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1.
Clin Genet ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733153

RESUMO

Maturity-Onset Diabetes of the Young (MODY) is a diabetes mellitus subtype caused by a single gene. The detection rate of the responsible gene is 27% in the United Kingdom, indicating that the causative gene remains unknown in the majority of clinically diagnosed MODY cases. To improve the detection rate, we applied comprehensive genetic testing using whole exome sequencing (WES) followed by Multiplex Ligation-dependent Probe Amplification (MLPA) and functional analyses. Twenty-one unrelated Japanese participants with MODY were enrolled in the study. To detect copy number variations (CNVs), WES was performed first, followed by MLPA analysis for participants who were negative on the basis of WES. Undetermined variants were analyzed according to their functional properties. WES identified 7 pathogenic and 3 novel likely pathogenic variants in the 21 participants. Functional analyses revealed that 1 in 3 variants was pathogenic. MLPA analysis applied to the remaining 13 undetermined samples identified 4 cases with pathogenic CNVs: 3 in HNF4A and 1 in HNF1B. Pathogenic variants were identified in 12 participants (12/21, 57.1%) - relatively high rate reported to date. Notably, one-third of the participants had CNVs in HNF4A or HNF1B, indicating a limitation of WES-only screening.

2.
BMC Pulm Med ; 24(1): 214, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698432

RESUMO

BACKGROUND: In western Yokohama, our hospital and primary care clinics manage adults with asthma via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system. METHODS: From 288 adults with well controlled asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters. RESULTS: Of the 99 patients enrolled, 17 (17.2%) experienced at least one exacerbation (insufficiently controlled (IC)), whereas, 82 (82.8%) remained in well controlled during the 3-year study period. Of well-controlled patients, 54 patients (54.5%) met the criteria for clinical remission under treatment (CR); the remaining 28 patients did not meet the CR criteria (WC). There were no differences in FeNO, FEV1, or FOT parameters at baseline among the IC, WC, and CR groups. The levels of FEV1 decreased gradually, whereas the levels of FeNO decreased significantly over 3 years. The levels of percent predicted FEV1 (%FEV1) significantly increased. We also observed significant improvement in FOT parameters; reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The CR group demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the IC or WC group. CONCLUSION: The decrease in FeNO and increase in %FEV1, we observed in all study participants suggest that the coordinated care system model benefits patients with asthma. Although it is difficult to predict at baseline which patients will experience an exacerbation, monitoring changes in FeNO and FEV1 is useful in managing patients with asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.


Assuntos
Asma , Espirometria , Humanos , Masculino , Feminino , Asma/fisiopatologia , Asma/terapia , Asma/diagnóstico , Volume Expiratório Forçado , Pessoa de Meia-Idade , Adulto , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Idoso , Teste da Fração de Óxido Nítrico Exalado
3.
Int J Radiat Biol ; : 1-9, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652836

RESUMO

PURPOSE: The effect of chronic low dose-rate radiation exposure on cancers was investigated by analyzing the data of mice experiments conducted at the Institute for Environmental Sciences (IES). This analysis focuses on the differences between malignant lymphomas and solid cancers. MATERIALS AND METHODS: The analysis is conducted based on the mathematical model introduced in our previous work. The model is expanded to analyze malignant lymphomas and solid cancers separately. Using the expanded model, the effect of chronic low dose-rate radiation on malignant lymphomas and solid cancers are discussed based on their occurrences, progressions, and mortalities. RESULTS: Non-irradiated control group and 20 mGy/day × 400 days irradiated groups are analyzed. The analysis showed that radiation exposure shortened mean life expectancy for both malignant lymphomas and solid cancers (shorter by 89.6 days for malignant lymphomas and 149.3 days for solid cancers). For malignant lymphomas, both the occurrence and the progression are affected by radiation exposure. The mean age at which malignant lymphoma developed in mice was shortened by 32.7 days and the mean progression period was shortened by 57.3 days. The occurrence of solid cancer is also affected by radiation exposure, wherein the mean age at which solid cancer develops was shortened by 147.9 days. However, no significant change in progression period of solid cancers was seen in the analysis. CONCLUSIONS: The analysis showed that the occurrence and mean lifespan are affected in both malignant lymphomas and solid cancers. The shortening of the progression period is only seen in malignant lymphoma, no significant change was observed in solid cancers.

4.
Int J Cancer ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688826

RESUMO

Mouse models are vital for assessing risk from environmental carcinogens, including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human-mouse difference in radiation-related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data on cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age-related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per-lifespan basis (0.72- and 0.71-fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 years per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species-independent radiation-induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation-associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans.

5.
Nat Commun ; 15(1): 3493, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684653

RESUMO

Extraterrestrial minerals on the surface of airless Solar System bodies undergo gradual alteration processes known as space weathering over long periods of time. The signatures of space weathering help us understand the phenomena occurring in the Solar System. However, meteorites rarely retain the signatures, making it impossible to study the space weathering processes precisely. Here, we examine samples retrieved from the asteroid Ryugu by the Hayabusa2 spacecraft and discover the presence of nonmagnetic framboids through electron holography measurements that can visualize magnetic flux. Magnetite particles, which normally provide a record of the nebular magnetic field, have lost their magnetic properties by reduction via a high-velocity (>5 km s-1) impact of a micrometeoroid with a diameter ranging from 2 to 20 µm after destruction of the parent body of Ryugu. Around these particles, thousands of metallic-iron nanoparticles with a vortex magnetic domain structure, which could have recorded a magnetic field in the impact event, are found. Through measuring the remanent magnetization of the iron nanoparticles, future studies are expected to elucidate the nature of the nebular/interplanetary magnetic fields after the termination of aqueous alteration in an asteroid.

6.
Intern Med ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38432962

RESUMO

Tosufloxacin tosilate is classified as a new quinolone antibacterial agent, which has been reported to cause crystal nephropathy. However, the origin of these crystal deposits has not yet been elucidated. We encountered a case of renal failure that progressed slowly owing to crystal-forming interstitial nephritis after long-term exposure to tosufloxacin. Mass spectrometry of the renal specimens revealed that tosufloxacin was deposited in the kidneys. The patient's renal function improved slowly with the withdrawal of tosufloxacin and steroid therapy. This is the first case to demonstrate the presence of crystal deposits consisting of tosufloxacin.

7.
J Anesth ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494577

RESUMO

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

8.
Patient Prefer Adherence ; 18: 623-633, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476588

RESUMO

Purpose: Fearful dental patients often cite various dental instruments or procedures as triggers for their dental fear. Thus, visual dental stimuli provoke anxiety. This preliminary study aimed to assess the level of aversion to visual stimuli in dental patients and compare it with that in dentists. Patients and Methods: A total of 43 dental patients (25 women, 18 men; average age, 29.9 ± 13.3 years; patient group) and 13 dentists (4 women, 9 men; average age, 28.2 ± 2.0 years; dentist group) were included. All participants had previously undergone dental treatment. The dental fear level was assessed using the self-reported Dental Fear Survey (DFS). Thirty-two images associated with dental treatment were prepared and classified into three categories: dental instruments, dental procedures, and the dental environment. All participants rated their level of disgust toward each image on a visual analog scale with scores ranging from 0 to 100. Results: In the patient group, the disgust ratings for tooth extraction, dental drilling, and local anesthesia were >60, which were significantly different from those in the dentist group (Mann-Whitney U-test, p<0.001, p=0.001, and p=0.001, respectively). The ranking order of the disgust ratings for the 32 images showed significant correlation between the patient and dentist groups (Spearman correlation coefficient, r=0.80, p<0.001). In the patient group, the disgust ratings for dental impressions and the interdental brush, dental light, and dental chair were significantly correlated with DFS scores (r=0.61, p<0.001; r=0.47, p=0.001; r=0.41, p=0.006; and r=0.40, p=0.008, respectively). Conclusion: This study revealed that patients have more negative feelings toward invasive procedures than dentists. However, a significant correlation was identified between the ranking of aversion-provoking dental stimuli by patients and dentists. Furthermore, the level of aversion to several dental-related items that do not cause pain was correlated with the dental fear level.

9.
iScience ; 27(2): 108967, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38352229

RESUMO

The dose-response characteristics of transcranial direct current stimulation (tDCS) remain uncertain but may be related to variability in brain electric fields due to individual anatomical factors. Here, we investigated whether the electric fields influence the responses to motor cortical tDCS. In a randomized cross-over design, 21 participants underwent 10 min of anodal tDCS with 0.5, 1.0, 1.5, or 2.0 mA or sham. Compared to sham, all active conditions increased the size of motor evoked potentials (MEP) normalized to the pre-tDCS baseline, irrespective of anterior or posterior magnetic test stimuli. The electric field calculated in the motor cortex of each participant had a nonlinear effect on the normalized MEP size, but its effects were small compared to those of other participant-specific factors. The findings support the efficacy of anodal tDCS in enhancing the MEP size but do not demonstrate any benefits of personalized electric field modeling in explaining tDCS response variability.

10.
Odontology ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308677

RESUMO

Dental drilling sounds can induce anxiety in some patients. This study aimed to use functional magnetic resonance imaging (fMRI) to assess the relationship between dental fear and auditory stimuli. Thirty-four right-handed individuals (21 women and 13 men; average age, 31.2 years) were selected. The level of dental fear was assessed using the dental fear survey (DFS). Based on a threshold DFS score > 52, participants were categorized into two groups: dental fear (DF) group (n = 12) and control group (n = 22). Two types of stimuli were presented in a single session: dental and neutral sounds. Cerebral activation during the presentation of these sounds was evaluated using contrast-enhanced blood oxygenation level-dependent fMRI. In the DF group, dental sounds induced significantly stronger activation in the left inferior frontal gyrus and left caudate nucleus (one-sample t test, P < 0.001). In contrast, in the control group, significantly stronger activation was observed in the bilateral Heschl's gyri and left middle frontal gyrus (one-sample t test, P < 0.001). Additionally, a two-sample t test revealed that dental sounds induced a significantly stronger activation in the left caudate nucleus in the DF group than in the control group (P < 0.005). These findings suggest that the cerebral activation pattern in individuals with DF differs from that in controls. Increased activation of subcortical regions may be associated with sound memory during dental treatment.

11.
Nihon Yakurigaku Zasshi ; 159(1): 44-47, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38171838

RESUMO

Mast cells and basophils share many characteristics, such as surface expression of the high affinity receptor of IgE, FcεRI, granule storage of histamine, which is released during their activation, and potentials to produce pro-/anti-inflammatory cytokines. These similar leukocytes, however, were found to have their own process of differentiation. Indeed, accumulating evidence suggests that these cells should play critical roles in type I allergy including anaphylaxis and in urticaria. Various inflammatory mediators derived from mast cells/basophils, such as histamine, platelet-activating factor, prostanoids, and leukotrienes, have been paid a particular attention to as the therapeutic targets for type I allergy and inflammatory diseases. Recent progress in the field of mast cell/basophil research has shed light on their physiological roles in bacterial infection, energy metabolism, and cutaneous/intestinal inflammation. This review makes a brief introduction of these recent studies, which are expected to provide novel therapeutic approaches for infectious and chronic inflammatory diseases.


Assuntos
Basófilos , Urticária , Humanos , Basófilos/metabolismo , Mastócitos/metabolismo , Histamina/metabolismo , Urticária/metabolismo , Citocinas/metabolismo
12.
BMC Res Notes ; 17(1): 12, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38167562

RESUMO

OBJECTIVE: While mixed dentition space analysis is a common practice in pediatric dentistry, digital models created using an intraoral scanner are not as widely used in clinical settings. This preliminary study used a very small sample size with one reference model and aimed to (1) compare the accuracy of mixed dentition space analysis using a digital model obtained from an optical impression with that of conventional plaster model-based analysis and (2) assess inter-examiner differences. RESULTS: The space required for the mandibular permanent canine and premolars and arch length discrepancy were calculated using each model. The largest significant difference between plaster- and digital model-based analyses was identified when the right arch length discrepancy was considered (-0.49 mm; 95% confidence interval: -0.95-0.03); however, the value was considered clinically insignificant. Significant inter-examiner differences were observed for six items of the plaster model; however, no such differences were observed when using the digital model. In conclusion, digital model space analysis may have the same level of accuracy as conventional plaster model analysis and likely results in smaller inter-examiner differences than plaster model analysis.


Assuntos
Dentição Mista , Imageamento Tridimensional , Criança , Humanos , Imageamento Tridimensional/métodos , Reprodutibilidade dos Testes , Modelos Dentários , Dente Canino , Arco Dental/diagnóstico por imagem , Desenho Assistido por Computador
13.
Sci Adv ; 10(3): eadi7203, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38241366

RESUMO

The Hayabusa2 spacecraft delivered samples of the carbonaceous asteroid Ryugu to Earth. Some of the sample particles show evidence of micrometeoroid impacts, which occurred on the asteroid surface. Among those, particles A0067 and A0094 have flat surfaces on which a large number of microcraters and impact melt splashes are observed. Two impact melt splashes and one microcrater were analyzed to unveil the nature of the objects that impacted the asteroid surface. The melt splashes consist mainly of Mg-Fe-rich glassy silicates and Fe-Ni sulfides. The microcrater trapped an impact melt consisting mainly of Mg-Fe-rich glassy silicate, Fe-Ni sulfides, and minor silica-rich glass. These impact melts show a single compositional trend indicating mixing of Ryugu surface materials and impactors having chondritic chemical compositions. The relict impactor in one of the melt splashes shows mineralogical similarity with anhydrous chondritic interplanetary dust particles having a probable cometary origin. The chondritic micrometeoroids probably impacted the Ryugu surface during its residence in a near-Earth orbit.

14.
Nihon Yakurigaku Zasshi ; 159(1): 31, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38171835
15.
BMC Complement Med Ther ; 24(1): 60, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281005

RESUMO

BACKGROUND: Sensitive gag reflexes prevent dental patients from receiving appropriate treatment. Aromatherapy helps patients relax during dental procedures. However, the effect of aromatherapy on the gag reflex caused by the stimulation of the oral cavity is unknown. This study aimed to evaluate whether aromatherapy reduces gag reflexes during oral stimulation. METHODS: In this randomized, placebo-controlled, single-blind, crossover study, the gag reflexes of 24 healthy individuals (12 females and 12 males; mean age: 34.3 ± 9.5 years) were quantified. A standard saliva ejector was slowly guided down the participant's throat to determine the maximum tolerance of the gag reflex, and the insertion distance was measured to quantify the gag reflex. All individuals participated in an aromatherapy session with peppermint essential oil and a placebo session with distilled water. The gag reflex was quantified before (baseline) and after each session. Another measurement was performed using nitrous oxide/oxygen inhalation as a positive control. RESULTS: Gag reflex values significantly increased after aromatherapy with both peppermint essential oil and placebo compared to baseline values (paired t-test, P < 0.001 and P = 0.014, respectively). The gag reflex value also increased significantly during nitrous oxide/oxygen inhalation (paired t-test, P < 0.001). There was no significant difference in the increase rate of gag reflex values between the positive control and aromatherapy interventions, but it was significantly lower after the placebo intervention (repeated measures analysis of variance, P = 0.003; post-hoc test, P = 0.83 and P = 0.02). CONCLUSION: Aromatherapy with peppermint essential oil has the potential for reducing gag reflex during dental procedures. TRIAL REGISTRATION: The study was registered in the University hospital Medical Information Network Clinical Trials Registry under the code UMIN000050616 (approved 17/03/2023).


Assuntos
Aromaterapia , Óleos Voláteis , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Óleos Voláteis/farmacologia , Aromaterapia/métodos , Estudos Cross-Over , Mentha piperita , Óxido Nitroso , Método Simples-Cego , Engasgo/fisiologia , Engasgo/prevenção & controle , Oxigênio
16.
J Pharmacol Exp Ther ; 389(1): 76-86, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38290974

RESUMO

Mast cell stabilizers, including disodium cromoglycate (DSCG), were found to have potential as the agonists of an orphan G protein-coupled receptor, GPR35, although it remains to be determined whether GPR35 is expressed in mast cells and involved in suppression of mast cell degranulation. Our purpose in this study is to verify the expression of GPR35 in mast cells and to clarify how GPR35 modulates the degranulation. We explored the roles of GPR35 using an expression system, a mast cell line constitutively expressing rat GPR35, peritoneal mast cells, and bone marrow-derived cultured mast cells. Immediate allergic responses were assessed using the IgE-mediated passive cutaneous anaphylaxis (PCA) model. Various known GPR35 agonists, including DSCG and newly designed compounds, suppressed IgE-mediated degranulation. GPR35 was expressed in mature mast cells but not in immature bone marrow-derived cultured mast cells and the rat mast cell line. Degranulation induced by antigens was significantly downmodulated in the mast cell line stably expressing GPR35. A GPR35 agonist, zaprinast, induced a transient activation of RhoA and a transient decrease in the amount of filamentous actin. GPR35 agonists suppressed the PCA responses in the wild-type mice but not in the GPR35-/- mice. These findings suggest that GPR35 should prevent mast cells from undergoing degranulation induced by IgE-mediated antigen stimulation and be the primary target of mast cell stabilizers. SIGNIFICANCE STATEMENT: The agonists of an orphan G protein-coupled receptor, GPR35, including disodium cromoglycate, were found to suppress degranulation of rat and mouse mature mast cells, and their antiallergic effects were abrogated in the GPR35-/- mice, indicating that the primary target of mast cell stabilizers should be GPR35.


Assuntos
Cromolina Sódica , Estabilizadores de Mastócitos , Ratos , Camundongos , Animais , Cromolina Sódica/farmacologia , Estabilizadores de Mastócitos/farmacologia , Mastócitos , Receptores Acoplados a Proteínas G/metabolismo , Imunoglobulina E/metabolismo , Imunoglobulina E/farmacologia , Degranulação Celular
17.
Int J Radiat Biol ; 100(2): 176-182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37755376

RESUMO

PURPOSE: In this paper, we described our mathematical model for radiation-induced life shortening in detail and applied the model to the experimental data on mice to investigate the effect of radiation on cancer-related life-shortening. MATERIALS AND METHODS: Our mathematical model incorporates the following components: (i) occurrence of cancer, (ii) progression of cancer over time, and (iii) death from cancer. We evaluated the progression of cancer over time by analyzing the cancer incidence data and cumulative mortalities data obtained from mice experiments conducted at the Institute for Environmental Sciences (IES). RESULTS: We analyzed non-irradiated control and 20 mGy/day × 400 days irradiated groups. In the analysis, all malignant neoplasms were lumped together and referred to as 'cancer'. Our analysis showed that the reduction in lifespan (104 days in median) was the result of the early onset of cancer (68 days in median) and the shortening of the cancer progression period (48 days in median). CONCLUSIONS: We described in detail our mathematical model for radiation-induced life-shortening attributed to cancer. We analyzed the mice data obtained from the experiment conducted at the IES using our model. We decomposed radiation-induced life-shortening into the early onset of cancer and the shortening of the cancer progression period.


Assuntos
Neoplasias Induzidas por Radiação , Camundongos , Animais , Doses de Radiação , Relação Dose-Resposta à Radiação , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/patologia , Raios gama , Modelos Teóricos
18.
Peptides ; 171: 171118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38012983

RESUMO

Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition characterized by widespread inflammation and pulmonary edema. Adrenomedullin (AM), a bioactive peptide with various functions, is expected to be applied in treating ARDS. Its functions are regulated primarily by two receptor activity-modifying proteins, RAMP2 and RAMP3, which bind to the AM receptor calcitonin receptor-like receptor (CLR). However, the roles of RAMP2 and RAMP3 in ARDS remain unclear. We generated a mouse model of ARDS via intratracheal administration of lipopolysaccharide (LPS), and analyzed the pathophysiological significance of RAMP2 and RAMP3. RAMP2 expression declined with LPS administration, whereas RAMP3 expression increased at low doses and decreased at high doses of LPS. After LPS administration, drug-inducible vascular endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-) showed reduced survival, increased lung weight, and had more apoptotic cells in the lungs. DI-E-RAMP2-/- mice exhibited reduced expression of Epac1 (which regulates vascular endothelial cell barrier function), while RAMP3 was upregulated in compensation. In contrast, after LPS administration, RAMP3-/- mice showed no significant changes in survival, lung weight, or lung pathology, although they exhibited significant downregulation of iNOS, TNF-α, and NLRP3 during the later stages of inflammation. Based on transcriptomic analysis, RAMP2 contributed more to the circulation-regulating effects of AM, whereas RAMP3 contributed more to its inflammation-regulating effects. These findings indicate that, while both RAMP2 and RAMP3 participate in ARDS pathogenesis, their functions differ distinctly. Further elucidation of the pathophysiological significance and functional differences between RAMP2 and RAMP3 is critical for the future therapeutic application of AM in ARDS.


Assuntos
Adrenomedulina , Síndrome do Desconforto Respiratório , Animais , Camundongos , Adrenomedulina/genética , Adrenomedulina/metabolismo , Inflamação , Lipopolissacarídeos , Proteína 2 Modificadora da Atividade de Receptores/genética , Proteína 2 Modificadora da Atividade de Receptores/metabolismo , Proteína 3 Modificadora da Atividade de Receptores/genética , Proteína 3 Modificadora da Atividade de Receptores/metabolismo , Proteínas Modificadoras da Atividade de Receptores/genética , Receptores de Adrenomedulina/genética , Receptores de Adrenomedulina/metabolismo , Síndrome do Desconforto Respiratório/genética
19.
J Youth Adolesc ; 53(5): 1155-1170, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38102531

RESUMO

During emerging adulthood, individuals' subjective well-being declines owing to challenges regarding identity, work, and romantic relationships. Although the relationships among personality traits, self-construal, and well-being have been examined, studies have focused on personal rather than relational subjective well-being. Furthermore, self-construal's moderating effect on the relationship between personality traits and subjective well-being remains unclear. Therefore, this study examined the relationships among the Big-five personality traits and subjective well-being (life satisfaction, happiness, and interdependent happiness) and the moderating effect of self-construal among 1548 Japanese emerging adults (Mage = 22.24, SD = 1.01). Regression analysis indicated that all aspects of subjective well-being were negatively associated with neuroticism and positively associated with extraversion, independent and interdependent self-construal. Further, agreeableness was positively associated with personal and relational well-being. Independent or interdependent self-construal can moderate the relationships between neuroticism, extraversion, and agreeableness and subjective well-being. Overall, these findings provide valuable insights for improving Japanese emerging adults' well-being.


Assuntos
Felicidade , Personalidade , Adulto , Humanos , Adulto Jovem , Neuroticismo , Análise de Regressão
20.
Neurosurgery ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38088551

RESUMO

BACKGROUND AND OBJECTIVES: Postoperative dysphagia is a common complication of anterior cervical diskectomy and fusion (ACDF), although its pathophysiology remains poorly understood. Patients with severe dysphagia may suffer from serious complications such as aspiration pneumonia, in addition to difficulty with oral intake or malnutrition; therefore, a prompt indicator for postoperative management would be helpful. We quantitatively evaluated the retropharyngeal space (RS) after ACDF and investigated its association with postoperative dysphagia. METHODS: This multicenter retrospective study analyzed the clinical data of 82 consecutive patients who underwent ACDF. The anteroposterior distance (APD) of the RS was measured at the C2 level using a lateral radiographic view on postoperative day 1. Postoperative dysphagia was subjectively assessed using the Bazaz-Yoo Dysphagia Severity Scale. We statistically evaluated the association between the APD of the RS and postoperative dysphagia. RESULTS: The mean APD of the RS in all 82 patients was 3.6 mm preoperatively and significantly increased to 8.2 mm postoperatively (P < .0001). Twenty-two patients (26.8%) had postoperative dysphagia. Multivariable analysis revealed that the postoperative APD was associated with postoperative dysphagia (odds ratio 1.27, 95% CI 1.10-1.50, P = .0007). The receiver operating characteristic curve (area under the curve 0.70, 95% CI 0.58-0.83) demonstrated that the postoperative APD of the RS cutoff value was 6.1 mm, with a sensitivity of 100% and a specificity of 35%. With this cutoff value, the positive and negative predictive values for postoperative dysphagia were 36% and 100%, respectively. CONCLUSION: Our data demonstrate that a value of 6.1 mm for the APD of the RS is an effective indicator for dysphagia after ACDF, which contributes to optimizing the patient management in the acute postoperative period.

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