Haemophilia care and outcome in a major haemophilia treatment centre in Malaysia.

INTRODUCTION/OBJECTIVE: The management of potential treatment-related complications and bleeding events in haemophilia is challenging in developing countries. Providing optimal care among these patients improve their quality of life (QOL) and life expectancy. This study explores the demographic characteristics and treatment outcome in a major haemophilia treatment centre in Malaysia. MATERIALS AND METHODS: A total of 260 patients were recruited in this retrospective cross-sectional analysis. Clinical data, including treatment regimens and outcome, were collected and analysed. RESULTS: A total of 211 patients were diagnosed with haemophilia A (HA) (severe disease, 72.5%) and 49 patients had haemophilia B (HB) (severe disease, 65.3%). The median age was 31 (IQR;2-84) years. Majority of the patients had at least one episode of musculoskeletal bleeding since diagnosis. The mean annual bleeding event (ABE) was 4.91 (SD±6.07) in 2018. Target joints were identified in 80.4% of the patients. Chronic arthropathy and synovitis collectively accounted for more than half of the musculoskeletal complications. 30.1% of the patients had contracted hepatitis C with less than half received treatment. Thirty-one patients (16.8%) with severe haemophilia developed inhibitor and 12 patients successfully underwent immune tolerance induction. More than three-quarters of the severe haemophilia patients were treated with factor concentrate prophylaxis. The mean prophylaxis dose for HA and HB were 41.3 (SD±19.1) and 48.6 (SD±21.5) IU/kg/week, respectively. In patients with severe disease, prophylaxis significantly reduced the ABE (5.45,9.03;p=0.005). CONCLUSION: The importance of utilising a low to moderate dose regimen as prophylaxis in haemophilic patients is highlighted in our study. Future studies should include QOL assessment will further improve the management in haemophilia.

Curie-Weiss behavior of liquid structure and ideal glass state.

We present the results of a structural study of metallic alloy liquids from high temperature through the glass transition. We use high energy X-ray scattering and electro-static levitation in combination with molecular dynamics simulation and show that the height of the first peak of the structure function, S(Q) - 1, follows the Curie-Weiss law. The structural coherence length is proportional to the height of the first peak, and we suggest that its increase with cooling may be related to the rapid increase in viscosity. The Curie temperature is negative, implying an analogy with spin-glass. The Curie-Weiss behavior provides a pathway to an ideal glass state, a state with long-range correlation without lattice periodicity, which is characterized by highly diverse local structures, reminiscent of spin-glass.

Clinical Implication of Tests for Prostate-specific Antigen in Brain-dead Organ Donors.

BACKGROUND: Although cancer screening tests are not mentioned under brain-dead organ donor care guidelines in Korea, we assessed the level of prostate-specific antigen (PSA), an important prostate cancer marker, and performed prostate biopsies when needed in brain-dead organ donors. We believe that insisting on a screening test for cancer diagnosis in donors' organs is important. MATERIALS AND METHODS: Data were collected between January 2010 and July 2015 from Ajou University Hospital. We retrospectively analyzed the PSA levels and prostate biopsy results in 111 male brain-dead organ donors (mean age, 48.4 years). RESULTS: The mean PSA level was 7.395 ng/mL (range, 0.062 to 61.780; reference, 0 to 4 ng/mL). Ultrasonography or computed tomographic examination did not reveal prostate cancer, and a rectal examination was not performed. After checking the PSA levels, prostate biopsies were performed in 16 patients based on the recommendations of a urologist, and 4 patients (3.6% of 111) were diagnosed with prostate cancer. All cancers involved adenocarcinomas (acinar type) histopathologically. In 2 patients, the Gleason score was 6 (3 + 3), whereas the other 2 showed a score of 7 (3 + 4). Among the patients diagnosed with prostate cancer, 1 donated his liver and corneas, and the remaining 3 could not donate. CONCLUSION: Well-defined cancer screening tests are needed in Korea. Additionally, when the probability of organ transplantation-induced cancer metastasis is low or a recipient is at a high risk owing to not receiving organs, the law should allow organ donation even if prostate cancer is diagnosed in the donor.

Outcome of alternative approach to displaced acetabular fractures.

INTRODUCTION: Anatomical reduction of displaced acetabular fracture is not without its' limitations and complications. This study is conducted to assess clinical and radiological outcomes as well as complications of treating displaced acetabular fractures with emphasis on anatomical reduction in weight-bearing area, mainly the posterior column, and imperfect reduction of the anterior column is acceptable. However, stability of both columns is mandatory. METHODS: It was a retrospective study carried out in a Level 1 arthroplasty and trauma centre. 23 patients (17 males, 6 females) with average age of 50.1 years (range, 36-68 years) with displaced acetabular fracture treated with combined incisions and plate-cable systems were included. There were 3 elementary and 18 associated fractures according to Letournel classification. Average follow-up was 23.5 months (range, 12-38.7 months). Mean operation time was 160min (range: 75-320min). Functional scores were evaluated using Harris Hip Score (HHS) whilst reduction was assessed by Matta criteria. Any displacement of reduction, osteoarthritis, heterotopic ossification, and other complications was recorded. RESULT: 65.2% (15/23) of the patients obtained excellent HHS and 21.7% (5/23) had good HHS. There were 12 anatomical, 6 imperfect, and 5 poor reductions. No displacement was recorded in final follow-up. Complications documented: three lateral femoral cutaneous nerve injuries, two conversions to total hip arthroplasty, three Brooker stage 1 heterotrophic ossification, one pulmonary embolism and one screw irritation. No incidence of wound breakdown, infection and radiological osteoarthritis was reported. CONCLUSIONS: Imperfect reduction of the anterior column provided clinical outcomes that are as good as total anatomical reduction. This approach minimizes soft tissue damage and reduces perioperative morbidities.

Effect of atomic size on undercoolability of binary solid solution alloy liquids with Zr, Ti, and Hf using electrostatic levitation.

We investigate the relationship between the excess volume and undercoolability of Zr-Ti and Zr-Hf alloy liquids by using electrostatic levitation. Unlike in the case of Zr-Hf alloy liquids in which sizes of the constituent atoms are matched, a remarkable increase of undercoolability and negative excess volumes are observed in Zr-Ti alloy liquids as a function of their compositional ratios. In this work, size mismatch entropies for the liquids were obtained by calculating their hard sphere diameters, number densities, and packing fractions. We also show that the size mismatch entropy, which arises from the differences in atomic sizes of the constituent elements, plays an important role in determining the stabilities of metallic liquids.

Evolution of atomic structure in Al75Cu25 liquid from experimental and ab initio molecular dynamics simulation studies.

X-ray diffraction and electrostatic levitation measurements, together with the ab initio molecular dynamics simulation of liquid Al(75)Cu(25) alloy have been performed from 800 to 1600 K. Experimental and ab initio molecular dynamics simulation results match well with each other. No abnormal changes were experimentally detected in the specific heat capacity over total hemispheric emissivity and density curves in the studied temperature range for a bulk liquid Al(75)Cu(25) alloy measured by the electrostatic levitation technique. The structure factors gained by the ab initio molecular dynamics simulation precisely coincide with the experimental data. The atomic structure analyzed by the Honeycutt-Andersen index and Voronoi tessellation methods shows that icosahedral-like atomic clusters prevail in the liquid Al(75)Cu(25) alloy and the atomic clusters evolve continuously. All results obtained here suggest that no liquid-liquid transition appears in the bulk liquid Al(75)Cu(25) alloy in the studied temperature range.

The prognostic impact of the neutrophil-to-lymphocyte ratio in patients with small-cell lung cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment. METHODS: We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital. RESULTS: In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS. CONCLUSIONS: NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.

The global response regulator ExpA controls virulence gene expression through RsmA-mediated and RsmA-independent pathways in Pectobacterium wasabiae SCC3193.

ExpA (GacA) is a global response regulator that controls the expression of major virulence genes, such as those encoding plant cell wall-degrading enzymes (PCWDEs) in the model soft rot phytopathogen Pectobacterium wasabiae SCC3193. Several studies with pectobacteria as well as related phytopathogenic gammaproteobacteria, such as Dickeya and Pseudomonas, suggest that the control of virulence by ExpA and its homologues is executed partly by modulating the activity of RsmA, an RNA-binding posttranscriptional regulator. To elucidate the extent of the overlap between the ExpA and RsmA regulons in P. wasabiae, we characterized both regulons by microarray analysis. To do this, we compared the transcriptomes of the wild-type strain, an expA mutant, an rsmA mutant, and an expA rsmA double mutant. The microarray data for selected virulence-related genes were confirmed through quantitative reverse transcription (qRT-PCR). Subsequently, assays were performed to link the observed transcriptome differences to changes in bacterial phenotypes such as growth, motility, PCWDE production, and virulence in planta. An extensive overlap between the ExpA and RsmA regulons was observed, suggesting that a substantial portion of ExpA regulation appears to be mediated through RsmA. However, a number of genes involved in the electron transport chain and oligogalacturonide metabolism, among other processes, were identified as being regulated by ExpA independently of RsmA. These results suggest that ExpA may only partially impact fitness and virulence via RsmA.

Analysis of flicker noise for improved data retention characteristics in silicon-oxide-high-k-oxide-silicon flash memory using N2 implantation.

In this paper, we fabricate planar-type Silicon-Oxide-High-k-Oxide-Silicon (SOHOS) and the planar-type SOHOS devices with N2 implantation of 3 x 10(15) dose in a tunneling oxide to determine the impact of N2 implantation in the tunneling oxide of a memory device. The N2 implantation device has better retention characteristics than the device with no implantation. In order establish the correlation between N2 implantation and retention characteristic improvement, the low frequency noise (1/f noise) characteristic is investigated. The normalized drain current noise (S(ID)/I(D)2) level of the N2 implantation device is higher than that of the device with no implantation, which means that N2 implantation causes more trap formation near the interface. Considering that N2 implantation does not affect the DC transfer characteristics, such as mobility and sub-threshold slope, this finding indicates that the increase in the 1/f noise level is due to oxide traps rather than to interface traps. Therefore, the retention characteristic improvement in the N2 implantation device can be explained by the generation of higher number of oxide traps and an increase in the potential barrier blocking the leakage path in the tunneling oxide.

Comparison between ultrasound-guided supraclavicular and infraclavicular approaches for subclavian venous catheterization in children--a randomized trial.

BACKGROUND: Ultrasound (US)-guided subclavian vein (SCV) catheterization via the supraclavicular (SC) or infraclavicular (IC) approaches can be useful in children. The purpose of this study was to compare the efficacy of these approaches. METHODS: This prospective, randomized study included 98 children who were <3 years old, and who were divided into two groups: the SC group (n=49) and the IC group (n=49). All SCV catheterizations were guided by US and performed by a single experienced anaesthesiologist. Data regarding puncture time, number of attempts, successful guidewire insertion, catheter insertion time, and complications were analysed. RESULTS: The median puncture time was longer in the IC group than the SC group (48 vs 36 s, P=0.02). Multiple attempts (number of attempts >3) were more frequently required in the IC group than the SC group (24.5 vs 6.1%, P=0.01). The incidence of guidewire misplacement was higher in the IC group than that of the SC group [10 (20.4%) vs 0 (0%), P=0.001]. Catheterization was successfully performed in all patients. No pneumothoraces or arterial punctures occurred in either group. CONCLUSION: During SCV catheterization under US guidance in paediatric patients, the SC approach yielded a shorter puncture time and decreased the incidence of guidewire misplacement when compared with the IC approach.

Influence of sintering temperature on the microstructure and thermoelectric properties of polycrystalline Fe1.9925P0.0075O3.

The solution combustion process is used to synthesize Fe1.9925P0.0075O3 nano-powders. The sintered Fe1.9925P0.0075O3 bodies are alpha-Fe2O3-based single phase with the rhombohedral structure. The electrical conductivity increases with an increase in sintering temperature because of an increase in grain size and density. The absolute value of the Seebeck coefficient escalates with an increase in sintering temperature up to 1000 degrees C, and then decreases with a further rise in its sintering temperature. The Fe1.9925P0.0075O3 sintered at 1000 degrees C shows the highest power factor, i.e., 1.39 x 10(-5) W m(-1) K(-2) at 700 degrees C.

Plasma human mammaglobin mRNA associated with poor outcome in patients with breast cancer.

Different treatment outcomes and prognoses in patients with breast cancer can be observed with similar clinical predictors; this is because the biology of breast cancer is complex and heterogenous, involving multiple unknown contributing factors. We looked for plasma human mammaglobin (hMAM) mRNA by RT-PCR in 82 Korean patients with breast cancer to determine if there is an association between the presence of plasma hMAM mRNA in these patients and known prognostic factors. The prognostic usefulness of detection of plasma hMAM mRNA expression in these patients was also evaluated by determining overall survival and event-free survival. A significant difference was observed in the rate of positivity of plasma hMAM mRNA between the early stages of cancer (stages I-II, 23.4%) and advanced stages (stages III-IV, 82.9%). The expression rates of estrogen receptor, progesterone receptor, and HER-2/neu in the breast tissue of these patients, by immunohistochemistry, were 69.5, 75.6, and 20.7%, respectively. In the univariate analysis, plasma hMAM expression was significantly correlated with high histological and nuclear grades, nodal metastasis, and negative estrogen receptor and progesterone receptor status. Patients negative for plasma hMAM mRNA had significantly higher rates of event-free survival compared to the patients positive for plasma hMAM mRNA. However, no significant association with overall survival was observed for expression of plasma hMAM mRNA (P = 0.16). Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer.

Electrical characteristic analysis using low-frequency noise in low-temperature polysilicon thin film transistors.

This study carried out an electrical characteristic analysis using low-frequency noise (LFN) in top gate p-type low-temperature polysilicon thin film transistors (LTPS TFTs) with different active layer thicknesses between 40 nm and 80 nm. The transfer characteristic curves show that the 40-nm device has better electrical characteristics compared with the 80-nm device. The carrier number fluctuation, with and without correlated mobility fluctuation model in both devices, has modeled well the measured noise. On the other hand, the trap density and coulomb scattering in the 40-nm device are smaller compared with the 80-nm device. To confirm the effectiveness of the LFN noise analysis, the trap densities at a grain boundary are extracted using in both devices the similar methods of Proano et al. and Levinson et al. That is, coulomb scattering, caused by the trapped charges at or near the interface, has a greater effect on the device with inferior electrical properties. Based on the LFN and the quantitative analysis of the trap density at a grain boundary, the interface traps between the active layer and the gate insulator can explain the devices' electrical degradation.

Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K+ channel.

AIM: Many kinds of K(+) channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K(+) channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K(+) (K(2P) ) channel expression levels are related to the migration of human breast cancer cells. METHODS: K(2P) channel gene/protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K(2P) channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK-3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique. RESULTS: Of K(2P) channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDA-MB-231 cells. CONCLUSION: These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.

Thermoelectric properties of Ca(1-x-y)Dy(x)CeyMnO3 for power generation.

The sintered Ca(1-x-y)Dy(x)CeyMnO3 bodies were a single phase with a perovskite structure without any impurity phases. The calculated crystallite sizes of the Ca(1-x-y)Dy(x)CeyMnO3 were in the range of 43.3 to 63.3 nm. The composition significantly affected their microstructural and thermoelectric characteristics. The doped Dy led to both an increase in the electrical conductivity as well as the absolute value of the Seebeck coefficient, resulting in an enhanced power factor. The highest power factor (5.1 x 10(-4) Wm(-1) K(-2)) was obtained for Ca(0.8)Dy(0.2)MnO3 at 800 degrees C. In this study, we systematically discussed the thermoelectric properties of the Ca(1-x-y)Dy(x)CeyMnO3, with respect to the substitution of Dy and/or Ce for Ca.

Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients.

PURPOSE: The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy. METHODS: One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones. RESULTS: For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9 months, p = 0.116; 7.0 vs. 7.8 months, p = 0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9 months, p = 0.014; 9.1 vs. 7.9 months, p = 0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p = 0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p = 0.005). CONCLUSIONS: ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.

Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients.

BACKGROUND: To analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr). RESULTS: Median age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum ß(2) microglobulin level, and platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.

In situ high-energy x-ray diffraction study of the local structure of supercooled liquid Si.

Employing the technique of electrostatic levitation, coupled with high-energy x-ray diffraction and rapid data acquisition methods, we have obtained high quality structural data more deeply into the supercooled regime of liquid silicon than has been possible before. No change in coordination number is observed in this temperature region, calling into question previous experimental claims of structural evidence for the existence of a liquid-liquid phase transition.

Difference in icosahedral short-range order in early and late transition metal liquids.

New short-range order data are presented for equilibrium and undercooled liquids of Ti and Ni. These were obtained from in situ synchrotron x-ray diffraction measurements of electrostatically levitated droplets. While the short-range order of liquid Ni is icosahedral, consistent with Frank's hypothesis, significantly distorted icosahedral order is observed in liquid Ti. This is the first experimental observation of distorted icosahedral short-range order in any liquid, although this has been predicted by theoretical studies on atomic clusters.