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1.
Nat Commun ; 15(1): 3141, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653975

RESUMO

Brightness illusions are a powerful tool in studying vision, yet their neural correlates are poorly understood. Based on a human paradigm, we presented illusory drifting gratings to mice. Primary visual cortex (V1) neurons responded to illusory gratings, matching their direction selectivity for real gratings, and they tracked the spatial phase offset between illusory and real gratings. Illusion responses were delayed compared to real gratings, in line with the theory that processing illusions requires feedback from higher visual areas (HVAs). We provide support for this theory by showing a reduced V1 response to illusions, but not real gratings, following HVAs optogenetic inhibition. Finally, we used the pupil response (PR) as an indirect perceptual report and showed that the mouse PR matches the human PR to perceived luminance changes. Our findings resolve debates over whether V1 neurons are involved in processing illusions and highlight the involvement of feedback from HVAs.


Assuntos
Neurônios , Optogenética , Estimulação Luminosa , Córtex Visual Primário , Animais , Neurônios/fisiologia , Córtex Visual Primário/fisiologia , Camundongos , Masculino , Humanos , Feminino , Percepção Visual/fisiologia , Ilusões/fisiologia , Ilusões Ópticas/fisiologia , Camundongos Endogâmicos C57BL , Pupila/fisiologia , Córtex Visual/fisiologia , Córtex Visual/citologia
2.
BMC Oral Health ; 24(1): 63, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195416

RESUMO

BACKGROUND: Oral health management has become increasingly important for acute inpatients. Older patients often require extended periods of medical care, and oral health management is necessary in the convalescent period following the acute period. During the convalescent period, oral health management remains unclear as convalescent hospitals have limited dental resources, and effective dental care must be provided if the objective of hospitalization is to improve life functions. This study aimed to clarify the relationship between daily functioning and oral health status at the time of admission to a convalescent hospital to aid in improving daily functioning in the convalescent period. METHODS: We included patients admitted to the rehabilitation department of a specific convalescent hospital from January to December 2021. A total of 375 patients were included in the study, with complete data records. At admission, we gathered information from the medical records, including the patient's age, sex, primary disease, Charlson Comorbidity Index, Mini Nutritional Assessment Short-Form (MNA-SF), Functional Oral Intake Scale (FOIS), Functional Independence Measure (FIM), number of teeth, and Oral Health Assessment Tool (OHAT). Statistical analysis was conducted using SPSS Ver. 27, with a significance level of 5%. RESULTS: The mean age of the 375 participants (189 men and 186 women) was 75.0 ± 12.1 years (range, 42-97 years), and over 80% were > 65 years. About 30% of major diseases could be attributed to strokes and fractures, followed by spinal cord and spine diseases. In non-stroke patients, multiple regression analysis using FIM motor, FIM cognitive, and FIM and OHAT total scores as objective variables showed that higher total scores of MNA-SF, FOIS, and lower modified Rankin Scale and OHAT were significantly associated with better FIMs. Lower OHAT scores were significantly associated with lower FOIS and MNA-SF scores, male sex, having fewer teeth, and poor dietary patterns. CONCLUSIONS: The convalescent period is an opportune time to provide intensive dental care due to the generally stable condition and extended hospital stay. Our results suggest that oral health management, such as dysphagia rehabilitation and denture treatment, is important for maintaining and improving independence, a key objective of convalescent rehabilitation, and malnutrition improvement.


Assuntos
Estado Funcional , Saúde Bucal , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pacientes Internados , Hospitalização , Administração Oral
3.
Neurosci Lett ; 814: 137465, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37659700

RESUMO

Neuroimaging studies have demonstrated the presence of a default mode network (DMN) which shows greater activity during rest, and an executive network (EN) which is activated during cognitive tasks. DMN and EN are thought to have competing functions. However, recent studies reported that the two networks show coactivation during some cognitive tasks. To clarify how DMN works and how DMN interacts with EN for cognitive control, we recorded EEG activities in the medial prefrontal (anterior DMN: aDMN), posterior cingulate/precuneus (posterior DMN: pDMN), and lateral prefrontal (EN) areas in the monkey. As cognitive tasks, we employed a monkey-monkey competitive video game (GAME) and a delayed-response (DR) task. We focused on theta oscillation because of its importance in cognitive control. We also examined theta band connectivity among the three network areas using the Granger causality analysis. DMN and EN were found to work cooperatively in both tasks. In all the three network areas, we found GAME-task-related, but no DR-task-related, increase in theta power from the resting level, maybe because of the higher cognitive demand associated with the GAME task performance. The information flow conveyed by the theta oscillation was directed more to aDMN than from aDMN for both tasks. The GAME-task-related increase in theta power in aDMN is supposed to be supported by more information flow conveyed by the theta oscillation from EN and pDMN.


Assuntos
Rede de Modo Padrão , Giro do Cíngulo , Neuroimagem , Lobo Parietal , Modalidades de Fisioterapia
4.
Sci Rep ; 13(1): 15427, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723239

RESUMO

Biennial Update Reports (BURs) are essential requirements from the United Nations Framework Convention on Climate Change (UNFCCC). However, many non-Annex I countries have not submitted these reports due to difficulties in compiling the inventories. We developed a satellite-based method for the top-down inverse estimation of CO2 emissions using partial-column data in the lower troposphere obtained by the Greenhouse Gases Observing Satellite, adopted to validate the Mongolian 2nd BUR (BUR2) for the energy sector in 2018. The estimated CO2 emissions were only 1.5% higher than those reported in the BUR2; these were also very close (4.2% smaller) to estimates from the Emission Database for Global Atmospheric Research. Mongolia is the first country to introduce an independent inverse estimate in its BUR, thereby increasing scientific transparency. Our method could be applied into other countries and could be incorporated into UNFCCC reporting guidelines, significantly improving global CO2 emission estimates.

5.
J Dent ; 136: 104632, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37506810

RESUMO

OBJECTIVE: To investigate the occurrence of mild cognitive impairment in edentulous patients up to 3 years after they received single-implant overdentures (1-IODs). METHODS: This was a follow-up study for a crossover randomized controlled trial comparing 1-IODs and conventional complete dentures, with patient satisfaction as the primary outcome. In the present study, the cognitive function of the patients, measured with the Japanese version of the Montreal cognitive assessment (MoCA-J), was evaluated as the secondary outcome at baseline and 2 months, 1 year, 2 years, and 3 years after 1-IOD placement. The total and domain (memory, executive function, visuospatial skills, language, attention, and orientation) MoCA-J scores of the patients at each timepoint were analyzed and compared. RESULTS: Twenty-two patients with edentulous mandibles received 1-IODs. Within-group comparisons revealed that the total MoCA-J scores at 1 year and 3 years after 1-IOD placement were significantly increased compared with baseline scores. Additionally, the memory domain scores at all timepoint were significantly increased compared with the baseline scores, and the executive function domain scores at the 2-month, 2-year and 3-year timepoint were significantly increased compared with the baseline scores. CONCLUSION: Patients with edentulous mandibles who underwent 1-IOD placement showed significantly improved total scores of MoCA-J after 1 year and 3 years of wearing 1-IODs. In addition, they showed significantly improved memory domain scores at 2 months, 1 year, 2 years, and 3 years after 1-IOD placement and executive function domain scores at 2 months, 2 years, and 3 years after 1-IOD placement. CLINICAL SIGNIFICANCE: The results of this study suggest that 1-IOD treatment for older adults, especially those with edentulous mandibles, may prevent cognitive decline regardless of the condition of the maxilla.


Assuntos
Implantes Dentários , Revestimento de Dentadura , Humanos , Idoso , Seguimentos , Qualidade de Vida , Prótese Total , Satisfação do Paciente , Cognição , Prótese Dentária Fixada por Implante , Mandíbula , Retenção de Dentadura
6.
Oncol Rep ; 49(5)2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36896786

RESUMO

Suprabasin (SBSN) is a secreted protein that is isolated as a novel gene expressed in differentiated keratinocytes in mice and humans. It induces various cellular processes such as proliferation, invasion, metastasis, migration, angiogenesis, apoptosis, therapy and immune resistance. The role of SBSN was investigated in oral squamous cell carcinoma (OSCC) under hypoxic conditions using the SAS, HSC­3, and HSC­4 cell lines. Hypoxia induced SBSN mRNA and protein expression in OSCC cells and normal human epidermal keratinocytes (NHEKs), and this was most prominent in SAS cells. The function of SBSN in SAS cells was analyzed using 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT); 5­bromo­2'­deoxyuridine (BrdU); cell cycle, caspase 3/7, invasion, migration, and tube formation assays; and gelatin zymography. Overexpression of SBSN decreased MTT activity, but the results of BrdU and cell cycle assays indicated upregulation of cell proliferation. Western blot analysis for cyclin­related proteins indicated involvement of cyclin pathways. However, SBSN did not strongly suppress apoptosis and autophagy, as revealed by caspase 3/7 assay and western blotting for p62 and LC3. Additionally, SBSN increased cell invasion more under hypoxia than under normoxia, and this resulted from increased cell migration, not from matrix metalloprotease activity or epithelial­mesenchymal transition. Furthermore, SBSN induced angiogenesis more strongly under hypoxia than under normoxia. Analysis using reverse transcription­quantitative PCR showed that vascular endothelial growth factor (VEGF) mRNA was not altered by the knockdown or overexpression of SBSN VEGF, suggesting that VEGF is not located downstream of SBSN. These results demonstrated the importance of SBSN in the maintenance of survival and proliferation, invasion and angiogenesis of OSCC cells under hypoxia.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Caspase 3 , Bromodesoxiuridina , Proliferação de Células/genética , Fatores de Crescimento do Endotélio Vascular , Movimento Celular , Hipóxia/genética , Linhagem Celular Tumoral , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Proteínas de Neoplasias
7.
Vaccine X ; 15: 100411, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38161990

RESUMO

To elucidate appropriate ways to induce behavior that prevents the spread of infection, we examined the association between COVID-19 vaccination and COVID-19-related information after more than 85% of the population had been vaccinated. Nonprobability quota sampling was used to recruit 2000 Tokyo residents as participants. The association between previous vaccine uptake and how much people thought they were affected by each of nine media, seven providers, and four content types of information was assessed using an online survey form. Subjective influence was assessed, and order logistic regression analyses were performed. We further calculated standardized partial regression coefficients for the independent variables. The results showed that while people did not think they were strongly affected by any COVID-19 information, significant positive associations between 9 of 20 variables, and significant negative associations between 7 of 20 variables were observed with vaccine uptake. The regression analysis involving the interaction terms between independent variables and sex showed a significant association between vaccine uptake and only daily conversation. Simple slope analysis showed a stronger positive association for females than for males. Regression analysis with interaction terms between each independent variable and age showed a significant association between vaccine uptake and print newspapers, social networking services, prefectural governors, family/relatives, accessibility, side effects, and supply visibility. Simple slope analysis also showed that the positive association between the subjective influence of newspapers and vaccine uptake was observed only for older people (≥69 years), and that of prefectural governors was more significant for older than younger people (≤32 years). In contrast, the trustworthy information provided by family/relatives was positively associated with vaccine uptake only for younger people. These results suggest that careful consideration must be given to the differences in age and sex to provide appropriate information that motivates Tokyo residents to receive vaccination during COVID-19 pandemic.

8.
Clin Oral Implants Res ; 33(12): 1265-1272, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36222311

RESUMO

OBJECTIVES: This prospective study aimed to compare the oral functions of removable partial dentures (RPDs) with those of implant-assisted removable partial dentures (IARPDs) with short implants and magnetic attachments in patients with mandibular Kennedy class I and II. MATERIAL AND METHODS: Thirty participants with mandibular Kennedy class I or II and at least three distal missing teeth were recruited. Oral functions, including mixing ability, comminuting ability, maximum bite force, and occlusal contact area, were assessed for RPDs (stage 0), IARPDs with healing caps (stage 1), and IARPDs with magnetic attachments (stage 2). The implants were loaded with occlusal force in stages 1 and 2. Finally, the data of the 27 participants who completed the evaluation at stage 2 were analyzed. The Wilcoxon signed-rank test with Bonferroni correction was used to assess the differences in the oral functions among the different stages. RESULTS: The implant survival rate was 93.8%. There were significant differences in the comminuting ability and occlusal contact area between stages 0 and 2 (p < .001 and p = .036, respectively) and stages 1 and 2 (p = .003 and p = .015, respectively). Regarding the maximum bite force, there was a significant difference between stages 1 and 2 (p = .018). However, there was no significant difference in the mixing ability between the three stages. CONCLUSIONS: Within the limitations of this study, it was concluded that IARPDs in the mandible with short implants and magnetic attachments may improve oral functions.


Assuntos
Prótese Parcial Removível , Saúde Bucal , Qualidade de Vida , Humanos , Fenômenos Magnéticos , Estudos Prospectivos , Satisfação do Paciente , Resultado do Tratamento
9.
J Dent ; 117: 103920, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34906619

RESUMO

Objective Patient satisfaction with single-implant overdentures (1-IODs) is unclear. This randomized crossover trial aimed to compare the general satisfaction, oral health-related quality of life, and patients' self-assessment between mandibular 1-IODs and experimental removable complete dentures (eRCDs). Methods New mandibular RCDs were fabricated for 22 patients with edentulous mandibles. After adapting to the RCDs, one implant was inserted in the mandibular midline. The participants were then randomly classified into groups 1 and 2. Group 1 received IODs for the first 2 months, while group 2 used eRCDs with a non-loaded implant in the midline. After 2 months, the treatment was switched. Four validated, patient-reported dental outcome measures were assessed: general satisfaction, Japanese version of the Oral Health Impact Profile for edentulous subjects (OHIP EDENT-J), General Oral Health Assessment Index (GOHAI), and Patient's Denture Assessment (PDA). The assessments were performed at the end of the IOD- and eRCD- use periods. Results General satisfaction was significantly higher during the IOD period (p = 0.002). Significant differences were observed in all domains of the OHIP, except orofacial pain (p = 0.084). Further, the total score (p<0.001) and the scores of the physical (p<0.001) and psychosocial functioning (p = 0.001) domains of the GOHAI differed significantly. The total PDA score (p = 0.001) and the scores of the function (p = 0.004), lower denture (p = 0.002), esthetics and speech (p = 0.026), and importance (p = 0.009) domains were significantly higher during the IOD period than during the eRCD period. Conclusion General satisfaction, oral health-related quality of life, and patient self-assessment scores were significantly higher for 1-IODs than for eRCDs. Clinical significance Within the limitations of this study, we found that mandibular single-implant overdentures may be an efficient alternative to mandibular experimental removable complete dentures due to higher general satisfaction, oral health-related quality of life, and patient self-assessment scores of dentures.


Assuntos
Implantes Dentários , Qualidade de Vida , Estudos Cross-Over , Prótese Dentária Fixada por Implante , Retenção de Dentadura , Prótese Total , Prótese Total Inferior , Revestimento de Dentadura , Estética Dentária , Humanos , Mandíbula , Satisfação do Paciente , Satisfação Pessoal , Autoavaliação (Psicologia)
10.
Sci Rep ; 9(1): 9165, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235830

RESUMO

An accurate knowledge of tissue optical properties (absorption coefficients, µa, and reduced scattering coefficients, µs') is critical for precise modeling of light propagation in biological tissue, essential for developing diagnostic and therapeutic optical techniques that utilize diffusive photons. A great number of studies have explored the optical properties of various tissue, and these values are not known in detail due to difficulties in the experimental determination and significant variations in tissue constitution. Especially, in situ estimates of the optical properties of brain tissue, a common measurement target in optical imaging, is a challenge because of its layer structure (where the thin gray matter covers the white matter). Here, we report an approach to in situ estimates of the µa and µs' of the gray and white matter in living rat and monkey brains by using femtosecond time-resolved measurements and Monte Carlo simulation. The results demonstrate that the µa of the gray matter is larger than that of the white matter, while there was no significant difference in the µs' between the gray and white matter. The optical properties of the rat brain were very similar to those of the monkey brain except for the µa of the gray matter here.


Assuntos
Encéfalo/citologia , Fenômenos Ópticos , Animais , Encéfalo/diagnóstico por imagem , Haplorrinos , Método de Monte Carlo , Imagem Óptica , Imagens de Fantasmas , Ratos , Fatores de Tempo
11.
Int J Cardiol ; 289: 91-98, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770263

RESUMO

AIMS: Pulmonary congestion is associated with poor prognosis following hospitalization for worsening heart failure (HF), although its quantification and optimal timing during HF hospitalization remains challenging. The aim of this study was to assess the prognostic value of radiographic pulmonary congestion at admission and discharge in patients with worsening HF. METHODS AND RESULTS: Clinical, echocardiographic, laboratory and chest X-ray data of 292 acute decompensated HF patients were retrospectively studied (follow-up 1 year). Lung congestion was blindly scored on chest X-ray performed at admission and discharge using a systematic 6-zone approach. Primary clinical outcome was a composite outcome of re-hospitalization for worsening HF or all cause death. Patients were stratified according to the median of congestion score index (CSI) at both admission (median CSI(A) = 1.33) and discharge (median CSI(D) = 0.33). BNP levels, LVEF and eGFR did not differ between CSI categories. In multivariable Cox regression analysis, discharge CSI (HR for 1-point increase = 1.83 [1.02 to 3.27] p = 0.04) and discharge BNP were significantly associated with the composite outcome whereas NYHA class, physical signs, admission CSI and echocardiographic data were not. Furthermore, discharge CSI significantly increased reclassification on top of clinical covariates (continuous NRI = 19.6% [4.0 to 30.0] p = 0.03 and IDI = 2.2% [0.0 to 7.6] p = 0.046) while discharge BNP did not significantly improve risk reclassification. CONCLUSIONS: Residual pulmonary congestion assessed by radiographic scoring predicts poor prognosis beyond physical assessment, echocardiographic parameters and BNP. These findings further support the capital prognostic value of radiographic pulmonary congestion in patients hospitalized for worsening HF.


Assuntos
Insuficiência Cardíaca/complicações , Pacientes Internados , Edema Pulmonar/diagnóstico , Radiografia Torácica/métodos , Medição de Risco/métodos , Doença Aguda , Idoso , Causas de Morte/tendências , Progressão da Doença , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Prognóstico , Circulação Pulmonar/fisiologia , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
12.
Clin Res Cardiol ; 108(5): 549-561, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30341579

RESUMO

AIMS: Estimated plasma volume status (ePVS) predicts prognosis in patients with heart failure (HF). It remains unclear whether admission, discharge or change ePVS best predicts post-discharge outcome in patients with acute decompensated heart failure (ADHF). METHODS: We retrospectively analyzed three cohort studies: 383 patients admitted at the Tokyo Medical University hospital, 165 patients admitted at the Centro Hospitalar do Porto and 164 patients admitted at the Nancy University Hospital (ICALOR study). ePVS at admission and at discharge as well as its change thereof were, respectively, calculated using the Duarte and Strauss formulas, both derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. The clinical outcome was a composite of re-hospitalization for worsening HF or all-cause mortality [corrected]. RESULTS: The primary outcomes occurred in 27.2% at 1 year (in the Tokyo cohort), 45.3% at 6 months (in the Porto cohort) and 53.9% at median terms of 298.3 days (in the ICALOR study). After adjusting for potential confounders including natriuretic peptide, discharge ePVS remained significantly associated with increased rates of composite outcome in the Tokyo and Porto cohorts and ICALOR study [hazard ratio (HR) 1.21 (1.01-1.44), p = 0.04; HR 1.45 (1.16-1.81), p < 0.01; HR 1.45 (1.16-1.81), p < 0.01, respectively]. In addition, a pooled analysis yielded a significant improvement in reclassification with discharge ePVS [net reclassification index 13.6% (5.9-22.7), p = 0.004]. CONCLUSIONS: As validated in three independent ADHF cohorts, ePVS at discharge was independently associated with post-discharge clinical outcomes and improved the risk stratification of patients admitted for ADHF on top of well-established prognostic markers.


Assuntos
Insuficiência Cardíaca/sangue , Volume Plasmático/fisiologia , Medição de Risco/métodos , Função Ventricular Esquerda/fisiologia , Doença Aguda , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
14.
Sci Rep ; 8(1): 12376, 2018 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-30120294

RESUMO

Information integration across the senses is fundamental for effective interactions with our environment. The extent to which signals from different senses can interact in the absence of awareness is controversial. Combining the spatial ventriloquist illusion and dynamic continuous flash suppression (dCFS), we investigated in a series of two experiments whether visual signals that observers do not consciously perceive can influence spatial perception of sounds. Importantly, dCFS obliterated visual awareness only on a fraction of trials allowing us to compare spatial ventriloquism for physically identical flashes that were judged as visible or invisible. Our results show a stronger ventriloquist effect for visible than invisible flashes. Critically, a robust ventriloquist effect emerged also for invisible flashes even when participants were at chance when locating the flash. Collectively, our findings demonstrate that signals that we are not aware of in one sensory modality can alter spatial perception of signals in another sensory modality.


Assuntos
Percepção Auditiva/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica , Adolescente , Adulto , Feminino , Humanos , Ilusões , Masculino , Estimulação Luminosa , Adulto Jovem
15.
Nat Commun ; 9(1): 1635, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29691372

RESUMO

A pure quantum state can fully describe thermal equilibrium as long as one focuses on local observables. The thermodynamic entropy can also be recovered as the entanglement entropy of small subsystems. When the size of the subsystem increases, however, quantum correlations break the correspondence and mandate a correction to this simple volume law. The elucidation of the size dependence of the entanglement entropy is thus essentially important in linking quantum physics with thermodynamics. Here we derive an analytic formula of the entanglement entropy for a class of pure states called cTPQ states representing equilibrium. We numerically find that our formula applies universally to any sufficiently scrambled pure state representing thermal equilibrium, i.e., energy eigenstates of non-integrable models and states after quantum quenches. Our formula is exploited as diagnostics for chaotic systems; it can distinguish integrable models from non-integrable models and many-body localization phases from chaotic phases.

16.
Cardiovasc Drugs Ther ; 32(2): 183-190, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29589153

RESUMO

BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly. METHODS: DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin. CONCLUSION AND PERSPECTIVES: DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).


Assuntos
Albuminúria/prevenção & controle , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão/epidemiologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Brain Nerve ; 69(4): 347-354, 2017 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-28424389

RESUMO

Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys. Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey PFCs, and proposed slightly different brain maps for both species. They assigned numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9. Areas 8 and 9 have both lateral and medial regions respectively. The lateral area 8 is important for conditional discrimination learning. The frontal eye field which occupies the most caudal region of area 8, is responsible for visual attention and control of eye movements. The lateral area 9 and area 9/46 are functionally similar to area 46 and play important roles in executive control. The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8 and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also known to show "default mode of brain activity" (i.e., more activity during rest than during cognitive task).


Assuntos
Olho , Lobo Frontal/fisiologia , Fenômenos Fisiológicos Oculares , Animais , Mapeamento Encefálico , Lobo Frontal/anatomia & histologia , Humanos
18.
J Neurosci ; 37(9): 2387-2394, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28154152

RESUMO

Methylphenidate (MPH; trade name Ritalin) is a widely used drug for the treatment of attention deficit hyperactivity disorder (ADHD) and is often used as a cognitive enhancer. Because MPH increases dopamine (DA) release by blocking the DA transporter in the human striatum, MPH is supposed to work on attention and cognition through a DA increase in the striatum. However, ADHD patients show impaired prefrontal cortex (PFC) function and MPH administration is associated with increased neural activity in the PFC. Although MPH is indicated to increase DA release in the rat PFC, there has been no study to examine MPH-induced DA changes in the human PFC because of technical difficulties associated with the low level of PFC DA receptors. Using the microdialysis technique, we examined the effects of oral administration of MPH on DA release in both the PFC and striatum in the monkey. We also tested the effect of MPH on cognitive task performance. As in human studies, in the striatum, both high and low doses of MPH induced consistent increases in DA release ∼30 min after their administrations. In the PFC, a consistent increase in DA release was observed 1 h after a high dose, but not low doses, of MPH. Low doses of MPH improved cognitive task performance, but a high dose of MPH made the monkey drowsy. Therefore, low-dose MPH-induced cognitive enhancement is supported by striatum DA increase.SIGNIFICANCE STATEMENT Methylphenidate (MPH) is a widely used drug for the treatment of attention deficit hyperactivity disorder and is often used as a cognitive enhancer. Although human positron emission tomography studies suggest that MPH works on attention and cognition through dopamine (DA) changes in the striatum, there has been no study to examine MPH-induced DA changes in the human prefrontal cortex (PFC). Using the microdialysis technique in monkeys, we found, for the first time, that low doses of MPH consistently increased DA release in the striatum but did not in the PFC. Cognitive enhancement effects of low doses of MPH are supposed to be supported by the striatum DA increase.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Metilfenidato/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Administração Oral , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Inibição Psicológica , Macaca mulatta , Masculino , Microdiálise , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Autoimagem , Fatores de Tempo
19.
Neuroimage ; 144(Pt A): 217-226, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27732887

RESUMO

Attention allows our brain to focus its limited resources on a given task. It does so by selective modulation of neural activity and of functional connectivity (FC) across brain-wide networks. While there is extensive literature on activity changes, surprisingly few studies examined brain-wide FC modulations that can be cleanly attributed to attention compared to matched visual processing. In contrast to prior approaches, we used an ultra-long trial design that avoided transients from trial onsets, included slow fluctuations (<0.1Hz) that carry important information on FC, and allowed for frequency-segregated analyses. We found that FC derived from long blocks had a nearly two-fold higher gain compared to FC derived from traditional (short) block designs. Second, attention enhanced intrinsic (negative or positive) correlations across networks, such as between the default-mode network (DMN), the dorsal attention network (DAN), and the visual system (VIS). In contrast attention de-correlated the intrinsically correlated visual regions. Third, the de-correlation within VIS was driven primarily by high frequencies, whereas the increase in DAN-VIS predominantly by low frequencies. These results pinpoint two fundamentally distinct effects of attention on connectivity. Information flow increases between distinct large-scale networks, and de-correlation within sensory cortex indicates decreased redundancy.


Assuntos
Atenção/fisiologia , Conectoma/métodos , Lobo Parietal/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Percepção de Movimento/fisiologia , Lobo Parietal/diagnóstico por imagem , Reconhecimento Visual de Modelos/fisiologia , Córtex Visual/diagnóstico por imagem , Adulto Jovem
20.
Brain Nerve ; 68(11): 1291-1299, 2016 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-27852020

RESUMO

Patients with the damage to the orbital region of the prefrontal cortex and monkeys with lesions in this area show impairment in emotional and motivational behavior. They also have difficulty in the extinction of learned behavior and in the reversal learning. This brain area is concerned with not only the value estimation of reward and aversive stimuli but also the expectation of these stimuli. The lateral prefrontal cortex plays an important role in the integration of emotion/motivation and cognition. The medial prefrontal cortex is concerned with action selection based on the previous reward history. The ventrolateral prefrontal cortex that comprises the anterior parts of the orbital and inferior medial prefrontal cortex plays an important role in emotion-based decision-making.


Assuntos
Cognição/fisiologia , Emoções/fisiologia , Motivação/fisiologia , Córtex Pré-Frontal/fisiologia , Recompensa , Animais , Tomada de Decisões/fisiologia , Humanos
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