PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS.

Peroxisomes are rapidly degraded during amino acid and oxygen deprivation by a type of selective autophagy called pexophagy. However, how damaged peroxisomes are detected and removed from the cell is poorly understood. Recent studies suggest that the peroxisomal matrix protein import machinery may serve double duty as a quality control machinery, where they are directly involved in activating pexophagy. Here, we explored whether any matrix import factors are required to prevent pexophagy, such that their loss designates peroxisomes for degradation. Using gene editing and quantitative fluorescence microscopy on culture cells and a zebrafish model system, we found that PEX13, a component of the peroxisomal matrix import system, is required to prevent the degradation of otherwise healthy peroxisomes. The loss of PEX13 caused an accumulation of ubiquitinated PEX5 on peroxisomes and an increase in peroxisome-dependent reactive oxygen species that coalesce to induce pexophagy. We also found that PEX13 protein level is downregulated to aid in the induction of pexophagy during amino acid starvation. Together, our study points to PEX13 as a novel pexophagy regulator that is modulated to maintain peroxisome homeostasis.Abbreviations: AAA ATPases: ATPases associated with diverse cellular activities; ABCD3: ATP binding cassette subfamily D member; 3ACOX1: acyl-CoA oxidase; 1ACTA1: actin alpha 1, skeletal muscle; ACTB: actin beta; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; CAT: catalase; CQ: chloroquine; Dpf: days post fertilization: FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; H2O2: hydrogen peroxide; HA - human influenza hemagglutinin; HBSS: Hanks' Balanced Salt Solution; HCQ; hydroxychloroquine; KANL: lysine alanine asparagine leucine; KO: knockout; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; MTORC2: mechanistic target of rapamycin kinase complex 2; MYC: MYC proto-oncogene, bHLH transcription factor; MZ: maternal and zygotic; NAC: N-acetyl cysteine; NBR1 - NBR1 autophagy cargo receptor; PBD: peroxisome biogenesis disorder; PBS: phosphate-buffered saline; PEX: peroxisomal biogenesis factor; PTS1: peroxisome targeting sequence 1; RFP: red fluorescent protein; ROS: reactive oxygen speciess; iRNA: short interfering RNA; SKL: serine lysine leucine; SLC25A17/PMP34: solute carrier family 25 member 17; Ub: ubiquitin; USP30: ubiquitin specific peptidase 30.

Carotid artery injury with cerebral infarction following head and neck blunt trauma: report of a case.

Blunt injury to the carotid artery is rare but may produce a devastating outcome with longterm morbidity. Initial recognition by clinicians is often difficult because of the diverse clinical manifestations, the delay in presentation of symptoms, and the associated multi-organ system injuries that accompany carotid injury. Early diagnosis and successful management of traumatic carotid artery injury require a high index of clinical suspicion. We report herein a 20-year-old male victim of internal carotid artery injury induced by a motorcycle accident, who initially presented with a clear consciousness and had normal computed tomogram (CT) of brain. Two days after injury, the patient suffered from left hemiplegia and coma. The follow-up brain CT showed acute infarction of right cerebrum and severe cerebral edema. Emergency craniotomy for brain decompression and anticoagulation therapy was carried out. After a three-month treatment, he was discharged and underwent regular follow-up in the outpatient department. Six months later, the patient had intact awareness but remained in a left-sided hemiparetic state.

Application of anthropometric indices in childhood obesity.

OBJECTIVES: The purpose of this study was to determine which anthropometric index can best predict childhood obesity and to investigate the interrelationship between these anthropometric indices and metabolic abnormalities. METHODS: This was a cross-sectional study. In March 2000, 2005 children aged 7 to 8 from the first grade of primary schools in Taichung City in Taiwan were enrolled in this study. Data were obtained on the children's anthropometry, blood pressure, and serum lipid profiles. Body mass index (cutoff points by international age- and sex-specific body mass index [BMI]) and weight-length index (WLI) were measured. The t test, the chi2 test, and stepwise multivariate logistic regression were used. All subjects were divided into four groups: Group 1, nonobese by BMI definition, WLI < 1.2; group 2, obese by BMI definition, WLI < 1.2; group 3, nonobese by BMI definition, WLI > or = 1.2; and group 4, obese by BMI definition, WLI > or = 1.2. RESULTS: There were 951 girls (47.43%) and 1,054 boys (52.57%). The mean age was 7.3 +/- 0.4 years. The prevalence of obesity was 4.21% in girls and 7.87% in boys using BMI definition, and 12.83% in girls and 14.14% in boys using WLI definition. The prevalence of obesity revealed an increased trend with age in both sexes, whether by BMI or WLI definition. Group 4 had the highest prevalence rate of all metabolic abnormalities, except hypertriglyceridemia. After controlling for age and sex, and with group 1 as a reference, odds ratios were considerably higher in group 3 for the risk of hypertension (2.73; 95% confidence interval [CI], 1.67-4.44) and hypertriglyceridemia (5.83; 95% CI, 1.42-23.95). Odds ratios were considerably higher in group 4 for the risk of hypertension (3.75; 95% CI, 2.31-6.07) and high level of low-density lipoprotein cholesterol (1.93; 95% CI, 1.32-2.82). CONCLUSIONS: The prevalence of obesity apparently differs depending on the definition of estimation. Childhood obesity exhibits significant correlation with some metabolic abnormalities. We hypothesize that, at present, both indices, BMI and WLI, should be used together to define childhood obesity in clinical practice until a more appropriate and excellent index can be established.

Which anthropometric indices best predict metabolic disorders in Taiwan?

OBJECTIVES: The aim of this survey was to assess the association between the three simple anthropometric indices (body mass index [BMI], waist-to-hip ratio (WHR), and waist circumference [WC]) and various metabolic disorders, and to identify which indices can best predict metabolic disorders in Taiwan. METHODS: A cross-sectional hospital-based survey was carried out from January to December 2000. We retrospectively analyzed the medical records of all the patients receiving periodic health examination with scheduled items at China Medical University Hospital. Anthropometric indices, metabolic profiles, and abdominal sonography were performed. A total of 746 people aged 19 to 87 were recruited as subjects for this study. The t test, chi2 test, and stepwise multivariate logistic regression were used. RESULTS: The subjects included 44.5% women and 55.5% men, with a mean age of 50.74 +/- 12.68 years. After controlling for the other covariables, stepwise multivariate logistic regression showed considerable statistical significance between overall obesity and hypertension, hypertriglyceridemia, hyperuricemia, and fatty liver. There is also statistical significance between abdominal obesity and abnormal ratio of total cholesterol HDL (high-density lipoprotein), hyperuricemia, and fatty liver. None of the indices revealed any association with hyperglycemia, hypercholesterolemia, abnormal low-density lipoprotein, or abnormal HDL. CONCLUSIONS: BMI and WC can best predict some metabolic disorders. For practical reasons, the combined measurement of BMI and WC is the simple and inexpensive anthropometric index for primary health care settings in the routine physical examinations of adults. We hope this study can establish the background data for further investigation on the epidemiology of anthropometric indices in Taiwan.

Acute thoracic aortic dissection presenting as sore throat: report of a case.

Acute dissection of the aorta can be one of the most dramatic of cardiovascular emergencies. Its symptoms can occur abruptly and progress rapidly. Prompt recognition and appropriate intervention is crucial. However, not all aortic dissections present with classic symptoms of abrupt chest, back, or abdominal pain, and the diagnosis may be missed. Aortic dissection presenting as a sore throat is quite unusual. A 53-year-old man presented with sore throat as the early symptom of an acute thoracic aortic dissection. Unfortunately, the diagnosis was delayed, and the patient died. Given the high morbidity and mortality after delayed recognition or misdiagnosis, aortic dissection should be considered in the differential diagnosis of a patient presenting with sore throat and normal findings of neck and throat, even when there is no classic symptoms.

Retrospective analysis of inflammatory parameters in acute pyelonephritis.

OBJECTIVE: Different parameters were compared in children with acute pyelonephritis in order to facilitate the early detection of vesicoureteral reflux (VUR) in primary healthcare settings. MATERIAL AND METHODS: This was a cross-sectional, hospital-based study. A total of 149 children with confirmed acute pyelonephritis were retrospectively analyzed between January 1999 and December 2000. The primary factors studied were body temperature, C-reactive protein level, white blood cell count and neutrophil ratio. RESULTS: The study population comprised 82 males (55.0%) and 67 females (45.0%). The mean age of the patients was 2.7 +/- 3.9 years (age range 1 day to 18 years; 75% <3 years old). Of 123 patients who underwent voiding cystourethrography, 34 (27.6%) had VUR. When raised C-reactive protein, leukocytosis and raised neutrophil ratio occurred together, the specificity and positive predictive value for predicting VUR were obviously increased, but sensitivity was radically decreased. After controlling for the other covariates, multivariate logistic regression analysis showed that factors significantly related to VUR were age (odds ratio = 1.3, 95% confidence interval 1.02-1.67; p < 0.05) and raised neutrophil ratio (odds ratio = 4.2, 95% confidence interval 1.1-16.5; p < 0.05). CONCLUSIONS: Our findings emphasize that the prevalence of VUR in children with acute pyelonephritis is extremely high. If a raised neutrophil ratio is observed, the potential risk of VUR is significantly increased in patients with clinically suspected acute pyelonephritis. Hence, the neutrophil ratio is recommended as an excellent parameter for predicting VUR.

Clinical analysis of the related factors in acute appendicitis.

BACKGROUND: In order to determine reliable clues for early diagnosis of acute appendicitis, this study was conducted to examine the related factors in patients with clinically suspected acute appendicitis. METHODS: We retrospectively analyzed 282 patients with the clinical diagnosis of acute appendicitis at China Medical College Hospital in Taiwan from January to December 2000. To study the significant related factors of acute appendicitis, the t-test, chi-square analysis, and multivariate logistic regression analysis were used. RESULTS: There were 153 males (54.3 percent) and 129 females (45.7 percent). The mean age was 30.3+/-17.4 years (range 1 to 81). The diagnostic rate of acute appendicitis was 86.2 percent. If the combination of elevated C-reactive protein, leukocytosis and elevated neutrophil ratio was used, satisfactory specificity and positive predictive value were achieved in diagnosing acute appendicitis. After controlling for the other covariates, the multivariate logistic regression analysis showed that the significant related factors of acute appendicitis were male sex (odds ratio = 3.4; 95 percent confidence interval = 1.6 to 7.3; p <0.01) and elevated neutrophil ratio (odds ratio = 4.6; 95 percent confidence interval = 2.0 to 10.6; p <0.001). CONCLUSIONS: If an elevated neutrophil ratio was observed, the probability of acute appendicitis was increased in patients with clinically suspected acute appendicitis. Thus, neutrophil ratio appears to be a good parameter for diagnosis of acute appendicitis in primary healthcare settings.

Hyperuricaemia and its related factors in Taiwanese middle-aged adults.

This study used data collected in Chung-Hsing Village to evaluate the relationship between hyperuricaemia and cardiovascular risk factors inTaiwanese middle-aged adults in May 1998. All of the government employees working at theTaiwan Provincial Government in Chung-Hsing Village aged 40-64 years were candidates for this study. Only 708 volunteers underwent blood tests. To study the significant related factors of hyperuricaemia, the t-test, chi2 analysis and multivariate logistic regression were used. The results showed that the significant related factors of hyperuricaemia are sex, obesity, hypertriglyceridaemia and renal function impairment. Hyperuricaemia is more common in middle-aged men than in middle-aged women. It is important to determine serum uric acid values if obesity, hypertriglyceridaemia or renal function impairment are apparent.

Risk factors for gallstone disease in a hospital-based study.

BACKGROUND: We investigated the risk factors for gallstone disease in Taiwan. METHODS: We retrospectively analyzed medical records of patients receiving periodic health examination at China Medical College Hospital from January to December 2000. A detailed history, physical examination, biochemical measurements, and abdominal ultrasonography were done. RESULTS: The 602 men (58.6%) and 426 women (41.4%) had a mean age of 49.2 +/- 12.8 years (range, 18 to 87). The prevalence of gallstone disease was 7.8% in women and 6.5% in men. After controlling for other covariates, multivariate logistic regression analysis showed that with a reference group aged less than 40 years as a comparison, both men and women aged 65 or older were more likely to have gallstone disease. CONCLUSIONS: Age in both sexes and hepatitis C virus infection in women were found to be risk factors for gallstone disease in our study population.

Aortic dissection presenting as acute lower extremity ischemia: report of a case.

Although not common, acute leg ischemia is an important element in the clinical presentation of a patient with aortic dissection. This report describes a case of aortic dissection in which the main feature at presentation was acute right leg ischemia. The angiography showed right common iliac artery and external iliac artery occlusion. Diagnosis was made by clinical evaluation and angiography. Embolectomy was then attempted immediately but failed. Aortic dissection was highly suspected and confirmed by emergency computed tomography. Fortunately, the patient had good recovery. Aortic dissection is potentially lethal if misdiagnosed or if recognition is delayed. As such, aortic dissection should be considered in the differential diagnosis.

Epidemiology of fatty liver in a hospital-based study in Taiwan.

BACKGROUND: The aim of this study was to assess the epidemiology of fatty liver in Taiwan. METHODS: We retrospectively analyzed the medical records of all patients receiving health examinations at China Medical College Hospital from January through December 2000. A total of 1,012 subjects were included for analysis. Data were analyzed using the t test, chi-square analysis, and multivariate logistic regression. RESULTS: Our cohort was comprised of 41.8% women and 58.2% men; mean age was 49.2 years. The prevalence of fatty liver was 36.9% in all subjects, and prevalence was higher in men than in women. After controlling for other covariates, the multivariate logistic regression analysis showed that the significant factors related to fatty liver were male sex, obesity, hyperglycemia, hypertriglyceridemia, elevated glutamate pyruvate transaminase level, and hyperuricemia. Elevated glutamate oxaloacetate transaminase level was negatively associated with fatty liver. CONCLUSIONS: The prevalence of fatty liver is high in Taiwan. This study establishes background data for further investigation.