Prominent corneal nerves in pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B.

BACKGROUND: Pure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves. Case presentation This report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations-namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium-in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations. CONCLUSION: Prominent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum's disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.

Characterisation of admissions and readmissions after 20 days of illness among COVID-19 patients.

INTRODUCTION: There has been an observed number of readmissions after an index COVID-19 admission, including admissions after an initial home quarantine. The purpose of this study was to identify the clinical characteristics and outcomes of COVID-19 patients who were readmitted or admitted after an initial home quarantine between 21 and 90 days of illness. MATERIALS AND METHODS: This was a single-centre retrospective cohort study comprising patients admitted to a state hospital in Selangor, Malaysia, between August and October 2021. The demographic data, clinical characteristics, presenting complaints, laboratory tests, organ dysfunction, use of invasive ventilation, intensive care unit (ICU) admissions, length of hospitalisation and mortality were collected and analysed. RESULTS: The analysis involved a total of 195 cases. More than a quarter of the cases (52 [26.7%]) were related to the initial COVID-19 infection. Nine cases (4.6%) required mechanical ventilation, while eight cases (4.1%) were admitted to the ICU. The overall mortality was 17 cases (8.7%). Surviving patients were younger (49.5 vs. 58.4 years), less likely to have diabetes mellitus (48.3% vs. 82.4%), or chronic kidney disease (12.9% vs. 41.2%); had higher levels of admission haemoglobin (12.6 vs. 9.1g/dL) and albumin (33.0 vs. 21.0g/L); lower white blood cells (10.2 vs. 13.0 × 109/L), creatinine (81.2 vs. 151.9µmol/L) and C-reactive protein (18.2 vs. 135.0mg/L) at admission; less likely to have MI (6.7% vs. 23.5%), sepsis (3.4% vs. 47.1%), or acute kidney injury (3.4% vs. 17.6%) and organ dysfunction (25.3% vs. 94.1%). CONCLUSION: Approximately a quarter of patients were admitted or readmitted due to direct COVID-19 complications between 21 and 90 days of illness. The baseline oxygen requirements at admission were independently associated with mortality, invasive mechanical ventilation and ICU admissions. Further research is needed to establish a risk model for patients returning to a hospital to predict their risk of post-COVID complications.

Association of dengue serotypes and its complications: a retrospective cohort study.

INTRODUCTION: Dengue fever is an arthropod-borne disease and has a wide clinical spectrum. It is hypothesised that dengue serotypes could be a possible factor for such phenomena and therefore be a possible predictor for the development of severe dengue. METHOD: A retrospective cohort study was done to explore the association between dengue serotypes and the various complications. All patients who underwent dengue serotyping from 1st January to 31st December 2018 in Tengku Ampuan Rahimah Hospital were selected. Serotypes were randomly done for admitted dengue patients. Notes were then retrieved for data collection. Secondary outcomes like length of stay and highest lactate level were also studied. Data analysis was done using SPSS version 20. RESULT: A total of 193 patient records were included in the analysis. Chi-square test for independence indicated that the proportion of dengue complications between male and female were significantly different (χ2(1) = 11.37, p = 0.001). Dengue serotype was not associated with the development of dengue complications, total number of dengue complications, length of admission, lactate level and survival among the serotypes. Results of the binary logistic regression showed that men have thrice the odds (AOR = 3.3, 95% CI: 1.6 6.7) for developing dengue complications. One patient was found to be co-infected with serotype 2 and 3. CONCLUSION: Our study did not reveal any association between the different dengue virus serotypes and its complications. Therefore, all dengue infection should be approached with equal meticulousness. There are possibilities that apart from serotype, dengue genotype and lineage would determine clinical outcome. However, more studies are required to study such associations.

[The role of neutrophil density in neutrophils-mediated inflammatory response induced by monosodium urate crystals].

Objective: To study the role of neutrophil density and molecular mechanism in neutrophils-mediated inflammatory response induced by monosodium urate (MSU) crystals. Methods: Polymorphonuclear neutrophils (PMNs) isolated from healthy human peripheral blood were treated with MSU crystals at different density (5×10(6)/ml, 20×10(6)/ml, 100×10(6)/ml) in vitro. The mean fluorescence intensity (MFI) of PMNs and production of reactive oxygen species (ROS) were detected by flow cytometry. The distribution of MSU crystals was observed by polarized light microscopy. The neutrophil extracellular traps (NETs) formation was detected by immune fluorescence. The cytokines in cell supernatant were measured by beads assay including interleukin 1ß (IL-1ß) , tumor necrosis factor α (TNFα) , interleukin 8 (IL-8) , interferon inducible protein 10 (IP-10) , macrophage inflammatory protein 1 (MIP-1) , monokine induced by interferon-γ (MIG) , macrophage inflammatory protein 1α (MIP-1α) , macrophage inflammatory protein 1ß (MIP-1ß) . Results: (1) After MSU crystal intervention, the side scatters (SSC) of neutrophils with medium-cell density (20×10(6)/ml) and high-cell density (100×10(6)/ml) were 128±13 and 93±9 respectively, both significantly lower than 170±19 in low-cell density (5×10(6)/ml) group.(2) Similarly, compared with low-cell density group, the MFI (lucifer yellow) of PMNs with high-cell density was 1.8±0.2, also significantly decreased (P<0.05). When co-treated with oxygenated adenosine triphosphate (oxATP), MFI of PMNs were all enhanced consistently. (3) In MSU crystals stimulated PMNs, after adding 2',7'-dichlorodihydrofluorescein diacetate, the MFI values were 0.85±0.32, 2.49±0.78, 4.54±1.02 in low cell density groups, medium cell density groups, and high cell density groups respectively, indicating that the generation of ROS was positively correlated with the increase of PMN density (P<0.05). After the intervention of oxATP, the ROS production was significantly reduced. (4) MSU crystal induced NETs formation, especially at high cell density. NETs formation promotes MSU crystal aggregation, which could be partially overcome by oxATP pretreatment. (5) The expression of cytokines were all significantly decreased in the supernatant of PMNs at high cell density exposed to MSU crystals compared with PMNs at medium cell density (P<0.05) . Conclusion: The PMN-mediated inflammation induced by MSU crystals is cell density dependent, and ATP may play a role in partially overcoming the process.

[Effects of transthyretin on biological behavior of retinal pigment epithelial cells and retinal microvascular epithelial cells].

Objective: To explore the effects of transthyretin (TTR) on biological behavior of retinal pigment epithelial cells (RPECs) and retinal microvascular epithelial cells (RMVECs). Methods: RPECs were cultured with exogenous TTR to explore the effect of TTR on the proliferation of RPECs. The expression of TTR of RPECs was silenced by TTR specific small interfering RNA and the expression of TTR was detected by using Western blotting to identify the efficacy of TTR silence. The level of vascular endothelial growth factor (VEGF) massage RNA was detected by using RT-PCR to identify the interaction between VEGF and TTR. The different proliferation and migration abilities of RMVECs with different expressions of TTR were measured by transwell system. Results: MTT assay showed that RPECs with 0 µmol/L TTR glowed faster than with 4 µmol/L TTR (t=18.08, P<0.0001). The expression level of TTR was decreased in the small interfering RNA group as compared with the negative control group (P<0.05). RT-PCR assay showed no differential expression of VEGF after the silencing of TTR (P>0.05). The transwell assay showed RMVECs with the silence of TTR proliferated more slowly than RMVECs without the treatment (t=4.901, P=0.0012), and also migrated more slowly (t=4.213, P=0.0029). Conclusions: TTR can inhibit the proliferation of RPECs and promote the proliferation and migration of RMVECs without the help of VEGF, the mechanism of which may be worth further study. (Chin J Ophthalmol, 2016, 52: 856-860).

[Lycopene protects against hypoxia/reoxygenation injury in mouse cardiomyocytes by inhibiting endoplasmic reticulum stress induced apoptosis].

OBJECTIVE: To investigate the effects of lycopene on primary cultured neonatal mouse cardiomyocytes with hypoxia/reoxgenation (H/R) injury and explore related mechanism. METHODS: Primary cultured neonatal mouse cardiomyocytes were randomly divided to control group (control); lycopene group (5 µmol/L, lyc); H/R group (4 hours hypoxia followed by 6 hours reoxgenation); lycopene+ H/R group (lyc+ H/R, the cardiomyocytes were incubated with 5 µmol/L lycopene for 4 hours before H/R treatment). The cell viability of cardiomyocytes was assessed by CCK-8 assay. The apoptotic rate of cardiomyocytes was evaluated by flow cytometry using AnnexinV-PI double staining. Western blot was used to determine the GRP78, CHOP, Bax and Bcl-2 protein expression in cardiomyocytes. The mRNA expressions of ATF6、eIF2α and sXbp-1 were detected by real-time PCR. The fluorescence intensity for reactive oxygen species (ROS) in cardiomyocytes was measured with Olympus fluorescence microscope. RESULTS: Compared to control group, the cell viability of cardiomyocytes was significantly reduced ((64.28±6.12)% vs. (100.00±4.98)%, P<0.01), the apoptotic rate ((24.42±1.76)% vs. (5.16±1.31)%, P<0.01) and ratio of Bax/Bcl-2 (2.33±0.20 vs. 1.00±0.09, P<0.01) significantly increased, the ATF6, eIF2α and sXbp-1 mRNA expression, the CHOP and GRP78 protein expression (1.98±0.15 vs. 1.00±0.12, 2.09±0.11 vs. 1.00±0.09) as well as fluorescence intensity for ROS ((262.13±22.03)% vs. (100.00±12.35)%) were markedly increased in H/R group (all P<0.01). Compared to the H/R group, pretreatment with lycopene markedly improved the cell viability of cardiomyocytes ((81.75±6.85)%, P<0.01), significantly decreased the apoptotic rate ((17.24±2.02)%, P<0.01) and ratio of Bax/Bcl-2(1.64±0.13, P<0.01), significantly down-regulated the mRNA expression levels of ATF6, eIF2α and sXbp-1, and the protein expression levels of CHOP (1.54±0.12) and GRP78 (1.53±0.12), significantly reduced the fluorescence intensity for ROS ((171.18±19.09)%, all P<0.01). CONCLUSIONS: Lycopene could attenuate hypoxia/reoxygenation-injury in primary cultured neonatal mouse cardiomyocytes, possibly through inhibiting the ER stress and alleviating the ER stress-induced apoptosis.

Effect of tea catechins on regulation of cell proliferation and antioxidant enzyme expression in H2 O2 -induced primary hepatocytes of goat in vitro.

Tea catechins (TC) are polyphenols that have potent antioxidant activity. The objectives of this study were to determine the effects of TC on antioxidant status of hepatocytes challenged with H2 O2 . Primary hepatocytes of goat were exposed to 1 mm H2 O2 without or with 5, 50 and 500 µg/ml TC. The cells were harvested at 48 h post-treatment to determine effects of TC on proliferation, apoptotic features and membrane integrity of cells, and expression of genes and activities of antioxidant enzymes. H2 O2 exposure caused damage to cells (p < 0.001). A lower concentration of TC (5 µg/ml) displayed a protective effect by inhibiting exorbitant cell proliferation and DNA degradation. Both H2 O2 exposure and TC pre-incubation affected expression of antioxidant enzymes at mRNA and protein levels (p < 0.001). The activities of catalase (CAT) (p = 0.027), CuZn-superoxide dismutase (CuZn-SOD) (p < 0.001) and glutathione peroxidase (GPx) (p < 0.001) increased with TC pre-incubation followed by H2 O2 challenge. Changes of CuZn-SOD activity induced by H2 O2 and TC basically paralleled the changes in the corresponding mRNA and protein levels, but the correlation in CAT and GPx expression displayed slightly different patterns at different concentrations of TC. These findings infer that oxidative stress can induce deleterious cellular responses and this unfavourable condition may be alleviated by treatment with TC.

First molecular detection of porcine circovirus type 4 (PCV4) in Malaysia.

Porcine circovirus type 4 (PCV4) is the newest member in the porcine circovirus family, first reported in 2020. To date, the presence of PCV4 has only been reported in China, South Korea and most recently in Thailand. Detection of PCV4 have been reported in various production stages of pigs from piglets, finishers to sows; associated with a myriad of clinical manifestations including porcine dermatitis and nephropathy syndrome (PDNS), postweaning multisystemic wasting syndrome (PMWS), respiratory, enteric and neurological diseases. While successful virus isolation and culture has yet to be reported, pathogenicity of PCV4 has been demonstrated through infectious clone studies. The objective of this study is to investigate the presence of PCV4 in Malaysian porcine population to update the epidemiology of porcine circoviruses in Malaysia. A total of 49 samples from commercial intensive pig farms, abattoir and wild boar population were subjected to conventional polymerase chain reaction assay to detect PCV4 capsid (cap) genome. Resulting cap nucleotide sequences were analyzed for maximum likelihood phylogeny relationship. Results revealed that PCV4 is present in Peninsular Malaysia at a molecular prevalence of 4.08% (2 / 49 samples). Both PCV4 positive samples originated from clinically healthy finishers. Malaysian PCV4 strains were classified as genotype PCV4b, and were found to be phylogenetically distinct from the China, South Korea and Thailand strains. With this latest update of the novel PCV4 in Malaysia, it is clear that more attention needs to be given to the investigation of novel porcine circoviruses (PCV) and management of PCV diseases.

Anatomical tilt lateral wrist X-ray - Not always 22°.

INTRODUCTION: Open Reduction and Internal Fixation (ORIF) with volar locking plates are commonly used to manage distal radial fractures. The anatomical tilt lateral (ATL) wrist X-ray is often required for evaluation of intra-articular screw penetration due to the screw position. This study aims to evaluate the correlation between the tube angulation given by performing radiographers for the ATL projection and the post-examination measurement of radial inclination (RI) on the Posterior Anterior (PA) wrist image. METHODS: A retrospective review was performed for 36 patients. A standardised method developed by Kreder et al. (1996) was used to measure the RI on the PA wrist image. All ATL images sent into Picture Archiving and Communications System (PACS) have the tube angulation applied annotated on the image. Pearson's correlation was used to analyse the co-relationship between the RI and the tube angle applied for ATL projection. RESULTS: The average angle of RI measured by the four observers was 19. Normality of 0.385 was established. A positive correlation (p = 0.792) between the RI and the tube angle applied for ATL was found. CONCLUSION: Our study found a strong positive correlation between the tube angulation applied by performing radiographers for the ATL projection and the post-examination RI measured on the PA wrist image by the independent reviewers. This suggests that radiographers can use the measured RI to apply the tube angulation when performing the ATL wrist X-ray, instead of estimating the tube angulation to be applied. IMPLICATIONS FOR PRACTICE: Using the measured RI to apply the tube angulation when performing the ATL wrist X-ray will ensure a more reliable and reproducible way that could reduce the number of repeated images and, thus, unnecessary radiation dose to patients.

3D Printing and Performance Study of Porous Artificial Bone Based on HA-ZrO2-PVA Composites.

An ideal artificial bone implant should have similar mechanical properties and biocompatibility to natural bone, as well as an internal structure that facilitates stomatal penetration. In this work, 3D printing was used to fabricate and investigate artificial bone composites based on HA-ZrO2-PVA. The composites were proportionally configured using zirconia (ZrO2), hydroxyapatite (HA) and polyvinyl alcohol (PVA), where the ZrO2 played a toughening role and PVA solution served as a binder. In order to obtain the optimal 3D printing process parameters for the composites, a theoretical model of the extrusion process of the composites was first established, followed by the optimization of various parameters including the spray head internal diameter, extrusion pressure, extrusion speed, and extrusion line width. The results showed that, at the optimum parameters of a spray head diameter of 0.2 mm, extrusion pressure values ranging from 1-3 bar, a line spacing of 0.8-1.5 mm, and a spray head displacement range of 8-10 mm/s, a better structure of biological bone scaffolds could be obtained. The mechanical tests performed on the scaffolds showed that the elastic modulus of the artificial bone scaffolds reached about 174 MPa, which fulfilled the biomechanical requirements of human bone. According to scanning electron microscope observation of the scaffold sample, the porosity of the scaffold sample was close to 65%, which can well promote the growth of chondrocytes and angiogenesis. In addition, c5.18 chondrocytes were used to verify the biocompatibility of the composite materials, and the cell proliferation was increased by 100% when compared with that of the control group. The results showed that the composite has good biocompatibility.

Creep Behavior of A356 Aluminum Alloy Reinforced with Multi-Walled Carbon Nanotubes by Stir Casting.

Lightweight aluminum alloy components are often used to manufacture a variety of engineering components in many industries. In recent years, researchers have studied the effect of improving the mechanical properties of metal alloys by incorporating nano-carbon into its structure. In this study, the effect of the addition of 0.2, 0.5, and 1 wt% of multi-walled carbon nanotubes (MWCNTs) on the stress-strain behavior and creep phenomenon of an A356 aluminum alloy were studied. The effect of nickel coating on 0.2 wt% MWCNTs was also investigated. Samples were prepared using the stir-casting method. The results revealed that the grain size became finer when MWCNT nano-particulates were introduced. Although the MWCNTs were distributed homogeneously in the A356 matrix, as confirmed by FESEM analysis, there were some agglomerations observed in a specific area with dimensions smaller than 100 nm. Nevertheless, the addition of MWCNTs was found to be beneficial in enhancing the hardness of alloys containing 0.2 wt%, 0.2 wt% nickel-coated, 0.5 wt%, and 1 wt% MWCNTs by 9%, 24%, 32%, and 15%, respectively, as compared with the unreinforced A345 matrix. It was also found that the 0.5 wt% MWCNT-A356 matrix exhibited an improvement in the creep lifetime by more than two orders of magnitude.

Accuracy of radiographer comment following a two-month experiential and blended learning in appendicular skeleton X-ray interpretation: The Singapore experience.

INTRODUCTION: The value of combined blended and experiential learning on radiographer diagnostic comment has not been explored. This study aims to examine the accuracy of image interpretation comment of radiographers who received a period of blended and experiential learning in Radiographer Abnormality Detection Systems (RADS). METHODS: We evaluated the diagnostic opinions of 13 radiographers who received a blended training and experiential learning (a process of self-learning and reflection) in RADS. Radiographers' opinions on 16,483 images were examined using the final radiologists' report as a reference standard. For each radiographer, we recorded the number of true positive, true negative, false positive and false negative opinions and MedCal® was used to calculate diagnostic performance and error rates. A t-test was used to assess whether the number of images read was associated with performance and whether the radiographers retained performance over time. RESULTS: Sensitivity ranged from 87.4 (84.0-90.2) to 98.9 (97.5-99.7) with a mean of 94.3 (93.6-94.8). Specificity varied from 96.4 (94.8-97.5) to 99.9 (99.41-100.0) with a mean of 98.2 (97.9-98.4). Diagnostic accuracy ranged from 93.1 (91.5-94.4) to 99.5 (98.9-99.8) with a mean of 96.9 (96.6-97.1). The mean false positive rate was 0.018 (range: 0.010-0.031) with a false negative rate of 0.057 (range: 0.026-0.11). There were no differences in performance between the first and latter nine months of providing opinions and the number of images reviewed was not associated with performance. CONCLUSION: Radiographers who received blended and experiential learning in RADS provide accurate diagnostic comments on plain emergency appendicular skeleton radiographs. IMPLICATION FOR PRACTICE: A combined blended and experiential learning can equip radiographers to provide diagnostic opinion on plain appendicular skeleton radiographs.

Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.

AIM: The Wnt/ß-catenin signaling network offers potential targets to diagnose and uncouple obesity from its metabolic complications. In this study, we investigate the role of the Wnt antagonist, secreted frizzled-related protein 1 (SFRP1), in promoting adipogenesis in vitro and adipose tissue expansion in vivo. METHODS: We use a combination of human and murine, in vivo and in vitro models of adipogenesis, adipose tissue expansion and obesity-related metabolic syndrome to profile the involvement of SFRP1. RESULTS: SFRP1 is expressed in both murine and human mature adipocytes. The expression of SFRP1 is induced during in vitro adipogenesis, and SFRP1 is preferentially expressed in mature adipocytes in human adipose tissue. Constitutive ectopic expression of SFRP1 is proadipogenic and inhibits the Wnt/ß-catenin signaling pathway. In vivo endogenous levels of adipose SFRP1 are regulated in line with proadipogenic states. However, in longitudinal studies of high-fat-diet-fed mice, we observed a dynamic temporal but biphasic regulation of endogenous SFRP1. In agreement with this profile, we observed that SFRP1 expression in human tissues peaks in patients with mild obesity and gradually falls in morbidly obese subjects. CONCLUSIONS: Our results suggest that SFRP1 is an endogenous modulator of Wnt/ß-catenin signaling and participates in the paracrine regulation of human adipogenesis. The reduced adipose expression of SFRP1 in morbid obesity and its knock-on effect to prevent further adipose tissue expansion may contribute to the development of metabolic complications in these individuals.

Virtual screening of selective multitarget kinase inhibitors by combinatorial support vector machines.

Multitarget agents have been increasingly explored for enhancing efficacy and reducing countertarget activities and toxicities. Efficient virtual screening (VS) tools for searching selective multitarget agents are desired. Combinatorial support vector machines (C-SVM) were tested as VS tools for searching dual-inhibitors of 11 combinations of 9 anticancer kinase targets (EGFR, VEGFR, PDGFR, Src, FGFR, Lck, CDK1, CDK2, GSK3). C-SVM trained on 233-1,316 non-dual-inhibitors correctly identified 26.8%-57.3% (majority >36%) of the 56-230 intra-kinase-group dual-inhibitors (equivalent to the 50-70% yields of two independent individual target VS tools), and 12.2% of the 41 inter-kinase-group dual-inhibitors. C-SVM were fairly selective in misidentifying as dual-inhibitors 3.7%-48.1% (majority <20%) of the 233-1,316 non-dual-inhibitors of the same kinase pairs and 0.98%-4.77% of the 3,971-5,180 inhibitors of other kinases. C-SVM produced low false-hit rates in misidentifying as dual-inhibitors 1,746-4,817 (0.013%-0.036%) of the 13.56 M PubChem compounds, 12-175 (0.007%-0.104%) of the 168 K MDDR compounds, and 0-84 (0.0%-2.9%) of the 19,495-38,483 MDDR compounds similar to the known dual-inhibitors. C-SVM was compared to other VS methods Surflex-Dock, DOCK Blaster, kNN and PNN against the same sets of kinase inhibitors and the full set or subset of the 1.02 M Zinc clean-leads data set. C-SVM produced comparable dual-inhibitor yields, slightly better false-hit rates for kinase inhibitors, and significantly lower false-hit rates for the Zinc clean-leads data set. Combinatorial SVM showed promising potential for searching selective multitarget agents against intra-kinase-group kinases without explicit knowledge of multitarget agents.

Virtual screening of Abl inhibitors from large compound libraries by support vector machines.

Abl promotes cancers by regulating cell morphogenesis, motility, growth, and survival. Successes of several marketed and clinical trial Abl inhibitors against leukemia and other cancers and appearances of reduced efficacies and drug resistances have led to significant interest in and efforts for developing new Abl inhibitors. In silico methods of pharmacophore, fragment, and molecular docking have been used in some of these efforts. It is desirable to explore other in silico methods capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as a virtual screening tool for searching Abl inhibitors from large compound libraries. SVM trained and tested by 708 inhibitors and 65,494 putative noninhibitors correctly identified 84.4 to 92.3% inhibitors and 99.96 to 99.99% noninhibitors in 5-fold cross validation studies. SVM trained by 708 pre-2008 inhibitors and 65 494 putative noninhibitors correctly identified 50.5% of the 91 inhibitors reported since 2008 and predicted as inhibitors 29,072 (0.21%) of 13.56M PubChem, 659 (0.39%) of 168K MDDR, and 330 (5.0%) of 6638 MDDR compounds similar to the known inhibitors. SVM showed comparable yields and substantially reduced false-hit rates against two similarity based and another machine learning VS methods based on the same training and testing data sets and molecular descriptors. These suggest that SVM is capable of searching Abl inhibitors from large compound libraries at low false-hit rates.

[Changes of BK(Ca) on vascular striaepericytes of D-galactose-induced aging model in guinea pigs].

Objective: The aging model of guinea pigs induced by D-galactose was set up to investigate the changes of BK(Ca) expression and function on cochlear pericytes and their relationship with age-related hearing loss. Methods: Thirty healthy 8-week-old guinea pigs were randomly divided into three groups, with 10 in each group: D-galactose aging model group, subcutaneous injection of D-galactose (500 mg/kg) daily for 6 weeks; saline control group, the same amount of saline was injected into the neck of the aging model group for 6 weeks; the blank control group, no treatment was performed. The threshold of auditory brainstem response (ABR) was detected. The content of BK(Ca) in the perivascular cells of the guinea pig cochlear cells was detected by immunofluorescence technique. The changes of peripheral current density and BK(Ca) current were detected by patch clamp technique. The data were analyzed by GraphPad Prism software. Results: Compared with the saline group and the control group, the ABR threshold and the amplitude of the wave I were significantly decreased in the aging model group, and the difference was statistically significant (P<0.01). Compared with the control group, the expression of BK(Ca) in the vascular pericytes of guinea pigs in the aging model group was significantly reduced (1.00±0.08 vs 0.27±0.03,the difference was statistically significant P<0.01), and the cell current density and BK(Ca) net current value were also significantly reduced with statistically significant (P<0.01). Conclusions: D-galactose can successfully induce guinea pig aging model, in which BK(Ca) expression decreases and net current value decreases in pericytes of cochlear striavascularis, and changes in BK(Ca) expression and function may be related to age-related hearing loss.

Effect of powder calcination on the sintering of hydroxyapatite.

The sintering behaviour of synthesized HA powder that was calcined at various temperatures ranging from 700 degrees C to 1000 degrees C was investigated in terms of phase stability, bulk density, Young's modulus and Vickers hardness. The calcination treatment resulted in higher crystallinity of the starting HA powder. Decomposition of HA phase to form secondary phases was not observed in all the calcined powders. The results also indicated that powder calcination (up to 900 degrees C) prior to sintering has negligible effect on the sinterability of the HA compacts. However, powder calcined at 1000 degrees C was found to be detrimental to the properties of sintered hydroxyapatite bioceramics.

Sintering behaviour of hydroxyapatite bioceramics.

The sintering behaviour of a commercial HA and synthesized HA was investigated over the temperature range of 700 degrees C to 1400 degrees C in terms of phase stability, bulk density, Young's modulus and Vickers hardness. In the present research, a wet chemical precipitation reaction was successfully employed to synthesize a submicron, highly crystalline, high purity and single phase stoichiometric HA powder that is highly sinteractive particularly at low temperature regimes below 1100 degrees C. It has been revealed that the sinterability of the synthesized HA was significantly greater than that of the commercial HA. The temperature for the onset of sintering and the temperature required to achieve densities above 98% of theoretical value were approximately 150 degrees C lower for the synthesized HA than the equivalent commercial HA. Nevertheless, decomposition of HA phase upon sintering was not observed in the present work for both powders.

An evaluation of the effects of renal artery stenting in renovascular hypertension.

Renal artery stenosis is a common cause (1-6%) of secondary hypertension. Renal artery stenting has recently been employed as an adjunct to antihypertensive medication. We evaluated 92 patients who underwent renal angiography of whom 30 were stented. There was a reduction (p < 0.01) in blood pressure immediately post renal artery stenting--systolic BP from 157 +/- 20 to 140 +/- 21 mmHg and diastolic BP from 81 +/- 13 to 72 +/- 12 mmHg was sustained at 6 months follow up (148 +/- 20/76 +/- 12 mmHg) in the outpatients' clinic. The amount of antihypertensive medication did not differ post stenting--2.7 +/- 1.2 pre vs 2.7 +/- 1.2 drugs post procedure. Renal artery stenting did not provide a 'cure' for any patient with atherosclerotic renovascular hypertension and until the results of randomized studies are known we believe use should be restricted.

An overview of the new test stand for H⁻ ion sources at FNAL.

A new test stand at Fermi National Accelerator Laboratory (FNAL) is being constructed to carry out experiments to develop and upgrade the present magnetron-type sources of H(-) ions of up to 80 mA at 35 keV in the context of the Proton Improvement Plan. The aim of this plan is to provide high-power proton beams for the experiments at FNAL. The technical details of the construction and layout of this test stand are presented, along with a prospective set of diagnostics to monitor the sources.