Do adolescents use choice to learn about their preferences? Development of value refinement and its associations with depressive symptoms in adolescence.

Independent decision making requires forming stable estimates of one's preferences. We assessed whether adolescents learn about their preferences through choice deliberation and whether depressive symptoms disrupt this process. Adolescents aged 11-18 (N = 214; participated 2021-22; Female: 53.9%; White/Black/Asian/Mixed/Arab or Latin American: 26/21/19/9/8%) rated multiple activities, chose between pairs of activities and re-rated those activities. As expected, overall, participants uprated chosen and downrated unchosen activities (dz = .20). This value refinement through choice was not evident in younger participants but emerged across adolescence. Contrary to our predictions, depressive symptoms were associated with greater value refinement. Despite this, more depressed adolescents reported lower value certainty and choice confidence. The cognitive processes through which choice deliberation shapes preference develop over adolescence, and are disrupted in depression.

Effect of supplementation of cryoprotectant solution with hydroxypropyl cellulose for vitrification of bovine oocytes.

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.

Immune response to hepatitis B vaccination and factors associated with poor immune response among healthcare workers.

BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem, and healthcare workers (HCWs) are at high risk for HBV infection. Current guidelines strongly recommend immunization and screening for high-risk groups. AIMS: We evaluated immunization and screening for HBV vaccination, assessed post-vaccination immune status of HCW's and characterized potential risk factors associated with poor immune response. MATERIALS AND METHODS: From January 2010 to December 2018, we retrospectively analyzed comprehensive health checkup data for a total of 303 HCWs who received an HBV vaccination. After vaccination, HBV surface antibody (anti-HBs) titers were collected and the distribution of immune response types was determined. Risk factors for poor immune responses were identified using logistic regression. RESULTS: A total of 213 HCWs were analyzed after exclusion based on the exclusion criteria. In total, 28 (13.2%) HCWs had anti-HBs titers <100 mIU/mL (hyporesponsive/nonresponsive groups), and 185 (86.8%) had anti-HBs titers ≥100 mIU/mL (hyperresponsive group). Follow-up observations found that 75% (21/28) of the hyporesponsive/nonresponsive groups did not have increased anti-HBs titers or did not maintain an increased response. A multivariate analysis showed that HBV antibody titers at the time of employment were a significant risk factor (OR, 6.12; CI, 1.34-27.93; P = 0.019). CONCLUSIONS: More attention should be paid to groups that are hyporesponsive/nonresponsive after vaccination and to those with low anti-HBs titers at the beginning of employment. HCWs can be further protected from HBV if their results are discussed at postvaccination follow-ups.

Antibacterial action of lactoferricin B like peptide against Escherichia coli: reactive oxygen species-induced apoptosis-like death.

AIMS: Emergence and rapid dissemination of antibiotic-resistant bacteria is becoming a severe problem to public health. The search for antimicrobial substitutes for antibiotics is necessary. Lactoferricin B like peptide (LBLP) is a 23-mer antimicrobial peptide (AMP), derived from the big centipede Scolopendra subspinipes mutilans. Although its antifungal effect and its mechanism have been reported, the antibacterial activity has not yet been elucidated. METHOD AND RESULTS: In this study, we investigated antibacterial activity of LBLP and its mode of action. LBLP showed potent antibacterial effect against pathogenic bacteria Escherichia coli and did not show haemolytic activity against human erythrocyte. The general antimicrobial mechanism of AMP is to disrupt the cell membrane, however, LBLP exerted its antibacterial activity by causing apoptosis-like death through reactive oxygen species (ROS) generation. LBLP-treated E. coli cells exhibited hallmarks of apoptosis, such as membrane depolarization, DNA fragmentation, caspase-like protein activation and phosphatidylserine exposure. These apoptotic features were attenuated by pretreatment of NAC, a representative ROS scavenger. CONCLUSIONS: These results demonstrate that LBLP exerted its antibacterial activity by generating ROS and inducing apoptosis-like death in E. coli. LBLP is not membrane destructive per se, but essentially a metabolic inhibitor. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactoferricin B like peptide is potential candidate to replace conventional antibiotics that are less effective because of its unique properties.

Synergistic antibacterial activity of gold nanoparticles caused by apoptosis-like death.

AIMS: Metal nanoparticles are promising materials for the management of infectious diseases as known to have various antimicrobial activities in pathogenic micro-organisms. Among them, gold nanoparticles (AuNPs) are used in a wide range of fields such as photodynamic therapy, molecular diagnostics and drug delivery because of their unique physicochemical properties. However, little is known about the synergistic antibacterial activity and mechanism of AuNPs on pathogenic bacteria. METHODS AND RESULTS: Combinations of AuNPs and cefotaxime and ciprofloxacin showed synergistic interaction against all Salmonella species, however the combination with kanamycin exhibited no interaction. We determined that AuNPs and in combinations with antibiotics exert its antibacterial effect through bacterial apoptosis-like death. AuNPs caused collapse of intracellular divalent cation homeostasis, and conventional antibiotics caused accumulation of reactive oxygen species, which induced apoptotic hallmarks such as membrane depolarization, caspase-like protein activation, cell filamentation and phosphatidylserine externalization. CONCLUSIONS: The cation homeostasis disruption by AuNPs and the accumulation of reactive oxygen species by conventional antibiotics synergistically affected bacterial cell death and induced apoptosis-like death in Salmonella cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The synergistic activity between AuNPs and antibiotics propose that the AuNPs are a potential antibacterial agent and adjuvant for antimicrobial chemotherapy.

Randomized clinical trial of the effect of gum chewing on postoperative ileus and inflammation in colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery that delays recovery and increases length of hospital stay. Gum chewing may reduce POI and therefore enhance recovery after surgery. The aim of the study was to evaluate the effect of gum chewing on POI, length of hospital stay and inflammatory parameters. METHODS: Patients undergoing elective colorectal surgery in one of two centres were randomized to either chewing gum or a dermal patch (control). Chewing gum was started before surgery and stopped when oral intake was resumed. Primary endpoints were POI and length of stay. Secondary endpoints were systemic and local inflammation, and surgical complications. Gastric emptying was measured by ultrasonography. Soluble tumour necrosis factor receptor 1 (TNFRSF1A) and interleukin (IL) 8 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Between May 2009 and September 2012, 120 patients were randomized to chewing gum (58) or dermal patch (control group; 62). Mean(s.d.) length of hospital stay was shorter in the chewing gum group than in controls, but this difference was not significant: 9·5(4·9) versus 14·0(14·5) days respectively. Some 14 (27 per cent) of 52 analysed patients allocated to chewing gum developed POI compared with 29 (48 per cent) of 60 patients in the control group (P = 0·020). More patients in the chewing gum group first defaecated within 4 days of surgery (85 versus 57 per cent; P = 0·006) and passed first flatus within 48 h (65 versus 50 per cent; P = 0·044). The decrease in antral area measured by ultrasonography following a standard meal was significantly greater among patients who chewed gum: median 25 (range -36 to 54) per cent compared with 10 (range -152 to 54) per cent in controls (P = 0·004). Levels of IL-8 (133 versus 288 pg/ml; P = 0·045) and TNFRSF1A (0·74 versus 0·92 ng/ml; P = 0·043) were lower among patients in the chewing gum group. Fewer patients in this group developed a grade IIIb complication (2 of 58 versus 10 of 62; P = 0·031). CONCLUSION: Gum chewing is a safe and simple treatment to reduce POI, and is associated with a reduction in systemic inflammatory markers and complications. REGISTRATION NUMBER: NTR2867 (http://www.trialregister.nl).

Tuberculosis before hematopoietic stem cell transplantation in patients with hematologic diseases: report of a single-center experience.

BACKGROUND: Few reports discuss the optimal management of patients diagnosed with tuberculosis (TB) before scheduled stem cell transplantation (SCT), who then proceed with transplantation. METHODS: We found 13 patients with TB before SCT (proven, n = 9; probable, n = 3; possible, n = 1) in the medical records of our institution. RESULTS: Most of the patients had pulmonary TB (n = 8; disseminated, n = 2; extrapulmonary, n = 3). Eight of 9 patients with proven disease had SCT after at least 100 days of anti-tuberculous medication, ranging from 103 to 450 days. None of those patients suffered TB-related events after SCT. However, 1 patient with proven pulmonary TB who underwent SCT after only 40 days of anti-tuberculous therapy subsequently died of TB meningitis. Patients with possible and probable disease had their transplants after 6-176 days of anti-tuberculous medication, and all were alive at the time of analysis. The entire duration of anti-tuberculous medication was 12 months in most cases. With a follow-up duration ranging from 0.7 to 87.5 months, 4 patients died, but TB was the cause of death in only 1 case. CONCLUSION: In conclusion, for proven cases of TB, SCT after >100 days of anti-tuberculous medication is probably feasible and safe, in terms of TB control, in patients with various hematologic diseases.

Identification of a novel antimicrobial peptide, scolopendin 1, derived from centipede Scolopendra subspinipes mutilans and its antifungal mechanism.

In this study, a novel antimicrobial peptide, scolopendin 1, was identified from adult centipedes, Scolopendra subspinipes mutilans using RNA sequencing. Scolopendin 1 exerted an antimicrobial activity without inducing haemolysis of human erythrocytes. In order to understand the antifungal mechanism, a reactive oxygen species (ROS) assay was performed, which indicated that scolopendin 1 induced ROS accumulation in Candida albicans. Evaluation of fungal viability using N-acetyl cysteine, a ROS scavenger, suggested that ROS are a major factor in scolopendin 1-induced fungal cell death. Co-staining of annexin V-fluorescein isothiocyanate (FITC) and propidium iodide, and TUNEL and 4',6-diamidino-2-phenylindole (DAPI) assays confirmed that ROS-induced fungal cell death is associated with apoptosis. To further investigate the mechanism that facilitates the progression of apoptosis, changes in intracellular Ca(2+) concentration and mitochondrial dysfunction were examined. Ca(2+) , a signalling molecule in the apoptotic pathway, was increased in the cytosol and mitochondria, and ROS accumulation triggered mitochondrial depolarization and the release of cytochrome c, a pro-apoptotic factor, from the mitochondria to the cytosol. Finally, the released cytochrome c activated intracellular caspase. The present study suggests that scolopendin 1 could emerge as a model molecule that targets the apoptotic pathway and provides a novel remedy.

Hibicuslide C-induced cell death in Candida albicans involves apoptosis mechanism.

AIM: To provide the observation that hibicuslide C-induced cell death in yeast Candida albicans involves apoptosis mechanism. METHODS AND RESULTS: Hibicuslide C was isolated from Abutilon theophrasti by column chromatography. In reactive oxygen species (ROS) assay, C. albicans treated with hibicuslide C showed increase in ROS, and its accumulation induced fungal cell death. In particular, hydroxyl radicals were a large part of the ROS. Mitochondrial dysfunction including mitochondrial depolarization and release of cytochrome c, which is a pro-apoptotic factor, was detected by JC-1 assay and Western blot. CaspACE FITC-VAD-FMK staining using caspase inhibitor showed metacaspase activation. Also, the increase in intracellular Ca(2+), which is a signal molecule of apoptosis, was detected by Fura-2AM and Rhod-2AM assays. Finally, annexin V-FITC and PI double staining and TUNEL assay confirmed that hibicuslide C induces early apoptosis followed by secondary necrosis in C. albicans. CONCLUSIONS: Hibicuslide C exerts antifungal activity against C. albicans through new mechanism inducing apoptosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Candida albicans is the common cause of nosocomial infections with high mortality. Our findings provide that hibicuslide C can be a model molecule that induces apoptosis in C. albicans.

Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia.

PURPOSE: This retrospective study was performed in order to investigate the clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia (VSB) in febrile neutropenic children in the context of the increase in incidence and antibiotic resistance of VSB. METHODS: We conducted this study among neutropenic children with underlying hematology/oncology diseases who were diagnosed with VSB at a single institution from April 2009 to June 2012. Clinical and laboratory characteristics of the children as well as antibiotic susceptibility of the causative viridans streptococci were evaluated. RESULTS: Fifty-seven episodes of VSB were diagnosed in 50 children. Severe complications occurred in four children (7.0%), and a death of one child (1.8%) was attributable to VSB. Acute myeloid leukemia was the most common underlying disease (70.2% of all cases), and 71.9% of all cases received chemotherapy including high-dose cytarabine. VSB occurred at a median of 13 days (range 8-21 days) after the beginning of chemotherapy, and fever lasted for a median of 4 days (range 1-21 days). The C-reactive protein level significantly increased within a week after the occurrence of VSB (p < 0.001) and the maximum C-reactive protein level showed a positive correlation with fever duration (r = 0.362, p = 0.007). Second blood cultures were done before the use of glycopeptides in 33 children, and negative results were observed in 30 children (90.9%). Susceptibilities to cefotaxime, cefepime, and vancomycin were 58.9, 69.1, and 100%, respectively. CONCLUSIONS: Severe complications of VSB in neutropenic febrile children were rare. We suggest glycopeptide use according to the results of blood culture and antibiotic susceptibility tests based on the susceptibility to cefepime and the microbiologic response to empirical antibiotic treatment not including glycopeptides in this study.

Effect of laser-induced temperature field on the characteristics of laser-sintered silver nanoparticle ink.

Laser sintering of metal nanoparticles is a key technology for high-performance printed electronics fabricated on heat-sensitive substrates such as glass or plastic. Although laser-sintered electronic devices have been successfully fabricated, the role of the induced temperature field in the laser sintering process has not been reported thus far. In this work, the effect of temperature on the laser sintering process is described for the first time using a two-dimensional transient heat conduction equation for inkjet-printed silver nanoparticle ink. The in situ electrical resistance was measured to estimate the transient thermal conductivity and hence the temperature of the sintered ink during the laser sintering process. To verify the estimated laser sintering temperature, the morphology of furnace-sintered silver nanoparticle ink was compared with that of laser-sintered ink. The electrical characteristics and surface morphology of laser-sintered ink are found to be related to the process temperature.

Infectious complications following allogeneic stem cell transplantation: reduced-intensity vs. myeloablative conditioning regimens.

BACKGROUND: In allogeneic stem cell transplantation (allo-SCT), reduced-intensity conditioning (RIC) is known for producing less regimen-related toxicity. However, whether or not RIC reduces the risk for infection and infection-related mortality (IRM) remains controversial. METHODS: We retrospectively analyzed infectious episodes and IRMs after allo-SCTs by time period and by the intensity of the conditioning regimen (RIC [n = 81] vs. myeloablative conditioning, MAC [n = 150]). RESULTS: The cumulative incidence of any kind of infection was lower in the RIC group through the entire period (72% vs. 87%; P = 0.007). The onset of infections was deferred in the RIC group as compared with the MAC group (P = 0.012). Bacteremia occurred less frequently in the RIC group through the entire period (5% vs. 14%; P = 0.044). However, the incidences of cytomegalovirus reactivation and disease, herpes zoster, virus-associated hemorrhagic cystitis, and invasive fungal infection were not different between the two groups. Furthermore, there was no difference in relapse-free survival and IRM between the two conditioning regimens. CONCLUSION: Careful monitoring and appropriate preventive/therapeutic strategies for infectious complications, comparable to those for allo-SCT recipients with MAC, should also be applied to those with RIC, especially after engraftment.

ATPase switches controlling DNA replication initiation.

Proteins that bind and hydrolyze ATP are frequently involved in the early steps of DNA replication. Recent studies of Saccharomyces cerevisiae suggest that two members of the AAA+ ATPase family--the origin recognition complex and Cdc6p--have separable roles for ATP binding and ATP hydrolysis during eukaryotic DNA replication. Intriguingly, the proposed regulation of these eukaryotic replication proteins by ATP has functional similarities to the ATP-dependent control of the DnaA and DnaC initiation factors from Escherichia coli. Comparison of the ATP regulation of these factors suggests that ATP binding and hydrolysis acts as a molecular switch that couples key events during initiation of replication. This switch results in a significant change in protein function.

Endoscopic submucosal resection of esophageal subepithelial lesions using band ligation.

Subepithelial lesions (SELs) are occasionally found in the esophagus during upper endoscopy. Sometimes endoscopic resection is needed for accurate diagnosis or in the rare cases of malignant transformation of SELs. In this case series, we evaluated the usefulness of endoscopic submucosal resection with a ligation device (ESMR-L) in esophageal SELs. Twenty-three patients with 25 esophageal SELs that were no larger than 13 mm and were localized within the muscularis mucosae or submucosa were enrolled. ESMR-L was successfully performed in all 25 SELs. The en bloc resection rate was 100% (25/25), and histologically complete resection was achieved in 24 lesions (24/25, 96%). After resection of the lesion by snare, minor immediate bleeding occurred in four cases, but there was no delayed bleeding or perforation.

Infectious complications associated with alemtuzumab use for allogeneic hematopoietic stem cell transplantation: comparison with anti-thymocyte globulin.

OBJECTIVES: To evaluate the incidence of infectious complications after receiving alemtuzumab as part of a conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in Korean patients. METHODS: From November 2004 to January 2006, 12 patients who received alemtuzumab-based conditioning regimens for allogeneic HSCT were evaluated retrospectively until death or until the end of the follow-up in July 2007; they were compared with 18 patients who received rabbit anti-thymocyte globulin (ATG)-containing conditioning regimens from January 2002 to January 2006. RESULTS: Post-engraftment infections occurred more frequently in the alemtuzumab recipients than in the ATG recipients; the mean number of infections, excluding cytomegalovirus (CMV) infections, per patient during the follow-up period was 2.6+/-1.4 vs. 1.0+/-0.8 (P=0.003), respectively. Although there was no statistical difference in the cumulative incidence of CMV infection between the 2 groups (91.7% vs. 55.6%, P=0.381), the alemtuzumab recipients had a higher incidence of CMV diseases (41.6% vs. 0%, P=0.0006) and a higher recurrence rate of CMV infection (90.0% vs. 27.3%, P=0.008) than did the ATG recipients, irrespective of the dose of alemtuzumab. Hemorrhagic cystitis (HC) (66.7% vs. 16.7%, P=0.009) and BK virus-associated HC (41.7% vs. 5.6%, P=0.026) developed more frequently in the alemtuzumab recipients. The all-cause mortality rate was not significantly different between the alemtuzumab and the ATG recipients (75% vs. 55.6%, P=0.28). CONCLUSION: Alemtuzumab recipients had a high incidence of CMV disease as well as BK virus-associated HC compared with the ATG recipients. The dose of alemtuzumab should be tailored to patients' risk; in addition, the implementation of the appropriate prophylaxis for CMV and early detection strategies for BK virus are recommended.

Population pharmacokinetics of intravenous itraconazole in patients with persistent neutropenic fever.

PURPOSE: Empirical use of intravenous (IV) itraconazole (ITZ) for febrile neutropenic patients has recently been introduced in Korea. This study was designed to investigate the population pharmacokinetics (PK) of IV-ITZ. METHODS: Sparse PK data were collected from febrile neutropenic patients undergoing empirical ITZ therapy at 200 mg/day after loading doses. NONMEM (Version. 5.1.1) was used to estimate population PK parameters. RESULTS: Forty-two patients were enrolled in the study. Mean population CL and V of IV-ITZ were 10 L/h and 1050 L, respectively. Body weight was the only contributing covariate of CL. The median simulated trough concentration of ITZ after 10 days was predicted to be about 700 ng/mL. CONCLUSIONS: In this study, we explored the population PK profile of ITZ given in IV formulation. We found that the current dosage regimen of IV-ITZ (200 mg/day) was appropriate to obtain therapeutic trough concentrations for neutropenic patients in Korea.

Fluoroquinolones versus trimethoprim-sulfamethoxazole for the treatment of Stenotrophomonas maltophilia infections: a systematic review and meta-analysis.

BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.

A report of the Malaysian dialysis registry of the National Renal Registry, Malaysia.

The Malaysian National Renal Registry was set up in 1992 to collect data for patients on renal replacement therapy (RRT). We present here the report of the Malaysian dialysis registry. The objectives of this papar are: (1) To examine the overall provision of dialysis treatment in Malaysia and its trend from 1980 to 2006. (2) To assess the treatment rate according to the states in the country. (3) To describe the method, location and funding of dialysis. (4) To characterise the patients accepted for dialysis treatment. (5) To analyze the outcomes of the dialysis treatment. Data on patients receiving dialysis treatment were collected at initiation of dialysis, at the time of any significant outcome, as well as yearly. The number of dialysis patients increased from 59 in 1980 to almost 15,000 in 2006. The dialysis acceptance rate increased from 3 per million population in 1980 to 116 per million population in 2006, and the prevalence rate from 4 to 550 per million population over the same period. The economically advantaged states of Malaysia had much higher dialysis treatment rates compared to the less economically advanced states. Eighty to 90% of new dialysis patients were accepted into centre haemodialysis (HD), and the rest into the chronic ambulatory peritoneal dialysis (CAPD) programme. The government provided about half of the funding for dialysis treatment. Patients older than 55 years accounted for the largest proportion of new patients on dialysis since the 1990s. Diabetes mellitus has been the main cause of ESRD and accounted for more than 50% of new ESRD since 2002. Annual death rate averaged about 10% on HD and 15% on CAPD. The unadjusted 5-year patient survival on both HD and CAPD was about 80%. Fifty percent of dialysis patients reported very good median QoL index score. About 70% of dialysis patients were about to work full or part time. There has been a very rapid growth of dialysis provision in Malaysia particularly in the older age groups. ESRD caused by diabetes mellitus, despite being a preventable and treatable cause of ESRD--has increased and accounted for more than 50% of incident dialysis patients. Death and survival rates on dialysis are comparable to those from other countries.

Architecture of the yeast origin recognition complex bound to origins of DNA replication.

In many organisms, the replication of DNA requires the binding of a protein called the initiator to DNA sites referred to as origins of replication. Analyses of multiple initiator proteins bound to their cognate origins have provided important insights into the mechanism by which DNA replication is initiated. To extend this level of analysis to the study of eukaryotic chromosomal replication, we have investigated the architecture of the Saccharomyces cerevisiae origin recognition complex (ORC) bound to yeast origins of replication. Determination of DNA residues important for ORC-origin association indicated that ORC interacts preferentially with one strand of the ARS1 origin of replication. DNA binding assays using ORC complexes lacking one of the six subunits demonstrated that the DNA binding domain of ORC requires the coordinate action of five of the six ORC subunits. Protein-DNA cross-linking studies suggested that recognition of origin sequences is mediated primarily by two different groups of ORC subunits that make sequence-specific contacts with two distinct regions of the DNA. Implications of these findings for ORC function and the mechanism of initiation of eukaryotic DNA replication are discussed.