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1.
Nanotechnology ; 35(12)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38061057

RESUMO

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

2.
BMC Cancer ; 23(1): 362, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081426

RESUMO

BACKGROUND: Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. METHODS: ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. DISCUSSION: ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. TRIAL REGISTRATION: NCT05230251 (ClinicalTrials.gov).


Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Qualidade de Vida , Tomografia Computadorizada por Raios X
3.
Br J Surg ; 108(11): 1331, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34179940
4.
Int J Oral Maxillofac Surg ; 49(4): 446-453, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31420120

RESUMO

Post-surgical neuropathy is a known complication of many surgical procedures for which few remedies are effective. This study used neurosensory assessments and biochemical assays to evaluate the efficacy of melatonin on nerve healing following orthognathic surgery. Thirty randomly allocated orthognathic patients were prophylactically administered either oral melatonin or identical placebo for 21 consecutive days. Pre- and post-surgical clinical parameters included subjective pain, numbness, and objective neurosensory function. Pre- and post-surgical biochemical parameters were serum hydrogen peroxide and antioxidant enzyme levels. Melatonin was found to significantly reduce subjective pain perception by 50% in the early postoperative days. A 30% reduction in subjective numbness perception was observed at 1-week postoperative, increasing to an over 80% reduction by 3 months postoperative (P<0.00001). Objective neurosensory testing showed a significant improvement in healing profile in the melatonin group. Postoperatively, the hydrogen peroxide concentration was lower in the melatonin group (P<0.00001), and the levels of antioxidant enzymes were higher (P<0.00001). The strong correlations between clinical outcomes and biochemical changes suggest a link between antioxidant effects and reduced postsurgical pain and sensory recovery. The study findings suggest that the prophylactic administration of melatonin confers significant clinical benefits in terms of reduced postoperative pain and opioid use and improved sensory recovery following surgery.


Assuntos
Melatonina , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Método Duplo-Cego , Humanos , Dor Pós-Operatória
5.
Neuroradiology ; 61(9): 991-1010, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31152191

RESUMO

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.


Assuntos
Circulação Cerebrovascular/fisiologia , Angiografia por Tomografia Computadorizada , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marcadores de Spin , Adulto Jovem
6.
J Neurosci Methods ; 314: 13-20, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658125

RESUMO

BACKGROUND: We previously showed that CT perfusion (CTP) and arterial spin labelled (ASL) MRI can localize the seizure onset zone in humans via postictal perfusion patterns. As a step towards improving the feasibility/ease of collecting postictal CBF data, we determined whether EEG electrodes need to be removed for CTP data collection and whether a cross-modality comparison between baseline ASL and postictal CTP data is possible. NEW METHOD: Five patients with epilepsy underwent postictal CTP scanning. Three patients had an interictal ASL scan; one patient had both an ASL and CTP interictal scan. Postictal CTP maps were quantitatively compared to 1) ASL maps averaged from 100 healthy controls, 2) each patient's baseline ASL map and 3) each patient's baseline CTP map. To assess for electrode artifacts, a phantom and one patient underwent CTP scanning with EEG electrodes in place. The acquired scans were assessed for artifacts and for postictal hypoperfusion. RESULTS: Focal postictal hypoperfusion was observable only in intra-modality comparisons (CTP to CTP) and not in cross-modality comparisons (CTP to ASL). EEG electrodes produced streaking artifact that decreased image quality and precluded quantitative analysis. COMPARISON WITH EXISTING METHODS(S): An intra-modality comparison of baseline CTP to postictal CTP was the only comparison method that showed localized hypoperfusion. CONCLUSIONS: Quantitative comparison between postictal CTP and baseline ASL scans is not feasible. Postictal hypoperfusion can be detected by CTP only when two CTP scans are collected and when metallic EEG electrodes are removed.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/fisiopatologia , Imagem de Perfusão/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Artefatos , Circulação Cerebrovascular , Eletroencefalografia/instrumentação , Eletroencefalografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Imagem de Perfusão/instrumentação , Imagens de Fantasmas , Tomografia Computadorizada por Raios X/instrumentação , Adulto Jovem
7.
Int J Biol Macromol ; 123: 255-260, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30419331

RESUMO

The polysaccharide, inulin, is considered the clinical gold standard for measuring glomerular filtration rate (GFR), an assessment of kidney filtering capacity and renal function, and therefore, is a prognostic indicator of chronic kidney disease (CKD). The classic method of measuring GFR is laborious, tedious and invasive. Therefore, estimated GFR (eGFR) has become the favoured measurement, but unfortunately suffers in its accuracy. Here, we describe the development of a near infrared dye-labeled inulin, Cy7.5-inulin conjugate, for use as an optical probe to accurately and non-invasively measure GFR in patients by transcutaneous pulse dye densitometer (TPDD). We have characterized the modifications made to inulin and the dye-polysaccharide conjugate by a number of analytical techniques and demonstrated that it is stable under experimental in vivo conditions. To this end, the probe has been successfully used in a pig model to accurately measure GFR non-invasively.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Inulina/isolamento & purificação , Insuficiência Renal Crônica/diagnóstico , Animais , Creatinina/química , Densitometria , Humanos , Inulina/química , Prognóstico , Insuficiência Renal Crônica/fisiopatologia , Suínos
8.
Transplant Proc ; 50(10): 3100-3104, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577173

RESUMO

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful.


Assuntos
Aloenxertos/irrigação sanguínea , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Adulto , Sistema Biliar/diagnóstico por imagem , Colangiopancreatografia por Ressonância Magnética , Tomografia Computadorizada de Feixe Cônico , Feminino , Artéria Hepática/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Masculino , Veia Porta/diagnóstico por imagem , Estudos Retrospectivos
9.
AJNR Am J Neuroradiol ; 39(11): 2027-2033, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30337436

RESUMO

BACKGROUND AND PURPOSE: Patients with aneurysmal SAH and good clinical status at admission are considered at a lower risk for delayed cerebral ischemia. Prolonged MTT may be associated with an increased risk. It is unclear whether this is dependent on clinical status. Our purpose was to determine whether increased MTT within 3 days of aneurysmal SAH compared with baseline is associated with a higher risk of delayed cerebral ischemia in patients with good (World Federation of Neurosurgical Societies I-III) versus poor (World Federation of Neurosurgical Societies IV-V) admission status. MATERIALS AND METHODS: This prolonged MTT was a multicenter, prospective cohort investigation of 87 patients with aneurysmal SAH. MTT was measured at admission before aneurysm treatment (MTT1) and following repair (MTT2) within 3 days of admission; MTTdiff was calculated as the difference between MTT2 and MTT1. Changes in MTT across time were assessed with repeated measures analyses. Risk of delayed cerebral ischemia or death was determined with multivariate logistic regression analysis. RESULTS: In patients with a good grade (n = 49), MTT was prolonged in patients who developed delayed cerebral ischemia, with MTTdiff significantly greater (0.82 ± 1.5) compared with those who did not develop delayed cerebral ischemia (-0.14 ± 0.98) (P = .03). Prolonged MTT was associated with a significantly higher risk of delayed cerebral ischemia or death (OR = 3.1; 95% CI, 1.3-7.4; P = .014) on multivariate analysis. In patients with poor grades (n = 38), MTTdiff was not greater in patients who developed delayed cerebral ischemia; MTT1 was significantly prolonged compared with patients with a good grade. CONCLUSIONS: Patients in good clinical condition following aneurysmal SAH but with increasing MTT in the first few days after aneurysmal SAH are at high risk of delayed cerebral ischemia and warrant close clinical monitoring.


Assuntos
Isquemia Encefálica/etiologia , Imagem de Perfusão/métodos , Hemorragia Subaracnóidea/classificação , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos
10.
Work ; 61(3): 403-411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30373993

RESUMO

BACKGROUND: Low back pain (LBP) is a common health problem with high reoccurrence rate. As patients with LBP are often found to be proprioception impaired, new proprioception exercises should be explored. Whole body vibration (WBV) has been proven to improve muscle function and proprioception. OBJECTIVE: The aim of this study was to determine the effects of WBV on spinal proprioception when WBV was administered in standing and seated postures. METHODS: Twenty healthy male individuals (mean age: 23.2±1.2 years) were recruited and randomly assigned to two WBV groups: WBV in standing or WBV in seated posture. Their body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination during dynamic motion in flexion and extension were assessed before, immediately after, 30 minutes after and 1 hour after 5 minutes of WBV (18 Hz, 6 mm amplitude) exposure. A Mixed ANOVA was used to analyze the effects of group and time factors on these four outcome measures. RESULTS: There were no significant interaction (group and time) and group effects on all outcome measures. Participants were found to have significant different time effect on body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination. CONCLUSIONS: WBV could significantly improve spinal proprioception including body posture, lumbar repositioning ability, maximum reaching distance and lumbopelvic coordination in healthy individuals. WBV protocol is recommended to confirm its clinical application for improving spinal proprioception and its effects on patients with LBP is warranted.


Assuntos
Traumatismos Ocupacionais/etiologia , Propriocepção/fisiologia , Medula Espinal/fisiologia , Vibração/efeitos adversos , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos Ocupacionais/fisiopatologia , Postura/fisiologia
11.
Lupus ; 27(11): 1854-1859, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30139297

RESUMO

Mesenchymal stem cell therapy is a promising candidate for the treatment of systemic lupus erythematosus (SLE). To exert their efficacy fully, mesenchymal stem cells must infiltrate efficiently into the lesion sites. Here, we examined the role of CXCR3 in mesenchymal stem cell infiltration into the kidney of MRL. Faslpr mice, which highly expressed CXCL10. The phenotypes, production of immunosuppressive mediators, and capacity to inhibit T and B cells of CXCR3-deficient mesenchymal stem cells were similar to those of wild-type mesenchymal stem cells. However, they showed less infiltration into the nephritic kidney, less conjugation with endothelial cells and weaker MMP-9 expression than did wild-type mesenchymal stem cells. Consequently, CXCR3-deficient mesenchymal stem cells did not ameliorate lupus symptoms in MRL. Faslpr mice in comparison with wild-type mesenchymal stem cells. In summary, our data suggest that upregulation of CXCR3 in mesenchymal stem cells will be a good strategy to increase their infiltration into the kidney, which will improve therapeutic outcomes in SLE.


Assuntos
Rim/patologia , Lúpus Eritematoso Sistêmico/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Linfócitos B/metabolismo , Expressão Gênica , Imunoglobulina G/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Receptores CXCR3/deficiência , Receptores CXCR3/genética
12.
Aliment Pharmacol Ther ; 47(12): 1673-1681, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29696665

RESUMO

BACKGROUND: Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients. AIM: To evaluate renal safety of TDF according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. METHODS: We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed. RESULTS: The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2 , 95% confidence interval [CI]: 13.76-17.70 vs 5.96 mL/min/1.73 m2 , 95% CI: 4.72-7.19; P < 0.001). The cumulative incidence of renal function deterioration was significantly higher in the TDF group (TDF vs ETV: 11.1%, 95% CI: 7.4-14.8 vs 1.7%, 95% CI: 1.0-2.4; P < 0.001). After adjusting for age, pre-existing CKD and diabetes, TDF was independently associated with an increased risk of renal function deterioration (HR 5.36, 95% CI: 2.16-13.35; P < 0.001). Pre-existing CKD (HR 6.71, 95% CI: 2.25-17.65), proteinuria (HR 3.39, 95% CI: 1.23-9.39), and haematuria (HR 4.25, 95% CI: 1.32-13.68) were also independent factors of renal dysfunction. CONCLUSION: By following the KDIGO guidelines, we confirmed that TDF was associated with a higher risk of renal dysfunction as compared to ETV.


Assuntos
Antivirais/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Tenofovir/efeitos adversos , Adulto , Antivirais/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Incidência , Rim/patologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Tenofovir/uso terapêutico
13.
Malays J Pathol ; 39(3): 321-326, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29279598

RESUMO

Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It results from the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon 147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature although affected carriers are usually asymptomatic and do not require intervention. Several case studies in this region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemia with one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobin Tak was found in a family of Malay ethnic origin. Cascade family screening was conducted while investigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previous Hb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand and Homozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric, had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineously married and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of the girl's blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinity haemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients with abnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.


Assuntos
Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Hemoglobinas Anormais/genética , Policitemia/genética , Pré-Escolar , Feminino , Homozigoto , Humanos , Linhagem
14.
J Neurol Sci ; 376: 206-210, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28431614

RESUMO

BACKGROUND AND PURPOSE: Using an extended CT perfusion acquisition (150s), we sought to determine the association between perfusion parameters and malignant edema after ischemic stroke. METHODS: Patients (from prospective study PROVE-IT, NCT02184936) with terminal internal carotid artery±proximal middle cerebral occlusion were involved. CTA was assessed for clot location and status of leptomeningeal collaterals. The following CTP parameters were calculated within the ischemic territory and contralaterally: permeability surface area product (PS), cerebral blood flow (CBF) and cerebral blood volume (CBV). PS was calculated using the adiabatic approximation to the Johnson and Wilson model. Outcome was evaluated by midline shift and infarction volume on follow-up imaging. RESULTS: Of 200 patients enrolled, 7 patients (3.5%) had midline shift≥5mm (2 excluded for poor-quality scans). Five patients with midline shift and 5 matched controls were analysed. There was no significant difference in mean PS, CBF and CBV within the ischemic territory between the two groups. A CBV threshold of 1.7ml/100g had the highest AUC=0.72, 95% CI=0.54-0.90 for early midline shift prediction, sensitivity and specificity were 0.83 and 0.67 respectively. CONCLUSION: Our preliminary results did not show significant differences in permeability surface area analysis if analysed for complete ischemic region. CBV parameter had the highest accuracy and there was a trend for the mean PS values for midline shift prediction.


Assuntos
Edema Encefálico/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Idoso , Área Sob a Curva , Edema Encefálico/fisiopatologia , Edema Encefálico/terapia , Doenças das Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/terapia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Feminino , Seguimentos , Humanos , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/terapia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Cell Death Dis ; 7: e2298, 2016 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-27441650

RESUMO

Maintaining mesothelial cell viability is critical to long-term successful peritoneal dialysis (PD) treatment. To clarify the viability mechanism of peritoneal mesothelial cells under PD solutions exposure, we examined the mechanisms of cellular response to this stress conditions. Here we report that the proteasome activity is inhibited when treated with PD solutions. Proteasome inhibition-mediated activation of salt-inducible kinase 2 (SIK2), an endoplasmic reticulum-resident protein, is important for mesothelial cell viability. SIK2 is mobilized to promote autophagy and protect the cells from apoptosis under PD solution or MG132 treatment. Immunofluorescence staining showed that SIK2 is colocalized with LC3B in the autophagosomes of mesothelial cells treated with PD solution or derived from patients undergoing PD treatment. SIK2 activation is likely via a two-step mechanism, upstream kinases relieving the autoinhibitory conformation of SIK2 molecule followed by autophosphorylation of Thr175 and activation of kinase activity. These results suggest that activation of SIK2 is required for the cell viability when proteasome activity is inhibited by PD solutions. Maintaining or boosting the activity of SIK2 may promote peritoneal mesothelial cell viability and evolve as a potential therapeutic target for maintaining or restoring peritoneal membrane integrity in PD therapy.


Assuntos
Soluções para Diálise/farmacologia , Células Epiteliais/efeitos dos fármacos , Diálise Peritoneal , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Cisteína Proteinase/farmacologia , Soluções para Diálise/química , Ativação Enzimática , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Leupeptinas/farmacologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pressão Osmótica , Peritônio/citologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Estresse Mecânico
16.
Psychiatry J ; 2016: 7146341, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27314005

RESUMO

Background. Several psychometric instruments are available for the diagnostic interview of subjects at ultra high risk (UHR) of psychosis. Their diagnostic comparability is unknown. Methods. All referrals to the OASIS (London) or CAMEO (Cambridgeshire) UHR services from May 13 to Dec 14 were interviewed for a UHR state using both the CAARMS 12/2006 and the SIPS 5.0. Percent overall agreement, kappa, the McNemar-Bowker χ (2) test, equipercentile methods, and residual analyses were used to investigate diagnostic outcomes and symptoms severity or frequency. A conversion algorithm (CONVERT) was validated in an independent UHR sample from the Seoul Youth Clinic (Seoul). Results. There was overall substantial CAARMS-versus-SIPS agreement in the identification of UHR subjects (n = 212, percent overall agreement = 86%; kappa = 0.781, 95% CI from 0.684 to 0.878; McNemar-Bowker test = 0.069), with the exception of the brief limited intermittent psychotic symptoms (BLIPS) subgroup. Equipercentile-linking table linked symptoms severity and frequency across the CAARMS and SIPS. The conversion algorithm was validated in 93 UHR subjects, showing excellent diagnostic accuracy (CAARMS to SIPS: ROC area 0.929; SIPS to CAARMS: ROC area 0.903). Conclusions. This study provides initial comparability data between CAARMS and SIPS and will inform ongoing multicentre studies and clinical guidelines for the UHR psychometric diagnostic interview.

17.
Int J Lab Hematol ; 38(4): 435-43, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27349818

RESUMO

INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately. METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR). RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously. CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase/métodos , Deleção de Sequência , Talassemia alfa/genética , Variações do Número de Cópias de DNA , Humanos , Malásia , Epidemiologia Molecular , Mutação , Fenótipo , Prevalência , Talassemia alfa/epidemiologia
18.
Genet Mol Res ; 15(2)2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27173219

RESUMO

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.


Assuntos
Hemoglobina A/genética , Hemoglobinas Anormais/genética , Talassemia alfa/genética , Humanos , Malásia , Mutação Puntual , Polimorfismo de Fragmento de Restrição , Talassemia alfa/etnologia
19.
Sci Rep ; 6: 26692, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27225309

RESUMO

In this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ~2-3 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.


Assuntos
Membrana Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Modelos Biológicos , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Membrana Celular/patologia , Humanos , Neoplasias Nasofaríngeas/patologia
20.
J Econ Entomol ; 109(2): 785-91, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26743217

RESUMO

Three hundred Reticulitermes virginicus (Banks) workers were exposed to three 1-cm3 wood blocks of either Quercus sp. (Red Oak), Populus sp. (Poplar), Pinus sp. (Pine), or Sequoia sp. (Redwood) placed into one of the three bioassay designs (no-, two-, and four-choice) for 21 d. Termite wood consumption was measured by wood weight loss, resistance class, and visual rating. Wood consumption rates were determined using four formulas in addition to two standardized visual rating scales (American Society for Testing and Materials [ASTM] and American Wood Protection Association [AWPA]) and a preference ranking obtained for each measure. The wood consumption formula, rating scale, and preference rankings were compared by bioassay design. The overall preference ranking of the four wood types as determined by the combination of all three designs was­1) Pine, 2) Red Oak, 3) Redwood, and 4) Poplar. Results indicate that bioassay design influenced both wood consumption and preference rankings. A no-choice design can determine aversion; a four-choice design the most preferred wood; and a two-choice design can illuminate the fine details of comparative preference. The different formulas employed for calculation of consumption rate influenced preference ranking in the no- and four-choice designs but not the two-choice design.


Assuntos
Preferências Alimentares , Isópteros , Madeira , Animais , Comportamento de Escolha , Pinus , Populus , Quercus , Sequoia
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