An audit cycle of consent form completion: A useful tool to improve junior doctor training.
Consent for surgical procedures is an essential part of the patient's pathway. Junior doctors are often expected to do this, especially in the emergency setting. As a result, the aim of our audit was to assess our practice in consenting and institute changes within our department to maintain best medical practice. An audit of consent form completion was conducted in March 2013. Standards were taken from Good Surgical Practice (2008) and General Medical Council guidelines. Inclusion of consent teaching at a formal consultant delivered orientation programme was then instituted. A re-audit was completed to reassess compliance. Thirty-seven consent forms were analysed. The re-audit demonstrated an improvement in documentation of benefits (91-100%) and additional procedures (0-7.5%). Additional areas for improvement such as offering a copy of the consent form to the patient and confirmation of consent if a delay occurred between consenting and the procedure were identified. The re-audit demonstrated an improvement in the consent process. It also identified new areas of emphasis that were addressed in formal teaching sessions. The audit cycle can be a useful tool in monitoring, assessing and improving clinical practice to ensure the provision of best patient care.


Performance of microbial induced carbonate precipitation for immobilizing Cd in water and soil.
Microbial induced carbonate precipitation (MICP) is known as a significant process for remediating heavy metals contaminated environment. In this study, a novel Cd-resistant ureolytic bacteria was isolated and identified as Enterobacter sp. Its performances for immobilizing Cd in solution and soil were systematically discussed at different treatment conditions. Results showed that initial pH and Cd concentration were important parameters to influence Cd removal rate. The maximal Cd removal rate in solution reached 99.50 % within 7 days by MICP. The precipitation produced in Cd removal process were characterized by X-ray diffraction, scanning electron microscopy and energy dispersive spectrometer to understand the removal mechanism. Analyses showed that Cd removal mechanism of CJW-1 was predominately via biominerals including calcites and vaterites to absorb Cd2+. Cd immobilization tests demonstrated that the highest Cd-immobilization rate in soil could reach 56.10 %. Although all treatments contribute to soil pH, fertility, and enzyme activities improvement, oyster shell wastes (OS) had a better effect on soil cation exchange capacity. All treatments had negative effects on soil respiration and bacterial community, but OS can alleviate such adverse influence. Our results emphasized that Cd-resistant ureolytic bacteria strain CJW-1 combined with OS had excellent ability and reuse value to remediate Cd-contaminated environment.


The submicrosomal distribution in rat and boar testis of some enzymes involved in androgen and 16-androstene biosynthesis.
The submicrosomal localization of enzymes involved in androgen and 16-androstene biosynthesis in rat and boar testis tissue has been studied. 16-androstene production was not evident in the rat testis but two enzymes concerned with androgen generation (17 alpha-hydroxy C21 steroid C-17,20 lyase; 17 beta-hydroxysteroid dehydrogenase, were found predominantly in agranular microsomes. In the boar testis the C-17,10 lyase had a similar distribution to the rat enzyme but the 17 beta-hydroxysteroid dehydrogenase was found to be evenly distributed between the two microsomal types. The enzyme system, "andien-betha synthetase", involved in the conversion of pregnenolone to 5,16-androstadien-3 beta-ol, was found mainly (66%) in the agranular microsomes but had a lower specific activity than those of the two enzymes of androgen biosynthesis that have been studied.


Economic evaluation of open versus laparoscopic hernia repair: some pragmatic considerations for the measurement of costs.
Laparoscopic hernia repair costs more than open repair. This increase in cost largely is because of the use of disposables. Indirect cost benefits of laparoscopic procedure because of a more rapid return to normal activity are different to calculate but may be present for select groups of patients.


Identification of a novel switch in the dominant forms of cell adhesion-mediated drug resistance in glioblastoma cells.
The failure of malignant cells to undergo apoptosis is a major obstacle in cancer therapy, and thus identifying the underlining molecules involved therein is imperative for improving patient survival. An important mechanism of drug resistance is cell adhesion-mediated drug resistance (CAM-DR). In this study we identify a novel switch by which glioblastoma multiforme (GBM) cells alter the mode of CAM-DR. In the absence of a microenvironmental cue provided by components of the extracellular matrix (ECM), GBM cells are able to employ an alternative, but equally effective, mode of CAM-DR by forming spheres via cell-cell interactions. Intriguingly, when inhibiting cell-cell interactions in the absence of ECM components, either by low cell density or by inhibition of gap junctions (intercellular connexin tunnels) through chemical inhibition with carbenoxyolone or co-incubation with the connexin-mimicking Gap 27 Cx37,43 peptide, GBM cells were sensitized to tumor necrosis factor-related apoptosis-inducing ligand- and CD95-induced apoptosis. By demonstrating that GBM cells can alternate from one form of CAM-DR (cell-substrate tethering) to another (homocellular cell-cell adhesion) and that inhibition of both forms is necessary for apoptosis sensitization, our findings not only have important implications for novel approaches to restore defective apoptosis programs, but also reveal a novel role of gap junctions in GBM.


Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells.
Intervertebral disc degeneration (IVDD) is an incurable, specific treatment-orphan disease with an increasing burden worldwide. Although great efforts have been made to develop new regenerative therapies, their clinical success is limited. Characterize the metabolomic and gene expression changes underpinning human disc degeneration. This study also aimed to disclose new molecular targets for developing and optimizing novel biological approaches for IVDD. Intervertebral disc cells were obtained from IVDD patients undergoing circumferential arthrodesis surgery or from healthy subjects. Mimicking the harmful microenvironment of degenerated discs, cells isolated from the nucleus pulposus (NP) and annulus fibrosus (AF) were exposed to the proinflammatory cytokine IL-1β and the adipokine leptin. The metabolomic signature and molecular profile of human disc cells were unraveled for the first time. The metabolomic and lipidomic profiles of IVDD and healthy disc cells were analyzed by high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Gene expression was investigated by SYBR green-based quantitative real-time RT-PCR. Altered metabolites and gene expression were documented. Lipidomic analysis revealed decreased levels of triacylglycerols (TG), diacylglycerol (DG), fatty acids (FA), phosphatidylcholine (PC), lysophosphatidylinositols (LPI) and sphingomyelin (SM), and increased levels of bile acids (BA) and ceramides, likely promoting disc cell metabolism changing from glycolysis to fatty acid oxidation and following cell death. The gene expression profile of disc cells suggests LCN2 and LEAP2/GHRL as promising molecular therapeutic targets for disc degeneration and demonstrates the expression of genes related to inflammation (NOS2, COX2, IL-6, IL-8, IL-1β, and TNF-α) or encoding adipokines (PGRN, NAMPT, NUCB2, SERPINE2, and RARRES2), matrix metalloproteinases (MMP9 and MMP13), and vascular adhesion molecules (VCAM1). Altogether, the presented results disclose the NP and AF cell biology changes from healthy to degenerated discs, allowing the identification of promising molecular therapeutic targets for intervertebral disc degeneration. Our results are relevant to improving current biological-based strategies aiming to repair IVD by restoring cellular lipid metabolites as well as adipokines homeostasis. Ultimately, our results will be valuable for successful, long-lasting relief of painful IVDD.


Impact of age, race, and obesity on hypertensive mechanisms and therapy.
Despite the demonstrated efficacy of traditional antihypertensive therapy in reducing blood pressure, hypertension continues to be a major cause of cardiovascular disease morbidity and mortality. Stepped-care therapy is a nonphysiologic approach that, due to potential metabolic derangements and stimulation of undesirable reflex responses, may not substantially reduce the cardiovascular and renal complications associated with hypertension or improve long-term survival in many hypertensive patients. Because of fundamental hemodynamic differences related to the age, race, and weight of hypertensive patients, drug treatment often elicits varying responses. Certain classes of drugs are not only more effective but also more appropriate from a physiologic standpoint in specific types of patients. Therapy selection based in part on hemodynamic mechanisms and demographic patterns is a more rational approach to patient management and may contribute to a better overall outcome than has been observed with conventional treatment.


The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia-reperfusion injury.
Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide. After EVNP, kidneys were reperfused with whole blood under standard conditions for 3 h to assess renal function and injury. During 1-h EVNP, the mean renal blood flow was numerically higher in the argon group (49.2 ± 16.2 mL/min/100 g; P = 0.320) compared with the nitrogen and oxygen groups (42.9 ± 18.64 and 37.71 ± 7.0 mL/min/100 g, respectively). Other measures of renal function and hemodynamics were not significantly different between the argon and control groups during this period. During reperfusion, no significant differences were found in functional parameters or inflammatory markers (P < 0.05). Histologic analysis revealed no significant change in morphology or hypoxia-inducible factor-1 alpha staining between gaseous groups. Nuclear hypoxia-inducible factor-1 alpha staining was observed only after 3 h of reperfusion. Our findings suggest that using 70% argon during 1 h of EVNP does not mediate a measurable organoprotective effect in an experimental porcine model of IRI.


Late-onset vascular complications of radiotherapy for primary brain tumors: a case-control and cross-sectional analysis.
Radiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT). We retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study. A total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%). Stroke prevalence is increased in long-surviving PBT patients treated with cranial RT. CV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.


Robot-assisted radical prostatectomy may induce inguinal hernia within the first 2 years: An 11-year single-surgeon experience of >400 cases.
At present, robot-assisted radical prostatectomy (RARP) is a gold standard in radical prostatectomy. The aim of this study was to evaluate the incidence, risk factors, and timing of occurrence of inguinal hernia (IH) after RARP.We included 427 patients with prostate cancer who underwent RARP by a single surgeon from February 2006 to August 2017. Incidence, clinical, and pathological factors were investigated to assess relationship with the development of IH.Postoperative IH occurred in 29 cases (6.79% of all RARP patients), whereas 22 cases (75.9% of all IH patients) occurred within the first 2 years. The median follow-up period was 5.2 years, and the median age of patients was 65 years. Postoperative IH occurrence was significantly associated with body mass index (BMI), smoking history, and low surgeon experience (P = .036, .023, and .048, respectively). However, low surgeon experience did not reach statistical significance after multivariate analysis.The overall incidence of IH after RARP was significantly associated with BMI and smoking history. With obvious incidence of IH within the first 2 years after operation which was not observed at the open prostatectomy, RARP itself may play a role in the development of IH.


Audiological Evaluation in Hypothyroid Patients and Effect of Thyroxine Replacement Therapy.
To do the audiological evaluation of patients with hypothyroidism and to assess status of hearing after thyroxin replacement therapy (TRT). Two groups were included: a hypothyroidism group (HG, n = 50), and a control group (CG, n = 50). Parameters studied: anominesic data, duration of hypothyroidism, comorbidities, cochleovestibular symptoms, biochemical and hormonal exams (TSH, FT4 and FT3), pure tone audiometry, impendence audiometry and BERA as where required. Mean age of the patients in HG was 26.5 ± 10.4 years. Male/Female ratio was 2.39. All HG patients had altered TSH values and 8% had diminished T4 values. Cochleovestibular symptoms were more common in hypothyroid patients (48%) than control (20%) p value. Pure Tone Audiometric threshold was found higher in 34% of cases. Sensorineural hearing loss was most common (76.46%) compared to conductive and mixed hearing loss. BERA showed significant prolonged absolute peak latency of wave III, inter peak latency (IPL) of wave I-III and reduced amplitude of wave Ia and Va. After thyroxine replacement therapy there was statistically significant improvement in hearing threshold in 46.42% ears (p < 0.05), (if ≥ 5 dB hearing improvement consider as significant). The significant improvement was also found in BERA, in amplitude of wave Va. Site of involvement was at several levels, middle ear, cochlear or retro-cochlear. HG patients had more cochleovestibular symptoms, higher audiometric thresholds, increase in latency of wave III, IPL of I-III and reduced Ia and Va amplitude in the BERA. After TRT improvement in hearing threshold and BERA was found.


Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia.
Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.


Characterization of monoacylglycerols and diacylglycerols rich in polyunsaturated fatty acids produced by hydrolysis of Musteleus mustelus liver oil catalyzed by an immobilized bacterial lipase.
The use of an immobilized Serratia. sp W3 lipase as a replacement for the standard pancreatic lipases in the hydrolysis of liver oil from the Musteleus mustelus was studied. Monoacylglycerols (MAGs) and diacylglycerols (DAGs) containing ω-3 polyunsaturated fatty acids, namely eicosapentaenoic and docosahexaenoic acids were produced in hexane solvent at reaction temperatures reaching 55 °C with a molar triacylglycerol conversion over than 75 ± 5% in 24 h showing excellent hydrolysis characteristics. The favorable conditions for the hydrolysis reaction allowed fats with higher melting points to be analyzed facilitating the coupling of the hydrolysis reaction to the later steps in the analytical protocol. The lipid composition was elucidated for the first time by employing a highly efficient UHPLC-MS method with a novel embedded linear retention index approach. MAGs and DAGs obtained during the enzymatic hydrolysis could be used for the production of glycerol based emulsifiers of nutritional interest.


Unsaturated fatty acid effect on cyclic AMP levels in human embryo lung fibroblasts.
The addition of arachidonic acid at 250 muM to cultures of human embryo lung fibroblasts (IMR-90) increases cellular cyclic AMP levels within 5 minutes to approximately 15-fold over basal. Other unsaturated fatty acids, 11, 14, 17-eicosatrienoic, linoleic, 8, 11, 14-eicosatrienoic and oleic also cause similar rapid elevation of cellular cyclic AMP. During this time interval, no detectable conversion of the added linoleic or arachidonic acids to prostaglandin is observed. These cells produce prostaglandins at measurable concentrations in response to treatment with ascorbic acid or bradykinin. Saturated fatty acids have no influence on cyclic AMP levels in these cells. This effect of unsaturated fatty acids on cellular cyclic AMP levels varies with the cell type. For example, smooth muscle and endothelial cells obtained from the calf pulmonary artery show very little or no increase in cellular cyclic AMP upon exposure to arachidonic acid.


Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab.
We investigated the combined effects of sarcopenia and inflammation on outcomes in patients with HCC treated with nivolumab. We reviewed 102 patients treated with nivolumab between 2017 and 2018. Sarcopenia was diagnosed when the L3 skeletal muscle indices were < 42 cm2/m2 and < 38 cm2/m2 in men and women, respectively. Baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count were used as surrogate markers of inflammation and immune cell reservoir. High NLR (hNLR) was defined as NLR ≥ 3, and severe lymphopenia (sLP) was defined as lymphocyte < 800/μL. The overall survival (OS) and progression-free survival (PFS) were analyzed. With a median follow-up of 21.9 (interquartile range, 8.3-58.3) months, patients with sarcopenia showed shorter OS than those without sarcopenia (median, 2.9 vs. 7.5 months, respectively). Patients with either hNLR or sLP exhibited inferior survival than those without risk factor (median OS, 2.8 vs. 14.5 months; median PFS, 1.3 vs. 3.7 months, respectively). Among 70 patients treated with RT, benefit of RT was observed in patients with sarcopenia or those without hNLR/sLP (all p < 0.05). After multivariable analysis, RT, hNLR/sLP, albumin-bilirubin (ALBI) grade, and alpha-fetoprotein were significantly associated with OS (all p < 0.05), and hNLR/sLP was also associated with decreased PFS together with ALBI grade, alpha-fetoprotein, and RT (all p < 0.05). The current study hypothetically demonstrated that the risk group stratified by hNLR/sLP outweighs the significance of sarcopenia in predicting outcomes after nivolumab. Furthermore, patients with sarcopenia might benefit from RT, especially those without risk factors of hNLR/sLP.


Metabolite concentrations in the developing brain estimated with proton MR spectroscopy.
The purpose of the present study was to estimate absolute concentrations and relaxation time constants of metabolites that were detectable with proton magnetic resonance (MR) spectroscopy in the healthy preterm, term, and infant brain. Five MR spectra were recorded for each infant by using STEAM (stimulated-echo acquisition mode) sequences with different TEs and TRs. Water was used as an internal standard. The T1 of choline-containing compounds (Cho) and the T1 of phosphocreatine plus creatine (PCr+Cr) decreased. The T2 of the N-acetyl-L-aspartate (NAA) resonance increased, probably because of a relatively larger signal overlap with glutamate in the most immature brains. The concentration of NAA almost doubled, whereas the Cho concentration showed only a nonsignificant tendency to decrease; therefore, the well-known increase in the ratio of NAA to Cho appears to be due mostly to an increase in NAA concentration. The concentration of PCr+Cr increased rapidly and reached adolescent values at approximately 4 months of age.


Expression pattern of embryonic stem cell markers in DFAT cells and ADSCs.
Mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability under the condition of ceiling method, named dedifferentiated fat cells (DFAT cells). These cells exhibit multilineage potential as adipose tissue-derived stromal cells (ADSCs). However, the stem molecular signature of DFAT cells and the difference distinct from ADSCs are still not sure. To study the molecular signature of DFAT cells better, highly purified mature adipocytes were obtained from rats and the purity was more than 98%, and about 98.6% were monocytes. These mature adipocytes dedifferentiated into fibroblast-like cells spontaneously by the ceiling culture method, these cells proliferated rapidly in vitro, grew in the same direction and formed vertex, and expressed extensively embryonic stem cell markers such as Oct4, Sox2, c-Myc, and Nanog, surface antigen SSEA-1, CD105, and CD31, moreover, these cells possessed ALP and telomerase activity. The expression level was Oct4 1.3%, Sox2 1.3%, c-Myc 1.2%, Nanog 1.2%, CD105 0.6%, CD31 0.6% and SSEA-1 0.4%, respectively, which was lower than that in ADSCs, but the purity of DFAT cells was much higher than that of ADSCs. In conclusion, DFAT cells is a highly purified stem cell population, and expressed some embryonic stem cell markers like ADSCs, which seems to be a good candidate source of adult stem cells for the future cell replacement therapy.


Dentate gyrus and CA3 GABAergic interneurons bidirectionally modulate signatures of internal and external drive to CA1.
Specific classes of GABAergic neurons play specific roles in regulating information processing in the brain. In the hippocampus, two major classes, parvalbumin-expressing (PV+) and somatostatin-expressing (SST+), differentially regulate endogenous firing patterns and target subcellular compartments of principal cells. How these classes regulate the flow of information throughout the hippocampus is poorly understood. We hypothesize that PV+ and SST+ interneurons in the dentate gyrus (DG) and CA3 differentially modulate CA3 patterns of output, thereby altering the influence of CA3 on CA1. We find that while suppressing either interneuron class increases DG and CA3 output, the effects on CA1 were very different. Suppressing PV+ interneurons increases local field potential signatures of coupling from CA3 to CA1 and decreases signatures of coupling from entorhinal cortex to CA1; suppressing SST+ interneurons has the opposite effect. Thus, DG and CA3 PV+ and SST+ interneurons bidirectionally modulate the flow of information through the hippocampal circuit.


Endoscopic removal of an inadvertently swallowed toothbrush in the emergency department.
A 16-year-old girl inadvertently swallowed a toothbrush during attempted manual induction of emesis. The 20 cm toothbrush was successfully removed via overtube facilitated endoscopy using a retractable snare while the patient was sedated in the emergency department.


Increased vascular endothelial cell markers in patients with disseminated intravascular coagulation.
We examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator (t-PA), and von Willebrand factor, in 80 patients with disseminated intravascular coagulation (DIC). The levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and FDP-D-dimer were significantly increased both before and after the onset of DIC, but were not correlated with organ failure or prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis than in those with good prognosis, and it was also lower in those with organ failure than in those without. Plasma TM, PAI-I, and t-PA levels were increased in DIC patients with organ failure or poor outcome, but were not significantly increased before the onset of DIC. We consider that the prognosis of patients with DIC might be related to organ failure or endothelial cell damage and that plasma levels of TM, PAI-I, and t-PA might be useful in the detection of these disorders and in assessing prognosis. A hypofibrinolytic state might enhance organ failure in patients with DIC.


Retinal ganglion cell layer thinning within one month of presentation for optic neuritis.
Spectral domain optical coherence tomography (SD-OCT) reveals retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (pRNFL) thinning in chronic optic nerve injury. At presentation, swelling of the pRNFL confounds evaluation of early axon loss. We studied whether the GCL+IPL thins before the pRNFL, the trajectory of GCL+IPL loss and relationship to vision. We prospectively evaluated 33 eyes (study) with new optic neuritis, using perimetry and SD-OCT with investigative three-dimensional layer segmentation and commercial two-dimensional segmentation to compute the GCL+IPL and pRNFL thickness. At presentation, GCL+IPL thickness (82.4±8.8 µm) did not differ from unaffected fellow eyes (81.2±6.7 µm), via the three-dimensional method, while the two-dimensional method failed in 9% of study eyes. At 1-2 months, there was thinning of the pRNFL in 10% and of the GCL+IPL in 93% of study eyes. GCL+IPL reduction was greatest during the first 2 months. GCL+IPL thinning at 1-2 months correlated with GCL+IPL thinning at 6 months (r=0.84, P=0.01) and presentation visual acuity (r=0.48, P=0.006) and perimetric mean deviation (r=0.52, P=0.003). GGL+IPL is an early biomarker of structural injury in optic neuritis as thinning develops within 1-2 months of onset, prior to pRNFL thinning.


Tertiary pediatric emergency department admission rates fall as waiting times increase.
To examine whether children in the same triage category presenting to a tertiary paediatric emergency department are more likely to be admitted to hospital if their wait is longer. Retrospectively during a 7-year period, we determined the admission rate of children with lower acuity triage scores and compared 3 groups; those seen in their recommended triage time (group A), those seen under twice their recommended time (group B), and those seen in over twice their recommended time (group C). Patients in groups B and C were less likely to be admitted for both triage categories 3 and 4 compared with group A (P < 0.005 for all admission rate comparisons). This held true in individual diagnostic groups. Predictably, but reassuringly, those patients waiting longer than the recommended category time are no more likely to get admitted and do not represent a grossly different subset of patients in terms of age and diagnosis. Further work is needed to identify, at the point of triage, the characteristics of children who are unlikely to deteriorate during their wait.


Bone marrow transplantation for diamond-blackfan anemia.
Patients with Diamond-Blackfan anemia (DBA) who are unresponsive to or intolerant of corticosteroids, experience treatment failure with other treatments, develop additional cytopenias or clonal disease, or opt for curative therapy are often treated with allogeneic bone marrow transplantation. We studied the transplantation outcomes of 61 DBA patients whose data were reported to the International Bone Marrow Transplant Registry between 1984 and 2000. The median age was 7 years (range, 1-32 years). Among 55 patients with available transfusion information, 35 (64%) had received > or =20 units of blood before transplantation. Most patients (67%) received their bone marrow grafts from an HLA-matched related donor. The median time to neutrophil recovery was 17 days (range, 10-119 days) and to platelet recovery was 23 days (range, 9-119 days). Five patients did not achieve neutrophil engraftment. The 100-day mortality was 18% (95% confidence interval, 10%-29%). Grade II to IV acute graft-versus-host disease occurred in 28% (range, 17%-39%) and chronic graft-versus-host disease in 26% (range, 15%-39%). The 3-year probability of overall survival was 64% (range, 50%-74%). In univariate analysis, a Karnofsky score > or =90 and transplantation from an HLA-identical sibling donor were associated with better survival. These data suggest that allogeneic bone marrow transplantation is effective for the treatment of DBA. Transplantation before deterioration of the performance status and from an HLA-identical sibling donor may improve survival.


Isolation of phenol-degrading Bacillus stearothermophilus and partial characterization of the phenol hydroxylase.
Bacillus stearothermophilus BR219, isolated from river sediment, degraded phenol at levels to 15 mM at a rate of 0.85 mumol/h (4 x 10(6) cells). The solubilized phenol hydroxylase was NADH dependent, exhibited a 55 degrees C temperature optimum for activity, and was not inhibited by 0.5 mM phenol.


Spatiotemporal dynamics of soil loss and sediment export in Upper Bilate River Catchment (UBRC), Central Rift Valley of Ethiopia.
Soil loss is one of the major challenges for agricultural production in the Ethiopian highlands. The rate and distribution of soil loss (SL) and sediment export (SE) are essential to map degradation "hotspot" areas for prioritizing soil and water conservation measures. The objective of this study was to estimate the dynamics of SL and SE in the Upper Bilate River Catchment of Central Ethiopia. The Sediment Delivery Ratio (SDR) module of the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model was used to estimate and map SL and SE. The primary input data were rainfall, soil data, land use, and other biophysical parameters of the study area. The model output confirmed that the average total soil loss of the catchment was 36.8 million ton/yr. It is modeled that soil loss doubles within 30 years. The average annual sediment export was about 3.62 ton/ha/yr. The mean annual soil loss of the study area was 23 ton/ha/yr, which exceeded the soil loss tolerance (SLT), estimated to range between (2-18 ton/ha/yr) in Ethiopia. Based on the soil erosion risk level, about 22% of the catchment area was classified as severely degraded, while 62 % was moderately degraded. Severe soil erosion prevails in the sub-watershed (SW)-5, SW-4, and SW-13. Therefore, these sub-watersheds need priority conservation action to restore the ecosystem processes of the study area.


Clinical characteristics and magnetic resonance imaging findings in nine patients with nonalcoholic Wernicke's encephalopathy: a retrospective study.
Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency. The most common cause of WE is alcoholism. However, there is a significant paucity of information in the existing literature relating to nonalcoholic WE. In this study, we investigated the clinical characteristics and neuroimaging findings of nine patients with nonalcoholic WE. We retrospectively collated clinical data from nine patients who had been diagnosed with WE in accordance with established criteria including age, gender, risk factors and clinical manifestations. We also collated initial hematological and neuroimaging findings. The mean age of the nine patients was 54.0±17.1 years; four of these patients (44.4%) were male. All nine patients had a history of fasting (range, 5-47 days) prior to WE. Four of the nine patients (44.4%) exhibited the classical triad, and eight (88.9%) showed alterations in mental status. Magnetic resonance imaging (MRI) scans showed that all nine patients had symmetric lesions of the medial thalamus. MRI also revealed other WE-related lesions in mammillary bodies (22.2%), the periaqueductal region (55.6%), the tectal plate of the midbrain (77.8%), cranial nerve nuclei (77.8%) and in the symmetric subcortical white matter (11.1%). Our analysis showed that fasting is a common cause of WE in nonalcoholic patients and that MRI is a useful tool for the diagnosis of WE. The most common MRI findings were symmetrical lesions of the medial thalamus lesions, followed by the tectal plate of the midbrain and cranial nerve nuclei.


Serum leptin and cholesterol values in suicide attempters.
The growing number of studies examining the relationship between suicide and lipid metabolism are based upon studies suggesting that cholesterol-lowering procedures may increase the risk of death due to suicide or impulsive-aggressive behavior. Leptin seems to be strongly associated with lipid metabolism. In the present study, serum total cholesterol and leptin levels were compared in 24 suicide attempters and 24 healthy controls. The patients with suicide attempts had significantly lower serum cholesterol and leptin levels than controls. There was a positive correlation between cholesterol and leptin levels in both groups. Our results suggest that suicide attempts seem to be associated with decreased serum cholesterol and leptin levels.


Intercalation of a Heterocyclic Ligand between Quartets in a G-Rich Tetrahelical Structure.
YES G-rich oligonucleotide VK2 folds into an AGCGA-quadruplex tetrahelical structure distinct and significantly different from G-quadruplexes, even though it contains four G3 tracts. Herein, a bis-quinolinium ligand 360A with high affinity for G-quadruplex structures and selective telomerase inhibition is shown to strongly bind to VK2. Upon binding, 360A does not induce a conformational switch from VK2 to an expected G-quadruplex. In contrast, NMR structural study revealed formation of a well-defined VK2-360A complex with a 1:1 binding stoichiometry, in which 360A intercalates between GAGA- and GCGC-quartets in the central cavity of VK2. This is the first high-resolution structure of a G-quadruplex ligand intercalating into a G-rich tetrahelical fold. This unique mode of ligand binding into tetrahelical DNA architecture offers insights into the stabilization of an AGCGA-quadruplex by a heterocyclic ligand and provides guidelines for rational design of novel VK2 binding molecules with selectivity for different DNA secondary structures.


Trisomy 14 in refractory anemia with excess of blasts in transformation.
Trisomy 14 was demonstrated on four occasions over a 2-year period in the bone marrow cells of a 63-year-old patient with refractory anemia with excess of blasts in transformation (RAEB-t). Trisomy 14 as the sole karyotype abnormality has been documented in only six malignancies, namely, in two cases of acute leukemias, one Philadelphia-negative chronic myeloid leukemia, one pancytopenia, and in two colonic polyps. In hematologic neoplasms, this rare primary change preferentially occurs in elderly adults and seems exclusively associated with the myeloid cell lineage.


CpGPAP: CpG island predictor analysis platform.
Genomic islands play an important role in medical, methylation and biological studies. To explore the region, we propose a CpG islands prediction analysis platform for genome sequence exploration (CpGPAP). CpGPAP is a web-based application that provides a user-friendly interface for predicting CpG islands in genome sequences or in user input sequences. The prediction algorithms supported in CpGPAP include complementary particle swarm optimization (CPSO), a complementary genetic algorithm (CGA) and other methods (CpGPlot, CpGProD and CpGIS) found in the literature. The CpGPAP platform is easy to use and has three main features (1) selection of the prediction algorithm; (2) graphic visualization of results; and (3) application of related tools and dataset downloads. These features allow the user to easily view CpG island results and download the relevant island data. CpGPAP is freely available at http://bio.kuas.edu.tw/CpGPAP/. The platform's supported algorithms (CPSO and CGA) provide a higher sensitivity and a higher correlation coefficient when compared to CpGPlot, CpGProD, CpGIS, and CpGcluster over an entire chromosome.


Visual literacy in the online environment.
Visual literacy combines words and graphics to enhance learning. Students are immersed in digital literacy and multimodal learning; therefore, it is important for educators to embrace visual literacy and strike out beyond printed text, PowerPoint slides, and discussion boards. This article describes the use of visual literacy as a tool to enhance student learning. An example demonstrating the application of visual literacy to teach transcultural nursing in an online environment is provided. The Web site containing a copy of the visual literacy teaching tool is also available to readers.


Optimal surgical cytoreduction of the upper abdomen and the diaphragm for advanced ovarian cancer using PlasmaJet™ energy.
To show the contribution of PlasmaJet™, technology using pur gaz plasma as electrically neutral source of energy to cut and coagulate tissue, in ovarian cancer surgery. A forty eight years old patient was diagnosed with an ovarian cancer. The first laparoscopy allowed one to make histological diagnosis (ovarian high-grade serous carcinoma) and determine that the disease was resecable, with a PCI to ten. The film shows the upper abdominal time of the cytoreduction surgery, using PlasmaJet™. The surgery included: stripping of the peritoneum of the right diaphragm and full thickness diaphragmatic resection, stripping of the peritoneum of left diaphragm splenectomy, resection of the greater and the lesser omentums, pelvic lymphadenectomy and para-aortic lymphadenectomy, posterior pelvectomy (Hudson) and appendicectomy. There were no postoperative complications (short or medium term). The PlasmaJet seems to be a very interesting instrument in this type of surgery, particularly in the dissection of adherent pathological areas, as diaphragmatic domes can be.


Effect of corticosteroid and cyclophosphamide in IgA nephropathy patients with heavy proteinuria and/or moderate-severe pathological changes.
The treatment of immunoglobulin (Ig) A nephropathy remains a subject of controversy. To clarify if it is justified to use corticosteroid and cyclophosphamide in the treatment of IgA nephropathy patients with heavy proteinuria and/or a moderate-severe pathological grading of at least grade II, we retrospectively analyzed the medical data of IgA nephropathy patients in our hospital. Totally 60 patients from 370 cases of biopsy-proved IgA nephropathy in our hospital between 1983 and 1999 met the selection criteria and were enrolled into this analysis. These patients received either corticosteroid alone or in combination with cyclophosphamide. The analysis of the progression of renal disease by serum creatinine and changes in the level of proteinuria were based on an on-treatment approach. Kidney survival curve was by Kaplan-Meier analysis and compared among different subgroups. Of the 60 patients, 20 cases (33.3%) (Group 1) reached a complete remission of proteinuria by prednisolone alone. The other cases received a combination therapy with corticosteroid and cyclophosphamide, which resulted in complete remission in 17 cases (28.3%) (Group 2), partial remission in 9 cases (15.0%) (Group 3) and complete resistance in 14 patients (23.3%) (Group 4). The renal survival rate was significantly worse in Group 4 (p < 0.05) as compared with other groups. We conclude that corticosteroid and combination therapy with corticosteroid and cyclophosphamide was effective treatment in 61.6% (Groups 1 and 2) of IgA nephropathy patients with heavy proteinuria and/or moderate-severe pathological lesions provided their initial serum creatinine level was < or = 3 mg/dl.


Tamoxifen enhances myoepithelial cell suppression of human breast carcinoma progression in vitro by two different effector mechanisms.
Our previous studies have indicated that myoepithelial cells surrounding ductal and acinar epithelium of glandular organs, such as the breast, exert multiple paracrine suppressive effects on incipient and developing cancers that arise from this epithelium. Myoepithelial cells and derived cell lines (HMS 1-6) exert these effects through the secretion of a number of different effector molecules that exert anti-invasive, anti-proliferative, and anti-angiogenic activities. Since previous basic and clinical studies have examined the role of estrogen agonists and antagonists on human breast cancer cells and because issues of hormone replacement therapy (HRT) and tamoxifen chemoprevention are such timely issues in breast cancer, we wondered whether or not hormonal manipulations might affect myoepithelial cells in vitro as far as their paracrine suppressive activities on breast cancer were concerned. The present in vitro study demonstrates that treatment of myoepithelial cells with tamoxifen but not 17beta-estradiol increases both maspin secretion and invasion-blocking ability. Furthermore tamoxifen but not 17beta-estradiol increases inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production by myoepithelial cells when they are co-cultured with conditioned media from or breast carcinoma cells directly. This increased myoepithelial NO exerts both autocrine and paracrine antiproliferative effects which can be blocked by inhibition of iNOS. 17beta-Estradiol, however, competes with all of these suppressive effects of tamoxifen suggesting that the mechanism of tamoxifen action is estrogen receptor mediated. Myoepithelial cells lack ER-alpha but express ER-beta. Tamoxifen, but not 17beta-estradiol, increases AP-1 CAT but not ERE-CAT activity. Again, 17beta-estradiol competes with the transcription-activating effects of tamoxifen. These experiments collectively suggest that the actions of tamoxifen on the increased secretion of maspin and increased production of NO by myoepithelial cells are mediated through ER-beta and the transcription-activation of an ER-dependent AP-1 response element.


Fetal membrane patch and biomimetic adhesive coacervates as a sealant for fetoscopic defects.
Iatrogenic preterm premature rupture of membranes after fetoscopic procedures affects 10-47% of patients, secondary to the non-healing nature of membranes and the separation of layers during the entry. In this study we developed an in vitro model to mimic the uterine wall-fetal membrane interface using a water column with one end sealed with human fetal membranes and poultry breast, and a defect was created with an 11 French trocar. Further, a fetal membrane patch in conjunction with multiphase adhesive coacervates modeled after the sandcastle worm bioadhesive was tested for sealing of an iatrogenic defect. The sealant withstood an additional traction of 12 g for 30-60 min and turbulence of the water column without leakage of fluid or slippage. The adhesive is non-toxic when in direct contact with human fetal membranes in an organ culture setting. A fetal membrane patch with multiphase adhesive complex coacervates may help to seal the defect and prevent iatrogenic preterm premature rupture of the membranes.


The prevalence of inherited thrombophilias in a Caucasian Australian population.
To describe the prevalence of four inherited thrombophilias and their combinations for the first time in a large Caucasian Australian population. Newborn screening cards of 883 Caucasian babies born in South Australia in 1986-1999 were de-identified and tested for the following inherited thrombophilic polymorphisms: factor V Leiden (G1691A), prothrombin gene mutation (G20210A), methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C, as well as compound heterozygosity for the MTHFR polymorphisms. The birth prevalences of heterozygosity and homozygosity for the four thrombophilic polymorphisms were: factor V Leiden 9.5% and 0.7%, prothrombin gene 4.1% and 0.2%, MTHFR C677T 37.3% and 12.4%, and MTHFR A1298C 38.3% and 11.8%, respectively. Compound heterozygosity for MTHFR C677T and A1298C was seen in 16.6% of the population. Overall, 64.2% and 24.5% of the population studied were homozygous and heterozygous, respectively, for at least one of the four polymorphisms studied. Inherited thrombophilic polymorphisms are common in the Caucasian Australian population. Knowledge of the background prevalence of these polymorphisms will allow further study of their associations in future disease research.


[Mandibular ossifying fibroma and compound odontoma: a case report].
A case diagnosed as ossifying fibroma and compound odontoma in the mandible was reported. The clinicopathological features, diagnosis, and treatment were discussed with the literature review.


Purification and characterization of a halotolerant intracellular protease from Bacillus subtilis strain FP-133.
A halotolerant strain FP-133, able to grow at concentrations of 0-12.5% (w/v) NaCl, was isolated from a fish paste and identified as Bacillus subtilis . B. subtilis strain FP-133 produced an intracellular protease which showed catalytic activity under saline conditions. The enzyme was purified to homogeneity 143-fold with a yield of 0.9%. The purified enzyme showed an optimum activity at a concentration of 5% (w/v) NaCl. After storage in 7.5% (w/v) NaCl at 4 degrees C for 24 h, the enzyme kept 100% of its activity. The molecular mass of the protease was determined to be 59 kDa by gel filtration; the protein consisted of four subunits each with a molecular mass of 14 kDa. The enzyme showed aminopeptidase activity. It acted on L-leucyl-p-nitroanilide, L-leucyl-beta-naphthylamide, and oligopeptides containing glycine, L-histidine, or L-leucine. The K(m ) and V (max) values for L-leucyl-p-nitroanilide were 18 microm and 2.2 mm/h mg, respectively. The enzyme was activated by Fe(2+), Fe(3+), and Ni(2+) in synergism with Mg(2+).


Microdomains shift and rotate in the lateral wall of cochlear outer hair cells.
Outer hair cell (OHC) electromotility, a response consisting of reversible changes in cell length and diameter induced by electrical stimulation, confers remarkable sensitivity and frequency resolution to the mammalian inner ear. Looking for a better understanding of this mechanism, we labeled isolated guinea pig OHCs with microspheres and, using high-speed video recording, investigated their movements at the apical, mid, and basal regions of osmotically and electrically stimulated cells. After hypoosmotic challenge, OHCs shortened and their diameter increased, with microspheres moving always toward the central plane; iso-osmolarity returned OHCs to their original shape and microspheres to their original positions. Under electrical stimulation, microspheres exhibited robust movements, with their displacement vectors changing in direction from random to parallel to the longitudinal axis of the cells with peak reorientation speeds of up to 6 rad/s and returning to random after 5 min without stimulation. Alterations in plasma-membrane cholesterol levels as well as cytoskeleton integrity affected microsphere responses. We concluded that microspheres attach to different molecular microdomains, and these microdomains are able to shift and rotate in the plane of the OHC lateral wall with a dynamics tightly regulated by membrane lipid composition and the cortical cytoskeleton.


The frequency of transforming growth factor-beta1 gene polymorphisms in a normal southern Iranian population.
Several single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele frequencies in different ethnic groups is useful for both population genetic analyses and association studies with immunological diseases. In this study, five SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian population using polymerase chain reaction-restriction fragment length polymorphism method. This population was in Hardy-Weinberg equilibrium for these SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in the normal southern Iranian population. Comparison of genotype and allele frequencies of TGFB SNPs between Iranian and other populations (meta-analysis) showed significant differences, and in this case the southern Iranian population seems genetically similar to Caucasoid populations. However, neighbour-joining tree using Nei's genetic distances based on TGF-beta1 allele frequencies showed that southern Iranians are genetically far from people from the USA, Germany, UK, Denmark and the Czech Republic. In conclusion, this is the first report of the distribution of TGFB1 SNPs in an Iranian population and the results of this investigation may provide useful information for both population genetic and disease studies.


Metabolic engineering and transcriptomic analysis of Saccharomyces cerevisiae producing p-coumaric acid from xylose.
Aromatic amino acids and their derivatives are valuable chemicals and are precursors for different industrially compounds. p-Coumaric acid is the main building block for complex secondary metabolites in commercial demand, such as flavonoids and polyphenols. Industrial scale production of this compound from yeast however remains challenging. Using metabolic engineering and a systems biology approach, we developed a Saccharomyces cerevisiae platform strain able to produce 242 mg/L of p-coumaric acid from xylose. The same strain produced only 5.35 mg/L when cultivated with glucose as carbon source. To characterise this platform strain further, transcriptomic analysis was performed, comparing this strain's growth on xylose and glucose, revealing a strong up-regulation of the glyoxylate pathway alongside increased cell wall biosynthesis and unexpectedly a decrease in aromatic amino acid gene expression when xylose was used as carbon source. The resulting S. cerevisiae strain represents a promising platform host for future production of p-coumaric using xylose as a carbon source.


In-stent restenotic lesions can rupture--a case against plaque sealing.
We present a case of plaque rupture located inside a restenotic stent. Intravascular ultrasound defined a lesion with a minimal lumen area (MLA) of 3.59 cm², plaque burden of 72%, and reference vessel luminal diameter of 4.0 mm with an external elastic membrane lumen cross-section area of 12.6 mm². There was a clearly identified plaque rupture, with a flap-like dissection within the stented segment. Virtual histology intravascular ultrasound confirmed that the adjacent plaque had necrotic core with a thin overlying fibrous cap. The remaining tissue next to the dissection plane was fibrotic. This case illustrates that neointimal hyperplasia may organize into an unstable plaque, with a thin fibrous cap overlying a lipid-rich necrotic core-a so-called virtual histology thin-capped fibroatheroma. As defined in the PROSPECT trial, the in-stent stenotic lesion in our case conformed to the definition of a high-risk plaque-it had an MLA < 4 mm², plaque burden was ≥ 70%, and there was >10% necrotic core. It became unstable and ruptured. The demonstrated findings of this case may sway physicians against sealing hemodynamically nonsignificant unstable plaques.


Intrauterine growing skull fracture.
Growing skull fractures with development of leptomeningeal cysts are rare complications of head injuries and have not been described in the perinatal period. The case history of a newborn with bilateral parietal fractures and the formation of a leptomeningeal cyst on one side detected at birth is presented. The importance of radiographic evaluation, including skull films, computered tomography, and magnetic resonance imaging, as well as the associated subarachnoid cyst and the age of presentation are discussed.


Investigation into three dimensional hip anatomy in anterior dislocation after THA. Influence of the position of the hip rotation centre.
The components position is a major factor under the surgeon's control in determining the risk of dislocation post total hip arthroplasty. The aim of this study was to investigate the proper three-dimensional components position including the centre of rotation in the case of anterior dislocation. Among 1764 consecutive patients who underwent total hip arthroplasty using a direct anterior approach, 27 experienced anterior dislocation. The three-dimensional hip anatomy was investigated in 12 patients who were paired with 12 patients from the same initial cohort who did not experience dislocation and also with 36 control patients with osteoarthritis. A pelvic Cartesian referential was defined to perform the acetabular analysis. The coordinates were expressed as percentages of the pelvic width, height and depth. The anteversion angles were measured. The hip centre of rotation was significantly shifted medially and posteriorly in the dislocation group when compared to the non-dislocation group and also to the control group. There was no significant difference in component angular position between the dislocation-group and the non-dislocation group. However, the stem anteversion in the dislocation group was increased in comparison to the mean natural femoral anteversion of the control group. A medial and posterior displacement of the hip rotation centre was found to correlate to anterior dislocation post total hip arthoplasty. These results suggest the importance of an accurate restoration of the centre of rotation, whilst avoiding an excessive acetabular reaming which may induce a medial and a posterior displacement. III comparative non randomised.


Cancer, scale and component reliability.
The incidence of cancer does not vary wildly between species of very different weights. Thus larger species have much lower incidence per pound. Nature, when necessary, can produce tissue that is much less cancer-prone than that of mice, or men. Flesh is only as cancer free as it needs to be. However animals defend themselves against cancer, large animals have to do it better, and may be the best place to look for the mechanisms.


Trucut biopsy of breast lesions: the first step toward international standards in developing countries.
The new concept in breast cancer diagnosis and treatment is based on a less invasive, more accurate and effective strategy, with a multidisciplinary approach in a specialised breast unit. When indicated, conservative surgery has replaced mastectomy with sentinel-node biopsy substituting routine axillary dissection. But the key factor in respect of these new standards is to confirm the cancer before going to the operating room. Trucut biopsy is performed instead of incisional or excisional biopsy and frozen section. The technique is reliable, simple, and reproducible, and not at all expensive; it can be adapted even for low-income developing countries. Between March 2006 and June 2010, 764 patients under clinical suspicion of cancer and/or with BIRADS (Breast Imaging Reporting and Data System) III-V in imaging in one university and one private hospital in Tehran, Iran underwent trucut biopsy (60% palpable and 40% non-palpable lesions). Cancer was found in 30.8% of the cases. In benign pathology, in concordance with clinical and imaging suspicion, surgery was omitted with short-term follow-up. For palpable symptomatic benign lesions surgery was performed to relieve the patient's symptoms. When the pathology report was not in concordance with clinical/imaging suspicion (1.8%), and in the presence of moderate and severe hyperplasia with or without atypia, in lobular and papillary lesions (4.9%) open biopsy was done to rule out cancer (10 added cancers, 1.3%; total cancers 32.1%). Cancer surgery was done as a single procedure in 89.8% of cases. Trucut biopsy for breast lesion assessment is the first step toward a new concept in breast cancer care. It is simple, reduces the number of surgeries (no surgery for non-symptomatic benign lesions and one surgery for cancer), and avoids diagnostic errors with full respect for the patient's rights. We insist on its routine use to extend international guidelines while decreasing the total cost of this common disease in all low-resource countries.


Comparison of the severity of sleep-disordered breathing in Asian and Caucasian patients seen at a sleep disorders center.
Race can be considered a risk factor for sleep-disordered breathing (SDB), with higher prevalences and greater severity of the disorder documented among persons of certain racial groups compared with others. Based on clinical observation, it was hypothesized that, other risk factors being equal, Asian patients with SDB have greater severity of their illness compared to Caucasian patients. A cross-sectional study was conducted at a sleep disorders clinic involving 105 Asian patients diagnosed as having SDB after undergoing polysomnography and 99 similarly diagnosed Caucasian patients matched for the following variables: age, gender and body mass index (BMI). The main outcome measure of interest was objective assessment of severity based on polysomnographic data of respiratory disturbance index (RDI) and minimum oxygen saturation (SaO2) during sleep. Symptom scores between patients of the two racial groups were also compared. There were significantly larger proportions of Asians compared to Caucasians with severe obstructive sleep apnea (OSAS) as defined by respiratory disturbance index (RDI) > or = 50 (25.0% vs 11.1%; P = 0.0288) or minimum oxygen saturation (SaO2) < or = 69% (20.6% vs 4.2%; P = 0.0113). The mean minimum SaO2 was significantly lower (P = 0.0001) while the mean (log transformed) esophageal pressure (Pes) value was significantly higher (P = 0.0090) in the Asian group. Logistic regression analysis showed that race was associated with severe SDB (RDI > or = 50) independent of age, sex and BMI. The estimated odds ratio for Asians having severe OSAS compared with Caucasians was 2.51 [95% Confidence Interval (CI) 0.98-6.64]. There was no significant difference in the severity of questionnaire-based symptoms of snoring, apneas during sleep and the median Epworth scores between Asian and Caucasian patients. Based on objective polysomnographic results, Asian patients with OSAS have greater severity of their illness compared to Caucasian patients matched for age, gender and BMI. There was, however, no significant difference in severity of questionnaire-based symptoms between Asian and Caucasian patients with SDB.


Size-biased dispersal prior to breeding in a damselfly: conflicting evidence from a natural population.
The sizes of adult damselflies (Coenagrion puella) that were marked at emergence and recaptured as mature adults at the natal pond and at the next nearest pond were compared. In addition the sizes of a much larger sample of animals that were never recaptured were compared with those that returned to breed at the natal pond. There was no statistically significant difference in mass or wing length between adults in either comparison. This result contrasts with a previous study on a coenagrionid species in which, from an equally small sample, some evidence of size-biased dispersal was detected (dispersing adults were larger than those returning).


Neurons that program what to do and in what order.
In this issue of Neuron, describe the activity of single neurons in the SEF of monkeys, an oculomotor area of the frontal lobe, during the performance of stereotyped sequences of saccades. The monkey had to look at one of two identical stimuli, but the only way to choose the "correct" stimulus was to learn and remember its position in each presentation of the sequence. SEF neurons could do it.


Medical students' attitudes and behaviour towards sexual health interviewing: short- and long-term evaluation of designated workshops.
Workshops aimed at promoting fourth-year medical students' attitudes towards and subsequent behaviour in talking to patients about sexual health are reported on. Improvements in attitudes are reported following the workshops in 1999-2000 with students being more likely to see the relevance of sexual health enquiry, feeling more confident and competent about broaching the subject and expressing greater intention to do so. One year on, comparison of the intervention and non-intervention group for attendance at the workshop showed no difference in the proportion who had subsequently asked patients questions about sex. The proportion of students asking patients rose from 47% in the fourth year to 92% by the fifth year. Issues of long-term evaluation and the importance of the informal relative to the formal curriculum are discussed.


Evaluation of mandibular anatomy related to sagittal split ramus osteotomy using 3-dimensional computed tomography scan images.
Sagittal split ramus osteotomy (SSRO) of the mandible is one of the most common surgical techniques to correct mandibular deformities. Measurement of nerve position using conventional methods has been reported in the literature, but surgeons have found that further investigation of the anatomical relationship is needed. The aim of this study was to attempt to increase the accuracy of treatment by using 3-dimensional computed tomography scan measurements. From the normal population, 20 females and 20 males were enrolled during planning of denture implants in Taiwan. The mean age was 28+/-6, ranging from 20 to 39 years old. Using 3D tomography data, nerve position at osteotomy sites was measured and the geometric relationship examined between the antilingula and mandibular foramen. The results gave the mean distance from buccal plate to mandibular canal at the second molar, from mandibular canal to inferior border of the mandibular body, from the mandibular foramen to the highest tip of the lingula, and from the mandibular foramen to the anterior margin of the oblique ridge. When applied to SSRO operations, the anatomic data provided by this study may help surgeons gain more understanding of nerve position during surgery.


Growth and catch-up growth of Australian infants of low birthweight.
The growth of 90 infants of low birthweight (1500-2499 g) has been studied longitudinally from birth to 2 years of age. Seventy-five per cent of those infants were of birthweight that was appropriate-for-gestational age (AGA) and of mean gestational age 33.6 weeks (boys) and 34.5 weeks (girls). Twenty-four per cent were small-for-gestational age (SGA) and of mean gestational age 39.4 weeks (boys) and 38.5 weeks (girls). The data showed that, when gestational age was considered, the growth of AGA infants was similar to that of full-term infants of normal birthweight; SGA infants displayed accelerated growth ('catch-up'), particularly in the first months of life with upward percentile crossing from below the 5th toward the 50th. These results provide further evidence of the need to consider gestational age and whether AGA or SGA when assessing the growth of low birthweight infants.


The Role of Vascular Risk Factors in Cognitive Impairment and Dementia and Prospects for Prevention.
One of the most challenging clinical expressions of population aging is cognitive impairment and dementia. Among risk factors for the development of dementia, modifiable vascular risk factors have emerged as contributors to both vascular and nonvascular types of dementia. Epidemiologic studies have been particularly informative in understanding the link between vascular risks and dementia across the life course. We discuss vascular risks for dementia and cognitive impairment and practical management recommendations.


Cloning and expressions of chop in loach (Misgurnus anguillicaudatus) and its response to hydrogen peroxide (H2O2) stress.
C/EBP [CCAAT/enhancer-binding protein]-homologous protein gene (chop) which plays an important role in endoplasmic reticulum stress-induced apoptosis was investigated here by RACE and qPCR in an aquaculture animal for the first time. The full-length cDNA sequence of loach (Misgurnus anguillicaudatus) chop was 2533 bp, encoding 266 amino acids. The expression level of loach chop changed during different early life stages, with the highest expression at the 8-cell stage. Among different tissues, loach chop predominantly was expressed in gill, spleen, and gonad. We performed a hydrogen peroxide (H2O2, a common-used disinfectant) stress trial to explore the role of loach chop, with three different concentrations (0 μM, 50 μM, and 100 μM) of H2O2. The 100-μM dose was lethal for half the population but the other concentrations did not result in mortality. The activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in loach gill, liver, and spleen decreased with extended stress time and increased H2O2 concentration. The expression levels of gill chop in loaches from the 100-μM group were significantly higher than those from the other two treatment groups at 12 and 24 h of exposure. atf4 and bax, two proapoptotic genes, were significantly upregulated in gills of loaches from the 100-μM group compared to the other two groups 18 h and 24 h after treatment. bcl2, an antiapoptotic gene, presented an opposite trend. These results indicated a close relationship between H2O2 stress and fish apoptosis with loach chop playing an important role in H2O2 stress response.


Through the zipper or pants down: Does it change uroflowmetry parameters in healthy males?
To evaluate if voiding through the zipper or voiding pants down would make any difference with regard to uroflowmetry parameters and postvoiding residual urine (PVR) volumes in healthy males with no lower urinary tract symptoms (LUTS). Healthy males over 18 years of age with no LUTS were prospectively evaluated using a uroflowmetry test. Each individual was asked to void through the zipper (group 1) and pants down (group 2) at different times. The uroflowmetry test was repeated if the voided volume did not exceed 150 mL. Uroflowmetry results such as voided volume, maximum flow rate (Qmax), average flow rate (Qave), and duration of voiding were noted. PVR volume was assessed using ultrasonography. Electromyography was not used. Data are shown as mean ± standard deviation. For statistical analysis, a paired t test was used to analyze parametric parameters. A total of 44 males were enrolled. The median age of the individuals was 24 (range 18-44 years). There were no statistically significant differences between the two measurements in terms of voided volume (307 ± 121 mL vs 325 ± 145 mL, P = .365) and duration of voiding (25 ± 11 s vs 23.8 ± 11.6 s, P = .526). However, there were statistically significant differences in Qmax (26.6 ± 6.7 mL/s vs 30.0 ± 8.2 mL/s, P = .001), Qave (14.4 ± 3.6 mL/s vs 16.2 ± 5.1 mL/s, P = .009), and PVR volumes (23.9 ± 19.4 mL vs 3.9 ± 9.6 mL, P = .0001). Voiding pants down shows higher flow rates and lower PVR than voiding through the zipper in individuals with no LUTS. Future studies with a larger number of individuals (including those with LUTS) and a broader age range cohort are required for solid conclusions.


Identification and characterization of a ubiquitinconjugating enzyme UBE2A gene from lamprey.
Ubiquitin-conjugating enzymes (E2s) play an important role in the mechanism of ubiquitin transfer. Although in most species many of these enzymes share high sequence and structural conservation, their existence and functions in the lamprey remain unknown. In this study, we identified and characterized a ubiquitin-conjugating enzyme (UBE2A)-like gene in lamprey. The gene, designated as LaUBE2A, contained a 456-bp open reading frame encoding a 152-amino acid protein with a typical UBC domain. Real-time PCR assay showed that LaUBE2A was expressed in various tissues of the adult lamprey, with higher levels in the leukocytes and muscle and lower levels in the skin and liver. The high conservation in amino acid sequence between LaUBE2A and UBE2As from Homo sapiens, Mus musculus, Cavia porcellus, and Alligator sinensi implied that the function of LaUBE2A may be similar to that of UBE2A.


Validated Stability Indicating Chromatographic Methods for Quantification of Imidocarb Dipropionate; Application for the Determination of Its Residues in Bovine Meat and Milk Samples.
Imidocarb dipropionate (IMD) is an immunomodulator agent commonly used for treatment of anaplasmosis in cattle. Thus, two sensitive, specific, and precise stability-indicating chromatographic methods have been developed, optimized, and validated for its determination in presence of its acid, alkaline, and oxidative stressed degradation products. The first method is based on separation of IMD and its forced induced degradation products on reversed phase cyano column using isocratic elution system consisted of sodium acetate buffer-methanol-acetonitrile (55: 30:15, v/v/v), pH 4.6 at a flow rate of 1.2 mL/min, and UV detection at 254 nm. The second method utilized TLC combined with densitometric determination of the separated bands at 254 nm. The separation was achieved using silica gel 60 F254 TLC plates with a mixture of ethyl acetate-methanol-ammonia-water (8.5:1:0.5:0.2, v/v/v/v) as a developing system. HPLC analysis was applied in range of 0.25-40 µg/mL with LOD of 0.073 µg/mL. While densitometric measurements showed linearity in the range of 0.1-1.8 µg/band with LOD of 0.02 µg/band. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for determination of IMD in its commercial veterinary formulations with good recoveries. Furthermore, the proposed HPLC method was extended to the determination of IMD residues in bovine meat and milk samples. Bovine meat, HPLC, Imidocarb dipropionate, Milk, TLC.


Membrane depolarization and depletion of intracellular calcium stores are associated with delay of apoptosis in human neutrophils.
Apoptosis occurs rapidly in human polymorphonuclear leukocytes (PMN) after exposure to 1 mM cycloheximide (CHX). We examined whether this form of stimulated apoptosis altered either resting cytosolic free Ca2+ concentrations ([free Ca]) or membrane potential (psi) in PMN and found no significant effects. However, manipulation of either PMN intracellular Ca2+ stores or psi was found to delay CHX-induced apoptosis. Depletion of PMN intracellular Ca2+ stores with thapsigargin caused membrane depolarization and significantly delayed CHX-induced apoptosis based on both morphological and annexin-V-fluorescein isothiocyanate binding criteria. Short-term suspension (4 h) of PMN in Ca2+-free buffer depleted internal Ca2+ stores, induced membrane depolarization at 2.5 h, and delayed spontaneous (24 h) apoptosis but had no effect on CHX-induced apoptosis. Rapid membrane depolarization with 150 mM KCl buffer significantly delayed CHX-induced apoptosis, suggesting that depolarization rather than Ca2+ stores depletion was the crucial event. Timing experiments revealed that depolarization within 12 min of CHX exposure significantly delayed apoptosis. Collectively, these observations suggest an early psi-sensitive step in the apoptosis pathway initiated by CHX. CHX exposure alone does not alter either resting PMN [free Ca] or psi; accompanying depolarization of plasma membrane (either electrochemically or via depletion of internal Ca2+ stores) delays CHX-induced apoptosis in a time-dependent manner.


Training parents of children with life-long and life-limiting conditions in the art of massage.
The aim of this study was to explore the experience of being a massage therapist on the Training and Support Programme (TSP) in relation to Continued Professional Development (CPD). The TSP instructs parents caring for children with life-long and life-limiting conditions in simple massage techniques. Data were collected by semi-structured interviews with six massage therapists who had worked on the TSP for between 112 and 4 years. Therapists reported a number of beneficial gains including increased knowledge about 'disabilities' in general and a greater understanding of caring for children with life-long and life-limiting conditions, more patience, enhanced confidence of their practice, ability to adapt, and compassion. All therapists felt privileged to be a part of the process of change that occurred for parents and their children during the TSP. The results of this study will add to the scarce literature concerning massage therapists' CPD and provide insight into their experiences of working with parents and their children with a range of life-long and life-limiting conditions.


Proximity of fast food restaurants to schools: do neighborhood income and type of school matter?
To investigate the proximity of fast food restaurants to public schools and examine proximity by neighborhood income and school level (elementary, middle, or high school). Geocoded school and restaurant databases from 2005 and 2003, respectively, were used to determine the percentage of schools with one or more fast food restaurants within 400 m and 800 m of all public schools in Los Angeles County, California. Single-factor analysis of variance (ANOVA) models were run to examine fast food restaurant proximity to schools by median household income of the surrounding census tract and by school level. Two-factor ANOVA models were run to assess the additional influence of neighborhood level of commercialization. Overall, 23.3% and 64.8% of schools had one or more fast food restaurants located within 400 m and 800 m, respectively. Fast food restaurant proximity was greater for high schools than for middle and elementary schools, and was inversely related to neighborhood income for schools in the highest commercial areas. No association with income was observed in less commercial areas. Fast food restaurants are located in close proximity to many schools in this large metropolitan area, especially high schools and schools located in low income highly commercial neighborhoods. Further research is needed to assess the relationship between fast food proximity and student dietary practices and obesity risk.


Papillary thyroid carcinoma in children: risk factors and complications of disease recurrence.
Optimal treatment of recurrent papillary thyroid carcinoma (PTC) in children remains controversial. We reviewed our experience with recurrent PTC to better identify children diagnosed with it. The objective of this study was to determine the risk factors, optimal treatment, complications, and prognosis of recurrent PTC in children. This is a retrospective review of all thyroid resections for children aged 18 years or younger who have PTC at a single institution from 1987 to 1999. Thirty-six children, 7 boys (19%) and 29 girls (81%), underwent initial cervical exploration for PTC. Lymph node involvement was noted in 25 patients (69%); however, there was no distal disease. An equal number of children underwent subtotal thyroidectomy (n = 18) and total (n = 18) thyroidectomy as their initial operation. Papillary thyroid carcinoma recurrences developed in 17 patients (47%) a median of 7 months (range, 1-43 months) after their initial operation. Recurrence was more common for patients with lymph node involvement (P < .01) and multiple nodules (P < .05) at presentation. Recurrence developed in 5 patients after subtotal thyroidectomy and in 12 patients after total thyroidectomy. Sixteen children with recurrent PTC had a second operation and 6 required a third operation. Total operative complications included 2 patients with permanent hypocalcemia and 1 patient with permanent recurrent laryngeal nerve injury, all of whom had a total thyroidectomy. No patient died; however, 3 continue to harbor disease. Mean follow-up for patients with PTC was 65 months (range, 15 to 144 months). Thyroid resection combined with selective use of radioactive iodine ablation is a safe and effective treatment for recurrent PTC in children. The best predictors of this recurrent disease are lymph node involvement and multiple thyroid nodules at presentation.


Enhanced activation of human dendritic cells by silencing SOCS1 and activating TLRs simultaneously.
There was established evidence that silencing the attenuator and activating the TLRs could activate the dendritic cells in synergic effects. In this study, we constructed a plasmid, namely pshS1NH, which encodes SOCS1-shRNA, NY-ESO-1-MAGE3 (HLA-A2*0201) fusion antigen and secretory HMGB1, an agent used to modify dendritic cells (DCs), aiming to generate potent DC vaccine against tumors. The SOCS1-shRNA could efficiently downregulate the expression of SOCS1, as indicated by real-time RT-PCR and Western blot. The fusion antigen was detected in the pshS1NH-DCs by PCR and Western blot. Simultaneously, HMGB1 level in the pshS1NH-DCs culture media was significantly higher than that in the control DCs culture media. Levels of Th1 cytokines in pshS1NH-DCs culture media, such as IL-1β, IL-6, TNF-α and IL-12p70, were dramatically higher than those in control DCs culture media. In addition, lymphocytes co-cultured with pshS1NH-DCs secreted dramatically higher level of IFN-γ, whereas no difference was detected in IL-4 levels. Taken together, these data suggest that pshS1NH-DCs may be a potential adjuvant immunotherapy for cancers in clinical applications.


Maternal sensitivity is associated with configural processing of infant's cues in preterm and full-term mothers.
Prematurity may affect mother-infant bonding and alter maternal sensitivity to infant's cues. Efficient perception of infants' facial and bodily cues is a crucial aspect of maternal sensitivity and may be challenged by prematurity, as infants' signals may not be easily intelligible. However, it is still unexplored how premature birth impacts the maternal ability to perceive infants' signals. To investigate whether prematurity influences the perceptual sensitivity of mothers to infants' cues and, in particular, the configural processing of the faces and bodies of familiar and unfamiliar infants. The inversion effect paradigm was used to evaluate the configural vs. detail-based processing of the face and body of own or others' infants. Preterm mothers were compared to full-term mothers with either low or high maternal sensitivity. Forty-three healthy full-term and twenty-one preterm mothers of infants aged about six months. Maternal sensitivity during dyadic interaction, gestational age, accuracy and reaction time in a delayed matching-to-sample task of upright vs. inverted body and face stimuli (i.e., inversion effect). Preterm mothers were found to be less sensitive than the full-term ones. Higher maternal sensitivity during dyadic interaction was associated with lower inversion effect for unfamiliar as compared to own infants' bodies. However, preterm mothers and full-term mothers with low sensitivity showed comparable inversion effect in perceiving unfamiliar infants' faces or bodies. Preterm birth per se does not directly affect body configural processing, but it may be associated to reduced maternal sensitivity, ultimately leading to a less refined perception of own infant's cues.


Yap-Myc signaling induces pancreatic stellate cell activation through regulating glutaminolysis.
The accumulation of activated myofibroblastic pancreatic stellate cells (MF-PSCs) induces pancreatic cancer desmoplasia. These MF-PSCs are derived from quiescent pancreatic stellate cells (Q-PSCs). MF-PSCs in pancreatic cancer tend to glycolysis. However, increased glycolysis alone could not be sufficient for the increased metabolic demands of MF-PSCs. Yap and Myc signaling activation is involved in pancreatic cancer metabolism. Since elucidating the metabolic processes of MF-PSCs may be a promising strategy to suppress pancreatic cancer desmoplasia, we explored whether glutaminolysis meets the bioenergetic and biosynthetic demands of Q-PSCs converted into MF-PSCs and whether this is mediated by Yap signaling to Myc. In this study, we found that during the transdifferentiation of Q-PSCs into MF-PSCs, glutaminolysis regulatory genes were upregulated, and suppression of glutaminolysis inhibited transdifferentiation. Disrupting glutaminolysis in MF-PSCs inhibited cell growth, mitochondrial respiration, and fibrogenesis, while treatment of MF-PSCs with DKG (a glutaminolysis metabolite) reversed these activities. The expression of glutaminase (GLS1), a rate-limiting enzyme in glutaminolysis, was upregulated by Yap overexpression. Yap upregulates Myc to regulate the expression of GLS1 in MF-PSCs. Yap and Myc inhibitors disrupted glutaminolysis and inhibited myofibroblastic activities in PSCs. Thus, Yap-Myc signaling controls glutaminolysis to activate PSCs and might be a therapeutic target for pancreatic cancer desmoplasia.


Effects of Female fruit-marking Pheromones on Oviposition, Mating, and Male Behavior in the Neotropical Species Rhagoletis conversa Bréthes and Rhagoletis brncici Frías (Diptera: Tephritidae).
Sex pheromones produced by females of Rhagoletis conversa Bréthes and Rhagoletis brncici Frías are deposited on the surface of fruits after the eggs are laid. These pheromones repel other females, preventing repeated oviposition on the same fruit. They also attract males, thus assisting mating. Observations were made on wild populations, and cross-species behavioral tests were performed on males. The pheromone released by females was significantly more attractive for males of the same species. The two species showed remarkable differences in mating behavior, in the duration of oviposition, and in the number of circuits made around the fruit after eggs were laid. A morphological analysis of flies collected from their respective host plants indicated great host fidelity and the reproductive isolation of the two species. Possibly, the specific male-arresting effect of this pheromone was important for the sympatric speciation and evolution of these sibling species.


Compliance behavior and long-term maintenance dialysis.
Compliance with the therapeutic regimen is a critical and frequently confusing concept both for chronic renal failure patients and for care-givers. A panel group of maintenance dialysis patients was followed over a period of 9 years to identify the variables associated with positive or negative compliance behavior. Individual patient changes in adherence to the therapeutic regimen over time were also examined. Significant differences related to social support, especially when the demographic variable of education was controlled, were found. Serendipitous and surprising results were also documented when compliance behavior was evaluated in relation to patient mortality. From the analysis of quantitative and qualitative data, a typology of "ritual" versus "reasoned" compliance was derived.


First-line radiofrequency ablation with or without artificial ascites for hepatocellular carcinomas in a subcapsular location: local control rate and risk of peritoneal seeding at long-term follow-up.
To compare the long-term local control of hepatocellular carcinoma (HCC) and risk of peritoneal seeding via percutaneous radiofrequency ablation (RFA) using artificial ascites with those of RFA without artificial ascites. The Institutional Review Board approved this retrospective study. From April 2005 to February 2008, 160 patients (121 men, 39 women; age range 36-79 years) with a single subcapsular HCC (mean size 2.19 cm) were treated with ultrasonography-guided percutaneous RFA as a first-line therapy. Forty-four patients were treated with RFA using artificial ascites, whereas the other 116 patients were treated without artificial ascites. The cumulative local tumour progression (LTP) and peritoneal seeding were compared in both groups using follow-up computed tomography (CT). Cumulative LTP rates were analysed using the Kaplan-Meier method and the log-rank test. Risk of peritoneal seeding was investigated by means of multivariate analysis. The overall median follow-up period was 52.5 months (range 13-76 months). The 1, 2, 4, and 6 year cumulative LTP rates were 17.1, 27.6, 35.2, and 35.2%, respectively, in the group with artificial ascites, and 8, 15.2, 26.6, and 34.4% in the group without artificial ascites, without significant difference (p = 0.332). The rates of peritoneal seeding were 6.8% (3/44) in the group with artificial ascites and 2.6% (3/116) in the group without artificial ascites, a non-significant difference (p = 0.347). The biopsy prior to RFA was the independent risk factor of peritoneal seeding regardless of the use of artificial ascites. Long-term local tumour control and risk of peritoneal seeding were comparable for RFA with or without artificial ascites when used as a first-line therapy for subcapsular HCC.


Kinetic patterns of treadmill walking in preadolescents with and without Down syndrome.
This study investigated the effect of both walking speed and external ankle load on the kinetic patterns of treadmill walking in preadolescents with and without Down syndrome (DS). Ten preadolescents with DS and ten age- and gender-matched children with typical development (TD) participated in this study. We manipulated two treadmill speeds and two external ankle loads. Treadmill speeds were equal to 75% and 100% of the preferred overground walking speed. Two load conditions were with and without external ankle load which was equal to 2% of body weight on each side. We used an instrumented treadmill to collect vertical ground reaction force (GRF). Both timing and magnitude of peak GRFs, the loading and unloading rates, and various impulses were calculated from the GRF data. The results show that the DS group produced a shorter duration of propulsion, a lower FZ2 (second peak GRF) and vertical propulsive impulse, a higher loading rate and a lower unloading rate than the TD group. At a faster treadmill speed the DS group increased the duration of propulsion, the unloading rate and the vertical propulsive impulse, but reduced the magnitude of FZ2. External ankle load helped the DS group increase FZ2 and vertical propulsive impulse and might facilitate the push off and the initiation of leg swing during treadmill walking. External ankle load may therefore be included in the future physical intervention and exercise programs for the DS group to strengthen leg muscles and develop more efficient push off during locomotion.


Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation.
Previous studies demonstrated that genistein protects mice from radiation-induced bone marrow failure. To overcome genistein's extremely low water solubility, a nanoparticle suspension of genistein has been formulated for more rapid dissolution. In the current study, we evaluated the radioprotective effects of a nanoparticle formulation of genistein on survival and hematopoietic recovery in mice exposed to total-body gamma irradiation. A single intramuscular injection of a saline-based genistein nanosuspension (150 mg/kg) administered to CD2F1 mice 24 h before 9.25 Gy (60)Co radiation exposure resulted in a 30-day survival rate of 95% compared to 25% in vehicle-treated animals. In mice irradiated at 7 Gy, the genistein nanosuspension increased mouse bone marrow cellularity from approximately 2.9% (vehicle treated) to 28.3% on day 7 postirradiation. Flow cytometry analysis demonstrated decreased radiation-induced hematopoietic stem and progenitor cell (HSPC, Lineage(-)/cKit(+)) death from 77.0% (vehicle) to 43.9% (genistein nanosuspension) with a significant recovery of clonogenicity 7 days after irradiation. The genistein nanosuspension also attenuated the radiation-induced elevation of proinflammatory factors interleukin 1 beta (IL-1β), IL-6 and cyclooxygenase-2 (COX-2) in mouse bone marrow and spleen, which may contribute to protecting HSPCs.


A HPTLC method for the determination of the mycotoxin zearalenone in cereal products.
An HPTLC method for the quantification of zearalenone (ZEA) in cereals and cereal products (wheat flour and malt) has been developed. ZEA was extracted with 50 ml of acetonitrile-purified water (9+1) with addition of 2 g NaCl. The extracts were further purified on VICAM ZearalaTest((tm)) immunoaffinity columns, then analysed by instrumental high-performance thin-layer chromatography (HPTLC) on silica gel plates with fluorescence detection. Ethyl acetate - n-hexane (1+1) was used as the mobile phase. The chromatogram was scanned in fluorescence mode after excitation at λ=254 nm with λ=400 nm measuring filter: SENS and SPAN parameters were 195 and 20, respectively. TheR F of ZEA under these conditions was 0.43.The recovery was 95% in the range 15-65 µg/kg cereal products; the mean relative standard deviation of repeatability (RSDr) was 7.6%. The limit of quantification (LoQ) of ZEA was 10 µg/kg. Validation of the method was performed according to the principles of the ICH for pharmaceutical analysis.


Scheduled and unscheduled DNA synthesis during development in conjugating Tetrahymena.
Autoradiography has been used to confirm and to extend previous microspectrophotometric studies (Doerder and DeBault, 1975) on the timing of DNA synthesis during conjugation in Tetrahymena thermophila. The majority of DNA synthesis occurs at the expected periods preceding gamete formation and the two postzygotic divisions and during macronuclear development. DNA in new macronuclei is endoreplicated in an extremely discontinuous fashion. Under starvation conditions, the first endoreplication (2C to 4C) occurs immediately after the second postzygotic division when both new macronuclei and new micronuclei replicate. The second endoreplication (4C to 8C) does not occur until after separation of conjugants. If mating cells are kept under prolonged starvation conditions (20-24 hr), refeeding induces a partially synchronous division, after which an unexpectedly high percentage of cells incorporate tritiated thymidine into both macro- and micronuclei. Two previously undescribed periods of DNA synthesis were observed in the micronuclei of conjugating Tetrahymena. The first occurs during the early stages of meiotic prophase, before full crescent elongation. The second takes place in an extended period corresponding to macronuclear anlagen development, before conjugants have separated. CsCl gradient analyses indicate that, in micronuclear fractions, only main band DNA is being synthesized in both of these periods. However, in macronuclear fractions from both stages, a significant fraction (approximately 20%) of the DNA being synthesized has the buoyant density of ribosomal DNA. The finding that macro- and micronuclear DNA can be synthesized simultaneously in a single cell, both during conjugation and after refeeding starved exconjugants, raises interesting questions of how macro- or micronuclear-specific histones are targeted to the appropriate nuclei.


Dietary lipids induce phase 2 enzymes in rat small intestine.
We examined the role of dietary lipids in determining the activities of glutathione S-transferase (GST) and UDPglucuronosyl-transferase (UGT) in rat small intestine. Male Wistar rats were fed a fat-free (FF) diet or isocaloric control diet containing 5% corn oil (CO) or 5% fish oil (FO) for 3 weeks. The activities of these enzymes were about 2-fold higher in rats fed the FO diet vs. the FF diet. Intermediate levels of enzyme activity were found in rats fed the CO diet. Diet-induced differences in enzyme levels were shown by immunoblotting. The highest levels of glutathione S-transferase and UDPglucuronosyltransferase were detected in rats fed the FO diet. The lowest levels of these enzymes were found in rats fed the FF diet. Intermediate levels of enzyme were detected in rats fed the CO diet. Thus, diet-induced differences in enzyme activities were paralleled by changes in enzyme levels. Fatty acid analysis of mucosal lipids showed that the FF and FO diets were associated with decreased levels of linoleic and arachidonic acids as compared with the CO diet.


Anterior spinal artery syndrome of the cervical hemicord.
Three patients developed signs of a unilateral cervical cord lesion 6 to 36 h after the acute onset of severe cervico-brachial pain. The neurological deficit progressed over 6 to 18 h. On the painful side a central Horner's syndrome, a hemiparesis with plegia of the hand, and a slight pallhypaesthesia were found. On the opposite side thermhypaesthesia and hypalgesia were noted with a level at the dermatome C5 or C6. T2-weighted MR images revealed in one patient a small area of increased signal intensity restricted to one half of the cervical cord, and electromyography in another patient showed after 6 months evidence of segmental chronic denervation. Both abnormalities were found at the clinically expected level. The findings are consistent with a small infarction of the cervical cord in the perfusion territory of a central (sulco-commissural) artery, a duplicated anterior spinal artery or an anterior spinal branch of the vertebral artery.


Religion, spirituality, and risk for incident posttraumatic stress disorder, suicidal ideation, and hazardous drinking in U.S. military veterans: A 7-year, nationally representative, prospective cohort study.
While religion and spirituality (R/S) have been linked to positive mental health outcomes, most studies have employed cross-sectional designs, which do not allow one to evaluate the utility of R/S in predicting these outcomes. To address this gap, this study analyzed data from a 7-year nationally representative, prospective cohort study of U.S. military veterans to examine the effects of R/S on the development of incident mental health outcomes in this population. Specifically, we examined the association between organizational religious activity (ORA), non-organizational religious activity (NORA), and intrinsic religiosity (IR), and the risk of incident PTSD, suicidal ideation (SI), and hazardous drinking (HD). Multivariable logistic regression analyses revealed that ORA predicted a lower incidence of PTSD and SI; NORA a greater risk of developing HD; and IR a lower risk of developing HD. These results suggest that religion and spirituality, assessed in a nationally representative sample of military veterans, predict risk of developing PTSD, SI, and HD, over and above sociodemographic factors and perceived social support. Clinical implications and strategies for incorporating R/S into mental health assessment and interventions in this population are discussed.


Identifying Blood Transcriptome Biomarkers of Alzheimer's Disease Using Transgenic Mice.
The testing of pathological biomarkers of Alzheimer's disease (AD), such as amyloid beta and tau, is time-consuming, expensive, and invasive. Here, we used 3xTg-AD mice to identify and validate putative novel blood transcriptome biomarkers of AD that can potentially be identified in the blood of patients. mRNA was extracted from the blood and hippocampus of 3xTg-AD and control mice at different ages and used for microarray analysis. Network and functional analyses revealed that the differentially expressed genes between AD and control mice modulated the immune and neuroinflammation systems. Five novel gene transcripts (Cdkn2a, Apobec3, Magi2, Parp3, and Cass4) showed significant increases with age, and their expression in the blood was collated with that in the hippocampus only in AD mice. We further assessed previously identified candidate biomarker genes. The expression of Trem1 and Trem2 in both the blood and brain was significantly increased with age. Decreased Tomm40 and increased Pink1 mRNA levels were observed in the mouse blood. The changes in the expression of Snca and Apoe mRNA in the mouse blood and brain were similar to those found in human AD blood. Our results demonstrated that the immune and neuroinflammatory system is involved in the pathophysiologies of aging and AD and that the blood transcriptome might be useful as a biomarker of AD.