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1.
Public Health ; 217: 115-124, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36878120

RESUMO

OBJECTIVES: The study aimed to evaluate the long-term metabolic risk profiles of Fukushima residents after the Great East Japan Earthquake of March 2011. STUDY DESIGN: This was a cross-sectional and a longitudinal design. METHODS: The Fukushima Health Database (FDB) contains 2,331,319 annual health checkup records of participants aged 40-74 years between 2012 and 2019. We checked the validity of the FDB by comparing the prevalence of metabolic factors with the National Database of Health Insurance Claims and Specific Health Checkups (NDB). We applied a regression analysis to determine the changes and project the trends of metabolic factors over the years. RESULTS: Compared to the NDB, the prevalence of metabolic factors in Fukushima was higher than the country average from 2013 to 2018, and they showed the same trends as those from the FDB. The prevalence of metabolic syndrome (MetS) increased from 18.9% in 2012 to 21.4% in 2019 (an annual increase of 2.74%) in men and from 6.8 to 7.4% (an annual increase of 1.80%) in women in Fukushima. The standardized prevalence of MetS, being overweight, and diabetes is projected to continue increasing, with disparities among subareas being higher in evacuees than in non-evacuees. An annual decrease of 0.38-1.97% in hypertension was mainly observed in women. CONCLUSIONS: The prevalence of metabolic risk is higher in Fukushima as compared to the country average. The increasing metabolic risk in subareas, including the evacuation zone, highlights the need to control MetS in Fukushima residents.


Assuntos
Diabetes Mellitus , Terremotos , Acidente Nuclear de Fukushima , Síndrome Metabólica , Masculino , Humanos , Feminino , Síndrome Metabólica/epidemiologia , Prevalência , Estudos Transversais , Diabetes Mellitus/epidemiologia , Japão/epidemiologia
2.
Public Health ; 224: 98-105, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37742586

RESUMO

OBJECTIVES: Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. STUDY DESIGN: This is a cohort study. METHODS: In 2015, 193,246 participants aged 40-74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet-smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity-sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. RESULTS: The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet-smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity-sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity-sleep" pattern showed a significant inverse association in non-overweight men. CONCLUSIONS: Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults.

3.
Ann Oncol ; 29(4): 992-997, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29401241

RESUMO

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration: UMIN Clinical Trial Registry, number UMIN000000819.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Glote/patologia , Neoplasias Laríngeas/radioterapia , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Clin Genet ; 94(1): 70-80, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29023671

RESUMO

Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, including secondary patients. Importantly, the study population is a racially, ethnically, and socially homogeneous population. In PAH patients, there is a high incidence of unique mutations in BMPR2, and several mutations are frequently observed in the Japanese population, suggesting that these common and recurring mutations may be highly pathogenic or have high penetrance, explaining why they are found frequently throughout the world. We have also mapped each breakpoint of exonic deletions/duplications and found that most break and rejoining points are in the Alu elements. Reviewing the distribution of the reported mutations on each exon of BMPR2 revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of BMPR2 gene mutations was 3-fold higher in females than males. Full elucidation of BMPR2-mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.


Assuntos
Povo Asiático/genética , Hipertensão Pulmonar Primária Familiar/epidemiologia , Hipertensão Pulmonar Primária Familiar/genética , Predisposição Genética para Doença , Alelos , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/terapia , Estudos de Associação Genética , Testes Genéticos , Humanos , Japão/epidemiologia , Mutação , Penetrância , Fenótipo , Vigilância da População , Prognóstico
5.
Phys Rev Lett ; 121(13): 137703, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30312059

RESUMO

Using a recent time-of-flight measurement technique with 1 ps time resolution and electron-energy spectroscopy, we develop a method to measure the longitudinal-optical-phonon emission rate of hot electrons traveling along a depleted edge of a quantum Hall bar. Comparison to a single-particle model implies the scattering mechanism involves a two-step process via an intra-Landau-level transition. We show that this can be suppressed by control of the edge potential profile, and a scattering length >1 mm can be achieved, allowing the use of this system for scalable single-electron device applications.

6.
Mol Psychiatry ; 21(7): 885-93, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27217147

RESUMO

Although numerous genetic studies have been conducted for bipolar disorder (BD), its genetic architecture remains elusive. Here we perform, to the best of our knowledge, the first trio-based exome sequencing study for BD to investigate potential roles of de novo mutations in the disease etiology. We identified 71 de novo point mutations and one de novo copy-number mutation in 79 BD probands. Among the genes hit by de novo loss-of-function (LOF; nonsense, splice site or frameshift) or protein-altering (LOF, missense and inframe indel) mutations, we found significant enrichment of genes highly intolerant (first percentile of intolerant genes assessed by Residual Variation Intolerance Score) to protein-altering variants in general population, an observation that is also reported in autism and schizophrenia. When we performed a joint analysis using the data of schizoaffective disorder in published studies, we found global enrichment of de novo LOF and protein-altering mutations in the combined group of bipolar I and schizoaffective disorders. Considering relationship between de novo mutations and clinical phenotypes, we observed significantly earlier disease onset among the BD probands with de novo protein-altering mutations when compared with non-carriers. Gene ontology enrichment analysis of genes hit by de novo protein-altering mutations in bipolar I and schizoaffective disorders did not identify any significant enrichment. These results of exploratory analyses collectively point to the roles of de novo LOF and protein-altering mutations in the etiology of bipolar disorder and warrant further large-scale studies.


Assuntos
Transtorno Bipolar/genética , Adolescente , Adulto , Exoma/genética , Família , Feminino , Predisposição Genética para Doença/genética , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação/genética , Transtornos Psicóticos/genética , Análise de Sequência de DNA/métodos
7.
Mol Pharm ; 14(12): 4734-4740, 2017 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-28985076

RESUMO

Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant-like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively). In the case of [3H]-mannitol, a robust permeation enhancement was achieved with 0.5 mM DDM (∼6-fold), whereas little effect was seen on the permeation of [3H]-propranolol. Concomitantly measured TEER values revealed a rapid onset of action of DDM with a swift recovery and complete restitution (>90%) within 4 h after washout. To localize the site(s) of action of DDM at the absorptive surface of Caco-2 cells, sulfo-NHS-SS-biotin, a membrane-impermeable compound, was applied apically. In the presence of 0.5 mM DDM, translocated biotin was found to be accumulated toward bicellular contacts, whereas no biotin permeation was observed in untreated control cells. Western blot analysis of DDM-treated and untreated Caco-2 cells revealed an interaction of DDM with specific tight junction associated proteins, resulting in a reduction of claudin-3 and -4 and also occludin, as well as a depletion of claudin-2 from lipid rafts. Collectively, the results presented provide a more in depth understanding of the molecular mechanism(s) underlying the permeation-enhancing actions of DDM.


Assuntos
Detergentes/farmacologia , Glucosídeos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Células CACO-2 , Humanos , Mucosa Intestinal/metabolismo , Manitol/farmacocinética , Permeabilidade/efeitos dos fármacos , Propranolol/farmacocinética , Junções Íntimas/metabolismo
8.
Nature ; 477(7365): 439-42, 2011 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-21938065

RESUMO

Single-electron circuits of the future, consisting of a network of quantum dots, will require a mechanism to transport electrons from one functional part of the circuit to another. For example, in a quantum computer decoherence and circuit complexity can be reduced by separating quantum bit (qubit) manipulation from measurement and by providing a means of transporting electrons between the corresponding parts of the circuit. Highly controlled tunnelling between neighbouring dots has been demonstrated, and our ability to manipulate electrons in single- and double-dot systems is improving rapidly. For distances greater than a few hundred nanometres, neither free propagation nor tunnelling is viable while maintaining confinement of single electrons. Here we show how a single electron may be captured in a surface acoustic wave minimum and transferred from one quantum dot to a second, unoccupied, dot along a long, empty channel. The transfer direction may be reversed and the same electron moved back and forth more than sixty times-a cumulative distance of 0.25 mm-without error. Such on-chip transfer extends communication between quantum dots to a range that may allow the integration of discrete quantum information processing components and devices.

9.
Phys Rev Lett ; 117(14): 146802, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27740812

RESUMO

Generating and detecting a prescribed single-electron state is an important step towards solid-state fermion optics. We propose how to generate an electron in a Gaussian state, using a quantum-dot pump with gigahertz operation and realistic parameters. With the help of a strong magnetic field, the electron occupies a coherent state in the pump, insensitive to the details of nonadiabatic evolution. The state changes during the emission from the pump, governed by competition between the Landauer-Buttiker traversal time and the passage time. When the former is much shorter than the latter, the emitted state is a Gaussian wave packet. The Gaussian packet can be identified by using a dynamical potential barrier, with a resolution reaching the Heisenberg minimal uncertainty ℏ/2.

10.
Phys Rev Lett ; 116(12): 126803, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-27058091

RESUMO

We report time-of-flight measurements on electrons traveling in quantum Hall edge states. Hot-electron wave packets are emitted one per cycle into edge states formed along a depleted sample boundary. The electron arrival time is detected by driving a detector barrier with a square wave that acts as a shutter. By adding an extra path using a deflection barrier, we measure a delay in the arrival time, from which the edge-state velocity v is deduced. We find that v follows 1/B dependence, in good agreement with the E[over →]×B[over →] drift. The edge potential is estimated from the energy dependence of v using a harmonic approximation.

11.
J Bioeth Inq ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969917

RESUMO

An ethical and legal framework is needed to regulate the rapidly developing human brain organoid research field properly. However, considering the legal issues involved in human brain organoid research remains underdeveloped and scattered. This article reviews the legal issues of human brain organoid research, grouping them into the following five broad themes: (1) consciousness, (2) legal status, (3) consent, (4) ownership, and (5) transplantation. The issues in each topic include both the urgent (e.g., appropriate forms of consent) and the speculative (e.g., protection of conscious human brain organoids). Therefore, we have attempted to be as explicit as possible about the timescale within which each issue will be realized and to prioritize each. Examining these issues has revealed legal issues specific to human brain organoid research and issues common to research in other fields. Further discussion of human brain organoid research from a legal perspective is needed in the future, considering discussions in related fields.

12.
Phys Rev Lett ; 111(21): 216807, 2013 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-24313516

RESUMO

We demonstrate the energy- and time-resolved detection of single-electron wave packets from a clock-controlled source transmitted through a high-energy quantum Hall edge channel. A quantum dot source is loaded with single electrons which are then emitted ~150 meV above the Fermi energy. The energy spectroscopy of emitted electrons indicates that at high magnetic field these electrons can be transported over several microns without inelastic electron-electron or electron-phonon scattering. Using a time-resolved spectroscopic technique, we deduce the wave packet size at picosecond resolution. We also show how this technique can be used to switch individual electrons into different electron waveguides (edge channels).

13.
Diabet Med ; 30(3): e101-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23181689

RESUMO

AIMS: Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia. METHODS: Self-identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara(®) and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α-amylase activity to determine whether these measures explained any differences in postprandial glycaemia. RESULTS: Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2-1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve. CONCLUSIONS: Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice-eating populations at high risk of diabetes.


Assuntos
Povo Asiático/etnologia , Glucose/farmacologia , Índice Glicêmico/fisiologia , Oryza , Edulcorantes/farmacologia , População Branca/etnologia , Adolescente , Adulto , Distribuição por Idade , Área Sob a Curva , Glicemia/metabolismo , China/etnologia , Feminino , Índice Glicêmico/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Período Pós-Prandial/fisiologia , Adulto Jovem
14.
Nat Nanotechnol ; 18(7): 727-732, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37169897

RESUMO

A series of recent experiments have shown that collision of ballistic electrons in semiconductors can be used to probe the indistinguishability of single-electron wavepackets. Perhaps surprisingly, their Coulomb interaction has not been seen due to screening. Here we show Coulomb-dominated collision of high-energy single electrons in counter-propagating ballistic edge states, probed by measuring partition statistics while adjusting the collision timing. Although some experimental data suggest antibunching behaviour, we show that this is not due to quantum statistics but to strong repulsive Coulomb interactions. This prevents the wavepacket overlap needed for fermionic exchange statistics but suggests new ways to utilize Coulomb interactions: microscopically isolated and time-resolved interactions between ballistic electrons can enable the use of the Coulomb interaction for high-speed sensing or gate operations on flying electron qubits.

15.
Magn Reson Med ; 67(3): 778-85, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22135228

RESUMO

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Imagem de Difusão por Ressonância Magnética/métodos , Gosserrelina/uso terapêutico , Nitrilas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Estudos de Viabilidade , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Resultado do Tratamento
16.
J Periodontal Res ; 47(5): 554-62, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22309231

RESUMO

BACKGROUND AND OBJECTIVE: Resistin is an adipocytokine that induces insulin resistance and is predominantly expressed in adipocytes and peripheral blood mononuclear cells. Resistin expression increases in inflammatory diseases as well as diabetes mellitus, and is upregulated by bacterial pathogens and proinflammatory cytokines. The aim of this study was to identify resistin in human gingival crevicular fluid, to compare the resistin levels in gingival crevicular fluid between subjects with and without periodontitis and diabetes mellitus and to investigate the regulation of resistin release from human neutrophils by Porphyromonas gingivalis lipopolysaccharide (P-LPS). MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from patients with chronic periodontitis (n = 24), patients with diabetes mellitus-related periodontitis (n = 18) and healthy subjects (n = 21). Resistin in gingival crevicular fluid was determined using western blot analysis and an ELISA kit. The glycated hemoglobin (HbA(1c)) value was obtained from patients with diabetes mellitus-related periodontitis by a medical interview. Human neutrophils were cultured with P-LPS (0-1000 ng/mL), or incubated with inhibitors of actin or microtubule polymerization in the absence or presence of P-LPS. The medium and cellular fractions were used for determination of resistin by ELISA. RESULTS: The resistin level in gingival crevicular fluid from patients with periodontitis or diabetes mellitus-related periodontitis was significantly higher than that of healthy subjects. The resistin level in gingival crevicular fluid was correlated with gingival index score, but not blood HbA(1c) value. The P-LPS increased resistin release from human neutrophils, and its induction was decreased by actin polymerization inhibitors. CONCLUSION: We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils.


Assuntos
Líquido do Sulco Gengival/química , Lipopolissacarídeos/farmacologia , Neutrófilos/efeitos dos fármacos , Porphyromonas gingivalis , Resistina/análise , Proteínas de Capeamento de Actina/farmacologia , Adulto , Idoso , Técnicas de Cultura de Células , Periodontite Crônica/sangue , Periodontite Crônica/metabolismo , Colchicina/farmacologia , Citocalasina B/farmacologia , Citocalasina D/farmacologia , Complicações do Diabetes/sangue , Complicações do Diabetes/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Nocodazol/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Índice Periodontal , Bolsa Periodontal/sangue , Bolsa Periodontal/metabolismo , Periodontite/sangue , Periodontite/metabolismo , Resistina/metabolismo , Moduladores de Tubulina/farmacologia
17.
J Periodontal Res ; 47(4): 488-99, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22220998

RESUMO

BACKGROUND AND OBJECTIVE: Gingival crevicular fluid is a bodily fluid transuded from periodontal tissues into the gingival crevice and periodontal pocket, and contains many species of components. Proteins in gingival crevicular fluid have been studied as markers for periodontal diseases. Mass spectrometric analysis is used for the analyses of proteins, lipids, saccharides and metals, and expected as an approach for disease diagnosis. For better analysis of the protein components in gingival crevicular fluid, we investigated proteins in gingival crevicular fluid samples from the healthy gingival crevice and periodontal pocket using mass spectrometry. MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from subjects who gave their informed consent and were periodontally healthy or had diseased pockets. These samples were electrophoretically separated, and each fraction on the gels was analysed by nano liquid chromatography coupled with tandem mass spectrometry. Antimicrobial peptides detected in gingival crevicular fluid were confirmed by western blotting. RESULTS: One hundred and four proteins were detected in gingival crevicular fluid samples from both healthy sites and sites of periodontitis; 64 proteins were contained only in gingival crevicular fluid from healthy sites and 63 proteins were observed only in gingival crevicular fluid from periodontitis sites. These proteins were blood-, cytoskeleton-, immunity-, inflammation- and lipid-related proteins and enzymes. Some proteins, including ceruloplasmin, glycogen phosphorylase, glutathione S-transferase, phosphoglycerate mutase, psoriasin, S100A11 and resistin, were identified for the first time in gingival crevicular fluid. Antimicrobial peptides, such as lactoferrin, α1-antitrypsin, lipocalin, S100A7, S100A8, S100A9 and cathelicidin, were observed by mass spectrometry and western blotting. CONCLUSION: Multiple protein components in gingival crevicular fluid were analysed at the same time using mass spectrometry, and this approach may be useful for the diagnosis of periodontal diseases.


Assuntos
Peptídeos Catiônicos Antimicrobianos/análise , Líquido do Sulco Gengival/química , Bolsa Periodontal/metabolismo , Periodontite/diagnóstico , Proteínas/análise , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Western Blotting , Estudos de Casos e Controles , Ceruloplasmina/análise , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Feminino , Líquido do Sulco Gengival/enzimologia , Glutationa Transferase/análise , Glicogênio Fosforilase/análise , Humanos , Masculino , Pessoa de Meia-Idade , Bolsa Periodontal/enzimologia , Fosfoglicerato Mutase/análise , Resistina/análise , Proteína A7 Ligante de Cálcio S100 , Proteínas S100/análise
18.
Spinal Cord ; 50(6): 440-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22270189

RESUMO

STUDY DESIGN: Three-dimensional kinematic analysis of car transfer (CT) movement in four adult males with C6 tetraplegia. OBJECTIVES: The aim of the present study was to assess the normal transfer technique movement from a wheelchair to a car (that is, CT) in subjects with tetraplegia. A better understanding of CT movement is invaluable knowledge for spinal cord injury rehabilitation. This type of knowledge will improve rehabilitation programs so that patients with tetraplegia will have greater societal participation. SETTING: School of Comprehensive Rehabilitation, Osaka Prefecture University, Osaka, Japan. METHODS: Four adult males with C6 tetraplegia, an impairment grade of A according to the American Spinal Injury Association guidelines, took part in the study. The subjects used their own wheelchair and car in our assessments of their CT movement technique. Movements were assessed using a three-dimensional video analysis system with six digital video cameras. CT data, which included lateral displacement of the head and buttocks, and angular displacement of neck flexion and trunk forward inclination, were collected and correlation coefficients were calculated. RESULTS: All four subjects demonstrated negative correlations in lateral displacements greater than 0.70. As for correlation coefficients of angular displacement, two subjects demonstrated negative correlations (r = -0.98 and r = -0.77) and one subject demonstrated a positive correlation (r = 0.75). The neck flexion and trunk forward inclination strategy was different among the four subjects. CONCLUSIONS: Each subject with C6 tetraplegia demonstrated different strategies during CT movement.


Assuntos
Movimento/fisiologia , Quadriplegia , Adulto , Automóveis , Fenômenos Biomecânicos , Humanos , Masculino , Pessoa de Meia-Idade , Quadriplegia/reabilitação , Traumatismos da Medula Espinal/reabilitação , Cadeiras de Rodas
19.
ESMO Open ; 7(3): 100512, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35688061

RESUMO

BACKGROUND: Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC. MATERIALS AND METHODS: A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, and fluorouracil 2400 mg/m2) plus bevacizumab biweekly were enrolled. The primary endpoint was the objective response rate (ORR). Plasma samples were collected at pre-treatment, 8 weeks after treatment, and progression in participants included in the biomarker study. The levels of circulating tumour DNA (ctDNA) and specific KRAS and NRAS variants were evaluated using real-time PCR assays. RESULTS: There were 62 patients (median age: 62.5 years, 92% performance status 0, 27% right side) who were assessable for efficacy and 51 for biomarker analysis. ORR was 75.8% (95% confidence interval 65.1% to 86.5%). The median progression-free survival was 12.1 months, and the median overall survival (OS) was 30.2 months. In 78% of patients, RAS mutations disappeared in the ctDNA at 8 weeks after treatment; these patients tended to have better outcomes than those with RAS mutations. Interestingly, RAS mutations remained undetectable during progression in 62% of patients. Survival analysis indicated that the median OS from progression was significantly longer in patients with RAS mutation clearance than in those with RAS mutation in the ctDNA at disease progression (15.1 versus 7.3 months, hazard ratio: 0.21, P = 0.0046). CONCLUSIONS: Our biomarker study demonstrated no RAS mutations in ctDNA at disease progression in 62% of patients with RAS-mutant mCRC. Both OS and post-progression survival were better in patients with clearance of RAS mutations in ctDNA after triplet-based chemotherapy.


Assuntos
DNA Tumoral Circulante , Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , DNA Tumoral Circulante/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Fluoruracila , Genes ras , Humanos , Leucovorina , Pessoa de Meia-Idade , Compostos Organoplatínicos , Estudos Prospectivos
20.
Phys Rev Lett ; 106(12): 126801, 2011 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-21517337

RESUMO

We report the observation of nonadiabatic excitations of single electrons in a quantum dot. Using a tunable-barrier single-electron pump, we have developed a way of reading out the excitation spectrum and level population of the dot by using the pump current as a probe. When the potential well is deformed at subnanosecond time scales, electrons are excited to higher levels. In the presence of a perpendicular magnetic field, the excited states follow a Fock-Darwin spectrum. Our experiments provide a simple model system to study nonadiabatic processes of quantum particles.

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