Antigen and receptor-driven regulatory mechanisms. VI. Demonstration of cross-reactive idiotypic determinants on azobenzenearsonate-specific antigen-binding suppressor T cells producing soluble suppressor factor(s).
The first detectable suppressor T cell (Ts) arising after i.v. administration of azobenzenearsonate- (ABA) conjugated syngeneic spleen cells to A/J mice has been studied for its receptor specificity and ability to produce soluble suppressor factor(s). This cell, termed Ts1, has a specific receptor for the eliciting antigen ABA, as demonstrated by selective binding to ABA protein- but not TNP protein-coated plastic dishes. The activity of ABA-Ts1 can be abrogated by treatment with anti-idiotypic antibodies made against anti-ABA antibodies of A/J mice (anti-CRI), indicating that these ABA-binding cells possess a surface receptor structure sharing idiotypic determinants with antibodies of the same specificity. Finally, soluble extracts from, antigen-adherent ABA-Ts1, but not nonadherent cells from the same spleen cell population, possess suppressive activity when assayed directly for afferent suppression or tested for their ability to trigger a second population of Ts (Ts2) in naive recipients. These findings demonstrate a close concordance between a T cell surface receptor, soluble T suppressor factors, and B cell derived antibody, all capable of direct recognition of the eliciting ABA antigen.


Relation of feedlot performance and certain physiological responses to the metabolizable protein and urea content of cattle diets.
An experiment was conducted to test the accuracy of the metabolizable protein system in predicting the amount of urea that would be useful in a corn-based cattle diet. Treatment diets included a basal, low-protein (7.8% CP) negative control (NC) with no supplemental N and a positive control (PC) that contained soybean meal. Urea was added to the NC diet in quantities calculated to be either 25% deficient (LU), equal to (MU) or 25% in excess (HU) of the urea fermentation potential ( UFP ). In vitro rumen fermentation studies were used to determine sequential ammonia production and digestible dry matter content of the diets. In a growth trial, 12 individually-fed Angus, Hereford and Angus X Hereford steers weighing an average of 213 kg were assigned randomly to each treatment diet. At the conclusion of the 112-d trial, rumen ammonia and jugular blood urea N (BUN) concentrations were determined on two steers from each treatment before feeding and at 1, 2, 3, 4 and 5 h postfeeding. In vitro ammonia concentrations of the NC and PC treatments were lower (P less than .05) than that of urea containing diets. In vivo rumen ammonia concentrations at 1 h postfeeding and BUN levels at 3 h postfeeding were low for both the NC and PC diets compared with urea-containing diets. Both of these values increased with each successive increase of added urea to the NC diet. During the initial 70 d of the growth trial, daily gains were improved (P less than .05) by addition of urea up to the MU level, which fulfilled the calculated UFP .(ABSTRACT TRUNCATED AT 250 WORDS)


The neuroprotective effect of a novel calmodulin antagonist, 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, in transient forebrain ischemia.
A novel calmodulin (CaM) antagonist DY-9760e, (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate), with an apparent neuroprotective effect in vivo, potently inhibits CaM-dependent nitric oxide synthase in situ. In the present study, we determined whether DY-9760e inhibits nitric oxide (NO) production and protein nitration by peroxynitrite (ONOO(-)) formation in the hippocampal CA1 region of gerbils after transient forebrain ischemia. In freely moving gerbils, NO production after 10-minute forebrain ischemia was monitored consecutively with in vivo brain microdialysis. Pretreatment with DY-9760e (50 mg/kg i.p.) significantly decreased the increased levels of NO(x)(-) (NO metabolites, NO(2)(-) plus NO(3)(-)) immediately after, 24 h after cerebral ischemia-reperfusion to the control levels of sham-operated animals. Western blot and immunohistochemical analyses using an anti-nitrotyrosine antibody as a marker of ONOO(-) formation indicated a marked increase in nitrotyrosine immunoreactivity in the pyramidal neurons of the CA1 region 2 h after reperfusion, and DY-9760e significantly inhibited increased nitrotyrosine immunoreactivity. Coincident with the inhibition of the NO production and protein tyrosine nitration, pretreatment with DY-9760e rescued the delayed neuronal death in the hippocampal CA1 region. These results suggest that the inhibitory effects of DY-9760e on the NO-ONOO(-) pathway partly account for its neuroprotective effects in cerebral ischemia.


Orientational Pair Correlations and Local Structure of Benzonitrile from Molecular Dynamics Simulations with Comparisons to Experiments.
We present an experimentally parametrized molecular dynamics study of single-molecule and collective orientational relaxation in neat benzonitrile through the analysis of the reorientational anisotropy and polarizability anisotropy time correlation function (PA-TCF). The simulations show that the PA-TCF is dominated by collective reorientation after 20 ps. Collective reorientation is found to be slower than single-molecule reorientation by a factor of 1.67, consistent with recent experiments. The simulations provide direct evidence of local antiparallel benzonitrile configurations. These structures, which have been the center of some debate, are responsible for the slower rate of collective versus single-molecule reorientation in the liquid. Further structural analysis indicates that significant Coulombic interactions between the nitrile group and hydrogen atoms on adjacent molecules play a role in the formation of the antiparallel structures. The single-molecule dynamics reflected in the anisotropy are complex and consist of a ballistic regime, restricted angular diffusion, and spatially anisotropic free diffusion. The principal components of the rotational diffusion tensor are independently obtained and shown to reproduce the free diffusion regime of the anisotropy for each principal axis according to the predictions of a previous theory.


Radiochemical cross-linking between proteins and RNA within 70 S ribosomal particles from E. coli MRE600.
In the absence of oxygen, gamma-irradiation produces covalent links between some ribosomal proteins and 16 S RNA to 23 S RNA, within 70 S ribosomes from E. coli MRE600. Under optimal conditions minimizing the structural modifications induced by radiations, in situ formed cross-links appear specific and reflect close RNA-protein contacts. In view of these results, the spatial organization of the 30 S, 50 S subunit interfaces is discussed. In addition, the gamma-irradiation technique reveals that subunit association induces modifications of some protein--RNA interactions.


Tissue turnover of aluminum and Ga-67: effect of iron status.
The purposes of this study were to evaluate the effect of nutritional status in regard to iron on aluminum distribution and turnover and to evaluate Ga-67 as a marker for aluminum. Anemic (n = 27) and normal (n = 30) rats were dosed by gavage with 0.8 mmoles of aluminum and 20 microCi Ga-67 in a 0.75 mol/l citrate solution and sacrificed 1, 3, 6, 9, 15, and 21 days later. Anemic rats generally retained more aluminum in their livers but less in tibias and spleens than normal rats. The half-lives of aluminum in liver (56 vs 17 days), muscle (33 vs 16 days), and serum (12 vs 8 days) were significantly greater in anemic than normal rats, respectively. Total body retention of Ga-67 could be described on the basis of a two-compartment model. The turnover of Ga-67 from the first compartment was rapid (half-life = 0.8 and 0.6 days) in anemic and normal rats, respectively, and was similar to the turnover of Ga-67 from the Gl tract (half-life = 0.7 and 0.6 days in anemic and normal rats, respectively). The turnover of Ga-67 from the second compartment was also rapid (2.8 vs 4.0 days in anemic and normal rats, respectively). Anemia affected the retention of Ga-67 more than the retention of aluminum; anemic rats retained more Ga-67 in their livers, spleens, kidneys, hearts, and muscles but less in their tibias than normal rats. In general, Ga-67 was not a satisfactory marker for aluminum distribution and turnover in normal and anemic rats.


Arsenic Transport in Rice and Biological Solutions to Reduce Arsenic Risk from Rice.
Rice (Oryza sativa L.) feeds ∼3 billion people. Due to the wide occurrence of arsenic (As) pollution in paddy soils and its efficient plant uptake, As in rice grains presents health risks. Genetic manipulation may offer an effective approach to reduce As accumulation in rice grains. The genetics of As uptake and metabolism have been elucidated and target genes have been identified for genetic engineering to reduce As accumulation in grains. Key processes controlling As in grains include As uptake, arsenite (AsIII) efflux, arsenate (AsV) reduction and AsIII sequestration, and As methylation and volatilization. Recent advances, including characterization of AsV uptake transporter OsPT8, AsV reductase OsHAC1;1 and OsHAC1;2, rice glutaredoxins, and rice ABC transporter OsABCC1, make many possibilities to develop low-arsenic rice.


Function of hepatic triglyceride lipase in lipoprotein metabolism.
Rat hepatic triglyceride lipase (H-TGL) was purified from liver tissue extracts by affinity chromatography on Sepharose 4B with covalently linked heparin. The purified rat H-TGL exhibited the properties previously described for this enzyme. Enzyme protein was injected into rabbits for anti-H-TGL antibody production. Antirat-H-TGL did not react against rat lipoprotein lipase (LPL) but inhibited H-TGL-activity both in vitro and in vivo greater than 90%. These antibodies were injected into rats and lipoprotein analyses were performed over a 36-hr period. It could be shown that inactivation of H-TGL by anti-H-TGL gamma-globulins in vivo led to an increase in total triglyceride concentration from 70 mg/dl to 230 mg/dl due to an increase in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) triglycerides 4 hr after antibody injection; a marked increase in high density lipoprotein (HDL) phospholipid concentration was observed with almost no change in HDL-cholesterol and HDL-triglycerides. This study documents the ability of antirat-H-TGL-gamma-globulins to inhibit H-TGL in vitro and in vivo. Furthermore, the inhibition of triglyceride removal in vivo demonstrated that this enzyme together with LPL is responsible for the catabolism of VLDL-triglyceride.


Haemonchus contortus and Trichostrongylus colubriformis did not adapt to long-term exposure to sheep that were genetically resistant or susceptible to nematode infections.
We tested the hypothesis that Haemonchus contortus and Trichostrongylus colubriformis would adapt to long-term exposure to sheep that were either genetically resistant or susceptible to H. contortus. Sheep genotypes were from lines with 10 years prior selection for low (resistant, R) or high (susceptible, S) faecal worm egg count (WEC) following H. contortus infection. Long-term exposure of H. contortus and T.colubriformis to R or S genotypes was achieved using serial passage for up to 30 nematode generations. Thus, we generated four nematode strains; one strain of each species solely exposed to R sheep and one strain of each species solely exposed to S sheep. Considerable host genotype differences in mean WEC during serial passage confirmed adequate nematode selection pressure for both H. contortus (R 4900 eggs per gram (epg), S 19,900 epg) and T. colubriformis (R 5300 epg, S 13,500 epg). Adaptation of nematode strain to host genotype was tested using seven cross-classified tests for H. contortus, and two cross-classified and one outbred genotype test for T. colubriformis. In the cross-classified design, where each strain infects groups of R, S or randomly bred control sheep, parasite adaptation would be indicated by a significant host genotype by nematode strain interaction for traits indicating parasite reproductive success; specifically WEC and, for H. contortus strains, packed cell volume. We found no significant evidence of parasite adaptation to host genotype (P>0.05) for either the H. contortus or T. colubriformis strains. Therefore, we argue that nematodes will not adapt quickly to sheep bred for nematode resistance, where selection is based on low WEC, although selecting sheep using a subset of immune functions may increase adaptation risk. Our results support the hypothesis that nematode resistance is determined by many genes each with relatively small effect. In conclusion, selection of sheep for nematode resistance using WEC should be sustainable in the medium to long-term.


Intratherapy or Posttherapy FDG PET or FDG PET/CT for Patients With Head and Neck Cancer: A Systematic Review and Meta-analysis of Prognostic Studies.
The objective of this study was to determine the predictive value of intra-therapy or posttherapy FDG PET or FDG PET/CT with regard to overall survival (OS) and event-free survival (EFS) outcomes for patients with head and neck cancer (HNC). A systematic search of the MEDLINE and EMBASE databases was performed. Studies in which PET/CT was performed during or after completion of primary therapy and for which survival outcomes were reported were included. OS and EFS were considered as outcomes. The pooled estimates of hazard ratios (HRs) and Mantel-Haenszel risk ratios (RRs) were generated for summary effects. Twenty-six studies were eligible for inclusion. The pooled HRs for OS (nine studies, 600 patients) and EFS (eight studies, 479 patients) were 3.55 (95% CI, 2.35-5.37) and 4.73 (95% CI, 2.61-8.56), respectively. Results from the RR analyses, including all 26 studies, showed that intratherapy or posttherapy PET/CT could significantly predict the 2-year and 3- to 5-year risk of death or disease progression. A positive PET result was associated with a more-than-sixfold increase in the risk of death within 2 years (2-year RR, 6.19 [95% CI, 3.04- 12.62]), which is attenuated--but remains significant--with longer follow-up (3- to 5-year RR, 2.42 [95% CI, 1.76-3.32]). The estimated pooled RRs for 2-year mortality were 8.31 (95% CI, 3.83-18.01) for posttherapy PET/CT versus 3.99 (95% CI, 1.43-11.10) for intratherapy PET/CT. Positive results of intratherapy or posttherapy PET/CT examinations strongly predict the risk of adverse events and death, particularly within 2 years but also up to 5 years, for patients with HNC.


DNA sequence losses on chromosomes 11p and 18q are associated with clinical outcome in lymph node-negative ductal breast cancer.
Histological and other markers alone cannot predict the risk of disease progression in node-negative breast cancer. Several genomic aberrations have been linked to clinical outcome in breast cancer. In this study, comparative genomic hybridization was applied to screen for specific DNA copy number gains and losses in 20 pT1/pT2 node-negative invasive ductal carcinomas with no disease recurrence with at least 8 years of follow-up and in 20 pT1/pT2 node-negative tumors with distant disease recurrence. The number of genomic aberrations (copy number gains and losses) per tumor was significantly higher in tumors with disease recurrence (P < 0.05). The number of genomic aberrations was associated with histological grade (P < 0.02). Within the group of tumors with disease recurrence, the total number of genetic aberrations per tumor (P < 0.02) and the number of DNA sequence losses per tumor (P < 0.01) were significantly associated with poor survival. Of the individual loci involved, only losses at chromosomes 11p (P < 0.002) and 18q (P < 0.004) were associated with poor survival in the recurrence group. Histological grade and loss of 18q were independent prognostic variables in multivariate analysis. This genome-wide analysis by comparative genomic hybridization suggests that node-negative ductal breast cancers with a high number of genomic aberrations have an increased risk of disease recurrence. The number of DNA sequence losses, particularly losses of chromosomes 11p and 18q, were associated with poor prognosis. Genes on chromosomes 11p and 18q may play a role in the progression of ductal breast carcinoma.


Special focus session: multidetector CT: abdominal visceral imaging.
Multidetector computed tomography (CT) has diffused rapidly into clinical imaging practice in a short time. Major improvements in relation to single-detector CT are faster image acquisition and improved z-axis resolution. Abdominal visceral imaging with multidetector CT uses both the vascular and parenchymal phases of contrast material enhancement to provide a combined angiographic and multipass organ-directed study. All examinations are performed with standard contrast material loads.


Outbreak of avian influenza H7N3 on a turkey farm in the Netherlands.
This case report describes the course of an outbreak of avian influenza on a Dutch turkey farm. When clinical signs were observed their cause remained unclear. However, serum samples taken for the monitoring campaign launched during the epidemic of highly pathogenic avian influenza in 2003, showed that all the remaining turkeys were seropositive against an H7 strain of avian influenza virus, and the virus was subsequently isolated from stored carcases. The results of a reverse-transcriptase pcr showed that a H7N3 strain was involved, and it was characterised as of low pathogenicity. However, its intravenous pathogenicity index was 2.4, characterising it as of high pathogenicity, suggesting that a mixture of strains of low and high pathogenicity may have been present in the isolate. The outbreak remained limited to three farms.


A physiologically based pharmacokinetic model of organophosphate dermal absorption.
The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3-106.9 microg/cm2 for parathion; 0.8-23.6 microg/cm2 for fenthion; 1.6-39.3 microg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 microl for ethanol; 20-80 microl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments.


Extracapsular femoral neck fractures treated with total hip arthroplasty: identification of a population with better outcomes.
Femoral neck fractures (FNF) are associated to patient's disability, reduced quality of life and mortality. None of the fixation devices commonly used for extracapsular (EC) FNF (i.e., dynamic hip screws (DHS) and intramedullary nails (IN)) is clearly superior to the other, especially in case of unstable fractures (31.A2 and 31.A3 according to AO/OTA classification). The aim of our study was to identify a sub-population of patients with EC fractures in which better outcomes could be obtainable using total hip arthroplasty (THA). All patients with EC unstable fractures treated with THA were included in the present study. Demographic data, American Society of Anesthesiologists (ASA) score, hospitalization length, transfusion rate, implant-related complications and mortality rate were collected. Clinical outcomes were evaluated using the Oxford Hip Score (OHS), while patients' general health status through the 12 Item Short Form questionnaires (SF-12). 30 patients (7 male; 23 female) with a mean age of 78.8 years were included. The 1-year mortality rate was 13.3%. The mean OHS was 27.5, while the mean SF-12 were 45.84 for the mental item and 41.6 for the physical one. Age was the only factor associated with the OHS and patients older than 75 years presented a 12- fold higher risk of developing bad outcomes. THA seems to be a viable option for unstable EC fractures, with good clinical outcomes, especially in patients younger than 75 years of age. The mortality rate associated with THA in EC fractures is low and anyway comparable with IN.


[Analgesic actions after local peripheral administration of Lornoxicam in a model of formalin test in the rat].
To investigate analgesic actions after local peripheral administration of Lornoxicam in an animal model of formalin test. Male Spague-Dawley rats were randomly divided into 3 groups, namely the control, the ipsilateral and the contralateral groups. Each group consisted of 8 rats. Thirty minutes prior to subcutaneous injections of 20 g/L formalin 50 microl into the plantar surface of the right hind-paw, the rats of ipsilateral group received Lornoxicam in the plantar surface of the right hind-paw, and the rats of contralateral group received Lornoxicam in the contralateral plantar surface of the hindpaw. Pain response was recorded for a period of 60 minutes. The summation of time (in seconds) spent in licking and biting responses to the injected paw during each 5 minutes block was analyzed for comparison. The pain response in the first phase (from 0 to 10 minutes) was not inhibited (P > 0.05). The pain response in the second phase (from 10 to 60 minutes) was inhibited in the ipsilateral group (P < 0.05). Local peripheral administration of Lornoxicam has analgesic effect on the rat's planta in the second phase of a formalin test model; the mechanism involved is mainly local, but not systemic.


Increased high-sensitivity C-reactive protein, erythrocyte sedimentation rate and lactic acid in stroke patients with internal carotid artery occlusion.
Internal carotid artery occlusion (ICAO) causes high annual rates of mortality and morbidity. It has been established that atherosclerosis is the normal cause of ICAO. As the pathogenesis of atherosclerosis may involve blood lipids, inflammatory factors and other biomarkers, the aim of this study was to assess the changes in these biomarkers and investigate the relationship between these biomarkers and the development of ICAO in stroke patients. A total of 89 ischaemic stroke inpatients with ICAO (ICAO group) and 89 without ICAO (control group) were studied, retrospectively. The serum was collected from each patient on the 3(rd) day of admission, to measure the lipid parameters and biomarkers, e.g. high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and lactic acid (LA). Histories were taken including age, gender, smoking history, and disease history. Additional analysis was carried out to compare between the genders and evaluate the association between certain biomarkers and ICAO. Among the 89 ICAO cases in this study, the serum levels of hs-CRP, ESR and LA were significantly higher than those in the control group (p ≤ 0.001). No significant differences were found in the mean levels of total cholesterol, triacylglycerol, HDL cholesterol or glucose, or the known risk factors. Gender also had no influence on these biomarkers. Logistic regression analysis indicated that hs-CRP, ESR and LA were significantly associated with ICAO (p ≤ 0.05). These results suggest that hs-CRP, ESR and LA are associated with ICAO in ischaemic stroke patients, but gender has no effect. Therefore, Hs-CRP, ESR and LA may be useful in the early detection of patients with ICAO.


The Role of Perceived Social Support on Quality of Life in People with Cardiovascular Diseases.
Cardiovascular Diseases (CVDs) are one of the major causes of hospitalization and mortality worldwide. Strengthening perceived social support and quality of life can reduce these problems. This study aimed to describe the role of perceived social support on cardiovascular patients' quality of life. This cross-sectional study was conducted from September 2020 to February 2021. We selected 150 cardiovascular patients through convenience sampling. The questionnaires included: the Persian version of the WHOQOL-BREF, Perceived Social Support, and demographic variables. Hierarchical linear regression was used to explore the association between perceived social support and quality of life. Data were analyzed by SPSS version 21.0 software. A P-value less than 0.05 is considered statistically significant. The demographic variables could predict 12.2% of the variance of quality of life in the first step. In the second step, after adjusting control variables and dimensions of social support, the predictability increased to 29% of the variance with the addition of variables. All dimensions of social support, excluding tangible assets support, were significant predictors of quality of life and monthly income status. Self-esteem support (β= 0.387) was the strongest predictor of quality of life in cardiovascular patients. Patients with higher perceived social support have a better quality of life than the other patients. Perceived social support is one of the strategies that can be utilized to improve quality of life and overcome disease in cardiovascular patients.


Acth-independent Cushing's syndrome: bilateral cortisol-producing adrenal adenomas.
ACTH-independent Cushing's syndrome (CS) usually results from a solitary adrenocortical adenoma. We recently encountered a patient with ACTH-independent CS associated with bilateral adrenal enlargement. The evaluation led us to consider some rare but interesting entities. The patient was a 69 year-old woman who had a 10-15 year history of controlled hypertension, back pain associated with osteoporosis, easy bruising, and truncal obesity. Her medications included conjugated estrogens. Physical examination revealed classical features of CS. She had a raised blue lesion on her buccal mucosa. Plasma cortisol concentrations were elevated at 36 (a.m.) and 38 (p.m.) microg/dL. Urinary free cortisol was normal at baseline (65 microg/24 hours) but failed to suppress adequately in response to the low-dose dexamethasone suppression test (75 microg/24 hours). The plasma ACTH concentration was undetectable. Plasma cortisol concentrations failed to suppress (37 microg/dL) with an 8 mg overnight dexamethasone test. A CT scan of the abdomen revealed bilateral adrenal masses. The possibilities of food-induced CS and primary pigmented nodular adrenal disease were excluded by a lack of marked stimulation in cortisol secretion to a mixed-meal and dermatologic confirmation of the buccal mucosa lesion as an angioma and not a blue nevus. Adrenal venous sampling showed cortisol secretion from both adrenals. The patient underwent bilateral adrenalectomy with pathology confirming bilateral adenomas. This case illustrates an unusual application of selective venous sampling in the CS evaluation and raises questions about the pathogenesis of cortisol-secreting adrenocortical adenomas.


[The Thule case. Mortality and hospitalization after the crash of an American B-52 bomber in 1968].
In 1968, a B-52 bomber carrying nuclear bombs crashed near the Thule US Air-Base in Greenland. By 1986, many cases of disease had been reported among Danish workers employed at the base. A database has been constructed from staff files of workers employed from 1963 to 1971. Of 4,322 workers, 98.7% were identified in 1987. The study group consisted of 1,202 workers employed during the clean up period (from the time of the crash until the last of the contaminated material had been removed). The reference group consisted of 3,120 workers employed outside the clean up period. No differences were found in total mortality, or mortality from cancer, heart disease or accidents between the groups after adjusting for age, marital status and length of employment. Mortality from suicide was lower in the study group. The hospitalization rates for the period 1977-1985 also showed no differences between the two groups. The conclusion of the register surveys is that no harmful effect on health due to the crash can be established by measuring mortality or hospital admissions.


[Dental problems and their management in uraemic patients].
Bad dental status is very often observed in hemodialyzed patients due to the fact of a frequent poor oral hygiene and, in addition of the traditional risk factors, the consequences of uraemic state and its treatment. However , among such immunodepressed patients, oral and dental lesions represent a risk of septic complications. Moreover some works point out the prevalence of inflammation and denutrition due to dental lesions in the uraemic population, with potential atherosclerosis. Therefore, in order to anticipate all these adverse effects and to restore their mouth to health, patients have to be encouraged to have regularly a full dental evaluation and correction if not elimination of all potential sources of infection and other complications. To ensure the best treatment, a close collaboration has to be established with dental practitioners who must be aware and convinced of the complexity of such patients: immunodepression due to uraemic state and sometimes to drug therapy; importance of prophylactic antibiotic therapy surrounding dental cares; cautions to hemostasis circumstances; adjusted use of some medications. To illustrate this matter, we report here a study involving 96 hemodialyzed patients who were investigated by panoramic radiography and clinical cross- examination about their dental complaints and habits. We then expose our practices and detail our collaboration with their dentists in establishing a plan of dental treatment.


[Evaluation of a strategy for the control of tuberculosis in a health district of andalusia, Spain].
Tuberculosis in Spain and Andalusia, the incidence rates above those of surrounding countries. Many authors emphasize the need for improved epidemiological information, the organization of health services and social support to patients. The aim of this study was to evaluate the results obtained after developing a strategy involving the three elements outlined in the Primary Care District of Andalusia. We followed up to 234 TB patients residing in the District and reported to the Epidemiological Surveillance System of Andalusia during the period 2004-2008. Were considered as indicators for evaluating the percentage of patients who completed treatment, the percentage of smear-positive contacts with study, new cases detected in the same and the incidence in children under 15 years. Of the 234 patients were followed up cash 95% of them completed treatment 182 (78%) died 18, moved from home, 10 and 12 still remained in treatment. Of the 130 cases that presented positive sputum studied 112 contacts (86%). 27 new cases were detected among the contacts studied, and the annual incidence in children under 15 years was 6.65 per 100,000 population. Tracking losses were reduced by 30%, and terminations of treatment and contact studies improved by 25% and 30% respectively compared to data from the whole of Andalusia. The strategy has helped improve the proposed assessment indicators. The% of new cases detected in studies of contacts and the annual incidence in children under 15 years was similar in this study than in Andalusia.


Food companies' calorie-reduction pledges to improve U.S. diet.
Heretofore, corporate voluntary pledges to improve the health of Americans have been linked neither to explicit measurable commitments nor to a framework for an independent evaluation. The Healthy Weight Commitment Foundation (HWCF), whose members include 16 of the nation's leading consumer packaged goods food and beverage manufacturers, voluntarily pledged to collectively remove 1 trillion calories from their products by 2012 (against a 2007 baseline), and 1.5 trillion calories by 2015. The pledge is designed to reduce the calorie gap commensurate with the HWCF companies' role in the U.S. diet. To date, no system exists for documenting the nutritional and public health impacts of industry-led changes in the food supply on individual diets. The current study represents a unique opportunity to understand how the consumer packaged goods food and beverage sector is changing and how these changes are associated with changes in the American diet. It presents data on national caloric sales from this sector, purchases of these goods by various subpopulations, and methods linking these to individual intakes of Americans. Findings show that HWCF companies accounted for approximately 25% of calories consumed in the U.S. in 2007 and that the 1.5 trillion-calorie pledge (about 14 calories/day/capita) accounts for 0.8% of the calories sold across all consumer packaged goods food and beverage brands in 2007. The authors hope that this evaluation will continue to create models and methods for demonstrating the effects of changes in the food supply on individual diets, particularly among those from vulnerable subpopulations.


Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response.
Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are not fully understood. Inflammatory response plays an important role in IR-induced tissue injury. Although increased proinflammatory cytokines have been detected in the kidney and the distant organs after renal IR, their original sources remain uncertain. In the present study, we investigated the acute effect of renal IR on hepatic inflammatory cytokine expression and the mechanism involved. Sprague-Dawley rats that were subjected to renal IR (ischemia for 45 min followed by reperfusion for 1 h or 6 h) had increased plasma levels of creatinine, urea, and transaminases, indicating kidney and liver injuries. There was a significant increase in the expression of proinflammatory cytokine mRNA (MCP-1, TNF-α, IL-6) in the kidney and liver in rats with renal IR. This was accompanied by a significant increase in proinflammatory cytokine protein levels in the plasma, kidney, and liver. Activation of a nuclear transcription factor kappa B (NF-κB) was detected in the liver after renal IR. The inflammatory foci and an increased myeloperoxidase (MPO) activity were detected in the liver after renal IR, indicating hepatic inflammatory response and leukocyte infiltration. These results suggest that renal IR can directly activate NF-κB and induce acute production of proinflammatory cytokines in the liver. Renal IR-induced hepatic inflammatory response may contribute to impaired liver function and systemic inflammation.


Microvascular decompression surgery for trigeminal neuralgia and hemifacial spasm: naunces of the technique based on experiences with 100 patients and review of the literature.
Microvascular decompression (MVD) surgery for trigeminal neuralgia and hemifacial spasm offers a relatively low-risk opportunity to treat cranial nerve hyperactivity-compression syndromes, which are associated with severe, disabling facial pain and spasm. Although a number of publications have described the technique in detail, combining the technical nuances from different schools of thought or neurosurgical training in an effort to increase the safety and efficacy of this procedure would be beneficial to the surgeon. The nuances of technique and operative findings from performing this procedure for the last 100 cases have been reviewed and combined. The author has reflected on his experience performing microvascular decompression operation. The specifics of operating room set-up, positioning, craniotomy, and intradural microsurgical methods are provided, including managing postoperative care and complications. In the presence of alternative methods of therapy, microvascular decompression operations should be performed with low risk to the patient. There is a learning curve involved with this operation and the surgeon should remain always critical of his/her performance and aspire for a "perfect" result.


Molecular processes of inhibition and stimulation of ATP synthase caused by the phytotoxin tentoxin.
F1-ATPase is the smallest mechanical motor known. Tentoxin, a cyclic peptide produced by phytopathogenic fungi, inactivates the F1 motor in sensitive plants at nanomolar to micromolar concentrations, whereas higher concentrations surpass the natural activity of the enzyme. Single molecule studies now have clarified the molecular steps involved in both processes. Inactivation delays the dwell time of a single step in the complete 360 degrees turn and results in an asymmetric rotation of the central rotor subunit. In contrast, rotation in the stimulated F1 particle is smooth and accompanied by strongly reduced ADP inhibition. Our study provides for the first time the direct observation of a noncompetitively inhibited state of the enzyme and directly visualizes the regulation of the molecular motor by an external natural compound. In addition, the ADP release step during catalysis was revealed by analysis of the single molecule rotation behavior. Hence, tentoxin is a sophisticated molecular tool to mark and control certain catalytic steps within the reaction pathway of the molecular F1 motor.


An evaluation of the accuracy and performance of lightweight GPS collars in a suburban environment.
The recent development of lightweight GPS collars has enabled medium-to-small sized animals to be tracked via GPS telemetry. Evaluation of the performance and accuracy of GPS collars is largely confined to devices designed for large animals for deployment in natural environments. This study aimed to assess the performance of lightweight GPS collars within a suburban environment, which may be different from natural environments in a way that is relevant to satellite signal acquisition. We assessed the effects of vegetation complexity, sky availability (percentage of clear sky not obstructed by natural or artificial features of the environment), proximity to buildings, and satellite geometry on fix success rate (FSR) and location error (LE) for lightweight GPS collars within a suburban environment. Sky availability had the largest affect on FSR, while LE was influenced by sky availability, vegetation complexity, and HDOP (Horizontal Dilution of Precision). Despite the complexity and modified nature of suburban areas, values for FSR (mean= 90.6%) and LE (mean = 30.1 m) obtained within the suburban environment are comparable to those from previous evaluations of GPS collars designed for larger animals and within less built-up environments. Due to fine-scale patchiness of habitat within urban environments, it is recommended that resource selection methods that are not reliant on buffer sizes be utilised for selection studies.


Nucleation and capture of large cell surface-associated microtubule arrays that are not located near centrosomes in certain cochlear epithelial cells.
This report deals with the as yet undetermined issue of whether cell-surface associated microtubules in certain cochlear epithelial cells are centrosomally nucleated and subsequently migrate to microtubule-capturing sites located at the surface regions in question. Alternatively, the cells may possess additional nucleating sites which are noncentrosomal and surface-associated. These alternative possibilities have been investigated for highly polarised epithelial cells called supporting cells in the mouse and guinea pig organ of Corti using antibodies to pericentrin and gamma-tubulin. There is substantial evidence that both proteins are essential components of microtubule-nucleating sites in cells generally. Each mature supporting cell possesses a large microtubule array that is remotely located with respect to its centrosome (more than 10 microns away). The antibodies bind to a cell's centrosome. No binding has been detected at 2 other microtubule-organising centres that are associated with the ends of the centrosomally-remote microtubule array while it is being constructed. Such arrays include thousands of microtubules in some of the cell types that have been examined. If all a cell's microtubules are nucleated by its centrosome then the findings reported above imply that microtubules escape from the centrosomal nucleating site and migrate to a new location. Furthermore capture of the plus and minus ends of the errant microtubules is taking place because both ends of a centrosomally-remote microtubule array are attached to sites that are precisely positioned at certain cell surface locations. Minus ends are locating targets with an exactitude comparable to that which has been demonstrated for plus ends in certain cell types. These cells apparently operate a single control centre strategy for microtubule nucleation that is complemented by precise positioning of plus and minus end-capturing sites at the cell surface.


Regulatory agencies' recommendations for medicine information leaflets: Are they in line with research findings?
The design of medicine information leaflets can determine whether a leaflet will be read or discarded by patients. It may also influence patients' ability to understand the information about their medicines within the leaflet. Researchers compared regulatory agencies' recommendations for medicine information leaflet design from New Zealand, the United Kingdom, the European Union, and the United States against recommended good design principles to determine the appropriateness, comprehensiveness, and consistency of their recommendations. Recommendations for medicine information leaflets varied between the regulatory agencies. There were some inconsistencies between the recommendations and some gaps were identified. There was little regulatory guidance given to creators of medicine information leaflets in New Zealand compared to other countries, and this could lead to manufacturer-produced information leaflets of a poorer quality. Up-to-date and enforceable guidance for creators of medicine information leaflets should be provided in all countries to ensure they are of an appropriate standard.


Concurrent self-regulatory efficacy as a mediator of the goal: exercise behaviour relationship.
Examining exercise as a single goal-directed behaviour, without acknowledging the influence of other concurrent goals, may oversimplify the self-regulation needed in daily life. Concurrent self-regulatory efficacy, confidence in one's ability to self-regulate the management of multiple goals, was explored as a potential mediator in the relationship between value of an exercise goal and future exercise behaviour. Undergraduate students were observed during a 4-week examination period where they faced greater than usual challenges to exercising regularly. Consistent with self-efficacy theory, concurrent self-regulatory efficacy was a significant partial mediator of the value of an exercise goal-exercise behaviour relationship.


Characterization of immunodominant linear B-cell epitopes on the carboxy terminus of the rinderpest virus nucleocapsid protein.
The nucleocapsid (N) protein of rinderpest virus (RPV) is one of the most abundant and immunogenic viral proteins expressed during natural or experimental infection. To identify immunogenic epitopes on the N protein, different forms of RPV N protein, including the full-length protein (N(1-525)), an amino-terminal construct (N(1-179)), and a carboxy-terminal construct (N(414-496)), were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins. The antigenicity of each recombinant protein was evaluated by Western immunoblotting. All recombinants were recognized by hyperimmune RPV bovine antisera, indicating that immunoreactive epitopes may be present at both ends of the N protein. However, GST-N(414-496) was much more antigenic than GST-N(1-179) when tested with sera from vaccinated cattle, suggesting that an immunodominant or highly immunogenic epitope(s) may be located at the carboxy terminus of the N protein. Epitope mapping with overlapping peptides representing different regions of the carboxy terminus (amino acids 415 to 524) revealed three nonoverlapping antigenic sites in regions containing the residues (440)VPQVRKETRASSR(452) (site 1), (479)PEADTDPL(486) (site 2), and (520)DKDLL(524) (site 3). Among these, antigenic site 2 showed the strongest reactivity with hyperimmune anti-RPV bovine sera in a peptide enzyme-linked immunosorbent assay but did not react with hyperimmune caprine sera raised against peste-des-petits-ruminants virus, which is antigenically closely related to RPV. Identification of an immunodominant linear antigenic site at the carboxy terminus of the N protein may provide an antigen basis for designing diagnostics specific for RPV.


Alteration of chloride secretion across canine tracheal epithelium by lipoxygenase products of arachidonic acid.
We examined whether the leukotrienes (LT) B4, C4, D4, and E4, and 5-, 12-, and 15-hydroxyeicosatetraenoic (HETE) acids alter the electrical properties of canine tracheal epithelium. Short-circuit current (ISC) increased by 20.3 +/- 4.3 and 25.9 +/- 6.5 microA/cm2 after LTC4 and LTD4 addition, was unchanged following LTB4, LTE4, 5-, or 15-HETE addition, and was decreased by 10 +/- 3% after 12-HETE addition. LTC4- and LTD4-induced increases in ISC were dependent on the presence of Cl and were equal to the increases in net 36Cl flux toward the mucosa. The cyclooxygenase inhibitor indomethacin (10(-5) M) or the phospholipase inhibitor mepacrine (10(-5) M) diminished increases in ISC. The release rate of prostaglandins E2 and F2 alpha and thromboxane B2 rose from 8.2 +/- 2.3, 2.3 +/- 0.5, and 1.1 +/- 0.5 to 15.5 +/- 3.3, 6.0 +/- 1.4, and 4.0 +/- 0.8 ng . cm-2 . h-1, respectively, after LTC4 addition, and from 6.9 +/- 1.4, 2.5 +/- 1.1, and 1.7 +/- 1.3 to 20.2 +/- 3.1, 10.5 +/- 3.1, and 5.2 +/- 2.4 ng . cm-2 . h-1, respectively, after LTD4 addition. The release rates of 6-keto-prostaglandin F1 alpha were unchanged. A thromboxane A2 mimetic, U46619, failed to increase ISC and thromboxane synthetase inhibitors OKY-046 and dazmegrel failed to inhibit the induced increases in ISC, suggesting that thromboxane has little effect on ISC. Thus lipoxygenase products of arachidonic acid can modulate Cl secretion by the canine tracheal epithelium and do so through the release of cyclooxygenase products, including prostaglandins E2 and F2 alpha.


Kinetic evidence for the obligatory formation of a 30S initiation complex in polyphenylalanine synthesis initiated with N-acetylphenylalanyl-5RNA.
The problem of whether the initiation of bacterial protein synthesis involves the obligatory formation of a 30S initiation complex intermediate was examined in a model system with N-acetylphenylalanyl-tRNA as initiator 5RNA nad poly(uridylic acid) as mRNA. The time courses of the formation of the 30S and 70S initiation complex with Escherichia coli ribosomes were measured simultaneously by stopping the reaction with dextran sulfate and differentiating the N-acetylphenylalanyl-tRNA bound to 30S ribosomal subunits from that bound to 70S ribosomes with RNase I, which hydrolyzes N-acetylphenylalanyl-tRNA bound to 30S subunits but not that bound to 70S ribosomes. A maximum in the 30S complex concentration was observed within the first 10-15 sec of the reaction, whereas 70S complex formed formed more slowly with a slight initial time lag. When an analog computer was programmed with rate constants determined separately for the formation of the 30S initiation complex from preformed 30S complex, kinetic curves very similar to the empirical curves were obtained for the entire time course of the reaction. The results show clearly that formation of the 70S complex obeys the kinetic laws for consecutive reactions, and the 30S complex is, therefore, an obligatory intermediate in the initiation of polyphenylalanine synthesis in the model system.


Exo-miRNAs as a New Tool for Liquid Biopsy in Lung Cancer.
Lung cancer is the predominant cause of cancer-related deaths. The high mortality rates are mainly due to the lack of diagnosis before the cancer is at a late stage. Liquid biopsy is a promising technique that could allow early diagnosis of lung cancer and better treatment selection for patients. Cell-free microRNAs have been detected in biological fluids, such as serum and plasma, and are considered interesting biomarkers for lung cancer screening and detection. Exosomes are nanovesicles of 30-150 nm and can be released by different cell types within the tumor microenvironment. Their exosomal composition reflects that of their parental cells and could be potentially useful as a biomarker for lung cancer diagnosis. This review summarizes the state-of-the-art of circulating microRNAs (miRNAs) in lung cancer, focusing on their potential use in clinical practice. Moreover, we describe the importance of exosomal miRNA cargo in lung cancer detection and their potential role during lung carcinogenesis. Finally, we discuss our experience with the analysis of circulating exosomal miRNAs in the bioMILD screening trial.


De novo mutation of CYBB gene in a boy presenting as intra-abdominal infection of Burkholderia contaminans: a case report.
Chronic granulomatous disease (CGD) is an inborn error of immunity. It is characterized by recurrent bacterial or fungal infections, including infections by Burkholderia species. This is due to respiratory burst dysfunction of phagocytes. Currently, there is no report on Burkholderia contaminans (B. Contaminans) infection in children with CGD. We present a previously healthy, 17-month-old Chinese boy infected with B. Contaminans in the intra-abdominal regions. Immunological screening, including assessment of cellular immunity and humoral immunity did not yield conclusive results. The level of nicotinamide adenine dinucleotide phosphatase (NADPH) activity was decreased and whole-exome sequencing identified a de novo mutation in the CYBB gene. For specific pathogens such as B. Contaminans, immune assessment should be carried out even if there is no positive medical history or specificity in basic immunity screening.


Nonpharmacological Alternatives to Benzodiazepine Drugs for the Treatment of Anxiety in Outpatient Populations: A Literature Review.
Overuse of benzodiazepine drugs to treat anxiety, mood, and sleep disorders is a growing problem in clinical practice. GABAergic medications (benzodiazepine drugs in particular) have side effects, drug interactions, and the potential to create tolerance and dependence in users. GABA-enhancing dietary supplements have similar and unique risks. Natural, non-chemical, anxiolytic treatments exist and can be safely recommended to patients. Three such treatments have been the focus of study in the past 20 years: mindfulness, meditation, and yoga. Growing evidence exists that these treatments can be safely recommended to patients with anxiety. [Journal of Psychosocial Nursing and Mental Health Services, 54(8), 35-42.].


Effects of novelty and oddity on visual selective attention.
Effects of novelty and of oddity on selective attention was investigated through tachistoscopic recognition. When a pre-exposure field consisted of dots of one colour, letters of a different colour were more likely to be identified than letters of the same colour. In displays of 10 letters, two letters differing in colour from the remainder were more likely to be identified. Tachistoscopic exposure precluded determination of responses by eye movements, and there were controls for chromatic adaptation and other factors that might have biased the results.


Inorganic-organic hybrid nanomaterials for therapeutic and diagnostic imaging applications.
Nanotechnology offers outstanding potential for future biomedical applications. In particular, due to their unique characteristics, hybrid nanomaterials have recently been investigated as promising platforms for imaging and therapeutic applications. This class of nanoparticles can not only retain valuable features of both inorganic and organic moieties, but also provides the ability to systematically modify the properties of the hybrid material through the combination of functional elements. Moreover, the conjugation of targeting moieties on the surface of these nanomaterials gives them specific targeted imaging and therapeutic properties. In this review, we summarize the recent reports in the synthesis of hybrid nanomaterials and their applications in biomedical areas. Their applications as imaging and therapeutic agents in vivo will be highlighted.


Acid-Base Polymeric Foams for the Adsorption of Micro-oil Droplets from Industrial Effluents.
Separation of toxic organic pollutants from industrial effluents is a great environmental challenge. Herein, an acid-base engineered foam is employed for separation of micro-oil droplets from an aqueous solution. In acidic or basic environments, acid-base polymers acquire surface charge due to protonation or dissociation of surface active functional groups. This property is invoked to adsorb crude oil microdroplets from water using polyester polyurethane (PESPU) foam. The physicochemical surface properties of the foam were characterized using X-ray photoelectron spectroscopy, inverse gas chromatography, electrokinetic analysis, and micro-computed tomography. Using the surface charge of the foam and oil droplets, the solution pH (5.6) for maximum separation efficacy was predicted. This optimal pH was verified through underwater wetting behavior and adsorption experiments. The droplet adsorption onto the foam was governed by physisorption, and the driving forces were attributed to electrostatic attraction and Lifshitz-van der Waals forces. The foam was regenerated and reused multiple times by simple compression. The lowest trace oil content in the retentate was 3.6 mg L-1, and all oil droplets larger than 140 nm were removed. This work lays the foundation for the development of a new class of engineered foam adsorbents with the potential to revolutionize water treatment technologies.


[Effect of prednisone and typhoid vaccine on the size of systemic neutrophil granulocyte pool].
Changes of total granulocyte pool in the organism were evaluated after administration of prednisone or typhoid vaccine. For this purpose the unsaturated capacity of serum vitamin B12 binding was determined. After administration of prednisone the rise of granulocytes in peripheral blood was associated with a rise in the unsaturated capacity of vitamin B12 binding by the serum which was not observed after administration of typhoid vaccine. This observation confirmed the suggestions that corticosteroids not only mobilize the bone marrow reserve of granulocytes but prolong also their survival in the organism.


Clinical characteristics and prognostic significance of chronic myeloid leukemia with rare BCR-ABL1 transcripts.
The prognostic significance of rare BCR-ABL1 transcripts is uncertain in the tyrosine kinase inhibitor (TKI) era. In this retrospective study, 40 (1.7%) patients with rare BCR-ABL1 transcripts were identified from a cohort of 2331 chronic myeloid leukemia (CML) patients; 4 types of rare transcripts were identified, including e1a2 (0.9%), e19a2 (0.4%), e13a3 (0.1%), and e14a3 (0.3%). Compared to patients with the typical transcript, those with the e1a2 transcript had an inferior response to TKIs and a worse outcome. Patients with the e19a2 transcript had a high rate of early optimal response to TKIs, but most of them later lost the complete cytogenetic response (CCyR) due to BCR-ABL1 mutations, resulting in a poor prognosis. Patients with the e13a3/e14a3 transcript responded well to TKIs and had a good outcome. These findings indicate that the type of BCR-ABL1 transcript should be considered when determining the treatment for CML patients in the TKI era.


Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system.
Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC-030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels. Mice were treated with vehicle or HC-030031 (18.75-300 mg/kg) before ifosfamide (400 mg/kg), 0.75% mustard oil (50 μL/colon), acetic acid 0.6% (10 mL/kg), zymosan (1 mg/cavity) or misoprostol (1 μg/cavity) injection. Visceral nociception was assessed through the electronic von Frey test or the writhing response. Ifosfamide-administered mice were euthanized for bladder analysis. The involvement of nitric oxide and the opioid system were investigated in mice injected with ifosfamide and mustard oil, respectively. The participation of resident peritoneal cells in acetic acid-, zymosan- or misoprostol-induced nociception was also evaluated. HC-030031 failed to protect animals against ifosfamide-induced bladder injury (p > 0.05). However, a marked antinociceptive effect against ifosfamide, mustard oil, acetic acid, zymosan and misoprostol was observed (p < 0.05). Neither L-arginine (600 mg/kg) nor naloxone (2 mg/kg) could reverse the antinociceptive effect of HC-030031. The reduction of the peritoneal cell population inhibited the acetic acid and zymosan-related writhes without interfering with the misoprostol effect. Our findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.


Microdistribution of 239Pu in the rat skeleton. Part I. Dose dependency.
Sixty-day-old male and female rats were injected intravenously with one of three doses of monomeric 239Pu (1.11, 11.1 and 111 kBq kg-1 body weight) and were killed 1, 7, 14 or 32 days after injection. The macroscopic distribution in the skeleton as well as the microscopic distribution in the distal femur and the lumbar vertebra were studied. In general, no significant differences between the two sexes and the normalized three dose levels were found. The concentrations and dose-rates in hard tissue, marrow and near bone surfaces were lowest in the femur diaphysis and highest in the distal femur metaphysis. In each bone region the dose-rate increased in the order marrow, hard tissue, periosteal and endosteal bone surfaces. The initial dose-rates on the endosteal bone surfaces ranged from 130 mGy d-1 (femur diaphysis) up to 300 mGy d-1 (distal femur metaphysis), corresponding to an average cumulative monthly dose of 2.2 Gy (femur diaphysis) and 7 Gy (distal femur metaphysis) normalized to an injected dose of 37 kBq kg-1 body weight. After the injection of 111 kBq kg-1 body weight radiation, induced morphological changes occur to the distal femur metaphysis 32 days after injection.


Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life.
Neuroborreliosis affects the nervous system after systemic infection with the spirochete Borrelia burgdorferi. Previously, cerebral vasculitis has been regarded as an extremely rare complication of neuroborreliosis. The data on the long-term outcome in patients with cerebral vasculitis due to neuroborreliosis are limited. The objective of this study was to perform a longitudinal analysis of cases of neuroborreliosis-associated cerebral vasculitis. We recruited all patients (n = 11) diagnosed with neuroborreliosis-associated in three neurological departments in an East German region. Inclusion criteria were sudden neurological deficits, magnetic resonance (MR) imaging findings that conform to cerebral ischemia or brain infarction, intrathecal synthesis of borrelia-specific antibodies, and non-atherosclerotic pathology of brain supplying arteries. Vasculitic changes were detected by digital subtraction angiography, MR angiography and/or transcranial Doppler ultrasound. Outcomes were measured by the modified Rankin scale (mRS) and EuroQoL Index. Cerebral vasculitis is a rare complication of Lyme disease (0.3% of all cases in the endemic area). Ten out of 11 patients diagnosed with neuroborreliosis-associated vasculitis cerebral vasculitis using clinical, radiological and immunological criteria developed ischemic stroke or transient ischemic attacks (TIA), 7 patients had recurrent stroke. Vasculitic alterations could be demonstrated in 8 patients that all except one developed ischemic lesions. The median mRS was 3 (range 0-4) at admission and 2 (range 0-6) at discharge. The posterior circulation was affected in 8 of 11 patients; thrombosis of the basilar artery was detected in 2 patients, one died in the acute stage. Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis. Lumbar puncture is needed for detection of this potentially life-threatening condition. Early recognition and adequate therapy would possibly improve outcome.


Detection of RAG protein-V(D)J recombination signal interactions near the site of DNA cleavage by UV cross-linking.
V(D)J recombination is initiated by double-strand cleavage at recombination signal sequences (RSSs). DNA cleavage is mediated by the RAG1 and RAG2 proteins. Recent experiments describing RAG protein-RSS complexes, while defining the interaction of RAG1 with the nonamer, have not assigned contacts immediately adjacent to the site of DNA cleavage to either RAG polypeptide. Here we use UV cross-linking to define sequence- and site-specific interactions between RAG1 protein and both the heptamer element of the RSS and the coding flank DNA. Hence, RAG1-DNA contacts span the site of cleavage. We also detect cross-linking of RAG2 protein to some of the same nucleotides that cross-link to RAG1, indicating that, in the binding complex, both RAG proteins are in close proximity to the site of cleavage. These results suggest how the heptamer element, the recognition surface essential for DNA cleavage, is recognized by the RAG proteins and have implications for the stoichiometry and active site organization of the RAG1-RAG2-RSS complex.


Rectosigmoidal bladder utilizing an intussuscepted ileal segment: a surgical technique for urinary diversion.
A novel technique of urinary diversion was designed by interposition of an intussuscepted ileal segment between the ureters and the rectosigmoidal pouch, thus preventing ureteral reflux as well as stenosis at the uretero-enteric anastomosis, possible occurrence of urocolonic carcinoma, and frequent evacuation or incontinence. Since all the procedures were limited to the lower abdominal cavity, the surgical invasiveness was compatible with that of an ileal conduit. Our early experience in 15 patients showed that this technique can be considered for those in whom the urethra is not available.


Evaluation of pheromones and a new trap for monitoring Agriotes lineatus and Agriotes obscurus in the Fraser Valley of British Columbia.
A prototype ground-based pheromone trap design, baited with various pheromone lures, was field tested for effectiveness in trapping male Agriotes obscurus and Agriotes lineatus click beetles in British Columbia. Pheromone dispensers containing geranyl octanoate and geranyl hexanoate in a 1:1 ratio caught the greatest numbers of A. obscurus, whereas those containing geranyl octanoate and geranyl butanoate in a 9 or 10:1 ratio caught high numbers of A. lineatus. Some differences in A. obscurus attraction to traps were observed between dispensers according to the manufacturer and the number of dispensers deployed in traps. The trap design and optimal pheromone dispensers tested would be suitable for monitoring or surveying A. obscurus and A. lineatus populations in North America.


Improving animal health for poverty alleviation and sustainable livelihoods.
Animals are vital to ensuring food security for individuals, families and communities in countries around the world. In this, the latest article in Veterinary Record's series promoting One Health, Andy Stringer, director of veterinary programmes at the Society for the Protection of Animals Abroad, discusses how improving animal health, particularly of poultry and working equids, has the potential to reduce poverty and promote food security and sustainable livelihoods in low-income countries.


[Successful oral administration of etoposide therapy for refractory malignant lymphoma treated with frequent combination chemotherapy].
A 67-year-old man was diagnosed as non-Hodgkin lymphoma (diffuse, mixed cell type, B cell) with clinical stage IV in March 1989. He had been treated many times with salvage chemotherapy on admission including CHOP-etoposide and ProMACE-Cyta BOM. Recurrence, however, occurred in two or three months after any therapy. He had a therapeutic history of chronic daily administration of etoposide. In November 1991, recurrence was found in the peripheral lymph node and the colon. A new regimen of oral administration of etoposide, 50 mg/day four times a week, was employed. Two months later, the peripheral lymph node swelling disappeared. Seven months later, the patient showed no signs of recurrence by Ga-scintigraphy. This therapy is being continued. It is suggested that anti-neoplastic activity of etoposide is dependent on the schedule of administration. This regimen is suggested to be effective in the treatment of patients with refractory malignant lymphoma.


Elastomeric Porous Poly(glycerol sebacate) Methacrylate (PGSm) Microspheres as 3D Scaffolds for Chondrocyte Culture and Cartilage Tissue Engineering.
Cartilage defects can be difficult to treat; therefore, tissue engineering of cartilage is emerging as a promising potential therapy. One interesting area of research explores the delivery of cells to the cartilage defect via scaffold-based cell delivery vehicles and microsurgery. This study explores the use of novel poly(glycerol sebacate) methacrylate (PGSm)-polymerised high internal phase emulsion (polyHIPE) microspheres as scaffolds with embedded cells for cartilage tissue engineering. Porous microsphere scaffolds (100 µm-1 mm diameter) were produced from emulsions consisting of water and a methacrylate-based photocurable resin of poly(glycerol sebacate). These resins were used in conjunction with a T-junction fluidic device and an ultraviolet (UV) curing lamp to produce porous microspheres with a tuneable size. This technique produced biodegradable PGSm microspheres with similar mechanical properties to cartilage. We further explore these microspheres as scaffolds for three-dimensional culture of chondrocytes. The microspheres proved to be very efficient scaffolds for primary chondrocyte culture and were covered by a dense extracellular matrix (ECM) network during the culture period, creating a tissue disk. The presence of glycosaminoglycans (GAGs) and collagen-II was confirmed, highlighting the utility of the PGSm microspheres as a delivery vehicle for chondrocytes. A number of imaging techniques were utilised to analyse the tissue disk and develop methodologies to characterise the resultant tissue. This study highlights the utility of porous PGSm microspheres for cartilage tissue engineering.


Assessing prosodic skills in five European languages: cross-linguistic differences in typical and atypical populations.
Following demand for a prosody assessment procedure, the test Profiling Elements of Prosody in Speech-Communication (PEPS-C), has been translated from English into Spanish, French, Flemish and Norwegian. This provides scope to examine receptive and expressive prosodic ability in Romance (Spanish and French) as well as Germanic (English and Flemish) languages, and includes the possibility of assessing these skills with regard to lexical tone (Norwegian). Cross-linguistic similarities and differences relevant to the translation are considered. Preliminary findings concerning 8-year-old neurotypical children speaking the five languages are reported. The appropriateness of investigating contrastive stress in Romance as well as Germanic languages is considered: results are reported for assessing this skill in Spanish and English speakers and suggest that in Spanish it is acquired much later than in English. We also examine the feasibility of assessing and comparing prosodic disorder in the five languages, using assessments of prosody in Spanish and English speakers with Williams syndrome as an example. We conclude that, with caveats, the original design of the UK test may indicate comparable stages of prosodic development in neurotypical children and is appropriate for the evaluation of prosodic skills for adults and children, both neurotypical and with impairment, in all five languages.


Immune-related genes of the larval Holotrichia parallela in response to entomopathogenic nematodes Heterorhabditis beicherriana LF.
Entomopathogenic nematodes (EPNs) emerge as compatible alternatives to conventional insecticides in controlling Holotrichia parallela larvae (Coleoptera: Scarabaeidae). However, the immune responses of H. parallela against EPNs infection remain unclear. In present research, RNA-Seq was firstly performed. A total of 89,427 and 85,741 unigenes were achieved from the midgut of H. parallela larvae treated with Heterorhabditis beicherriana LF for 24 and 72 h, respectively; 2545 and 3156 unigenes were differentially regulated, respectively. Among those differentially expressed genes (DEGs), 74 were identified potentially related to the immune response. Notably, some immune-related genes, such as peptidoglycan recognition protein SC1 (PGRP-SC1), pro-phenoloxidase activating enzyme-I (PPAE-I) and glutathione s-transferase (GST), were induced at both treatment points. Bioinformatics analysis showed that PGRP-SC1, PPAE-I and GST were all involved in anti-parasitic immune process. Quantitative real-time PCR (qRT-PCR) results showed that the three immune-related genes were expressed in all developmental stages; PGRP-SC1 and PPAE-I had higher expressions in midgut and fat body, respectively, while GST exhibited high expression in both of them. Moreover, in vivo silencing of them resulted in increased susceptibility of H. parallela larvae to H. beicherriana LF. These results suggest that H. parallela PGRP-SC1, PPAE-I and GST are involved in the immune responses to resist H. beicherriana LF infection. This study provides the first comprehensive transcriptome resource of H. parallela exposure to nematode challenge that will help to support further comparative studies on host-EPN interactions.


Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.
Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction. The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction. Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up. The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months. Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations. In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations. clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31.


Apoptosis induced by baicalin involving up-regulation of P53 and bax in MCF-7 cells.
Anticancer effect of baicalin (1) has been well documented. However, the molecular mechanisms underlying the cytotoxicity of baicalin in cancer cells remain unclear. In the present study, we examined the potential roles of p53, bax, and bcl-2 in baicalin-triggered apoptosis in MCF-7 cells, a cell line derived from human breast cancer. The results showed that cell proliferation was significantly inhibited by baicalin in a dose- and time-dependent manner. Flow cytometric analysis also revealed that most of the baicalin-treated MCF-7 cells were arrested in the G(0)/G(1) phase. Significant amount of cells underwent apoptotic cell death 24 h following baicalin treatment. Typical apoptotic characteristics such as chromatin condensation and the formation of apoptotic bodies were noted 48 h following baicalin exposure. Semi-quantitative analysis using RT-PCR revealed dramatic elevation of mRNA levels of proapoptotic molecules p53 and bax, but not the anti-apoptotic bcl-2. Consistently, significant elevation of p53 and bax was substantiated by the western blot. Collectively, the data demonstrated that baicalin-induced apoptotic cell death in the breast cancer cells involves the up-regulation of proapoptotic p53 and bax, implying potential crucial roles of bax and p53 in the baicalin-induced apoptosis.


Animal models for the effective development of atrophic vaginitis therapies: possibilities and limitations.
Vaginal atrophy (VA) is an inflammation of the vagina that develops when there is a significant decrease in levels of the estrogen. Prolonged periods of hypoestrogenism may induce severe VA and treatment is essential. This is a significant problem which requires more focused attention for the development of existing and future therapies. This review evaluates the suitable animal models of VA, including: mice, rodents and non-human primates. It focuses particularly on the possibilities and limitations of these in vivo models for the effective development of VA therapies. Hormone replacement therapy (HRT) has been prescribed and successfully used for VA. However, some studies have shown that HRT may be linked to an increased risk of breast cancer, coronary heart diseases and others risks. Thus, there is a growing interest in effective and safe alternatives to VA symptoms. There are, however, a number of things that must be considered for future drug discovery efforts. One major consideration is what animal model should be used and whether the model is appropriate for the study aim. Similarly, research studies must also consider the influencing factors on these animal models, so that these models can effectively mimic the actual disease. The authors also highlight the need to standardize research parameters to produce more reliable and reproducible data.


3DPhenoFish: Application for two- and three-dimensional fish morphological phenotype extraction from point cloud analysis.
Fish morphological phenotypes are important resources in artificial breeding, functional gene mapping, and population-based studies in aquaculture and ecology. Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor. More importantly, manual measurement is highly dependent on operational experience, which can lead to subjective phenotyping results. Here, we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional (3D) point cloud data. Algorithms for background elimination, coordinate normalization, image segmentation, key point recognition, and phenotype extraction were developed and integrated into an intuitive user interface. Furthermore, 18 key points and traditional 2D morphological traits, along with 3D phenotypes, including area and volume, can be automatically obtained in a visualized manner. Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software. Using 3DPhenoFish, we performed high-throughput phenotyping for four endemic Schizothoracinae species, including Schizopygopsis younghusbandi, Oxygymnocypris stewartii, Ptychobarbus dipogon, and Schizothorax oconnori. Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation (>0.94) with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species. In summary, we developed an efficient, accurate, and customizable tool, 3DPhenoFish, to extract morphological phenotypes from point cloud data, which should help overcome traditional challenges in manual measurements. 3DPhenoFish can be used for research on morphological phenotypes in fish, including functional gene mapping, artificial selection, and conservation studies. 3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.


Association of follicle-to-oocyte index and clinical pregnancy in IVF treatment: A retrospective study of 4,323 fresh embryo transfer cycles.
The aim of this study is to investigate whether the follicle-to-oocyte index [FOI: (number of retrieved oocytes/antral follicle count) × 100] was associated with clinical pregnancy after fresh cleavage transfer. The framework used to organize this study is retrospective cohort analysis. The study was performed in a single in vitro fertilization center in a public hospital. In total, 4,323 fresh embryo transfer cycles from 1 August 2011 to 31 January 2022 were retrospectively analyzed. Data were designated into three groups according to FOI tertile values. There are no interventions in this study. The primary outcome measure is the clinical pregnancy rate (CPR). A total of 4,323 patients were included in the study. According to their FOI, patients were divided into low (FOI ≤ 0.70, n = 1,434), medium (FOI = 0.71-0.95, n = 1,070), and high (FOI = 0.96-1.00, n = 1,819) tertile groups. A significant statistical increase in the CPR from the lowest to the highest tertile FOI group was detected (47.28%, 51.78%, and 51.57%; P =0.026). After adjusted for potential confounders, multivariate logistic regression analysis revealed a positive association between FOI and CPR [odds ratio (OR) = 1.57; 95% confidence interval (CI): 1.18-2.11]. Each standard deviation increments in FOI (SD = 0.24) corresponded to a 20% increase in the CPR. Trend analysis also showed that FOI tertile groups were positively associated with CPR (P for trend = 0.010). Smooth curve fitting indicated the existence of a linear relationship across the entire range of FOI. No optimal cutoff value of FOI for prognosing CPR was found in smooth curve fitting analysis. Moreover, subgroup analyses suggested that the association was significantly stronger in the single cleavage transfer cycle (OR = 2.04; 95% CI: 1.14-3.65). FOI is an independent variable in prediction for CPR in fresh embryo transfer cycle, especially in the single cleavage transfer cycle.


Isoform-specific increase of spastin stability by N-terminal missense variants including intragenic modifiers of SPG4 hereditary spastic paraplegia.
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder selectively affecting axons of spinal cord motoneurons. Classical mutations in the most frequent HSP gene SPAST (spastin protein) act through haploinsufficiency by abolishing the activity of a C-terminal ATPase domain or by interfering with expression from the affected allele. N-terminal missense variants have been suggested to represent rare polymorphisms, to cause unusually mild phenotypes, and to aggravate the effect of a classical mutation. We confirm these associations for p.S44L but do not detect two other variants (p.E43Q; p.P45Q) in HSP patients and controls. We show that neither of several disease mechanisms associated with classical SPAST mutations applies to the N-terminal variants. Instead, all three alterations enhance the stability of one of two alternative spastin isoforms. Their phenotypic effect may thus not be mediated by haploinsufficiency but by increasing isoform competition for interacting proteins, substrates or oligomerization partners.


Treatment with megestrol acetate improves human immunodeficiency virus-associated immune thrombocytopenia.
Splenic macrophage Fc gamma receptors participate in the pathophysiology of immune cytopenias, and in such disorders, the beneficial effects of glucocorticoids are in part mediated by decreased expression of macrophage Fc gamma receptors. In the animal model, progesterones, like glucocorticoids, inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone frequently used for treating human immunodeficiency virus (HIV)-associated anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia with shortened platelet survival and increased platelet-associated immunoglobulin G (IgG) who were being treated with MA for anorexia-cachexia were prospectively studied for a 6-month period to assess the potential role of progesterones in the treatment of immune thrombocytopenia. Treatment with MA for non-consecutive periods of 2 months and 1 month significantly increased platelet count and platelet survival without significant alteration of platelet-associated immunoglobulin levels. Of the 28 patients studied, 22 presented a complete response, 19 presented a complete response 1 month after finishing the MA treatment regimen, and 12 remained in complete response for a further month. Expression of Fc gamma receptors (Fc gamma RI and Fc gamma RII) by peripheral blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes were significantly decreased by the MA treatment. Decreased expression and functioning of these receptors significantly correlated with platelet counts and survival times, but no relationship was found with platelet-associated immunoglobulin, circulating immune complexes, body mass index, plasma HIV load, or CD4 lymphocyte levels. These results suggest that treatment with progesterones, like MA, may be an alternative therapy for immune cytopenias, with few side effects.


Modern approaches to the management of metastatic epidural spinal cord compression.
Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency requiring prompt treatment to maximize neurologic function, ambulatory function and local control. Traditionally, options for MESCC included external beam radiation therapy with or without surgery. Surgery has usually been reserved for the patient with optimal performance status, single level MESCC or mechanical instability. Advances in external beam radiation therapy such as the development of stereotactic body radiation therapy have allowed for the delivery of high-dose radiation, allowing for both long-term pain and local control. Surgical advances, such as separation surgery, minimal access spine surgery and percutaneous instrumentation, have decreased surgical morbidity. This review summarizes the latest advances and evidence in MESCC to enable modern management.


Spin and charge order in the doped hubbard model: long-wavelength collective modes.
Determining the properties of the two-dimensional Hubbard model is an outstanding problem in physics. Applying recent advances in constrained path auxiliary-field quantum Monte Carlo techniques and simulating large rectangular supercells, we characterize the magnetic and charge properties in the ground state as a function of doping. At intermediate interaction strengths, an incommensurate spin density wave (SDW) state is found, with antiferromagnetic order and essentially homogeneous charge correlation. The wavelength of the collective mode decreases with doping, as does its magnitude. The SDW order vanishes beyond a critical doping. As the interaction is increased, the holes go from a wavelike (delocalized) to a particlelike (localized) state, and charge ordering develops which eventually evolves into stripelike states.


Streptococcus grouping latex kits: evaluation of five commercially available examples.
This study compares a recently introduced latex agglutination test for the serogrouping of beta-haemolytic streptococci against four internationally used commercial kits. The new kit is Prolex-Blue (Pro-Lab Diagnostics) and the comparators are Streptex (Murex), PathoDx (DPC), Streptococcus Grouping kit (Oxoid) and Prolex-White (Pro-Lab Diagnostics). A total of 302 consecutive clinical isolates are tested against all five kits, following the individual manufacturer's protocol, for both accuracy and speed. In addition, the data produced permits determination of the strengths or weaknesses of the kits against individual serotypes. Prolex-Blue proved to be both accurate and rapid, with a sensitivity of 99% and a specificity of 100%. Furthermore, average time to agglutination was substantially less than achieved by three of the other four kits evaluated.


The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals.
The evolution of genomic imprinting, the parental-origin specific expression of genes, is the subject of much debate. There are several theories to account for how the mechanism evolved including the hypothesis that it was driven by the evolution of X-inactivation, or that it arose from an ancestrally imprinted chromosome. Here we demonstrate that mammalian orthologues of imprinted genes are dispersed amongst autosomes in both monotreme and marsupial karyotypes. These data, along with the similar distribution seen in birds, suggest that imprinted genes were not located on an ancestrally imprinted chromosome or associated with a sex chromosome. Our results suggest imprinting evolution was a stepwise, adaptive process, with each gene/cluster independently becoming imprinted as the need arose.


Interaction of LDS-751 and rhodamine 123 with P-glycoprotein: evidence for simultaneous binding of both drugs.
The P-glycoprotein efflux pump, an ABC superfamily member, can export a wide variety of hydrophobic drugs, natural products, and peptides from cells, powered by the energy of ATP hydrolysis. Transport substrates appear to first partition into the membrane and then interact with the protein within the cytoplasmic leaflet. Two drug binding sites within P-glycoprotein have been described which interact allosterically, the H-site (binds Hoechst 33342) and the R-site (binds rhodamine 123); however, the structural and functional relationship between the various binding sites appears complex. In this work, we have used fluorescence spectroscopic approaches to characterize the interaction of the transporter with LDS-751 and rhodamine 123, both of which are believed to bind to the putative R-site based on functional transport studies. By carrying out single and sequential dual fluorescence titrations of purified P-glycoprotein with the two substrates, we observed that bound LDS-751 interacted with bound rhodamine 123. Rhodamine 123 and LDS-751 showed a reciprocal negative interaction, each reducing the binding affinity of the other by 5-fold, indicating that the two compounds were simultaneously bound to the protein to form a ternary complex. Fitting of the dependence of the apparent Kd for LDS-751 binding on rhodamine 123 concentration suggested that the two compounds interacted noncompetitively. We conclude that the two-site drug binding model for P-glycoprotein requires modification. The putative R-site appears large enough to accommodate two compounds simultaneously. The locations where LDS-751 and rhodamine 123 bind are likely adjacent to each other, possibly overlapping, and may be within a hydrophobic pocket.


Functional approach to a Class II patient with upper first molar impaction.
The lack of the left first molar maxillary and the left second molar maxillary, caused respectively by impaction and agenesis is a very rare case, which determines an important occlusal imbalance and asymmetrical mandible movement. A gnatologic and functional orthodontic approach were planned to improve the retrognathic mandible and the muscular activity using kinesiograph and electromyography.


Investigation on size tolerance of pore defect of girth weld pipe.
Welding quality control is an important parameter for safe operation of oil and gas pipes, especially for high-strength steel pipes. Size control of welding defect is a bottleneck problem for current pipe construction. As a key part of construction procedure for butt-welding of pipes, pore defects in girth weld is difficult to ignore. A three-dimensional non-linear finite element numerical model is established to study applicability of size control indices based on groove shape and softening phenomenon of material in heat-affected zone of practical pipe girth weld. Taking design criteria of pipe as the basis, basic tensile, extremely tensile and extremely compressive loading conditions are determined for pipe stress analysis, and failure criteria based on flow stress is employed to perform stress analysis for pipe girth weld with pore defect. Results show that pipe girth welding stresses of pores at various radial locations are similar. Whereas, stress for pores of different sharpness varied significantly. Besides, tolerance capability of API 5L X90 grade pipe to pore defect of girth weld is lower than that of API 5L X80 grade pipe, and size control index of 3 mm related to pore defect in current standards is applicable to API 5L X80 and X90 grade girth welded pipes with radially non-sharp pore defects.


Hepatocellular carcinoma in Taiwan.
Hepatocellular carcinoma (HCC) is common in Taiwan. The age-adjusted incidence rates have been increasing, from approxiimately 15/100 000 in the 1980s to approximately 30/100 000 recently. The main causes are chronic hepatitis B and C infections, with >90% of patients positive for hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (anti-HCV). Before 1990, approximately 80% of patients with HCC were positive for HBsAg. The infection is mainly from perinatal mother-to-infant transmission. HCV is the second important cause, accounting for approximately 70% of HBsAg negative patients. Overall, 5-10% patients have infections of both viruses. In HBsAg negative-anti-HCV negative patients, polymerase chain reaction assay still reveals the key role of HBV. Epidemiologic studies also reveal the important role of HBV. In a nested case-control study, cumulative incidence of HCC was 10% after nine years of follow-up in hepatitis B e-antigen (HBeAg) positive carriers, with a relative risk of 60.2 compared to 9.6 in HBeAg negative carriers. The role of high viral load was confirmed when another community-based prospective study of 3644 HBsAg carriers stratified by serum hepatitis B virus (HBV) DNA levels correlated well with the occurrence of HCC, especially in carriers with levels >10(5) copies/mL. Genotype C infection contributed more to hepatocarcinogenesis than genotype B. Although HBV is dominant in causing HCC, in the last two decades the relative importance of HCV has changed. The proportion of anti-HCV positive cases has increased. In some areas of southern Taiwan where HCV infection is rampant, HCV-associated HCC have surpassed HBV-associated cases. To control hepatitis B, a mass neonatal vaccination program against hepatitis B was launched in 1984. The HBsAg carrier rate decreased from the historical 15-20% to < 1% after vaccination. Most importantly, annual incidence of childhood HCC has decreased from 0.67 to 0.19/100 000 children. To control hepatitis C, besides interrupting the transmission routes and screening blood donors with anti-HCV, treatment with interferon and ribavirin was implemented on a national basis in 2003. Through these efforts, virally-induced HCC will be controlled in 20-30 years, and a decrease of approximately 85% is anticipated by 2040. Then, HCC will not be commonly seen in Taiwanese people, and the major cause of HCC will be non-viral factors that lead to cirrhosis, such as non-alcoholic steatohepatitis.


A semi-automatic motion-constrained Graph Cut algorithm for Pedestrian Detection in thermal surveillance videos.
This article presents a semi-automatic algorithm that can detect pedestrians from the background in thermal infrared images. The proposed method is based on the powerful Graph Cut optimisation algorithm which produces exact solutions for binary labelling problems. An additional term is incorporated into the energy formulation to bias the detection framework towards pedestrians. Therefore, the proposed method obtains reliable and robust results through user-selected seeds and the inclusion of motion constraints. An additional advantage is that it enables the algorithm to generalise well across different databases. The effectiveness of our method is demonstrated on four public databases and compared with several methods proposed in the literature and the state-of-the-art. The method obtained an average precision of 98.92% and an average recall of 99.25% across the four databases considered and outperformed methods which made use of the same databases.


Posttraumatic Stress, Depression, and Sleep Among Young Survivors of Violence.
Survivors of violence often suffer psychological harm in addition to physical wounds. This study explored (1) the prevalence of Posttraumatic Stress Disorder (PTSD) symptoms, depression symptoms, and disordered sleep among young, violently injured, emergency department patients; and (2) how PTSD and depression symptoms are associated with sleep quality. Clinical scales for PTSD (PCL-5), depression (PHQ-8), and sleep (PROMIS®) were completed by 88 survivors of violent assault (gunshot, stabbing or assault) one month or less after presenting to an urban emergency department. High proportions of participants met criteria for prospective PTSD (59.1%), major depression (44.3%) or disordered sleep (34.1%), with 27.3% meeting criteria for all three conditions. Poorer sleep quality was correlated with higher levels of depression symptoms and PTSD symptoms. Survivors of violence experience symptoms that may further impair their sleep and behavioral health. Emergency providers should ask survivors about sleep/trauma symptoms and consider referral to trauma-informed behavioral health care.