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The increased risk for post-COVID-19 condition after the Omicron-dominant wave remains unclear. This population-based study included 25,911 persons in Japan 20-69 years of age with confirmed SARS-CoV-2 infection enrolled in the established registry system during July-August 2022 and 25,911 age- and sex-matched noninfected controls who used a self-reported questionnaire in January-February 2023. We compared prevalence and age- and sex-adjusted odds ratios of persistent COVID-19 symptoms (lasting ≥2 months). We evaluated factors associated with post-COVID-19 condition by comparing cases with and without post-COVID-19 condition. We analyzed 14,710 (8,392 cases and 6,318 controls) of 18,183 respondents. Post-COVID-19 condition proportion among cases was 11.8%, higher by 6.3% than 5.5% persistent symptoms among controls. Female sex, underlying medical conditions, mild to moderate acute COVID-19, and vaccination were associated with post-COVID-19 condition. Approximately 12% had post-COVID-19 condition during the Omicron-dominant wave, indicating the need for longer follow-up.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Persona de Mediana Edad , Femenino , Masculino , Japón/epidemiología , Adulto , Factores de Riesgo , Anciano , Prevalencia , Adulto Joven , Síndrome Post Agudo de COVID-19 , Estudios de Casos y ControlesRESUMEN
BackgroundDisasters such as earthquakes, terrorism, and pandemics have triggered post-traumatic stress disorder (PTSD), and discrimination against the affected individuals has been linked to the development of PTSD. However, there is limited evidence regarding the association between discrimination against coronavirus disease 2019 (COVID-19) patients and probable PTSD in Japan.MethodsWe conducted a cross-sectional study utilizing a web-based questionnaire targeting individuals who had contracted the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sapporo City. A total of 4247 individuals with laboratory-confirmed SARS-CoV-2 infection spanning from February 2020 to February 2022 completed the questionnaire (response rate: 15.9%). Probable PTSD was measured using the three-item Posttraumatic Diagnostic Scale. The stratified exact logistic regression was applied to calculate the odds ratios (OR) of probable PTSD for COVID-19-related discrimination with adjusted factors.ResultsThis study included 3626 patients who had a history of SARS-CoV-2 infection. Among them, 321 patients (8.9%) experienced COVID-19-related discrimination. The prevalence of probable PTSD was 19.6% (63/321) among the patients who experienced COVID-19-related discrimination, and 4.6% (152/3305) among those who had not encountered such discrimination. The adjusted OR of COVID-19-related discrimination for probable PTSD was 4.68 (95% confidence interval [95% CI], 3.36-6.53). The population attributable fraction of probable PTSD attributable to COVID-19-related discrimination among COVID-19 patients was estimated to be 23.4% (95% CI, 21.5-25.3).ConclusionThe comprehensive epidemiological survey of COVID-19 patients in Japan showed that COVID-19-related discrimination was associated with a higher prevalence of probable PTSD. Mitigating discrimination could be helpful to attenuate PTSD in future pandemics.
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OBJECTIVES: To examine prevalence and risk factors for post-COVID-19 condition (PCC) in a paediatric population. METHODS: The study included patients aged 5-17 years with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection between 1 March 2021 and 30 April 2022 and matched non-infected controls from Yao City, Japan. We compared parent-reported symptoms persisting ≥2 months (present at 3 months post-infection for patients) between the groups. COVID-19 vaccination data was obtained from the Vaccination Registry. RESULTS: Among 8167 invited individuals, 3141 (1800 cases, mean age: 10.4 years, 46.1% females; 1341 controls, mean age 10.5 years, 47.1% females) participated. Patients had elapsed average 273 (185-605) days from infection, and 1708 (94.9%) experienced mild acute symptoms. Patients had higher odds of having persistent symptoms than did controls (6.3% vs 2.2%, adjusted odds ratio [aOR]: 3.15, 95% confidence interval: 2.08-4.77), with 53.6% of them reporting current disruption due to the symptoms. Older age, low household income, pre-existing allergy, and autonomic nervous system disease were associated with increased risks of developing PCC; two prior vaccination doses reduced these risks (aOR: 0.53, 0.29-0.96). CONCLUSION: SARS-CoV-2 infection, including omicron infections heighten persistent symptom risk in the paediatric population, necessitating preventive strategies, notably vaccination.
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COVID-19 , SARS-CoV-2 , Humanos , Femenino , Niño , Masculino , COVID-19/epidemiología , Estudios de Casos y Controles , Factores de Riesgo , Adolescente , Japón/epidemiología , Prevalencia , Preescolar , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Síndrome Post Agudo de COVID-19RESUMEN
Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 +polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.
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We conducted a cross-sectional survey among SARS-CoV-2-positive persons and negative controls in Sapporo, Japan, to clarify symptoms of long COVID. We collected responses from 8,018 participants, 3,694 case-patients and 3,672 controls. We calculated symptom prevalence for case-patients at 2-3, 4-6, 7-9, 10-12, and 13-18 months after illness onset. We used logistic regression, adjusted for age and sex, to estimate the odds ratio (OR) for each symptom and control reference. We calculated symptom prevalence by stratifying for disease severity, age, and sex. At 4-18 months from illness onset, ORs for anosmia, ageusia, dyspnea, alopecia, and brain fog were consistently >1, whereas ORs for common cold-like, gastrointestinal, and dermatologic symptoms were <1. Time trend ORs increased for diminished ability to concentrate, brain fog, sleep disturbance, eye symptoms, and tinnitus. Clinicians should focus on systemic, respiratory, and neuropsychiatric symptoms among long COVID patients.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Estudios de Casos y Controles , Japón/epidemiología , Estudios TransversalesRESUMEN
ABSTRACT: Shimozawa, Y, Kurihara, T, Kusagawa, Y, Hori, M, Numasawa, S, Sugiyama, T, Tanaka, T, Suga, T, Terada, RS, Isaka, T, and Terada, M. Point prevalence of the biomechanical dimension of dysfunctional breathing patterns among competitive athletes. J Strength Cond Res 37(2): 270-276, 2023-There is growing evidence of associations between altered biomechanical breathing patterns and numerous musculoskeletal and psychological conditions. The prevalence of dysfunctional and diaphragmatic breathing patterns is unknown among athletic populations. The purpose of this study was to examine the prevalence of dysfunctional and diaphragmatic breathing patterns among athletic populations with a clinical measure to assess the biomechanical dimension of breathing patterns. Using a cross-sectional design, 1,933 athletes across multiple sports and ages were screened from 2017 to 2020. Breathing patterns were assessed using the Hi-Lo test in the standing position. Scores of the Hi-Lo test were determined based on the presence or absence of abdominal excursion, anterior-posterior chest expansion, superior rib cage migration, and shoulder elevation. The Hi-Lo test scores were used to categorize observational breathing mechanics as dysfunctional and diaphragmatic breathing patterns. The prevalence of athletes with dysfunctional breathing patterns was 90.6% (1,751 of 1,933). Athletes with diaphragmatic breathing patterns accounted for 9.4% of all athletes in our sample (182 of 1,933). There were no differences in the proportion of breathing patterns between male and female athletes ( p = 0.424). Breathing patterns observations were associated with sport-setting categories ( p = 0.002). The highest percentages of dysfunctional breathers were in middle school student athletes (93.7%), followed by elementary school student athletes (91.2%), high school student athletes (90.6%), professional/semiprofessional athletes (87.5%), and collegiate athletes (84.8%). The current study observed that dysfunctional breathing patterns (90.6%) in the biomechanical dimension were more prevalent than diaphragmatic breathing pattern (9.4%) among competitive athletes. These results suggest that clinicians may need to consider screening breathing patterns and implementing intervention programs aimed to improve the efficiency of biomechanical dimensions of breathing patterns in athletic populations. This study may help raise awareness of impacts of dysfunctional breathing patterns on athletes' health and performance.
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Traumatismos en Atletas , Deportes , Humanos , Masculino , Femenino , Niño , Prevalencia , Estudios Transversales , Atletas , Respiración , Traumatismos en Atletas/epidemiologíaRESUMEN
BACKGROUND: Cigarette smoke contains many oxidants and free radicals which may affect the association between vegetable and fruit intake and colorectal cancer (CRC) risk. However, this relationship remains unclear. OBJECTIVE: This study aimed to investigate the associations between vegetable and fruit intake and CRC risk by smoking status. METHODS: The Japan Public Health Center-based Prospective Study is a population-based prospective cohort study. Participants completed a self-administered questionnaire in 1995-1999 (baseline survey) and were followed through to 2013. At the baseline survey, 89,283 residents (41,797 men and 47,486 women) aged 45-74 years were included. Participants were asked about their lifestyle and dietary habits. To investigate the association of vegetable and fruit intake with risk of CRC, Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We analyzed the relationship between vegetable and fruit intake and CRC risk stratified by sex and smoking status. RESULTS: During follow-up, 2261 participants were diagnosed with CRC. Overall, vegetable and fruit intake were not associated with CRC risk in either sex. When stratified by sex and smoking status, CRC risk among male never smokers was inversely associated with intake of vegetables and fruit combined (HR: 0.72; 95% CI: 0.53, 0.98; highest vs lowest quartile p trend = 0.01) and fruit alone (HR: 0.62; 95% CI: 0.45, 0.86; p trend < 0.01). CONCLUSIONS: Cigarette smoking may affect the association between vegetable and fruit intake and CRC risk among men.
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Neoplasias Colorrectales , Verduras , Adulto , Humanos , Masculino , Femenino , Estudios Prospectivos , Frutas , Japón/epidemiología , Salud Pública , Modelos de Riesgos Proporcionales , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Fumar/efectos adversos , Fumar/epidemiología , Factores de RiesgoRESUMEN
Introduction: This present study aimed to compare ultrasonographic measures of femoral articular cartilage during two-year seasons between collegiate rugby players who have attended supervised rehabilitation following intracapsular knee joint injury and those without a history of knee injury. Methods: Using a prospective observational study design, 12 male collegiate rugby players with a previous history of intracapsular knee joint injury who have received and completed supervised rehabilitation following their injury and 44 players without knee joint injury participated in this study. Ultrasonographic images were used to verify changes in femoral articular cartilage thickness and cross-sectional area (CSA) with or without a previous history of knee joint injury over two consecutive rugby seasons. Results: Significant time main effects were observed for the lateral condylar thickness (p < 0.001), the intercondylar thickness (p = 0.001), the medial condylar thickness (p < 0.001), and CSA (p < 0.001). No significant interactions nor group main effects were identified for all femoral articular cartilage (p < 0.05). Conclusions: Collegiate rugby players demonstrated a decrease in femoral articular cartilage thickness and CSA over two-year consecutive rugby seasons. These findings indicate that engaging in collegiate rugby induces alterations in femoral articular cartilage structure. Furthermore, there were no differences in all femoral cartilage outcome measures between rugby players with and without a previous history of traumatic knee joint injury. Therefore, attending supervised rehabilitation at the time of their knee joint injury appeared to reduce the impact of a previous history of intracapsular knee joint injury on the change in femoral articular cartilage thickness and CSA among active rugby players.
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Although the introduction of tumor necrosis factor (TNF) inhibitors represented a significant advance in the treatment of rheumatoid arthritis (RA), traditional anti-TNFα antibodies are somewhat immunogenic, and their use results in the formation of anti-drug antibodies (ADAs) and loss of efficacy (secondary failure). Ozoralizumab is a trivalent, bispecific NANOBODY® compound that differs structurally from IgGs. In this study we investigated the suppressant effect of ozoralizumab and adalimumab, an anti-TNFα IgG, on arthritis and induction of ADAs in human TNF transgenic mice. Ozoralizumab markedly suppressed arthritis progression and did not induce ADAs during long-term administration. We also developed an animal model of secondary failure by repeatedly administering adalimumab and found that switching from adalimumab to ozoralizumab was followed by superior anti-arthritis efficacy in the secondary-failure animal model. Moreover, ozoralizumab did not form large immune complexes that might lead to ADA formation. The results of our studies suggest that ozoralizumab, which exhibited low immunogenicity in the animal model used and has a different antibody structure from that of IgGs, is a promising candidate for the treatment of RA patients not only at the onset of RA but also during secondary failure of anti-TNFα treatment.
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Anticuerpos Monoclonales Humanizados , Artritis Reumatoide , Adalimumab/farmacología , Adalimumab/uso terapéutico , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Humanos , Inmunoglobulina G , Ratones , Ratones Transgénicos , Inhibidores del Factor de Necrosis TumoralRESUMEN
This study aimed to examine anterior femoral cartilage morphology before (pre-season) and after (post-season) a 5-month competitive season in collegiate ruby players with and without a previous history of traumatic injury to ligamentous, meniscus, and/or cartilage structures at the knee joint. Using a prospective cohort design, 42 male collegiate rugby players with a previous history of traumatic intracapsular knee joint injury and 124 players without knee injury history were included in this study. Ultrasonography assessments of anterior femoral cartilage were performed before (pre-season) and following a 5-month athletic season (post-season). Rugby players with a history of traumatic knee joint injury had greater lateral condylar thickness (2.37 ± 0.35 mm, p = 0.03), intercondylar thickness (2.51 ± 0.47 mm, p = 0.03), and partial area (44.67 ± 7.28mm2, p = 0.02) compared to control players (lateral = 2.23 ± 0.35 mm, intercondylar = 2.32 ± 0.47 mm, partial area = 41.60 ± 7.26 mm2), regardless of pre-and post-season assessment time points. Pre-season ultrasonography assessment of lateral condylar thickness (2.34 ± 0.47 mm, p = 0.02), medial condylar thickness (2.05 ± 0.43 mm, p = 0.03), and partial area (44.10 ± 9.23 mm2, p = 0.001) were significantly greater than the post-season ultrasonography assessment time point (lateral = 2.26 ± 0.43 mm, medial = 1.98 ± 0.43 mm, partial area = 42.17 ± 8.82 mm2), regardless of group membership. Rugby players with a history of intracapsular knee joint injury displayed altered anterior femoral cartilage size via ultrasonography assessments. Regardless of a presence of injury history, collegiate rugby players showed a decrease in cartilage thickness and partial area following a 5-month competitive season.
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Traumatismos en Atletas/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Fútbol Americano/lesiones , Fútbol Americano/fisiología , Traumatismos de la Rodilla/diagnóstico por imagen , Adolescente , Traumatismos en Atletas/complicaciones , Traumatismos en Atletas/patología , Cartílago Articular/patología , Estudios de Casos y Controles , Fémur , Humanos , Traumatismos de la Rodilla/complicaciones , Traumatismos de la Rodilla/patología , Masculino , Osteoartritis de la Rodilla/etiología , Estudios Prospectivos , Factores de Riesgo , Estaciones del Año , Factores de Tiempo , Ultrasonografía , Adulto JovenRESUMEN
PURPOSE: This study examined the relationships of knee extensor strength and quadriceps femoris size with sprint performance in sprinters. METHODS: Fifty-eight male sprinters and 40 body size-matched male non-sprinters participated in this study. The knee extensor isometric and isokinetic strengths were measured using a dynamometer. The isokinetic strength measurements were performed with slow and fast velocities at 60°/s and 180°/s, respectively. The quadriceps femoris muscle volume (MV) was measured using magnetic resonance imaging. The relative knee extensor strengths and quadriceps femoris MV were calculated by normalizing to body mass. RESULTS: Absolute and relative knee extensor strengths during two velocity isokinetic contractions, but not during isometric contraction, were significantly higher in sprinters than in non-sprinters (P = 0.047 to < 0.001 for all). Such a significant difference was also observed for relative quadriceps femoris MV (P = 0.018). In sprinters, there were positive correlations between all three knee extensor strengths and quadriceps femoris MV (r = 0.421 to 0.531, P = 0.001 to < 0.001 for all). The absolute and relative strengths of the fast-velocity isokinetic knee extension correlated negatively with personal best 100-m sprint time (r = -0.477 and -0.409, P = 0.001 and < 0.001, respectively). In contrast, no such significant correlations were observed between absolute and relative quadriceps femoris MVs and personal best 100-m sprint time. CONCLUSIONS: These findings suggest that despite the presence of the relationship between muscle strength and size, the knee extensor strength may be related to superior sprint performance in sprinters independently of the quadriceps femoris muscularity.
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Prior studies reported the association of reproductive factors with breast cancer (BC), but the evidence is inconsistent. We conducted a pooled analysis of nine cohort studies in Japan to evaluate the impact of six reproductive factors (age at menarche/age at first birth/number of births/age at menopause/use of female hormones/breastfeeding) on BC incidence. We conducted analyses according to menopausal status at the baseline or at the diagnosis. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by applying Cox proportional-hazards model in each study. These hazard ratios were integrated using a random-effects model. Among 187,999 women (premenopausal: 61,113, postmenopausal: 126,886), we observed 873 premenopausal and 1,456 postmenopausal cases. Among premenopausal women, use of female hormones significantly increased BC incidence (HR: 1.53 [1.04-2.25]). Although P value for trend was not significant for age at first birth and number of births (P for trend: 0.15 and 0.30, respectively), women giving first birth at ages ≥36 experienced significantly higher BC incidence than at ages 21-25 years, and women who had ≥2 births experienced significantly lower BC incidence than nulliparous women. Among postmenopausal women, more births significantly decreased BC incidence (P for trend: 0.03). Although P value for trend was not significant for age at first birth and age at menopause (P for trend: 0.30 and 0.37, respectively), women giving first birth at ages 26-35 years experienced significantly higher BC incidence than at ages 21-25 years, and women with age at menopause: ≥50 years experienced significantly higher BC incidence than age at menopause: ≤44 years. BC incidence was similar according to age at menarche or breastfeeding history among both premenopausal and postmenopausal women. In conclusion, among Japanese women, use of female hormones increased BC incidence in premenopausal women, and more births decreased BC incidence in postmenopausal women.
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Neoplasias de la Mama/epidemiología , Historia Reproductiva , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Lactancia Materna , Niño , Estudios de Cohortes , Intervalos de Confianza , Estrógenos/administración & dosificación , Femenino , Humanos , Incidencia , Japón/epidemiología , Edad Materna , Menarquia , Menopausia , Persona de Mediana Edad , Paridad , Posmenopausia , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
BACKGROUND: The frequency of laughter has been associated with cardiovascular disease and related biomarkers, but no previous studies have examined association between laughter and changes in blood pressure levels. We sought to identify temporal relationships between frequency of laughter in daily life and systolic and diastolic blood pressure changes in participants from 2010 through 2014. METHODS: Participants were 554 men and 887 women aged 40-74 years who answered self-administered questionnaire quantifying frequency of laughter at baseline. We measured participant blood pressure levels twice using automated sphygmomanometers for each year from 2010 to 2014. The associations between laughter and changes in blood pressure over time were analyzed using linear mixed-effect models. RESULTS: There was no significant difference in blood pressure according to frequency of laughter at baseline in either sex. Men with frequency of laughter 1 to 3 per month or almost never had significantly increased systolic and diastolic blood pressure levels over the 4-year period (time-dependent difference: 0.96 mm Hg (95% confidence interval [CI], -0.2 to 1.8; P = 0.05). Changes in blood pressure associated with infrequent laughter (ie, 1 to 3 per month or almost never) were evident in men without antihypertensive medication use over 4 years (0.94 mm Hg; 95% CI, -0.2 to 2.0; P = 0.09) and men who were current drinkers at baseline (1.29 mm Hg; 95% CI, -0.1 to 2.3; P = 0.04). No significant difference was found between frequency of laughter and systolic (0.23 mm Hg; 95% CI, -1.0 to 1.5; P = 0.72) and diastolic (-0.07 mm Hg; 95% CI, -0.8 to 0.7; P = 0.86) blood pressure changes in women. CONCLUSIONS: Infrequent laughter was associated with long-term blood pressure increment among middle-aged men.
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Presión Sanguínea/fisiología , Risa/fisiología , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Femenino , Humanos , Japón/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
The joint moment arm (MA) dimension is related to joint torque in adults. However, this relationship remains unexplored in children. In this study, we aimed to determine the relationship between MA and joint torque of the knee extensors in this young population. The quadriceps femoris muscle volume (MV) and knee extensor MA in 20 preadolescent boys (age: 10.7 ± 0.9 years) were measured using magnetic resonance imaging. The knee extensor isometric and isokinetic torques were measured using a dynamometer. The isokinetic torque measurements were performed using slow and fast angular velocities at 60°/s and 180°/s respectively. The knee extensor torque-producing capacities were assessed as the knee extensor isometric or isokinetic torque per the quadriceps femoris MV. The quadriceps femoris MV correlated significantly with all three knee extensor isometric and isokinetic torques (r = 0.513-0.804, p < .05 for all). The knee extensor MA also correlated significantly with the three knee extensor isometric and isokinetic torques (r = 0.701-0.806, p ≤ .001 for all). Furthermore, the knee extensor MA correlated significantly with all three knee extensor torque-producing capacities (r = 0.488-0.701, p < .05 for all). These findings suggest that in addition to adults, greater MA plays an important role in achieving higher joint torque production of the knee extensors in preadolescent boys. This study is the first to determine the impact of MA dimension on joint torque production in children.
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Brazo/fisiología , Rodilla/fisiología , Movimiento , Músculo Esquelético/fisiología , Niño , Humanos , Imagen por Resonancia Magnética , Masculino , Contracción Muscular , Músculo Esquelético/diagnóstico por imagen , TorqueRESUMEN
OBJECTIVE: The torque-producing capacity can be assessed as maximal isometric torque per muscle size. Nevertheless, the factors contributing to this capacity remain poorly understood. In general, the magnitude of joint torque production is determined not only by muscle size but also by joint moment arm (MA). Based on this background, we hypothesized that longer MA would be related to higher torque-producing capacity despite a given muscle size. To test this hypothesis, we examined the relationship between MA and toque-producing capacity in the knee extensors. The quadriceps femoris muscle volume (MV) and knee extensor MA in 30 healthy young men were measured using magnetic resonance imaging. The knee extensor isometric torque was measured using a dynamometer. The knee extensor torque-producing capacity was calculated as the knee extensor isometric torque per quadriceps femoris MV. RESULTS: The quadriceps femoris MV and knee extensor MA correlated significantly with the knee extensor isometric torque (r = 0.785 and 0.790, respectively, both Ps < 0.001). Furthermore, the knee extensor MA correlated significantly with the knee extensor torque-producing capacity (r = 0.635, P < 0.001). These findings suggest that longer MA is an important factor for achieving higher torque-producing capacity in the human knee extensors.
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Brazo , Rodilla , Humanos , Contracción Isométrica , Rodilla/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Masculino , Músculo Esquelético , Músculo Cuádriceps/diagnóstico por imagen , TorqueRESUMEN
OBJECTIVES: We developed S (+)-flurbiprofen plaster (SFPP), a novel NSAID patch containing S (+)-flurbiprofen (SFP), a potent cyclooxygenase (COX) inhibitor. The purpose of this study was to assess efficacy of SFPP by analysing its effect on the gait disturbance and measuring the prostaglandin E2 (PGE2 ) production in synovial fluid in a rat model of knee arthritis. METHODS: Knee inflammation was induced in rats by intra-articular injection of a yeast suspension. Subsequently, an NSAID patch containing SFP, ketoprofen or loxoprofen was applied over the affected knee. Gait was assessed at 2, 4 and 6 h after application of the patch. The PGE2 concentration in the synovial fluid was measured after the gait assessment. KEY FINDINGS: Application of SFPP (0.125, 0.25, 0.5 or 1 mg/sheet) was followed by a decrease in the visual gait score at all the doses examined. In the case of the other two NSAID patches, only the ketoprofen patch (1 or 2 mg/sheet) and loxoprofen patch (5 mg/sheet) produced a decrease in the visual gait score. All of the NSAID patches decreased the PGE2 production in the synovial fluid. CONCLUSIONS: These results suggest the potential usefulness of SFPP as an analgesic patch in patients with inflammatory joint pain.
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Analgésicos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Dinoprostona/metabolismo , Flurbiprofeno/uso terapéutico , Marcha/efectos de los fármacos , Líquido Sinovial/efectos de los fármacos , Líquido Sinovial/metabolismo , Animales , Artritis Experimental/inducido químicamente , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Cetoprofeno/uso terapéutico , Masculino , Fenilpropionatos/uso terapéutico , Ratas , Parche TransdérmicoRESUMEN
AIM: Data for long-term trends in blood pressures, body mass index (BMI), and their relations are needed to set future intervention priorities for prevention of cardiovascular disease. The objective of this study was to investigate these trends revealed by repeated cross-sectional surveys conducted from 1963 to 2013 in a Japanese community. METHODS: Men and women aged 40-79 years who participated in annual cardiovascular checkups were enrolled, and the number of participants ranged between 1,776 and 2,366 with consistently high participation rates for both sexes aged 60-69 years. Sex- and age-specific mean systolic and diastolic blood pressures were calculated using mixed effects modeling for repeated measurement, and the prevalence of hypertension with and without obesity (BMI ≥ 25 kg/m2) were also calculated. RESULTS: Sex- and age-specific mean systolic and diastolic blood pressures declined irrespective of antihypertensive medication use in both men and women from 1963-1966 to 2009-2013, while mean BMI increased among men of all ages and women of ages 60-69 and 70-79 years. For both sexes aged 60-69 years, the prevalence of hypertension with obesity increased, but the prevalence of hypertension without obesity was still higher that with obesity. CONCLUSIONS: Despite the transition to increased BMI levels, targeting non to obese hypertension remains important in addition to targeting obese hypertension for cardiovascular disease prevention.
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Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/etiología , Hipertensión/complicaciones , Obesidad/complicaciones , Adulto , Factores de Edad , Anciano , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Salud PúblicaRESUMEN
Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.
Asunto(s)
Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/tratamiento farmacológico , Flurbiprofeno/farmacología , Administración Cutánea , Analgésicos/administración & dosificación , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Experimental/patología , Ciclooxigenasa 1/efectos de los fármacos , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/farmacología , Edema/tratamiento farmacológico , Flurbiprofeno/administración & dosificación , Humanos , Masculino , Mycobacterium , Dolor/tratamiento farmacológico , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes , Parche TransdérmicoRESUMEN
Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50 = 8.97 nM) and COX-2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically.