a mixture of lead acetate and acetic acid at room temperature with stirring for only 5-8 min to complete the nanocrystal growth. Adjusting the volume of acetic acid and Na2 SeSO3 solution added enabled the size of the nanocrystals to be tuned, with average edge lengths of 13 to 121 nm attained. Changes in solution color revealed very different crystal growth rates for the 13 and 121 nm nanocubes. The PbSe cubes exhibit size-dependent absorption bands in the ultraviolet and visible-light region; the band positions show progressive redshifts with increasing particle size. Slight photocatalytic activity upon 532 nm laser irradiation of the nanocubes suggests the presence of higher energy levels in the band structure of PbSe. The synthetic conditions can be easily scaled up to obtain a large quantity of PbSe nanocubes for applications.

8.
CA Cancer J Clin ; 62(4): 220-41, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22700443

RESUMO

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.


Assuntos
Neoplasias/epidemiologia , Neoplasias/terapia , Sistema de Registros/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos , American Cancer Society , Terapia Combinada , Feminino , Humanos , Incidência , Masculino , Prevalência , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
9.
Postgrad Med J ; 95(1124): 307-313, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209183

RESUMO

BACKGROUND: Growing evidence shows links between septicaemia and non-multiple sclerosis demyelinating syndromes (NMSDS); nevertheless, epidemiological data are still very limited. This study aimed to explore the relationship between septicaemia and NMSDS in a general population. METHODS: The study included 482 781 individuals diagnosed with septicaemia and 1 892 825 age/sex-matched non-septicaemia patients for the comparison. Data were drawn from a population-based nationwide National Health Insurance Research Database Taiwan, from 1 January 2002 to 31 December 2011. The two cohorts of patients with and without septicaemia were followed up for the occurrence of NMSDS. The Cox-proportional hazard regression model was performed to estimate adjusted HR after multivariate adjustment. RESULTS: Individuals with septicaemia had a 4.17-fold (95% CI 3.21 to 5.4, p < 0.001) higher risk to develop NMSDS compared with those without septicaemia. Patients aged <65 years had a greater NMSDS risk (<45 years: HR = 6.41, 95% CI 3.65 to 11.3, p < 0.001; 45-64 years: HR = 6.66, 95% CI 3.98 to 11.2, p < 0.001). Furthermore, females with septicaemia and individuals with higher severity of septicaemia were associated with increased risks of developing NMSDS. CONCLUSIONS: Our results indicated that patients with septicaemia were likely to develop NMSDS. A possible contributing role of septicaemia in increasing the hazard of NMSDS is proposed, based on the outcome that individuals with higher severity of septicaemia carried elevated threat of encountering NMSDS.


Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Sepse/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Desmielinizantes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/imunologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
10.
Postgrad Med J ; 95(1120): 72-77, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30936249

RESUMO

BACKGROUND: Primary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed to a great risk for developing sleep apnoea (SA). METHODS: In this retrospective longitudinal study, the data obtained from the Longitudinal Health Insurance Database in Taiwan were analysed. The study included 1346 patients with PHDs who were initially diagnosed and 5348 patients who were randomly selected and age/sex matched with the study group as controls. PHDs, SA, comorbidities and other confounding factors were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification. Cox proportional hazards regressions were employed to examine adjusted HRs after adjusting with confounding factors. RESULTS: Our data revealed that patients with PHDs had a higher risk (HR 2.17, 95% CI 1.259 to 3.739, p<0.05) to develop SA compared with matched cohorts, whereas patients with migraine exhibited a high risk (HR 2.553, 95% CI 1.460 to 4.395, p<0.01). The results showed that patients with PHDs aged 18-44 exhibited highest risk of developing SA. In addition, males with PHDs exhibited an HR 3.159 (95% CI 1.479 to 6.749, p<0.01) for developing SA, respectively. The impact of PHDs on SA risk was progressively increased by various follow-up time intervals. CONCLUSION: Our results suggest that PHDs are linked to an increased risk for SA with sex-dependent and time-dependent characteristics.


Assuntos
Transtornos da Cefaleia Primários/complicações , Síndromes da Apneia do Sono/etiologia , Adulto , Idoso , Feminino , Transtornos da Cefaleia Primários/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Taiwan/epidemiologia
11.
Cell Microbiol ; 19(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27665576

RESUMO

Lipoprotein lipase (LPL) has been identified as an anti-hepatitis C virus (HCV) host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti-HCV. The functional activation of peroxisome proliferator-activated receptor (PPAR) α signal by LPL transducing into hepatocytes was investigated in HCV-infected cells, primary human hepatocytes, and in HCV-core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARα in Huh7 cells and primary human hepatocytes were elevated by physiologically ranged LPL treatment of either very-low density lipoprotein or HCV particles. The LPL-induced hepatic PPARα activation was weakened by blocking the LPL enzymatic activity, and by preventing the cellular uptake of free unsaturated fatty acids with either albumin chelator or silencing of CD36 translocase. The knockdowns of PPARα and CD36 reversed the LPL-mediated suppression of HCV infection. Furthermore, treatment with LPL, like the direct activation of PPARα, not only reduced the levels of apolipoproteins B, E, and J, which are involved in assembly and release of HCV virions, but also alleviated hepatic lipid accumulation induced by core protein. HCV-core transgenic mice exhibited more hepatic miR-27b, which negatively regulates PPARα expression, than did the wild-type controls. The induction of LPL activity by fasting in the core transgenic mice activated PPARα downstream target genes that are involved in fatty acid ß-oxidation. Taken together, our study reveals dual beneficial outcomes of LPL in anti-HCV and anti-steatosis and shed light on the control of chronic hepatitis C in relation to LPL modulators.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Hepacivirus/fisiologia , Hepatite C/metabolismo , Lipase Lipoproteica/fisiologia , Fígado/enzimologia , Animais , Antígenos CD36/metabolismo , Linhagem Celular Tumoral , Expressão Gênica , Hepatite C/virologia , Hepatócitos/enzimologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Lipólise , Lipoproteínas VLDL/metabolismo , Fígado/virologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , PPAR alfa/metabolismo , Proteínas do Core Viral/fisiologia
15.
Nanotechnology ; 28(38): 38LT02, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28721944

RESUMO

We explore the use of cubic-zinc peroxide (ZnO2) as a switching material for electrochemical metallization memory (ECM) cell. The ZnO2 was synthesized with a simple peroxide surface treatment. Devices made without surface treatment exhibits a high leakage current due to the self-doped nature of the hexagonal-ZnO material. Thus, its switching behavior can only be observed when a very high current compliance is employed. The synthetic ZnO2 layer provides a sufficient resistivity to the Cu/ZnO2/ZnO/ITO devices. The high resistivity of ZnO2 encourages the formation of a conducting bridge to activate the switching behavior at a lower operation current. Volatile and non-volatile switching behaviors with sufficient endurance and an adequate memory window are observed in the surface-treated devices. The room temperature retention of more than 104 s confirms the non-volatility behavior of the devices. In addition, our proposed device structure is able to work at a lower operation current among other reported ZnO-based ECM cells.

16.
Acta Neurol Taiwan ; 25(2): 56-59, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27854093

RESUMO

PURPOSE: We had recently reported one case at American Journal of Emergency Medicine about centralvariant posterior reversible encephalopathy syndrome (PRES) in an 84-year-old woman with an initial misdiagnosis as central pontine myelinolysis (CPM). Here, we introduce another case of centralvariant PRES in a 49-year-old man mimicking as acute brainstem infarction in the cranial computed tomography (CT) findings. CASE REPORT: A 49-year-old man was admitted to the emergency department with a 5-day history of vertigo, cognitive decline, and difficulty in walking. Neurologic examination revealed drowsiness with a Glasgow Coma Scale score of 12 (eye opening: 3, best verbal response: 4, and best motor response: 5), slow movement in pursuit and saccades, and gait instability with a Medical Research Council scale of grade 4-5. Non-contrast cranial CT showed hypodense lesions in the pons, and antiplatelet agent was initiated for presumed pons infarction. However, the brain magnetic resonance imaging (MRI) demonstrated vasogenic edema in the corresponding area, consistent with the diagnosis of central-variant PRES. CONCLUSION: This case report raises the awareness that when hypodense brainstem lesions on brain CT in patients with progressive neurological dysfunction, the rare condition of central-variant PRES should be considered in the differential diagnosis to avoid inadequate management. Cranial magnetic resonance imaging (MRI) may help in diagnosis and dealing with of these patients with similar radiological and clinical abnormalities.


Assuntos
Edema Encefálico/diagnóstico por imagem , Infartos do Tronco Encefálico/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Headache Pain ; 17(1): 97, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27770406

RESUMO

BACKGROUND: Although the comorbidity of migraine and restless legs syndrome (RLS) has been well-documented, the association between RLS and migraine frequency has yet to be elucidated. The present study aims to evaluate the prevalence of RLS among individuals who experience low-frequency, high-frequency, or chronic migraine presenting with and without aura. METHODS: We conducted a cross-sectional, case-controlled study involving 505 participants receiving outpatient headache treatment. Standardized questionnaires were administered to collect information on experiences of migraine, RLS, sleep quality, anxiety, depression, and demographics. Participants were categorized into low-frequency (1-8/month), high-frequency (9-14/month), and chronic (≥15/month) headache groups. RLS was diagnosed according to the criteria outlined by the International RLS Study Group (IRLSSG). The Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality and identify symptoms of anxiety and depression. Associations between migraine frequency and RLS prevalence were investigated using multivariate linear and logistic regression. RESULTS: Univariate analysis revealed an effect of migraine frequency on RLS prevalence (p = 0.026), though this effect did not persist following adjustment for baseline characteristics (p = 0.256). The trend was robust in patients whose migraines presented with auras (p univariate = 0.002; p multivariate = 0.043) but not in those without auras (p univariate and p multivariate > 0.05). Higher anxiety [odds ratio (OR) = 1.18, p = 0.019] and sleep disturbance (OR = 1.17, p = 0.023) scores were associated with higher RLS prevalence. CONCLUSIONS: Higher migraine frequency correlates with a higher prevalence of RLS, particularly among patients with auras.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Enxaqueca com Aura/epidemiologia , Enxaqueca sem Aura/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários , Adulto Jovem
18.
J Headache Pain ; 17(1): 108, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27905079

RESUMO

BACKGROUND: Headache such as migraine is associated with stroke. Studies focused on primary headache disorders (PHDs) as a risk factor for stroke are limited. The purpose of this population-based cohort study was to explore whether patients with PHDs were at a high risk for developing stroke. METHODS: A total of 1346 patients with PHDs were enrolled and compared with 5384 age-, gender- and co-morbidity-matched control cohorts. International Classification of Diseases, Clinical Modification codes were administered for the definition of PHDs, stroke, and stroke risk factors. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR). RESULTS: PHDs patients exhibited a 1.49 times (95% CI :1.15-1.98, p < 0.01) higher risk for developing ischaemic stroke compared with that of control cohorts. Both migraine (HR = 1.22, 95% CI :1.13-1.97, p < 0.05) and tension-type headache (HR = 2.29, 95% CI :1.22-2.80, p < 0.01) were associated with an increased risk of ischemic stroke. Females with PHDs were at greater risk of developing ischaemic stroke (HR = 1.49, 95% CI :1.13-1.90, p < 0.01) than those without PHDs. PHDs patient aged 45 to 64 years displayed significantly higher risk to develop ischaemic stroke (HR = 1.50, 95% CI: 1.11-2.10, p < 0.05) than the matched controls. The impact of PHDs on ischaemic stroke risk became gradually apparent by different following time intervals beyond 2 years after first diagnosis. CONCLUSION: PHDs is suggestive of an incremental risk for ischaemic stroke with gender-dependent, age-specific and time-dependent characteristics.


Assuntos
Transtornos da Cefaleia Primários/diagnóstico , Transtornos da Cefaleia Primários/epidemiologia , Vigilância da População , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Estudos de Coortes , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Vigilância da População/métodos , Distribuição Aleatória , Fatores de Risco , Taiwan/epidemiologia , Cefaleia do Tipo Tensional/diagnóstico , Cefaleia do Tipo Tensional/epidemiologia
19.
J Neurosci ; 34(11): 3959-68, 2014 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-24623773

RESUMO

We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical "empty basiconic neuron" system.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Farneseno Álcool , Neurônios Receptores Olfatórios/fisiologia , Receptores Odorantes/fisiologia , Animais , Animais Geneticamente Modificados , Comportamento Animal/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/anatomia & histologia , Feminino , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/fisiologia , Masculino , Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Odorantes , Receptores Odorantes/genética , Olfato/fisiologia
20.
Acta Neurol Taiwan ; 24(1): 11-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26179684

RESUMO

PURPOSE: Occipital condyle syndrome (OCS) is a rare cause of headache. This study herein reports a case in which a unique headache and tongue deviation appear as symptoms of the first presentation of a malignant tumor. CASE REPORT: A healthy 67-year-old male presented with a unilateral shooting pain in the occipital region, accompanied by slurred speech and difficulty swallowing. Neurological examinations later revealed atrophy and mild fasciculation of the tongue. The clinical symptoms and MRI results suggested OCS. Screening for tumor markers showed an elevated CEA. The chest CT revealed a lobulated soft-tissue mass in the lower left lobe, and a CTguided biopsy confirmed the diagnosis of adenocarcinoma. A whole body bone scan found multiple foci. The adenocarcinoma was graded pT2bN3M1b, stage IV. The headache improved with a prescription of prednisone, 60 mg to be taken daily. With three months of treatment, clinical examinations showed that the patient was free of pain and that there had been no progression of the atrophy or deviation of the tongue. CONCLUSION: The possible etiology of OCS includes a primary tumor or metastatic lesion that directly invades the base of the skull. Determining the underlying causes of OCS can be challenging, but MR imaging is currently the diagnostic tool of choice. An awareness of the features of OCS in healthy adults may be able to lead to earlier diagnosis of the underlying etiology and efficient relief of the symptoms.


Assuntos
Adenocarcinoma/patologia , Cefaleia/etiologia , Doenças do Nervo Hipoglosso/etiologia , Neoplasias Pulmonares/patologia , Osso Occipital/inervação , Neoplasias da Base do Crânio/complicações , Idoso , Humanos , Doenças do Nervo Hipoglosso/fisiopatologia , Masculino , Neoplasias da Base do Crânio/secundário , Síndrome , Língua/patologia
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