Phylogenetic Analysis of the Synnema-Producing Genus Synnemapestaloides.
Synnemapestaloides rhododendri, the type species of the genus Synnemapestaloides, is a pathogen of Rhododendron brachycarpum. This fungus produces six-celled conidia with appendages at both end cells, and are generated by annellidic conidiogenous cells on the synnema. These conidial structures are similar to those of the genus Pestalotia. The monotypic genus Synnemapestaloides is currently classified in the family Amphisphaeriaceae solely based on conidial morphology. Here we demonstrate that Synnemapestaloides represents a distinct genus in the family Sporocadaceae (Amphisphaeriales) based on differences in the nucleotide sequences of the partial large subunit rDNA gene, the rDNA internal transcribed spacer, and the partial β-tubulin. The genus most closely related to Synnemapestaloides is Seimatosporium and the species most similar to Synnemapestaloides rhododendri is Seim. foliicola which produces short synnema-like conidiomata (sporodochia). These results demonstrate that Seim. foliicola should be transferred to Synnemapestaloides, and also demonstrate that Sporocadaceae can have synnematal in addition to pycnidial and acervular conidiomata.


Associations of quality of life with health-related characteristics among children with autism.
We examine whether behavioral, mental health, and physical health characteristics of children with autism are associated with baseline and change in health-related quality of life. We measured health-related quality of life with the Pediatric Quality of Life Inventory 4.0 total scores from children enrolled in the Autism Treatment Network. We used linear mixed model regressions with random slopes. Predictors of lower health-related quality of life at baseline included demographic and insurance characteristics, diagnosis, higher Child Behavior Checklist internalizing and externalizing scores, sleep problems by Children's Sleep Habits Questionnaire, seizures, gastrointestinal problems, and mental health problems. Several characteristics had different associations over time. This study demonstrates that in addition to behavioral and autism-related characteristics, physical and mental health conditions are associated with health-related quality of life in children with autism.


Computational analysis of siRNA recognition by the Ago2 PAZ domain and identification of the determinants of RNA-induced gene silencing.
RNA interference (RNAi) is a highly specialized process of protein-siRNA interaction that results in the regulation of gene expression and cleavage of target mRNA. The PAZ domain of the Argonaute proteins binds to the 3' end of siRNA, and during RNAi the attaching end of the siRNA switches between binding and release from its binding pocket. This biphasic interaction of the 3' end of siRNA with the PAZ domain is essential for RNAi activity; however, it remains unclear whether stronger or weaker binding with PAZ domain will facilitate or hinder the overall RNAi process. Here we report the correlation between the binding of modified siRNA 3' overhang analogues and their in vivo RNAi efficacy. We found that higher RNAi efficacy was associated with the parameters of lower Ki value, lower total intermolecular energy, lower free energy, higher hydrogen bonding, smaller total surface of interaction and fewer van der Waals interactions. Electrostatic interaction was a minor contributor to compounds recognition, underscoring the presence of phosphate groups in the modified analogues. Thus, compounds with lower binding affinity are associated with better gene silencing. Lower binding strength along with the smaller interaction surface, higher hydrogen bonding and fewer van der Waals interactions were among the markers for favorable RNAi activity. Within the measured parameters, the interaction surface, van der Waals interactions and inhibition constant showed a statistically significant correlation with measured RNAi efficacy. The considerations provided in this report will be helpful in the design of new compounds with better gene silencing ability.


Circadian time dependence of murine tolerance for carboplatin.
A large amplitude circadian rhythm in murine tolerance for the anticancer agent, carboplatin (cyclobutane dicarboxylatoplatinum II, CBDCA) was demonstrated. Two studies were performed in a total of 266 male B6D2F1 mice standardized by LD 12:12. In the first experiment CBDCA (80 mg/kg/day) was administered intravenously (iv) daily for three consecutive days at all six circadian stages (3, 7, 11, 15, 19, or 23 hr after light onset, HALO). CBDCA dosing at 15 HALO resulted in 58% long-term survivors as compared to 0% after treatment at 3 or 23 HALO (chi 2 = 28; p less than 0.001). In the second experiment, CBDCA (72 or 80 mg/kg/day X 3 days, iv) was administered at any of three circadian stages (0, 8, or 16 HALO). Mice were killed, blood was collected, and seven tissues were obtained 5 and 10 days after the first dose, in order to determine serum urea and creatinine concentrations, leukocyte and red blood cell counts, and to evaluate histologic lesions. No renal toxicity was encountered. Bone marrow and colon mucosa were the major target tissues of CBDCA in these dosages and schedules. CBDCA dosing at 16 HALO was least toxic to the bone marrow as assessed by peripheral leukocyte count and histologic score (p from ANOVA less than 0.05). Histologically assessed lesions of the colon mucosa were less severe after CBDCA dosing at 16 HALO as compared to those at 8 HALO, and significantly so for the lowest dosage tested (p approximately 0.05). Uptake of CBDCA 24 hr after the third dose ranged from 23 micrograms/g of dry tissue in the colon to 7 micrograms/g in the duodenum. Mean tissue concentrations increased between Day 4 and Day 10 for the liver and spleen, and remained similar for the kidney. No consistent circadian dependence was found with regard to Day 4 mean Pt uptake in different tissues, whereas the lowest Day 10 Pt concentrations corresponded to CBDCA dosing at 16 HALO for all tissues investigated. Toxicity did not appear to be directly related to the total platinum concentration in these tissues.


Long-term temporal stability of measured inattention and impulsivity in typical and referred children.
This study investigates the stability of measured inattention and impulsivity in children. The Gordon Diagnostic System (GDS) assesses inattention and impulsivity and has been administered in the same manner since its 1983 publication. GDS scores were compared between the 1983 standardization sample and a recent typical sample of 445 children, 562 children with ADHD-Combined (ADHD-C) type, 235 with ADHD-Inattentive (ADHD-I) type, and 231 with autism. Typical children earned a GDS composite standard score of 100, consistent with the normal mean of 100 in the 1983 standardization sample. Means for children with ADHD-C, ADHD-I, and autism were 70, 78, and 76, respectively, approximately two standard deviations below the normal mean. As measured by the GDS, children are no more or less inattentive and impulsive today than in 1983, suggesting that inattention and impulsivity are stable neurobiological traits largely unaffected by cultural, educational, and environmental factors.


Assessment of Neurodevelopment, Nutrition, and Inflammation From Fetal Life to Adolescence in Low-Resource Settings.
Efforts to improve child neurodevelopment are critical to health, equity, and sustainable development, particularly in low-resource settings in the United States and globally. The colliding epidemics of food insecurity, infectious diseases, and noncommunicable diseases interact and impact neurodevelopment. Understanding the complex relationships between nutrition, inflammation, and neurodevelopment can inform clinical and public health interventions to improve outcomes. This article reviews key definitions, tools, and considerations for the assessment of nutrition, inflammation, and child neurodevelopment. The effectiveness of existing assessment tools to reflect status and biology, particularly in relation to each other, and to predict long-term changes in health is examined. The aim of this review is to present the extant evidence, identify critical research gaps, and suggest a research agenda for future longitudinal and intervention studies to address the assessment of nutrition, inflammation, and child neurodevelopment, particularly in low-resource settings. Despite research gaps, there is a strong relationship between nutrition, inflammation, environmental factors, and child neurodevelopment, which emphasizes the need to evaluate targeted, early interventions to improve long-term health and well-being.


Anger Can Help: A Transactional Model and Three Pathways of the Experience and Expression of Anger.
Anger is a significant human emotion with far-reaching implications for individuals and relationships. We propose a transactional model of anger that highlights its relational relevance and potentially positive function, in addition to problematic malformations. By evolutionary design, physical, self-concept, or attachment threats all similarly trigger diffuse physiological arousal, psychologically experienced as anger-emotion. Anger is first a signaling and motivational system. Anger is then formed to affirming, productive use or malformed to destructive ends. A functional, prosocial approach to anger organizes it for protective and corrective personal and relational adaptation. In our model, threat perception interacts with a person's view of self in relation to other to produce helpful or harmful anger. Inflated or collapsed views of self in relation to other produce distinct manifestations of destructive anger that are harmful to self, other, and relationship. Conversely, a balanced view of self in relation to other promotes constructive anger and catalyzes self, other, and relationship healing. Clinical use of the model to shape healing personal and relational contact with anger is explored.


Comparative phylogenetic analyses of the adaptive radiation of Lake Tanganyika cichlid fish: nuclear sequences are less homoplasious but also less informative than mitochondrial DNA.
Over 200 described endemic species make up the adaptive radiation of cichlids in Lake Tanganyika. This species assemblage has been viewed as both an evolutionary reservoir of old cichlid lineages and an evolutionary hotspot from which the modern cichlid lineages arose, seeding the adaptive radiations in Lakes Victoria and Malawi. Here we report on a phylogenetic analysis of Lake Tanganyika cichlids combining the previously determined sequences of the mitochondrial ND2 gene (1047 bp) with newly derived sequences of the nuclear RAG1 gene (approximately 700 bp of intron 2 and approximately 1100 bp of exon 3). The nuclear data-in agreement with mitochondrial DNA-suggest that Lake Tanganyika harbors several ancient lineages that did not undergo rampant speciation (e.g., Bathybatini, Trematocarini). We find strong support for the monophyly of the most species-rich Tanganyikan group, the Lamprologini, and we propose a new taxonomic group that we term the C-lineage. The Haplochromini and Tropheini both have an 11-bp deletion in the intron of RAG1, strongly supporting the monophyly of this clade and its derived position. Mapping the phylogenetically informative positions revealed that, for certain branches, there are six times fewer apomorphies in RAG1. However, the consistency index of these positions is higher compared to the mitochondrial ND2 gene. Nuclear data therefore provide, on a per-base pair basis, less but more reliable phylogenetic information. Even if in our case RAG1 has not provided as much phylogenetic information as we expected, we suggest that this marker might be useful in the resolution of the phylogeny of older groups.


Micropreparative fraction collection in microfluidic devices.
Micropreparative fraction collection following microchip-based electrophoretic analysis of biomolecules is of major importance for a variety of biomedical applications. In this paper, we present a microfabricated device-based fraction collection system. Various size DNA fragments were separated and collected by simply redirecting the desired portions of the detected sample zones to corresponding collection wells using appropriate voltage manipulations. The efficiency of sampling and collection of the fractions was enhanced by placing a cross channel at or downstream of the detection point. Following the detection of the band of interest, the potentials were reconfigured to sampling/collection mode, so that the selected sample zone migrated to the appropriate collection well of the microdevice. The potential distribution assured that the rest of the analyte components in the separation column was retarded, stopped, or reversed, increasing in this way the spacing between the sample zone being collected and the immediately following one. By this means, a precise collection of spatially close consecutive bands could be facilitated. Once the target sample fraction reached the corresponding collection well, the potentials were switched back to separation mode. Alternation of the separation/detection and sampling/collection cycles was repeated until all required sample zones were physically isolated. The integrated device consists of a sample introduction, separation, fraction sampling, and fraction collection compartments. The feasibility of the fraction collection technique was tested on a mixture of dsDNA fragments. The amounts of DNA collected in this way were enough for further downstream sample processing, such as conventional PCR-based analysis.


Human pythiosis in Thailand.
Pythium insidiosum is a protoctista and causes diseases in plants and animals. In Thailand it can cause a unique human infection of three types. The first type is a subcutaneous lesion in thalassaemic patients, with the pathological findings of a granulomatous reaction, diffuse infiltration, and oedema of the vessel walls. The patients responded to a saturated solution of potassium iodide. The second type is chronic inflammation and occlusion of blood vessels mainly in the lower extremities which results in gangrene or aneurysm formation. This type of infection is only found in thalassaemic patients and leads to amputation of the affected extremities or resection of the involved arteries. The third type is keratitis. This type of infection may or may not be associated with thalassaemia. The clinical signs and symptoms do not differentiate it from other types of myocotic keratitis. The patients end up with keratoplasty, evisceration or enucleation. Thailand is an agricultural country, and there are plenty of swampy areas and several plants to support the life cycle of Pythium. Moreover, many people suffer from thalassaemia, and there is no drug available for Pythium. Pythiosis plays an important role in medicine in Thailand.


Environmental distribution of per- and polyfluoroalkyl substances (PFAS) on Svalbard: Local sources and long-range transport to the Arctic.
The environmental distribution of per- and polyfluoroalkyl substances (PFAS) in water, snow, sediment and soil samples taken along the west coast of Spitsbergen in the Svalbard archipelago, Norwegian Arctic, was determined. The contribution of potential local primary sources (wastewater, firefighting training site at Svalbard airport, landfill) to PFAS concentrations and long-range transport (atmosphere, ocean currents) were then compared, based on measured PFAS levels and composition profiles. In remote coastal and inland areas of Spitsbergen, meltwater had the highest mean ΣPFAS concentration (6.5 ± 1.3 ng L-1), followed by surface snow (2.5 ± 1.7 ng L-1), freshwater (2.3 ± 1.1 ng L-1), seawater (1.05 ± 0.64 ng L-1), lake sediments (0.084 ± 0.038 ng g-1 dry weight (dw)) and marine sediments (<method detection limit (MDL)-0.46 ng g-1 dw, median 0.015 ng g-1 dw). Perfluoroalkyl sulfonates (PFSA) and 6:2 fluorotelomer sulfonate (FTSA) were predominant in water and soil samples influenced by local sources, while perfluoroalkyl carboxylates (PFCA) were predominant in water and sediment from remote coastal and inland areas of Svalbard. The PFAS composition profiles observed in remote areas indicated that atmospheric transport and oxidation of volatile precursors is an important source of PFCA on Svalbard. Shorter-chain PFAS such as perfluorobutanoate (PFBA) were the predominant PFAS in freshwater, reflecting replacement of C8-chained PFAS with shorter-chained compounds. The comparatively high PFAS (especially PFBA) concentration in meltwater indicated that melting of snow and ice during the Arctic spring is an important diffuse local PFAS source. This source may become even more important with climate warming-induced melting of Arctic glaciers and ice sheets. Further studies of mobilisation and transport of PFAS in the Arctic region are needed to confirm this trend.


A cationic poly(2-oxazoline) with high in vitro transfection efficiency identified by a library approach.
To date, cationic polymers with high transfection efficiencies (TE) often have a high cytotoxicity. By screening an 18-membered library of cationic 2-oxazoline-based polymers, a polymer with similar TE as linear poly(ethylene imine) but no detectable cytotoxicity at the investigated concentrations could be identified. The influence of the polymer side chain hydrophobicity and the type and content of amino groups on the pDNA condensation, the TE, the cytotoxicity, the cellular membrane interaction as well as the size, charge, and stability of the polyplexes was studied. Primary amines and an amine content of at least 40% were required for an efficient TE. While polymers with short side chains were non-toxic up to an amine content of 40%, long hydrophobic side chains induced a high cytotoxicity.


Catamenial psychosis in an adolescent girl.
We report the case of an adolescent girl who was 14 years old at initial presentation. A shy, immature and timid individual, she began to have recurring, progressive episodes characterised by insomnia, paranoia, distorted thinking and mood instability with a mix of depressive and manic-like symptoms. An extensive medical work up was unrevealing. Her family noted a pattern that coincided with her menstrual cycle. An endocrine consult was obtained, and the diagnosis of catamenial psychosis was performed. After treatment with leuprolide, resulting in a shutdown of the hypothalamic-pituitary-ovarian axis, the patient's symptoms were resolved completely.


Morphea and Eosinophilic Fasciitis: An Update.
Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.


Determinants of geographic inequalities in HPV vaccination in the most populated region of France.
In France, there are recommendations and reimbursements for human papillomavirus (HPV) vaccination but no HPV vaccination programs. Therefore, vaccination is largely determined by parents' initiative, which can lead to inequalities. The objective of this study was to determine the factors associated with poorer vaccination coverage rates in the most populated region of France. The data of this study were obtained from the National Health Insurance between 2011 and 2013. Correlations between vaccination initiation rate (at least 1 dose reimbursed) and socio-demographic/cultural factors were assessed using Pearson's product-moment correlation coefficient. Multivariate analyses were performed using logistic regression. In total, 121,636 girls received at least one HPV vaccine dose. The vaccination rate for girls born from 1996 to 1999 was 18.7%. Disparities in vaccination coverage rates were observed between the 8 departments of the region, ranging from 12.9% to 22.6%. At the department level, unemployment, proportion of immigrants and foreigners, and coverage by CMU health insurance ("Couverture Maladie Universelle", a health insurance plan for those who are not otherwise covered through business or employment and who have a low income) were significantly inversely correlated with vaccination rates, whereas urban residence, medical density, income and use of medical services were not related to coverage. In the multivariate model, only the percentage of foreigners remained independently associated with lower vaccination coverage. At the individual level, the use of medical services was a strong driver of HPV vaccination initiation. We observed geographic disparities in HPV vaccination initiation coverage. Even if no clear factor was identified as a vaccination determinant, we observed a failure of vaccination only based on parents' initiative. Therefore, an organized policy on HPV vaccination, such as school-based programs, can help improve coverage rates.


Reduction and fixation of displaced intracapsular fractures of the proximal femur.
Intracapsular fractures of the femoral neck are one of the most common fractures in the elderly. The incidence of these fractures will increase significantly in the next decades as a result of increasing life expectancy. Although treatment of these fractures by closed or open reduction and internal fixation is standard in young patients, arthroplasty is the standard treatment in geriatric patients in most countries. Comorbidities of the patients and current socioeconomic changes in healthcare led to reconsideration of closed reduction and internal fixation of femoral neck fractures as an alternative treatment modality. With correct decision-making, proper reduction, and proper consideration of the biomechanical principle of three-point fixation, minimally invasive screw fixation of femoral neck fractures is a safe and inexpensive procedure even in elderly patients. The purpose of the current review was to give an overview of the history, current techniques and developments, results, limitations, and complications of closed reduction and internal fixation of intracapsular femoral neck fractures.


Deafferentation of the Superior Colliculus Abolishes Spatial Summation of Redundant Visual Signals.
Two visual signals appearing simultaneously are detected more rapidly than either signal appearing alone. Part of this redundant target effect (RTE) can be attributed to neural summation that has been proposed to occur in the superior colliculus (SC). We report direct evidence in two neurological patients for neural summation in the SC, and that it is mediated by afferent visual information transmitted through its brachium. The RTE was abolished in one patient with a hemorrhage involving the right posterior thalamus that damaged part of the SC and that disrupted its brachium; and in another patient in whom the SC appeared intact but deafferented due to traumatic avulsion of its brachium. In addition reaction time for unilateral targets in the contralesional field was slowed in both patients, providing the first evidence that visual afferents to the SC contribute to the efficiency of target detection.


Evidence that colicin X is microcin B17.
The DNA replication inhibitor microcin B17 is a peptide antibiotic produced by Escherichia coli strains carrying plasmid pMccB17. Here we present evidence that antibiotic activities previously named colicin X are probably identical to microcin B17. Our results include comparison of the conditions of production of the antibiotics, their mode of action, cross-immunity of producer strains, and cross-resistance of resistant mutants. Plasmids encoding colicin X have been identified and shown to have a region of significant homology with the microcin B17-producing region of pMccB17 DNA.


Exogenous norepinephrine constricts cerebral arterioles via alpha 2-adrenoceptors in newborn pigs.
The purpose of this study was to determine whether exogenous norepinephrine mediates cerebrovascular constriction via alpha 1- or alpha 2-adrenoceptors in anesthetized neonatal pigs. Diameters of pial arterioles in anesthetized piglets, 1--6 days old, were investigated using a "closed" cranial window. We examined constrictor effects of norepinephrine on pial arterioles in the absence and presence of relatively selective alpha 1-(prazosin) and alpha 2-(yohimbine) adrenoceptor antagonists (1 mg/kg i.v.). Yohimbine and prazosin inhibited pial arteriolar constriction induced by topical application of clonidine and phenylephrine (10(-6) and 10(-4) M, respectively), and yohimbine did not affect the response to topical phenylephrine. In one group diameter was 188 +/- 13 (mean +/- SEM) micron during control and 146 +/- 12 micron during 10(-5) M norepinephrine (22 +/- 5% constriction). Following yohimbine the same vessels did not constrict significantly. In another group 10(-5) M norepinephrine constricted arterioles by 22 +/- 5%, and this response was unaffected by prazosin (24 +/- 5% constriction). We conclude that pial arterioles are responsive to both alpha 1- and alpha 2-adrenoceptor agonists, that intravenous administration of prazosin and yohimbine results in these drugs crossing the blood-brain barrier and inhibiting constrictor effects of agonists, and that norepinephrine constricts pial arterioles predominantly via alpha 2-adrenoceptors.


Evidence of phenotypic stability after transduction of fluorescent proteins in two human tongue cancer cell lines.
This study investigated the phenotypic stability and biological properties of two human tongue cancer cell lines after transduction of fluorescent proteins. The human tongue cancer cell lines UM1 and UM2 were cultured with GFP and RFP lentiviral particles stock for 72h. Cells with successful transduction of fluorescent proteins were selected in a medium containing G418 antibiotics for two weeks. The proliferation rates of parental and transduced cell lines were evaluated by their population doubling time (PDT). Transduction efficiency was assessed by fluorescence microscope and flow cytometry. The transduced cells in passage 1, 2, 10, 20 and 30 were collected to check the stability of fluorescent protein expression. Phenotypic stability of the transduced cells was detected by means of cell morphology, cell surface markers and cell function evaluating essay. The proliferation rates of the transduced cell lines showed no significant difference compared to their parental cells. Successful transduction with high efficiency (99% up) was demonstrated. High fluorescence expression on both transduced cells was detected until the thirtieth generation. UM1 and UM1-GFP displayed mesenchymal cell characteristics, while UM2 and UM2-RFP cell lines showed properties characteristic of epithelial. Two human tongue cancer cell lines of epithelial and mesenchymal phenotype respectively, have been successfully labelled with green and red fluorescent proteins. The fluorescence maintained a high expression rate over thirty generations without influencing the original morphological phenotype and cadherin expression.


Evaluation of adenosine deaminase (ADA) isoenzymes activity and tumor necrosis factor-α (TNFα) concentration in chronic heart failure.
Chronic heart failure (CHF) has recently been considered as an inflammatory disease. Enhanced production of tumor necrosis factor-α (TNFα) in CHF patients has been proved. To compensate deleterious effects of TNα, the concentration of adenosine is increased in CHF. However, concurrent determination of serum TNFα and enzymatic activities of ADA and its ADA1 and ADA2 isoenzymes, as the main regulators of adenosine concentration, has not yet been carried out. Blood samples were collected from 52 CHF patients and 55 healthy controls. Laboratory routine tests were performed, and after determining the concentration of TNFα, total ADA (tADA) as well as ADA1 and ADA2 isoenzyme activities were measured. Mean concentration of TNFα increased over 2 fold in CHF patients (12.54 ± 11.69 pg/ml compared with 6.0 ± 6.58 pg/ml in controls). The highest level of TNFα was observed in patients with the final stage of the disease (NHYA IV subgroup), according to the New York Heart Association classification. tADA activity was significantly lower in CHF patients compared with controls (19.29 ± 9.73 and 24.3 ± 6.01 U/L, respectively). ADA2 activity markedly decreased in CHF patients and showed a direct correlation with tADA (r = 0.641, P = 0001). In addition, the lowest levels of tADA and ADA2 activities were observed in patients from the 4(th) quartile of NYHA classification. Adenosine deaminase activity is reduced in CHF patients to give rise to the concentration of adenosine, thereby attenuating pathologic consequences of CHF. Therefore, it is concluded that ADA activity is of paramount importance in pathophysiology of heart failure and might be used for diagnostic purposes or treatment targets.


Current diagnosis and treatment of vestibular neuritis: a narrative review.
Vertigo is the sensation of self-motion of the head or body when no self-motion is occurring or the sensation of distorted self-motion during an otherwise normal head movement. Representative peripheral vertigo disorders include benign paroxysmal positional vertigo, Ménière disease, and vestibular neuritis. Vestibular neuritis, also known as vestibular neuronitis, is the third most common peripheral vestibular disorder after benign paroxysmal positional vertigo and Ménière disease. The cause of vestibular neuritis remains unclear. However, a viral infection of the vestibular nerve or ischemia of the anterior vestibular artery is known to cause vestibular neuritis. In addition, recent studies on immune-mediated mechanisms as the cause of vestibular neuritis have been reported. The characteristic clinical features of vestibular neuritis are abrupt true-whirling vertigo lasting for more than 24 hours, and no presence of cochlear symptoms and other neurological symptoms and signs. To accurately diagnose vestibular neuritis, various diagnostic tests such as the head impulse test, bithermal caloric test, and vestibular-evoked myogenic potential test are conducted. Various treatments for vestibular neuritis have been reported, which are largely divided into symptomatic therapy, specific drug therapy, and vestibular rehabilitation therapy. Symptomatic therapies include generalized supportive care and administration of vestibular suppressants and antiemetics. Specific drug therapies include steroid therapy, antiviral therapy, and vasodilator therapy. Vestibular rehabilitation therapies include generalized vestibular and customized vestibular exercises.


Quality of cost evaluations of physician continuous professional development: Systematic review of reporting and methods.
We sought to evaluate the reporting and methodological quality of cost evaluations of physician continuing professional development (CPD). We conducted a systematic review, searching MEDLINE, Embase, PsycInfo, and the Cochrane Database for studies comparing the cost of physician CPD (last update 23 April 2020). Two reviewers, working independently, screened all articles for inclusion. Two reviewers extracted information on reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), and on methodological quality using the Medical Education Research Study Quality Instrument (MERSQI) and a published reference case. Of 3338 potentially eligible studies, 62 were included. Operational definitions of methodological and reporting quality elements were iteratively revised. Articles reported mean (SD) 43% (20%) of CHEERS elements for the Title/Abstract, 56% (34%) for Introduction, 66% (19%) for Methods, 61% (17%) for Results, and 66% (30%) for Discussion, with overall reporting index 292 (83) (maximum 500). Valuation methods were reported infrequently (resource selection 10 of 62 [16%], resource quantitation 10 [16%], pricing 26 [42%]), as were descriptions/discussion of the physicians trained (42 [68%]), training setting (42 [68%]), training intervention (40 [65%]), sensitivity analyses of uncertainty (9 [15%]), and generalizability (30 [48%]). MERSQI scores ranged from 6.0 to 16.0 (mean 11.2 [2.4]). Changes over time in reporting index (initial 241 [105], final 321 [52]) and MERSQI scores (initial 9.8 [2.7], final 11.9 [1.9]) were not statistically significant (p ≥ 0.08). Methods and reporting of HPE cost evaluations fall short of current standards. Gaps exist in the valuation, analysis, and contextualization of cost outcomes.


Effect of phytic acid used as etchant on bond strength, smear layer, and pulpal cells.
This study aimed to evaluate the effect of phytic acid (IP6), used as etchant, on resin-dentin bond strength, smear layer removal, and the viability of pulpal cells. Flat dentin surfaces with smear layer were etched with 1% IP6 for 60, 30, or 15 s; in the control group 37% phosphoric acid (PA) was used. Dentin surfaces were rinsed, blot-dried, and bonded with an etch-and-rinse adhesive, followed by composite build-ups. The specimens were subjected to tensile testing after 24 h of water storage at 37°C, and failure modes were determined using scanning electron microscopy. The effectiveness of IP6 to remove the smear layer was observed using scanning electron microscopy. To evaluate the effect on pulpal cells, solutions of 0.1 and 0.01% IP6 and of 3.7 and 0.37% PA were prepared and rat pulpal cells were treated with these solutions for 6 and 24 h. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results demonstrated that all application times of IP6 produced bond-strength values that were significantly higher than that of the control. Phytic acid effectively removed the smear layer and plugs, thus exposing the collagen network. Phytic acid had a minimal effect on pulpal cells, whereas PA resulted in a marked decrease in their viability.


[The diagnosis of subclinical hepatic encephalopathy].
Subclinical hepatic encephalopathy, has been recognized in patients with cirrhosis, irrespectively of its etiology. Patients exhibit different cognitive deficits (in visual-spatial perception, attention, concentration, constructional ability, etc.), which are not detectable during standard neurological examination, but adversely affect daily functioning. The prevalence of this disorder among patients with cirrhosis is estimated to vary from 30 to 84% according to various studies. We presented the pathogenesis of subclinical hepatic encephalopathy. We discussed psychometric tests, which were the most important and sensitive diagnostic tools in this disorder. The significance of the abnormalities in the electrophysiological examination (EEG, visual evoked potentials, P300 wave, event-related potentials) and in computed tomography, magnetic resonance imaging, single photon emission computed tomography and proton-magnetic resonance spectroscopy were presented.


Investigation of membrane disruption in the reaction catalyzed by cholesterol oxidase.
Dye leakage experiments were undertaken to investigate the membrane disruption properties of cholesterol oxidase. Inspection of the X-ray crystal structures of cholesterol oxidase suggested that an active-site "lid" opens in order to bind substrate [Li, J., Vrielink, A., Brick, P., & Blow, D. M. (1993) Biochemistry 32, 11507-11515]. We tested whether the interaction of the putative active-site lid with the membrane was sufficiently disruptive of the membrane structure to cause leakage or lysis of the cell membrane. Vesicles (100 nm) composed of egg phosphatidylcholine, 2-palmitoyl-3-oleoyl-1-sn-phosphatidylethanolamine, and 2-palmitoyl-3-oleoyl-1-sn-phosphatidylcholine were used in this study to mimic biomembranes. To separate the effects of membrane binding from conversion of cholesterol to cholest-4-en-3-one, the active-site mutant E361Q was utilized. In the reaction catalyzed by E361Q, isomerization of the cholest-5-en-3-one intermediate is suppressed and cholest-5-en-3-one is the major product isolated. Furthermore, E361Q produces cholest-5-en-3-one 20-fold more slowly than wild type produces cholest-4-en-3-one from cholesterol. Wild-type and E361Q cholesterol oxidases bind to vesicles with an apparent K(D) of approximately 25 microM, as measured by quenching of intrinsic tryptophan fluorescence, irrespective of headgroup size and cholesterol content. Membrane disruption was measured by leakage of the encapsulated marker carboxyfluorescein. Leakage was observed with cholesterol-containing vesicles and wild-type enzyme only; the rate of leakage was dependent on the rate of cholest-4-en-3-one production. E361Q did not induce membrane disruption, regardless of vesicle type tested. Thus, binding of cholesterol oxidase to the membrane and partitioning of cholesterol into the active site does not sufficiently perturb the bilayer to cause leakage of vesicle contents. Formation of the product cholest-4-en-3-one, however, does increase membrane permeability. Expansion of the lipid bilayer upon conversion of cholesterol to cholest-4-en-3-one is the likely cause of this increased permeability.


Disulfide bond cleavage: a redox reaction without electron transfer.
By using Car-Parrinello molecular dynamics (CPMD) simulations we have simulated a mechanically induced redox reaction. Previous single-molecule atomic force microscopy (AFM) experiments demonstrated that the reduction of disulfide bonds in proteins with the weak reducing agent dithiothreitol depends on a mechanical destabilization of the breaking bond. With reactive molecular dynamics simulations the single steps of the reaction mechanism can be elucidated and the motion of the electrons can be monitored. The simulations show that the redox reaction consists of the heterolytic cleavage of the S--S bond followed by a sequence of proton transfers.


Finite-temperature gauge theory from the transverse lattice.
Numerical computations are performed and analytic bounds are obtained on the excited spectrum of glueballs in SU(inifinity) gauge theory, by transverse lattice Hamiltonian methods. We find an exponential growth of the density of states, implying a finite critical (Hagedorn) temperature. It is argued that the Nambu-Goto string model lies in a different universality class.


DYNAMICS OF SEXUAL SELECTION IN DIPLOID POPULATIONS.
We describe results for a diploid, two-locus model for the evolution of a female mating preference directed at an attractive male trait that is subject to viability and/or fertility selection. Using computer simulation, we studied a large, random sample of parameter values, assuming additivity of alleles at the preference locus and partial dominance at the trait locus. Simulation results were classifiable into nine types of parameter sets, each differing in equilibria, evolutionary trajectories, and rates of evolution. For many parameters, evolutionary trajectories converged on curves within the allelic frequency plane and subsequently evolved along the curves toward fixation. Neutrally stable curves of equilibria did not occur in Fisherian models that assume only viability and sexual selection unless there is complete dominance at the trait locus. The Fisherian models also exhibited oscillation of allelic frequencies and unique polymorphic equilibria. "Sexy son" models in which attractive males had reduced fertility were much less likely to lead to increase in traits and preferences than were the Fisherian models. However, if less fertile males had increased viability, trait polymorphisms and fixation of rare "sexy" alleles occurred. In general, the behavior of the diploid model was much more complex than that of analogous haploid or polygenic models.


Molecular characterisation of methicillin-resistant Staphylococcus aureus (MRSA) isolated at a large referral hospital in Zambia.
Methicillin-resistant Staphylococcus aureus (MRSA) is globally recognized as an important public health problem. Whereas comprehensive molecular typing data of MRSA strains is available, particularly in Europe, North America and Australia, similar information is very limited in sub-Saharan Africa including Zambia. In this study, thirty two clinical isolates of Staphylococcus aureus, collected at a large referral hospital in Lusaka, Zambia between June 2009 and December 2012 were analysed by Staphylococcal cassette chromosome mec (SCCmec), Staphylococcus protein A gene typing (spa) and detection of the Panton-Valentine Leukocidin genes (pvl). Three SCCmec types were identified namely SCCmec type IV (65.6%), SCCmec type III (21.9%), SCCmec type I (3.1%). Nine point four percent (9.4%) of the isolates were untypable. Five spa types, which included a novel type, were detected and the most prevalent spa type was t064 (40.6%). Other spa types included spa types t2104 (31.3%), t355 (3.1%) and t1257 (21.9%). The pvl genes were detected in 3 out of 32 isolates. These molecular typing data indicated that the MRSA strains collected in Lusaka were diverse. Although the source of these MRSA was not established, these results stress the need for assessing infection prevention and control procedures at this health-care facility in order to curtail possible nosocomial infections. Furthermore, country-wide surveillance of MRSA in both the community and health-care facilities is recommended for infection prevention and control. To our knowledge, this represents the first study to characterise MRSA using molecular tools in Zambia.


Impact of sonography on diagnosis of scrotal diseases: a multicenter study.
Scrotal ultrasound was carried out since 1980 in five centers. 1,971 cases presenting with pathological conditions of scrotal content were reviewed to asses limitations and possibilities of the method. Scrotal sonography was found to be a highly reliable method to distinguish between intra- and extratesticular lesions. The data presented reveal that sonography is not capable of differentiating reliably between benign and malignant lesions. In the decision-making process ultrasound is sometimes of great help to the urologist but surely no substitution for careful examination and history taking.


Complications After Cosmetic Surgery Tourism.
Cosmetic surgery tourism characterizes a phenomenon of people traveling abroad for aesthetic surgery treatment. Problems arise when patients return with complications or need of follow-up care. To investigate the complications of cosmetic surgery tourism treated at our hospital as well as to analyze arising costs for the health system. Between 2010 and 2014, we retrospectively included all patients presenting with complications arising from cosmetic surgery abroad. We reviewed medical records for patients' characteristics including performed operations, complications, and treatment. Associated cost expenditure and Diagnose Related Groups (DRG)-related reimbursement were analyzed. In total 109 patients were identified. All patients were female with a mean age of 38.5 ± 11.3 years. Most procedures were performed in South America (43%) and Southeast (29.4%) or central Europe (24.8%), respectively. Favored procedures were breast augmentation (39.4%), abdominoplasty (11%), and breast reduction (7.3%). Median time between the initial procedure abroad and presentation was 15 days (interquartile range [IQR], 9) for early, 81.5 days (IQR, 69.5) for midterm, and 4.9 years (IQR, 9.4) for late complications. Main complications were infections (25.7%), wound breakdown (19.3%), and pain/discomfort (14.7%). The majority of patients (63.3%) were treated conservatively; 34.8% became inpatients with a mean hospital stay of 5.2 ± 3.8 days. Overall DRG-related reimbursement premiums approximately covered the total costs. Despite warnings regarding associated risks, cosmetic surgery tourism has become increasingly popular. Efficient patients' referral to secondary/tertiary care centers with standardized evaluation and treatment can limit arising costs without imposing a too large burden on the social healthcare system. 4.


An Approach towards Increasing Prediction Accuracy for the Recovery of Missing IoT Data Based on the GRNN-SGTM Ensemble.
The purpose of this paper is to improve the accuracy of solving prediction tasks of the missing IoT data recovery. To achieve this, the authors have developed a new ensemble of neural network tools. It consists of two successive General Regression Neural Network (GRNN) networks and one neural-like structure of the Successive Geometric Transformation Model (SGTM). The principle of ensemble topology construction on two successively connected general regression neural networks, supplemented with an SGTM neural-like structure, is mathematically substantiated, which improves the accuracy of prediction results. The effectiveness of the method is based on the replacement of the summation of the results of the two GRNNs with a weighted summation, which improves the accuracy of the ensemble operation in general. A detailed algorithmic implementation of the ensemble method as well as a flowchart of its operation is presented. The parameters of the ensemble operation are determined by optimization using the brute-force method. Based on the developed ensemble method, the solution of the task of completing the partially missing values in the real monitoring dataset of the air environment collected by the IoT device is presented. By comparing the performance of the developed ensemble with the existing methods, the highest accuracy of its performance (by the parameters of Mean Absolute Percentage Error (MAPE) and Root Mean Squared Error (RMSE) accuracy) among the most similar in this class has been proved.


Using the Inflammacheck Device to Measure the Level of Exhaled Breath Condensate Hydrogen Peroxide in Patients With Asthma and Chronic Obstructive Pulmonary Disease (The EXHALE Pilot Study): Protocol for a Cross-Sectional Feasibility Study.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) are common conditions that affect over 5 million people in the United Kingdom. These groups of patients suffer significantly from breathlessness and recurrent exacerbations that can be difficult to diagnose and go untreated. A common feature of COPD and asthma is airway inflammation that increases before and during exacerbations. Current methods of assessing airway inflammation can be invasive, difficult to perform, and are often inaccurate. In contrast, measurement of exhaled breath condensate (EBC) hydrogen peroxide (H2O2) is performed during normal tidal breathing and is known to reflect the level of global inflammation in the airways. There is a need for novel tools to diagnose asthma and COPD earlier and to detect increased airway inflammation that precedes an exacerbation. The aim of this study was to explore the use of a new handheld device (called Inflammacheck) in measuring H2O2 levels in EBC. We will study whether it can measure EBC H2O2 levels consistently and whether it can be used to differentiate asthma and COPD from healthy controls. We will perform a cross-sectional, feasibility, pilot study of EBC H2O2 levels, as measured by Inflammacheck, and other markers of disease severity and symptom control in patients with asthma and COPD and volunteers with no history of lung disease. Participants will be asked to provide an exhaled breath sample for measurement of their EBC H2O2 using Inflammacheck. The result will be correlated with disease stage, spirometry, fractional exhaled nitric oxide (FeNO), and symptom control scores. This study's recruitment is ongoing; it is anticipated that the results will be available in 2018. The EXhaled Hydrogen peroxide As a marker of Lung diseasE (EXHALE) pilot study will provide an evaluation of a new method of measuring EBC H2O2. It will assess the device's consistency and ability to distinguish airway inflammation in asthma and COPD compared with healthy controls.


The Effect of a Lifestyle Modification Education on Adiposity Measures in Overweight and Obese Nonalcoholic Fatty Liver Disease Patients.
Obesity is increasingly associated with nonalcoholic fatty liver disease (NAFLD) and weight loss through a combination of dietary modifications and increased physical activity is a primary goal of therapy in this disease. Therefore, this study was conducted to evaluate the effects of a lifestyle modification education on adiposity measures, physical activity, and total calorie intake in overweight and obese NAFLD patients. During 8 weeks, 82 obese patients were randomly assigned into either an intervention group (n = 41) receiving a lifestyle modification education or to a control group (n = 41) receiving usual care. Total calorie intake, physical activity, and body composition indices were measured before and after the intervention. Thirty-six patients in intervention group and 33 in control group completed the study. The analysis of body composition variables did not show any significant reduction for percent of body fat, abdominal circumference, waist to hip ratio, visceral fat area, age matched of body, and soft lean mass (SLM) of the trunk (P > 0.05). On the other hand, a significant reduction in weight, body mass index, mass of body fat (MBF), SLM, and MBF of the trunk was observed after 2 months of intervention compared to the controls (P < 0.05). A significant reduction was observed in total calorie intake of intervention group as compared to the control group. Physical activity status did not show any significant improvements after 2 months of intervention. Our lifestyle modification education and its guidelines could be used in obese patients with NAFLD to improve their body composition measurements and to lose weight. This could result in significant long-term benefits in NAFLD patients.


Classification of commercial Catuaba samples by NMR, HPLC and chemometrics.
For over a century, Catuaba has been used in Brazilian folk medicine as an aphrodisiac even though the identity of the plant material employed is often uncertain. The species recommended by the Brazilian Pharmacopeia is Anemopaegma arvense (Bignoniaceae), but many other plants, regionally known as Catuaba, are commercialised. Frequently, the quality control of such a complex system is based on chemical markers that do not supply a general idea of the system. With the advent of the metabolomics approach, a global analysis of samples becomes possible. It appears that (1)H-NMR is the most useful method for such application, since it can be used as a wide-spectrum chemical analysis technique. Unfortunately, the generated spectra is complex so a possible approach is to look at the metabolite profile as a whole using multivariate methods, for example, by application of principal component analysis (PCA). In the present paper, we describe for the first time a proton high-resolution magic angle spinning nuclear magnetic resonance ((1)H-HR-MAS NMR) method coupled with PCA for the metabolomic analysis of some commercial Catuaba samples, which provided a reduction in the time required for such analysis. A comparative study of HPLC, HR-MAS and liquid-NMR techniques is also reported.


When and How to Adjust Non-Pharmacological Interventions Concurrent with Booster Vaccinations Against COVID-19 - Guangdong, China, 2022.
With the large-scale roll-out of the coronavirus disease 2019 (COVID-19) booster vaccination effort (a vaccine dose given 6 months after completing primary vaccination) in China, we explore when and how China could lift non-pharmacological interventions (NPIs) against COVID-19 in 2022. Using a modified susceptible-infectious-recovered (SIR) mathematical model, we projected the COVID-19 epidemic situation and required medical resources in Guangdong Province, China. If the number of people entering from overseas recovers to 20% of the number in 2019, the epidemic in 2022 could be controlled at a low level by a containment (215 local cases) or suppression strategy (1,397 local cases). A mitigation strategy would lead to 21,722 local cases. A coexistence strategy would lead to a large epidemic with 6,850,083 local cases that would overwhelm Guangdong's medical system. With 50% or 100% recovery of the 2019 level of travelers from overseas, the epidemic could also be controlled with containment or suppression, but enormous resources, including more hotel rooms for border quarantine, will be required. However, coexistence would lead to an uncontrollable epidemic with 12,922,032 local cases. With booster vaccinations, the number of travelers from overseas could increase slightly in 2022, but a suppression strategy would need to be maintained to ensure a controllable epidemic.


[Immunological response of mice to diphtheria toxoid].
Following the determination of immunological response in mice, by titration, 1.5 Lf diphtheria toxoid was found as an optimal plasma cell activator. Groups of mice were subcutaneously injected with 1.5 Lf diphteria toxoid and on 2, 3, 4, 6, 10, 15 and 25th days of injection mice were killed and their blood, spleen, thymus, lymph nodes and lungs preserved. Section from these specimens were stained by methyl-green, pyronine and toluidine. Lymphocytes, plasma cells, and mast cells were counted in 10-20 fields in each preparation. Mature plasma cell ratio was calculated against lymphocyte counts. Mature plasma cell and mast cell counts and ratios of test mice were found increased when compared with that of normal control mice. The difference in thymus, spleen and lungs was found to be insignificant, however it was significant, p less than 0.05 in lymph. nodes. Maximum cell counts were seen at ten days. The sera of the test mice were also examined for humoral antibodies with precipitation and Römer's skin test. on 2, 3, 4, 6 and 10th days no antitoxin could be demonstrated in the sera of the test mice in controls either. In the sera taken on 15 and 25th days antitoxin was detected.


Investigation of Human Dental Pulp Cells on a Potential Injectable Poly(lactic-co-glycolic acid) Microsphere Scaffold.
Poly(lactic-co-glycolic acid) (PLGA) has been extensively explored in the tissue engineering field with good biocompatibility and biodegradability. PLGA microspheres' injectable potency makes it highly desirable in dentin-pulp complex regeneration. Therefore, we investigated the cell adhesion, proliferation, odontogenic differentiation, and matrix mineralization of human dental pulp cells (HDPCs) on a PLGA microsphere scaffold. We hypothesized that this scaffold might be suitable for dentin-pulp complex regeneration. PLGA microsphere scaffolds were fabricated using the double-emulsion solvent extraction technique with or without type I collagen surface modification. HDPCs were isolated from freshly extracted premolar or third molar teeth with patients' informed consent and ethical approval. Fourth-passage HDPCs (1 × 105 cells/ml) were seeded onto surface-modified or -unmodified PLGA microspheres and cultured in vitro. Cell adhesion, proliferation, and alkaline phosphatase activity were evaluated at different time points. Odontogenic-related gene expression (DMP1, DSPP, COL1, OPN, and OCN) were analyzed using quantitative real-time polymerase chain reaction. After 8 weeks of culture, samples were observed under scanning electron microscopy. Surface modification using type I collagen significantly enhanced HDPC attachment to the PLGA microspheres and promoted cell spreading. Alkaline phosphatase activity and odontogenic-related gene expression of HDPCs cultured with PLGA microsphere scaffolds were enhanced significantly compared with HDPCs cultured without PLGA microsphere scaffolds. After 8 weeks of culture, HDPCs combined with PLGA microspheres formed 3-dimensional structures. Partial degradation of the scaffolds and matrix mineralization were also observed. HDPCs can adhere to the PLGA microspheres, proliferate and differentiate into odontoblastlike cells, and form a 3-dimensional complex with matrix mineralization. This study may provide insight into the clinical dentin-pulp complex restoration with HDPCs and PLGA microsphere constructs.


Antifungal activities and active ingredients of Melodinus suaveolens Champ. ex Benth.
Four Melodinus species with antifungal activity were found in survey of the floral resources, in Shiwan Mountain Natural Reserve, Guangxi Province, China. Crude methanolic extracts of the twigs and leaves of Melodinus suaveolens exhibited potent antifungal activities against the plant pathogenic fungi Colletotrichum musae, Colletotrichum graminicola, Colletotrichum gloeosporioides and Alternaria musae, and the ethyl acetate fraction inhibited these pathogens at rates of 85.37, 91.47, 72.77 and 89.87%, respectively (5 mg/mL). A new compound, (2R, 3S, 5S, 6R)-1-O-methyl- chiro-inositol was isolated from the ethyl acetate fraction, along with 15 known compounds. The antifungal activities of compounds (1-16) were evaluated for the first time. Compound (4) had potent antifungal activity against C. gloeosporioides, C. graminicola and A. musae.


Fatal intoxication with methoxetamine.
Methoxetamine (MXE) is a new synthetic drug of abuse structurally related to ketamine and phencyclidine. A case of a 29-year-old male with acute toxicity related to the analytically confirmed use of MXE is reported. The man was found dead at his residence. Biological material was analyzed using liquid chromatography-tandem mass spectrometry. The concentration of MXE in urine of the deceased was 85 μg/mL. Despite the vial containing the blood sample being destroyed during transportation and the blood leaking out into the cardboard packaging, the blood level of MXE was estimated. After determination of the cardboard grammage (approx. 400 g/m(3) ) and the mean mass of the blood obtained after drying (0.1785 ± 0.0173 g per 1 mL), the estimated blood concentration of MXE was found to be 5.8 μg/mL. The high concentration of MXE in blood and urine and the circumstances of the case indicate an unintentional, fatal intoxication with this substance.


Biomedicalization and alcohol studies: implications for policy.
The reduction of alcohol problems to genetic and biological processes is not new; however, biomedicalization is progressively dominating how alcohol issues are viewed in the U.S. This paper illustrates the process of biomedicalization in the alcohol field by examining: 1) the organizational move of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to the National Institutes of Health in 1992; 2) the emphasis on biomedical goals in NIAAA's five-year Strategic Plan; 3) increased NIAAA funding of biomedical research from 1990-2002; and, 4) trends in the growing proportion of biomedical information provided in NIAAA's Reports to Congress. The implications of this dominance of the biomedical approach on policy are profound. As biomedicalization prevails as a dominant lens by which alcohol problems are framed, policymakers will tend to move towards individualistic solutions to social problems. Broader community and societal based efforts to understand and control alcohol problems may be increasingly replaced by a focus on individuals thereby omitting important environmental factors.


Bio-inspired transition metal-organic hydride conjugates for catalysis of transfer hydrogenation: experiment and theory.
Taking inspiration from yeast alcohol dehydrogenase (yADH), a benzimidazolium (BI(+) ) organic hydride-acceptor domain has been coupled with a 1,10-phenanthroline (phen) metal-binding domain to afford a novel multifunctional ligand (L(BI+) ) with hydride-carrier capacity (L(BI+) +H(-) ⇌L(BI) H). Complexes of the type [Cp*M(L(BI) )Cl][PF6 ]2 (M=Rh, Ir) have been made and fully characterised by cyclic voltammetry, UV/Vis spectroelectrochemistry, and, for the Ir(III) congener, X-ray crystallography. [Cp*Rh(L(BI) )Cl][PF6 ]2 catalyses the transfer hydrogenation of imines by formate ion in very goods yield under conditions where the corresponding [Cp*Ir(L(BI) )Cl][PF6 ] and [Cp*M(phen)Cl][PF6 ] (M=Rh, Ir) complexes are almost inert as catalysts. Possible alternatives for the catalysis pathway are canvassed, and the free energies of intermediates and transition states determined by DFT calculations. The DFT study supports a mechanism involving formate-driven RhH formation (90 kJ mol(-1) free-energy barrier), transfer of hydride between the Rh and BI(+) centres to generate a tethered benzimidazoline (BIH) hydride donor, binding of imine substrate at Rh, back-transfer of hydride from the BIH organic hydride donor to the Rh-activated imine substrate (89 kJ mol(-1) barrier), and exergonic protonation of the metal-bound amide by formic acid with release of amine product to close the catalytic cycle. Parallels with the mechanism of biological hydride transfer in yADH are discussed.


Comparison of the effect of cisapride and metoclopramide on morphine-induced delay in gastric emptying.
1. The effects of metoclopramide or cisapride on morphine-induced delay in gastric emptying in patients before surgery were compared. 2. Forty patients were allocated randomly to receive one of four premedications i.m.: placebo only, morphine 10 mg alone, morphine 10 mg with metoclopramide 10 mg and morphine 10 mg with cisapride 10 mg. Gastric emptying after each premedication was assessed indirectly from the rate of absorption of oral paracetamol. 3. Cisapride 10 mg reversed the delay in gastric emptying due to morphine. Its effects were significantly greater than those of metoclopramide 10 mg.


Development of a New Ultra-High-Precision Magnetic Abrasive Finishing for Wire Material Using a Rotating Magnetic Field.
In this paper, we propose a new ultra-high-precision magnetic abrasive finishing method for wire material which is considered to be difficult with the existing finishing process. The processing method uses a rotating magnetic field system with unbonded magnetic abrasive type. It is believed that this process can efficiently perform the ultra-high-precision finishing for producing a smooth surface finish and removing a diameter of wire material. For such a processing improvement, the following parameters are considered; rotational speed of rotating magnetic field, vibration frequency of wire material, and unbonded magnetic abrasive grain size. In order to evaluate the performance of the new finishing process for the wire material, the American Iron and Steel Institute (AISI) 1085 steel wire was used as the wire workpiece. The experimental results showed that the original surface roughness of AISI 1085 steel wire was enhanced from 0.25 µm to 0.02 µm for 60 s at 800 rpm of rotational speed. Also, the performance of the removed diameter was excellent. As the result, a new ultra-high-precision magnetic abrasive finishing using a rotating magnetic field with unbonded magnetic abrasive type could be successfully adopted for improving the surface roughness and removing the diameter of AISI 1085 steel wire material.


Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) spa type t127, Sequence Type (ST)1, quickly spreads and persists among young pigs.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clones other than Clonal Complex (CC)398, as CC1, have been isolated in pigs in some countries, and appeared to be prevalent in Italy. The aim of this study was to evaluate the capability of Sequence Type (ST)1, CC1, LA-MRSA clone to colonize and to be transmitted among piglets. Eighteen caesarean-derived/colostrum-deprived piglets of 35 days of age were assigned randomly to three groups: four seeder piglets were contaminated with a spa type t127, ST1, SCCmec V, MRSA (Group A), 10 MRSA-negative piglets were exposed to Group A after 2 days post-contamination, dpc (Group B) and 4 piglets were used as control group (Group C). Piglets were evaluated until 44 dpc (Group A) or at 42 days post-exposure, dpe (Group B) and then euthanized and necropsied. All nasal and skin cultures of Group A resulted MRSA-positive throughout the experiment starting from two dpc, while Group C tested always MRSA-negative. At first sampling, all Group B piglets became positive and remained positive throughout the experiment. This is the first colonization/transmission study with a CC1 LA-MRSA in pigs. The results add further knowledge on the ability of CC1 LA-MRSA to colonize pigs, and on colonization/transmission patterns, both suggesting good host adaptation.


Progressive increase of the Tpeak-Tend interval is associated with ischaemia-induced ventricular fibrillation in a porcine myocardial infarction model.
Repolarization indices of ECG have been widely assessed as predictors of ventricular arrhythmias. However, little is known of the dynamic changes of these parameters during continuous monitoring in acute ischaemic episodes. The objective of the study was to evaluate repolarization-related predictors of ventricular fibrillation (VF) during progression of experimental myocardial infarction. Myocardial infarction was induced in 27 pigs by 40-min balloon inflation in the left anterior descending coronary artery, and 12-lead ECG was continuously recorded. Rate-corrected durations of the total Tpeak-Tend intervals measured from the earliest T-wave peak to the latest T-wave end in any lead were determined at baseline and at minute 1, 2, 5, and then every 5th minute of occlusion. There were 7 early (1-3 min) and 10 delayed (15-30 min) VFs in 16 pigs. Baseline Tpeak-Tend did not differ between animals with and without VF. Tpeak-Tend interval rapidly increased immediately after balloon inflation and was greater in VF-susceptible animals at 2-15 min compared with the animals that never developed VF (P < 0.05). Tpeak-Tend was tested as a predictor of delayed VFs. Median Tpeak-Tend at 10th min of occlusion was higher in delayed VF group (n = 10) than in animals without VF (n = 11): 138 [IQR 121-148] ms vs. 111 [IQR 106-127] ms, P = 0.02. Tpeak-Tend ≥123 ms (10th min) predicted delayed VF episodes with HR = 4.5 95% CI 1.1-17.8, P = 0.031. Tpeak-Tend prolongation during ischaemia progression predicts VF in the experimental porcine myocardial infarction model and warrants further testing in clinical settings of acute coronary syndromes.


The concepts of family doctor and factors affecting choice of family doctors among Hong Kong people.
To identify concepts including misconceptions among the community members regarding family doctors, and determine factors affecting decisions on which doctor to consult in different clinical scenarios. Household telephone survey conducted between 4 and 13 September 2006. Hong Kong community. Cantonese-speaking Hong Kong residents aged 18 years or more were targeted. Randomly selected participants were asked to complete a questionnaire, which was designed based on a literature search and subsequent focus group discussions. Among the 1811 households with eligible subjects to survey, 1204 completed the questionnaire (response rate, 67%). More than 85% considered a family doctor to be the first doctor they wanted to see even if it was inconvenient. "Clearly knowing my physical conditions", "fast-acting and effective treatment", and "doctor with friendly and sincere attitude" were the three most important factors influencing the choice of a family doctor. When affected by flu-like symptoms, 65% would go to a private clinic, 20% to a general out-patient clinic, 6% to a designated clinic with staff approved by their respective medical insurance/medical benefit scheme, and 5% to a private hospital outpatient clinic. Among the latter two groups, 65% consulted the same doctor every time when they felt sick. More than 50% of those willing to have regular follow-up by a family doctor for hypertension and diabetes paid more than HK$300 per month. Approximately 64% might consider having regular follow-up at a general out-patient clinic by a nurse specialist. Hong Kong inhabitants already have their own ideas regarding how to care for their own health, and what kind of family doctors they prefer. This survey should help both doctors and health care policy makers to realign their current thinking, and thus provide a platform for the development of a primary care model unique to Hong Kong.


The suitability of cells from different tissues for use in tissue-engineered skin substitutes.
Tissue-engineered skin substitutes may be a future remedy for burn wounds and chronic wounds, as wound contraction and scar formation cannot be prevented with the current standard treatment. The aim of this study therefore was to identify readily available sources of fibroblasts suitable for dermal substitution. Three different tissues were studied: dermal tissue from split-skin graft, subcutaneous fat tissue and eschar tissue obtained through debridement of burn wounds. We determined the cellular profile and the cell numbers immediately after isolation and after 2 and 14 days of fibroblast culture using flow cytometry and cell counting with a cytometer. In addition, parts of the isolated cell suspensions were seeded directly into a porous collagen dermal substitute to investigate contraction over time. Various cell types were isolated from the three different tissues, but after 14 days of culturing predominantly fibroblasts (>90%) were detected. Keratinocytes, granulocytes and macrophages, if present, disappeared within 14 days. In the cell populations derived from dermal tissue, the percentage of myofibroblasts had decreased significantly by day 14 (from 8% to 3%, P=0.028). In contrast, this percentage had increased in the cell populations derived from fat and eschar (from 23% to 40% and from 20% to 38%, respectively). The fibroblast yield from dermal tissue after 2 weeks of culturing (50 x 10(6) cells/g of tissue) was significantly higher than the yield from fat and eschar tissue (2 x 10(6) cells/g of each tissue, P=0.029). Immunohistochemistry of collagen matrices seeded and cultured with fat- and eschar-derived cells revealed a high prevalence of myofibroblasts, whereas hardly any myofibroblasts were detected in the matrices seeded with dermal cells. The contraction of the eschar matrices was highest (74+/-6% remaining area), whereas dermal matrices contracted significantly less (92+/-7% remaining area, P=0.029) with intermediate contraction for fat matrices. We conclude that fibroblast cultures can be established from dermal tissue, fat tissue and eschar tissue. Dermis is the best fibroblast source for use in skin substitutes as it yields the highest numbers of fibroblasts with minimal numbers of myofibroblasts.


Simultaneous induction of non-canonical autophagy and apoptosis in cancer cells by ROS-dependent ERK and JNK activation.
Chemotherapy-induced reduction in tumor load is a function of apoptotic cell death, orchestrated by intracellular caspases. However, the effectiveness of these therapies is compromised by mutations affecting specific genes, controlling and/or regulating apoptotic signaling. Therefore, it is desirable to identify novel pathways of cell death, which could function in tandem with or in the absence of efficient apoptotic machinery. In this regard, recent evidence supports the existence of a novel cell death pathway termed autophagy, which is activated upon growth factor deprivation or exposure to genotoxic compounds. The functional relevance of this pathway in terms of its ability to serve as a stress response or a truly death effector mechanism is still in question; however, reports indicate that autophagy is a specialized form of cell death under certain conditions. We report here the simultaneous induction of non-canonical autophagy and apoptosis in human cancer cells upon exposure to a small molecule compound that triggers intracellular hydrogen peroxide (H(2)O(2)) production. Whereas, silencing of beclin1 neither inhibited the hallmarks of autophagy nor the induction of cell death, Atg 7 or Ulk1 knockdown significantly abrogated drug-induced H(2)O(2)-mediated autophagy. Furthermore, we provide evidence that activated extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) are upstream effectors controlling both autophagy and apoptosis in response to elevated intracellular H(2)O(2). Interestingly, inhibition of JNK activity reversed the increase in Atg7 expression in this system, thus indicating that JNK may regulate autophagy by activating Atg7. Of note, the small molecule compound triggered autophagy and apoptosis in primary cells derived from patients with lymphoma, but not in non-transformed cells. Considering that loss of tumor suppressor beclin 1 is associated with neoplasia, the ability of this small molecule compound to engage both autophagic and apoptotic machineries via ROS production and subsequent activation of ERK and JNK could have potential translational implications.


The N170 event-related potential differentiates congruent and incongruent gaze responses in gaze leading.
To facilitate social interactions, humans need to process the responses that other people make to their actions, including eye movements that could establish joint attention. Here, we investigated the neurophysiological correlates of the processing of observed gaze responses following the participants' own eye movement. These observed gaze responses could either establish, or fail to establish, joint attention. We implemented a gaze leading paradigm in which participants made a saccade from an on-screen face to an object, followed by the on-screen face either making a congruent or incongruent gaze shift. An N170 event-related potential was elicited by the peripherally located gaze shift stimulus. Critically, the N170 was greater for joint attention than non-joint gaze both when task-irrelevant (Experiment 1) and task-relevant (Experiment 2). These data suggest for the first time that the neurocognitive system responsible for structural encoding of face stimuli is affected by the establishment of participant-initiated joint attention.


RAPD analysis of the interspecific somatic hybrids: Solanum bulbocastanum (+) S. tuberosum.
The diploid Mexican species S. bulbocastanum (blb) was used as a source of late blight resistance in somatic hybridization with the potato (S. tuberosum, tbr) dihaploid H-8105. The produced 2x blb (+) 2x tbr H-8105 somatic hybrids did not retain the blb parent's characteristic high resistance to P. infestans. The revealed aneuploidy of blb (+) tbr H-8105 hybrids indicated a possible loss of individual blb chromosome(s) carrying the resistance genes. Four hybrid clones differing in terms of their ploidy, morphology and growth potential were analysed for the presence of all twelve blb chromosomes (linkage groups). The RAPD markers assigned to particular chromosomes were selected on the basis of the linkage map of S. bulbocastanum constructed by Naess et al., Mol. Gen. Genom. 265 (2001) 694-704. Of the 86 markers analysed, twelve (14%) were common for blb and H-8105, while 34 (40%) and 40 (46%) markers were specific for the blb and H-8105 genome, respectively; this confirms the differences between the nuclear genomes of the two species. Seventeen markers (20%) present in one or the other parent were absent in the hybrids, and only one new marker was found in the hybrids. The poorly growing, aneuploid and chimeric hybrids had the same band profiles as the well growing, morphologically normal hybrids, except for two bands that were present only in normal hybrids. The presence of eleven blb linkage groups in the blb (+) tbr H-8105 hybrids was confirmed. The markers specific for the second linkage group (chromosome 2) of blb were not present in the RAPD patterns of the somatic hybrids analysed, suggesting a loss or rearrangement of this chromosome in the combined nuclear genome of the hybrids.


The effect of drought on the development and yielding of two different varieties of the fodder broad bean (Vicia faba minor).
A factorial experiment was performed in the fodder broad bean to analyse effects of soil drought on the development and yield components of two varieties of different morphotype: 'Nadwiślański' (traditional) and 'Tim' (determinate growth habit). Plants were grown in Mitscherlich's pots under three different soil moistures: 70%, 50% and 30% of field water capacity. The soil water shortage contributed to a considerable depression in the developmental characteristics and yield traits of both varieties. Under all conditions, the variety 'Nadwiślański yielded more seeds than did 'Tim'. The traditional variety was more resistant to drought than the new 'Tim'.


[Postoperative acute pancreatitis (PAP). Direct personal experience].
Eight different cases of APP observed after intervents made near the pancreas (partial gastrectomy for ulcer, papillosphincteroplasty, DCP) are presented. The clinical stage, the therapeutic attempts, the results are studied. The clinical stage, the therapeutic attempts, the results are studied. In order to value the role of the pancreatic trauma in causing the APP the Authors have checked in addition 14 cases in which a direct action on the pancreas was present. In these cases noticeable amylasemic increases have not been observed except one cases of APP after DCP. Hypothesizing the role of a duodenal hyperpressure in causing the reflux of duodenal juice into the Wirsung then in causing an APP, the Authors report the results obtained after the introduction of a catheter into the duodenum in order to make it empty untily the renewal of peristalsis, during the papillosphincteroplasty and partial gastrectomy for ulcer. The Authors suggest that the duodenal emptying could be a method to prevent the APP. The prevention by the usually adopted drugs as aprotininum and glucagonum was ineffective, as well as other surgical techniques. High mortality: 5 cases on 8.


Travellers returning with measles from Thailand to Finland, April 2012: infection control measures.
Countries with no autochthonous measles run the risk of the virus being imported by travellers and transmitted to unprotected citizens. In April 2012, two travellers from Finland and one from Estonia were diagnosed with measles after returning from Phuket, Thailand. They were contagious on their return flights and subsequently exposed several individuals, prompting extensive infection control measures. Two secondary cases were detected: one child who had received one vaccine dose and another who was fully vaccinated.


Effect of Chalcogenophenes on Chiroptical Activity of Twisted Tetracenes: Computational Analysis, Synthesis and Crystal Structure Thereof.
The synthesis of multiply substituted acenes is still a relevant research problem, considering their applications and future potential. Here we present an elegant synthetic protocol to afford tetra-peri-substituted naphthalene and tetracene from their tetrahalo derivatives by a Pd(0)-catalyzed C-C cross-coupling method in a single step. The newly synthesized tetracenes were characterized by NMR, HRMS, UV-vis spectrophotometry, and single-crystal X-ray diffraction (SCXRD). In addition, the first systematic computational study of the effect of chalcogenophenyl substitutions on the chiroptical properties of twistacenes was reported here. The gas phase computational studies using density functional theory (DFT) on a series of chalcogenophene-substituted tetracenes revealed that their chiroptical activity could be systematically increased via the atomistic tuning of peripheral substituents.


Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model.
Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative phenotype. Accordingly, Fn has been implicated in numerous wound healing studies, yet remains untested in its fibrillar conformation as found in fetal skin. Here, we show that high extensional (∼1.2 ×105 s-1) and shear (∼3 ×105 s-1) strain rates in rotary jet spinning (RJS) can drive high throughput Fn fibrillogenesis (∼10 mL/min), thus producing nanofiber scaffolds that are used to effectively enhance wound healing. When tested on a full-thickness wound mouse model, Fn nanofiber dressings not only accelerated wound closure, but also significantly improved tissue restoration, recovering dermal and epidermal structures as well as skin appendages and adipose tissue. Together, these results suggest that bioprotein nanofiber fabrication via RJS could set a new paradigm for enhancing wound healing and may thus find use in a variety of regenerative medicine applications.


[Stromal tumour of the small intestine as a rare cause of gastrointestinal bleeding].
The study presents a difficult to detect case of tumour of the small intestine in a 71-year-old patient. The first and only symptom of the sickness was gastrointestinal bleeding. Routine diagnostic methods failed to detect its source. Successful diagnosis was obtained only intraoperatively.


Angiotensin II stimulates protein kinase D-dependent histone deacetylase 5 phosphorylation and nuclear export leading to vascular smooth muscle cell hypertrophy.
Angiotensin II (Ang II) induces the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs), which is implicated in the pathogenesis of hypertension, atherosclerosis, and diabetes. In this study, we tested the hypothesis that histone deacetylases 5 (HDAC5) and its signal pathway play a role in Ang II-induced VSMC hypertrophy. VSMCs were isolated from the thoracic aortas of male Sprague-Dawley rats and treated with Ang II. We found that Ang II rapidly stimulated phosphorylation of HDAC5 at Serine259/498 residues in a time- and dose- dependent manner. Ang II receptor-1, protein kinase C, and protein kinase D1 (PKD1) mediated HDAC5 phosphorylation. Furthermore, we observed that Ang II stimulated HDAC5 nuclear export, which was dependent on its PKD1-dependent phosphorylation. Consequently, both inhibiting PKD1 and HDAC5 Serine259/498 to Alanine mutant significantly attenuated Ang II-induced myocyte enhancer factor-2 (MEF2) transcriptional activity and protein synthesis in VSMCs. These findings demonstrate for the first time that PKD1-dependent HDAC5 phosphorylation and nuclear export mediates Ang II-induced MEF2 activation and VSMC hypertrophy, and suggest that PKD1 and HDAC5 may emerge as potential targets for the treatment of pathological vascular hypertrophy.


Which primary care model? A qualitative analysis of ward-based outreach teams in South Africa.
Globally, models of extending universal health coverage through primary care are influenced by country-specific systems of health care and disease management. In 2015 a rapid assessment of the ward-based outreach component of primary care reengineering was commissioned to understand implementation and rollout challenges. This article aims to describe middle- and lower-level managers' understanding of ward-based outreach teams (WBOTs) and the problems of authority, jurisdiction and practical functioning that arise from the way the model is constructed and has been operationalised. Data are drawn from a rapid assessment of National Health Insurance (NHI) pilot sites in seven provinces. The study used a modified version of CASCADE. Peer-review teams of public health researchers and district/sub-district managers collected data in two sites per province between March and July 2015. Respondents unequivocally support the strategy to extend primary health care services to people in their homes and communities both because it is responsive to the family context of individual health and because it reaches marginal people. They, however, identify critical issues that arise from basing WBOTs in facilities, including unspecific team leadership, inadequate supervision, poorly constituted teams, limited community reach and serious infrastructural and material under-provision. Many of the shortcomings of a facility-based extension model can be addressed by an independently resourced, geographic, community-based model of fully constituted teams that are clinically and organisationally supported in an integrated district health system. However, a community-oriented primary care approach will still have to grapple with overarching framework problems.


Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer.
We wished to critically examine the level of activity of weekly paclitaxel in a patient population with well-characterized platinum/paclitaxel-resistant (3-week schedule) ovarian cancer. Eligibility criteria for this phase II trial included the following: ovarian and fallopian tube cancers or primary carcinoma of the peritoneum; prior initial therapy with platinum/paclitaxel; and failure to respond to treatment (progression or stable disease as best response), or a response duration of less than 3 months, or if the response was more than 3 months, retreatment with both agents required and failure to respond a second time or the response duration was less than 3 months. Measurable or assessable disease (CA-125 response criteria) was required. Patients received weekly paclitaxel (80 mg/m(2)) until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. Fifty-three patients (52 assessable for toxicity and 51 for response) were entered onto this multi-institution trial. Of 248 total cycles (887 doses), only 13 (1%) were modified (dose reduction or treatment delay) because of side effects. Therapy was discontinued in five patients because of toxicity (four because of peripheral neuropathy, and one because of painful fingernail beds). Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an objective response (four by CA-125 criteria, and nine by > or = 50% reduction of measurable disease). Weekly paclitaxel (80 mg/m(2)) is generally well tolerated and is an active second-line regimen against ovarian cancer that has demonstrated resistance to platinum/paclitaxel delivered on an every-3-week schedule.


Cerebral aspergillosis presenting as a mass lesion.
Fungal infections of the central nervous system (CNS) are almost always a surprising finding. Their presentation is usually subtle, often without any diagnostic characteristics, and they are frequently mistaken for pyogenic abscesses, or brain tumors. Aspergillosis of the central nervous system is an uncommon infection, mainly occurring in immunocompromised patients. It may present in several forms, including meningitis, mycotic aneurysms, infarcts and a tumoral form. We report an intracranial granuloma due to Aspergillus fumigatus involving the anterior cranial fossa and the frontal lobe. The clinical symptoms began one year before admission. Final diagnosis was made after craniotomy. The patient was treated with an extensive excision of the cerebral mass and medical antifungal therapy (intravenous amphotericin B), but she failed to respond to these treatments and died.


Study of calcium absorption in man: a kinetic analysis and physiologic model.
A physical model of calcium absorption was developed from analysis of data obtained on 23 subjects, including 13 patients having a variety of abnormalities of calcium metabolism. The model was tested and found consistent in all subjects studied. This technique provides a quantitative description of the rate of entry of oral dose of (47)Ca into the circulation as a function of time by analysis of serum or forearm radioactivity in response to intravenous and oral administration of (47)Ca. The kinetics of the absorption process as proposed by the model are characterized by an initial delay phase of 15-20 min, by a maximal rate of absorption at 40-60 min after ingestion, and by 95% completion of the absorption within 2(1/2) hr. Partial identification of the physiological counterparts of the model was possible by introduction of the isotope at various levels of the gut. Although the region of the duodenum was found to have the greatest rate of absorption per unit length in normal subjects, it was least responsive to stimulation by parathyroid hormone and suppression by calcium loading. Furthermore, the response of the gut to parathyroid hormone was delayed, whereas the suppression of absorption by intravenous or oral calcium loading was rapid and dramatic. The implications of these observations are discussed.


The accuracy of nurses' knowledge about survival rates for early cancer in four sites.
To consider the role of nurse education in the development of a body of professional knowledge about cancer, trained nurses (n = 372), learners (n = 160) and auxiliaries (n = 238) were asked, by means of a postal questionnaire, to estimate the 5-year survival rates for early cancers in four sites: breast, cervix, skin and lung. Among trained nurses only a minority had accurate knowledge; four to five out of ten answering accurately for breast, cervix and lung, but only two in ten for skin. All three grades were less well informed about skin cancer. For all sites trained nurses were more likely to be accurate than learners or auxiliaries, but the variations were statistically significant only for skin and cervix. Taking auxiliaries as a baseline the degree of differentiation between their knowledge and that of the SRNs was disappointing. Nurses' reliance on bedside experience as their major source of information about cancer is suggested as one explanation for their levels of knowledge. The implications both for the nurse's role in health education and for nursing education are discussed.


Seasonal distributions of the western cherry fruit fly (Diptera: Tephritidae) among host and nonhost fruit trees.
Seasonal distributions of the western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), in sweet cherry (Prunus avium (L.) L.) (major host), black hawthorn (occasional developmental host) (Crataegus douglasii Lindley), and other trees were determined in a ponderosa pine ecosystem in Washington state, USA. The hypothesis that most fly dispersal from cherry trees occurs after fruit senesce or drop was tested, with emphasis on movement to black hawthorn trees. Sweet cherry fruit developed earlier than black hawthorn, bitter cherry (common host), choke cherry, and apple fruit. Flies were usually captured first in sweet cherry trees but were caught in bitter cherry and other trees throughout the season. Peak fly capture periods in sweet cherry began around the same time or slightly earlier than in other trees. However, peak fly capture periods in black hawthorn and other nonsweet cherry trees continued after peak periods in sweet cherry ended, or relative fly numbers within sweet cherry declined more quickly than those within other trees. Larvae were reared from sweet and bitter cherry but not black hawthorn fruit. Results provide partial support for the hypothesis in that although R. indifferens commonly disperses from sweet cherry trees with fruit, it could disperse more, or more flies are retained in nonsweet cherry trees after than before sweet cherries drop. This could allow opportunities for the flies to use other fruit for larval development. Although R. indifferens infestation in black hawthorn was not detected, early season fly dispersal to this and other trees and fly presence in bitter cherry could make fly management in sweet cherry difficult.


Using multivariate decoding to go beyond contrastive analyses in consciousness research.
Contrasting conditions with and without awareness has been the preferred method for investigating the neural correlates of consciousness (NCC) for decades, yet recently it has been suggested that further insights can be made by moving beyond this method, specifically by meticulously controlling that potential precursors and consequences of the NCC are not mistaken for an NCC. Here, we briefly review the advantages and potential pitfalls of existing paradigms going beyond the contrastive method, and we propose multivariate decoding of neural activity patterns as a supplement to other methods. Specifically, we emphasize the ability of multivariate decoding to detect which patterns of neural activity are consistently predictive of conscious experiences at the single trial level. This is relevant as the "NCC proper" is expected to be consistently predictive whereas processes that are consequences of consciousness may not occur on every trial (making them less predictive) and prerequisites of consciousness may be present on some trials without conscious experience (making them less predictive).


The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.
In a previous study we compared the influence of several growth factors on cancer cells in culture and observed that transforming growth factor-beta (TGF-beta) enhanced the invasiveness of several breast cancer cell lines. The objective of the present study was to determine the influence of three unique antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells. The chemotactic activity of TGF-beta was assayed in vitro using collagen IV-coated transwell chambers with either MCF-7 or MDA-MB-231 human breast cancer cells. The cells were pretreated with antiestrogen for 4 days, harvested and placed in the upper transwell chamber. TGF-beta was added to the lower chamber and cell migration and collagenase release were determined following a 6-hour incubation. In this study TGF-beta enhanced the chemotaxis of both cell types with a much greater effect on the MDA-MB-231 cells. However, TGF-beta-mediated chemotaxis of the MCF-7 cells was inhibited by antiestrogen pretreatment while TGF-beta-mediated chemotaxis of the MDA-MB-231 cells was not altered. Further, neither TGF-beta nor antiestrogen treatment altered collagenase release from either cell line. The data demonstrate that pure antiestrogens are capable of inhibiting TGF-beta-mediated chemotaxis in estrogen receptor (ER)-positive breast cancer cells by a mechanism which is independent of collagenase release. Finally, the results of this study suggest a coupling of the TGF-beta and ER signaling pathways and indicate that TGF-beta may be an important therapeutic target for the treatment or inhibition of breast cancer metastasis.


Video-based training to improve perceptual-cognitive decision-making performance of Australian football umpires.
Decision-making is a central component of the in-game performance of Australian football umpires; however, current umpire training focuses largely on physiological development with decision-making skills development conducted via explicit lecture-style meetings with limited practice devoted to making actual decisions. Therefore, this study investigated the efficacy of a video-based training programme, aimed to provide a greater amount of contextualised visual experiences without explicit instruction, to improve decision-making skills of umpires. Australian football umpires (n = 52) were recruited from metropolitan and regional Division 1 competitions. Participants were randomly assigned to an intervention or control group and classified according to previous umpire game experience (i.e., experienced; less experienced). The intervention group completed a 12-week video-based decision-making training programme, with decision-making performance assessed at pre-training, and 1-week retention and 3-week retention periods. The control group did not complete any video-based training. Results indicated a significant Group (intervention; Control) × Test interaction (F(1, 100) = 3.98; P = 0.02, partial ῆ2 = 0.074), with follow-up pairwise comparisons indicating significant within-group differences over time for the intervention group. In addition, decision-making performance of the less experienced umpires in the intervention group significantly improved (F(2, 40) = 5.03, P = 0.01, partial ῆ2 = 0.201). Thus, video-based training programmes may be a viable adjunct to current training programmes to hasten decision-making development, especially for less experienced umpires.