Some children with idiopathic toe walking display sensory processing difficulties but not all: A systematic review.
Idiopathic toe walking (ITW) is a diagnosis for children who toe walk without another diagnosis known to cause toe walking. Recent research has suggested that children with ITW may have mild motor planning challenges and sensory processing differences. The primary aim of this systematic review was to determine whether children diagnosed with ITW have differences in their sensory processing compared to typically developing children. Secondary aims included determining how sensory processing was assessed in this population and documenting the broad clinometric and psychometric properties of any assessment tools. MEDLINE, CINAHL, AMED and Embase were searched for relevant literature in English. Studies were eligible for inclusion if they described children aged 3 and 18 with idiopathic toe walking and reported a sensory processing domain. Twelve articles met the inclusion criteria; however, only two papers included data permitting meta-analysis. Meta-analyses of vibration perception threshold using a random effect model were not significant (p = 0.31). Other data were synthesised by narrative and showed a high heterogeneity across multiple sensory processing domains. This study highlights that despite children with ITW often conceptualised as possessing sensory processing challenges, there is little evidence supporting this theory. Further research on sensory processing in children with this gait pattern is necessary.


Soil carbon pools and fluxes in urban ecosystems.
The transformation of landscapes from non-urban to urban land use has the potential to greatly modify soil carbon (C) pools and fluxes. For urban ecosystems, very little data exists to assess whether urbanization leads to an increase or decrease in soil C pools. We analyzed three data sets to assess the potential for urbanization to affect soil organic C. These included surface (0-10 cm) soil C data from unmanaged forests along an urban-rural gradient, data from "made" soils (1 m depth) from five different cities, and surface (0-15 cm) soil data of several land-use types in the city of Baltimore. Along the urban-rural land-use gradient, we found that soil organic matter concentration in the surface 10 cm varied significantly (P=0.001). In an analysis of variance, the urban forest stands had significantly (P=0.02) higher organic C densities (kg m(-2) to 1 m depth) than the suburban and rural stands. Our analysis of pedon data from five cities showed that the highest soil organic C densities occurred in loamy fill (28.5 kg m(-2)) with the lowest occurring in clean fill and old dredge materials (1.4 and 6.9 kg m(-2), respectively). Soil organic C densities for residential areas (15.5 +/- 1.2 kg m(-2)) were consistent across cities. A comparison of land-use types showed that low density residential and institutional land-uses had 44 and 38% higher organic C densities than the commercial land-use type, respectively. Our analysis shows that as adjacent land-use becomes more urbanized, forest soil C pools can be affected even in stands not directly disturbed by urban land development. Data from several "made" soils suggests that physical disturbances and inputs of various materials by humans can greatly alter the amount C stored in these soils.


Perceived privacy in home office and musculoskeletal complaints: a test of family-work conflict, work-family conflict, and relaxation as mediators.
Many employees have had to telework all year during the COVID-19 pandemic. Even though working from home has many advantages, there are also some disadvantages worth to consider. Lack of privacy is a relevant factor when it comes to the development of severe musculoskelatal issues. This study investigated the link between perceived privacy in home office and musculoskeletal complaints (MSCs). Family-work conflict (FWC), work-family conflict (WFC), and relaxation were tested as potential mediators for the relationship between perceived privacy and MSCs. The present study's questionnaire was filled out by 287 teleworking employees. Hypotheses were tested via multiple mediation analyses examining levels of perceived privacy in home office, and its relationship on MSCs. Furthermore, the underlying effect of FWC, WFC, and MSCs were tested with a structural equation model. As assumed, lack of privacy while working at home was linked to individuals more frequently experiencing MSCs. However, the structural equation model showed no significant mediation effect. Work design efforts must address privacy while employees perform telework at home to prevent MSCs.


Parental perception of optimal surgical age for correction of cryptorchidism: a multicenter surveillance study.
To perform a multicenter survey to determine how many parents understood the optimal time for surgical correction of cryptorchidism in children. We enrolled 377 parents of patients who had recently undergone surgical correction of cryptorchidism. These parents were divided into 3 groups according to their indicated preference of the optimal patient age for surgical correction: group 1 (<1 year old, 39 parents, 10.3%), group 2 (1-2 years old, 169 parents, 44.8%), and group 3 (>3 years, 169 parents, 44.8%). The mean age of the children who underwent orchiopexy was 4.9 ± 5.2 years. The interval from diagnosis to surgical correction of cryptorchidism was 17.1 ± 29.8, 15.4 ± 14.4, and 29.0 ± 24.4 months in groups 1, 2, and 3, respectively (P < .001). The mean age of the parents was significantly associated with the perception of the optimal time for surgical correction of cryptorchidism (P = .021 and P = .002). The number of highly educated parents was lowest in group 3 (P < .001). The number of parents with >2 children was 69.2% in group 1, 71.0% in group 2, and 84.0% in group 3 (P = .009). In group 3, the parents often delayed surgery because of the patient being too young (49.1%) and the parents' expectations of spontaneous descent (48.5%). Parents younger in age, with higher education levels and with fewer children, preferred early orchiopexy. Active intervention by a physician and public education for parents might be necessary to encourage earlier treatment of cryptorchidism.


Cashew apple byproduct: Gastroprotective effects of standardized extract.
The incidence of gastric mucosa lesions in the adult population has increased mainly due to the continued use of nonsteroidal anti-inflammatory drugs (NSAIDs). The cashew (Anacardium occidentale L.) is a tropical tree, cultivated in several countries, whose barks, leaves and pseudofruit (cashew apple) are popularly used in traditional medicine for the treatment of many diseases, including gastric ulcer. Our study evaluated the potential gastroprotective effect of the carotenoid and anacardic acids-enriched aqueous extract (CAE), prepared from cashew apple pomace, in the dose-repeated acetylsalicylic acid (ASA)-induced gastric lesions model in rats. After randomly distribution into five group (G1 - G5, n = 8 animals/group), male Wistar rats were daily treated with ASA solution (200 mg/kg, 5 ml/kg, G2 - G5) or potable water (Satellite group, G1) during 14 days. From 8th to 14th experimental day, rats in G3 - G5 groups were orally treated with CAE (50, 100 and 500 mg/kg, 5 ml/kg, respectively). Body weight was measured on 0, 7th and 14th day. On the 14th experimental day, all surviving animals were euthanized for macroscopic evaluation of the inner organs and stomach removal. After weighting, each stomach was properly prepared for biochemical analysis [myeloperoxidase activity (MPO), reduced glutathione analysis (GSH), IL-1β, CXCL2/MIP-2, TNF-α and IL-10 levels]. At the most efficient dose (100 mg/kg, p.o.), CAE-treated animals showed a slight improvement in the macroscopic aspect of gastric mucosa associated with significant (p < 0.05) reduced levels of IL-1β, CXCL2/MIP-2, and MPO activity besides increased levels of GSH (partially), and IL-10 in stomach tissues. The present study demonstrated that the carotenoid and anacardic acids-enriched extract obtained from cashew apple pomace is a promising raw material for the development of herbal medicine and/or functional food supplements for the adjuvant treatment of NSAIDs-induced gastric ulcers.


[Structure of a community of testate amoebae in a sphagnum dominated bog in upper sura flow (middle Volga territory)].
Fifty nine species of testate amoebae were found in a sphagnum moss bog located in the upper Sura flow (Volga highland). The active diversity in communities of sphagnum moss biotopes was formed by 24 species. Minimal species diversity (3 species) and maximum density of organisms were noted in the driest habitat. In the habitats with the medium humidity levels, the level of species richness was similar (13-16 species) and the total density was determined by redox characteristics of the environment: under the conditions of oxygen deficit, it was two to three times lower than in an oxidized environment. The species composition specificity in sphagnum moss biotopes was determined by the degree of humidity: in the driest habitats, Arcella arenaria predominated; in the biotopes with medium humidity, Nebella tenella and Hyalosphenia elegans; and in the most humid biotopes, Hyalosphenia papilio and Heleopera sphagni. Communities of testate amoebae differed by species composition and integral characteristics at different sphagnum moss horizons: the abundance and species richness increased with depth. The proportion of living individuals in the total number of tests was 35 to 75%.


Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas-Machine Learning Analysis.
Post-operative endocrine outcomes in patients with non-functioning pituitary adenoma (NFPA) are variable. The aim of this study was to use machine learning (ML) models to better predict medium- and long-term post-operative hypopituitarism in patients with NFPAs. We included data from 383 patients who underwent surgery with or without radiotherapy for NFPAs, with a follow-up period between 6 months and 15 years. ML models, including k-nearest neighbour (KNN), support vector machine (SVM), and decision tree models, showed a superior ability to predict panhypopituitarism compared with non-parametric statistical modelling (mean accuracy: 0.89; mean AUC-ROC: 0.79), with SVM achieving the highest performance (mean accuracy: 0.94; mean AUC-ROC: 0.88). Pre-operative endocrine function was the strongest feature for predicting panhypopituitarism within 1 year post-operatively, while endocrine outcomes at 1 year post-operatively supported strong predictions of panhypopituitarism at 5 and 10 years post-operatively. Other features found to contribute to panhypopituitarism prediction were age, volume of tumour, and the use of radiotherapy. In conclusion, our study demonstrates that ML models show potential in predicting post-operative panhypopituitarism in the medium and long term in patients with NFPM. Future work will include incorporating additional, more granular data, including imaging and operative video data, across multiple centres.


In vitro genotoxic effects of the insecticide deltamethrin in human peripheral blood leukocytes: DNA damage ('comet' assay) in relation to the induction of sister-chromatid exchanges and micronuclei.
Deltamethrin, a synthetic dibromo-pyrethroid insecticide, is extensively used in agriculture, forestry and in household products because of its high activity against a broad spectrum of insect pests (both adults and larvae), its low animal toxicity and its lack of persistence in the environment. Data on the genotoxicity and carcinogenicity of deltamethrin are rather controversial, depending on the genetic system or the assay used. The aim of this study was to further evaluate the potential genotoxic activity of deltamethrin. The in vitro genotoxicity of deltamethrin has been evaluated by assessing the ability of the insecticide to damage DNA (as evaluated using the single-cell microgel-electrophoresis or 'comet' assay) or induce sister-chromatid exchanges (SCE) and micronuclei (MN) in human peripheral blood leukocytes. All treatments were conducted with and without the presence of an external bioactivation source (+/- S9mix). The results indicate that deltamethrin, in the presence of metabolic activation (+ S9mix), is able to induce DNA damage (double- and single-strand breaks, alkali-labile sites and open excision repair sites) as revealed by the increasing tail moment values observed with increasing doses. The frequency of SCE and MN were not statistically increased in deltamethrin-treated cells as compared to controls, both with and without S9mix. However, lower deltamethrin doses were tested, as compared to 'comet' assay, because of cytotoxicity.


The effect of local bone density on mechanical failure after internal fixation of pertrochanteric fractures.
The aim of this prospective study was to investigate the effect of local hip bone density on mechanical failure after fixation of pertrochanteric fractures and to establish possible risk factors for the failures. A total of 136 consecutive patients presenting a closed unilateral pertrochanteric fracture were enrolled. The patients were treated with a sliding hip screw or an intramedullary nail. Dual energy X-ray absorptiometry measurements for bone density of the contralateral hip were made within 4 weeks postoperatively. Follow-up evaluations on the standard radiographs were documented for any mechanical failure including loss of reduction, screw or blade cut-out, lateral migration of the screw or blade, and implant breakage. Secondary outcomes were also recorded including patient characteristics and fixation construct variables as possible predictors for mechanical failure. At a minimum of 2 years of follow-up, 38 patients were reported with mechanical failure at an estimated risk of 27.9 %. The local bone density measurements for the study population showed no difference between patients with (0.710 g/cm(2)) and without (0.726 g/cm(2)) mechanical failure (P = 0.180). We also observed no significant correlation between local bone density and failure in patients with good fracture reduction (P = 0.862). The multivariate regression analysis identified fracture type (P < 0.001) and quality of fracture reduction (P < 0.001) as being independent predictors for mechanical failure, whereas local bone density was not (P = 0.658). Local hip bone density does not appear to have a significant influence on mechanical failure after internal fixation of pertrochanteric fractures. Stable fractures and fractures with good reduction are expected to obtain satisfactory outcomes.


Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment.
Cancer treatment has evolved rapidly due to major advances in tumor immunity research. However, due to the complexity, heterogeneity, and immunosuppressive microenvironment of tumors, the overall efficacy of immunotherapy is only 20%. In recent years, nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility, precise targeting, and controlled drug delivery. However, the clinical application of nanomedicine also faces many problems concerning biological safety, and the synergistic mechanism of nano-drugs with immunity remains to be elucidated. Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity. Finally, the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.


Exploring the quality of life (QOL) in the Indian software industry: a public health viewpoint.
Our objectives were to describe the QOL and its determinants among software professionals of Kolkata, and to compare the same according to information technology (IT) and IT-enabled services (ITeS) sub-sectors. An institution-based cross-sectional study was conducted among software professionals of Kolkata applying a two-stage stratified random sampling technique. The WHO QOL BREF questionnaire was administered along with a list of pertinent variables. Overall, the analysis for 338 software professionals (177 IT and 161 ITeS) clearly demonstrated significant differences between mean scores of these two sectors for each of the six outcome domains of WHO QOL BREF. Multilevel multivariate analysis outlined 13 significant predictors of QOL-four positive (age, regular fitness regimes, foreign placements and changing companies frequently) and the rest of the nine, negative (multiple sex partners, multiple addictions, extended working hours, night-shift duties, income, expenditure, carrying office work home, current illness and ITeS company type). Our study helps in obtaining a clear understanding of the multifaceted risk factors prevailing in this sector, the majority of which can be effectively addressed by specific health promotional interventions. A dedicated health policy is mandated at both government and company levels.


A role for increased mRNA stability in the induction of endothelin-1 synthesis by lipopolysaccharide.
An association exists between infection and cardiovascular diseases, including atherosclerosis, stroke and myocardial infarction. This may involve endothelin-1 (ET-1) which has been implicated in these and other vascular pathologies. ET-1 synthesis is controlled primarily by the level of its mRNA and numerous stimuli, including infection, lead to elevated ET-1 levels. Here, we have investigated the regulation of ET-1 release and preproET-1 (ppET-1) mRNA in bovine aortic endothelial cells by lipopolysaccharide (LPS). ET-1 release from bovine aortic endothelial cells was stimulated by LPS and reporter gene assays implicated LPS-induced ppET-1 transcription. However, changes in transcription were modest compared to increases in ET-1 synthesis. Therefore, ppET-1 mRNA levels were measured by real-time reverse transcription-polymerase chain reaction. The effect of LPS on ppET-1 mRNA levels was more marked than on transcription (1.2-fold increase in transcription vs. 5.5-fold increase in ppET-1 mRNA). Analysis of ppET-1 mRNA stability by real-time reverse transcription-polymerase chain reaction showed that LPS increased its half-life by approximately 2-fold. Thus, upregulated ppET-1 mRNA and hence increased ET-1 synthesis may be due to both increased transcription and reduced mRNA degradation. These effects of LPS on mRNA stability may be a key mechanism in vascular pathologies through which many proteins are induced in response to infection.


Clinical and histologic studies of neuronal intestinal dysplasia.
Over a period of 10 years we have treated 10 patients with neuronal intestinal dysplasia (NID), including 3 in whom the entire intestinal tract was affected by NID, and one in whom small intestinal NID coexisted with total colonic aganglionosis. Three of these 4 patients have died and the one survivor requires parenteral feeding. The six patients with less extensive NID have all been treated successfully; three have required surgery (Duhamel procedure in 2 and colostomy in 1), but 3 responded to conservative measures. We have made detailed histologic studies, including acetylcholinesterase activity in all cases, silver impregnation studies in 4, and immunohistochemical investigation of the peptidergic innervation of the bowel in one case. Follow-up rectal biopsies have not shown any significant morphological changes with time, but functional improvement does occur and we suggest that the myenteric ganglia in NID may have the capacity for functional maturation.


An engineer's approach to data collection and planning.
The hospital planner should imitate the engineer in his approach to gathering data on which planning programs must be based. The information must come from all groups involved in the hospital's operation, and each piece of data must then be evaluated for its individual contribution to the overall project.


Synthesis, biodistribution and micro-PET imaging of radiolabeled antimitotic agent T138067 analogues.
Radiolabeled antimitotic agents [11C]T138067 and [18F]T138067 have been synthesized for evaluation as new potential positron emission tomography (PET) biomarkers for cancer imaging. In vivo biodistribution and micro-PET imaging of [11C]T138067 were performed in breast cancer animal models MCF-7 transfected with IL-1alpha implanted athymic mice and MDA-MB-435 implanted athymic mice. The results suggest that the uptakes of [11C]T138067 in both MCF-7 transfected with IL-1alpha tumor and MDA-MB-435 tumor are non-specific binding.


Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations.
Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates proteins in mitochondria. Curiously, metazoa lack Hsp78. Hence, whether metazoan mitochondria reactivate aggregated proteins is unknown. Here, we establish that a mitochondrial AAA+ protein, Skd3 (human ClpB), couples ATP hydrolysis to protein disaggregation and reactivation. The Skd3 ankyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activity. A mitochondrial inner-membrane protease, PARL, removes an autoinhibitory peptide from Skd3 to greatly enhance disaggregase activity. Indeed, PARL-activated Skd3 solubilizes α-synuclein fibrils connected to Parkinson's disease. Human cells lacking Skd3 exhibit reduced solubility of various mitochondrial proteins, including anti-apoptotic Hax1. Importantly, Skd3 variants linked to 3-methylglutaconic aciduria, a severe mitochondrial disorder, display diminished disaggregase activity (but not always reduced ATPase activity), which predicts disease severity. Thus, Skd3 is a potent protein disaggregase critical for human health.


The role of fibrates in the prevention of cardiovascular disease--a pooled meta-analysis of long-term randomized placebo-controlled clinical trials.
Fibrates are effective antilipidemic agents with peroxisome proliferator-activated receptor agonist activity, but clinical trial data on their role in cardiovascular prevention are conflicting. We conducted a systematic review and meta-analysis of randomized clinical trials to evaluate their role in prevention of cardiovascular events. A total of 36,489 patients from 10 published randomized placebo-controlled trials were analyzed using the Mantel-Haenszel fixed-effects model. Odds ratios were computed for cardiovascular outcomes from data pooled from the selected trials, and statistical significance was tested using the z-test statistic (2-sided alpha error <.05). Fibrates significantly reduced plasma total cholesterol and triglyceride levels by about 8% and 30%, respectively, and raised high-density lipoprotein cholesterol levels by about 9% compared with placebo. The odds of all-cause mortality tended to be higher (P = .08), and the odds of noncardiovascular mortality were significantly higher (P = .004) with the use of fibrates. However, these significant differences did not persist after exclusion of trials using clofibrate as the study drug. Fibrates did not significantly reduce the odds of cardiovascular mortality (P = .68), fatal myocardial infarction (MI) (P = .76), or stroke (P = .56). On the other hand, fibrates significantly reduced the odds of nonfatal MI by about 22% (P < .00001). The odds of developing cancer were not significantly higher with the use of fibrates (P = .98), nor were the odds of cancer-related death (P = .17). In conclusion, our meta-analysis revealed that the long-term use of fibrates significantly reduces the occurrence of nonfatal MI but has no significant effect on other adverse cardiovascular outcomes.


Swollen and collapsed lyotropic lamellar rheology.
We have investigated linear rheological properties and the structure-flow relationship of the swollen (Lam(1)) and collapsed (Lam(2)) lamellar phases, formed on didodecyldimethylammonium bromide (DDAB)/lecithin/water ternary system at 25 degrees C. Both lamellar phases behaved like Bingham fluids and showed remarkable yield stresses. At rest the Lam(1) phase, which is characterized by densely packed vesicles whose sizes increase as the water content decreases in accordance to evolution of (2)H NMR spectral profiles of D(2)O, resulted in a strong elastic gel-like response. On the other hand, the Lam(2) phase, formed at high surfactant concentrations, showed a weak-gel viscoelasticity and (2)H NMR spectral patterns which are typical of planar bilayered structures. The increase of the quadrupole splitting as the water content decreases was assumed as a strong evidence of size increasing of the lamellar domains. We have demonstrated that by using dynamic rheology and the derived relaxation time spectra, along with (2)H NMR spectra of D(2)O, it is possible to differentiate between equilibrium lamellar structures occurring in a broad interval of total surfactant concentration. In addition, a shear-thickening regime, observed at intermediate shear-rate values, highlighted the onset of out-equilibrium lamellar structures which were present both on Lam(1) and Lam(2) phases.


Control from the brainstem of synchrony of discharge between gamma motoneurones in the cat.
An assessment has been made of the effect of partial and complete section of the spinal cord on the discharges of gamma motoneurones to hind limb muscles in the decerebrated cat. The degree to which the discharges of pairs of individual gamma motoneurones exhibit short-term synchrony and the variability in interspike intervals of the discharge in individual neurones was measured. Variability of discharge was assessed as coefficient of variation of interspike intervals and degree of synchronization assessed from cross correlation analysis. The discharges of gamma motoneurones in the decerebrated cat with intact spinal cord are regular (low coefficient of variation) and show no tendency to synchrony for up to 24 h following decerebration. Section of the more medial part of the dorsolateral funiculus, on either side of the thoracic spinal cord, resulted in a less regular discharge and the development of short-term synchrony between gamma motoneurones. A dependence of synchrony on variability of discharge was established. The synchrony and increased variability in the spinal cat persisted for at least 24 h. Both were markedly reduced following administration of the precursors of monoamines (either L-Dopa or 5-HTP). We conclude that a bilateral, monoaminergic pathway descending in the dorsolateral funiculus from the brainstem controls synchrony of gamma motoneurone discharge in the decerebrated cat. The possibility is discussed that synchrony of discharge between alpha motoneurones may be controlled by a similar pathway.


The genetic toxicity of human carcinogens and its implications.
23 chemicals and chemical combinations have been designated by the International Agency for Research on Cancer (IARC) as causally associated with cancer in humans. The literature was searched for reports of their activity in the Salmonella mutagenicity assay and for evidence of their ability to induce chromosome aberrations or micronuclei in the bone marrow of mice or rats. In addition, the chemical structures of these carcinogens were assessed for the presence of electrophilic substituents that might be associated with their mutagenicity and carcinogenicity. The purpose of this study was to determine which human carcinogens exhibit genetic toxicity in vitro and in vivo and to what extent they can be detected using these two widely employed short-term tests for genetic toxicity. The results of this study revealed 20 of the 23 carcinogens to be active in one or both short-term tests. Treosulphan, for which short-term test results are not available, is predicted to be active based on its structure. The remaining two agents, asbestos and conjugated estrogens, are not mutagenic to Salmonella; asbestos is not likely to induce cytogenetic effects in the bone marrow and the potential activity of conjugated estrogens in the bone marrow is difficult to anticipate. These findings show that genetic toxicity is characteristic of the majority of IARC Group 1 human carcinogens. If these chemicals are considered representative of human carcinogens, then two short-term tests may serve as an effective primary screen for chemicals that present a carcinogenic hazard to humans.


Decreased virulence of duck Tembusu virus harboring a mutant NS2A with impaired interaction with STING and IFNβ induction.
Our previous studies revealed that duck Tembusu virus (DTMUV) NS2A inhibited IFNβ signaling pathway by competitively binding to STING with TBK1, leading to reducing the phosphorylation of TBK1. Herein, we found that the 114-143 aa region of NS2A is critical for its interaction with STING and suppression of STING-mediated IFNβ signaling. We further identified the amino acids at positions L129, N130, L139, R140 and F143 of NS2A critical for NS2A-STING interaction. Subsequently, single residue substitution in the NS2A protein was introduced into the DTMUV replicon and infectious clone. The replicons with NS2A L129A and L130A mutations significantly inhibited viral genome RNA replication. The rDTMUV NS2A L129A, L139A and R140A mutant viruses yielded significantly lower titer levels than WT in both BHK-21 and DEF cells, with much more obvious effect on the viral genome level, and infectious virions formed outside of infected cells. Especially, the rDTMUV L129A mutant showed a significantly lower mortality in both embryos and ducks than WT. All NS2A-mutants decreased the weight gain of infected ducklings and reduced the viral loads in the spleen relative to WT. However, no significant differences of viral loads were observed in the blood, thymus, or liver. Our findings extend our previous study on the immune evasion role of flavivirus NS2A protein. The targeted therapy of disabling the viral strategies developed for evading innate defense can be applied to the development of attenuated flaviviruses.


Levamisole-activated single-channel currents from muscle of the nematode parasite Ascaris suum.
1. The patch-clamp technique was used to examine levamisole-activated channels in muscle vesicles from Ascaris suum. Cell-attached and isolated inside-out patches were used. 2. Levamisole (1-90 microM), applied to the extracellular surface, activated channels which had apparent mean open-times in the range 0.80-2.85 ms and linear I/V relationships with conductances in the range 19-46 pS. Ion-replacement experiments showed the channels to be cation selective. 3. The kinetics of the channels were analysed. Generally open- and closed-time distributions were best fitted by two, and three exponentials respectively, indicating the presence of at least two open states and at least three closed states. The distributions of burst-times were best-fitted by two exponentials. 4. Channel open- and burst-times were voltage-sensitive: at low levamisole concentrations (1-10 microM), they increased with hyperpolarization. At higher concentrations of levamisole (30 microM and 90 microM) flickering channel-block was observed at hyperpolarized potentials. Using a simple channel-block model, values for the blocking dissociation constant, KB were determined as 123 microM at -50 mV, 46 microM at -75 mV and 9.4 microM at -100 mV. 5. At the higher concentration of levamisole (30 microM and 90 microM) long closed-times separating 'clusters' of bursts were observed, at both hyperpolarized and depolarized membrane potentials and this was interpreted as desensitization.


Physician-patient communication about dietary supplements.
Describe the content and frequency of provider-patient dietary supplement discussions during primary care office visits. Inductive content analysis of 1477 transcribed audio-recorded office visits to 102 primary care providers was combined with patient and provider surveys. Encounters were collected in Los Angeles, CA (2009-2010), geographically diverse practice settings across the United States (2004-2005), and Sacramento, CA (1998-1999). Providers discussed 738 dietary supplements during encounters with 357 patients (24.2% of all encounters in the data). They mentioned: (1) reason for taking the supplement for 46.5% of dietary supplements; (2) how to take the supplement for 28.2%; (3) potential risks for 17.3%; (4) supplement effectiveness for 16.7%; and (5) supplement cost or affordability for 4.2%. Of these five topics, a mean of 1.13 (SD=1.2) topics were discussed for each supplement. More topics were reviewed for non-vitamin non-mineral supplements (mean 1.47 (SD=1.2)) than for vitamin/mineral supplements (mean 0.99 (SD=1.1); p<0.001). While discussions about supplements are occurring, it is clear that more discussion might be needed to inform patient decisions about supplement use. Physicians could more frequently address topics that may influence patient dietary supplement use, such as the risks, effectiveness, and costs of supplements.


Alternative medicine or "alternative" patients: a qualitative study of patient-oriented decision-making processes with respect to complementary and alternative medicine.
Theory and clinical practice suggest that complementary and alternative medicine (CAM) decision-making processes may differ from those used in conventional medicine. If so, understanding the differences could improve patient-provider communication around treatment options. To examine patient-oriented decision-making processes relative to CAM use. Adults with chronic rheumatological disorders who utilize allopathic medicine only, CAM only, or both. An exploratory, cross-sectional naturalistic design with thematic and content analyses. Three distinct decision paths were developed, differing substantially on the importance of provider trust, disease severity/prognosis, willingness to experiment, intuitive/spiritual factors, and outcomes evidence. These divergent decision paths indicate the possibility of "alternative patients," not just "alternative therapies." Since informed decisions, tailored to the patient, would likely lead to sustainable improvements in health care outcomes, the findings may facilitate providers' capacity to effectively advise patients about treatment alternatives and CAM use.


Augmentation of hemagglutination-inhibition (HI) antibodies in gilts of breeding age by large dosages of human A/New Jersey/76 influenza vaccine.
Fifteen gilts of breeding age were studied. Four received three 4 ml. doses three weeks apart of an experimental killed swine influenza vaccine containing A/Swine/ill/65 antigen, four received three ml. doses three weeks apart of a human influenza vaccine containing A/New Jersey/76 antigen and three received two doses of human influenza vaccine followed by a 3 ml. third dose of experimental swine influenza vaccine. All except one vaccinate responded to two doses of vaccine by the time of the third dose of vaccine. HI titers were highest four weeks after the third dose of vaccine. Geometric mean titers were highest in animals receiving human influenza vaccine containing A/New Jersey/76. Titer profiles dropped markedly by 60 days after the third vaccination.


Effect of neem limonoids on lactate dehydrogenase (LDH) of the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Insecta: Lepidoptera: Pyralidae).
Neem is derived from the neem tree Azadirachta indica A. Juss. (Meliaceae), and its primary insecticidal component is the tetranortriterpenoid azadirachtin and other limonoids. The effect of neem limonoids azadirachtin, salannin, deacetylgedunin, gedunin, 17-hydroxyazadiradione and deacetylnimbin on enzyme lactate dehydrogenase (LDH) activity of the rice leaffolder (RLF) Cnaphalocrocis medinalis (Lepidoptera: Pyralidae) larvae was investigated. There was a decrease in enzyme activity relative to the control at all concentrations tested. When fed a diet of rice leaves treated with neem limonoids in bioassays, gut tissue enzyme, LDH levels in rice leaffolder larvae are affected. These results indicate neem limonoids affect LDH activity. These effects are most pronounced in early instar larvae. Azadirachtin was the most potent in of all the limonoids in all experiments indicating strong enzyme inhibition. Clear dose-response relationships were established with respect to LDH activity.


Formation of N-bridgehead 1,2,5-thiadiazolium and selenadiazolium rings through an intramolecular cyclisation reaction.
Treatment of N-lithiopyridylketimide derivatives Li[R(C=N)py] (R=Ph, py) with ECl(2) (E=S, Se) affords the fused thiadiazolium and selenadiazolium salts [RC(6)H(4)N(2)E]Cl [1]Cl and [2]Cl containing a bridgehead N atom through intramolecular coordination.


Recent development of eco-friendly nanocomposite carbon paste electrode for voltammetric determination of Cd(II) in real samples.
Using eco-friendly, cheap, and available adsorbents is promising for the determination of metal ions. So, this study focuses on the modification of graphite reinforcement carbon paste electrode (GRCPE) with mango seed kernel (MSK) for voltammetric determination of Cd(II). Moreover, to increase the surface area of this adsorbent, it was prepared in nanosized that formed nanoparticles of mango seed kernel (MSK-NPs). The developed nanocomposite electrode of carbon paste electrode modified with nanoparticles of mango seed kernel (MSK-NPs@GRCPE) was characterized using Fourier transform infrared (FTIR) and Scanning electron microscopy (SEM). The effect of pH, buffer solution, and supporting electrolyte as experimental conditions were optimized through differential pulse adsorptive anodic stripping voltammetric method (DPAdASV). Britton-Robinson buffer pH = 3.9 at Eacc = - 1400 mV, tacc = 30 s, pulse width = 10 ms and sampling time = 8 ms were the optimum conditions for determination of Cd(II). The LOD and LOQ of MSK-NPs@GRCPE were calculated at 5.44 × 10-9 and 1.65 × 10-8 M, respectively. Compared with bare graphite reinforcement carbon paste electrode (BGRCPE), the nanocomposite MSK-NPs@GRCPE has a lower detection limit, indicating that the presence of MSK-NPs could greatly improve the response to Cd(II). The practical applicability of the electrode was verified by the determination of Cd(II) in chocolate and white rice samples. The results show high selectivity and sensitivity for Cd(II) in real samples.


Immunoglobulin M monoclonal gammopathies of undetermined significance and indolent Waldenstrom's macroglobulinemia recognize the same determinants of evolution into symptomatic lymphoid disorders: proposal for a common prognostic scoring system.
To evaluate the clinicohematologic variables at diagnosis that are prognostically related to neoplastic progression in patients with immunoglobulin M (IgM) monoclonal gammopathies of undetermined significance (MGUS), and indolent Waldenström's macroglobulinemia (IWM), and propose a scoring system to identify subsets of patients at different risk. We evaluated 217 patients with IgM MGUS and 201 with IWM (male-female ratio, 131:86 and 117:84; mean age, 63.7 and 63.6 years, respectively) diagnosed on the basis of serum monoclonal component (MC) levels and bone marrow lymphoplasmacytic infiltration degree. The variables selected by univariate analyses were multivariately investigated; on the basis of their individual relative hazards, a scoring system was devised to identify subsets of patients at different risk of evolution. After a median follow-up of 56.1 and 60.2 months, 15 of 217 MGUS and 45 of 201 IWM patients, respectively, required chemotherapy for symptomatic WM (13 and 36), non-Hodgkin's lymphoma (2 and 6) and amyloidosis (0 and 3). The median time to evolution (TTE) was not reached for MGUS and was 141.5 months for IWM. The variables adversely related to evolution were qualitatively the same in both groups: MC levels, Hb concentrations and sex. A scoring system based on these parameters identified three risk groups with highly significant differences in TTE in both groups (P < .0001). MGUS and IWM identify disease entities with different propensities for symptomatic neoplastic evolution. As both have the same prognostic determinants of progression, we propose a practical scoring system that, identifying different risks of malignant evolution, may allow an individualized clinical approach.


Multilocus phylogeny and phylogenomics of Eriochrysis P. Beauv. (Poaceae-Andropogoneae): Taxonomic implications and evidence of interspecific hybridization.
Species delimitation is a vital issue concerning evolutionary biology and conservation of biodiversity. However, it is a challenging task for several reasons, including the low interspecies variability of markers currently used in phylogenetic reconstructions and the occurrence of reticulate evolution and polyploidy in many lineages of flowering plants. The first phylogeny of the grass genus Eriochrysis is presented here, focusing on the New World species, in order to examine its relationships to other genera of the subtribe Saccharinae/tribe Andropogoneae and to define the circumscriptions of its taxonomically complicated species. Molecular cloning and sequencing of five regions of four low-copy nuclear genes (apo1, d8, ep2-ex7 and ep2-ex8, kn1) were performed, as well as complete plastome sequencing. Trees were reconstructed using maximum parsimony, maximum likelihood, and Bayesian inference analyses. The present phylogenetic analyses indicate that Eriochrysis is monophyletic and the Old World E. pallida is sister to the New World species. Subtribe Saccharinae is polyphyletic, as is the genus Eulalia. Based on nuclear and plastome sequences plus morphology, we define the circumscriptions of the New World species of Eriochrysis: E. laxa is distinct from E. warmingiana, and E. villosa is distinct from E. cayennensis. Natural hybrids occur between E. laxa and E. villosa. The hybrids are probably tetraploids, based on the number of paralogues in the nuclear gene trees. This is the first record of a polyploid taxon in the genus Eriochrysis. Some incongruities between nuclear genes and plastome analyses were detected and are potentially caused by incomplete lineage sorting and/or ancient hybridization. The set of low-copy nuclear genes used in this study seems to be sufficient to resolve phylogenetic relationships and define the circumscriptions of other species complexes in the grass family and relatives, even in the presence of polyploidy and reticulate evolution. Complete plastome sequencing is also a promising tool for phylogenetic inference.


Adaptation of BHK cells producing a recombinant protein to serum-free media and protein-free medium.
In this work a recombinant BHK21 clone producing a fusion protein with potential application in tumour target therapy was adapted to five different serum-free media (SFM) and to a protein-free medium (PFM). Only the PFM did not require a gradual adaptation to cell growth in the absence of serum. All tested SFM required a gradual adaptation (up to 35 days). For the majority of the SFM tested, cell specific productivity was not affected by the decrease in serum concentration during adaptation; however, cell growth was significantly affected by the serum decrease. Both cell growth and productivity were increased when PFM SMIF6 was used instead of the control medium. Long term measurements (approximately 100 days) of cell specific productivity for PFM and the two best SFM showed that productivity was maintained. This indicates the media capability to be used in long term production processes.


SH3BP2 is a critical regulator of macrophage and osteoclast response to M-CSF and RANKL stimulation.
The protein Src homology 3 domain-binding protein 2 (SH3BP2) is a regulator of tumor necrosis factor (TNF)-alpha generation in macrophages and of osteoclast differentiation. SH3BP2 regulates bone marrow monocyte responses to macrophage and osteoclast differentiation signals downstream of the receptors for macrophage colony-stimulating factor and receptor activator of nuclear factor kappaB ligand. SH3BP2 is a potential target for the development of novel anti-TNF-alpha therapeutic interventions as well as a target for suppression of osteoclastogenesis.


Intra-individual reproducibility of galectin-1, haptoglobin, and nesfatin-1 as promising new biomarkers of immunometabolism.
Galectin-1, haptoglobin, and nesfatin-1 have recently emerged as promising biomarkers implicated in immunometabolism. However, whether single blood measurements of these analytes could be suitable for large-scale human studies has not yet been evaluated. The concentrations of galectin-1, haptoglobin, and nesfatin-1 were measured over a 4-month period in 207 healthy adults with median age of 56.7 years. Biomarker intra-individual reproducibility was assessed based on calculation of intraclass correlation coefficients (ICCs) and examining Bland-Altman plots. The overall ICCs were excellent for nesfatin-1 (ICC: 0.89 (95% CI: 0.86, 0.92), and good for galectin-1 and haptoglobin (ICCs: 0.70 (95% CI: 0.61, 0.77) and 0.67 (95% CI: 0.57, 0.74), respectively). Bland-Altman plots supported a high level of agreement between repeated biomarker measurements. Assay measurements of galectin-1, haptoglobin, and nesfatin-1 showed good to excellent within-subject reproducibility over a 4-month period, indicating that they may serve as feasible and reliable biomarkers for assessing metabolic inflammation in population research.


Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.
Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.


Synthesis of novel antifungal agents (2).
Synthesis of novel cyclohexyl analogs of restricticin using intramolecular radical cyclization and their in vitro and in vivo antifungal activities are described.


Preliminary assessment of toxicity of aerosol samples from central-west Brazil using Artemia spp. bioassays.
The present study reports the development of a bioassay using Artemia spp. to analyse the preliminary ecotoxicity of atmospheric aerosols (PM), which can affect the environment and human health. Herein, PM samples were collected in the city of Goiânia (Brazil) in 2016, extracted with ultrapure water and subsequently filtered through membranes with different pore sizes (100, 0.8, and 0.22 μm), and the extracts employed in the bioassays. The mortality rates (endpoint analysed) declined to membranes with smaller pore sizes (15 ± 4%, 47 ± 10% and 43 ± 9% for pore sizes of 100 μm, 0.8 μm and 0.22 μm, respectively). In general, the toxicity of the extract depended on its concentration, except for the sample with a higher negative particle surface charge, which presents a lower affinity for the negatively charged surfaces of cellular membranes. Moreover, although the PM concentration was higher for the sample collected during the dry season (September), the mortality rate was not significantly different to that determined for a sample with similar physical and chemical characteristics collected in the rainy season (December). This result demonstrates the importance of monitoring PM toxicities and their chemical and physical characteristics, in addition to their concentrations. Therefore, the new protocol to provide a preliminary analysis of the toxicity of the extracts of aerosol emerges as a useful, accessible, and fast tool for monitoring possible environmental hazards, and can simplify fieldwork.


Crustal movement and strain distribution in East Asia revealed by GPS observations.
East Asia is bounded by the Indian plate to the southwest and the Pacific and Philippine plates to the east, and has undergone complex tectonic evolution since ~55 Ma. In this study, we collect and process three sources of GPS datasets, including GPS observations, GPS positioning time series, and published GPS velocities, to derive unified velocity and strain rate fields for East Asia. We observed southward movement and arc-parallel extension along the Ryukyu Arc and propose that the maximum principal stress axis (striking NEE) in North China could be mainly induced by westward subduction of the Pacific plate and the southward movement of the Ryukyu Arc. The large EW-trending sinistral shear zone that bounds North China has been created by eastward movement of South China to the south and westward subduction of the Pacific plate to the north. GPS velocity profiles and strain rates also demonstrate that crustal deformation in mainland China is controlled by northeastward collision of the Indian plate into Eurasia and westward subduction of the Pacific and Philippine Sea plates beneath Eurasia. In particular, the India-Eurasia continental collision has the most extensive impact, which can reach as far as the southern Lake Baikal. The viscous behavior of the subducting Pacific slab also drives interseismic deformation of North China. The crustal deformation caused by Philippine oceanic subduction is small and is limited to the region between the southeast coast of mainland China and Taiwan island. However, the principal compressional strain around eastern Taiwan is the largest in the region.


A retrospective Evaluation of fluconazole for the treatment of Candida glabrata fungemia.
Candida glabrata accounts for 21% of Candida bloodstream isolates in the United States and ranges from susceptible-dose-dependent to resistant to fluconazole. A fluconazole dose of 800 mg/d ( approximately 12 mg/kg per day) is predicted to produce peak plasma concentrations that surpass the susceptible-dose-dependent MIC breakpoint of 16 to 32 mug/mL. Accordingly, the Infectious Diseases Society of America treatment guidelines for candidiasis recommend fluconazole 12 mg/kg per day as an alternative option for treatment of C glabrata fungemia. The main objective of this study was to evaluate fluconazole retrospectively as a treatment for C glabrata fungemia. Data were collected through a database that stores patient information electronically and can be accessed and queried, and chart review at Barnes-Jewish Hospital (St. Louis, Missouri) from January 1999 to August 2002. Eligible patients who had at least 1 positive blood culture for C glabrata and received at least 1 dose of fluconazole were identified through the electronic query. Chart reviews of these patients followed. The primary outcomes were fungemia eradication and in-hospital mortality. Of the total 124 cases of C glabrata fungemia identified, 54 patient charts were evaluable. Chart review revealed that 65% (17/26) of patients receiving fluconazole as the sole antifungal therapy had successful bloodstream eradication of C glabrata, whereas approximately 54% (15/28) of patients who were changed from fluconazole to an amphotericin B formulation had successful bloodstream eradication. Although no association was found between fluconazole dose and fungemia eradication in the entire study population, higher doses of fluconazole (> or =400 mg/d) were more likely to achieve fungemia eradication than lower doses (< or =400 mg/d) in the subset of patients who received only fluconazole (P = 0.042). Mortality rates were approximately 24% (4/17) and 40% (6/15) in patients having successful bloodstream eradication with fluconazole alone and with fluconazole followed by amphotericin B, respectively, compared with 38% (3/8) in patients with persistent fungemia who received fluconazole alone. Fluconazole was a viable therapy for C glabrata fungemia, with bloodstream eradication in 65% of patients and mortality rates of 24% to 40% in this retrospective chart review.


Reduction of Cr(VI) to Cr(III) using silicon nanowire arrays under visible light irradiation.
We report an efficient visible light-induced reduction of hexavalent chromium Cr(VI) to trivalent Cr(III) by direct illumination of an aqueous solution of potassium dichromate (K2Cr2O7) in the presence of hydrogenated silicon nanowires (H-SiNWs) or silicon nanowires decorated with copper nanoparticles (Cu NPs-SiNWs) as photocatalyst. The SiNW arrays investigated in this study were prepared by chemical etching of crystalline silicon in HF/AgNO3 aqueous solution. The Cu NPs were deposited on SiNW arrays via electroless deposition technique. Visible light irradiation of an aqueous solution of K2Cr2O7 (10(-4)M) in presence of H-SiNWs showed that these substrates were not efficient for Cr(VI) reduction. The reduction efficiency achieved was less than 10% after 120 min irradiation at λ>420 nm. Addition of organic acids such as citric or adipic acid in the solution accelerated Cr(VI) reduction in a concentration-dependent manner. Interestingly, Cu NPs-SiNWs was found to be a very efficient interface for the reduction of Cr(VI) to Cr(III) in absence of organic acids. Almost a full reduction of Cr(VI) was achieved by direct visible light irradiation for 140 min using this photocatalyst.


Corrigendum to "Artificial Neural Network to Predict Varicocele Impact on Male Fertility through Testicular Endocannabinoid Gene Expression Profiles".
[This corrects the article DOI: 10.1155/2018/3591086.].


"EMG" for thoracic outlet syndrome.
Electrodiagnostic testing is reliable for the diagnosis of TOS. It helps localize and quantify a lesion in the brachial plexus. It is also important to rule out other segmental or systemic neuropathies.


Possible concurrence of TDP-43, tau and other proteins in amyotrophic lateral sclerosis/frontotemporal lobar degeneration.
Transactivation response DNA-binding protein 43 kDa (TDP-43) has been regarded as a major component of ubiquitin-positive/tau-negative inclusions of motor neurons and the frontotemporal cortices in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Neurofibrillary tangles (NFT), an example of tau-positive inclusions, are biochemically and morphologically distinguished from TDP-43-positive inclusions, and are one of the pathological core features of Alzheimer disease (AD). Although ALS/FTLD and AD are distinct clinical entities, they can coexist in an individual patient. Whether concurrence of ALS/FTLD-TDP-43 and AD-tau is incidental is still controversial, because aging is a common risk factor for ALS/FTLD and AD development. Indeed, it remains unclear whether the pathogenesis of ALS/FTLD is a direct causal link to tau accumulation. Recent studies suggested that AD pathogenesis could cause the accumulation of TDP-43, while abnormal TDP-43 accumulation could also lead to abnormal tau expression. Overlapping presence of TDP-43 and tau, when observed in a brain during autopsy, should attract attention, and should initiate the search for the pathological substrate for this abnormal protein accumulation. In addition to tau, other proteins including α-synuclein and amyloid β should be also taken into account as candidates for an interaction with TDP-43. Awareness of a possible comorbidity between TDP-43, tau and other proteins in patients with ALS/FTLD will be useful for our understanding of the influence of these proteins on the disease development and its clinical manifestation.


Solids, organic load and nutrient concentration reductions in swine waste slurry using a polyacrylamide (PAM)-aided solids flocculation treatment.
Increased swine production results in concentration of wastes generated within a limited geographical area, which may lead to land application rates exceeding the local or regional assimilatory capacity. This may result in pollutant transfer through surface water or soil-groundwater systems, environmental degradation, and/or odor concerns. Existing swine waste pit storage and lagoon treatment technologies may be inadequate to store or treat waste prior to land application without these concerns resulting. Efficient swine waste solids separation may reduce environmental health concerns and generate a value-added bioresource (solids). This study evaluated the efficiency of a polyacrylamide (PAM) flocculant-aided solids separation treatment to reduce pollution indicator concentrations in raw (untreated) swine waste slurry. Swine waste slurry solids separation efficiency through gravity settling (sedimentation) was evaluated before and after the addition of a proprietary polymeric (PAM) flocculant. Results indicated that polymer amendments at concentrations of 62.5-750 mg/l improved slurry solids separation efficiency and significantly reduced concentrations of other associated aquatic pollution indicators in a majority of analyses conducted (33 of 50 total analyses conducted). Results also suggested that PAM-aided solids separation from swine waste slurry might facilitate further treatment and/or disposal and therefore reduce associated environmental degradation potential.


Exercise-induced rhinitis: a common disorder that adversely affects allergic and nonallergic athletes.
Exercise is a well-established trigger for allergic disorders such as asthma, urticaria, and anaphylaxis, but the effect of exercise on rhinitis has not been well described. To survey individuals with and without nasal allergy who exercise regularly to determine the prevalence and nature of nasal symptoms induced by indoor exercise. An original, self-administered questionnaire to evaluate exercise-induced rhinitis (EIR) was distributed to adults who were receiving allergy immunotherapy at a community allergy practice and to members of a community athletic club. Nasal symptoms that occur indoors (runny nose, nasal congestion, postnasal drip) were primarily evaluated. Comparisons with outdoor EIR were determined. The perception of adverse effects of rhinitis on exercise was evaluated. Sixty-six (40%) of the 164 patients indicated that their indoor EIR adversely affected athletic performance, and this finding occurred more frequently in patients with nasal allergy vs unaffected individuals (53.1% vs 27.7%; P = .009). Of the 61.0% who reported increased rhinitis with indoor exercise, rhinorrhea was the most common symptom experienced (48.8%). Indoor EIR occurred more frequently in patients with nasal allergy vs unaffected individuals (69.1% vs 53.0%; P = .04). Outdoor EIR occurred in 56.1% of the total population, and patients with nasal allergy reported significantly more rhinitis with outdoor exercise compared with unaffected individuals (71.6% vs 41.0%; P < .001). Exercise-induced rhinitis, predominantly rhinorrhea, commonly occurs in athletes regardless of underlying nasal allergy. A history specific to indoor and outdoor exercise triggers needs to be part of the complete rhinitis history so that specific treatment can be directed.


[The significance of central, peripheral and binocular vision for parachute jumping (author's transl)].
In this study personal observations during parachute jumping under various visual conditions are recorded. Jumps were executed with reduced visual acuity, monocular vision, and hemianopic defects of the visual fields. The conclusions regarding admission to parachute jumping drawn from the author's personal observations are discussed.


In vitro assessment of cobalt oxide particle toxicity: identifying and circumventing interference.
The continuing development of nanotechnology necessitates the reliable assessment of potential adverse health consequences associated with human exposures. The physicochemical properties of nanomaterials can be responsible for unexpected interactions with components of classical toxicity assays, which may generate erroneous interpretations. In this paper, we describe how particle interference can be observed in in vitro toxicity tests (CellTiter Blue, CyQUANT, WST-1 and CellTiter-Glo assay) and in cell biology tests using flow cytometry (cell cycle analysis). We used cobalt oxide (Co3O4) particles as an example, but these assays can be performed, in principle, regardless of the nanoparticle considered. We have shown that cobalt particles interfere with most of these tests. We adapted the protocol of the CellTiter-Glo assay to circumvent this interference and demonstrated that, using this protocol, the toxicity level is consistent with results obtained using the clonogenic assay, which is considered to be the reference test. Before assessing particle toxicity using in vitro toxicity tests, interference testing should be performed to avoid false interpretations. Furthermore, in some cases of interference, protocol adaptation can be considered to allow the reliable use of these quick and convenient in vitro tests.


Impaired expression of BCAT1 relates to muscle atrophy of mouse model of sarcopenia.
The underlying mechanism of muscle atrophy in sarcopenia is still not fully understood; branched chain aminotransferase 1(BCAT1) isocitrate dehydrogenase-1 encodes an evolutionarily conserved cytoplasmic aminotransferase for glutamate and branched-chain amino acids (BCAAs), thus constituting a regulatory component of cytoplasmic amino and keto acid metabolism. In human gliomas carrying wild-type isocitrate dehydrogenase-1, BCAT1 promotes cell proliferation through amino acid catabolism. Hence, the goals of this study were to unravel the potential role of BCAT1 expression in muscle atrophy and to explore the mechanisms underlying this process. We first measured Bcat1 expression by RT-qPCR and western blotting in murine and cellular models of muscle atrophy. To understand how the Bcat1-driven changes sustained muscle cell growth, we analyzed reactive oxygen species (ROS) levels and activation of the mTORC1/S6K1 pathway in muscle cells. Furthermore, we performed Cell Counting Kit-8(CCK8) assays and fluorescence staining to evaluate growth rate of cells and ROS levels. Finally, we verified that depletion of Bcat1 impairs the growth rate of muscle cells and increases ROS levels, indicating that muscle atrophy resulted from the downregulation of the mTORC1/S6K1 pathway. Data were analyzed by two-tailed unpaired Student's t-test or Mann-Whitney U test for two groups to determine statistical significance. Statistical analyses were performed using GraphPad Prism version 6.0 and SPSS 16.0 software. Bcat1 expression level in skeletal muscles was lower in murine and cellular models of sarcopenia than in the control groups. Bcat1 knockdown not only suppressed the growth of muscle cells but also increased the production of ROS. Impaired cell growth and increased ROS production was rescued by co-introduction of an shRNA-resistant Bcat1 cDNA or addition of the mTORC1 stimulator MYH1485. Muscle cells with Bcat1 knockdown featured lower mTORC1 and S6K1 phosphorylation (pS6K1) than NT muscle cells. Addition of either shRNA-resistant Bcat1 cDNA or MYH1485 rescued the suppression of cell growth, increase in ROS production, and decrease in pS6K1. The branched chain amino acids catabolic enzyme BCAT1 is essential for the growth of muscle cells. BCAT1 expression contributes to sustained growth of muscle cells by activating mTOR signaling and reducing ROS production.


Family history of chronic illness, preterm gestational age and smoking exposure before pregnancy increases the probability of preeclampsia in Omo district in southern Ethiopia: a case-control study.
Preeclampsia is a complex syndrome that is considered a disorder specific to pregnancy. However, research indicates that diffuse maternal endothelial damage may persist after childbirth. On the other hand, women who had a history of pre-eclampsia are at an increased risk of vascular disease. Considering that the multifactorial nature of pre-eclampsia in a remote health setting, knowledge of risk factors of preeclampsia gives epidemiological significance specific to the study area. Therefore, this study aimed to identify the determinants of preeclampsia among pregnant women attending perinatal service in Omo district Hospitals in southern Ethiopia. An institution-based unmatched case-control study design was conducted among women visiting for perinatal service in Omo District public hospitals between February to August 2018. A total of 167 cases and 352 controls were included. Data were collected via face-to-face interviews. Bivariable and multivariable logistic regression analysis were computed to examine the effect of the independent variable on preeclampsia using Statistical Package for Social Sciences version 26 window compatible software. Variables with a p-value of less than 0.05 were considered statistically significant. Factors that were found to have a statistically significant association with pre-eclampsia were primary relatives who had history of chronic hypertension (AOR 2.1, 95% CI: 1.06-4.21), family history of diabetes mellitus (AOR 2.35; 95% CI: 1.07-5.20), preterm gestation(AOR = 1.56, 95%CI, 1.05-2.32), and pre-conception smoking exposure (AOR = 4.16, 95%CI, 1.1-15.4). The study identified the risk factors for pre-eclampsia. Early detection and timely intervention to manage pre-eclampsia, and obstetric care providers need to emphasize women at preterm gestation and a history of smoking before pregnancy.


Comparisons of immunisation accessibility between non-US born and US-born children in New York City.
New York City (NYC) has the second highest immigrant population in the USA; with many migrants from countries outside the USA being inadequately immunised. To assess the immunisation status of this population, the NYC Department of Health's Family Health Services Division designed and implemented a study in order to examine how accessible the immunisation service was to immigrant families who wished to have their children immunised. A one time cross-sectional design was used in this study and data was collected, by means of a survey, in the NYC Department of Health's Immunisation Clinics. These were the major walk-in and free of charge immunisation facilities for children in NYC. Descriptive and Chi square statistics were used to analyse the data from this survey. Of 270 children surveyed, 211 (78%) were born outside the US; of these, 116 (55%) reported that apart from the NYC Department of Health's Immunisation Clinics they had no other access to immunisation services. There was a significant difference in the accessibility to immunisation services between non-US-born and US-born children. The factors that influenced the accessibility by non-US-born children compared with US-born children included health insurance, family income, primary language and years of residence in the US. How they came to hear about immunisation services and general knowledge regarding immunisation were not significantly different between these two groups and these were not significant factors which affected accessibility to immunisation services among children. Major steps have been taken in NYC to help increase access to immunisation services by using free public health immunisation programs. Such programs should be expanded to target non-US-born children and their parents. Such educational and outreach programs need to be culturally sensitive.


RISA-HPLC analysis of lung bacterial colonizers of cystic fibrosis children.
Microbiological analysis of sputum samples, from children affected by cystic fibrosis (CF) and showing signs of acute or chronic infections, is routinely performed by culture-dependent approaches involving selective media and biochemical tests. These identification schemes are time-consuming, and may lead to false negative results. The aim of this work was to evaluate the efficacy of a Ribosomal Intergenic Spacer Analysis (RISA) coupled to high performance liquid chromatography (HPLC) for the detection and monitoring of CF lung microbial colonizers including Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, the Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. These RISA-HPLC analyses were performed over a 10-months period on infants (below 18 months) and children that were or were not yet known to be colonised by P. aeruginosa. The RISA-HPLC profiles were found specific of the patients' microbial communities. A specific P. aeruginosa RISA-HPLC peak corresponding to 550 bp PCR products was recorded, and used to investigate P. aeruginosa persistence through time and after various therapeutic treatments. The RISA-HPLC profiles showed the CF children to be colonized by few bacterial species, and sometimes revealed peaks corresponding to bacterial species that were not detected by the selective plating approaches. Significant RISA-HPLC infra-specific variations were observed for most bacterial colonizers of CF lungs except P. aeruginosa. These species could yield as much as 5 distinct RISA-HPLC peaks, with some of these profiles being strain-specific. RISA-HPLC shows a great potential for revealing colonization by novel emerging pathogens, and for evaluating the efficacy of therapeutic treatments on the global bacterial community of CF lungs.


Polymerase chain reaction for Mycobacterium tuberculosis: impact on clinical management of refugees with pulmonary infiltrates.
Screening for pulmonary tuberculosis (TB) in war refugees entering low-prevalence countries for TB is a common policy, but workup strategies are difficult and expensive. Prospective screening of war refugees for TB by chest radiograph and evaluation of the impact of additional polymerase chain reaction (PCR) testing for Mycobacterium tuberculosis complex (MTB) on clinical management in case of pulmonary infiltrates suspicious for TB. Academic university medical center. A total of 3,119 adult war refugees from the Kosovo war were screened by chest radiograph on arrival. Refugees with pulmonary infiltrates suspicious for TB were hospitalized, and a standardized diagnostic workup was performed. Of 3,119 adult war refugees screened for TB, 29 patients (0.9%) were identified with pulmonary infiltrates suspicious for TB; 103 specimens (76 sputa; 27 BAL fluids) were collected for acid-fast smear (AFS), PCR, and culture. The prevalence of culture-proven TB infection in this population was 27.6%. Sensitivity for PCR was higher compared with AFS for all specimens (64% vs 20%; p < 0.01) and also for each refugee with at least one positive specimen finding (100% vs 37.5%; p = 0.025). More important, the negative predictive value for three consecutive PCRs (in two sputa and one BAL) was 100%. Repeated PCR testing for MTB in a population of asymptomatic war refugees with pulmonary infiltrates highly suggestive of TB is significantly more sensitive than AFS. Three negative PCR results allow discharge from isolation, thus reducing the economic burden of isolation strategies.


[The mandibular rest position: relation to the rest vertical dimension].
The concept of the mandibular rest position and the clinical significance of the mandibular resting posture with respect to dental treatment are discussed. The controversy regarding the belief that mandibular resting posture is constant and inviolate is considered on the basis of clinical observations and scientific investigations.


Dynamic changes of genomic methylation profiles at different growth stages in Chinese Tan sheep.
Tan sheep, an important local sheep breed in China, is famous for their fur quality. One-month-old Tan sheep have white, curly hair with beautiful flower spikes, commonly known as "nine bends", which has high economic value. However, the "nine bends" characteristic gradually disappears with age; consequently, the economic value of the Tan sheep decreases. Age-related changes in DNA methylation have been reported and may be responsible for age-induced changes in gene expression. Until now, no genome-wide surveys have been conducted to identify potential DNA methylation sites involved in different sheep growth stages. In this study we investigated the dynamic changes of genome-wide DNA methylation profiles in Tan sheep using DNA from skin and deep whole-genome bisulfite sequencing, and compared the DNA methylation levels at three different growth stages: 1, 24, and 48 months old (mon1, mon24, and mon48, respectively). In this study, 11 skin samples from three growth stages (four for mon1, four for mon24, and three for mon48) were used for DNA methylation analysis and gene expression profiling. There were 52, 288 and 236 differentially methylated genes (DMGs) identified between mon1 and mon24, mon1 and mon48, and mon24 and mon48, respectively. Of the differentially methylated regions, 1.11%, 7.61%, and 7.65% were in the promoter in mon1 vs. mon24, mon24 vs. mon48, and mon1 vs. mon48, respectively. DMGs were enriched in the MAPK and WNT signaling pathways, which are related to age growth and hair follicle morphogenesis processes. There were 51 DMGs associated with age growth and curly fleece formation. Four DMGs between mon1 and mon48 (KRT71, CD44, ROR2 and ZDHHC13) were further validated by bisulfite sequencing. This study revealed dynamic changes in the genomic methylation profiles of mon1, mon24, and mon48 sheep, and the percentages of methylated cytosines were 3.38%, 2.85% and 4.17%, respectively. Of the DMGs, KRT71 and CD44 were highly methylated in mon1, and ROR2 and ZDHHC13 were highly methylated in mon48. These findings provide foundational information that may be used to develop strategies for potentially retaining the lamb fur and thus improving the economic value of Tan sheep.


Luminescence properties and energy transfer of the near-infrared phosphor Ca3In2Ge3O12:Cr3+,Nd3.
The double doping strategy based on energy transfer is an effective way to regulate the NIR spectral distribution. In this work, Ca3In2Ge3O12:xNd3+ (CIG:xNd3+) and Ca3-x In1.93Ge3O12:0.07Cr3+,yNd3+ (CIG:0.07Cr3+,yNd3+) phosphors are successfully prepared via a high-temperature solid-state method. CIG:0.07Cr3+ shows broadband emission centered at 804 nm, which covers most of the excitation peaks of Nd3+ ions. Under excitation at 480 nm, Cr3+ can provide effective energy transfer to Nd3+. In addition, CIG:0.07Cr3+,0.15Nd3+ has good temperature stability, and maintains 68.98% of the room-temperature intensity at 150 °C. The phosphors can convert short-wave photons to long-wave photons and enhance solar cell utilization, demonstrating the potential application of this material in solar spectral conversion technology.


Conservative management of low back pain.
The importance of using appropriate conservative care in the management of low back pain has been increasingly stressed in recent years, initially as a backlash to the many failures following surgical intervention (particularly repeated surgeries), and, more recently, as a means of controlling health care costs and instituting patient-centered systems of care. It is difficult to define and determine just what "appropriate conservative care" is and should be. Perhaps even more important in this current era of health care reform is the question of who makes this determination.


Design and implementation of a wireless capsule suitable for autofluorescence intensity detection in biological tissues.
We report on the design, fabrication, testing, and packaging of a miniaturized system capable of detecting autofluorescence (AF) from mammalian intestinal tissue. The system comprises an application-specific integrated circuit (ASIC), light-emitting diode, optical filters, control unit, and radio transmitter. The ASIC contains a high-voltage charge pump and single-photon avalanche diode detector (SPAD). The charge pump biases the SPAD above its breakdown voltage to operate in Geiger mode. The SPAD offers a photon detection efficiency of 37% at 520 nm, which corresponds to the AF emission peak of the principle human intestinal fluorophore, flavin adenine dinucleotide. The ASIC was fabricated using a commercial triple-well high-voltage CMOS process. The complete device operates at 3 V and draws an average of 7.1 mA, enabling up to 23 h of continuous operation from two 165-mAh SR44 batteries.


Photochemical detection in high-performance liquid chromatography and its application to cannabinoid analysis.
A novel technique of on-line photochemical derivatization is described which can enhance considerably both the sensitivity and specificity of detection in high-performance liquid chromatography (HPLC).. Material eluting from the column is irradiated with a high flux of UV light, which may induce a reaction to form fluorescent or highly UV-absorbing products. The irradiated eluent then passes into a suitable detector. The photochemical reactor as a neglible effect on resolution, and reaction is achieved in 1-5 sec. An example of the use of this technique is in the detection of cannabinol CBN), a component of cannabis, which is converted into a highly fluorescent compound on irradiation with UV light. Thus, if a sample containing CBN is chromatographed and the column eluent irradiated, CBN can be detected (as the fluorescent photoproduct) with a sensitivity of less than 1 ng. If the chromatogram is then repeated without UV irradiation, only naturally fluorescent products are detected. A compairson of the two chromatograms allows these to be eliminated and leads to a very high specificity for the method. This approach is being developed as the basis of a rapid, sensitive and specific method for the detection of cannabinoids in body fluids. It is expected, however, that photochemical derivatization will extend the use of HPLC to many substances that cannot be satisfactorily detected at present.


Reversed distal femoral locking plate for failed proximal femoral nail with non-union of proximal femoral fractures.
Failure of proximal femoral fracture managed by proximal femoral nail (PFN) leads to a very difficult situation to handle with conventional techniques, and reversed distal femoral locking compression plate (DF-LCP) is of great benefit in these selective cases. Twelve patients with ununited proximal femoral fractures including subtrochanteric fractures with a failed PFN implant were included in the study. All patients with periprosthetic fractures and fractures treated by implants other than PFN were excluded from this study. All fractures went into union in an average time of nine months and 15 days with no implant failures. The mean time of re-osteosynthesis after the primary index surgery of PFN was one year eight months. Mean surgical time of re-osteosynthesis was 110 minutes, and average blood loss during surgery was 550 ml. The PFM is one of the most commonly used implant for unstable proximal femur fractures. The use of PFN is technically demanding and is associated with high failure rates. Although dynamic compression screw (DCS), proximal femoral locking plate (PF-LCP) and other implants can be used in these failed situations, they are associated with a high complication rate. The reversed DF-LCP is a rescue implant for these complex situations. Apart from anatomical and biomechanical advantages, there are several other clinical benefits of using DF-LCP. We conclude that DF-LCP is a potential and safe implant of choice for the management of nonunion associated with failed PFN. It may be considered an implant of choice as rescue from such a complex situation. It offers several anatomical, biomechanical and clinical advantages over other available conventional implants.


Treatment planning in molecular radiotherapy.
In molecular radiotherapy a radionuclide or a radioactively labelled pharmaceutical is administered to the patient. Treatment planning therefore comprises the determination of activity to administer. This administered activity should maximize tumour cell sterilization while minimizing normal tissue damage. In this work we present different approaches that are frequently used for determining the suitable activity. These approaches may be cohort- based as in chemotherapy, or patient-specific using dosimetry based on individual biokinetics. The approaches are different with respect to the input complexity, the corresponding costs and - in consequence - the quality of the therapy. In addition, a general scheme for data collection and analysis is proposed. To develop an effective and safe treatment, elaborate data need to be obtained. The main challenges, however, are collecting these complex data and analyse them properly.


Colorectal Sessile Serrated Lesion Detection Using Linked Color Imaging: A Multicenter, Parallel Randomized Controlled Trial.
Linked color imaging (LCI) is a novel technology that improves the color differences between colorectal lesions and the surrounding mucosa. The present study aims to compare the detection of colorectal sessile serrated lesions (SSL) using LCI with white light imaging (WLI). A large-scale, multicenter, parallel prospective randomized controlled trial was conducted in 4 hospitals in China. The participants were randomly assigned to the LCI group and WLI group. The primary endpoint was the SSL detection rate (SDR). A total of 884 patients were involved in the intention-to-treat analysis, with 441 patients in the LCI group and 443 patients in the WLI group. The total polyp detection rate, adenoma detection rate, and SDR were 51.8%, 35.7%, and 8.6%, respectively. The SDR was significantly higher in the LCI group than in the WLI group (11.3% vs 5.9%, P = .004). Furthermore, LCI significantly increased the number of polyps and adenomas detected per patient, when compared with WLI (P < .05). In addition, there was higher detection rate of diminutive and flat lesions in the LCI group (P < .05). Multivariate analysis revealed that LCI is an independent factor associated with SDR (hazard ratio, 1.990; 95% confidence interval, 1.203-3.293; P = .007), along with withdrawal time (hazard ratio, 1.157; 95% confidence interval, 1.060-1.263; P = .001) and operator experience (hazard ratio, 1.850; 95% confidence interval, 1.045-3.273; P = .035). LCI is significantly superior to WLI for SSL detection, and may improve polyp and adenoma detection. LCI can be recommended as an appropriate method for routine inspection during colonoscopy (http://www.chictr.org.cn number, ChiCTR2000035705).


Factors That Prevent Progression to Transcatheter Aortic Valve Implantation (TAVI).
Transcatheter aortic valve implantation (TAVI) is increasingly used for intermediate- and high-risk patients with severe symptomatic aortic stenosis (AS). However, safe undertaking of the procedure may be precluded by various anatomic factors. This study sought to identify prevalence of factors that prevent progression to TAVI. TAVI candidates with severe AS undergoing workup coronary angiography and iliac vessel angiography (±cardiac-gated CT) were identified and factors precluding TAVI were reviewed retrospectively from a single-centre cardiac database over a 10-year period. 197 patients were included; mean age was 81.5±6.5years (±SD); 46.2% were male. 26.9% of TAVI candidates could not proceed to femoral access TAVI due to various factors including unsuitable peripheral vasculature (13.2%), untreated coronary artery disease (CAD) deemed high risk for TAVI (8.1%), unfavourable aortic characteristics (4.1%), and low-lying coronary ostia (1.5%). Factors associated with unsuitable femoral vasculature included female gender (p<0.01) and any CAD (p=0.03). Factors associated with the presence of unrevascularised CAD included male gender (p<0.01), estimated glomerular filtration rate (eGFR)<30mL/min/1.73m2 (p=0.02), history of CAD (p<0.01), while prior percutaneous coronary intervention (PCI) or bypass surgery were protective (both p<0.01). Rates of progression to TAVI have increased over the last 10 years (p<0.01) from 58.3% prior to 2012 to 83.7% in 2016 and 2017, while incidence of unsuitable peripheral vasculature preventing TAVI (p=0.01) and CAD deemed unsuitable for TAVI (p=0.04) have both decreased. Non-progression to TAVI among higher risk patients with severe AS has become less common over the last 10 years with improvements in operator experience, lower profile devices, and wider ranges of valve sizes.


Post-infarct treatment with [Pyr(1)]apelin-13 improves myocardial function by increasing neovascularization and overexpression of angiogenic growth factors in rats.
Ischemic heart disease is the leading cause of mortality in the world. Angiogenesis is important for cardiac repair after myocardial infarction (MI) as restores blood supply to the ischemic myocardium and preserves cardiac function. Apelin is a peptide that has been recently shown to potentiate angiogenesis. The aim of this study was to investigate angiogenic effects of [Pyr(1)]apelin-13 in the rat model of post-MI. Male Wistar rats (n=36) were randomly divided into three groups: (1) sham (2) MI and (3) MI treated with [Pyr(1)]apelin-13 (MI+Apel). MI animals were subjected to 30min left anterior descending coronary artery (LAD) ligation and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr(1)]apelin-13 (10nmol/kg/day) was administered i.p. for 5 days. Hemodynamic functions by catheter introduced into the left ventricle (LV), myocardial fibrosis by Masson׳s trichrome staining, gene expression of vascular endothelial growth factor-A (VEGFA), VEGF receptor-2 (Kdr), Ang-1 (angiopoietin-1), Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2) and eNOS by Real-time polymerase chain reaction (Real-Time PCR) and myocardial angiogenesis by CD31 imunostaining were assessed at day 14 post-MI. Post-infarct treatment with [Pyr(1)]apelin-13 improved LV function and decreased myocardial fibrosis. [Pyr(1)]apelin-13 treatment led to a significant increase in the expression of VEGFA, Kdr, Ang-1, Tie2 and eNOS. Further, treatment with [Pyr(1)]apelin-13 promoted capillary density. [Pyr(1)]apelin-13 has angiogenic and anti-fibrotic activity via formation of new blood vessels and overexpression of VEGFA, Kdr, Ang-1, Tie2 and eNOS in the infarcted myocardium which could in turn repair myocardium and improve LV function.


Changes in Proteins in Saliva and Serum in Equine Gastric Ulcer Syndrome Using a Proteomic Approach.
Changes in the salivary proteome in 12 horses with the two diseases included in equine gastric ulcer syndrome (EGUS), equine glandular gastric disease (EGGD) (n = 6) and equine squamous gastric disease (ESGD) (n = 6), were evaluated using a high-resolution LC-MS/MS analysis of TMT-labelled peptides and compared to 10 healthy control horses. Serum was also analysed for comparative purposes. The comparison between the horses with EGGD and controls showed significant changes in 10 salivary proteins, whereas 36 salivary proteins were differently abundant between ESGD and control groups. The most upregulated proteins in the case of EGGD were related to immune activation whereas, in horses with ESGD, the most significantly changed proteins were associated with squamous cell regulation and growth. Compared to serum, saliva showed a higher number of proteins with significant changes and a different pattern of changes. The proteins identified in our study, in addition to providing new information about the pathophysiological mechanisms in these diseases, could have the potential to be novel biomarkers for the diagnosis or monitoring of EGGD and ESGD.


Coronary insufficiency in children: Review of literature and report of a rare case with unknown aetiology.
Myocardial ischemia due to coronary artery disease is a rare condition in children. The reported causes of this condition include vasculitis; commonest being Kawasaki' disease, pre-mature atherosclerosis due to familial dyslipidemias, congenital coronary artery anomalies and post-operative complications of procedures requiring coronary artery re-implantation in children, e.g. arterial switch procedure and Ross procedure. Allograft arteriopathy after heart transplantation is a more recent addition to this list (Mavroudis et al., 1996). Surgical procedures required for the treatment of coronary artery disease in children include, but are not limited to coronary artery re-implantation, re-routing, augmentation of the osteum, and coronary artery bypass grafting (CABG). We present our experience of a rare case of triple vessel coronary artery disease of unknown aetiology in a child, treated with coronary artery bypass grafting procedure.


Rapid determination of zearalenone in edible oils by HPLC with fluorescence detection.
A fast, cost-efficient, sensitive and accurate assay method for zearalenone in edible oils is described, as an alternative to gel permeation chromatography (GPC). Oil samples were extracted with an alkaline mixture of methanol and water (methanol +10 g/l aqueous ammonium carbaminate solution, pH 9; 9 + 1, v+v). The pH of the extract was neutralized with hydrochloric acid and then concentrated to dryness. The residue was dissolved with HPLC solvent, and zearalenone was determined by high-performance liquid chromatography with fluorometric detection (HPLC-FLD). The method was successfully validated for two matrices, maize oil and rapeseed oil. The recovery rate was 87%, and the coefficient of variation was 2.8% in a rapeseed oil sample contaminated with 27 µg zearalenone/kg. At a signal-to-noise ratio of 3:1, the method detection limit was 10 µg/kg, which was considered to be adequate in view of the present European Union maximum level of 400 µg/kg.


Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers.
Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G > C, within the second repeat of the 3R alleles. We studied the relationship between tumoural TS mRNA expression levels and TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher TS mRNA levels in the tumour than the 2R/2R-2R/3R genotypes (P = 0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in TS gene expression between the 3RG/3RG genotype and 2R/2R-2R/3RC-2R/3RG genotype subset was observed (P = 0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G > C polymorphism may be an important factor in determining TS mRNA expression levels, and warrant further investigation of the role of TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series.


Lack of cortistatin or somatostatin differentially influences DMBA-induced mammary gland tumorigenesis in mice in an obesity-dependent mode.
Somatostatin (SST) and cortistatin (CORT), two structurally and functionally related peptides, share a family of widespread receptors (sst1-5) to exert apparently similar biological actions, including endocrine/metabolic regulation and suppression of tumor cell proliferation. However, despite their therapeutic potential, attempts to apply SST-analogs to treat breast cancer have yielded unsatisfactory results. Actually, the specific roles of SST and CORT in mammary gland tumorigenesis (MGT), particularly in relation to metabolic dysregulation (i.e. obesity), remain unknown. The role of endogenous SST and CORT in carcinogen-induced MGT was investigated under normal (lean) and obesity conditions. To that end, SST- and CORT-knockout (KO) mice and their respective littermate-controls, fed low-fat (LF) or high-fat (HF) diets, were treated with 7,12-dimethyl-benza-anthracene (DMBA) once a week (wk) for 3 wk, and MGT was monitored for 25 wk. Additionally, we examined the effect of SST or CORT removal in the development of the mammary gland. Lack of SST did not alter DMBA-induced MGT incidence under lean conditions; conversely, lack of endogenous CORT severely aggravated DMBA-induced MGT in LF-fed mice. These differences were not attributable to altered mammary gland development. HF-diet modestly increased the sensitivity to DMBA-induced carcinogenesis in control mice, whereas, as observed in LF-fed CORT-KO, HF-fed CORT-KO mice exhibited aggravated tumor incidence, discarding a major influence of obesity on these CORT actions. In marked contrast, HF-fed SST-KO mice exhibited much higher tumor incidence than LF-fed SST-KO mice, which could be associated with higher mammary complexity. Endogenous SST and CORT distinctly impact on DMBA-induced MGT, in a manner that is strongly dependent on the metabolic/endocrine milieu (lean vs. obese status). Importantly, CORT, rather than SST, could represent a major inhibitor of MGT under normal/lean-conditions, whereas both neuropeptides would similarly influence MGT under obesity conditions. The mechanisms mediating these different effects likely involve mammary development and hormones, but the precise underlying factors are still to be fully elucidated. However, our findings comprise suggestive evidence that CORT-like molecules, rather than classic SST-analogs, may help to identify novel tools for the medical treatment of breast cancer.


Characterization of phiCFP-1, a virulent bacteriophage specific for Citrobacter freundii.
Citrobacter freundii, a Gram-negative bacterium, causes many opportunistic infections. Bacteriophage phiCFP-1 was isolated and characterized by its ability to lyse the multidrug-resistant clinical C. freundii strain P10159. Transmission electron microscopy showed that the phage has an icosahedral head and a short tail, making it a Podoviridae family member. In a single-step growth experiment, phiCFP-1 exhibited an eclipse period of 20 min and a burst size of 100 particles per cell. Its genome assembled as a circular molecule when genomic sequencing was completed. However, based on genome content and organization, it was categorized as a classic T7-related phage, and such phages are known to have linear genomes with direct terminal repeats. With the quick and simple method established herein, the 38,625-bp linear double-stranded DNA with 229-bp direct terminal repeats was accurately identified. The genome contained 43 putative open reading frames and no tRNA genes. Using a proteomics-based approach, seven viral and two host proteins from purified phiCFP-1 particles were identified. Comparative genomics and recombination analyzes revealed close genetic relatedness among phiCFP-1, phiYeO3-12/vB_YenP_AP5 (from Yersinia enterocolitica O3), and phiSG-JL2 (from Salmonella enterica).


Development and Initial Psychometrics of a Generic Treatment Integrity Measure Designed to Assess Practice Elements Targeting Social, Emotional, and Behavioral Outcomes in Early Childhood Settings.
Though treatment integrity measurement is important for research intended to promote social and behavioral outcomes of children at risk for emotional and behavioral disorders (EBDs) in early childhood settings, measurement gaps exist in the field. This paper reports on the development and preliminary psychometric assessment of the treatment integrity measure for early childhood settings (TIMECS), an observational measure designed to address existing measurement gaps related to treatment integrity with tier 2 interventions in the early childhood field. To assess the preliminary score reliability (interrater) and validity (construct, discriminant) of the TIMECS, live observations (N = 650) in early childhood classrooms from 54 teachers (92.6% female, 7.4% male; 61.1% White) and 91 children (M age = 4.53 years, SD = .44; 45.1% female, 54.9% male; 45.1% Black) at risk for EBDs were scored by 12 coders using the TIMECS and an observational measure designed to assess teacher-child interactions. Teachers also self-reported on the quality of the teacher-child relationship. Interrater reliability (intraclass correlation coefficients, ICC [2,2]) for the quantity (i.e., adherence) item scores had a mean of .81 (SD = .07; range from .68 to .95), and the quality (i.e., competence) item scores had a mean of .69 (SD = .08; range from .52 to .80). Scores on the TIMECS Quantity and Quality items and scales showed evidence of construct validity, with the magnitude of the correlations suggesting that the quantity and quality items assess distinct components of treatment integrity. A TIMECS quantity scale also showed promise for intervention evaluation research by discriminating between teachers who had and had not been trained in a specific evidence-based intervention targeting social and behavioral skills in early childhood. The findings support the potential of the TIMECS to assess treatment integrity of teacher-delivered practices designed to address child social and behavioral outcomes of children at risk for EBDs in early childhood settings.