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1.
J Oral Biosci ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734177

RESUMO

BACKGROUND: The trigeminal spinal subnucleus caudalis (Sp5C), also known as the medullary dorsal horn, receives orofacial somatosensory inputs, particularly nociceptive inputs, from the trigeminal nerve. In the Sp5C, excitatory and inhibitory neurons, glutamatergic and GABAergic/glycinergic neurons, respectively, form the local circuits. The axons of the glutamatergic neurons in lamina I ascend toward the thalamic and parabrachial nuclei, and this projection is the main pathway of orofacial nociception. Additionally, the axons of the higher brain regions, including the locus coeruleus, dorsal raphe, and cerebral cortex, are sent to the Sp5C. HIGHLIGHT: Among these descending projections, this review focuses on the functional profiles of the corticotrigeminal projections to the Sp5C, along with their anatomical aspects. The primary and secondary somatosensory and insular cortices are of particular interest. CONCLUSION: Corticotrigeminal projections from the somatosensory cortex to the Sp5C play a suppressive role in nociceptive information processing, whereas recent studies have demonstrated a facilitative role of the insular cortex in nociceptive information processing at the Sp5C level.

4.
J Cardiol ; 83(6): 394-400, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37802203

RESUMO

BACKGROUND: Although major guidelines recommend the routine introduction of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers for patients with ST-segment elevation myocardial infarction (STEMI), evidence regarding the target blood pressure (BP) or pulse rate (PR) at hospital discharge is sparse. This retrospective study aimed to compare the clinical outcomes in patients with STEMI between those with good BP and PR control and those with poor BP or PR control. METHODS: We included 748 patients with STEMI who received both ACE inhibitors/ARBs and beta-blockers at hospital discharge, and divided them into a good control group (systolic BP ≤140 mmHg and PR ≤80 bpm, n = 564) and a poor control group (systolic BP >140 mmHg or PR >80 bpm, n = 184). The primary endpoint was major cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction, and re-admission for heart failure. RESULTS: During the median follow-up duration of 568 days, a total of 119 MACE were observed. The Kaplan-Meier curves showed that MACE were more frequently observed in the poor control group (p = 0.009). In the multivariate Cox hazard analysis, the good control group was inversely associated with MACE (HR 0.656, 95 % CI: 0.444-0.968, p = 0.034) after controlling for multiple confounding factors. CONCLUSIONS: The good control of systolic BP and PR at discharge was inversely associated with long-term adverse events in STEMI patients treated with both ACE inhibitors/ARBs and beta blockers. This study suggests the importance of titration of ACE inhibitors/ARBs and beta-blockers for better clinical outcomes in patients with STEMI.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Pressão Sanguínea , Frequência Cardíaca , Alta do Paciente , Estudos Retrospectivos , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Resultado do Tratamento
5.
Brain Res ; 1822: 148617, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37805008

RESUMO

Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day 1), a LiCl i.p. injection after an IOAS on Day 2, and an IOAS on Day 3 (CTA group). The subtraction images of Day 3 of the SHAM group, which received a 0.9 % NaCl (saline) injection instead of a LiCl on Day 2, from those of Day 3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem.


Assuntos
Fluordesoxiglucose F18 , Paladar , Ratos , Animais , Paladar/fisiologia , Cloreto de Lítio , Aprendizagem da Esquiva/fisiologia , Núcleo Solitário , Sacarina/farmacologia , Tomografia por Emissão de Pósitrons , Neurotransmissores
6.
Neuropharmacology ; 238: 109649, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393988

RESUMO

Insulin plays roles in brain functions such as neural development and plasticity and is reported to be involved in dementia and depression. However, little information is available on the insulin-mediated modulation of electrophysiological activities, especially in the cerebral cortex. This study examined how insulin modulates the neural activities of inhibitory neurons and inhibitory postsynaptic currents (IPSCs) in rat insular cortex (IC; either sex) by multiple whole-cell patch-clamp recordings. We demonstrated that insulin increased the repetitive spike firing rate with a decrease in the threshold potential without changing the resting membrane potentials and input resistance of fast-spiking GABAergic neurons (FSNs). Next, we found a dose-dependent enhancement of unitary IPSCs (uIPSCs) by insulin in the connections from FSNs to pyramidal neurons (PNs). The insulin-induced enhancement of uIPSCs accompanied decreases in the paired-pulse ratio, suggesting that insulin increases GABA release from presynaptic terminals. The finding of miniature IPSC recordings of the increased frequency without changing the amplitude supports this hypothesis. Insulin had little effect on uIPSCs under the coapplication of S961, an insulin receptor antagonist, or lavendustin A, an inhibitor of tyrosine kinase. The PI3-K inhibitor wortmannin or the PKB/Akt inhibitors, deguelin and Akt inhibitor VIII, blocked the insulin-induced enhancement of uIPSCs. Intracellular application of Akt inhibitor VIII to presynaptic FSNs also blocked insulin-induced enhancement of uIPSCs. In contrast, uIPSCs were enhanced by insulin in combination with the MAPK inhibitor PD98059. These results suggest that insulin facilitates the inhibition of PNs by increases in FSN firing frequency and IPSCs from FSNs to PNs. (250 words).


Assuntos
Córtex Insular , Insulina , Ratos , Animais , Insulina/farmacologia , Ratos Transgênicos , Células Piramidais , Neurônios GABAérgicos , Transmissão Sináptica , Potenciais Pós-Sinápticos Inibidores
7.
Ann Rheum Dis ; 82(11): 1455-1463, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37468219

RESUMO

OBJECTIVES: Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs. METHODS: We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment. RESULTS: Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment. CONCLUSIONS: Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.

8.
Am J Clin Dermatol ; 24(5): 837-847, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37233897

RESUMO

BACKGROUND: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options. OBJECTIVE: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment. METHODS: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient's visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain). RESULTS: A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo (P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea. CONCLUSIONS: Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed. CLINICALTRIALS: GOV: NCT04057937.


Assuntos
População do Leste Asiático , Psoríase , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Dor , Prurido/tratamento farmacológico , Prurido/etiologia , Método Duplo-Cego , Resultado do Tratamento , Índice de Gravidade de Doença
9.
BMJ Open ; 13(4): e064159, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37094891

RESUMO

OBJECTIVES: Evaluate the experiences and perceptions of patients participating in a simulated clinical trial and identify ways to enhance future patient-centric trial designs. DESIGN: International, multicentre, non-interventional, virtual clinical trial visits with patient debriefs and advisory boards. SETTING: Virtual clinic visits and accompanying advisory boards. PARTICIPANTS: Nine patients with palmoplantar pustulosis for simulated trial visits; 14 patients and patient representatives for advisory boards. MAIN OUTCOME MEASURES: Qualitative responses to trial documentation, visit schedule and logistics, and trial design were collected during patient debriefs. Results were discussed at two virtual advisory board meetings. RESULTS: Patients identified key barriers to participation and potential difficulties encountered when attending trial visits and completing assessments. They also proposed recommendations to overcome these challenges. Patients recognised the need for comprehensive informed consent forms, but recommended use of non-technical language, brevity and additional support to aid understanding. Other trial documentations should be relevant to the disease and include known efficacy and safety of the study drug. Patients were concerned about receiving placebo, stopping existing medications and being unable to receive the study drug after trial completion; therefore, patients and physicians recommended an open-label extension following trial completion. Trial visits were too numerous (n=20) and too long (3-4 hours each); patients recommended improvements to the design to make best use of their time and reduce unnecessary waiting. They also requested financial and logistical support. Patients expressed a desire for study outcomes that matter to them, related to their ability to undertake normal daily activities and not be a burden to others. CONCLUSIONS: Simulated trials are an innovative method for assessing trial design and acceptance from a patient-centric perspective, enabling specific improvements to be made prior to trial initiation. Incorporation of recommendations from simulated trials could enhance trial recruitment and retention, and optimise trial outcomes and data quality.

10.
Ann Rheum Dis ; 82(6): 809-819, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36918189

RESUMO

OBJECTIVES: Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance. METHODS: We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis. RESULTS: Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s. CONCLUSIONS: An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.


Assuntos
Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Transcriptoma , Perfilação da Expressão Gênica , Células Dendríticas
11.
J Oral Sci ; 65(2): 77-80, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36823134

RESUMO

PURPOSE: Inhibitory synaptic currents from fast-spiking neurons (FSNs), a typical gamma-aminobutyric acid (GABA)ergic interneuron in the cerebral cortex, to pyramidal neurons are facilitated by insulin. FSNs frequently show electrical synapses to FSNs, however, the effect of insulin on these electrical synapses is unknown. The aim of this study was to evaluate effects of insulin on electrical synaptic potentials between FSNs. METHODS: Electrical synaptic potentials via gap junctions between FSNs were recorded to examine how insulin modulates these potentials in the rat insular cortex (IC). RESULTS: Bath application of insulin (10 nM), which increases the spike firing rate of pyramidal neurons and unitary inhibitory postsynaptic currents recorded from FSN to pyramidal neuron connections, slightly but significantly increased electrical synaptic currents. The mean ratio of electrical synapses, the coupling coefficient that is obtained by postsynaptic voltage responses divided by presynaptic voltage amplitude, was 8.3 ± 1.1% in control and 9.2 ± 1.1% (n = 14) during 10 nM insulin application. Input resistance and voltage responses to large hyperpolarizing currents (-140 pA) were not changed by insulin. CONCLUSION: These results suggest that insulin facilitates spike synchronization by increasing electrical synaptic currents via gap junctions of GABAergic FSNs in the IC.


Assuntos
Córtex Insular , Insulina , Ratos , Animais , Insulina/farmacologia , Transmissão Sináptica/fisiologia , Córtex Cerebral/fisiologia , Junções Comunicantes , Interneurônios/fisiologia , Potenciais de Ação/fisiologia
12.
ACR Open Rheumatol ; 5(2): 93-102, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36651871

RESUMO

OBJECTIVE: Idiopathic inflammatory myopathies (IIM) demonstrate characteristic clinical phenotypes depending on the myositis-specific antibody (MSAs) present. We aimed to identify common or MSA-specific immunological pathways in different immune cell types from peripheral blood by transcriptome analysis. METHODS: We recruited 33 patients with IIM who were separated into the following groups: 15 patients with active disease at onset and 18 with inactive disease under treatment. All patients were positive for MSAs: anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in 10 patients, anti-Mi-2 Ab in 7, and anti-aminoacyl-transfer RNA synthetase (ARS) Ab in 16. The patients were compared with 33 healthy controls. Twenty-four immune cell types sorted from peripheral blood were analyzed by flow cytometry, RNA sequencing, and differentially expressed gene analysis combined with pathway analysis. RESULTS: The frequencies of memory B cell types were significantly decreased in active patients, and the frequency of plasmablasts was prominently increased in active patients with anti-MDA5 Ab in comparison with healthy controls. The expression of type I interferon (IFN)-stimulated genes of all immune cell types was increased in the active, but not inactive, patients. Endoplasmic reticulum stress-related genes in all IIM memory B cells and oxidative phosphorylation-related genes in inactive IIM double negative B cells were also increased, suggesting prominent B cell activation in IIM. Furthermore, active patients with anti-MDA5 Ab, anti-Mi-2 Ab, or anti-ARS Ab were distinguished by IFN-stimulated and oxidative phosphorylation-related gene expression in plasmablasts. CONCLUSION: Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA-specific immunological pathways in IIM.

14.
Disabil Rehabil ; 45(24): 4094-4100, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36408857

RESUMO

PURPOSE: Few studies have reported changes in the accumulation patterns of physical activity over a year after stroke. This study characterized the longitudinal changes in physical activity levels and their accumulation patterns for a 1-year follow-up period in stroke survivors. MATERIALS AND METHODS: In this single-center, prospective, longitudinal observational study, 47 stroke survivors were assessed at rehabilitation discharge and at 6 and 12 months post-discharge. Physical activity was evaluated, and measures included the number of steps, walking duration, total number of bouts per day, and intensity (light, moderate-to-vigorous) and spread (short, medium, and long bouts). RESULTS: There were no significant main or interaction effects of time on any physical activity variables. Light physical activity accounted for 90% of all walking bouts and 70% of walking duration. Regarding moderate-to-vigorous physical activity (MVPA), 85% of walking bouts and 35% of walking duration were accumulated in short and medium bouts. The number of long-bout MVPA was three per day. CONCLUSIONS: Physical activity levels and accumulation patterns were highly stable throughout the 12-month follow-up period. Accumulating light physical activity and intermittent MVPA is important for maintaining physical activity levels in stroke survivors. These findings will promote a better understanding of disability and rehabilitation practice.IMPLICATIONS FOR REHABILITATIONPhysical activity levels and accumulation patterns were highly stable throughout the 12-month follow-up period.The accumulation of moderate-to-vigorous physical activity in long bouts might be challenging for stroke survivors.Accumulating light physical activity and intermittent moderate-to-vigorous physical activity may be acceptable for stroke survivors.


Assuntos
Assistência ao Convalescente , Acidente Vascular Cerebral , Humanos , Seguimentos , Estudos Prospectivos , Alta do Paciente , Exercício Físico , Sobreviventes
15.
J Cardiol ; 81(6): 544-552, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36565995

RESUMO

BACKGROUND: Epidemiological studies reported that acute myocardial infarction (AMI) occurs more often in winter season or days with low temperatures. However, most of these studies did not distinguish ST-elevation myocardial infarction (STEMI) from AMI. The purpose of this study was to investigate the relationship between temperature and the occurrence of STEMI. METHODS: We reviewed all daily temperature in Saitama City between January 2015 and December 2021 (2557 days) and divided them into days in which our institution received STEMI (days with STEMI) and days in which our institution did not receive STEMI (days without STEMI). RESULTS: The daily maximum temperature was significantly lower in days with STEMI than in days without STEMI [20.0 °C (68.0 °F) versus 21.2 °C (70.2 °F), p = 0.001]. The maximum temperature was significantly lower in days with STEMI than in days without STEMI in the elderly [19.9 °C (67.8 °F) versus 21.1 °C (70.0 °F), p = 0.003], whereas this trend was weaker in the non-elderly [20.2 °C (68.4 °F) versus 20.9 °C (69.6 °F), p = 0.171]. Furthermore, the maximum temperature was significantly lower in days with STEMI than in days without STEMI in male [20.0 °C (68.0 °F) versus 21.1 °C (70.0 °F), p = 0.002], whereas this trend was weaker in females [20.0 °C (68.0 °F) versus 20.9 °C (69.6 °F), p = 0.169]. CONCLUSIONS: The daily temperatures were significantly lower in days with STEMI than in days without STEMI, and this relationship was pronounced in elderly or male patients.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Temperatura , Fatores de Risco , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Cidades
16.
J Dermatol ; 50(3): 319-326, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36342070

RESUMO

Psoriasis impacts various aspects of patients' health-related quality of life and is associated with sleep problems. However, research discussing the associations between interleukin-17 blockage therapies and sleep problems in patients with psoriasis is insufficient. We aimed to assess the effectiveness of brodalumab in alleviating sleep problems in real-life patients with plaque psoriasis. This analysis was part of the single-arm, open-label, multicenter, prospective, cohort study, ProLOGUE (study period October 2017-March 2020), which involved Japanese patients with plaque psoriasis. Assessments included correlation of Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R) scores (Sleep Problems Index-II [SPI-II] and MOS Sleep-R subscale scores) with multiple patient-reported outcome scores and the Psoriasis Area and Severity Index (PASI) at baseline. Additionally, change from baseline in MOS Sleep-R scores was assessed at weeks 12 and 48 of brodalumab treatment. Seventy-three patients were enrolled (male 82.2%, median age 54.0 years). At baseline, the SPI-II score correlated with the Patient Health Questionnaire-8 score (Spearman correlation coefficient [ρ] = -0.474) and weakly correlated with the Itch Numeric Rating Scale (NRS; ρ = -0.366), Skin Pain NRS (ρ = -0.275), and all Treatment Satisfaction Questionnaire for Medication-9 domain scores (ρ = 0.270, ρ = 0.303, and ρ = 0.322 for effectiveness, convenience, and global satisfaction, respectively) but did not correlate with the PASI score. The SPI-II score and MOS Sleep-R subscale scores, except the Snoring score (p = 0.0319), did not significantly change from baseline to week 12 of brodalumab treatment. In conclusion, treatment with brodalumab did not improve overall sleep problems in real-life patients with plaque psoriasis, suggesting that sleep problems require attention in daily clinical practice (Japan Registry of Clinical Trials identifier, jRCTs031180037).


Assuntos
Psoríase , Transtornos do Sono-Vigília , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais/uso terapêutico , Qualidade de Vida , Estudos de Coortes , Estudos Prospectivos , Resultado do Tratamento , Índice de Gravidade de Doença , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia
18.
Nutrients ; 14(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364870

RESUMO

Mobile applications are increasingly used in healthcare. We have developed a smartphone healthcare application, CALO mama Plus, that can register daily diet, exercise, mood, and sleep quality, calculate dietary intake, and provide advice using artificial intelligence technology. This 3-month randomized controlled trial tested the hypothesis that CALO mama Plus could promote body weight reduction in Japanese adults with overweight or obesity. We recruited office workers as participants. The key eligibility criteria were an age of 20-65 years and a body mass index of 23-40 kg/m2. The primary outcome was body weight change over 3 months. We enrolled 141 participants and randomly assigned them to the intervention (n = 72) and control (n = 69) groups. The intervention group used CALO mama Plus, and the control group did not receive any intervention. The change in body weight was -2.4 ± 4.0 kg and -0.7 ± 3.3 kg in the intervention and control groups, respectively. An analysis of covariance adjusted for related variables showed a significant between-group difference in body weight change (-1.60 kg; 95% confidence interval -2.83 to -0.38; p = 0.011). The present study suggests that CALO mama Plus effectively promotes weight loss.


Assuntos
Aplicativos Móveis , Adulto , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Smartphone , Inteligência Artificial , Redução de Peso , Sobrepeso/terapia , Índice de Massa Corporal , Peso Corporal , Atenção à Saúde
19.
J Autoimmun ; 133: 102907, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126366

RESUMO

OBJECTIVE: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. METHODS: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls. RESULTS: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling. CONCLUSION: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.


Assuntos
Artrite Reumatoide , Linfócitos T CD4-Positivos , Humanos , Artrite Reumatoide/genética , Receptores de Antígenos de Linfócitos T/genética
20.
JAAD Int ; 8: 146-153, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35942062

RESUMO

Background: Patients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment. Objective: To assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis. Methods: As a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48. Results: Seventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching. Limitations: Unclear generalizability of the results to other biologics. Conclusion: Treatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin.

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