A Synonymous Genetic Alteration of LMX1B in a Family with Nail-Patella Syndrome

The gene responsible for nail-patella syndrome, LMX1B, has recently been identified on chromosome 9q. Here we present a patient with nail-patella syndrome and an autosomal dominant pattern of inheritance. A 17-year-old girl visited our clinic for the evaluation and treatment of proteinuria. She had dystrophic nails, palpable iliac horns, and hypoplastic patellae. Electron microscopy of a renal biopsy showed irregular thickening of the glomerular basement membrane. A family history over three generations revealed five affected family members. Genetic analysis found a change of TCG to TCC, resulting in a synonymous alteration at codon 219 in exon 4 of the LMX1B gene in two affected family members. The same alteration was not detected in an unaffected family member. This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B

Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase–mediated apoptosis of HeLa cells

We show that caspase-3 cleaves Cdc6 at D290/S and D442/G sites, producing p32-tCdc6 (truncated Cdc6) and p49-tCdc6, respectively, during etoposide- or tumor necrosis factor (TNF)-α–induced apoptosis. The expression of these tCdc6 proteins, p32- and p49-tCdc6, promotes etoposide-induced apoptosis. The expression of tCdc6 perturbs the loading of Mcm2 but not Orc2 onto chromatin and activates ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) kinase activities with kinetics similar to that of the phosphorylation of Chk1/2. The activation kinetics are consistent with elevated cellular levels of p53 and mitochondrial levels of Bax. The tCdc6-induced effects are all suppressed to control levels by expressing a Cdc6 mutant that cannot be cleaved by caspase-3 (Cdc6-UM). Cdc6-UM expression attenuates the TNF-α–induced activation of ATM and caspase-3 activities. When ATM or ATR is down-expressed by using the small interfering RNA technique, the TNF-α– or tCdc6-induced activation of caspase-3 activities is suppressed in the cells. These results suggest that tCdc6 proteins act as dominant-negative inhibitors of replication initiation and that they disrupt chromatin structure and/or induce DNA damage, leading to the activation of ATM/ATR kinase activation and p53–Bax-mediated apoptosis

Impact of Depression on Work Productivity and Its Improvement after Outpatient Treatment with Antidepressants

AbstractObjectiveDepressive disorders influence socioeconomic burden at both the individual and organizational levels. This study estimates the lost productive time (LPT) and its resulting cost among workers with major depressive disorder (MDD) compared with a comparison group. It also estimates the change in productivity after 8 weeks of outpatient psychiatric treatment with antidepressants.MethodsWorking patients diagnosed with MDD without other major physical or mental disorders were recruited (n = 102), along with age- and sex-matched healthy controls from the Seoul Metropolitan area (n = 91). The World Health Organization's Health and Work Performance Questionnaire and the Hamilton Rating Scale for Depression were utilized to measure productivity and severity of depression, respectively, at baseline and at 8 weeks of treatment.ResultsThe LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group. Workers with MDD averaged costs due to LPT at 33.4% of their average annual salary, whereas the comparison group averaged costs of 2.5% of annual salary. After 8 weeks of treatment, absenteeism and clinical symptoms of depression were significantly reduced and associated with significant improvement in self-rated job performance (31.8%) or cost savings of $7508 per employee per year.ConclusionsWe confirmed that significant productivity loss arises from MDD and that this loss can be reduced with psychiatric intervention after a time period as short as 8 weeks. Mental health professionals should work with employers to devise a cost-effective system to provide workers with accessible quality care

Cytoprotective Effect of Phloroglucinol on Oxidative Stress Induced Cell Damage via Catalase Activation

Abstract We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H 2 O 2 ), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H 2 O 2 induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H 2 O 2 induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway

Impact of Fatty Liver on Acute Pancreatitis Severity

Aim. Acute pancreatitis is typically a mild disease, but some patients develop severe courses. Fatty liver changes are seen in patients with acute pancreatitis, but its clinical significance has not been well-studied. We aimed to investigate the relationship between fatty liver and the severity of acute pancreatitis. Methods. Unenhanced CT images of patients with acute pancreatitis were retrospectively reviewed by a radiologist, and mean hepatic and splenic attenuation was measured in Hounsfield units (HU). Fatty liver was defined as mean hepatic/splenic HU<1. Results. Among 200 patients, fatty liver was found in 67 (33.5%) and nonfatty liver in 133 (66.5%). Compared with patients without fatty liver, the severity of pancreatitis and levels of serum C-reactive protein were higher in fatty liver patients. The prevalence of local complications, persistent organ failure, and mortality were also higher in patients with fatty liver. Even after adjusting for age, sex, body mass index, and cause of pancreatitis, fatty liver was significantly associated with moderately severe or severe acute pancreatitis. Conclusions. Fatty liver may play a prognostic role in acute pancreatitis. Fatty liver could be incorporated into future predictive scoring models

Miniature DC-DC Boost Converter for Driving Display Panel of Notebook Computer

This paper proposes a miniature DC-DC boost converter to drive the display panel of a notebook computer. To reduce the size of the circuit, the converter was designed to operate at a switching frequency of 1 MHz. The power conversion efficiency improved using a passive snubber circuit that consisted of one inductor, two capacitors, and two diodes; it reduced the switching losses by lowering the voltage stress of the switch and increased the voltage gain using charge pumping operations. An experimental converter was fabricated at 2.5 cm &times; 1 cm size using small components, and tested at input voltage 5 V &le; VIN &le; 17.5 V and output current 30 mA &le; IO &le; 150 mA. Compared to existing boost converters, the proposed converter had ~7.8% higher power conversion efficiency over the entire range of VIN and IO, only ~50% as much voltage stress of the switch and diodes, and a much lower switch temperature TSW = 49.5 &deg;C. These results indicate that the proposed converter is a strong candidate for driving the display panel of a notebook computer

High-Efficiency Asymmetric Forward-Flyback Converter for Wide Output Power Range

This paper proposes an asymmetric forward-flyback dc-dc converter that has high power-conversion efficiency ��e over a wide output power range. To solve the problem of ringing in the voltage of the rectifier diodes and the problem of duty loss in the conventional asymmetric half-bridge (AHB) converter, the proposed converter uses a voltage doubler structure with a forward inductor Lf in the second stage, instead of using the transformer leakage inductance, to control output current. Lf resonates with the capacitors in the voltage doubler to achieve a zero-voltage turn-on of switches and a zero-current turn-off of diodes for a wide output power range. The proposed converter could operate at a wider input voltage range than the other AHB converters. ��e was measured as 95.9% at output power Po = 100 W and as 90% at Po = 10 W, when the converter was operated at input voltage 390 V, output voltage 142 V, and switching frequency 100 kHz. ? 2016 IEEE.1133Nsciescopu

Off-Time Control of LLC Resonant Half-Bridge Converter to Prevent Audible Noise Generation Under a Light-Load Condition

This paper presents a control method that can prevent audible noise generation in an LLC resonant half-bridge dc-dc converter under a light-load condition, while achieving the same input voltage range and power-conversion efficiency eta(e) as the burst-control method that generates an audible noise. The proposed method reduces switching and conduction losses at light load by skipping several pairs of switch-control pulses, while varying the switching frequency less than the normal-control method does. This skip-control method enables the LLC resonant converter to have a large magnetizing inductance, and to have high eta(e) over a wide range of load variation. At an input voltage of 385 V, an output voltage of 24 V, and a resonant frequency of 180 kHz, the proposed method achieved eta(e) >= 85.46% for an output power range of 7.2-360 W; the highest eta(e) was 96.08% at P-o = 336 W.11Nsciescopu