Sleep quality according to chronotype in nurses working 8-hour shifts.

BACKGROUND: To date, studies have been focused on sleep disturbances of nurses working during night shifts. There is a lack of understanding regarding the sleep quality of nurses working in the rapid rotation system for each type of shift work. AIMS: To determine the relationship between chronotype and sleep quality according to shift type (i.e. day, evening and night shifts) in nurses working 8-hour rotating shifts. METHODS: A cross-sectional, descriptive study was conducted from two tertiary hospitals in South Korea from December 2021 to September 2022, including nurses working 8-hour rotating shifts (N = 74). They completed questionnaires to measure general, occupational and sleep-related characteristics, chronotype, insomnia severity and daytime sleepiness. Additionally, sleep parameters were collected from actigraphy and sleep diaries for 7 days. RESULTS: A total of 64% of nurses had an evening chronotype and 37% of nurses had an intermediate chronotype. Nurses had significantly less total sleep time and worsened sleep latency and efficiency during the day shift compared to other shift types. Compared to nurses with an intermediate chronotype, those with an evening chronotype had poorer sleep quality during day shift work. CONCLUSIONS: Strategies to enhance nurses' sleep quality during day shifts should consider a two-level approach: individual approaches, such as improving sleep hygiene, and administrative approaches, such as establishing a chronotype-based shift system for scheduling.

Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging.

The circadian clock is the biological mastermind governing orderly execution of bodily processes throughout the day. In recent years, an emerging topic of broad interest is clock-modulatory agents, including small molecules both of synthetic and natural origins, and their potential applications in disease models. Nobiletin is a naturally occurring flavonoid with the greatest abundance found in citrus peels. Extensive research has shown that Nobiletin is endowed with a wide range of biological activities, yet its mechanism of action remains unclear. We recently found through unbiased chemical screening that Nobiletin impinges on the clock machinery to activate temporal control of downstream processes within the cell and throughout the body. Using animal models of diseases and aging, we and others illustrate potent beneficial effects of Nobiletin on cellular energetics in both periphery and brain to promote healthy aging. Given its excellent safety profile, Nobiletin may represent a promising candidate molecule for development of nutraceutical and chronotherapeutic agents against chronic and age-related neurodegenerative diseases.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Influence of various levels of milk by-products in weaner diets on growth performance, blood urea nitrogen, diarrhea incidence, and pork quality of weaning to finishing pigs.

OBJECTIVE: This study was conducted to evaluate various levels of milk by-product in weaning pig diet on growth performance, blood profiles, carcass characteristics and economic performance for weaning to finishing pigs. METHODS: A total of 160 weaning pigs ([Yorkshire×Landrace]×Duroc), average 7.01±1.32 kg body weight (BW), were allotted to four treatments by BW and sex in 10 replications with 4 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with various levels of milk by-product (Phase 1: 0%, 10%, 20%, and 30%, Phase 2: 0%, 5%, 10%, and 15%, respectively). During weaning period (0 to 5 week), weaning pigs were fed experimental diets and all pigs were fed the same commercial feed during growing-finishing period (6 to 14 week). RESULTS: In the growth trial, BW, average daily gain (ADG), and average daily feed intake (ADFI) in the nursery period (5 weeks) increased as the milk by-product level in the diet increased (linear, p<0.05). Linear increases of pig BW with increasing the milk product levels were observed until late growing period (linear, p = 0.01). However, there were no significant differences in BW at the finishing periods, ADG, ADFI, and gain:feed ratio during the entire growing-finishing periods. The blood urea nitrogen concentration had no significant difference among dietary treatments. High inclusion level of milk by-product in weaner diet decreased crude protein (quadratic, p = 0.05) and crude ash (Linear, p = 0.05) of Longissimus muscle. In addition, cooking loss and water holding capacity increased with increasing milk product levels in the weaner diets (linear, p<0.01; p = 0.05). High milk by-product treatment had higher feed cost per weight gain compared to non-milk by-products treatment (linear, p = 0.01). CONCLUSION: Supplementation of 10% to 5% milk by-products in weaning pig diet had results equivalent to the 30% to 15% milk treatment and 0% milk by-product supplementation in the diet had no negative influence on growth performance of finishing pigs.

Adult chronic myelomonocytic leukemia with trisomy 11: a case report.

Chronic myelomonocytic leukemia (cmml) is an indolent disease in the category of myelodysplastic and myeloproliferative neoplasms, which can often evolve into acute leukemic neoplasms. Although cytogenetic abnormalities such as trisomy 8 or absence of chromosome Y are well known, few reports about cmml with trisomy 11 have been published. Here, we report a case of cmml with trisomy 11 as the sole chromosomal abnormality, resulting in a very poor outcome. Based on a bone marrow specimen, cmml-1 with trisomy 11 was diagnosed in a 79-year-old man presenting with anemia and atypical peripheral blood cells. Because of the patient's age, he was followed without receiving anticancer treatment. Two months after his diagnosis, the patient's leucocytosis and anemia rapidly worsened, with increasing numbers of immature peripheral cells, which was strongly suggestive of leukemic transformation. Because of acute kidney injury superimposed on chronic kidney disease that led to poor performance status, cytotoxic chemotherapy was not considered feasible, and the patient was transferred to a hospice care facility.

Combinations of eight key mutations in the X/preC region and genomic activity of hepatitis B virus are associated with hepatocellular carcinoma.

Accumulation of eight key mutations located in the X/preC regions of the hepatitis B virus (HBV) genome (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A and G1899A) is a risk marker for the development of hepatocellular carcinoma (HCC). In this study, we analysed the 8 key mutations in 442 serum samples collected from 310 non-HCC and 132 HCC patients to identify the combinations linked to HCC. After the patients were stratified according to the age groups and mutation combinations, clinical parameters were compared between the HCC and the non-HCC groups. Analyses were focused on patient ≥40 years of age infected by HBV genotype C with A1762T and G1764A mutations in the basal core promoter region (BCP double mutation). In patients with ≥6 mutations, the combination of [G1613A + C1653T + A1846T + G1896A] mutations was closely linked to HCC, whereas no specific single or double mutation combination was associated with HCC. In patients with ≤5 mutations, HBeAg and HBV DNA serum titres were lower in the HCC group than those in the non-HCC group. Unlike the number of mutations, no specific combination correlated with advanced clinical stage in HCC. Of the BCP double mutation-based HBV mutant types, combinations of ≥6 mutations that include G1613A + C1653T + A1846T + G1896A, and combinations of ≤5 mutations with reduced HBeAg production, may be more specific indicators of HCC risk than only the number of mutations or any specific combination(s).

Comparability and utility of body composition measurement vs. anthropometric measurement for assessing obesity related health risks in Korean men.

BACKGROUND: Obesity is commonly assessed by body mass index (BMI) of which limitations come from an inability to distinguish body fat mass from lean mass. Several anthropometric measurements, including BMI, waist circumference, waist-to-height ratio and waist-to-hip ratio have been used to predict metabolic syndrome. The purpose of this study was to evaluate the utility of FMI or BF% combined with previous known anthropometric indices to assess the risk of metabolic syndrome in clinical practice. METHODS: In 5534 men visiting a hospital for health check-ups, blood tests, anthropometric measurements and body composition analysis using BIA were performed. Logistic regression analysis was performed to compare the odds ratios for metabolic syndrome and each component of metabolic syndrome among BMI, waist-to-height ratio, waist-to-hip ratio, FMI and BF%. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for metabolic syndrome was compared between several measurements. The net reclassification improvement with integrated discrimination improvement was used for assessing value of body composition measurement. RESULTS: The adjusted odds ratios of metabolic syndrome was 1.80 (95% CI, 1.71-1.89) for FMI and 1.15 (95% CI, 1.13-1.17) for BF%. Odds ratio of each metabolic component was highest for FMI among several anthropometric and body composition measurements. AUCs using the ROC curve for metabolic syndrome was highest for waist-to-height ratio, 0.823 (95% CI, 0.808-0.837) by National Cholesterol Education Program criteria. FMI caused a mild increase in integrated discrimination improvement when combined with waist-to-height ratio. CONCLUSIONS: Waist-to-height ratio seems to be the best screening tool for evaluating metabolic syndrome in Korean men, and adding FMI could result in a modest increase in integrated discrimination improvement.

Uterine angiomyolipoma with metastasis in a woman with tuberous sclerosis: a case report.

Extrarenal angiomyolipomas (AMLs) have been reported at various anatomical sites such as the liver, spleen, abdominal wall, retroperitoneum, oral cavity, penis, spermatic cord, skin, and lung but are infrequently described in gynecological regions. However, only a few cases of extrarenal AML in the uterus have been reported. The authors describe a case of uterine AML in a 41-year-old woman with evidence of tuberous sclerosis. Initial diagnosis concluded with myoma based on the interpretation of imaging and other pathological parameters. However, after successful laparoscopic surgical staging, AML was diagnosed. To date, the feasibility of laparoscopic surgical diagnosis and the risks associated with this technique have not been reported. The authors briefly review the implementation of laparoscopic surgical staging to diagnose uterine AML.

Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea.

OBJECTIVE: Previous studies have comprehensively investigated the prevalence and various potential risk factors for delirium among patients with advanced cancer admitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehensive association between delirium and various risk factors among patients with advanced cancer in an acute palliative care setting using a patient-based multicenter registry cohort. PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclusion criteria. There were 127 out of 2,124 patients (prevalence, 6.0%; 95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793; 95% CI, 1.246 to 2.581), male sex (OR, 1.675; 95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019; 95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566; 95% CI, 1.176 to 10.810), underweight (OR, 1.826; 95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942; 95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497; 95% CI, 6.920 to 22.568), and mental illness (OR, 2.333; 95% CI, 1.251 to 4.352). CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was associated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, underweight, current use of opioid medication, and a history of delirium and mental illness. Our findings suggest physicians should pay attention to delirium in patients with advanced cancer admitted to the APCU with the above risk factors.

Age- and weight-adjusted warfarin initiation nomogram for ischaemic stroke patients.

OBJECTIVES: Specific guidelines for initial dosing of warfarin in ischaemic stroke patients have not been developed. Therefore, we have developed an age- and weight-adjusted warfarin initiation nomogram (AW-WIN) for ischaemic stroke patients and then evaluated the efficacy and safety of AW-WIN compared with physician-determined warfarin dosing (PDWD). METHODS: The age- and weight-adjusted warfarin initiation nomogram was administered to 104 acute ischaemic stroke patients between January 2008 and February 2009. A historical control group (PDWD) of 96 patients was selected from comparable patients who were discharged with warfarin during the previous year. Time-to-therapeutic international normalized ratios (INRs) and the incidence of excessive anticoagulation were compared in the AW-WIN and PDWD groups. RESULTS: The general characteristics, risk factors, and stroke mechanism of the AW-WIN and PDWD groups did not differ significantly. The mean time to INR ≥ 2.0 was significantly shorter in the AW-WIN than in the PDWD group (4.9 ± 0.7 vs. 6.2 ± 0.8 days, P = 0.0008). After adjustment for potential confounding variables, the AW-WIN group reached target INR faster than the PDWD group (hazard ratio, 1.76; 95% confidence interval, 1.26-2.45; P = 0.001). The time-to-therapeutic INR ≥1.7 was shorter (P = 0.0002), the proportion of patients with therapeutic INR (2-3) at 5 days was higher (P = 0.002), and the rate of excessive anticoagulation of ≥3.5 INR during hospitalization was lower (P = 0.024) in the AW-WIN than in the PDWD group. CONCLUSIONS: AW-WIN reduces the time to target INR and the risk of excessive anticoagulation. AW-WIN may be an efficient and safe method of anticoagulation during the acute phase of ischaemic stroke.

The role of serum adipocyte fatty acid-binding protein on the development of metabolic syndrome is independent of pro-inflammatory cytokines.

BACKGROUND AND AIM: Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults. METHODS AND RESULTS: A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P<0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P<0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P<0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P<0.001) CONCLUSION: Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.

The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non-collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non-syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon-intron boundaries of the DSPP gene based on the candidate gene approach. Direct sequencing of PCR products and allele-specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.

Nano-scaled Pt/Ag/Ni/Au contacts on p-type GaN for low contact resistance and high reflectivity.

We synthesized the vertical-structured LED (VLED) using nano-scaled Pt between p-type GaN and Ag-based reflector. The metallization scheme on p-type GaN for high reflectance and low was the nano-scaled Pt/Ag/Ni/Au. Nano-scaled Pt (5 A) on Ag/Ni/Au exhibited reasonably high reflectance of 86.2% at the wavelength of 460 nm due to high transmittance of light through nano-scaled Pt (5 A) onto Ag layer. Ohmic behavior of contact metal, Pt/Ag/Ni/Au, to p-type GaN was achieved using surface treatments of p-type GaN prior to the deposition of contact metals and the specific contact resistance was observed with decreasing Pt thickness of 5 A, resulting in 1.5 x 10(-4) ohms cm2. Forward voltages of Pt (5 A)/Ag/Ni contact to p-type GaN showed 4.19 V with the current injection of 350 mA. Output voltages with various thickness of Pt showed the highest value at the smallest thickness of Pt due to its high transmittance of light onto Ag, leading to high reflectance. Our results propose that nano-scaled Pt/Ag/Ni could act as a promising contact metal to p-type GaN for improving the performance of VLEDs.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance.

Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.

Weight gain within the normal weight range predicts ultrasonographically detected fatty liver in healthy Korean men.

OBJECTIVES: We performed a prospective study to determine whether weight gain predicts future ultrasonographically detected fatty liver (USFL) in a lean adult population. METHODS: Among 15,347 Korean male workers, aged 30-59 years, who participated in a health check-up programme in 2002, a USFL-free cohort of 4246 non-diabetic men was followed until September 2007. Alcohol consumption was assessed by a questionnaire. Weight change for each subject was calculated as the difference between baseline and subsequent measurements. Biochemical tests for liver and metabolic function were done. The primary outcome was ultrasound-diagnosed fatty liver. A standard Cox proportional hazards model and time-dependent Cox model were performed. RESULTS: During 16,829.7 person-years of follow-up, 622 participants developed USFL. After adjusting for age, the period from visit 1 to visit 2, BMI, HDL-C, triglyceride, uric acid, alanine aminotransferase, and HOMA-IR, the risk for USFL increased with increasing quartiles of weight change (p for trend <0.001). This association remained significant when weight change and covariates, except age and the period from visit 1 to visit 2, were modelled as time-dependent variables. Subjects in the fourth quartile (weight gain > or =2.3 kg) were at significantly elevated risk for USFL (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.01 to 1.58). These associations did not change, even in normal weight men with a baseline BMI between 18.5 and 22.9 kg/m(2) (n = 2186). CONCLUSION: Weight gain per se appears to increase the risk for developing USFL. Thus, avoiding weight gain, even among lean adult individuals, can be helpful in preventing this disease.

Age and body weight adjusted warfarin initiation program for ischaemic stroke patients.

BACKGROUND: Despite its proven effect, anticoagulation is not recommended to the acute ischaemic stroke due to the risk of bleeding complications. The purpose of this study is development of individualized warfarin initiation program for acute or subacute stroke patients. METHODS: Among stroke patients who regularly visited out-patient clinics, we included patients who have continuously taken the same dose of warfarin as the prothrombin time remained at target International Nomarlized Ratio (INR). We assessed potential variables that affect the maintenance dose of warfarin. Using these variables, we developed an individualized warfarin initiation program. RESULTS: The median warfarin maintenance dose (interquartile range) in the 321 included patients was 4 (3-5) mg per day. Age (adjusted R(2) = 0.221, P < 0.001) and body weight (added to age, adjusted R(2) = 0.238, P = 0.008) were significant predicting factors of the dose. We classified the maintenance doses into high (HG), standard, and low group (LG) based on the distribution of maintenance doses. Decision tree analysis categorized younger (or=55 kg) patients into HG, and very old (>or=80 years old) or low body weight (<55 kg among those >56 years old) patients into LG. We recommend 7 mg of warfarin as a standard initial dose, but 10 mg was recommended for HG patients and 5 mg for LG. CONCLUSION: We expect that this individualized program may reduce the time to target INR without excessive anticoagulation. Further prospective studies are needed to reveal the efficacy and safety of applying this program for acute stroke patients.

Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist.

Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15 synthetic peptides spanning approximately 80% of chromogranin A, one (bovine chromogranin A344-364 [RSMRLSFRARGYGFRGPGLQL], or catestatin) was a potent, dose-dependent (IC50 approximately 200 nM), reversible secretory inhibitor on pheochromocytoma and adrenal chromaffin cells, as well as noradrenergic neurites. An antibody directed against this peptide blocked the inhibitory effect of chromogranin A proteolytic fragments on nicotinic-stimulated catecholamine secretion. This region of chromogranin A is extensively processed within chromaffin vesicles in vivo. The inhibitory effect was specific for nicotinic cholinergic stimulation of catecholamine release, and was shared by this chromogranin A region from several species. Nicotinic cationic (Na+, Ca2+) signal transduction was specifically disrupted by catestatin. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. This small domain within chromogranin A may contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release from chromaffin cells and neurons.

A study on setting of the fatigue limit of temporary dental implants.

A temporary dental implant is a medical device which is temporarily used to support a prosthesis such as an artificial tooth used for restoring patient's masticatory function during implant treatment. It is implanted in the oral cavity to substitute for the role of tooth. Due to the aging and westernization of current Korean society, the number of tooth extraction and implantation procedures is increasing, leading to an increase in the use and development of temporary dental implants. Because an implant performs a masticatory function in place of a tooth, a dynamic load is repeatedly put on the implant. Thus, the fatigue of implants is reported to be the most common causes of the fracture thereof. According to the investigation and analysis of the current domestic and international standards, the standard for fatigue of implant fixtures is not separately specified. Although a test method for measuring the fatigue is suggested in an ISO standard, it is a standard for permanent dental implants. Most of the test standards for Korean manufacturers and importers apply 250 N or more based on the guidance for the safety and performance evaluation of dental implants. Therefore, this study is intended to figure out the fatigue standard which can be applied to temporary dental implants when measuring the fatigue according to the test method suggested in the permanent dental implant standard. The results determined that suitable fatigue standards of temporary dental implants should be provided by each manufacturer rather than applying 250 N. This study will be useful for the establishment of the fatigue standards and fatigue test methods of the manufacturers and importers of temporary dental implants.

Enhanced Phosphorylation of Bax and Its Translocation into Mitochondria in the Brains of Individuals Affiliated with Alzheimer's Disease.

BACKGROUND: Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer's disease (AD), the detailed mechanism of cell death in AD is still poorly understood. METHOD: We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation. RESULTS: Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress. CONCLUSION: The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.