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1.
Environ Res ; 243: 117744, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38092240

RESUMEN

Microbial fuel cells (MFCs) hold considerable promise for harnessing the substantial energy resources present in wastewater. However, their practical application in wastewater treatment is limited by inadequate removal of organic matter and inefficient power recovery. Previous studies have investigated aeration as a method to enhance the removal of organic matter, but this method is energy-intensive. To address this issue, this study proposed using MFC-recovered bioelectricity for aeration, thereby mitigating the associated expenses. An air-cathode MFC with multi-anode was constructed and optimized to maximize electricity supply for aeration. Carbon-felt anodes were chosen as the most effective anode configuration, due to the high abundance of electroactive bacteria and genes observed in the biofilm generated on their surface. By incorporating six carbon felt anodes, the MFC achieved a 1.7 and 1.1 fold enhancement in the maximum power and current density, respectively. The optimized MFC unit achieved a stable current density of 0.32 A/m2 and achieved COD removal of 60% in the long-term operation of 140 days in a 50 L reactor. In a reactor scaled up to 1600 L, 72 MFCs successfully powered a mini air pump work for 10 s after an 81-s charging period. The intermittent aeration resulted in partial increases in DO concentrations to 0.03-3.5 mg/L, which is expected to promote the removal of nitrogen compounds by the nitrification-anammox process. These groundbreaking results lay the foundation for self-sustaining wastewater treatment technologies.


Asunto(s)
Fuentes de Energía Bioeléctrica , Purificación del Agua , Aguas Residuales , Electricidad , Carbono , Electrodos
2.
Kyobu Geka ; 77(7): 521-525, 2024 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-39009550

RESUMEN

The remodeling of sinus of Valsalva( Yacoub operation) is being standardized by adding annular fixation and technique for cusp prolapse as a refined method of valve sparing aortic root repair. It is important to design whole configurations of Valsalva sinus( diameters of aortic annulus and sino-tubular junction) according to the patient's geometric height (geometric height-oriented strategy). In this paper, we summarized our tips of remodeling of sinus of Valsalva operation.


Asunto(s)
Seno Aórtico , Humanos , Seno Aórtico/cirugía , Válvula Aórtica/cirugía
3.
Eur J Pediatr ; 181(3): 1055-1061, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34716798

RESUMEN

The study on robot-assisted therapy in a pediatric field has not been applied sufficiently in clinical settings. The purpose of this pilot study is to explore the potential therapeutic effects of a group robot intervention (GRI), using dog-like social robot (SR) 'aibo' in pediatric ward. GRI by aibo was conducted for those children with chronic illness (127 in total) who are hospitalized in National Centre for Child Health and Development (NCCHD), and their caregivers (116 in total), from March to April 2018. The observer made structured behavioural observation records, based on which qualitative research on the features of their words and conducts, were carried out. As a result, first, during the GRI, about 2/3 of total expression by children were positive, while about 1/4 were negative or inappropriate. On the other hand, as seen in the 'change' group, those children who had originally responded with negative expression eventually came to express positive expression, while getting involved in a ternary relationship or participating in a session more than once. Secondly, as for the expression from the caregivers during the GRI, active expressions such as 'participation' and 'exploration' accounted for the 2/3, while 1/3 turned out to be rather placid expressions such as 'watch over' or 'encourage.'Conclusion: There has not been any precedent study on the features of words and conducts expressed by patients and their caregivers during the GRI by aibo. The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting. What is Known: • The study on robot-assisted therapy in a pediatric field has only just begun. • Though many kinds of social robot have been reportedly used so far, none has yet to be applied in clinical settings What is New: • Our study revealed the features of words and behaviour expressed by the patients and their caregivers, when dog-like social robot 'aibo' was used for a group robot intervention in the pediatric ward. • The outcome suggests that aibo could possibly be used as a tool for group robot-assisted therapy in the pediatric treatment setting.


Asunto(s)
Cuidadores , Robótica , Animales , Niño , Perros , Humanos , Pacientes Internos , Proyectos Piloto , Interacción Social
4.
Pediatr Int ; 64(1): e14981, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34480819

RESUMEN

BACKGROUND: The coronavirus disease 2019 pandemic has changed people's lives dramatically. Few data on the acute effects of the pandemic on children's daily lives and well-being have been published to date. This study aimed to capture its effects on Japanese children during the first peak of the outbreak. METHODS: We conducted a web-based, anonymous cross-sectional survey targeting Japanese children aged 7-17 years and parents/guardians of children aged 0-17 years. Eligible individuals were invited to participate in the survey from April 30 to May 31, 2020. This self-report questionnaire examined daily life and behaviors, psychological symptoms, well-being, quality of life, and positive parenting or abusive behaviors at the very beginning of the outbreak. RESULTS: A total of 2,591 children and 6,116 parents/guardians participated in our survey. Sixty-two percent of children reported screen time exceeding 2 h. Twenty percent of children reported abusive behaviors by family members. Nine in ten parents/guardians of school-aged children reported that their child had at least one acute stress symptom in the past month. Average mental health subscale scores from KINDLR questionnaire on quality of life were lower than the national average for all grades. Nearly half of parents/guardians refrained from seeking medical care for the child's symptoms. CONCLUSIONS: The COVID-19 pandemic had serious acute impacts on Japanese children's daily lives, well-being, family relationships, and health-care utilization, including some impacts that are potentially long-lasting; thus, proactive interventions and services are needed, as well as longitudinal surveys.


Asunto(s)
COVID-19 , Calidad de Vida , Niño , Humanos , Pandemias , Estudios Transversales , COVID-19/epidemiología , Encuestas y Cuestionarios , Responsabilidad Parental , Padres/psicología
5.
Psychiatry Clin Neurosci ; 75(12): 394-400, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34549856

RESUMEN

AIM: Children with special health care needs (CSHCN) are those who require more care for their physical, developmental, or emotional differences than their typically developing peers. Among a wide range of burdens that caregivers of CSHCN experience, the mental burden of caregivers is still not well investigated. This study aimed at examining the relationship between caring for CSHCN and mothers' anxiety/depression. METHODS: This study used data from the Tokyo Early Adolescence Survey, a population-based cross-sectional survey. Using screening questionnaires, we evaluated the prevalence of CSHCN and identified their primary caregivers. Focusing on mothers as caregivers, we analyzed the relationship between having CSHCN and mothers' anxiety/depression, and between the severity of children's condition and mothers' anxiety/depression. We further determined what mediates these relationships using path analyses. RESULTS: Among 4003 participants, we identified 502 CSHCN (12.5%), and 93% of responding caregivers were mothers. We found that mothers with CSHCN were significantly more anxious/depressed than those without CSHCN, which was closely related to the severity of children's condition. The mediation effect of social support on the relation between CSHCN and mothers' anxiety/depression was statistically significant. CONCLUSION: Mothers of CSHCN were more anxious/depressed than other mothers in this study. Social support was indicated to have a significant mediating effect on the relationship between CSHCN and mothers' anxiety/depression. Our results suggest that considering ways to offer social support may effectively relieve the mental stress experienced by mothers of CSHCN.


Asunto(s)
Ansiedad , Depresión , Niños con Discapacidad , Madres/psicología , Adolescente , Adulto , Ansiedad/epidemiología , Niño , Estudios de Cohortes , Estudios Transversales , Depresión/epidemiología , Niños con Discapacidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Madres/estadística & datos numéricos , Tokio/epidemiología
6.
BMC Pediatr ; 20(1): 467, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33023527

RESUMEN

BACKGROUND: Suicide is the leading cause of death among Japanese adolescents. However, knowledge gaps regarding contemporary demographics and factors associated with suicidality among Japanese adolescents are a major concern. This study examined the prevalence of suicidality among Japanese adolescents and investigated associated factors. METHODS: A population-based questionnaire survey investigating general health was administered to 22,419 adolescents aged 13-18 years. The 29-item questionnaire covered emotional status, family function, cyberbullying, suicidality, and stressors (e.g., relationships with parents/friends, school performance, and sexual identity). We conducted multiple logistic regression analysis to identify factors associated with suicidality in this population. RESULTS: The prevalence of suicidal ideation was 21.6% in males and 28.5% in females, and that of attempted suicide was 3.5% in males and 6.6% and in females. Bullying and stress related to family relationships had the strongest associations with suicidality. Exposure to cyberbullying had the highest odds ratio for both junior high (3.1, 95% confidence interval [CI] 2.1-4.4) and high school students (3.6, 95% CI 2.5-5.3). Other factors significantly associated with suicidality were sex, emotional status, and stress about relationships with friends, sexual identity, school records, and academic course. Adolescents accessed a variety of resources to cope with stressors, with the Internet being the most common resource consulted. CONCLUSIONS: Suicidality is commonly experienced among Japanese adolescents. Although there are many associated risk factors, cyberbullying is of particular concern. Recognition of factors associated with adolescent suicidality will inform further research and suicide prevention efforts for healthcare providers and families.


Asunto(s)
Suicidio , Adolescente , Femenino , Humanos , Japón/epidemiología , Masculino , Prevalencia , Factores de Riesgo , Ideación Suicida , Encuestas y Cuestionarios
7.
BMC Musculoskelet Disord ; 21(1): 44, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959156

RESUMEN

BACKGROUND: Peripheral nerve injury causes limb muscle/bone atrophy, leading to chronic pain. However, the mechanisms underlying muscle/bone atrophy after peripheral nerve injury remain unknown. It was recently reported that M1 macrophages are the main factors responsible for neurogenic inflammation after peripheral nerve injury. We hypothesized that M1 macrophages are important in muscle/bone atrophy after nerve injury. Therefore, we investigated the influence of M1 macrophages on muscle/bone atrophy after nerve injury in mice to prevent muscle/bone atrophy by suppressing M1 macrophages. METHODS: Hindlimb muscle weight and total bone density were measured in a chronic constriction injury (CCI) mouse model. Immunohistochemical analysis and intravital microscopy were performed to visualize hindlimb muscles/bones, and cells were quantified using flow cytometry. We compared M1 macrophage infiltration into muscles/bones and muscle/bone atrophy between macrophage depletion and untreated groups. We also investigated muscle/bone atrophy using administration models for anti-inflammatory and neuropathic pain drugs. RESULTS: Peripheral nerve injury caused significant reduction in muscle weight and total bone density at 1 and 3 weeks after CCI, respectively, compared with that in controls. Osteoclast numbers were significantly higher at 1 week after CCI in the CCI group than in the control group. M1 macrophage infiltration into muscles was observed from 2 h after CCI via intravital microscopy and 1 week after CCI, and it was significantly higher 1 week after CCI than in the control group. In the macrophage depletion group, dexamethasone, pregabalin, and loxoprofen groups, M1 macrophage infiltration into muscles/bones was significantly lower and muscle weight and total bone density were significantly higher than in the untreated group. CONCLUSIONS: M1 macrophage infiltration exacerbates muscle/bone atrophy after peripheral nerve injury. By suppressing M1 macrophages at the neural injury local site, muscle/bone atrophy could be avoided.


Asunto(s)
Macrófagos/patología , Atrofia Muscular/etiología , Atrofia Muscular/patología , Traumatismos de los Nervios Periféricos/complicaciones , Traumatismos de los Nervios Periféricos/patología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
8.
J Oncol Pharm Pract ; 25(7): 1558-1563, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30180775

RESUMEN

BACKGROUND: Collaboration between pharmacists, doctors, and nurses in outpatient treatment is beneficial; however, such services are limited in Japan due to the lack of a healthcare reimbursement fee for outpatient pharmacy services at outpatient clinic. OBJECTIVE: We evaluated the impact of a service in which clinical pharmacists collaborated with an oncologist at an outpatient clinic in the treatment of adverse drug reactions in outpatient cancer chemotherapy. METHODS: We performed a retrospective cohort study using patients' medical records and treatment diaries. Subjects were patients who received outpatient chemotherapy via a clinical pharmacist collaboration service provided by six outpatient pharmacists and an oncologist at an outpatient clinic between June and August 2016. RESULTS: During the study period, the total number of outpatient services was 2508, with 2055 (81%) related to chemotherapy. The six outpatient pharmacists provided interventions to 498 of the 2055 cases (24%). Of the 498 interventions, 103 (20%), in addition to oncologist's prescription, were suggested treatments for adverse drug reactions due to cancer chemotherapy. Oncologists approved a total of 82 prescription suggestions from pharmacists (79%) to 63 patients. Fifty-seven percent (n = 47) of the adverse drug reactions were improved following the pharmacists' suggested prescriptions. CONCLUSIONS: This is the first study to clarify the benefits of outpatient pharmacy services in which pharmacists collaborate with oncologists at an outpatient clinic for the management of adverse drug reactions in cancer patients in Japan.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Colaboración Intersectorial , Neoplasias/tratamiento farmacológico , Servicio de Farmacia en Hospital , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oncólogos , Farmacéuticos , Estudios Retrospectivos
9.
BMC Musculoskelet Disord ; 20(1): 273, 2019 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-31159812

RESUMEN

BACKGROUND: Previous studies have indicated that trunk muscle strength decreases with chronic low back pain, and is associated with poor balance, poor functional performance, and falls in older adults. Strengthening exercises for chronic low back pain are considered the most effective intervention to improve functional outcomes. We developed an innovative exercise device for abdominal trunk muscles that also measures muscle strength. The correlation between muscle weakness, as measured by our device, the presence of chronic low back pain, and decreased physical ability associated with a risk of falling were evaluated in older women. METHODS: Thirty-eight elderly women, who could walk without support during daily activities and attended our outpatient clinic for treatment of chronic low back pain, knee or hip arthritis, or osteoporosis, were included in this study. Anthropometric measurements were performed. Grip power and one-leg standing time with eyes open were measured, and abdominal trunk muscle strength was measured using our device. History of falling in the previous 12 months was noted. Subjects with chronic low back pain (visual analog scale score ≥ 20 mm) for over 3 months were assigned to the low back pain group (n = 21). The remaining subjects formed the non-low back pain group (n = 17). RESULTS: Abdominal muscle strength of subjects in the low back pain group, and with history of falling, was significantly lower compared with that of subjects in the non-low back pain group, and in subjects without a history of falling, respectively. There was a moderate positive correlation between abdominal trunk muscle strength and one-leg standing time with eyes open. CONCLUSION: We measured abdominal muscle strength in older women with chronic low back pain using our device, and it was significantly lower than that of those without chronic low back pain. Muscle weakness was associated with a history and risk of falling.


Asunto(s)
Músculos Abdominales/fisiopatología , Accidentes por Caídas/estadística & datos numéricos , Dolor de la Región Lumbar/complicaciones , Debilidad Muscular/diagnóstico , Accidentes por Caídas/prevención & control , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Terapia por Ejercicio/instrumentación , Terapia por Ejercicio/métodos , Femenino , Humanos , Dolor de la Región Lumbar/fisiopatología , Dolor de la Región Lumbar/terapia , Fuerza Muscular/fisiología , Debilidad Muscular/etiología , Debilidad Muscular/fisiopatología
10.
J Emerg Med ; 54(4): 410-418, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29439891

RESUMEN

BACKGROUND: Bleeding from hemorrhagic shock can be immediately controlled by blocking the proximal part of the hemorrhagic point using either resuscitative thoracotomy for aortic cross-clamping or insertion of a large-caliber (10-14Fr) resuscitative endovascular balloon occlusion of the aorta (REBOA) device via the femoral artery. However, such methods are very invasive and have various complications. With recent progress in endovascular treatment, a low-profile REBOA device (7Fr) has been developed. OBJECTIVE: The objective of this study was to report our experience of this low-profile REBOA device and to evaluate the usefulness of emergency physician-operated REBOA in life-threatening hemorrhagic shock. METHODS: Ten patients with refractory hemorrhagic shock underwent REBOA using this device via the femoral artery. All REBOA procedures were performed by emergency physicians. The success rate of the insertion, vital signs, and REBOA-related complications were evaluated. RESULTS: Median age was 54 years (interquartile range 33-78 years). The causes of hemorrhagic shock were trauma (n = 4; 1 blunt and 3 penetrating), ruptured abdominal aortic aneurysm (n = 3), and obstetric hemorrhage (n = 3). Two patients had cardiopulmonary arrest upon arrival. REBOA procedure was successful in all patients, and all became hemodynamically stable to undergo definitive interventions after REBOA. There were no REBOA-related complications. The mortality rate within 24 h and 30 days was 40%. CONCLUSIONS: This REBOA device was useful for emergency physicians in life-threatening hemorrhagic shock because of its ease in handling and low invasiveness.


Asunto(s)
Aorta/lesiones , Oclusión con Balón/normas , Hemorragia/terapia , Adulto , Anciano , Aorta/fisiopatología , Oclusión con Balón/métodos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/métodos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Resucitación/métodos , Estudios Retrospectivos , Choque Hemorrágico/epidemiología , Choque Hemorrágico/prevención & control , Choque Hemorrágico/cirugía
11.
J Orthop Sci ; 23(3): 459-463, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29429888

RESUMEN

BACKGROUND: The aim of this study was to evaluate local recurrence and survival outcomes after frozen autograft total en bloc spondylectomy for metastatic spinal tumors. METHODS: We retrospectively analyzed data from 91 patients with metastatic spinal tumors who underwent frozen autograft total en bloc spondylectomy at our institution between May 2010 and April 2015. We assessed the incidence, primary cancer type, and sites of local recurrence. Risk factors for local recurrence were also examined through the statistical analysis of 17 items, including clinico-pathological characteristics, treatment history, and preoperative or surgical complications. Survival outcomes were evaluated with particular attention paid to the presence of local recurrence. RESULTS: The median follow-up duration was 27.4 months (range, 4-66 months). Local recurrence was diagnosed in 10 of 91 patients (11.0%). The sites of recurrence were intradural in 4 cases, epidural in 3 cases, in a vertebral body adjacent to the resected vertebral body in 2 cases, and in the paraspinal muscle in 3 cases. None of the patients had recurrence from the liquid nitrogen-treated tumor-bearing autograft. There were no local recurrences of renal cell carcinoma, thyroid cancer, or lung cancer. Multivariate analysis indicated that radiotherapy history was the only risk factor for local recurrence (odds ratio, 6.26; 95% confidence interval, 1.21-45.62; p = 0.04). The 2-year survival rate was significantly lower for the recurrence group than for the non-recurrence group (p < 0.05). CONCLUSIONS: A history of radiation was the only risk factor for local recurrence. Patients with recurrence had a significantly worse prognosis than those without recurrence.


Asunto(s)
Vértebras Lumbares/cirugía , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Anciano , Trasplante Óseo , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Neoplasias de la Columna Vertebral/mortalidad , Tasa de Supervivencia , Trasplante Autólogo
12.
Ann Vasc Surg ; 44: 420.e7-420.e10, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28479427

RESUMEN

We report a case of inferior mesenteric artery aneurysm (IMAA) after the replacement of the thoracoabdominal aorta for a chronic dissected thoracoabdominal aortic aneurysm in which the celiac artery and superior mesenteric artery were occluded. We performed the resection of the IMAA and the revascularization of the superior mesenteric artery, inferior mesenteric artery, and meandering artery. The patient's postoperative course was uneventful, without bowel ischemia. From the findings of intraoperative flow measurement of the visceral arteries, revascularization of the superior mesenteric artery was judged to be appropriate in this situation.


Asunto(s)
Aneurisma/etiología , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Arteria Celíaca , Arteria Mesentérica Inferior , Arteria Mesentérica Superior , Oclusión Vascular Mesentérica/etiología , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/fisiopatología , Aneurisma/cirugía , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aortografía/métodos , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/fisiopatología , Arteria Celíaca/cirugía , Circulación Colateral , Angiografía por Tomografía Computarizada , Constricción Patológica , Humanos , Masculino , Arteria Mesentérica Inferior/diagnóstico por imagen , Arteria Mesentérica Inferior/cirugía , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/fisiopatología , Arteria Mesentérica Superior/cirugía , Oclusión Vascular Mesentérica/diagnóstico por imagen , Oclusión Vascular Mesentérica/fisiopatología , Oclusión Vascular Mesentérica/cirugía , Circulación Esplácnica , Resultado del Tratamiento , Grado de Desobstrucción Vascular
13.
Lab Invest ; 96(1): 49-59, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26568295

RESUMEN

In kidney glomeruli, mesangial cells provide structural support to counteract for expansile forces caused by pressure gradients and to regulate the blood flow. Glomerular injury results in proliferation and aberrant migration of mesangial cells, which is the pathological characteristic of mesangial proliferative glomerulonephritis. To date, molecular changes that occur in mesangial cells during glomerular injury and their association with the pathogenesis of glomerulonephritis remain largely unclear. During the search for proteins regulating the morphology of mesangial cells, we found that afadin, a multi-domain F-actin-binding protein, and ß-catenin are expressed in cell-cell contact sites of cultured mesangial cells and mesangial cells in vivo. Afadin forms a protein complex with ß-catenin in glomeruli and in cultured mesangial cells. Protein expression of afadin at mesangial intercellular junctions was dramatically decreased in mesangial proliferative nephritis in rats and in patients with glomerulonephritis. RNA interference-mediated depletion of afadin in cultured mesangial cells did not affect proliferation rate but resulted in delayed directional cell migration. Furthermore, reorientation of the Golgi complex at the leading edges of migrating cells in wound-healing assay was disturbed in afadin-depleted cells, suggesting the role of aberrant migratory polarity in the pathogenesis of proliferative glomerulonephritis. These data shed light on glomerulonephritis-associated changes in cell-cell adhesion between mesangial cells, which might be related to migratory polarity.


Asunto(s)
Movimiento Celular/fisiología , Polaridad Celular/fisiología , Glomerulonefritis/metabolismo , Células Mesangiales/citología , Células Mesangiales/metabolismo , Proteínas de Microfilamentos/metabolismo , Animales , Células Cultivadas , Niño , Femenino , Células HEK293 , Humanos , Riñón/química , Riñón/citología , Riñón/metabolismo , Masculino , Ratas , beta Catenina/metabolismo
14.
Kidney Int ; 87(1): 225-32, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25054775

RESUMEN

In this multicenter, open-label, randomized controlled trial, we determined whether 2-month prednisolone therapy for steroid-sensitive nephrotic syndrome was inferior or not to 6-month therapy despite significantly less steroid exposure. The primary end point was time from start of initial treatment to start of frequently relapsing nephrotic syndrome. The pre-specified non-inferiority margin was a hazard ratio of 1.3 with one-sided significance of 5%. We randomly assigned 255 children with an initial episode of steroid-sensitive nephrotic syndrome to either 2 - or 6-month treatment of which 246 were eligible for final analysis. The total prednisolone exposure counted both initial and relapse prednisolone treatment administered over 24 months. Median follow-up in months was 36.7 in the 2-month and 38.2 in the 6-month treatment group. Time to frequent relaps was similar in both groups; however, the median was reached only in the 6-month group (799 days). The hazard ratio was 0.86 (90% confidence interval, 0.64-1.16) and met the non-inferior margin. Time to first relapse was also similar in both groups: median day 242 (2-month) and 243 (6-month). Frequency and severity of adverse events were similar in both groups. Most adverse events were transient and occurred during initial or relapse therapy. Thus, 2 months of initial prednisolone therapy for steroid-sensitive nephrotic syndrome, despite less prednisolone exposure, is not inferior to 6 months of initial therapy in terms of time to onset of frequently relapsing nephrotic syndrome.


Asunto(s)
Glucocorticoides/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Prednisolona/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Recurrencia
15.
Nature ; 459(7247): 712-6, 2009 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-19412163

RESUMEN

A20 is a negative regulator of the NF-kappaB pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation. It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappaB in response to a variety of external stimuli; recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk. However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wild-type A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by downregulation of NF-kappaB activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappaB activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappaB activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappaB caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.


Asunto(s)
Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Silenciador del Gen , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/fisiopatología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Animales , Apoptosis/fisiología , Línea Celular , Proteínas de Unión al ADN , Expresión Génica , Genoma/genética , Humanos , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
16.
Clin Exp Nephrol ; 19(5): 933-8, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25595442

RESUMEN

BACKGROUND: End-stage renal disease (ESRD) in children is considered a rare, but serious condition. Epidemiological and demographic information on pediatric ESRD patients around the world is important to better understand this disease and to improve patient care. The Japanese Society for Pediatric Nephrology (JSPN) reported epidemiological and demographic data in 1998. Since then, however, there has been no nationwide survey on Japanese children with ESRD. METHODS: The JSPN conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011. RESULTS: The average incidence of ESRD was 4.0 per million age-related population. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2 % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis. Initial treatment modalities in patients who commenced renal replacement therapy (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT mortality rate was 18.2 deaths per 1000 person-years of observation. CONCLUSION: The incidence of ESRD is lower in Japanese children than in children of other high-income countries. Since 1998, notably, there has been a marked increase in pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.


Asunto(s)
Fallo Renal Crónico/epidemiología , Adolescente , Pueblo Asiatico , Causas de Muerte , Niño , Preescolar , Estudios Transversales , Femenino , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Encuestas Epidemiológicas , Humanos , Incidencia , Lactante , Recién Nacido , Japón/epidemiología , Riñón/anomalías , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/estadística & datos numéricos , Masculino , Diálisis Peritoneal/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Terapia de Reemplazo Renal , Análisis de Supervivencia , Sistema Urinario/anomalías , Adulto Joven
17.
Kidney Int ; 86(3): 548-57, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24694988

RESUMEN

Mesangial cell migration, regulated by several growth factors, is crucial after glomerulopathy and during glomerular development. Directional migration requires the establishment of a polarized cytoskeletal arrangement, a process regulated by coordinated actin dynamics and focal adhesion turnover at the peripheral ruffles in migrating cells. Here we found high expression of the actin cross-linking protein EPLIN (epithelial protein lost in neoplasm) in mesangial cells. EPLIN was localized in mesangial angles, which consist of actin-containing microfilaments extending underneath the capillary endothelium, where they attach to the glomerular basement membrane. In cultured mesangial cells, EPLIN was localized in peripheral actin bundles at focal adhesions and formed a protein complex with paxillin. The MEK-ERK (extracellular signal-regulated kinase) cascade regulated EPLIN-paxillin interaction and induced translocalization of EPLIN from focal adhesion sites to peripheral ruffles. Knockdown of EPLIN in mesangial cells enhanced platelet-derived growth factor-induced focal adhesion disassembly and cell migration. Furthermore, EPLIN expression was decreased in mesangial proliferative nephritis in rodents and humans in vivo. These results shed light on the coordinated actin remodeling in mesangial cells during restorative remodeling. Thus, changes in expression and localization of cytoskeletal regulators underlie phenotypic changes in mesangial cells in glomerulonephritis.


Asunto(s)
Adhesión Celular , Movimiento Celular , Proteínas del Citoesqueleto/metabolismo , Glomerulonefritis Membranoproliferativa/metabolismo , Células Mesangiales/fisiología , Proteínas de Microfilamentos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Actinas/metabolismo , Adolescente , Animales , Células Cultivadas , Niño , Proteínas del Citoesqueleto/genética , Expresión Génica , Glomerulonefritis por IGA/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Proteínas de Microfilamentos/genética , Paxillin/metabolismo , ARN Mensajero/metabolismo , Ratas , Antígenos Thy-1/metabolismo
18.
Nephrol Dial Transplant ; 29(2): 376-84, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24081861

RESUMEN

Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal dysfunction. Dent disease is caused by mutations in at least two genes, i.e. CLCN5 and OCRL1, and its genetic background and phenotypes are common among European countries and the USA. However, only few studies on Dent disease in Japan, which was originally called 'low-molecular-weight proteinuric disease', have been reported thus far. In this study, we analysed genetic background and clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease patients. The results demonstrated that the genetic basis of Japanese Dent disease was nearly identical to those of Dent disease in other countries. Of 86 unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of which were novel, and the remaining 14 patients showed no mutations in CLCN5 or OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the patients were relatively young, six patients (8%) showed apparent renal dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe and the USA.


Asunto(s)
Canales de Cloruro/genética , ADN/genética , Enfermedad de Dent/genética , Mutación , Monoéster Fosfórico Hidrolasas/genética , Proteinuria/etiología , Adolescente , Adulto , Biomarcadores/orina , Niño , Preescolar , Análisis Mutacional de ADN , Enfermedad de Dent/complicaciones , Enfermedad de Dent/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Lactante , Japón/epidemiología , Masculino , Fenotipo , Proteinuria/genética , Proteinuria/orina , Estados Unidos/epidemiología , Adulto Joven
19.
Nephrol Dial Transplant ; 29(1): 81-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24042019

RESUMEN

BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal-dominant disorder caused by LMX1B mutation. In patients with the renal lesions typical of NPS without skeletal or nail findings, it is described as nail-patella-like renal disease (NPLRD). However, the pathogenesis of NPLRD is largely unknown. METHODS: A 6-year-old girl with microscopic haematuria and mild proteinuria was diagnosed with NPLRD because of an aberrantly thickened glomerular basement membrane (GBM) and deposition of Type III collagen in the GBM observed by electron microscopy. Immunohistological analyses of podocyte protein expression were performed on biopsy tissues. Sequence analysis of LMX1B was performed, and the functional consequences of the detected mutation were analysed by luciferase reporter assay. RESULTS: When analysing molecules that are important for podocyte development, maintenance and maturation, CD2AP expression was found to be altered in the podocytes. A novel LMX1B missense mutation (R246Q) was identified. Functional analyses revealed partial but significant impairment of R246Q transcriptional activity. However, no dominant-negative effect of R246Q was detected, which suggests that NPLRD is caused by LMX1B haploinsufficiency. CONCLUSIONS: This is the first report on LMX1B mutation identified in a patient with NPLRD. Residual transcriptional activity would account for normality of the nails and patella in this case. Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.


Asunto(s)
Proteínas con Homeodominio LIM/genética , Mutación Missense/genética , Síndrome de la Uña-Rótula/genética , Nefritis Hereditaria/genética , Factores de Transcripción/genética , Animales , Niño , Femenino , Humanos , Inmunohistoquímica , Riñón/patología , Síndrome de la Uña-Rótula/patología , Nefritis Hereditaria/patología , Podocitos/metabolismo
20.
Pediatr Nephrol ; 29(9): 1553-60, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24705794

RESUMEN

BACKGROUND: Circulating factor(s) has been thought to be the underlying cause of focal segmental glomerulosclerosis (FSGS), and recent studies foster this idea by demonstrating increased soluble urokinase receptor (suPAR) levels in the serum of FSGS patients. METHODS: To explore the possible contribution of suPAR in FSGS pathogenesis, we analyzed serum suPAR levels in 17 patients with FSGS and compared them with those in patients with steroid-sensitive nephrotic syndrome, chronic glomerulonephritis, or non-glomerular kidney diseases. RESULTS: Serum suPAR levels in patients with FSGS were higher than those in patients with steroid-sensitive nephrotic syndrome or chronic glomerulonephritis, but not higher than those in patients with non-glomerular kidney diseases. suPAR levels negatively correlate with estimated glomerular filtration rate and were decreased after renal transplantation in patients with FSGS as well as in those with non-glomerular kidney diseases. Furthermore, 6 FSGS patients with post-transplant recurrence demonstrated that suPAR levels were not high during the recurrence. CONCLUSIONS: Based on our results, elevated suPAR levels in FSGS patients were attributed mainly to decreased glomerular filtration. These data warrant further analysis for involvement of possible circulating factor(s) in FSGS pathogenesis.


Asunto(s)
Tasa de Filtración Glomerular/fisiología , Glomeruloesclerosis Focal y Segmentaria/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Adolescente , Niño , Preescolar , Femenino , Humanos , Trasplante de Riñón , Masculino
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