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1.
Phys Rev Lett ; 125(25): 257001, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33416373

RESUMO

The field-induced superconductor-insulator transition (SIT) in two-dimensional (2D) systems is a famous example of a quantum phase transition. However, an emergence of an anomalous metallic state induced by field has been a long-standing problem in 2D superconductors. While theories predicted that the emergence is attributed to strong phase fluctuations of the superconducting order parameter due to quantum fluctuations, usual resistance measurements have not probed them directly. Here, using Nernst effect measurements, we uncover superconducting fluctuations in the vicinity of the field-induced metallic state in an amorphous Mo_{x}Ge_{1-x} thin film. The field range where the vortex Nernst signals are detectable remains nonzero toward zero temperature, and it locates inside the metallic state defined by the magnetoresistance, indicating that the metallic state results from quantum vortex liquid (QVL) with phase fluctuations due to quantum fluctuations. Slow decay of transport entropy of vortices in the QVL with decreasing temperature suggests that the metallic state originates from broadening of a quantum critical point in SIT.

2.
J Biopharm Stat ; 30(5): 834-853, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32310707

RESUMO

Precision medicine is an emerging approach for disease treatment and prevention that accounts for individual variability in genes, environment, and lifestyle. Cancer is a genomic disease; therefore, the dose-efficacy and dose-toxicity relationships for molecularly targeted agents in cancer most likely differ, based on the genomic mutation pattern. The individualized optimal dose - the maximal efficacious dose with a clinically acceptable safety profile - may vary depending on the genomic mutation patterns and should be determined prior to the use of these agents in precision medicine. In addition, genes that influence the individualized optimal doses should be identified in early-phase development. In this study, we propose a novel dose-finding approach to identify the individualized optimal dose for molecularly targeted agents in phase I cancer trials. Individualized optimal dose determination and gene selection were conducted simultaneously based on L1 and L2 penalized regression. Similar to most reported dose-finding approaches, this study considers non-monotonic patterns for dose-efficacy and dose-toxicity relationships, as well as correlations between efficacy and toxicity outcomes based on multinomial distribution. Our dose-finding algorithm is based on the predictive probability calculated with an estimated penalized regression model. We compare the operating characteristics between the proposed and existing methods by simulation studies under various scenarios.


Assuntos
Ensaios Clínicos Fase I como Assunto/estatística & dados numéricos , Genômica/estatística & dados numéricos , Medicina de Precisão/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Algoritmos , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/genética , Simulação por Computador , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Humanos , Modelos Estatísticos , Terapia de Alvo Molecular/estatística & dados numéricos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética
3.
Nanotechnology ; 30(12): 125202, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30620940

RESUMO

We have studied the formation process of the metal atomic filament for metal sulfide atomic switches by electrical measurement. The switching between ON and OFF states of the atomic switch is controlled by the application of the bias voltage for the atomic switches. The SET (OFF â†’ ON) and RESET (ON â†’ OFF) voltages were investigated for the atomic switch where the Ag2S or Cu2S layer were sandwiched between the Pt and Ag or Cu electrodes. The SET and RESET voltages of the Ag/Cu2S/Pt and Cu/Ag2S/Pt were close to those of the Ag/Ag2S/Pt atomic switch, and different from those of the Cu/Cu2S/Pt atomic switch. These results indicated that the dominant chemical species of the making and breaking part of the metal filament was Ag, and that the source of the metal filament was both the sulfide layer and the metal electrode.

4.
Phys Chem Chem Phys ; 21(31): 16910-16913, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31123746

RESUMO

We have studied the stretch dependence of the electronic structure and vibrational energy for the 4,4'-bipyridine (BPY) single molecule junction, which was fabricated by the mechanically controllable break junction (MCBJ) using the highly stable nano MCBJ electrodes. The electronic structure and vibrational energy of the single molecule junction were studied by the current-voltage (I-V) curve and surface enhanced Raman scattering (SERS), respectively. The simultaneous SERS and I-V curve measurements revealed the lowest unoccupied molecular orbital (LUMO) and vibrational energy of the C-C stretching mode decreased with an increase in the metal-molecule distance. The molecular orbital energy shift and vibrational energy shift can be explained by the change in the degree of the hybridization of molecular and metal orbitals.

5.
Public Health ; 173: 58-68, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254679

RESUMO

OBJECTIVES: Stunting is a significant cause of poor cognitive performance and lower school achievement. Stunting is observed among pre-school children in several areas in Africa; however, not all children are affected, and children with and without stunting are seen in the same communities. Therefore, this study aimed to identify nutritional and other factors that prevent stunting that may exist in local communities. STUDY DESIGN: This is a prospective cohort study. METHODS: Data were extracted from the Health and Demographic Surveillance System conducted in Kwale County, Kenya. The cohort consisted of all households with children less than five years old, within a radius of 2.2 km from a local health centre. A dietary pattern (DP) survey with a semi-quantitative food frequency questionnaire was conducted on caretakers of children who were voluntary participated from the cohort between June 2012 and August 2012. Using cluster analysis, the children were assigned to a DP group. Logistic regression analysis was applied to calculate the adjusted odds ratios (aORs) of DPs for stunting controlling for other factors. RESULTS: In total, 402 children were included in the analysis. By cluster analysis, three DPs were identified: protein-rich DP; traditional DP; and traditional DP complemented by breastfeeding. The aOR of a child becoming stunted from a normal height during the study period among children who received a traditional DP compared with those who had a protein-rich DP was 2.78 (95% confidence interval [CI]: 1.02-7.55). However, the aOR for children who were already stunted at the start of the study and had a traditional DP was 1.49 (95% CI: 0.82-2.72). Increased aORs of stunting were observed among children aged over 12 months compared with children aged 6-11 months, and the effects of DPs were modified by age in months from 12 to 35 months; however, the effects were near the null value for children over 36 months of age, although these were not statistically significant. CONCLUSIONS: We found that the traditional DP showed a higher risk for stunting compared with the protein-rich DP, and the most vulnerable age range for stunting was between 12 and 35 months. Interventions to prevent stunting should focus on providing 12- to 35-month-old children with locally available, protein-rich foods.


Assuntos
Dieta , Abastecimento de Alimentos/estatística & dados numéricos , Transtornos do Crescimento/etiologia , Estado Nutricional , Aleitamento Materno , Pré-Escolar , Análise por Conglomerados , Estudos de Coortes , Características da Família , Feminino , Transtornos do Crescimento/epidemiologia , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Razão de Chances , Estudos Prospectivos , Inquéritos e Questionários
6.
Neuropathol Appl Neurobiol ; 44(6): 563-573, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29319907

RESUMO

AIMS: The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP). METHODS: The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis. RESULTS: Whereas C-terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C-terminal ErbB4 in PSP. Double immunofluorescence for C-terminal ErbB4 and phospho-tau revealed co-localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N-terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons. CONCLUSIONS: Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.


Assuntos
Encéfalo/metabolismo , Emaranhados Neurofibrilares/metabolismo , Neurônios/metabolismo , Receptor ErbB-4/metabolismo , Paralisia Supranuclear Progressiva/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuregulina-1/metabolismo , Emaranhados Neurofibrilares/patologia , Neurônios/patologia , Paralisia Supranuclear Progressiva/patologia
7.
Scand J Immunol ; 87(5): e12655, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29484687

RESUMO

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through 2 main pathways, immunoglobulin E-dependent and E-independent activation. In the latter pathway, mast cells are activated by a diverse range of basic molecules (collectively known as basic secretagogues) through Mas-related G protein-coupled receptors (MRGPRs). In addition to the known basic secretagogues, here, we discovered several endogenous protein and enzyme fragments (such as chaperonin-10 fragment) that act as bioactive peptides and induce immunoglobulin E-independent mast cell activation via MRGPRX2 (previously known as MrgX2), leading to the degranulation of mast cells. We discuss the possibility that MRGPRX2 responds various as-yet-unidentified endogenous ligands that have specific characteristics, and propose that MRGPRX2 plays an important role in regulating inflammatory responses to endogenous harmful stimuli, such as protein breakdown products released from damaged or dying cells.


Assuntos
Degranulação Celular/imunologia , Imunoglobulina E/imunologia , Mastócitos/imunologia , Proteínas do Tecido Nervoso/imunologia , Fragmentos de Peptídeos/imunologia , Receptores Acoplados a Proteínas G/imunologia , Receptores de Neuropeptídeos/imunologia , Animais , Linhagem Celular Tumoral , Chaperonina 10/imunologia , Células HEK293 , Humanos , Mastócitos/metabolismo , Proteínas do Tecido Nervoso/genética , Células PC12 , Ratos , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Suínos
8.
Acta Neurol Scand ; 137(4): 392-399, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29250772

RESUMO

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non-competitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial-onset seizures (POS) from Asia-Pacific. MATERIALS & METHODS: This multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1-3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once-daily placebo or perampanel 4, 8, or 12 mg over a 6-week titration and 13-week maintenance double-blind period. Enzyme-inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double-blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment-emergent adverse events (TEAEs) were also monitored. RESULTS: Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose-proportional reductions in seizure frequency: -10.8% with placebo and -17.3% (P = .2330), -29.0% (P = .0003), and -38.0% (P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability. CONCLUSIONS: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.


Assuntos
Anticonvulsivantes/uso terapêutico , Piridonas/uso terapêutico , Convulsões/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Ásia , Método Duplo-Cego , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Piridonas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
9.
Scand J Med Sci Sports ; 28(3): 1263-1271, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29144568

RESUMO

The most common events during which anterior cruciate ligament (ACL) injuries occur in football are pressing situations. This study aimed to describe the knee and hip joint kinematics during pressing situations in football games to identify kinematic patterns in actions with a high risk for ACL injuries. We filmed 5 female collegiate football matches and identified 66 pressing situations. Five situations with a large distance between the trunk and foot placements in the sagittal plane were analyzed using a model-based image-matching technique. The mean knee flexion angle at initial contact (IC) was 13° (range, 8°-28°) and increased by 11° (95% confidence interval [CI], 3°-14°) at 40 ms after IC. As for knee adduction and rotation angles, the knee positions were close to neutral at IC, and only minor knee angular changes occurred later in the sequences. The mean hip flexion was 25° (range, 8°-43°) at IC and increased by 22° (95% CI, 11°-32°) after 100 ms. The hip was also externally rotated by 7° (range, -19° to 3°) at IC, and gradually rotated internally, reaching 10° of internal rotation (range, -5° to 27°) at 100 ms after IC. This study suggests that the observed knee valgus, internal hip and knee rotation, and static hip flexion previously reported in non-contact ACL injury events are unique to injury situations. In contrast, neither rapid knee valgus nor increased internal rotation was seen in non-injury pressing maneuvers.


Assuntos
Lesões do Ligamento Cruzado Anterior/etiologia , Traumatismos em Atletas/etiologia , Amplitude de Movimento Articular , Futebol/lesões , Fenômenos Biomecânicos , Feminino , Articulação do Quadril , Humanos , Articulação do Joelho , Rotação , Gravação em Vídeo
10.
Clin Exp Immunol ; 188(1): 22-35, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27936495

RESUMO

Various transcription factors are also known to enhance or suppress T helper type 17 (Th17) differentiation. We have shown previously that the development of collagen-induced arthritis was suppressed in T-bet transgenic (T-bet Tg) mice, and T-bet seemed to suppress Th17 differentiation through an interferon (IFN)-γ-independent pathway, although the precise mechanism remains to be clarified. The present study was designed to investigate further the mechanisms involved in the regulation of Th17 differentiation by T-bet over-expression, and we found the new relationship between T-bet and aryl hydrocarbon receptor (AHR). Both T-bet Tg mice and IFN-γ-/- -over-expressing T-bet (T-bet Tg/IFN-γ-/- ) mice showed inhibition of retinoic acid-related orphan receptor (ROR)γt expression and IL-17 production by CD4+ T cells cultured under conditions that promote Th-17 differentiation, and decreased IL-6 receptor (IL-6R) expression and signal transducer and activator of transcription-3 (STAT-3) phosphorylation in CD4+ T cells. The mRNA expression of ahr and rorc were suppressed in CD4+ T cells cultured under Th-17 conditions from T-bet Tg mice and T-bet Tg/IFN-γ-/- mice. CD4+ T cells of wild-type (WT) and IFN-γ-/- mice transduced with T-bet-expressing retrovirus also showed inhibition of IL-17 production, whereas T-bet transduction had no effect on IL-6R expression and STAT-3 phosphorylation. Interestingly, the mRNA expression of ahr and rorc were suppressed in CD4+ T cells with T-bet transduction cultured under Th17 conditions. The enhancement of interleukin (IL)-17 production from CD4+ T cells by the addition of AHR ligand with Th17 conditions was cancelled by T-bet over-expression. Our findings suggest that T-bet over-expression-induced suppression of Th17 differentiation is mediated through IFN-γ-independent AHR suppression.


Assuntos
Diferenciação Celular , Expressão Gênica , Interferon gama/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais , Proteínas com Domínio T/genética , Células Th17/citologia , Células Th17/metabolismo , Animais , Artrite Experimental/genética , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Diferenciação Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Imunomodulação , Imunofenotipagem , Interferon gama/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Modelos Biológicos , Fator de Transcrição STAT3/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th17/imunologia , Transdução Genética
11.
Eur J Clin Microbiol Infect Dis ; 36(10): 1839-1845, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28477235

RESUMO

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.


Assuntos
Antibacterianos/farmacologia , Parede Celular/metabolismo , Daptomicina/farmacologia , Regulação Bacteriana da Expressão Gênica , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Idoso , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Mutação de Sentido Incorreto , Fenótipo
12.
Ann Oncol ; 27(11): 2090-2096, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27573564

RESUMO

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Sorafenibe , Resultado do Tratamento
13.
Clin Exp Immunol ; 185(3): 348-60, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27083148

RESUMO

Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with poor prognosis and high mortality. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of pulmonary γδT cells in IP. In wild-type (WT) mice exposed to bleomycin, pulmonary γδT cells were expanded and produced large amounts of interferon (IFN)-γ and interleukin (IL)-17A. Histological and biochemical analyses showed that bleomycin-induced IP was more severe in T cell receptor (TCR-δ-deficient (TCRδ(-/-) ) mice than WT mice. In TCRδ(-/-) mice, pulmonary IL-17A(+) CD4(+) Τ cells expanded at days 7 and 14 after bleomycin exposure. In TCRδ(-/-) mice infused with γδT cells from WT mice, the number of pulmonary IL-17A(+) CD4(+) T cells was lower than in TCRδ(-/-) mice. The examination of IL-17A(-/-) TCRδ(-/-) mice indicated that γδT cells suppressed pulmonary fibrosis through the suppression of IL-17A(+) CD4(+) T cells. The differentiation of T helper (Th)17 cells was determined in vitro, and CD4(+) cells isolated from TCRδ(-/-) mice showed normal differentiation of Th17 cells compared with WT mice. Th17 cell differentiation was suppressed in the presence of IFN-γ producing γδT cells in vitro. Pulmonary fibrosis was attenuated by IFN-γ-producing γδT cells through the suppression of pulmonary IL-17A(+) CD4(+) T cells. These results suggested that pulmonary γδT cells seem to play a regulatory role in the development of bleomycin-induced IP mouse model via the suppression of IL-17A production.


Assuntos
Bleomicina/administração & dosagem , Doenças Pulmonares Intersticiais/imunologia , Pulmão/imunologia , Fibrose Pulmonar/imunologia , Linfócitos T/imunologia , Células Th17/patologia , Animais , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular , Modelos Animais de Doenças , Interferon gama/biossíntese , Interleucina-17/biossíntese , Interleucina-17/sangue , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibrose Pulmonar/fisiopatologia , Receptores de Antígenos de Linfócitos T gama-delta/deficiência
14.
Osteoporos Int ; 27(12): 3495-3502, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27341809

RESUMO

We conducted a prospective comparative study of the effect of teriparatide therapy for preventing vertebral-failure-type PJK after reconstructive surgery for adult spinal deformity. Prophylactic teriparatide improved the volumetric bone mineral density and fine bone structure of the vertebra above the upper-instrumented vertebra and reduced the incidence of vertebral-failure-type PJK. INTRODUCTION: Proximal junctional kyphosis (PJK) is a complication after corrective surgery for spinal deformity. This study sought to determine whether teriparatide (TP) is an effective prophylactic against PJK type 2 (vertebral fracture) in surgically treated patients with adult spinal deformity (ASD). METHODS: Forty-three patients who started TP therapy immediately after surgery and 33 patients who did not receive TP were enrolled in this prospective case series. These patients were female, over 50, surgically treated for ASD, and followed for at least 2 years. Preoperative and postoperative standing whole-spine X-rays and dual-energy X-ray absorptiometry scans, and multidetector CT images obtained before and 6 months after surgery were used to analyze the bone strength in the vertebra above the upper-instrumented vertebra (UIV+1). RESULTS: Mean age was 67.9 years. After 6 months of treatment, mean hip-bone mineral density (BMD) increased from 0.721 to 0.771 g/cm2 in the TP group and decreased from 0.759 to 0.729 g/cm2 in the control group. This percent BMD change between groups was significant (p < 0.05). The volumetric BMD (326 to 366 mg/cm3) and bone mineral content (BMC) (553 to 622 mg) at UIV+1 were also significantly increased in TP group. The bone volume/tissue volume ratio increased from 46 to 54 % in the TP group, and the trabecular bone thickness and number increased by 14 and 5 %, respectively. At the 2-year follow-up, the PJK type 2 incidence was significantly lower in the TP group (4.6 %) than in the control group (15.2 %; p = .02). CONCLUSIONS: Prophylactic TP treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.


Assuntos
Densidade Óssea/efeitos dos fármacos , Coluna Vertebral/efeitos dos fármacos , Teriparatida/uso terapêutico , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Coluna Vertebral/anormalidades , Coluna Vertebral/cirurgia , Resultado do Tratamento
15.
Nanotechnology ; 27(29): 295603, 2016 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-27284690

RESUMO

Typical thermostable and flexible polyimide polymers exhibit many excellent properties such as strong mechanical and chemical resistance. However, in contrast to single-crystal substrates like silicon or sapphire, polymers mostly display disordered and rough surfaces, which may result in instability and degradation of the interfaces between thin films and polymer substrates. As a step toward the development of next-generation polymer substrates, we here report single-atom-layer imprinting onto the polyimide sheets, resulting in an ultrasmooth 0.3 nm high atomic step-and-terrace surface on the polyimides. The ultrasmooth polymer substrates are expected to be applied to the fabrication of nanostructures such as superlattices, nanowires, or quantum dots in nanoscale-controlled electronic devices. We fabricate smooth and atomically stepped indium tin oxide transparent conducting oxide thin films on the imprinted polyimide sheets for future use in organic-based optoelectronic devices processed with nanoscale precision. Furthermore, toward 2D polymer substrate nanoengineering, we demonstrate nanoscale letter writing on the atomic step-and-terrace polyimide surface via atomic force microscopy probe scratching.

16.
Spinal Cord ; 54(9): 656-61, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26620877

RESUMO

STUDY DESIGN: A cross-sectional study. OBJECTIVES: Neuropathic pain (NP) after spinal cord injury (SCI) tends to be hard to treat, and its heterogeneous properties make it difficult to identify and characterize. This study was conducted to assess the characteristics of SCI-related NP in detail. SETTING: A single hospital for SCI rehabilitation. METHODS: This study included 72 patients who were seen at our hospital in 2012 and 2013 and who had sustained SCI at least 3 months before enrollment. The patients completed the Neuropathic Pain Symptom Inventory (NPSI) and the Short Form (SF)-36 Health Inventory. The NPSI score was analyzed for correlations with clinical presentations of SCI and SF-36 subitems. RESULTS: Paresthesia/dysesthesia was the most common subtype of NP after SCI. With regard to location, below-level superficial NP was significantly more intense than at-level pain. Patients who underwent surgery showed significantly less evoked pain compared with patients with non-surgery. Patients reported significantly more severe pain if >1 year had elapsed after the SCI. Patients with an American Spinal Injury Association Impairment Scale grade of B for completeness of injury reported more intense NP than those with other grades. Among the SF-36 subitems, NP correlated significantly with bodily pain, general health and mental health. CONCLUSION: NP in SCI patients was significantly associated with the location of pain, the time period since the injury, surgery and quality-of-life factors. A more detailed understanding of the characteristics of NP may contribute to better strategies for relieving the pain associated with SCI.


Assuntos
Neuralgia/etiologia , Qualidade de Vida/psicologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/cirurgia , Estatística como Assunto , Estatísticas não Paramétricas
17.
Rhinology ; 54(3): 221-30, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27107025

RESUMO

BACKGROUND: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. METHODS: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. RESULTS: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. CONCLUSIONS: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.


Assuntos
Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual/métodos , Adulto , Biomarcadores/sangue , Cryptomeria , Método Duplo-Cego , Feminino , Fatores de Transcrição Forkhead/sangue , Humanos , Imunoglobulinas/sangue , Interleucina-10/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Rinite Alérgica Sazonal/imunologia , Células Th1 , Células Th2 , Resultado do Tratamento
18.
Tissue Antigens ; 86(6): 406-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26449183

RESUMO

Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.


Assuntos
Cadeias beta de HLA-DP/genética , Hepatite B Crônica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Criança , Progressão da Doença , Feminino , Frequência do Gene , Genes MHC da Classe II , Predisposição Genética para Doença , Genótipo , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/imunologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Lupus ; 24(7): 659-68, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25391543

RESUMO

OBJECTIVE: The objective of this paper is to identify predictors for the response to treatment of acute lupus hemophagocytic syndrome (ALHS). METHODS: We reviewed seven cases with ALHS admitted to our hospital and published ALHS cases identified in the 2001-2014 Medline database, and then conducted univariate and multivariate analyses to identify predictors for the response to treatment. RESULTS: Review of our cases showed a significant and negative correlation between serum ferritin and anti-DNA antibody (p = 0.0025). All three patients treated with cyclosporine A (CsA) were considered responders despite high serum ferritin and corticosteroid resistance. We also reviewed 93 patients with ALHS identified in 46 articles. Multiple logistic regression analysis identified C-reactive protein (CRP) (OR 0.83, p = 0.042) and hemoglobin (OR 1.53, p = 0.026) measured at diagnosis of ALHS as significant predictors of the response to corticosteroid monotherapy. Moreover, among 32 patients treated with CsA, serum ferritin was significantly higher in CsA responders (12163 ± 16864 µg/l, n = 22) than in non-responders (3456 ± 6267/µg/l, p = 0.020, n = 10). Leukocyte count was significantly lower in the CsA responders (1940.0 ± 972.3/µl) than in the non-responders (3253 ± 2198/µl, p = 0.034). CONCLUSION: Low CRP and high hemoglobin can predict a positive response to corticosteroid monotherapy while high serum ferritin and low leukocyte count can predict a positive response to CsA in patients with ALHS and therefore, when corticosteroid monotherapy is not effective in such cases, CsA could be the first choice of an additional immunosuppressive agent.


Assuntos
Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Anticorpos Antinucleares/sangue , Proteína C-Reativa/metabolismo , Ciclosporina/uso terapêutico , Feminino , Ferritinas/sangue , Hemoglobinas/metabolismo , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
20.
East Afr Med J ; 91(3): 83-93, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26859036

RESUMO

OBJECTIVES: To describe the roles of Traditional Birth Attendants (TBAs), to determine the perceptions of TBAs and Skilled Birth Attendants (SBAs) towards the policy discouraging home delivery by TBAs and to establish the working relationship between TBAs and SBAs in Kwale, Kenya. DESIGN: Community based cross-sectional study. SETTING: Mwaluphamba, Kinango and Golini locations of Kwale County, Kenya. SUBJECTS: Fifty eight participants were involved in the study. Interviews were conducted with 22 TBAs and 8 SBAs as well as 3 FGDs with 28 TBAs were carried out in July 2012. MAIN OUTCOME MEASURES: Roles of TBAs, policy awareness and support as well as the working relationship between TBAs and SBAs. RESULTS: Before delivery, the main role of TBAs was checking position of the baby in the womb (86%) while during delivery, the main role was stomach massage (64%). However, majority (95%) of the TBAs did not provide any after delivery. All SBAs and 59% of TBAs were aware of the policy while 88% SBAs and 36% of TBAs supported it. The working relationship between TBAs and SBAs mainly involved the referral of women to health facilities (HFs). Sometimes, TBAs accompanied women to the HF offering emotional support until after delivery. CONCLUSION: TBAs in Kwale have a big role to play especially during pregnancy and delivery periods. Awareness and support of the policy as well as the collaboration between SBAs and TBAs should be enhanced in Kwale.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Política de Saúde , Parto Domiciliar , Tocologia , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Gravidez
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