The Relationship between Psychological Distress and Physical Frailty in Japanese Community-Dwelling Older Adults: A Cross-Sectional Study.

BACKGROUND: Older adults' mental health and physical frailty have been a frequent research focus, but few studies have investigated the relationship between them. OBJECTIVES: To investigate the association between mental health and physical frailty in community-dwelling older Japanese people. DESIGN: Cross-sectional study from the Itoshima Frail Study. SETTING: Itoshima City, Fukuoka, Japan. PARTICIPANTS: A total of 919 community-dwelling older individuals aged 65-75 years. MEASUREMENTS: Physical frailty was measured based on five criteria proposed by the Fried scale, and the subjects were classified into three groups: robust, pre-frailty, and frailty. Psychological distress was used to assess the subjects' mental health, with the Kessler 6-Item Psychological Distress Scale (K6) score; the subjects were divided into three groups based on their K6 score: 0-1, 2-4, and ≥5. Psychological distress was defined by K6 score ≥5. Ordinal logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) between the psychological distress and physical frailty status. RESULTS: Psychological distress was identified in 190 subjects (20.7%). Forty-six subjects (5.0%) presented with physical frailty, and 24 subjects (2.6%) had both psychological distress and physical frailty. With the increase in the K6 score, more subjects had pre-frailty and physical frailty (p<0.001). Significant positive associations were observed between psychological distress and the risks of pre-frailty (OR 2.94, 95%CI: 1.95-4.43) and frailty (OR 10.71, 95%CI: 4.68-24.51), even in a multivariable-adjusted analysis. In a subgroup analysis of components of frailty, one-point increment in K6 score was associated with higher odds of shrinking and fatigue. CONCLUSION: A severe psychological distress was associated with increased risks of physical frailty and the frailty sub-items of shrinking and fatigue in community-dwelling older Japanese adults.

COVID-19 transmission in dental and oral/maxillofacial surgical practice during pandemic: questionnaire survey in 51 university hospitals in Japan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major public health problem. Dental procedures that generate aerosols are considered to impose a high risk of infection; therefore, dental professionals, such as dentists and dental hygienists, may be at high risk of viral transmission. However, few studies have reported COVID-19 clusters in dental care settings. AIM: To investigate whether dental and oral/maxillofacial procedures are associated with the occurrence of COVID-19 clusters and measures taken to prevent nosocomial infection in dental clinics. METHODS: An online questionnaire survey on clinical activities (administrative control), infection control measures (environmental/engineering control, personal protective equipment, etc.), and confirmed or probable COVID-19 cases among patients and clinical staff was administered to the faculties of the dental and oral/maxillofacial surgical departments of university hospitals. FINDINGS: Fifty-one faculty members completed the questionnaire. All members were engaged in the treatment of dental and oral surgical outpatients and actively implemented standard precautions. Fourteen faculty members treated patients with COVID-19, but no infections transmitted from the patients to the medical staff were observed. In seven facilities, patients were found to have the infection after treatment (medical staff came in close contact), but there was no transmission from patients to medical staff. Four facilities had medical staff with infections, but none of them exhibited disease transmission from staff to patients. CONCLUSION: COVID-19 clusters are unlikely to occur in dental and oral surgical care settings if appropriate protective measures are implemented.

Odontogenic chronic rhinosinusitis patients undergoing tooth extraction: oral surgeon and otolaryngologist viewpoints and appropriate management.

OBJECTIVE: This study aimed to propose appropriate management for odontogenic chronic rhinosinusitis. METHOD: Thirty-one adult patients with odontogenic chronic rhinosinusitis undergoing maxillary extraction were retrospectively analysed. Patients with (n = 21) and without (n = 10) oroantral fistula on computed tomography were classified. Functional endoscopic sinus surgery was performed when sinusitis did not improve after extraction. The critical indicators for surgical requirement in the management of odontogenic chronic rhinosinusitis were analysed. RESULTS: Sinusitis significantly improved after extraction in both groups. Patients without oroantral fistula had significantly more severe remnant sinusitis than those with oroantral fistula after extraction on computed tomography (p = 0.0037). The requirement for functional endoscopic sinus surgery was statistically significant for patients without orofacial fistula over those with orofacial fistula (p < 0.0001). The surgical improvement ratio was 93 per cent. CONCLUSION: The absence of oroantral fistula and severe sinusitis can be critical indicators for the requirement of functional endoscopic sinus surgery after extraction in the management of odontogenic chronic rhinosinusitis.

Physical Frailty and Risk of Needing Long-Term Care in Community-Dwelling Older Adults: a 6-Year Prospective Study in Japan.

OBJECTIVE: To examine the association between physical frailty and risk of needing long-term care, and compare the predictive value and clinical usefulness of a simple frailty scale (FRAIL) with that of the original Cardiovascular Health Study (CHS) criteria. DESIGN AND SETTING: A 6-year prospective cohort study of community-dwelling older adults in a west Japanese suburban town. PARTICIPANTS: 1,554 older adults aged 65 years and over who were initially free of long-term care needs at baseline. MEASUREMENTS: Physical frailty was defined by the CHS criteria and the FRAIL scale. The onset of needing long-term care was ascertained using national records of certification of long-term care needs. Cox proportional hazard models were used to estimate the association between physical frailty and risk of needing long-term care. Decision curve analysis was performed to compare the clinical usefulness of the two physical frailty criteria. RESULTS: During a median follow-up of 5.8 years, 244 were ascertained as needing long-term care. Baseline physical frailty was significantly associated with elevated risk of needing long-term care, with a multivariable-adjusted hazard ratio (HR) of 2.00 (95% confidence interval [CI], 1.32-3.02) for being frail and 1.50 (95% CI, 1.10-2.03) for being pre-frail as defined by the CHS criteria, compared with being robust (p for trend = 0.001). Similar results were found for physical frailty defined by the FRAIL scale, with a multivariable-adjusted HR (95% CIs) of 2.11 (1.25-3.56) for being frail and 1.73 (1.28-2.35) for being pre-frail vs. being robust (p for trend < 0.001). The two physical frailty criteria had similar net benefits in identifying individuals at high risk for needing long-term care. CONCLUSIONS: Physical frailty is significantly associated with an increased risk of needing long-term care in community-dwelling older adults in Japan. Compared with the original CHS criteria, the simple FRAIL scale has comparable predictive value and clinical usefulness for identifying individuals at risk for needing long-term care.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study.

A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen of teriparatide, while also improving safety. INTRODUCTION: While a 56.5-µg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-µg teriparatide can provide comparable efficacy to the 56.5-µg once-weekly regimen while improving safety. METHODS: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-µg twice-weekly group (n = 277) or the 56.5-µg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2-L4) bone mineral density (BMD) at final follow-up. RESULTS: The percentage changes in lumbar spine (L2-L4) BMD at final follow-up in the 28.2-µg twice-weekly and 56.5-µg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400-2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (- 1.6%), non-inferiority of the 28.2-µg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-µg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-µg twice-weekly group. CONCLUSIONS: A 28.2-µg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-µg once-weekly regimen while improving safety. CLINICAL TRIAL REGISTRATION: JapicCTI-163477 .

Oxygen surface exchange properties and surface segregation behavior of nanostructured La0.6Sr0.4Co0.2Fe0.8O3-δ thin film cathodes.

Cathode materials with highly reactive surfaces and long-term stability are required to achieve high-performance solid oxide fuel cells (SOFCs). In this study, a promising cathode material, La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF), was prepared as a nanostructured thin film using pulsed laser deposition (PLD) on gadolinia-doped ceria (GDC)-buffered YSZ single crystal substrates having (100) and (111) orientations. Characterization revealed intrinsic differences among the as-grown LSCF thin films in terms of dominant crystalline orientation and nanostructure depending on GDC preparation as well as the YSZ substrate orientation. Evaluation of the oxygen exchange properties using the isotope exchange depth profile method revealed that LSCF thin films grown on (111) GDC/YSZ exhibited higher values of the apparent surface exchange coefficient compared to LSCF thin films grown on (100) GDC/YSZ. However, when subjected to long-term annealing at high temperatures, the former exhibited a stronger tendency to surface segregation as compared to the latter. These behaviors are correlated with the intrinsic properties of LSCF thin films, including the nanostructure, the possible effects attributed to SrO activity, and the stability of perovskite surfaces which would drive surface segregation. These results have implications for tailoring the performance of cathode thin films by understanding the dependence of oxygen exchange properties and surface segregation on driving forces such as surface chemistry and nanostructure.

A large-aperture high-sensitivity avalanche image intensifier panel.

A large-aperture high-sensitivity image intensifier panel that consists of an avalanche photodiode array and a light-emitting diode array is presented. The device has 40% quantum efficiency, over 104 optical gain, and 80-ns time resolution. The aperture size of the device is 20 cm, and with the current manufacturing process, it can be scaled to arbitrarily larger sizes. The device can intensify the light from a single particle scintillation emission to an eye-visible bright flash. The image resolution of the device is currently limited by the size of the avalanche photodiode that is 2 mm, although it can be scaled to smaller sizes in the near future. The image intensifier is operated at a small voltage, typically +57 V. The device can be applied to various applications, such as scintillation imaging, night vision cameras, and an image converter from non-visible light (such as infrared or ultraviolet) to visible light.

Long-term oral bisphosphonates delay healing after tooth extraction: a single institutional prospective study.

Tooth extraction in patients receiving bisphosphonates is thought to be a risk factor for osteonecrosis of the jaw (ONJ); however, ONJ did not develop, even when tooth extraction was performed with continued oral bisphosphonate therapy. A drug holiday from bisphosphonates before tooth extraction may not be necessary. INTRODUCTION: It is controversial whether bisphosphonate withdrawal is necessary prior to invasive procedures such as tooth extraction in order to prevent bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study aimed to evaluate the clinical safety of continuing oral bisphosphonate therapy in patients undergoing tooth extraction. METHODS: We prospectively enrolled 132 patients (20 men, 112 women) who were receiving oral bisphosphonates for the prevention or treatment of osteoporosis and required tooth extraction. All patients were managed using an identical protocol, which included preoperative antibiotic prophylaxis and did not necessarily require complete wound closure. The patients were classified into groups according to the duration of bisphosphonate administration: < 2 years (n = 51), 2-5 years (n = 41), 5-10 years (n = 28), and > 10 years (n = 12). The groups were compared regarding the time taken for the extraction socket to heal, and the occurrence of BRONJ. Follow-up duration was at least 3 months. RESULTS: A total of 274 teeth were removed. Long-term oral bisphosphonate therapy for > 5 years significantly delayed the healing of the extraction socket in comparison with administration for < 5 years; however, BRONJ did not develop in any group. There was no prolongation of wound healing due to systemic risk factors such as glucocorticoid administration and diabetes mellitus. There were no adverse skeletal events such as bone fracture. CONCLUSIONS: Patients who underwent tooth extraction with continued oral bisphosphonate therapy showed delayed healing of the extraction socket as the cumulative administration period prolonged, but BRONJ did not develop.

Physical Frailty Is Associated with Longitudinal Decline in Global Cognitive Function in Non-Demented Older Adults: A Prospective Study.

OBJECTIVES: To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. DESIGN AND SETTING: A prospective population-based study in a west Japanese suburban town, with two-year follow-up. PARTICIPANTS: Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). MEASUREMENTS: Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. RESULTS: Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. CONCLUSION: Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

OBP-401-GFP telomerase-dependent adenovirus illuminates and kills high-metastatic more effectively than low-metastatic triple-negative breast cancer in vitro.

We previously described the development of a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of MDA-MB-231 human breast cancer in nude mice. The isolated variant is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared with 2 of 12 of the parental cell line. OBP-401 is a telomerase-dependent cancer-specific, green fluorescent protein (GFP)-expressing adenovirus. OBP-401 was used to infect parental MDA-MB-231P cells and high-metastatic MDA-MB-231H and MDA-MB-231HLN isolated from a lymph node metastasis and MDA-MB-231HLM isolated from a lung metastasis. Time-course imaging showed that OBP-401 labeled MDA-MB-231HP, MDA-MB-231HLN, and MDA-MB-231HLM cells more brightly than MDA-MB-231 parental cells. OBP-401 killed MDA-MB-231H, MDA-MB-231HLN, and MDA-MB-231HLM cells more efficiently than MDA-MB-231P parental cells. These results indicate that OBP-401 could infect, label and then kill high-metastatic MDA-MB-231 more efficiently than low-metastatic MDA-MB-231.

Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study).

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. INTRODUCTION: The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. METHODS: This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. RESULTS: The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. CONCLUSIONS: Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

Risk of haemolytic uraemic syndrome caused by shiga-toxin-producing Escherichia coli infection in adult women in Japan.

Shiga-toxin-producing Escherichia coli (STEC) infections usually cause haemolytic uraemic syndrome (HUS) equally in male and female children. This study investigated the localization of globotriaosylceramide (Gb3) in human brain and kidney tissues removed from forensic autopsy cases in Japan. A fatal case was used as a positive control in an outbreak of diarrhoeal disease caused by STEC O157:H7 in a kindergarten in Urawa in 1990. Positive immunodetection of Gb3 was significantly more frequent in female than in male distal and collecting renal tubules. To correlate this finding with a clinical outcome, a retrospective analysis of the predictors of renal failure in the 162 patients of two outbreaks in Japan was performed: one in Tochigi in 2002 and the other in Kagawa Prefecture in 2005. This study concludes renal failure, including HUS, was significantly associated with female sex, and the odds ratio was 4·06 compared to male patients in the two outbreaks. From 2006 to 2009 in Japan, the risk factor of HUS associated with STEC infection was analysed. The number of males and females and the proportion of females who developed HUS were calculated by age and year from 2006 to 2009. In 2006, 2007 and 2009 in adults aged >20 years, adult women were significantly more at risk of developing HUS in Japan.

Color-coding cancer and stromal cells with genetic reporters in a patient-derived orthotopic xenograft (PDOX) model of pancreatic cancer enhances fluorescence-guided surgery.

Precise fluorescence-guided surgery (FGS) for pancreatic cancer has the potential to greatly improve the outcome in this recalcitrant disease. To achieve this goal, we have used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. The telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. The PDOX was previously grown in a red fluorescent protein (RFP) transgenic mouse that stably labeled the PDOX stroma cells bright red. The color-coded PDOX model enabled FGS to completely resect the pancreatic tumors including stroma. Dual-colored FGS significantly prevented local recurrence, which bright-light surgery or single-color FGS could not. FGS, with color-coded cancer and stroma cells has important potential for improving the outcome of recalcitrant-cancer surgery.

CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population.

Many types of cancer display heterogeneity in various features, including gene expression and malignant potential. This heterogeneity is associated with drug resistance and cancer progression. Recent studies have shown that the expression of a major protein quality control ubiquitin ligase, carboxyl terminus of Hsc70-interacting protein (CHIP), is negatively correlated with breast cancer clinicopathological stages and poor overall survival. Here we show that CHIP acts as a capacitor of heterogeneous Bcl-2 expression levels and prevents an increase in the anticancer drug-resistant population in breast cancer cells. CHIP knockdown in breast cancer cells increased variation in Bcl-2 expression levels, an antiapoptotic protein, among the cells. Our results also showed that CHIP knockdown increased the proportion of anticancer drug-resistant cells. These findings suggest that CHIP buffers variation in gene expression levels, affecting resistance to anticancer drugs. In single-cell clones derived from breast cancer cell lines, CHIP knockdown did not alter the variation in Bcl-2 expression levels and the proportion of anticancer drug-resistant cells. In contrast, when clonal cells were treated with a mutagen, the variation in Bcl-2 expression levels and proportion of anticancer drug-resistant cells were altered by CHIP knockdown. These results suggest that CHIP masks genetic variations to suppress heterogeneous Bcl-2 expression levels and prevents augmentation of the anticancer drug-resistant population of breast cancer cells. Because genetic variation is a major driver of heterogeneity, our results suggest that the degree of heterogeneity in expression levels is decided by a balance between genetic variation and the buffering capacity of CHIP.

Marked improvement of insulin sensitivity without enhancement of GLP-1 and insulin secretion after Roux-en-Y gastric bypass surgery in a mildly obese patient with diabetes.

Roux-en-Y gastric bypass is an option of treatment for morbidly obese patients with diabetes. However, the value of the operation in mildly obese patients is not established. We report the first prospective systematic endocrine and metabolic analysis in a mildly obese patient who underwent a Roux-en-Y gastric bypass. In a 49-year-old man with BMI 32.6 kg/m(2) having type 2 diabetes, intramucosal gastric cancer was treated by partial gastrectomy with Roux-en-Y gastric bypass. Pre-operatively, he received 53 U/day insulin and the HbA1c value was 63 mmol/mol: meal tolerance test showed diabetic hyperglycemia and low insulin sensitivity with attenuated insulin secretion and normal glucagon-like peptide 1(7-36) secretion. After the operation, hypoglycemic agent was stopped. Body weight reduced from 84.0 to 77.0 kg within 2 weeks and increased thereafter to 79.4 kg at 4 months later, when the degree of hyperglycemia was unchanged as indexed by a HbA1c value of 62 mmol/mol. Upon repeated meal tolerance test, no increase of glucagon-like peptide 1 and insulin secretion, but significantly improved hepatic and peripheral insulin sensitivity were found, compared to the preoperative meal tolerance test. Marked dissociation of endocrine and metabolic effects of Roux-en-Y gastric bypass, that is, absence of increased glucagon-like peptide 1/insulin secretion with improvement of insulin sensitivity, was found in a mildly obese patient with type 2 diabetes.

SATB1 collaborates with loss of p16 in cellular transformation.

Tumor progression is associated with invasiveness and metastatic potential. The special AT-rich binding protein 1 (SATB1) has been identified as a key factor in the progression of breast cancer cells to a malignant phenotype and is associated with progression of human tumors. In normal development, SATB1 coordinates gene expression of progenitor cells by functioning as a genome organizer. In contrast to progenitor and tumor cells, SATB1 expression in nontransformed cells is not compatible with proliferation. Here we show that SATB1 expression in mouse embryonic fibroblasts induces cell cycle arrest and senescence that is associated with elevated p16 protein levels. Deletion of p16 overcomes the SATB1-induced senescence. We further provide evidence for an interaction of SATB1 with the retinoblastoma (RB)/E2F pathway downstream of p16. A combined deletion of the RB proteins, RB, p107 and p130 (triple-mutant; TM), prevents SATB1-induced G1 arrest, which is restored upon the reintroduction of RB into SATB1-expressing TM fibroblasts. SATB1 interacts with the E2F/RB complex and regulates the cyclin E promoter in an E2F-dependent manner. These findings demonstrate that p16 and the RB/E2F pathway are critical for SATB1-induced cell cycle arrest. In the absence of p16, SATB1 causes anchorage-independent growth and invasive phenotype in fibroblasts. Our data illustrate that p16 mutations collaborate with the oncogenic activity of SATB1. Consistent with our finding, a literature survey shows that deletion of p16 is generally associated with SATB1 expressing human cell lines and tumors.

Case report of a successful liver transplantation for acute liver failure due to mitochondrial respiratory chain complex III deficiency.

Mitochondrial respiratory chain disorders can cause acute liver failure in infants and children. Liver transplantation, however, has rarely been indicated for patients with mitochondrial respiratory chain disorders, because of the extrahepatic involvement. Herein we reported a case of acute liver failure with mitochondrial respiratory chain complex III deficiency treated by liver transplantation. At 2 years after transplantation, there were no extrahepatic manifestations. We suggest that mitochondrial disorders should be considered to be a cause of liver failure in infancy and that liver transplantation can be a life-saving treatment.

Induction of hypertrophic chondrocyte-like phenotypes by oxidized LDL in cultured bovine articular chondrocytes through increase in oxidative stress.

OBJECTIVE: It has been reported that the lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor 1 (LOX-1) is expressed by chondrocytes in osteoarthritis (OA) cartilage and that Ox-LDL binding to LOX-1 increases intracellular oxidative stress in cultured bovine articular chondrocytes (BACs). It was recently demonstrated that reactive oxygen species (ROS) induce hypertrophic differentiation of chondrocytes in the growth plate. It has also been shown that activated chondrocytes in OA have hypertrophic chondrocyte-like phenotypes. The purpose of this study was to determine whether Ox-LDL induces hypertrophic chondrocyte-like phenotypes in BACs. DESIGN: Changes in type X collagen (COL10) and runt-related transcription factor 2 (Runx2) mRNA expression in BACs after Ox-LDL stimulation were investigated using real-time polymerase chain reaction (PCR). Western blotting and immunofluorescent cell staining were used to investigate changes in protein level. The antioxidant N-acetyl cysteine (NAC) was used to ascertain whether oxidative stress is involved in COL10 and Runx2 expression. We induced LOX-1 knockdown cells using small interfering RNA (siRNA) to examine the receptor specificity of Ox-LDL. RESULTS: COL10 expression was upregulated by Ox-LDL in a time- and dose-dependent manner. Immunofluorescent staining showed that Ox-LDL increased COL10 production in the extracellular matrix. Ox-LDL-induced upregulation of COL10 was suppressed by pretreatment with NAC and siRNA. Expression of Runx2 was upregulated by Ox-LDL and H(2)O(2), and these effects were suppressed by NAC pretreatment. CONCLUSION: Ox-LDL binding to LOX-1 induces a hypertrophic chondrocyte-like phenotype through oxidative stress, indicating that Ox-LDL plays a role in the degeneration of cartilage.

[Long term outcome of arterial switch surgery for transposition of the great arteries: evaluation of the reconstruction of the pulmonary artery].

We assessed the effect of reconstructing the pulmonary artery during arterial switch surgery for transposition of the great arteries on late pulmonary stenosis. Sixty-five patients who underwent Lecompte procedure between September 1991 and December 2006 were divided, by the procedure used chronologically to reconstruct the pulmonary artery, into group XP (single pantaloon patch with equine pericardium, n = 11), group P (direct reconstruction, n = 47), and group AP (single pantaloon patch with fresh autopericardium, n = 7). Outcome and pulmonary stenosis on the most recent ultrasound cardiography (UCG) were compared in the 3 groups. The median follow-up was 13, 7.5, and 1.3 years, respectively. Both early and late mortalities were 1.5% (1/65). Although percutaneous trans-pulmonary angioplasty was necessary in 1, 13, and 3 patients, there was 1, 1, and 0 reoperation for pulmonary stenosis in the 3 groups, respectively. Pulmonary stenosis (pulmonary arterial maximum flow velocity > 3 m/sec on UCG) was present in 4 (40%). 14 (30%). and 3 patients (43%). Although there was no significant difference among the 3 procedures in preventing pulmonary stenosis 10 years after arterial switch surgery, direct reconstruction of the pulmonary artery may show a superior outcome, in particular, over 10 years after arterial switch surgery.