Epizootic hemorrhagic disease outbreak in a captive facility housing white-tailed deer (Odocoileus virginianus), bison (Bison bison), elk (Cervus elaphus), cattle (Bos taurus), and goats (Capra hircus) in Colorado, U.S.A.
An ungulate research facility in Fort Collins, Colorado, U.S.A., experienced mortality in white-tailed deer (Odocoileus virginianus) because of epizootic hemorrhagic disease virus (EHDV) infection from 20 August 2007 through 26 September 2007. Epizootic hemorrhagic disease virus (EHDV) was detected by reverse transcriptase polymerase chain reaction and virus isolation from the spleen and lung tissues of two white-tailed deer. Virus neutralization tests were performed on pre- and postoutbreak sera from other species maintained in the same facility, including bison (Bison bison), elk (Cervus elaphus), domestic cattle (Bos taurus), and domestic goats (Capra hircus), as well as postoutbreak sera from the surviving white-tailed deer. Serum samples that represented all species in the facility neutralized EHDV-1 and EHDV-2 either before or after the outbreak. The animals that neutralized EHDV-1 did not neutralize EHDV-2. No clinical signs attributable to EHDV infection were noted in any of the species other than the deer during the outbreak. Although experimental EHDV infections have been reported in bison and elk, natural exposures have not been previously documented in these species in North America. The roles that elk, bison, cattle, and goats might play in the epidemiology of EHDV in a close-contact multispecies situation remain unknown.


A questionnaire technique for assessing the stress at work.
Subjective perception of the stress at work is a phenomenon reflecting the experience-mediated relationship between the sum of objective conditions of work and the sum of individual's traits available to cope with demands of the work environment. This relationship is mirrored in the function of the whole organism and can be described using the formula S = f (E, D), where S = the state of the organism, E = exposure (i.e. the sum of all stressors the organism is exposed to), and D = disposition (i.e. the sum of traits the organism has available to cope with these stressors). Based on these theoretical considerations, a questionnaire has been developed as a tool for assessing the work stress in different groups of occupations. This "Work Stress Assessment" (WSA) questionnaire was used in a group of 4800 female employees from various branches of the printing industry. Of a total of 160 questionnaire items, 98 items were selected and used to assess the workload in these employees, using a 5-point rating scale of evaluation. The responses were processed statistically, separately for 3531 blue-collar and 1269 white-collar respondents. The use of the factor analysis method revealed that the two groups of jobs had 16 factors in common, 3 factors were specific for blue-collar and 2 factors for white-collar jobs. Judged by factor components, the responses of subjects were well structured and the perceived stress at work turned out to well reflect the reality of conditions of work, which confirms the construct validity of this methodical approach based on the subjective perception of occupational stress. High coefficients of consistency (0.959 for blue-collar and 0.946 for white-collar occupations) point to the reliability of this questionnaire technique. Thus, the WSA questionnaire appears to suitably complement the other methodical approaches aimed at assessing the stress at work in different groups of occupations.


Subpopulations of regulatory T cells in rheumatoid arthritis, systemic lupus erythematosus, and Behcet's disease.
Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and activated Treg (aTreg), have been discovered. The authors investigated the relationship between the change of Treg, aTreg and rTreg and autoimmune diseases. Treg cells and those subpopulations were analyzed by using the human regulatory T cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13 systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls. The proportion of Treg cells was significantly lower in RA (3.8% ± 1.0%) (P < 0.001) and BD (3.3% ± 0.5%) (P < 0.01) compared to healthy controls (5.0% ± 1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% ± 0.2%) (P = 0.008) and BD (0.3% ± 0.1%) (P = 0.013) compared to healthy controls (0.6% ± 0.3%). The rTreg cells showed no significant differences. The ratio of aTreg to rTreg was lower in RA patients (0.4% ± 0.2%) than that in healthy controls (0.7% ± 0.4%) (P = 0.002). This study suggests that the decrement of aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations would be more informative than total Treg cells in investigating mechanism of autoimmune disease.


IPC synthase as a useful target for antifungal drugs.
Inositol phosphorylceramide (IPC) synthase is a common and essential enzyme in fungi and plants, which catalyzes the transfer of phosphoinositol to the C-1 hydroxy of ceramide to produce IPC. This reaction is a key step in fungal sphingolipid biosynthesis, therefore the enzyme is a potential target for the development of nontoxic therapeutic antifungal agents. Natural products with a desired biological activity, aureobasidin A (AbA), khafrefungin, and galbonolide A, have been reported. AbA, a cyclic depsipeptide containing 8 amino acids and a hydroxyl acid, is a broad spectrum antifungal with strong activity against many pathogenic fungi such as Candida spp., Cryptococcus neoformans, and some Aspergillus spp. Khafrefungin, an aldonic acid ester with a C22 long alkyl chain, has antifungal activity against C. albicans, Cr. Neoformans, and Saccharomyces cerevisiae. Galbonolide A is a 14-membered macrolide with fungicidal activity against clinically important strains, and is especially potent against Cr. neoformans. These classes of natural products are potent and specific antifungal agents. We review current progress in the development of IPC synthase inhibitors with antifungal activities, and present structure-activity relationships (SAR), physicochemical and structural properties, and synthetic methodology for chemical modification.


Immune gene and cell enrichment is associated with a good prognosis in ependymoma.
Approximately 50% of children with ependymoma will suffer from tumor recurrences that will ultimately lead to death. Development of more effective therapies and patient stratification in ependymoma mandates better prognostication. In this study, tumor gene expression microarray profiles from pediatric ependymoma clinical samples were subject to ontological analyses to identify outcome-associated biological factors. Histology was subsequently used to evaluate the results of ontological analyses. Ontology analyses revealed that genes associated with nonrecurrent ependymoma were predominantly immune function-related. Additionally, increased expression of immune-related genes was correlated with longer time to progression in recurrent ependymoma. Of those genes associated with both the nonrecurrent phenotype and that positively correlated with time to progression, 95% were associated with immune function. Histological analysis of a subset of these immune function genes revealed that their expression was restricted to a subpopulation of tumor-infiltrating cells. Analysis of tumor-infiltrating immune cells showed increased infiltration of CD4(+) T cells in the nonrecurrent ependymomas. No genomic sequences for SV40, BK, JC, or Merkel polyomaviruses were found in nonrecurrent ependymoma. This study reveals that up-regulation of immune function genes is the predominant ontology associated with a good prognosis in ependymoma and it provides preliminary evidence of a beneficial host proinflammatory and/or Ag-specific immune response.


Solvent-Induced Formation of Novel Ni(II) Complexes Derived from Bis-Thiosemicarbazone Ligand: An Insight from Experimental and Theoretical Investigations.
In this work, we report solvent-induced complexation properties of a new N2S2 tetradentate bis-thiosemicarbazone ligand (H2LI), prepared by the condensation of 4-phenylthiosemicarbazide with bis-aldehyde, namely 2,2'-(ethane-1,2-diylbis(oxy)dibenzaldehyde, towards nickel(II). Using ethanol as a reaction medium allowed the isolation of a discrete mononuclear homoleptic complex [NiLI] (1), for which its crystal structure contains three independent molecules, namely 1-I, 1-II, and 1-III, in the asymmetric unit. The doubly deprotonated ligand LI in the structure of 1 is coordinated in a cis-manner through the azomethine nitrogen atoms and the thiocarbonyl sulfur atoms. The coordination geometry around metal centers in all the three crystallographically independent molecules of 1 is best described as the seesaw structure. Interestingly, using methanol as a reaction medium in the same synthesis allowed for the isolation of a discrete mononuclear homoleptic complex [Ni(LII)2] (2), where LII is a monodeprotonated ligand 2-(2-(2-(2-(dimethoxymethyl)phenoxy)ethoxy)benzylidene)-N-phenylhydrazine-1-carbothioamide (HLII). The ligand LII was formed in situ from the reaction of LI with methanol upon coordination to the metal center under synthetic conditions. In the structure of 2, two ligands LII are coordinated in a trans-manner through the azomethine nitrogen atom and the thiocarbonyl sulfur atom, also yielding a seesaw coordination geometry around the metal center. The charge and energy decomposition scheme ETS-NOCV allows for the conclusion that both structures are stabilized by a bunch of London dispersion-driven intermolecular interactions, including predominantly N-H∙∙∙S and N-H∙∙∙O hydrogen bonds in 1 and 2, respectively; they are further augmented by less typical C-H∙∙∙X (where X = S, N, O, π), CH∙∙∙HC, π∙∙∙π stacking and the most striking, attractive long-range intermolecular C-H∙∙∙Ni preagostic interactions. The latter are found to be determined by both stabilizing Coulomb forces and an exchange-correlation contribution as revealed by the IQA energy decomposition scheme. Interestingly, the analogous long-range C-H∙∙∙S interactions are characterized by a repulsive Coulomb contribution and the prevailing attractive exchange-correlation constituent. The electron density of the delocalized bonds (EDDB) method shows that the nickel(II) atom shares only ~0.8|e| due to the σ-conjugation with the adjacent in-plane atoms, demonstrating a very weak σ-metalloaromatic character.


Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25.
Mutations in the forkhead-like 7 (FKHL7) gene have been recently shown to cause juvenile glaucoma and anterior segment anomalies. We report on a three-generation family with Axenfeld-Rieger syndrome (ARS), harboring an alteration in the FKHL7 gene. Genetic linkage analyses excluded the ARS phenotype from chromosomes 4q25 and 13q14, the locations of the PITX2 and RIEG2 loci, respectively. Evidence of linkage was observed with markers at 6p25, near the FKHL7 gene. Direct sequencing of FKHL7 detected a C67T mutation that segregated with the ARS phenotype in this family, but was not detected in over 80 control chromosomes. This mutation is predicted to cause a nonsense mutation of the FKHL7 protein (Gln23Stop) upstream of the forkhead DNA-binding domain, and thus to generate a truncated FKHL7 protein product. This discovery broadly implicates FKHL7 in ocular, craniofacial, dental, and umbilical development.


A clampless anastomosis technique using the aortic cannula mounted by a prosthetic graft for a severely calcified aorta in a patient with subclavian steal syndrome.
Patients with severely calcified aorta are at high risk of embolic stroke during surgery and it is not feasible to clamp the aorta, necessitating alternative surgical strategies. We present a clampless anastomosis technique using the aortic cannula mounted by a prosthetic graft for a severely calcified aorta in a patient with subclavian-vertebral artery steal syndrome.


Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale and study design.
Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post-MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a prospective, randomized, double-blind, placebo-controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3-month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post-MI LV remodeling.


American Football Position-Specific Neurometabolic Changes in High School Athletes: A Magnetic Resonance Spectroscopic Study.
Reports estimate between 1.6-3.8 million sports-related concussions occur annually, with 30% occurring in youth male American football athletes. Many studies report neurophysiological changes in these athletes, but the exact reasons for these changes remain elusive. Investigation of injury mechanics highlights a need to address how player position might impact these changes. Here, 55 high school American football athletes (20 linemen; 35 non-linemen) underwent magnetic resonance spectroscopy four times over the course of a football season-once prior to the season (Pre), twice during (In1, In2), and once following (Post) to quantify metabolites (N-acetyl aspartate, choline, creatine, myo-inositol, and glutamate/glutamine) in the dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1). Head acceleration events (HAEs) were monitored at each practice and game. Spectroscopic and HAE data were analyzed by imaging session and player position. Linear regression analyses were conducted between metabolite levels and HAEs, and metabolite levels in football athletes were compared with age-and gender-matched non-contact athletes. Across-season (i.e., between Pre and In1, In2, Post), different DLPFC and M1 metabolites decreased (p < 0.05) according to player position (i.e., linemen vs. non-linemen). The majority of regression results involved DLPFC metabolites in linemen, where metabolite levels were higher from Pre to Post, with increasing HAE load. Comparisons with control athletes revealed higher metabolite levels in football athletes both before and after the season. This study highlights the importance of player position when conducting analyses on American football athletes and demonstrates elevated DLPFC and M1 brain metabolites in football athletes compared with control athletes at both Pre and Post, suggesting potential HAE-related neurocompensatory mechanisms.


Predictive Significance of Claudin-3 for Epithelial Barrier Dysfunction in Chronic Rhinosinusitis With Nasal Polyps.
The abnormal expression of tight junction (TJ) plays a vital role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, there is no appropriate tool to distinguish and diagnose epithelial barrier defects in clinical practice. This study aimed to evaluate the predictive value of claudin-3 for epithelial barrier dysfunction in CRSwNP. In this study, TJ protein levels were evaluated by real-time quantitative polymerase chain reaction, immunofluorescent, and immunohistochemistry staining in control subjects and CRSwNP patients. The receiver operating characteristic (ROC) curve was created to assess the predictive value of TJ breakdown in clinical outcomes. In vitro, human nasal epithelial cells were cultured at the air-liquid interface to analyze the transepithelial electrical resistance (TER) level. The expression levels of occludin, tricellulin, claudin-3, and claudin-10 were decreased (all P < 0.05), and those of claudin-1 was increased (P < 0.05) in CRSwNP patients as compared to healthy subjects. Additionally, claudin-3 and occludin levels were negatively correlated with the computed tomography score in CRSwNP (all P < 0.05), and the ROC curve indicated that the claudin-3 level had the most predictive accuracy in evaluating epithelial barrier disruption (area under the curve = 0.791, P < 0.001). Finally, the time-series analysis showed the highest correlation coefficient between TER and claudin-3 (cross-correlation function = 0.75). In this study, we suggest that claudin-3 could be a valuable biomarker for predicting nasal epithelial barrier defects and disease severity in CRSwNP.


Spontaneous Coronary Artery Dissection: Review of Possible Pathophysiological Risk Factors.
Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS) that typically affects the younger and healthier female population without the typical ACS risk factors such as hypertension, diabetes, or hyperlipidemia. The clinical presentation of SCAD can be diverse and the diagnosis is typically by coronary angiography but also can require advanced imaging such as intravascular ultrasound or optical coherence tomography. Past studies have shown the atypical patient characteristics of SCAD patients among ACS patients. The main challenge is that the exact pathophysiology of SCAD is unknown. Potential pathophysiological risk factors are discussed including fibromuscular dysplasia, other arteriopathies, pregnancy and female sex hormone changes, migraines, inflammatory conditions, and stress. The current understanding of these risk factors along with potential pathophysiological mechanisms are discussed. There still remain many areas of additional investigation in understanding this rare cause of ACS.


Free and bound tryptophan in human plasma during the perinatal period.
The concentration of tryptophan and the degree of binding of the amino acid to protein were examined in human plasma during the perinatal period. Both total and unbound (free) tryptophan were higher in cord vein plasma than in the maternal circulation, the concentration gradient being approximately 1 : 2. The proportion of the total plasma tryptophan concentration that was not bound to protein was less in cord vein plasma than in the maternal circulation. After birth the proportion in infant plasma fell significantly. Both total and free tryptophan fell during the first 24 hours of postnatal life. Total tryptophan returned to the cord vein plasma level 6--8 days after birth whilst free tryptophan failed to increase during the period of the observations. In premature infants total and free tryptophan also declined in concentration 12--24 hours after birth, suggesting the phenomenon to be related to birth rather than to gestational age. Phenylalanine remained unchanged whilst tyrosine increased in concentration during the first 80 hours of postnatal life. Thus, the availability of tryptophan to the tissues appears to decline during the immediate postnatal period and the results suggest that the requirement for tryptophan during this time may exceed the supply from standard artifical milk preparations.


Sex Differences in the Correlation between Fatigue Perception and Regional Gray Matter Volume in Healthy Adults: A Large-Scale Study.
The relationship between fatigue perception and regional gray matter volume (rGMV) has seldom been studied in healthy adults. Therefore, this study aimed to analyze sex differences in the correlation between rGMV and fatigue perception using Chalder's fatigue questionnaire (CFQ). The CFQ was used to analyze the sexual features of rGMV related to the degree of perceived fatigue in 2955 healthy adults (male = 1560, female = 1395) of various ages (20-89 years, median 56). A higher CFQ score denotes a higher perceived fatigue level by the participant. According to the CFQ scores in males, the volumes of the right orbital part of the inferior frontal gyrus and left precuneus were negatively correlated (i.e., smaller rGMV had a higher CFQ score), whereas the left angular gyrus was positively correlated. In females, the right inferior temporal gyrus was negative, whereas the left middle temporal gyrus and right putamen were positive (i.e., larger rGMV had a higher CFQ score). The lack of identified regions in this large-scale study between males and females might be related to sex differences in clinical or pathological fatigue morbidities. Additionally, the sex differences in the negative or positive correlations between rGMV and fatigue perception may contribute to a better understanding of the neuronal mechanism in the early stages of fatigue development.


Comparison of the Rate of Posterior Capsule Opacification Following Combined Treatment With Topical Dexamethasone 0.1% Plus Ketorolac 0.5% Eye Drops Versus Dexamethasone 0.1% Alone: A Two-Year, Randomized Clinical Investigation.
Background and aim The use of non-steroidal anti-inflammatory drugs in animals decreases the incidence of posterior capsular opacification (PCO) following cataract surgery. We evaluated the rate of PCO in patients with cataract surgery and foldable "in the bag" posterior chamber intraocular lens (PC-IOL) implantation treated with combined dexamethasone 0.1% plus ketorolac tromethamine 0.5% versus dexamethasone 0.1% alone. Materials and methods A total of 114 eyes of 101 patients underwent uneventful corneal small-incision phacoemulsification with primary implantation of a foldable acrylic PC-IOL (AcrySof®, Alcon, Fort Worth, USA). Postoperatively for four weeks, group 1 eyes were treated with dexamethasone 0.1% plus ketorolac tromethamine 0.5% ophthalmic solutions four times daily for each whereas group 2 eyes were treated with dexamethasone 0.1% alone. Other regiments were the same for each group. Patients were evaluated between one- and four-year following surgery. The frequency and timing of severe PCO following surgery that needed Nd:YAG laser posterior capsulotomy were recorded and evaluated. Results The mean (SEM) age of group 1 (n = 54) and group 2 (n = 60) at operation was similar (62.8 ± 2.2 vs. 60.6 ± 1.7 years, respectively). Eighty-eight patients had unilateral cataract and 13 cases had bilateral disease. Overall, the mean follow-up duration was 24.7 months postoperatively (range, 15-48). Clinically significant PCO that finally needed Nd:YAG laser application developed in two eyes (3.7%) in group 1 and in four eyes (6.6%) in group 2, and the difference was not statistically significant (p>0.05). The mean month at capsulotomy was 26.5 in group 1 and 24.3 months in group 2 eyes (p>0.05). Conclusions Topical instillation of ketorolac ophthalmic solution in the immediate period after phacoemulsification and PC-IOL implantation did not seem to influence the incidence of PCO formation two years after cataract surgery.


[Why patients lose weight after bariatric operations].
The obesity epidemic is in Germany as well as worldwide a major health problem which is associated with increased morbidity and mortality. Bariatric surgery is currently the most effective therapy for significant and sustained weight loss. The most common form of bariatric surgery worldwide is Roux-en-Y gastric bypass surgery. The underlying mechanisms behind the superiority of this procedure are unclear and remain to be elucidated, but recent findings suggest that gastrointestinal hormones play an important role rather than malabsorption or restriction. It appears that gastric bypass surgery alters the physiology of weight regulation and eating behaviour in patients who have undergone the procedure. Gastrointestinal hormones have recently been found to be an important element in the physiology of appetite regulation due to the signals from the periphery to the brain. It is the purpose of this article to review the current knowledge about the regulation of body weight and eating behaviour by gastrointestinal hormones and how their levels are altered after bariatric surgery.


Helicobacter pylori and coronary heart disease: which directions for future studies?
Classical risk factors explain the pathogenesis of coronary heart disease (CHD) in only a proportion of cases; therefore, the need to investigate the possible role of "new" agents has incited intense research. Since 1994, a number of studies regarding the possible involvement of Helicobacter pylori (H. pylori) have been published with conflicting results. Establishing a causal link between this infection and CHD would be of major public health importance, since the eradication of the bacterium is easy and much less expensive than long-term treatment of the other risk factors. The main cause of this discordance was the vast heterogeneity of such studies: sufficiently powerful design was found only in few investigations, CHD was defined with a low degree of homogeneity, biases were obvious in the control groups, thus giving room for large variation in the adjustment of potential confounding factors. The present paper attempts to highlight the future directions towards which research should be headed in this area to establish a causal role of H. pylori infection in the pathogenesis of CHD. Future research should take three directions: 1) prospective population-based studies in which the incidence or the recurrence of CHD be evaluated in correlation with H. pylori status, 2) intervention trials, focusing separately on the chronic and acute phases of coronary heart disease and, 3) studies of physiopathology (both in the animal model and humans) to understand the potential biological plausibility.


Changes in fibre-adherent and fluid-associated microbial communities and fermentation profiles in the rumen of cattle fed diets differing in hay quality and concentrate amount.
The rumen microbiota enable important metabolic functions to the host cattle. Feeding of starch-rich concentrate feedstuffs to cattle has been demonstrated to increase the risk of metabolic disorders and to significantly alter the rumen microbiome. Thus, alternative feeding strategies like the use of high-quality hay, rich in sugars, as an alternative energy source need to be explored. The aim of this study was to investigate changes in rumen microbial abundances in the liquid and solid-associated fraction of cattle fed two hay qualities differing in sugar content with graded amounts of starchy concentrate feeds using Illumina MiSeq sequencing and quantitative polymerase chain reaction. Operational taxonomic units clustered separately between the liquid and the solid-associated fraction. Phyla in the liquid fraction were identified as mainly Firmicutes, Proteobacteria and Bacteroidetes, whereas main phyla of the fibre-associated fraction were Bacteroidetes, Fibrobacteres and Firmicutes. Significant alterations in the rumen bacterial communities at all taxonomic levels as a result of changing the hay quality and concentrate proportions were observed. Several intermicrobial correlations were found. Genera Ruminobacter and Fibrobacter were significantly suppressed by feeding sugar-rich hay, whereas others such as Selenomonas and Prevotella proliferated. This study extends the knowledge about diet-induced changes in ruminal microbiome of cattle.


Striatal hypermetabolism in limbic encephalitis.
Striatal hypermetabolism on 18FDG-PET scan is a neuroradiological finding that has been described in association with autoimmune disorders such as Sydenham chorea, lupus or antiphospholipid syndrome. Here, we report three patients with non-paraneoplastic limbic encephalitis characterized by 18FDG-PET hypermetabolism of both striata, in contrast with diffuse hypometabolism in the rest of the brain. All patients developed subacute dementia, and antibodies to voltage-gated potassium channels were found in all cases. Brain metabolism and neurological status improved within a few months of immunosuppressive therapy. The finding of striatal hypermetabolism on 18FDG-PET images could thus be highly indicative of limbic encephalitis associated with anti-neuropil antibodies. It could be of significant help in the diagnosis of this rare and treatable condition, and may also provide a useful marker of disease outcome.


Broad-Spectrum Bactericidal Activity of a Synthetic Random Copolymer Based on 2-Methoxy-6-(4-Vinylbenzyloxy)-Benzylammonium Hydrochloride.
Low-molecular-weight organic ammonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Unfortunately, short-term functionality and high toxicity limit their clinical application. On the contrary, the equivalent macromolecular ammonium salts, derived from the polymerization of monomeric ammonium salts, have demonstrated improved antibacterial potency, a lower tendency to develop resistance, higher stability, long-term activity, and reduced toxicity. A water-soluble non-quaternary copolymeric ammonium salt (P7) was herein synthetized by copolymerizing 2-methoxy-6-(4-vinylbenzyloxy)-benzylammonium hydrochloride monomer with N, N-di-methyl-acrylamide. The antibacterial activity of P7 was assessed against several multidrug-resistant (MDR) clinical isolates of both Gram-positive and Gram-negative species. Except for colistin-resistant Pseudomonas aeruginosa, most isolates were susceptible to P7, also including some Gram-negative bacteria with a modified charge in the external membrane. P7 showed remarkable antibacterial activity against isolates of Enterococcus, Staphylococcus, Acinetobacter, and Pseudomonas, and on different strains of Escherichia coli and Stenotrophomonas maltophylia, regardless of their antibiotic resistance. The lowest minimal inhibitory concentrations (MICs) observed were 0.6-1.2 µM and the minimal bactericidal concentrations (MBC) were frequently overlapping with the MICs. In 24-h time-kill and turbidimetric studies, P7 displayed a rapid non-lytic bactericidal activity. P7 could therefore represent a novel and potent tool capable of counteracting infections sustained by several bacteria that are resistant to the presently available antibiotics.


Effects of an augmented postoperative fluid protocol on wound healing in cardiac surgery patients.
Cardiac surgery patients are vulnerable to hypoperfusion postoperatively and often have subcutaneous tissue oxygen tension less than 50 mm Hg. Hypovolemia most likely contributes to this hypoperfusion and may lead to impaired wound healing. To determine if a modified postoperative fluid replacement protocol would result in improved tissue oxygen tension, blood flow, and healing in cardiothoracic surgery patients. A total of 166 cardiac surgery patients, 18 to 90 years old, participated in a randomized, 2-group, repeated-measures study. The experimental group received fluid augmentation during the first 36 hours after surgery; the control group received standard postoperative replacement fluids. Subcutaneous tissue oxygen tension and temperature were measured 8, 18, and 36 hours after surgery. Tissue cellularity and accumulation of hydroxyproline were evaluated in tissue obtained from subcutaneous expanded polytetrafluoroethylene tubes. Wound complications were evaluated by using the ASEPSIS Wound Scoring System. Tissue oxygen levels, tissue cellularity, and accumulation of hydroxyproline were similar in the 2 groups. A negative correlation (P = .01) existed between higher tissue oxygen values and lower (better) ASEPSIS leg wound scores. More than 80% of the patients had tissue oxygen levels of 50 mm Hg or less at each time of measure. Many values were 30 to 40 mm Hg less than the ideal for control of bacteria and healing. The frequency of low oxygen levels is consistent with data from earlier studies. Determination of other interventions to improve subcutaneous tissue perfusion in cardiac surgery patients is needed.


In vitro susceptibility of avian mycoplasmas to enrofloxacin, sarafloxacin, tylosin, and oxytetracycline.
In vitro susceptibility of avian Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) to enrofloxacin, sarafloxacin, tylosin, and oxytetracycline was determined by a serial broth dilution method. The minimum inhibitory concentration (MIC) was recognized by a conversion of the pH indicator phenol red in culture media to a yellow color. Each isolate or type strain of mycoplasma was tested in two replicates. The MICs of tylosin, enrofloxacin, sarafloxacin, and oxytetracycline against five isolates and two reference strains of MG (approximately 10(5) colony-forming units [CFU]/ml) were 0.05, 0.14, 0.37, and 1.30 microg/ml, respectively. The MICs of the four antimicrobial agents against six isolates and one reference strain of MS (approximate 10(5) CFU/ml) were 0.13, 1.82, 1.76, and 0.91 microg/ml, respectively. There were no differences (P > 0.05) between tylosin, enrofloxacin, and sarafloxacin against MG, but these three antibiotics were different (P < 0.05) from oxytetracycline. The MIC value of tylosin against MS was different (P < 0.05) from those of sarafloxacin and enrofloxacin, but it was not different (P > 0.05) from that of oxytetracycline.


The added value of online user-generated content in traditional methods for influenza surveillance.
There has been considerable work in evaluating the efficacy of using online data for health surveillance. Often comparisons with baseline data involve various squared error and correlation metrics. While useful, these overlook a variety of other factors important to public health bodies considering the adoption of such methods. In this paper, a proposed surveillance system that incorporates models based on recent research efforts is evaluated in terms of its added value for influenza surveillance at Public Health England. The system comprises of two supervised learning approaches trained on influenza-like illness (ILI) rates provided by the Royal College of General Practitioners (RCGP) and produces ILI estimates using Twitter posts or Google search queries. RCGP ILI rates for different age groups and laboratory confirmed cases by influenza type are used to evaluate the models with a particular focus on predicting the onset, overall intensity, peak activity and duration of the 2015/16 influenza season. We show that the Twitter-based models perform poorly and hypothesise that this is mostly due to the sparsity of the data available and a limited training period. Conversely, the Google-based model provides accurate estimates with timeliness of approximately one week and has the potential to complement current surveillance systems.


Synthesis of [11C]interleukin 8 using a cell-free translation system and L-[11C]methionine.
Positron emission tomography (PET), which requires a compound labeled with a positron emitter radioisotope as an imaging probe, is one of the most useful and valuable imaging modalities in molecular imaging. It has several advantages over other imaging modalities, particularly in sensitive and quantitative investigations of molecular functions and processes in vivo. Recent advances in biopharmaceuticals development have increased interest in practical methods for proteins and peptides labeling with positron emitter radioisotope for PET molecular imaging. Here, we propose a novel approach for preparing positron emitter-labeled proteins and peptides based on biochemical synthesis using a reconstituted cell-free translation system. In this study, [(11)C]interleukin 8 (IL-8; MW 9.2 kDa) was successfully synthesized by the cell-free system in combination with l-[(11)C]methionine. The in vitro biochemical reaction proceeded smoothly and gave maximum radioactivity of [(11)C]IL-8 at 20 min with a radiochemical yield of 63%. Purification of [(11)C]IL-8 was achieved by conventional cation exchange and ultrafiltration methods, resulting in enough amount of radioactivity with excellent radiochemical purity (>95%) for small-animal imaging. This study clearly demonstrates that cell-free protein production system combined with positron emitter-labeled amino acid holds great promise as a novel approach to prepare radiolabeled proteins and peptides for PET imaging.


Analgesic synergy and improved motor function produced by combinations of mu-delta- and mu-kappa-opioids.
This study evaluated the effects of intrathecal administration of a low-analgesic dose of the selective mu-agonist DAMGO co-administered with sequentially increasing doses of either the selective delta-agonist DPDPE or the selective kappa-agonist, U50,488H on mechanical nociceptive thresholds in the rat. Potent analgesic synergy was observed with both combinations. Since an elevation in nociceptive threshold can result from motor deficits, as well as true analgesia, we also evaluated the effects of the combination regimens on motor coordination using a rotarod apparatus. The combination regimens produced significantly less motor deficits than those observed when DPDPE and U50,488H were administered as single agents. These findings of enhanced analgesia with decreased motor side-effects associated with administration of fixed mu/delta or mu/kappa combinations suggest that co-administration of opiates that act at different receptors may constitute a superior approach to the treatment of pain.


In vitro degradation behavior of silica nanoparticles under physiological conditions.
Understanding the degradability of silica nanoparticles is significant for the rational design of desired nanomaterials for various biomedical applications. However, the effect of the intrinsic properties of silica nanoparticles, such as particle shape, surface chemistry, and porosity, on kinetic degradation process under different extrinsic conditions has still received little attention. Herein, mesoporous silica nanoparticles (MSNs) with different aspect ratios (ARs, 1, 2, and 4), the corresponding PEG-functionalized MSNs, and amorphous Stöber spherical silica nanoparticles were specially designed and their degradation was evaluated in in vitro simulated physiological media. The results show that shape, surface properties and porosity of nanoparticles, as well as the component of simulated physiological media, play important roles in tuning the degradation kinetics and behaviors. Sphere-shaped MSNs have a faster degradation rate than rod-shaped counterparts. Naked MSNs are eroded from particle external surface, while PEGylated MSNs from interior of particles. And spherical MSNs display more extensive degradation than amorphous silica nanoparticles. The presence of fetal bovine serum (FBS) in Dulbecco's Modified Eagle's Medium (DMEM) can accelerate the degradation process. These results can provide useful guidelines for the rational design of silica nanoparticles for biomedical applications.


The significance of bivariate cytokeratin and DNA flow cytometry in paraffin-embedded specimens of non-small cell lung cancer.
The presence of non-tumor cells inside cancer tissue is one of the causes of errors in cell cycle analysis by DNA flow cytometry. The recent establishment of bivariate cytokeratin and DNA flow cytometry has made feasible the accurate assessment of tumor proliferative activity. Bivariate flow cytometry and immunohistochemistry examinations of paraffin-embedded specimens were performed in 92 patients with non-small cell lung cancer (NSCLC). Determination of the S-phase fraction by flow cytometry, with cytokeratin gating (CK-gated SPF) and without gating (ungated SPF), and the expression of proliferating cell nuclear antigen by immunohistochemistry (PCNA labeling index), were used to assess cancer cell proliferation. Two tumors had DNA histograms with a coefficient of variation of more than 8.0% and were excluded from the flow cytometric analysis. In DNA diploid tumors (n = 25), the ungated SPFs (8.7 +/- 3.6%) showed a lower distribution than the CK-gated SPFs (14.3 +/- 4.7%) (P < 0.0001). In DNA aneuploid tumors (n = 65), there was no difference in distribution between the ungated SPFs (15.0 +/- 8.3%) and the CK-gated SPFs (15.1 +/- 7.1%) (P = 0.94). The CK-gated SPF and the PCNA labeling index of an individual tumor had a good correlation (P < 0.0001), and this agreed with the result showing that DNA diploid and aneuploid tumors had equal proliferative activity (P = 0.64 and P = 0.63, respectively). The technique using CK-gating markedly improved the SPF measurement in DNA diploid tumors. This assessment showed no difference in proliferative activity between DNA diploid and aneuploid tumors in NSCLC. Bivariate cytokeratin and DNA flow cytometry is an accurate and objective method for cancer-specific analysis, and will surely be informative in clinical oncology.


Body mass index and use of mammography screening in the United States.
Obese and underweight women may be less likely to seek cancer screening because of health status, self-perception, and body image related to non-desirable weight. This study examined the relationship between body mass index (BMI) and mammography screening, using the data from the year 2000 United States National Health Interview Survey. This study included 7692 white and 1496 black female participants aged 40-80, who were randomly selected. Body mass index (kg/m2), based on self-reported weight and height, was compared between women with and without a mammogram in the past 2 years using logistic regression. Compared to women with normal body mass index, underweight and extremely obese women were more likely to have no screening mammograms in the past 2 years (odds ratio (OR) = 1.8, 95% confidence interval (CI), 1.2-2.6 for underweight women; odds ratio = 1.3, 95% confidence interval, 1.0-1.8 for extremely obese women). When data were analyzed by race, the odds ratio estimates were 1.8 for underweight white women (95% confidence interval, 1.3-2.7) and 1.4 for extremely obese white women (95% confidence interval, 1.0-1.9). The corresponding odds ratio estimates were close to 1.0 for black women. Underweight and extreme obesity may increase the risk of underusing screening mammography. The association between body mass index especially underweight and underuse of mammography might exist primarily in white women.


[VDT worker's posture and workload in free-address office system].
A free-address system is a new office layout in which a worker can freely sit in their favorite place with a computer and materials. Since this layout has recently been introduced in offices, we conducted a questionnaire survey which aimed to clarify the effects of the free-address system on visual display terminals (VDT) workers' posture and workload. A total of 203 male VDT workers who were system engineers aged 20 to 59 using a notebook computer were evaluated, of whom 150 used the free-address layout, and 53 used the fixed-address layout. The free-address layout was effective in the improvement of individual work space compared with the fixed-address layout. Also, in this layout the worker did not feel dissatisfaction with communication or support between workers. However, workers using the free-address layout assumed an unsuitable work posture, without adjusting the height of their chairs. Furthermore, this layout might have risk factors which increase neck/shoulder and low back stiffness and/or pain. Therefore, the free-address layout may have incipient problems, and it will be necessary to examine further the effects of this layout on VDT worker's health.


Dietary exposure of three passerine species to PCDD/DFs from the Chippewa, Tittabawassee, and Saginaw River floodplains, Midland, Michigan, USA.
Dietary exposure of house wrens (Troglodytes aedon), tree swallows (Tachycineta bicolor), and eastern bluebirds (Sialia sialis) to polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzo-p-dioxins (PCDDs) near Midland, Michigan (USA) was evaluated based on site-specific data, including concentrations of residues in bolus samples and individual invertebrate orders and dietary compositions by study species. Site-specific dietary compositions for the three species were similar to those reported in the literature, but differed in their relative proportions of some dietary items. Oligocheata (non-depurated) and Brachycera (Diptera) contained the greatest average concentrations of ΣPCDD/DFs of the major site-specific dietary items collected via food web-based sampling. Average ingestion values of ΣPCDD/DFs from site-specific bolus-based and food web-based dietary concentrations for nestlings at study areas (SAs) were 6- to 20-fold and 2- to 9-fold greater than at proximally located reference areas (RAs), respectively. Average ingestion values of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ(WHO - Avian)) from site-specific bolus-based and food web-based dietary concentrations for nestlings at SAs were 31- to 121-fold and 9- to 64-fold greater than at proximally located RAs, respectively. Estimates of ΣPCDD/DFs and TEQ(WHO - Avian) tissue concentrations based on nestling dietary exposures were greater than those measured. Plausible explanations include nestling metabolism of 2,3,7,8-tetrachlorodibenzofuran and assimilation rates of less than the 70% assumed to occur over the nestling growth period. Profiles of the relative concentrations of individual PCDD/DF congeners in samples of invertebrates and bolus at SAs on the Tittabawassee River downstream of the source of contamination were dominated by 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (22% to 44%) and 2,3,7,8-tetrachlorodibenzofuran (18% to 50%).


Determination of hydride affinities of various aldehydes and ketones in acetonitrile.
The hydride affinities of 21 typical aldehydes and ketones in acetonitrile were determined by using an experimental method, which is valuable for chemists choosing suitable reducing agents to reduce them. The focus of this paper is to introduce a very facile experimental method, which can be used to determine the hydride affinities of various carbonyl compounds in solution.


Zinc status in pregnancy and the occurrence of anencephaly in Turkey.
Serum and hair zinc concentrations were measured in samples taken from 29 mothers with neural tube defects (NTD) (mainly anencephaly) at delivery. The control group consisted of 20 healthy mothers with normal offspring and 40 nonpregnant women 18 to 34 years of age, from middle income backgrounds. The mean maternal serum and hair zinc concentrations in the NTD group were lower than those of control mothers and the nonpregnant women. The zinc levels in the blood (plasma, red blood cells) and hair of 8 newborn infants with NTD (4 being anencephalic) were compared with those of normal newborn infants. The mean zinc concentration in the hair of malformed babies (250.4 +/- 85.2 micrograms/g) was significantly higher than that of normal infants (193.4 +/- 39.2 micrograms/g) (p less than 0.05) while the mean plasma zinc concentration was significantly lower (59.48 +/- 9.18 micrograms/dl compared with 68.75 +/- 10.89 micrograms/dl) (p less than 0.01). No difference was found between the mean values of red blood cell zinc levels for the two groups of infants. Maternal zinc deficiency was thought to be one of the factors responsible for NTD in Turkey.


Thermal conductivity, Fermi pockets and superconductivity in underdoped cuprates.
The electronic contribution to thermal conductivity is studied in models of underdoped cuprates where the normal state has a pocketed Fermi surface with circumference ∼x (hole concentration) and the superconducting state is formed by opening a gap in the Fermi pocket. The physical consequences of the Fermi pocket are studied by comparing the thermal conductivity computed in four different models: (1) an ordinary d-wave superconductor with four Dirac Fermi points; (2) a normal metal with a pocketed Fermi surface; (3) a superconductor formed by spinon-holon binding in the t-J model; (4) a phenomenological d-wave Bardeen-Cooper-Schrieffer (BCS) superconductor with superconductivity formed by opening a gap on the pocketed Fermi surface. Our results suggest that thermal conductivity provides useful information to distinguish between different scenarios of the normal-to-superconducting transition in underdoped cuprates.


Fibroblast growth factor 23 and phosphate homeostasis.
The current review highlights recent advances in the area of renal tubular phosphate transport and its regulation by fibroblast growth factor 23 (FGF23), a potent regulator of phosphate homeostasis. Recent studies demonstrate that FGF23 binds to both membrane and soluble form of α-klotho to activate FGF receptor signaling pathways. Parathyroid hormone and FGF23 equivalently decrease sodium-dependent phosphate cotransport but the effect is not additive, suggesting a shared but not synergistic mechanism of action. Crosstalk occurs downstream of parathyroid hormone-receptor and FGF23-receptor signaling and converge at the level of the scaffolding protein, sodium-hydrogen exchanger regulatory factor-1. A novel mechanism for phosphate efflux through the basolateral membrane of renal proximal tubular epithelia via an atypical G-protein coupled receptor, Xenotropic and polytropic retrovirus receptor 1 (XPR1), was recently identified. Conditional deletion of Xpr1 gene in renal proximal tubules in mice leads to hypophosphatemic rickets and Fanconi syndrome establishing an important role for XPR1 in phosphate homeostasis. A novel anti-FGF23 antibody, burosumab, was recently approved to treat X-linked hypophosphatemia, a human disorder of FGF23 excess. Significant advances in understanding the cellular and molecular aspects of renal tubular phosphate transport and its regulation by FGF23 has led to the discovery of novel therapeutics to treat human disorders of phosphate homeostasis.


The care system assessment model and its operationalization.
The care system assessment model is intended to help community planning bodies for HIV services conduct systematic evaluations of existing care systems, with an eye toward changing them to make services more accessible to people living with HIV (PLWH) from underserved minority communities. The model has four structural and three cultural/behavioral dimensions. The structural dimensions are system comprehensiveness, capacity, integration, and accessibility; the cultural/behavioral dimensions are service acceptability, technical competencies (of both providers and potential system users), and client health-seeking behaviors. This chapter describes the model's dimensions and ways to operationalize them through document reviews and other methods.


In vitro toxicity of trichothecenes on human haematopoietic progenitors.
The culture of human haematopoietic progenitors, Colony-Forming-Unit Granulocyte and Macrophage (CFU-GM), has been performed in the presence of four trichothecenes, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), and deoxynivalenol (DON). Our results showed that trichothecenes were cytotoxic for human haematopoietic progenitors. This work and the analysis of results described in the literature allowed us to propose that the haematologic lesions observed during human intoxication could be due to a destruction of haematopoietic progenitors such as granulocytic and macrophage colony-forming cells.


Behavioral interventions to increase HPV vaccination acceptability among mothers of young girls.
To determine the most effective ways to present human papillomavirus (HPV) vaccine risk and benefit information to mothers in Hispanic, African American, and White communities, to increase mothers' intentions to vaccinate their daughters against HPV. The study used a 3 x 2 between-subjects factorial design, involving 3 different risk presentation formats (graphical HPV statistics, nongraphical HPV statistics, or no-statistics control) and the presence or absence of rhetorical questions (RQ). Data were collected from a national sample of 471 mothers of girls ages 11-16. The primary outcome variable was mothers' intention to vaccinate their daughters against HPV. Secondary outcomes included mothers' self-reported message comprehension and perceptions of daughters' vulnerability to HPV infection, infection severity, vaccine efficacy, and obstacles to immunization. Results showed that both risk presentation format and RQs had an overall positive effect on mothers' intention to vaccinate their daughters. However, the interventions appear to be more effective when used separately than when used in combination. Each of these interventions is brief and could easily be implemented by health care providers as well as in patient health communication literature.


Relationship among sexual desire, sexual satisfaction, and quality of life in middle-aged and older adults.
The authors examined the association among sexual desire, sexual satisfaction, and quality of life in a sample of community participants. They predicted that quality of life would be positivity correlated with sexual satisfaction and that sexual desire would indirectly influence quality of life. This research showed that elderly adults' sexual desire and sexual satisfaction decrease with age and that nearly 40% of the interviewees still had sexual activity one or more times every month. The results revealed that sexual desire does not directly influence quality of life, but it does have a direct effect on sexual satisfaction; hence, sexual satisfaction will indirectly affect quality of life.


[Formation of the skeletal system of white rat and golden hamster embryos during experimental hypovitaminosis B1].
In pregnant females B1-hypovitaminosis was induced by injecting various doses of oxythiamine--a specific antimetabolite for B1 vitamin. The rat and hamster embryos were respectively treated on the 20th and 15th days of development after the technique suggested by Dauson-Dyban with staining the osseous anlages of the skeletons with alizarine red. The results of the investigations performed in 193 skeletons of the rat embryos and in 196 skeletons of the golden hamster embryos revealed a progressive decrease, as the dose of oxythiamine increased, in length of ossification anlages of the extremity bones. However, susceptibility to lesions in various bones of the extremity and skull skeletons was not similar under conditions of progressive oxythiamine-induced B1-hypovitaminosis and depended on time of their anlage formations.


In-hospital cardiac arrest.
To review the current management of in-hospital cardiac arrest and to identify variables that influence outcomes, OLDMEDLINE from 1950 to 1966 and MEDLINE from 1966 to March 2005 were searched using the keywords cardiopulmonary resuscitation, cardiac arrest, in hospital, and adult. Secondary sources were derived from review publications and personal communications by one of the authors. There is no secure evidence that the ultimate outcomes after cardiopulmonary resuscitation in settings of in-hospital cardiac arrest have improved in the >40 yrs that followed the landmark report by Kouwenhoven, Jude, and Knickerbocker, which launched the modern era of cardiopulmonary resuscitation. A paucity of objective measurements preclude secure protocols for sequencing of interventions and, even more, when to initiate and discontinue cardiopulmonary resuscitation. The preparedness of both physicians and nursing professionals to implement the published guidelines has itself been questioned. Whereas early access defibrillation with automated external defibrillators may be of benefit in out-of-hospital settings, there has as yet been no secure evidence that automated external defibrillators have had a favorable impact on in-hospital cardiopulmonary resuscitation when used on infrequent occasions by first responders. This contrasts with the much greater success of advanced life support providers and especially when electrical defibrillation is promptly performed by expertly trained personnel after onset of cardiac arrest. Outcomes are therefore improved in critical care settings and especially in coronary care units in which patients are continuously monitored.


Retinal pigment epithelium disorder in Vogt-Koyanagi-Harada disease revealed by hyperosmolarity response of ocular standing potential.
The hyperosmolarity response of the ocular standing potential was examined in 14 eyes of 7 cases of Harada's disease between 8 and 1,341 days after the onset of the disease. The hyperosmolarity response remained normal at the initial stage of the disease when choroiditis, retinal detachment and iridocyclitis were the main manifestations. The hyperosmolarity response was suppressed when depigmentation of the fundus progressed to the stage of the "sunset glow" appearance. The present study suggests that a sensitivity reduction to osmotic stress takes place in the retinal pigment epithelium concomitantly with the transition from the stage of depigmentation to the stage of "sunset glow". This dysfunction can be disclosed by the hyperosmolarity response, but not by the conventional examination of the light peak/dark trough ratio of the ocular standing potential.


Cytogenetics and molecular genetics of bone and soft-tissue tumors.
The cytogenetic and molecular findings in bone and soft-tissue sarcomas are summarized. A table presenting all such tumors, with their specific translocations and the genes involved, is included, along with a list of those tumors that most likely result from a stepwise process of numerous genetic changes.


Clinical Results of Arteriovenous Fistulas Constructed Using Autologous Vessels in End-Stage Renal Disease Patients on Hemodialysis.
For hemodialysis patients with end-stage renal disease (ESRD), it is important to construct an efficient vascular access with a superior patency rate. This study investigated the factors influencing the efficiency of arteriovenous fistulas (AVFs) constructed using an autologous vessel and evaluated the necessity of ultrasonography as a preoperative tool for AVF construction. A retrospective analysis was performed of 250 patients in whom an AVF was constructed using an autologous vessel due to ESRD at our institution from January 2009 to April 2016. The 1-, 3-, and 5-year patency rates for all subjects were 87.6%, 85.6%, and 84.4%, respectively. The patients who underwent a preoperative evaluation of their vessels via ultrasonography had better patency rates than those who did not. Superior patency rates were found in patients under 65 years of age or with an anastomotic vein diameter of 3 mm or more. The 1-year patency rate and the diameter of the anastomotic vein showed a positive relationship. Ultrasonography is strongly recommended for AVF construction, and efforts should be made to increase the patency rate in patients over 65. Superior clinical results can be expected when an AVF is made using an autologous vessel with an anastomotic vein diameter of at least 3 mm.


Poor efficacy of TNF inhibitors in non-radiographic axial spondyloarthritis in the absence of objective signs: A bicentric retrospective study.
To compare BASDAI 50 response rate to TNFi in axial spondyloarthritis (axSpA) depending on the presence or not of objective signs of axSpA and to look for predictive factors of TNFi efficacy. Patients diagnosed with axSpA according to ASAS criteria "clinical arm" and treated between January 2001 and September 2015 with TNFi were included. First group included patients with at least one objective sign such as arthritis, dactylitis, enthesitis, uveitis, inflammatory bowel disease, elevated C-reactive protein or radiological sacroiliitis, and second group included non-radiographic axSpA (nr-axSpA) patients without any objective sign corresponding to patients with inflammatory back pain and either a good response to NSAID or a SpA family history. The primary outcome was the TNFi efficacy, defined as an achievement of BASDAI 50 at 3 months. The secondary outcomes were BASDAI 50 achievement over 1 year and analysis of predictive factors of TNFi response. We included 84 nr-axSpA patients without any objective signs and 84 axSpA patients with objective signs (48.2% r-axSpA and 52.8% nr-axSpA). BASDAI 50 achievement rates were significantly higher in patients with objective signs than in patients without, at 3 months (45.1% versus 13.7%, P<0.0001) and at any of the visit-time points over the first year (61.9% versus 21.4%, P<0.0001). In multivariate analysis, overweight/obesity and sacroiliitis on MRI were respectively negative and positive predictive factors of TNFi efficacy in the total population at 3 months (OR=0.32, 95%CI [0.11, 0.96], P=0.041 and OR=6.92, 95% CI (2.41, 19.8), P<0.0001, respectively). TNFi should be used with caution in axSpA when objective signs are absent as only 13.7% of these patients were BASDAI 50 responders at 3 months.


Assessing the real-time activation of the cannabinoid CB1 receptor and the associated structural changes using a FRET biosensor.
The cannabinoid receptor 1 (CB1) is mainly expressed in the nervous system and regulates learning, memory processes, pain and energy metabolism. However, there is no way to directly measure its activation. In this study, we constructed a CB1 intramolecular fluorescence resonance energy transfer (FRET) sensor, which could measure CB1 activation by monitoring structural changes between the third intracellular loop and the C-terminal tail. CB1 agonists induced a time- and concentration-dependent increase in the FRET signal, corresponding to a reduction in the distance between the third intracellular loop and the C-terminal tail. This, in turn, mobilized intracellular Ca2+, inhibited cAMP accumulation, and increased phosphorylation of the ERK1/2 MAP kinases. The activation kinetics detected using this method were consistent with those from previous reports. Moreover, the increased FRET signal was markedly inhibited by the CB1 antagonist rimonabant, which also reduced phosphorylation of the ERK1/2 MAP kinases. We mutated a single cysteine residue in the sensor (at position 257 or 264) to alanine. Both mutation reduced the agonist-induced increase in FRET signal and structural changes in the CB1 receptor, which attenuated phosphorylation of the ERK1/2 MAP kinases. In summary, our sensor directly assesses the kinetics of CB1 activation in real-time and can be used to monitor CB1 structure and function.


Mortality in Swedish dairy calves and replacement heifers.
The mortality of 8,964 heifer calves born in 122 dairy herds in southwest Sweden in 1998 to 2000 was monitored from January 1998 until December 2000. Farmers were requested to send carcasses for necropsy from animals that died from 1 d of age to first calving. Age and seasonal patterns of mortality were investigated using Kaplan-Meier curves. The median herd-level mortality risk was 2.1%. In total, 3.1% of the animals died before 90 d of age, 0.9% between d 91 and 210, and 2.2% between d 211 and first calving or d 810 (27 mo of age). The median age at death was 50 d and the risk of dying was highest during the first week of life. Of the 421 dead animals, 236 (56%) were subjected to either postmortem examination or were diagnosed as having died from trauma based on information from the farmers. In total, pneumonia was the most common cause of death (27%). However, in calves less than 31 d old, enteritis was the most common cause of death; in young stock 211 to 450 d old, trauma dominated; and in young stock more than 450 d old, trauma and calving-related diseases accounted for a majority of the mortality. The largest proportion of deaths was observed from January to March, and in June. Kaplan-Meier curves suggested that housing in small-group pens was associated with the lowest mortality (other housing systems were single pens and large-group pens with automatic milk feeders), but the association was not significant.


C-P bond formation of cyclophanyl-, and aryl halides via a UV-induced photo Arbuzov reaction: a versatile portal to phosphonate-grafted scaffolds.
A new versatile method for the C-P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method's potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.


Crystallization and preliminary X-ray diffraction studies of an alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123.
An NAD(+)-dependent psychrophilic alcohol dehydrogenase (ADH) from the Antarctic psychrophile Moraxella sp. TAE123 has been purified to homogeneity. The enzyme consists of four identical subunits, each containing two Zn ions. Protein crystals suitable for X-ray diffraction were obtained under optimized salting-out crystallization conditions using ammonium sulfate as a precipitating agent. The crystals are hexagonal bipyramids and belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = 136.4, c = 210.7 A. They contain one protein homotetramer in the asymmetric unit. Diffraction data were collected to 2.2 A under cryogenic conditions using synchrotron radiation.


Assessment of dysphonia due to benign vocal fold lesions by acoustic and aerodynamic indices: a multivariate analysis.
The goal was to identify acoustic and aerodynamic indices that allow the discrimination of a benign organic dysphonic voice from a normal voice. Fifty-three patients affected by dysphonia caused by vocal folds benign lesions, and a control group were subjected to maximum phonation time (MPT) measurements, GRB perceptual evaluations and acoustic/aerodynamic tests. All analyzed variables except the airflow variation coefficient were significantly different between the two groups. The unique significant factors in the discrimination between healthy and dysphonic subjects were the aerodynamic indices of MPT and Glottal efficiency index, and the acoustic index Shimmer. These results show that a combination of three parameters can discriminate a voice deviance and highlight the importance of a multidimensional assessment for objective voice evaluation.


Evaluation of liver test abnormalities in a patient-centered medical home: do liver test patterns matter?
Abnormal liver tests are extremely common in clinical practice, present with varying patterns and degrees of elevation, and can signal liver injury from a variety of causes. Responding to these abnormalities requires complex medical decision-making and merits investigation in primary care. This retrospective study investigates the association of patterns of liver test abnormality with follow-up in primary care. Using administrative data, this study includes patients with abnormal liver tests seen between 2007 and 2016 in a patient-centered medical home. Liver tests examined include serum bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Patients entered the cohort on the first liver test elevation. The outcome examined was completion of repeat testing, and the proportions of patients without follow-up were compared by patterns of index abnormality. 9545 patients met the inclusion criteria. Of these, 6155 (64.5%) possessed one liver test abnormality and 3390 (35.5%) possessed multiple abnormalities on index testing. Overall 1119 (11.7%) patients did not have repeat testing performed during the study period. A greater proportion of patients with lone abnormalities lacked repeat testing compared with those patients with multiple abnormalities. Differences in repeat testing appeared when comparing clinical patterns of abnormality, with higher proportions of follow-up in patients with testing suggestive of cholestasis. Over 11% of patients with abnormal liver tests did not undergo repeat testing during the study period. Repeat testing occurred more often in patients with multiple abnormalities and in clinical patterns suggestive of cholestasis. This study highlights a potential opportunity to improve quality of care.


Evaluation of the optimal neutrophil gelatinase-associated lipocalin value as a screening biomarker for urinary tract infections in children.
Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker in the detection of kidney injury. Early diagnosis of urinary tract infection (UTI), one of the most common infections in children, is important in order to avert long-term consequences. We assessed whether serum NGAL (sNGAL) or urine NGAL (uNGAL) would be reliable markers of UTI and evaluated the appropriate diagnostic cutoff value for the screening of UTI in children. A total of 812 urine specimens and 323 serum samples, collected from pediatric patients, were analyzed. UTI was diagnosed on the basis of culture results and symptoms reported by the patients. NGAL values were measured by using ELISA. NGAL values were more elevated in the UTI cases than in the non-UTI cases, but the difference between the values were not statistically significant (P=0.190 for sNGAL and P=0.064 for uNGAL). The optimal diagnostic cutoff values of sNGAL and uNGAL for UTI screening were 65.25 ng/mL and 5.75 ng/mL, respectively. We suggest that it is not appropriate to use NGAL as a marker for early diagnosis of UTI in children.


An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.
At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.


[Correspondence and effect on the clinical laboratory of the medical examination and treatment reward revision].
Since 2007, the rate of hospital bankruptcy has been rapidly increasing, and we face the crisis of a collapse in the medical care system. Even in hospitals that continue to operate, more than 70% are losing money. In the Department of Clinical Laboratory, the budget cannot be balanced using the present medical service fee payment system in the microbial examination field. Hospital managers may first consider outsourcing medical services from departments showing a budget imbalance. However, they should be aware that a decrease in medical services increases overall medical expenditure in the hospital.


Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology.
We have investigated the effect of sequence-specific antisense phosphorothioate-modified oligodeoxyribonucleotides (PS-ODNs) targeting different regions of each of the 3032-kDa protein complex (antigen 85 complex) encoding genes on the multiplication of Mycobacterium tuberculosis. Single PS-ODNs to one of the three mycolyl transferase transcripts, added either once or weekly over the 6-wk observation period, inhibited bacterial growth by up to 1 log unit. A combination of three PS-ODNs specifically targeting all three transcripts inhibited bacterial growth by approximately 2 logs; the addition of these PS-ODNs weekly for 6 wk was somewhat more effective than a one-time addition. Targeting the 5' end of the transcripts was more inhibitory than targeting internal sites; the most effective PS-ODNs and target sites had minimal or no secondary structure. The effect of the PS-ODNs was specific, as mismatched PS-ODNs had little or no inhibitory activity. The antisense PS-ODNs, which were highly stable in M. tuberculosis cultures, specifically blocked protein expression by their gene target. PS-ODNs targeting the transcript of a related 24-kDa protein (mpt51) had little inhibitory effect by themselves and did not increase the effect of PS-ODNs against the three members of the 3032-kDa protein complex. The addition of PS-ODNs against the transcripts of glutamine synthetase I (glnA1) and alanine racemase (alr) modestly increased the inhibitory efficacy of the 3032-kDa protein complex-specific PS-ODNs to approximately 2.5 logs. This study shows that the three mycolyl transferases are highly promising targets for antituberculous therapy by using antisense or other antimicrobial technologies.


Iron deficiency, cognition, mental health and fatigue in women of childbearing age: a systematic review.
It is known that Fe deficiency has a negative impact on cognitive function in children by altering brain energy metabolism and neurotransmitter function. It is unclear whether Fe deficiency has detrimental effects on cognition, mental health and fatigue in women of childbearing age. Our aim was to systematically review the literature to determine whether Fe deficiency in women of childbearing age affects cognition, mental health and fatigue, and whether a change in Fe status results in improvements in cognition, mental health and fatigue. Studies using Fe supplement interventions were reviewed to examine the effect of Fe deficiency in women of childbearing age (13-45 years) on their cognition, mental health and fatigue. English-language articles ranging from the earliest record to the year 2011 were sourced. The quality of retrieved articles was assessed and the Fe pathology, cognitive, mental health and fatigue data were extracted. Means and standard deviations from cognitive test data were included in meta-analyses of combined effects. Of the 1348 studies identified, ten were included in the review. Three studies showed poorer cognition and mental health scores and increased fatigue with Fe deficiency at baseline. Seven studies reported an improvement in cognitive test scores after Fe treatment. Results of three of these studies were included in meta-analyses of the effect of Fe supplement intervention on cognition. The results of the meta-analyses showed a significant improvement in Arithmetic scores after treatment (P < 0·01), but no effect on Digit Symbol, Digit Span or Block Design. While an improvement in cognition after Fe treatment was seen in seven out of ten studies, the evidence base is limited by poor study quality and heterogeneity across studies. Additional high-quality studies using consistent measures are warranted.


Effects of combining field strengths on auditory functional MRI group analysis: 1.5T and 3T.
To evaluate effects of combining functional magnetic resonance imaging (fMRI) data acquired from different field strengths on group analysis as a function of the number of subjects at each field strength. In all, 28 subjects (18 at 3T) participated in an auditory task of passively listening to a 0.75s segment of jazz music in an event-related design. Results of single-subject analysis were combined to create all possible subject combinations for a group size of eight subjects from each of the 3T and 1.5T pools, comprising subject mixtures of (3T/1.5T) 0/8, 2/6, 4/4, 6/2, and 8/0. Group analysis performance of each subject permutation was measured by receiver operating characteristic (ROC) curves and activation overlap maps. While area under ROC curves, extent of activation in the gold standard region, and reliability of activation increased with the number of 3T subjects, marginal gain decreased. ROC performance overlap across mixtures was observed, indicating that some combinations of subjects markedly outperformed others. For detection of activation, 4/4 was arguably the minimum mixture level that was comparable to 3T-only group results. Inclusion of 1.5T data does not necessarily reduce the validity of group analysis. Lower field strength data was found only to limit detection power, but did not affect specificity. Within the limits of realignment error, these results should also extend to group longitudinal analyses of subject mixtures from different field strengths.


Long-term results over 10 years of anterior corpectomy and fusion for multilevel cervical myelopathy.
Retrospective long-term outcome analysis over more than 10 years. To assess the long-term results of anterior corpectomy and fibular strut grafting over > or =4 disc levels for cervical myelopathy, and identify factors affecting the late deterioration in clinical outcome. Few studies have shown long-term results after anterior corpectomy and strut grafting. There is little detailed information about the long-term effects of multilevel anterior corpectomy and fusion for cervical myelopathy. A total of 31 cases were available for the 10-year follow-up after surgery (86% follow-up rate). Clinical results and radiographic measurements were obtained before surgery, 3 months after surgery, and at follow-up. There were 3 patients who had deterioration of the Japanese Orthopedic Association score of 1 point because of increasing hand numbness; 1 patient had adjacent disc degeneration, and 1 had pseudarthrosis without additional stenosis on magnetic resonance imaging. Adjacent disc degeneration did not affect the clinical results (P = 0.76). The long-term follow-up showed stable clinical results for more than 10 years, which depended on the thorough removal of the possible causes of the myelopathy, such as ossification of the posterior longitudinal ligament or a degenerated disc. Adjacent disc degeneration has minimal effects on the long-term clinical results after anterior long fusion.


Applying data envelopment analysis to preventive medicine: a novel method for constructing a personalized risk model of obesity.
Data envelopment analysis (DEA) is a method of operations research that has not yet been applied in the field of obesity research. However, DEA might be used to evaluate individuals' susceptibility to obesity, which could help establish effective risk models for the onset of obesity. Therefore, we conducted this study to evaluate the feasibility of applying DEA to predict obesity, by calculating efficiency scores and evaluating the usefulness of risk models. In this study, we evaluated data from the Takahata study, which was a population-based cohort study (with a follow-up study) of Japanese people who are >40 years old. For our analysis, we used the input-oriented Charnes-Cooper-Rhodes model of DEA, and defined the decision-making units (DMUs) as individual subjects. The inputs were defined as (1) exercise (measured as calories expended) and (2) the inverse of food intake (measured as calories ingested). The output was defined as the inverse of body mass index (BMI). Using the β coefficients for the participants' single nucleotide polymorphisms, we then calculated their genetic predisposition score (GPS). Both efficiency scores and GPS were available for 1,620 participants from the baseline survey, and for 708 participants from the follow-up survey. To compare the strengths of the associations, we used models of multiple linear regressions. To evaluate the effects of genetic factors and efficiency score on body mass index (BMI), we used multiple linear regression analysis, with BMI as the dependent variable, GPS and efficiency scores as the explanatory variables, and several demographic controls, including age and sex. Our results indicated that all factors were statistically significant (p < 0.05), with an adjusted R2 value of 0.66. Therefore, it is possible to use DEA to predict environmentally driven obesity, and thus to establish a well-fitted model for risk of obesity.


Survey of overnight academic hospitalist supervision of trainees.
In 2003, Accreditation Council for Graduate Medical Education (ACGME) announced the first in a series of guidelines related to the residency training. The most recent recommendations include explicit recommendations regarding the provision of on-site clinical supervision for trainees of internal medicine. To meet these standards, many internal medicine residency programs turned to hospitalist programs to fill that need. However, much is unknown about the current relationships between hospitalist and residency programs, specifically with regard to supervisory roles and supervision policies. We aimed to describe how academic hospitalists currently supervise housestaff during the on-call, or overnight, period and hospitalist program leader their perceptions of how these new policies would impact trainee-hospitalist interactions.


[Atrial fibrillation and heart failure: cause or effect?].
The association between atrial fibrillation and heart failure is well documented. Heart failure is one of the established predisposing conditions for the development of atrial fibrillation; conversely, heart failure is a common condition in patients with atrial fibrillation. In patients with heart failure the atrial electrophysiologic properties might be modified by hemodynamic overloading and neurohumoral activation. Atrial fibrillation promotes heart failure with multiple mechanisms including uncontrolled heart rate, loss of atrioventricular synchrony, irregularity in the ventricular rhythm, valvular regurgitation and neurohormonal effects. Treatment includes correction of neurohumoral activation, prevention of thromboembolism, maintenance of sinus rhythm, and pharmacologic and interventional control of ventricular rate. The results of recent trials (PIAF-Pharmacological Intervention in Atrial Fibrillation, RACE-RAte Control versus Electrical cardioversion for persistent atrial fibrillation, AFFIRM-Atrial Fibrillation Follow-up Investigation of Rhythm Management) suggest that a rate control strategy can be better than rhythm control, particularly in patients at high risk of relapse, like those with left ventricular dysfunction.


Accidental implant screwdriver aspiration: A case series report with literature review and proposed action protocol.
This article presents the first reported case series of three cases of aspiration of a dental implant screwdriver, which was successfully removed by flexible bronchoscopy. The report highlights preventive measures that can be taken in the dental office and the clinical signs and symptoms of the presence of a dental implant screwdriver in the bronchial tree. The nine reports published to date on this phenomenon are reviewed and compared, and an action protocol for dental practitioners, anaesthetists and pulmonologists is proposed to address this emergency. Some early and late complications are also described.


[Comparison between the serum concentration of alpha-tocopherol in puerperal women assisted in public and private maternities in Northeastern Brazil].
To compare the concentration of serum alpha-tocopherol during the postpartum period in women admitted to public and private hospitals in Natal (RN), Brazil. The study included 209 women in the postpartum period, 96 of them from private hospitals and 113 from public hospitals, studied between 24 and 48 hours postpartum. Inclusion criteria were: mothers aged 12 years or more, without diseases associated with pregnancy, who had given birth to a singleton with no malformations. Clinically decompensated women with multiple fetuses were excluded. A 5 mL blood sample was obtained from each participant under fasting conditions, before the first meal of the day. The concentration of alpha-tocopherol in serum (µg/dL) was determined by high performance liquid chromatography (HPLC). The statistical difference between means was tested by the Student's t-test. The mean concentration of alpha-tocopherol was 1.115.7 µg/dL in puerperae from the public network and 1.355.7 ± 397.6 µg/dL in puerperae from the private network , with a significant difference between groups (p=0.000687). Vitamin E concentration was determined individually and an alpha-tocopherol level <11.6 µmol/L or <499.6 µg/dL was considered to indicate deficiency. Vitamin E deficiency was detected in 5.3% of puerperae from the public network (n=6), whereas no deficiency was detected among women from the private network. However, low concentrations of alpha-tocopherol (11.6 to 16.2 µmol/L or 499.6 to 697.7 µg/dL) was detected in both groups, i.e., in 9.7% of the women from the public network (n=11) and in 4.2% for the women from the private network (n=4). These results highlight that women assisted in the public sector were more vulnerable to developing low concentrations of alpha-tocopherol than women assisted in the private sector.


Combination of structural and functional connectivity explains unique variation in specific domains of cognitive function.
The relationship between structural and functional brain networks has been characterised as complex: the two networks mirror each other and show mutual influence but they also diverge in their organisation. This work explored whether a combination of structural and functional connectivity can improve the fit of regression models of cognitive performance. Principal Component Analysis (PCA) was first applied to cognitive data from the Human Connectome Project to identify latent cognitive components: Executive Function, Self-regulation, Language, Encoding and Sequence Processing. A Principal Component Regression approach with embedded Step-Wise Regression (SWR-PCR) was then used to fit regression models of each cognitive domain based on structural (SC), functional (FC) or combined structural-functional (CC) connectivity. Executive Function was best explained by the CC model. Self-regulation was equally well explained by SC and FC. Language was equally well explained by CC and FC models. Encoding and Sequence Processing were best explained by SC. Evaluation of out-of-sample models' skill via cross-validation showed that SC, FC and CC produced generalisable models of Language performance. SC models performed most effectively at predicting Language performance in unseen sample. Executive Function was most effectively predicted by SC models, followed only by CC models. Self-regulation was only effectively predicted by CC models and Sequence Processing was only effectively predicted by FC models. The present study demonstrates that integrating structural and functional connectivity can help explaining cognitive performance, but that the added explanatory value (in-sample) may be domain-specific and can come at the expense of reduced generalisation performance (out-of-sample).


Cytokine expression of skin T-lymphocytes from patients with atopic dermatitis.
We analysed the cytokine profile of skin T cells by establishing 11 T-cell lines from adult patients with moderate-to-severe atopic eczema using T-cell growth factors interleukin-2 and interleukin-4. We compared T-cell lines from lesional skin of atopic dermatitis patients with those from non-atopic skin of patients with other skin diseases, observing that T-cell lines of patients with atopic dermatitis unstimulated cultures expressed a Th1 profile. After stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, the cytokine expression showed rapid initial upregulation of Th2 followed by a Th1 profile. Furthermore, strong upregulation of interleukin-10 was observed after 24 h stimulation. Our findings suggest that skin T-lymphocytes from atopic dermatitis patients seem to consist of a heterogenous population of Th1 and Th2 or Th0 cells and the results for secreted cytokines indicate that T-cell lines from each inflammatory skin disease showed the corresponding disease-specific original cytokine profile.


Virtual reality and gaming systems to improve walking and mobility for people with musculoskeletal and neuromuscular conditions.
Improving walking for individuals with musculoskeletal and neuromuscular conditions is an important aspect of rehabilitation. The capabilities of clinicians who address these rehabilitation issues could be augmented with innovations such as virtual reality gaming based technologies. The chapter provides an overview of virtual reality gaming based technologies currently being developed and tested to improve motor and cognitive elements required for ambulation and mobility in different patient populations. Included as well is a detailed description of a single VR system, consisting of the rationale for development and iterative refinement of the system based on clinical science. These concepts include: neural plasticity, part-task training, whole task training, task specific training, principles of exercise and motor learning, sensorimotor integration, and visual spatial processing.


Biofortification of Three Cultivated Mushroom Species with Three Iron Salts-Potential for a New Iron-Rich Superfood.
Mushrooms fortified with iron (Fe) can offer a promising alternative to counter the worldwide deficiency problem. However, the factors that may influence the efficiency of fortification have not yet been fully investigated. The aim of this study was to compare the effects of three Fe forms (FeCl3 6H2O, FeSO4 7H2O, or FeHBED) in three concentrations (5, 10, or 50 mM) for three mushroom species (Pleurotus eryngii, P. ostreatus, or Pholiota nameko) on their chemical composition, phenolic compounds, and organic acid production. The most effective metal accumulation of all the investigated species was for the 50 mM addition. FeCl3 6H2O was the most favorable additive for P. eryngii and P. nameko (up to 145 and 185% Fe more than in the control, respectively) and FeHBED for P. ostreatus (up to 108% Fe more than in control). Additionally, P. nameko showed the highest Fe accumulation among studied species (89.2 ± 7.51 mg kg-1 DW). The creation of phenolic acids was generally inhibited by Fe salt supplementation. However, an increasing effect on phenolic acid concentration was observed for P. ostreatus cultivated at 5 mM FeCl3 6H2O and for P. eryngii cultivated at 5 mM FeCl3 6H2O and 5 mM FeSO4 7H2O. In the case of organic acids, a similar situation was observed. For P. ostreatus, FeSO4 7H2O and FeHBED salts increased the formation of the determined organic acids in fruiting bodies. P. eryngii and P. nameko were characterized by a much lower content of organic acids in the systems supplemented with Fe. Based on the obtained results, we recommend starting fortification by preliminarily indicating which form of the element is preferred for the species of interest for supplementation. It also seems that using an additive concentration of 50 mM or higher is most effective.


Long-Term Management of Pulmonary Embolism: A Review of Consequences, Treatment, and Rehabilitation.
The concept of pulmonary embolism is evolving. Recent and emerging evidence on the treatment of specific patient populations, its secondary prevention, long-term complications, and the unmet need for rehabilitation has the potential to change clinical practice for the benefit of the patients. This review discusses the recent evidence from clinical trials, observational studies, and guidelines focusing on anticoagulation treatment, rehabilitation, emotional stress, quality of life, and the associated outcomes for patients with pulmonary embolism. Guidelines suggest that the type and duration of treatment with anticoagulation should be based on prevalent risk factors. Recent studies demonstrate that an anticoagulant treatment that is longer than two years may be effective and safe for some patients. The evidence for extended treatment in cancer patients is limited. Careful consideration is particularly necessary for pulmonary embolisms in pregnancy, cancer, and at the end of life. The rehabilitation and prevention of unnecessary deconditioning, emotional distress, and a reduced quality of life is an important, but currently they are unmet priorities for many patients with a pulmonary embolism. Future research could demonstrate optimal anticoagulant therapy durations, follow-ups, and rehabilitation, and effective patient-centered decision making at the end of life. A patient preferences and shared decision making should be incorporated in their routine care when weighing the benefits and risks with primary treatment and secondary prevention.


Polysaccharide-Based Drug Delivery Systems for the Treatment of Periodontitis.
Periodontal diseases are worldwide health problems that negatively affect the lifestyle of many people. The long-term effect of the classical treatments, including the mechanical removal of bacterial plaque, is not effective enough, causing the scientific world to find other alternatives. Polymer-drug systems, which have different forms of presentation, chosen depending on the nature of the disease, the mode of administration, the type of polymer used, etc., have become very promising. Hydrogels, for example (in the form of films, micro-/nanoparticles, implants, inserts, etc.), contain the drug included, encapsulated, or adsorbed on the surface. Biologically active compounds can also be associated directly with the polymer chains by covalent or ionic binding (polymer-drug conjugates). Not just any polymer can be used as a support for drug combination due to the constraints imposed by the fact that the system works inside the body. Biopolymers, especially polysaccharides and their derivatives and to a lesser extent proteins, are preferred for this purpose. This paper aims to review in detail the biopolymer-drug systems that have emerged in the last decade as alternatives to the classical treatment of periodontal disease.


Impact of Chronic Statin Therapy on Postprocedural Contrast-Induced Nephropathy in Patients Undergoing Non-Emergent Percutaneous Coronary Intervention.
Following percutaneous coronary intervention (PCI), elevations in serum creatinine level and declines in glomerular filtration rate are common. Prior studies have demonstrated benefit of chronic statin therapy in the prevention of contrast-induced nephropathy (CIN); however, it is unknown whether chronic statin therapy reduces the incidence of CIN in the non-emergent PCI setting. Using the 2004-2005 Cornell Angioplasty Registry, a total of 1171 consecutive patients were selected for analysis. The population was divided into two groups: (1) patients on chronic (≥30 days) statin therapy prior to PCI (n = 874); and (2) patients not on chronic statin therapy (n = 297). Patients taking chronic statin therapy were more likely to have diabetes mellitus (35.7% vs 22.6%; P<.001), previous myocardial infarction (36.3% vs 20.5%; P<.001), previous PCI (38.9% vs 16.2%; P<.001), and previous coronary artery bypass graft surgery (19.5% vs 11.4%; P=.01). Statin users were also more likely to be taking long-term aspirin (77.8% vs 59.6%; P<.001) and clopidogrel therapy (29.9% vs 14.1%; P<.001). Baseline serum creatinine levels were comparable between the two groups, as were procedural characteristics. The incidence of CIN following PCI was not significantly different between patients on chronic statin therapy versus those not on chronic statin therapy (4.2% vs 5.4%; P=.42). However, after multivariate adjustment, chronic statin therapy was associated with a lower incidence of CIN (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05-0.94; P=.04). Acute heart failure on admission and the urgency of the procedure (urgent vs elective PCI) were also independent predictors for developing CIN (OR, 3.04; 95% CI, 1.45-6.66 [P=.01] and OR, 2.80; 95% CI, 1.42-5.55 [P=.01], respectively). Long-term mortality rates were similar between those on chronic statin therapy and those not on statins. CIN occurred in 4.5% of patients following non-emergent PCI. Multivariate analysis demonstrated that chronic statin therapy decreased the odds of developing CIN in patients undergoing PCI.


A postmortem examination of poly-L lactic acid interference screws 4 months after implantation during anterior cruciate ligament reconstruction.
This is a report of a postmortem examination of an implanted bioabsorbable interference screw used for patellar tendon graft fixation during anterior cruciate ligament reconstruction. Examination was conducted 4 months after implantation. Examination included radiographic, arthroscopic, and magnetic resonance evaluations as well as histologic and mechanical pullout testing. Examination showed no evidence of tunnel widening, lytic bone changes, or inflammatory or foreign body reaction. Pullout and histologic testing indicated that appropriate bone plug incorporation was occurring. We believe the results of this case suggest that the use of bioabsorbable poly-L lactic acid interference screws is a safe and efficacious alternative to metallic screws during anterior cruciate ligament reconstruction.