Evaluation of a bedside whole-blood rapid troponin T assay in the emergency department. Rapid Evaluation by Assay of Cardiac Troponin T (REACTT) Investigators Study Group.
To evaluate the performance of a new bedside whole-blood rapid assay for cardiac troponin T (cTnT) in patients presenting to the ED with symptoms consistent with acute coronary ischemia. A prospective, observational trial was performed in 8 participating medical centers. Serial blood samples were obtained on presentation to the ED and 3 and 6 hours later. The cTnT whole-blood rapid assays were performed immediately at the site. Treating physicians and patients were blinded to the results of the rapid assays. Serum samples were analyzed at the core laboratory for serum cTnT, creatine kinase (CK)-MB, and myoglobin. The sensitivity of the rapid assay for detecting acute myocardial infarction (AMI) was compared with the sensitivities of serum cTnT, CK-MB, and myoglobin assays. Of 721 patients, 102 were diagnosed as having AMI. The median elapsed time from symptom onset to ED arrival was 3 hours. The sensitivities of the rapid assay for detecting AMI were 19.6%, 59.0%, and 69.7% at 0, 3, and 6 hours, respectively. The sensitivities of the serum cTnT assay (p-values for comparison with the rapid assay for cTnT) were 25.0% (p = 0.18), 69.6% (p = 0.04), and 79.8% (p = 0.02) at 0, 3, and 6 hours, respectively. The CK-MB and myoglobin sensitivities were 21.9%, 64.5%, and 81.0%; and 43.8%, 77.4%, and 71.4%, respectively. There were 7 patients with AMI who had negative rapid assay readings and positive serum cTnT levels; 4 of these patients were enrolled at the same site. Twenty patients not diagnosed as having AMI had at least one positive rapid assay. Fourteen of these 20 patients had a diagnosis of clinically relevant cardiac disease. The sensitivity of this whole-blood rapid cTnT assay for detecting AMI is comparable to that of current serum assays and offers the advantage of providing rapid bedside results. Discrepancies between serum and whole-blood assays for cTnT noted in this study may indicate the need for further education for the test reader prior to patient use.


Brain-derived neurotrophic factor and airway fibrosis in asthma.
Airway remodeling in asthma driven by inflammation involves proliferation of epithelial cells and airway smooth muscle (ASM), as well as enhanced extracellular matrix (ECM) generation and deposition, i.e., fibrosis. Accordingly, understanding profibrotic mechanisms is important for developing novel therapeutic strategies in asthma. Recent studies, including our own, have suggested a role for locally produced growth factors such as brain-derived neurotrophic factor (BDNF) in mediating and modulating inflammation effects. In this study, we explored the profibrotic influence of BDNF in the context of asthma by examining expression, activity, and deposition of ECM proteins in primary ASM cells isolated from asthmatic vs. nonasthmatic patients. Basal BDNF expression and secretion, and levels of the high-affinity BDNF receptor TrkB, were higher in asthmatic ASM. Exogenous BDNF significantly increased ECM production and deposition, especially of collagen-1 and collagen-3 (less so fibronectin) and the activity of matrix metalloproteinases (MMP-2, MMP-9). Exposure to the proinflammatory cytokine TNFα significantly increased BDNF secretion, particularly in asthmatic ASM, whereas no significant changes were observed with IL-13. Chelation of BDNF using TrkB-Fc reversed TNFα-induced increase in ECM deposition. Conditioned media from asthmatic ASM enhanced ECM generation in nonasthmatic ASM, which was blunted by BDNF chelation. Inflammation-induced changes in MMP-2, MMP-9, and tissue inhibitor metalloproteinases (TIMP-1, TIMP-2) were reversed in the presence of TrkB-Fc. These novel data suggest ASM as an inflammation-sensitive source of BDNF within human airways, with autocrine effects on fibrosis relevant to asthma.


Impact of alcohol habits and smoking on the risk of new-onset atrial fibrillation in hypertensive patients with ECG left ventricular hypertrophy: the LIFE study.
The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF. However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment. In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double-blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol-based antihypertensive therapy were followed for a mean of 4.8 years. At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study. New-onset AF occurred in 353 (4%) patients. Univariate Cox analyses showed that intake of alcohol > 10 units/week compared with less or no alcohol intake predicted new-onset AF (Hazard ratio, HR = 1.60 [95% CI 1.02-2.51], p = 0.043). Multivariate Cox regression analysis showed that intake of alcohol > 10 units/week predicted new-onset AF (p = 0.010) independently of most other univariate predictors, except when also baseline serum cholesterol, serum potassium and urinary albumin/creatinine ratio were included in the model (HR = 1.60 [95% CI 0.94-2.72], p = 0.081). Impact of smoking was not significant in Cox univariate or multivariate analyses, and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF. Up to 10 drinks of alcohol per week appears to be safe with respect to the risk for AF in hypertensive patients with LVH. Our data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH.


Rural-Urban Differences in Diagnosed Cervical Artery Dissection in New York State.
Cervical artery dissection (CeAD) is a leading cause of stroke in young adults. Incidence estimates may be limited by under- or overdiagnosis. We aimed to investigate if CeAD diagnosis would be higher in urban centers compared to rural regions of New York State (NYS). For this ecological study, administrative codes were used to identify CeAD discharges in the NYS Statewide Planning and Research Cooperative System (SPARCS) from 2009 to 2014. Rural Urban Commuting Area (RUCA) codes were taken from the US Department of Agriculture and included the classifications metropolitan, micropolitan, small town, and rural. Negative binomial models were used to calculate effect estimates and 95% confidence limits (eβ; 95% CL) for the association between RUCA classification and the number of dissections per ZIP code. Models were further adjusted by population. Population information was obtained from the US Census Bureau on 1,797 NYS ZIP codes (70.7% of NYS ZIP codes), 826 of which had at least 1 CeAD-related discharge from 2009 to 2014. Nonrural ZIP codes were more likely to report more CeAD cases relative to rural areas even after adjusting for population (metropolitan effect = eβ 5.00; 95% CI: 3.75-6.66; micropolitan effect 3.02; 95% CI: 2.16-4.23; small town effect 2.34; 95% CI: 1.58-3.47). CeAD diagnosis correlates with population density as defined by rural-urban status. Our results could be due to underdiagnosis in rural areas or overdiagnosis with increasing urbanicity.


High-risk adverse drug reactions: consideration of limited dialysis therapy for toxic epidermal necrolysis (TEN).
Toxic epidermal necrolysis (TEN) is a rare but often lethal drug reaction involving the skin. Treatment is often centered around suppurative care, and the mortality rate remains unacceptably high, although the clinical and epidemiological features of TEN have been well documented for decades. Recent studies have placed an emphasis on certain medications in the pathophysiology of severe TEN, and our colleagues previously reported several cases of clinical improvement in TEN patients following hemodialysis. Here, we discuss the major considerations for initiating dialysis in TEN patients. By doing so, we hope to encourage others to explore this potential avenue for treating TEN, one of the most serious medical emergencies in the field of dermatology.


Quantum Photovoltaic Cells Driven by Photon Pulses.
We investigate the quantum thermodynamics of two quantum systems, a two-level system and a four-level quantum photocell, each driven by photon pulses as a quantum heat engine. We set these systems to be in thermal contact only with a cold reservoir while the heat (energy) source, conventionally given from a hot thermal reservoir, is supplied by a sequence of photon pulses. The dynamics of each system is governed by a coherent interaction due to photon pulses in terms of the Jaynes-Cummings Hamiltonian together with the system-bath interaction described by the Lindblad master equation. We calculate the thermodynamic quantities for the two-level system and the quantum photocell including the change in system energy, the power delivered by photon pulses, the power output to an external load, the heat dissipated to a cold bath, and the entropy production. We thereby demonstrate how a quantum photocell in the cold bath can operate as a continuum quantum heat engine with a sequence of photon pulses continuously applied. We specifically introduce the power efficiency of the quantum photocell in terms of the ratio of output power delivered to an external load with current and voltage to the input power delivered by the photon pulse. Our study indicates a possibility that a quantum system driven by external fields can act as an efficient quantum heat engine under non-equilibrium thermodynamics.


Autoantibodies to extracellular matrix protein 1 in lichen sclerosus.
Lichen sclerosus is a common acquired inflammatory disorder of skin and mucous membranes. The aetiology is unknown, although HLA-subtype susceptibility and high rates of other autoimmune disorders suggest that autoantibodies to specific mucocutaneous antigens are involved. The clinicopathological similarities between lichen sclerosus and lipoid proteinosis, which results from mutations in extracellular matrix protein 1 (ECM1), suggest this protein as an autoantigen. We analysed serum autoantibody profiles in 171 individuals (86 with lichen sclerosus, 85 healthy controls) by immunoblotting of extracts from normal human skin and lipoid proteinosis skin (lacking ECM1). We generated a full-length glutathione-S-transferase fusion protein for ECM1 to confirm specific immunoreactivity. We affinity-purified serum from patients with lichen sclerosus and did indirect immunofluorescence microscopy on normal skin with or without preabsorption with recombinant ECM1. By immunoblotting, IgG autoantibodies were found in 20 (67% [95% CI 45-84]) of 30 lichen sclerosus serum samples. The highest titre was 1 in 20. The bands were not detected in ECM1-deficient substrate. These samples, and those from 56 other patients with lichen sclerosus, showed immunoreactivity to the recombinant ECM1 protein (64 of 86 positive; 74% [65-84]). Only six (7% [2-13]) of 85 control serum samples were positive. Affinity-purified IgG from serum of patients with lichen sclerosus labelled skin similarly to a polyclonal antibody to ECM1. The positive staining was blocked by preabsorption with excess recombinant ECM1 protein. These findings provide evidence for a specific humoral immune response to ECM1 in lichen sclerosus and offer insight into disease diagnosis, monitoring, and approaches to treatment.


Effect of fudosteine on mucin production.
Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.


Diagnosis of human immunodeficiency virus type 1 infection with different subtypes using rapid tests.
We evaluated six rapid tests for their sensitivity and specificity in diagnosing human immunodeficiency virus type 1 (HIV-1) infection using 241 specimens (172 HIV-1 positive, 69 HIV-1 negative) representing different HIV-1 subtypes (A [n = 40], B [n = 47], C [n = 28], E [n = 42], and F [n = 7]). HIVCHEK, Multispot, RTD and SeroStrip were 100% sensitive and specific. Capillus failed to identify two of eight subtype C specimens (overall sensitivity of 98. 85%), while the SUDS test (the only test approved by the Food and Drug Administration) gave false-positive results for 5 of 69 seronegative specimens (specificity of 93.24%). Our results suggest that although rapid tests perform well in general, it may be prudent to evaluate a rapid test for sensitivity and specificity in a local population prior to its widespread use.


Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a probe of the pore.
We compared the effects of mutations in transmembrane segments (TMs) TM1, TM5, and TM6 on the conduction and activation properties of the cystic fibrosis transmembrane conductance regulator (CFTR) to determine which functional property was most sensitive to mutations and, thereby, to develop a criterion for measuring the importance of a particular residue or TM for anion conduction or activation. Anion substitution studies provided strong evidence for the binding of permeant anions in the pore. Anion binding was highly sensitive to point mutations in TM5 and TM6. Permeability ratios, in contrast, were relatively unaffected by the same mutations, so that anion binding emerged as the conduction property most sensitive to structural changes in CFTR. The relative insensitivity of permeability ratios to CFTR mutations was in accord with the notion that anion-water interactions are important determinants of permeability selectivity. By the criterion of anion binding, TM5 and TM6 were judged to be likely to contribute to the structure of the anion-selective pore, whereas TM1 was judged to be less important. Mutations in TM5 and TM6 also dramatically reduced the sensitivity of CFTR to activation by 3-isobutyl 1-methyl xanthine (IBMX), as expected if these TMs are intimately involved in the physical process that opens and closes the channel.


[Hospital infection surveillance in 5 Roman intensive care units].
The A.A. carried out a survey on hospital acquired infection (HAI) in the intensive care units (ICU) of five roman hospitals. The study monitored the following site-specific infection rates: pneumonia (PNE), blood stream infections (BSI), urinary tract infections (UTI), surgical site infections (SSI). According to CDC definitions all patients developing infection 48 hours or more after ward admission were included. Furthermore risk factors (i.e. age, sex, SAPS II), invasive procedures (i.e. endotracheal intubation, vascular and urinary catheterisation), microbiological isolates and their antibiotic susceptibility were screened. The overall 503 patients characteristics (i.e., age, length of stay, case-mix...) showed the wards as general ICU's. Although the SAPS II score was similar, mortality (18.2%-42.9%) and general infection rates (15.4%-40.4%) among the five ICU's were considerably variable (p < 0.05), as HAI episodes distribution by type: PNE (37-88%), BSI (6-42%), UTI (6-24%), SSI (3-7%) (p < 0.05). Also device-associated infection rates such as Ventilator-associated PNE (11.6-24.6@1000), Vascular catheter-associated BSI (3.4-19.2@1000). Urinary catheter-associated UTI (2.6-14.0@1000) and invasive procedures management were different. Among the infected patients the most commonly isolated microorganisms were P. aeruginosa and Staphylococcus spp., which presented a considerable antibiotic resistance. The study showed: 1) sampling (i.e. blood cultures, tracheal aspirate and urine samples) and laboratory methodology indispensable for a correct HAI diagnosis were not standardized in the five ICU's; 2) hospital infection control policy was not carried out in all ICU's. The study showed a lack of standardization which limits the comparability of the general roman ICU's.


Spike synchronization in the cortex/basal-ganglia networks of Parkinsonian primates reflects global dynamics of the local field potentials.
Cortical local field potentials (LFPs) reflect synaptic potentials and accordingly correlate with neuronal discharge. Because LFPs are coherent across substantial cortical areas, we hypothesized that cortical spike correlations could be predicted from them. Because LFPs recorded in the basal ganglia (BG) are also correlated with neuronal discharge and are clinically accessible in Parkinson's disease patients, we were interested in testing this hypothesis in the BG, as well. We recorded LFPs and unit discharge from multiple electrodes, which were placed in primary motor cortex or in the basal ganglia (striatum and pallidum) of two monkeys before and after rendering them parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We used the method of partial spectra to construct LFP predictors of the spike cross-correlation functions (CCFs). The predicted CCF is an estimate of the correlation between two neurons under the assumption that their association is explained solely by the association of each with the LFP recorded on a third electrode. In the normal condition, the predictors account for cortical rate covariations but not for the association among the tonically active neurons of the striatum. In the parkinsonian condition, with the appearance of 10 Hz oscillations throughout the cortex-basal ganglia networks, the LFP predictors account remarkably better for the CCFs in both the cortex and the basal ganglia. We propose that, in the parkinsonian condition, the cortex-basal ganglia networks are more tightly related to global modes of brain dynamics that are echoed in the LFP.


Recent progress on phenotype-based discovery of dengue inhibitors.
Dengue fever is the world's most prevalent mosquito-borne viral disease caused by the four serotypes of dengue virus, which are widely spread throughout tropical and sub-tropical countries. There has been an urgent need to identify an effective and safe dengue inhibitor as a therapeutic and a prophylactic agent for dengue fever. Most clinically approved antiviral drugs for the treatment of human immunodeficiency syndrome-1 (HIV-1) and hepatitis C virus (HCV) target virally encoded enzymes such as protease or polymerase. Inhibitors of these enzymes were typically identified by target-based screening followed by optimization via structure-based design. However, due to the lack of success to date of research efforts to identify dengue protease and polymerase inhibitors, alternative strategies for anti-dengue drug discovery need to be considered. As a complementary approach to the target-based drug discovery, phenotypic screening is a strategy often used in identification of new chemical starting points with novel mechanisms of action in the area of infectious diseases such as antibiotics, antivirals, and anti-parasitic agents. This article is an overview of recent reports on dengue phenotypic screens and discusses phenotype-based hit-to-lead chemistry optimization. The challenges encountered and the outlook on dengue phenotype-based lead discovery are discussed at the end of this article.


Does the association between mitral valve prolapse and panic disorder really exist?
Although the possible relationship between panic disorder and mitral valve prolapse (MVP) attracted considerable research interest in the 1980s and 1990s, the reported prevalence of MVP in these patients has been inconsistent and widely variable. Clinical and epidemiologic studies have produced controversial data on possible association or definite causal relationship between these 2 entities. The primary objective of the present review was to summarize the current state of knowledge on the association between panic disorder and MVP, including the influence of diagnostic criteria for MVP on the controversial results. We searched MEDLINE, LILACS, and EMBASE databases using the keywords panic and mitral. Inclusion criteria were articles concerning the reciprocal association of MVP and panic disorder, published from the earliest dates available through December 2006. All relevant articles published in English, Spanish, or Portuguese and reporting original data related to the association of MVP and panic disorder were included. Forty articles fulfilling the criteria for inclusion in this review were identified. Even though the reported prevalence of MVP in panic disorder varied from 0% to 57%, a significant association between the 2 disorders was documented in 17 of the 40 studies. Such inconsistent results were due to sampling biases in case or control groups, widely different diagnostic criteria for MVP, and lack of reliability of MVP diagnosis. None of the reviewed studies used the current state-of-the-art diagnostic criteria for MVP to evaluate the volunteers. Apparently, the more elaborate the study methodology, the lower the chance to observe a significant relationship between these 2 conditions. Published results are insufficient to definitely establish or to exclude an association between MVP and panic disorder. If any relationship does actually exist, it could be said to be infrequent and mainly occur in subjects with minor variants of MVP. To clarify this intriguing issue, future studies should mainly focus on the observed methodological biases and particularly should use the current criteria for MVP as the standard for evaluation.


Negative but Not Positive Alcohol-Related Consequences Tend to Occur Above the Heavy Episodic Drinking Threshold: A Daily Study of Young Adult Heavy Drinkers.
This study used event-level data to identify the threshold (i.e. number of standard alcoholic drinks) at which specific negative and positive alcohol-related consequences are likely to occur. Ninety-six college students aged 18-20 reporting weekly heavy episodic drinking (HED) or at least one negative alcohol-related consequence in the past 2 weeks completed ecological momentary assessment over 28 days. Participants reported number of standard drinks consumed and negative (e.g. nausea) and positive (e.g. new friend) alcohol-related consequences on 492 drinking nights. The area under the receiver operating characteristic (AUROC) curve measured the ability of an increasing number of drinks consumed to discriminate between nights with versus without a given consequence. The Youden Index method was used to identify the optimal threshold of drinks for each consequence. Thresholds were examined for each consequence by participants' biological sex and heavy drinking status. Across subgroups, most consequences occurred on nights where participants reported higher consumption levels relative to nights where consequences did not occur. Thresholds for negative consequences ranged between four and nine drinks and thresholds for positive consequences were between three and six drinks. Many negative consequences are likely to occur following the traditional HED threshold of 4+/5+ drinks (females/males), with more severe consequences occurring at slightly higher thresholds. Positive consequences are likely to occur at lower thresholds. There may be an optimal number of drinks that maximize positive while minimizing negative consequences for heavy drinking college students.


Subretinal macrophages produce classical complement activator C1q leading to the progression of focal retinal degeneration.
The role of the alternative complement pathway and its mediation by retinal microglia and macrophages, is well-established in the pathogenesis of Age-Related Macular Degeneration (AMD). However, the contribution of the classical complement pathway towards the progression of retinal degenerations is not fully understood, including the role of complement component 1q (C1q) as a critical activator molecule of the classical pathway. Here, we investigated the contribution of C1q to progressive photoreceptor loss and neuroinflammation in retinal degenerations. Wild-type (WT), C1qa knockout (C1qa-/-) and mice treated with a C1q inhibitor (ANX-M1; Annexon Biosciences), were exposed to photo-oxidative damage (PD) and were observed for progressive lesion development. Retinal function was assessed by electroretinography, followed by histological analyses to assess photoreceptor degeneration. Retinal inflammation was investigated through complement activation, macrophage recruitment and inflammasome expression using western blotting, qPCR and immunofluorescence. C1q was localised in human AMD donor retinas using immunohistochemistry. PD mice had increased levels of C1qa which correlated with increasing photoreceptor cell death and macrophage recruitment. C1qa-/- mice did not show any differences in photoreceptor loss or inflammation at 7 days compared to WT, however at 14 days after the onset of damage, C1qa-/- retinas displayed less photoreceptor cell death, reduced microglia/macrophage recruitment to the photoreceptor lesion, and higher visual function. C1qa-/- mice displayed reduced inflammasome and IL-1β expression in microglia and macrophages in the degenerating retina. Retinal neutralisation of C1q, using an intravitreally-delivered anti-C1q antibody, reduced the progression of retinal degeneration following PD, while systemic delivery had no effect. Finally, retinal C1q was found to be expressed by subretinal microglia/macrophages located in the outer retina of early AMD donor eyes, and in mouse PD retinas. Our data implicate subretinal macrophages, C1q and the classical pathway in progressive retinal degeneration. We demonstrate a role of local C1q produced by microglia/macrophages as an instigator of inflammasome activation and inflammation. Crucially, we have shown that retinal C1q neutralisation during disease progression may slow retinal atrophy, providing a novel strategy for the treatment of complement-mediated retinal degenerations including AMD.


Complications of smallpox vaccination, 1968. Results of a statewide survey in Alaska.
A survey was made to determine the incidence in Alaska of complications of smallpox vaccination during 1968. Of the 206 medical personnel responding to the questionnaire, 20 (or 9.7 percent) observed a complication. Twenty-six complications were reported, 20 of which occurred in primary vaccinees. Accidental implantation was the most common complication, but two cases of eczema vaccinatum and two of generalized vaccinia were observed. There were no deaths or cases of postvaccinial encephalitis or vaccinia necrosum. Of the 26 complications, 19 were theoretically preventable.


Analysis of spatiotemporal pattern correction using a computational model of the auditory periphery.
The purpose of this study was to determine the cause of poor experimental performance of a spatiotemporal pattern correction (SPC) scheme that has been proposed as a hearing aid algorithm and to determine contexts in which it may provide benefit. The SPC scheme is intended to compensate for altered phase response and group delay differences in the auditory nerve spiking patterns in impaired ears. Based on theoretical models of loudness and the hypothesized importance of temporal fine structure for intelligibility, the compensations of the SPC scheme are expected to provide benefit; however, preliminary experiments revealed that listeners preferred unprocessed or minimally processed speech as opposed to complete SPC processed speech. An improved version of the SPC scheme was evaluated with a computational auditory model in response to a synthesized vowel at multiple SPLs. The impaired model auditory nerve response to SPC-aided stimuli was compared to the unaided stimuli for spectrotemporal response similarity to the healthy auditory model. This comparison included analysis of synchronized rate across auditory nerve characteristic frequencies and a measure of relative phase response of auditory nerve fibers to complex stimuli derived from cross-correlations. Analysis indicates that SPC can improve a metric of relative phase response at low SPLs, but may do so at the cost of decreased spectrotemporal response similarity to the healthy auditory model and degraded synchrony to vowel formants. In-depth analysis identifies several technical and conceptual problems associated with SPC that need to be addressed. These include the following: (1) a nonflat frequency response through the analysis-synthesis filterbank that results from time-varying changes in the relative temporal alignment of filterbank channels, (2) group delay corrections that are based on incorrect frequencies because of spread of synchrony in auditory nerve responses, and (3) frequency modulations in the processed signal created by the insertion of delays. Despite these issues, SPC provided benefit to an error metric derived from auditory nerve response cross-correlations at low SPLs, which may mean phase adjustment is achieved at the expense of other metrics, but could be beneficial for low-level speech.


Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: a preliminary randomized controlled trial.
Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions' similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout.


Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells.
Alpha-lipoic acid, which becomes a powerful antioxidant in its reduced form, has been suggested as a dietary supplement to treat diseases associated with excessive oxidant stress. Because the vascular endothelium is dysfunctional in many of these conditions, we studied the uptake, reduction, and antioxidant effects of alpha-lipoic acid in cultured human endothelial cells (EA.hy926). Using a new assay for dihydrolipoic acid, we found that EA.hy926 cells rapidly take up and reduce alpha-lipoic acid to dihydrolipoic acid, most of which is released into the incubation medium. Nonetheless, the cells maintain dihydrolipoic acid following overnight culture, probably by recycling it from alpha-lipoic acid. Acute reduction of alpha-lipoic acid activates the pentose phosphate cycle and consumes nicotinamide adenine dinucleotide phosphate (NADPH). Lysates of EA.hy926 cells reduce alpha-lipoic acid using both NADPH and nicotinamide adenine dinucleotide (NADH) as electron donors, although NADPH-dependent reduction is about twice that due to NADH. NADPH-dependent alpha-lipoic acid reduction is mostly due to thioredoxin reductase. Pre-incubation of cells with alpha-lipoic acid increases their capacity to reduce extracellular ferricyanide, to recycle intracellular dehydroascorbic acid to ascorbate, to decrease reactive oxygen species generated by redox cycling of menadione, and to generate nitric oxide. These results show that alpha-lipoic acid enhances both the antioxidant defenses and the function of endothelial cells.


Feeding strategies to optimize vanillin production by Amycolatopsis sp. ATCC 39116.
The growing consumer demand for natural products led to an increasing interest in vanillin production by biotechnological routes. In this work, the biotechnological vanillin production by Amycolatopsis sp. ATCC 39116 is studied using ferulic acid as precursor, aiming to achieve maximized vanillin productivities. During biotech-vanillin production, the effects of glucose, vanillin and ferulic acid concentrations in the broth proved to be relevant for vanillin productivity. Concerning glucose, its presence in the broth during the production phase avoids vanillin conversion to vanillic acid and, consequently, increases vanillin production. To avoid the accumulation of vanillin up to a toxic concentration level, a multiple-pulse-feeding strategy is implemented, with intercalated vanillin removal from the broth and biomass recovery. This strategy turned out fruitful, leading to 0.46 g L-1 h-1 volumetric productivity of vanillin of and a production yield of 0.69 gvanillin gferulic acid-1, which are among the highest values reported in the literature for non-modified bacteria.


Magnetic solid phase extractions of Co(II) and Hg(II) by using magnetized C. micaceus from water and food samples.
A new bio-MSPE sorbent based on the use of C. micaceus and γ-Fe2O3 magnetic nanoparticle was prepared for the preconcentrations of Co(II) and Hg(II). Critical parameters including pH, flow rate, quantity of C. micaceus, quantity of γ-Fe2O3 magnetic nanoparticle, eluent (type, concentration and volume), sample volume, and foreign ions were examined. Surface structure and variations after interaction with Co(II) and Hg(II) of bio-MSPE sorbent were investigated by FT-IR, SEM, and EDX. The impact of bio-MSPE column reusage was also tested. The biosorption capacities were determined as 24.7 mg g-1 and 26.2 mg g-1, respectively for Co(II) and Hg(II). Certified reference materials were utilized to find out the accuracy of the prepared bio-MSPE method. This novel bio-MSPE method was accomplished by being applied to real food and water samples. In particular, it will be possible to make use of C. micaceus as new alternatives, in environmental biotechnology applications.


Assessment of sexual drive and desire in women with premenstrual dysphoric disorder who have been treated with fluoxetine.
Objective To explore the impact of treatment with fluoxetine on sexual drive and desire (SDD) in women with premenstrual dysphoric disorder (PMDD). Methods Data were collected during a randomised, controlled, double-blind trial evaluating the efficacy of fluoxetine 20 or 60 mg/day versus placebo in the treatment of women with PMDD. Study subjects rated their SDD on the Premenstrual Tension Scale, Self Rating (PMTS-SR) during their follicular and luteal phases of the placebo run in cycles and the double-blind treatment cycles. Data were analyzed using chi-square test. Results Data were available for 184 subjects who rated their SDD during the follicular and luteal phases of two baseline (placebo) cycles and the following two treatment cycles. There was a trend for more women on fluoxetine to report improvement in luteal phase SDD compared to women on placebo (P=0.057). Conclusions Our data, contrary to expectations, suggest that fluoxetine treatment may restore SDD in women who experience decreased SDD as part of a cluster of symptoms associated with PMDD. Future trials with SSRIs should include specific measures of sexual functioning to further examine the potential beneficial versus side effects of these medications as they relate to phases of the menstrual cycle.


A 25-year retrospective study of Chlamydia psittaci in association with equine reproductive loss in Australia.
Introduction. Chlamydia psittaci is primarily a pathogen of birds but can also cause disease in other species. Equine reproductive loss caused by C. psittaci has recently been identified in Australia where cases of human disease were also reported in individuals exposed to foetal membranes from an ill neonatal foal in New South Wales.Hypothesis/Gap Statement. The prevalence of C. psittaci in association with equine reproductive over time and in different regions of Australia is not known.Aim. This study was conducted to detect C. psittaci in equine abortion cases in Australia using archived samples spanning 25 years.Methodology. We tested for C. psittaci in 600 equine abortion cases reported in Australia between 1994 to 2019 using a Chlamydiaceae real-time quantitative PCR assay targeting the 16S rRNA gene followed by high-resolution melt curve analysis. Genotyping and phylogenetic analysis was performed on positive samples.Results. The overall prevalence of C. psittaci in material from equine abortion cases was 6.5 %. C. psittaci-positive cases were detected in most years that were represented in this study and occurred in Victoria (prevalence of 7.6 %), New South Wales (prevalence of 3.9 %) and South Australia (prevalence of 15.4 %). Genotyping and phylogenetic analysis showed that the C. psittaci detected in the equine abortion cases clustered with the parrot-associated 6BC clade (genotype A/ST24), indicating that infection of horses may be due to spillover from native Australian parrots.Conclusion. This work suggests that C. psittaci has been a significant agent of equine abortion in Australia for several decades and underscores the importance of taking appropriate protective measures to avoid infection when handling equine aborted material.


Mouse glomerular epithelial cells in culture with features of podocytes in vivo express aminopeptidase A and angiotensinogen but not other components of the renin-angiotensin system.
The binding of antibodies to podocytic antigens such as the Heymann antigen or aminopeptidase A may lead to the induction of a membranous glomerulonephritis in several species. To study the possible future interactions of antibodies with antigens on these podocytes, epithelial cells from isolated mouse glomeruli were cultured. By indirect immunofluorescence, the cells were positive for cytokeratin, vimentin, desmin, and the ZO-1 protein, a component of the tight junction complex. When rat monoclonal antibodies were used, the cells were also positive for the hydrolases aminopeptidase A and dipeptidyl peptidase IV, and they stained with ASD-33, a monoclonal antibody that recognized an epitope only present on the cell membranes of mouse podocytes. They were negative for the von Willebrand factor and did not stain with a monoclonal antibody (ASD-13) that binds to endothelial cells of glomeruli and peritubular capillaries. By electron microscopy, the cells showed tight junctions but lacked Weibel Palade bodies (endothelium), desmosomes, and cilia (parietal epithelium). The mRNA expression of several components of the renin-angiotensin system was also examined, and some factors indirectly coupled to the renin-angiotensin system component angiotensin II in this podocytic culture by RT-PCR analysis. mRNA Expression for the angiotensin II degrading hydrolase aminopeptidase A and angiotensinogen was found, but this was not found for any other component of this system, such as renin, angiotensin-converting enzyme, or the angiotensin II receptors AT1a, AT1b, and AT2. Low mRNA expression for dipeptidyl peptidase IV was observed. In addition, expression of the growth factors transforming growth factor-beta and interleukin-7, and the extracellular matrix components fibronectin, laminin B2, perlecan, and collagen IV alpha 1, was observed. Given these characteristics, a glomerular epithelial cell culture with features of podocytes in vivo that will allow future studies on the interaction of anti-aminopeptidase A monoclonal antibodies and angiotensin II with aminopeptidase A was established. This is of interest in light of the observation that injection of mice with anti-aminopeptidase A antibodies causes an acute albuminuria.


K(ATP) channel therapeutics at the bedside.
The family of potassium channel openers regroups drugs that share the property of activating adenosine triphosphate-sensitive potassium (K(ATP)) channels, metabolic sensors responsible for adjusting membrane potential-dependent functions to match cellular energetic demands. K(ATP) channels, widely represented in metabolically-active tissue, are heteromultimers composed of an inwardly rectifying potassium channel pore and a regulatory sulfonylurea receptor subunit, the site of action of potassium channel opening drugs that promote channel activity by antagonizing ATP-induced pore inhibition. The activity of K(ATP) channels is critical in the cardiovascular adaptive response to stress, maintenance of neuronal electrical stability, and hormonal homeostasis. Thereby, K(ATP) channel openers have a unique therapeutic spectrum, ranging from applications in myopreservation and vasodilatation in patients with heart or vascular disease to potential clinical use as bronchodilators, bladder relaxants, islet cell protector, antiepileptics and promoters of hair growth. While the current experience in practice with potassium channel openers remains limited, multitude of ongoing investigations aims at defining the benefit of this emerging family of therapeutics in diverse disease conditions associated with metabolic distress.


Simulation of patient encounters using a virtual patient in periodontology instruction of dental students: design, usability, and learning effect in history-taking skills.
Simulations are important educational tools in the development of health care competence. This study describes a virtual learning environment (VLE) for diagnosis and treatment planning in oral health care. The VLE is a web-based, database application where the learner uses free text communication on the screen to interact with patient data. The VLE contains forms for history taking, clinical images, clinical data and X-rays. After reviewing the patient information, the student proposes therapy and makes prognostic evaluations of the case in free text. A usability test of the application was performed with seven dental students. The usability test showed that the software responded with correct answers to the majority of the free text questions. The application is generic in its basic functions and can be adapted to other dental or medical subject areas. A randomised controlled trial was carried out with 39 students who attended instruction in history taking with problem-based learning cases, lectures and seminars. In addition, 16 of the 39 students were randomly chosen to practise history taking using the virtual patient prior to their first patient encounter. The performance of each student was recorded on video during the patient sessions. The type and order of the questions asked by the student and the degree of empathy displayed towards the patient were analysed systematically on the videos. The data indicate that students who also undertook history taking with a virtual patient asked more relevant questions, spent more time on patient issues, and performed a more complete history interview compared with students who had only undergone standard teaching. The students who had worked with the virtual patient also seemed to have more empathy for the patients than the students who had not. The practising of history taking with a virtual patient appears to improve the capability of dental students to take a relevant oral health history.


Hyperbaric oxygen for mTBI-associated PCS and PTSD: Pooled analysis of results from Department of Defense and other published studies.
Some clinical trials report improvement in persistent post-concussive symptoms (PCS) with hyperbaric oxygen (HBO2) following mild traumatic brain injury (mTBI), but questions remain regarding the utility of HBO2 for PCS, the effects of HBO2 on post-traumatic stress disorder (PTSD), and the influences of sham control exposures. A systematic review and pooled analysis was conducted to summarize available evidence for HBO2 in mTBI-associated PCS ± PTSD. Data aggregated from four Department of Defense (DoD) studies with participant-level data (n=254) were grouped into pooled HBO2 and sham intervention groups. Changes from baseline to post-intervention on PCS, PTSD, and neuropsychological measures were assessed using linear mixed models to evaluate main intervention and intervention-by-baseline PTSD effects. Potential dose-response relationships to oxygen partial pressures were investigated. Intervention effects from three other published studies with summary-level participant data (n=135) were also summarized.. Pooled DoD data analyses indicated trends toward improvement favoring HBO2 for PCS (Rivermead Total Score: -2.3, 95% CI [-5.6, 1.0], p=0.18); PTSD (PTSD Checklist Total Score: -2.7, 95% CI [-5.8, 0.4], p=0.09); and significant improvement in verbal memory (CVLT-II Trial 1-5 Free Recall: 3.8; 95% CI [1.0, 6.7], p=0.01). A dose-response trend to increasing oxygen partial pressure was also found, with a greater HBO2 effect in mTBI-associated PTSD suggested. The direction of results was consistent with other published studies. A definitive clinical trial, with an appropriate control group, should be considered to identify the optimal HBO2 dosing regimen for individuals with mTBI-associated PTSD ± PCS.


The effect of perch access during pullet rearing and egg laying on physiological measures of stress in White Leghorns at 71 weeks of age.
Egg laying strains of chickens have a strong motivation to perch. Providing caged chickens with perches allows them to perform their natural perching behavior and also improves their musculoskeletal health due to exercise. Little is known about the effect of perch access for hens on physiological measures of stress. Our hypothesis was that denying chickens access to perches would elicit a stress response. The objective of this study was to determine the effect of perch access during all or part of life cycle on physiological homeostasis in caged 71-wk-old White Leghorn hens. A total of 1,064 chicks were assigned randomly to cages with and without perches (n = 14 pullet cages/perch treatment) on day of hatch. As pullets aged, chicks were removed from cages to provide more space. At 17 wk of age, 324 chickens in total were assigned to laying cages consisting of 4 treatments with 9 replicates per treatment. Treatment 1 chickens never had access to perches during their life cycle. Treatment 2 chickens had access to perches only from 17 to 71 wk of age (laying phase). Treatment 3 chickens had access to perches only from hatch to 16.9 wk of age (pullet phase). Treatment 4 chickens always had access to perches during their life cycle. At 71 wk of age, chickens were sampled for measurement of plasma catecholamines (epinephrine, norepinephrine, and dopamine) and corticosterone; blood serotonin and Trp; fluctuating asymmetry of shank length and width; and adrenal weight. Only shank width differed among treatments. Chickens with previous exposure to perches during the pullet phase had wider shanks than chickens without access to perches (P = 0.006), suggesting that early perching promoted skeletal development. These results suggest that a stress response was not elicited in 71-wk-old White Leghorn hens that always had access to perches compared with hens that never had access to perches during all or part of their life cycle.


A small decrease of plastid transketolase activity in antisense tobacco transformants has dramatic effects on photosynthesis and phenylpropanoid metabolism.
Transketolase (TK) catalyzes reactions in the Calvin cycle and the oxidative pentose phosphate pathway (OPPP) and produces erythrose-4-phosphate, which is a precursor for the shikimate pathway leading to phenylpropanoid metabolism. To investigate the consequences of decreased TK expression for primary and secondary metabolism, we transformed tobacco with a construct containing an antisense TK sequence. The results were as follows: (1) a 20 to 40% reduction of TK activity inhibited ribulose-1,5-bisphosphate regeneration and photosynthesis. The inhibition of photosynthesis became greater as irradiance increased across the range experienced in growth conditions (170 to 700 micromol m(-2) sec(-1)). TK almost completely limited the maximum rate of photosynthesis in saturating light and saturating CO(2). (2) Decreased expression of TK led to a preferential decrease of sugars, whereas starch remained high until photosynthesis was strongly inhibited. One of the substrates of TK (fructose-6-phosphate) is the starting point for starch synthesis, and one of the products (erythrose-4-phosphate) inhibits phosphoglucose isomerase, which catalyzes the first reaction leading to starch. (3) A 20 to 50% decrease of TK activity led to decreased levels of aromatic amino acids and decreased levels of the intermediates (caffeic acid and hydroxycinnamic acids) and products (chlorogenic acid, tocopherol, and lignin) of phenylpropanoid metabolism. (4) There was local loss of chlorophyll and carotene on the midrib when TK activity was inhibited by >50%, spreading onto minor veins and lamina in severely affected transformants. (5) OPPP activity was not strongly inhibited by decreased TK activity. These results identify TK activity as an important determinant of photosynthetic and phenylpropanoid metabolism and show that the provision of precursors by primary metabolism colimits flux into the shikimate pathway and phenylpropanoid metabolism.


Sound processing in amateur musicians and nonmusicians: event-related potential and behavioral indices.
To increase our understanding of auditory neurocognition in musicians, we compared nonmusicians with amateur band musicians in their neural and behavioral sound encoding accuracy. Mismatch negativity and P3a components of the auditory event-related potentials were recorded to changes in basic acoustic features (frequency, duration, location, intensity, gap) and abstract features (melodic contour and interval size). Mismatch negativity was larger in musicians than in nonmusicians for location changes whereas no statistically significant group difference was observed in response to other feature changes or in abstract-feature mismatch negativity. P3a was observed only in musicians in response to location changes. This suggests that when compared with nonmusicians, even amateur musicians have neural sound processing advantages with acoustic information most essential to their musical genre.


Characterization of the "red zone" of knee meniscus: MR imaging and histologic correlation.
To determine the extent and vascularity of knee menisci with conventional and gadolinium-enhanced magnetic resonance (MR) imaging in cadaveric specimens, with histologic findings as the reference standard, and to investigate signal intensity changes in menisci and perimeniscal soft tissues in symptomatic patients. Radial dimensions and enhancement patterns of menisci were recorded and compared in (a) 12 cadaveric menisci examined with conventional and gadolinium-enhanced intermediate-weighted and fat-suppressed T1-weighted spin-echo MR imaging, high-spatial-resolution T1-weighted and fast low-angle shot MR imaging, and gross anatomic and histologic specimens and (b) 18 patients examined with conventional and gadolinium-enhanced fat-suppressed T1-weighted spin-echo MR imaging. No differences in radial measurements of the meniscus were found for different MR techniques (P =.551). Despite the presence of vessels in the peripheral 10%-15% of the menisci, no enhancement of menisci was detected in specimens or patients. Perimeniscal soft-tissue enhancement adjacent to the posterior horn was greater than that adjacent to the anterior horn (P <.05), and enhancement of the lateral meniscal body was greater than that of the medial meniscal body (P <.05). The wedge-shaped low-signal-intensity structure seen on MR images represents the entire meniscus. Intravenous injection of contrast material does not appear to be useful for differentiation of the vascularized from the nonvascularized zone of the meniscus.


Organoid in colorectal cancer: progress and challenges.
Patient-derived tumor organoids (PDOs) currently represent important modeling tools in pre-clinical investigation of malignancies. Organoid cultures conserve the genetic and phenotypic characteristics of the original tumor and maintain its heterogeneity, allowing their application in many research fields. PDOs derived from colorectal cancer (CRC) have been used for genetic modeling to investigate the function of driver genes. Some researchers have been exploring the value of CRC PDOs in chemotherapy, targeted therapy, and radiotherapy response prediction. The successful generation of PDOs derived from CRC could deepen our understanding of CRC biology and provide novel tools for cancer modeling, for realizing precision medicine by assessing specimens from individual patients ex vivo. The present review discusses recently reported advances in CRC PDOs and the challenges they face as pre-clinical models in CRC research.


Reactivity of T lymphotropic retrovirus antibody (12/1-2) in man: comparison of epidermis with other epithelial cells.
The reactivity of a monoclonal antibody against human T lymphotropic retrovirus (antibody 12/1-2, recognising the HTLV-1 p19 internal core viral protein) with benign and malignant cutaneous biopsy specimens was examined and compared with results obtained on normal skin, on various other human cells and tissues, and on immunoblotted extracts of tonsil squamous epithelium. In keeping with previous studies, 12/1-2 labelled a proportion of the thymic epithelial stroma and the entire layer of basal cells in stratified non-keratinized and keratinized epithelium. Furthermore, antibody 12/1-2 reacted with basal cell carcinomas and showed an essentially identical staining pattern in normal skin, cutaneous T cell lymphomas, and a range of benign dermatoses. The dot blot preparations showed that 12/1-2 recognised an antigen associated with keratin intermediate filaments. These data indicate that antibody 12/1-2 forms a useful marker for subsets of epithelial cells, which presumably participate in T cell education, and that a range of cutaneous disorders of widely different aetiology show no abnormalities in epithelial expression of this antigen.


Neuropsychological investigation of "the amazing memory man".
Mnemonists, memory champions, and persons with highly superior autobiographical memory (HSAM) are apparently rare breeds, with no more than a few dozen cases of each described in the neuroscientific literature. This report describes a newly discovered HSAM case who has extraordinary memory for a wider range of material than has heretofore been described. Subject MM was interviewed about his personal life and administered standard clinical tests of cognition and personality, as well as experimental tasks assessing personal and generic episodic and semantic memory. Finally, he was studied with high resolution structural MRI of the medial temporal lobes, as well as brain connectivity analysis using resting-state functional MRI. MM's ability to recall general factual information, historical facts and dates, sports statistics, and popular culture, as well as personal life experiences, is exceptional, even though he performs in only the average range on tests of intellect and new learning ability. Unlike most mnemonists, he denies using any specific mnemonic strategy and, unlike many other HSAM cases, is unable to recall highly specific details of days in his adult life. Structural brain imaging in MM reveals atypical anatomy in his left temporal lobe, and functional neuroimaging suggests greater than usual connectivity of the left hippocampus with premotor, prefrontal and retrosplenial cingulate cortex. These observations are discussed in the context of previous studies of mnemonists and HSAM cases, some of which implicate hyperconnectivity among components of an expanded memory network in extraordinary memory retrieval. (PsycINFO Database Record


Link between defoliation and light treatments on root vitality of five understory shrubs with different resistance to insect herbivory.
Understory shrubs are frequently attacked by insect herbivores. However, very little is known regarding possible interactions between light condition, defoliation (D) and fine root vitality (% live roots) and metabolic activity, and whether different plant strategies (compensation, trade-off and equilibrium) to defoliation depend on individual species light requirements. To explore the response of roots to such conditions, an experiment was established in which we experimentally removed 50% of leaves in 1-year-old seedlings of Sambucus nigra, Cornus sanguinea, Prunus serotina, Frangula alnus and Corylus avellana grown in 15% and full sunlight. On average, defoliation leads to a 15% reduction in fine root (< 2 mm) vitality (% live roots). However, a statistically significant reduction in root vitality after defoliation was detected only in those species that are less herbivorized in nature (48% in S. nigra and 5% in C. sanguinea). On average, shade conditions (L) resulted in 18% decline in root vitality, and the effects of defoliation were also 22% higher than for plants grown in full light. Root vitality in both treatments (D and L) was significantly correlated with their dry mass, concentration of total phenol (TPh) and carbon to nitrogen ratio, and negatively correlated with nitrogen, soluble carbohydrates, starch and total non-structural carbohydrates (TNC). To a large extent, root vitality and chemistry varied by species. Higher root vitality was related to higher concentrations of phenolics, more than to N and TNC concentrations. Concentrations of phenolics also differed significantly between defoliated plants and controls. However, in defoliated plants, an increase in TPh was observed only in two species, which belong to two different groups in light requirements and susceptibility to insect grazing (C. sanguinea and P. serotina). This study indicated that higher vitality of roots occurred in species that are characterized by higher insect defoliation under natural conditions. It is likely that higher root vitality of these species was related to their high level of TPh and tannins. This was especially noticeable for the reduced light treatment, which represents natural conditions under which insect defoliation is highest. Our results suggest that varied strategies of resource allocation were used by the different species in response to variations in light and defoliation.


[Dynamics and scientific prognosis of stomach cancer].
Stomach cancer will remain one of the most prevalent malignant neoplasms on a global scale and in the foreseeable future. Its etiology is considered to comprise many factors including damaging environmental factors, genetic disorders and risk factors of Helicobacter pylori infection.


A comparison of the potency of newly developed oximes (K347, K628) and currently available oximes (obidoxime, HI-6) to counteract acute neurotoxic effects of Tabun in rats.
The ability of newly developed oximes (K347, K628) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oximes (obidoxime, HI-6) using a functional observational battery. The neuroprotective effects of the oximes studied (K347, K628, obidoxime, HI-6) combined with atropine on rats poisoned with tabun at a sublethal dose (220 microg/kg i.m.; 80% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by a functional observational battery and automatic measurement of motor activity at 24 hours following tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive 24 hours following tabun challenge. Both newly developed oximes (K347, K628) combined with atropine are able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings but they do not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease the tabun-induced acute neurotoxicity is higher than that of the oxime HI-6 and it is slightly slower than the neuroprotective efficacy of obidoxime. As the neuroprotective potency of both newly developed oximes (K347, K628) is not as high as the potency of obidoxime, they are not a suitable replacement for obidoxime for the treatment of acute tabun poisonings.


An ICF-based assessment schedule to facilitate the assessment and reporting of functioning in manual medicine - low back pain as a case in point.
This paper outlines the first steps toward developing the ICF-based assessment schedule for manual medicine with a focus on low back pain (LBP). It reports on the results of a consensus process to develop the default and optional versions of the set of ICF categories (ManMed Set) the assessment schedule should cover, and gives insight in expert input toward building a toolbox of instruments for assessing the ManMed Set categories. A scoping review and qualitative study were conducted, each resulting in a list of ICF categories. These categories, along with the categories of the ICF Generic-30 Set, Comprehensive ICF Core Set for LBP, and from an existing Delphi study, served as the starting point for an established consensus process to decide on the ManMed Set. After alternating plenary and working group sessions, an iterative ranking process and cut-off calculation, the multi-professional and international group of 20 experts in manual medicine included 23 categories in the default ManMed version (16 + the ICF Generic-7 Set categories) and 25 in the optional version. Their development is a major step toward developing an assessment schedule that can be employed in standardizing the assessment and reporting of functioning in manual medicine, initially of LBP patients.Implications for rehabilitationThe ICF assessment schedule for manual medicine has potential use in supporting rehabilitation practice, such as for planning interventions, defining rehabilitation goals, and measuring and documenting functioning outcomes.It can be used to promote interdisciplinary coordination of care and facilitate communication between members of a multidisciplinary rehabilitation team within manual medicine and beyond.The ICF assessment schedule for manual medicine can facilitate rehabilitation and manual medicine research by providing evidence for optimizing rehabilitation practice.


Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays.
A chemical selection procedure has been used to prepare a hybrid hybridoma cell line (P4C1) following fusion of two previously established hybridomas secreting antiperoxidase and antisubstance P, respectively. P4C1 secretes bispecific monoclonal antibody alongside the two parental antibodies, with no visible inactive heterologous heavy-light chain pairs. The bispecific monoclonal antibody is thus easy to purify in excellent yields. The advantage of its monovalency for one antigen and simultaneous binding of a marker enzyme has been explored for its potential use in competitive immunoassays. Its use in immunocytochemistry led to major improvements in sensitivity, signal-to-noise ratio, simplification of staining procedures, and ultrastructural preservation of subcellular elements. Particularly remarkable was that, unlike conventional procedures, the immunoreaction with the bispecific monoclonal antibody was homogeneously distributed across the entire thickness of a 50-micron section.


Antioxidant enzymes mediate survival of breast cancer cells deprived of extracellular matrix.
Metastasis by cancer cells relies upon the acquisition of the ability to evade anoikis, a cell death process elicited by detachment from extracellular matrix (ECM). The molecular mechanisms that ECM-detached cancer cells use to survive are not understood. Striking increases in reactive oxygen species (ROS) occur in ECM-detached mammary epithelial cells, threatening cell viability by inhibiting ATP production, suggesting that ROS must be neutralized if cells are to survive ECM-detachment. Here, we report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after ECM-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. Conversely, silencing antioxidant enzyme expression in multiple breast cancer cell lines caused ATP reduction and compromised anchorage-independent growth. Notably, antioxidant enzyme-deficient cancer cells were compromised in their ability to form tumors in mice. In aggregate, our results reveal a vital role for antioxidant enzyme activity in maintaining metabolic activity and anchorage-independent growth in breast cancer cells. Furthermore, these findings imply that eliminating antioxidant enzyme activity may be an effective strategy to enhance susceptibility to cell death in cancer cells that may otherwise survive ECM-detachment.


Prospective randomized study of the tolerability and efficacy of combination therapy for hypertensive chronic kidney disease: results of the PROTECT-CKD study.
We conducted a randomized, open-label trial to determine which of the antihypertensive drugs was most beneficial for CKD patients with hypertension in spite of treatment with an angiotensin receptor blocker (ARB). Patients 20-75 years of age who had CKD according to the definition in the K/DOQI Guidelines and hypertension (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg) with the usual dose of an ARB were randomly assigned to receive losartan 50 mg plus 5 mg of the calcium channel blocker amlodipine (CCB group, n = 37), 5 mg of the angiotensin-converting enzyme inhibitor enalapril (ACEI group, n = 36), or 12.5 mg of the thiazide diuretic hydrochlorothiazide (HCTZ group, n = 36). The primary endpoints were changes in blood pressure (BP), ratio of urinary excretion of protein to creatinine (UPCR), tolerability, and eGFR during the 12-month treatment period compared with control period. There were no significant differences in BP and tolerability between the three groups. The percentage changes in UPCR at 12 months after start of the combination therapy were significantly different in the HCTZ group (-26.3 ± 11.1 %, mean ± SE) and CCB group (+46.7 ± 33.6 %, p < 0.05), while eGFR was significantly lower in the HCTZ group than in the ACEI group or CCB group at 4 months but not at 12 months. Addition of diuretics, CCB, or ACEI to ARB was equally effective for the control of hypertension in CKD, while, in terms of urinary excretion of protein, diuretics may be better than CCB.


Psychoactive substance use among Arab adolescent school dropouts in Israel: a phenomenon and its implications.
This comprehensive study is the first to examine rates of legal and illegal psychoactive substance use and their predictors specifically among Arab adolescent school dropouts. It investigates the links between sociodemographic, interpersonal, cognitive and personality characteristics and use rates. Four hundred and seventy-six Arab adolescents aged 12-18 from throughout Israel, who had dropped out of school, participated in the study in late 2004. Sampling was done using a cluster method in order to choose specific localities. Participants completed self-report questionnaires assessing substance use and other variables. Legal substances--alcohol and tobacco--were used by 36% and 30% of the respondents, respectively, in the previous year. Being male, non-religious and having higher behavioural intentions and positive attitudes regarding use increased the odds of substance use. The best predictors of alcohol use were gender and religiosity, each raising the odds of use by 3.5. The best predictor of tobacco use was gender, raising the odds by 12.7. The best predictors of illegal use, behavioural intentions and risk perception, each doubled the odds of use. These and other results facilitate a better understanding of substance use among Arab adolescent dropouts and can foster the development of appropriate prevention and intervention programmes for this underserved population.


A Novel Collaboration to Reduce the Travel-Related Cost of Residency Interviewing.
Interviewing for residency is a complicated and often expensive endeavor. Literature has estimated interview costs of $4,000 to $15,000 per applicant, mostly attributable to travel and lodging. The authors sought to reduce these costs and improve the applicant interview experience by coordinating interview dates between two residency programs in Chicago, Illinois. Two emergency medicine residency programs scheduled contiguous interview dates for the 2015-2016 interview season. We used a survey to assess applicant experiences interviewing in Chicago and attitudes regarding coordinated scheduling. Data on utilization of coordinated dates were obtained from interview scheduling software. The target group for this intervention consisted of applicants from medical schools outside Illinois who completed interviews at both programs. Of the 158 applicants invited to both programs, 84 (53%) responded to the survey. Scheduling data were available for all applicants. The total estimated cost savings for target applicants coordinating interview dates was $13,950. The majority of target applicants reported that this intervention increased the ease of scheduling (84%), made them less likely to cancel the interview (82%), and saved them money (71%). Coordinated scheduling of interview dates was associated with significant estimated cost savings and was reviewed favorably by applicants across all measures of experience. Expanding use of this practice geographically and across specialties may further reduce the cost of interviewing for applicants.


GmBTB/POZ, a novel BTB/POZ domain-containing nuclear protein, positively regulates the response of soybean to Phytophthora sojae infection.
Phytophthora sojae is a destructive pathogen of soybean [Glycine max (L.) Merr.] which causes stem and root rot on soybean plants worldwide. However, the pathogenesis and molecular mechanism of plant defence responses against P. sojae are largely unclear. Herein, we document the underlying mechanisms and function of a novel BTB/POZ protein, GmBTB/POZ, which contains a BTB/POZ domain found in certain animal transcriptional regulators, in host soybean plants in response to P. sojae. It is located in the cell nucleus and is transcriptionally up-regulated by P. sojae. Overexpression of GmBTB/POZ in soybean resulted in enhanced resistance to P. sojae. The activities and expression levels of enzymatic superoxide dismutase (SOD) and peroxidase (POD) antioxidants were significantly higher in GmBTB/POZ-overexpressing (GmBTB/POZ-OE) transgenic soybean plants than in wild-type (WT) plants treated with sterile water or infected with P. sojae. The transcript levels of defence-associated genes were also higher in overexpressing plants than in WT on infection. Moreover, salicylic acid (SA) levels and the transcript levels of SA biosynthesis-related genes were markedly higher in GmBTB/POZ-OE transgenic soybean than in WT, but there were almost no differences in jasmonic acid (JA) levels or JA biosynthesis-related gene expression between GmBTB/POZ-OE and WT soybean lines. Furthermore, exogenous SA application induced the expression of GmBTB/POZ and inhibited the increase in P. sojae biomass in both WT and GmBTB/POZ-OE transgenic soybean plants. Taken together, these results suggest that GmBTB/POZ plays a positive role in P. sojae resistance and the defence response in soybean via a process that might be dependent on SA.


[Status of central hemodynamics in elderly patients with different types of anesthesia during laparoscopic operations for colon cancer].
Comparative analysis of central hemodynamics changes in 54 elderly patients with colon cancer during laparoscopic interventions. Physical status - ASA II-III. Were used 3 methods of anesthesia maintenance. In the 1-st group applied total intravenous anesthesia (TIVA) with myoplegia and ALV in the 2nd group surgical intervention was performed under the co-epidural anesthesia with intravenous potentiation with myoplegia and ALV; the 3rd group operations were performed under combination of epidural anesthesia with sevorane potentiation with myoplegia and ALV. The best results were obtained in groups with combined types of anaesthesia - epidural anesthesia with intravenous potentiation with myoplegia and ALV and epidural anesthesia with sevorane potentiation with myoplegia and ALV.


Planktonic Euryarchaeota are a significant source of archaeal tetraether lipids in the ocean.
Archaea are ubiquitous in marine plankton, and fossil forms of archaeal tetraether membrane lipids in sedimentary rocks document their participation in marine biogeochemical cycles for >100 million years. Ribosomal RNA surveys have identified four major clades of planktonic archaea but, to date, tetraether lipids have been characterized in only one, the Marine Group I Thaumarchaeota. The membrane lipid composition of the other planktonic archaeal groups--all uncultured Euryarchaeota--is currently unknown. Using integrated nucleic acid and lipid analyses, we found that Marine Group II Euryarchaeota (MG-II) contributed significantly to the tetraether lipid pool in the North Pacific Subtropical Gyre at shallow to intermediate depths. Our data strongly suggested that MG-II also synthesize crenarchaeol, a tetraether lipid previously considered to be a unique biomarker for Thaumarchaeota. Metagenomic datasets spanning 5 y indicated that depth stratification of planktonic archaeal groups was a stable feature in the North Pacific Subtropical Gyre. The consistent prevalence of MG-II at depths where the bulk of exported organic matter originates, together with their ubiquitous distribution over diverse oceanic provinces, suggests that this clade is a significant source of tetraether lipids to marine sediments. Our results are relevant to archaeal lipid biomarker applications in the modern oceans and the interpretation of these compounds in the geologic record.


Pre-operative evaluation of abdominal aortic aneurysms: ultrasound or computed tomography?
Evaluation of aortic aneurysms by ultrasound (US) or computed tomography (CT) is now commonplace and their use often reflects personal preferences given their similar diagnostic accuracy. Knowledge of anatomic details may be very helpful in the planning of the surgical procedure. Involvement of the supra-renal aorta, relative position of the renal arteries, intra-aneurysmal thrombus, and extension to the iliac arteries were retrospectively evaluated by both techniques to determine which modality was more valuable in the preoperative evaluation of abdominal aortic aneurysms. A group of 58 patients was reviewed. An infra-renal aortic aneurysm was identified in all instances by both methods. The supra-renal aorta was always well visualized by CT but not by US. The origin of at least one renal artery was seen in only 11% of the cases by US but in 100% by CT. CT demonstrated the left renal vein in all cases, while only 41% were demonstrated by US. Intra-aneurysmal thrombus was depicted by both methods but its distribution within the sac and the characteristics of the thrombus were apparent on CT but not on US. Aneurysmal involvement of the iliac arteries was present in 19% of the patients. CT detected all cases but only 14% were demonstrated by US. Both methods accurately diagnose abdominal aortic aneurysms. Supplementary data regarding proximal and distal extension, characteristics of the thrombus, relationship to the renal vessels, and adjacent major veins can be obtained by CT and usually not by US. This information is of value in the planning and execution of the indicated surgical procedure.


Coping planning: a patient-centred and strengths-focused approach to suicide prevention training.
Suicide is a leading cause of premature death and, despite significant investment, the prevalence rate has remained relatively stable for more than a decade. Theoretically, the use of 'safety planning' as a response to suicidality likely maintains suicide as a potential solution for vulnerable people. This paper describes a theoretically-supported paradigm shift from safety planning to 'coping planning' to improve patient outcomes and improve the confidence and competence of clinicians working with people with suicidality. Coping planning is a strategy used to support people with acute distress. Its components of 'caring', 'collaborating' and 'connecting' reinforce existing strengths, promote self-efficacy and link people with more intensive supports, as needed. Coping planning overcomes the limitations of existing approaches. It reframes suicide prevention from managing patients disclosing suicidality to ensuring patients have minimally sufficient temporary support to help them cope. This approach has the potential to promote coping self-efficacy and prevent deterioration that leads to suicide.


Rpr1, a gene required for Rpg1-dependent resistance to stem rust in barley.
Rpg1 is a stem rust resistance gene that has protected barley from severe losses for over 60 years in the US and Canada. It confers resistance to many, but not all, pathotypes of the stem rust fungus Puccinia graminis f. sp. tritici. A fast neutron induced deletion mutant, showing susceptibility to stem rust pathotype Pgt-MCC, was identified in barley cv. Morex, which carries Rpg1. Genetic and Rpg1 mRNA and protein expression level analyses showed that the mutation was a suppressor of Rpg1 and was designated Rpr1 (Required for P. graminis resistance). Genome-wide expression profiling, using the Affymetrix Barley1 GeneChip containing approximately 22,840 probe sets, was conducted with Morex and the rpr1 mutant. Of the genes represented on the Barley1 microarray, 20 were up-regulated and 33 were down-regulated by greater than twofold in the mutant, while the Rpg1 mRNA level remained constant. Among the highly down-regulated genes (greater than fourfold), genomic PCR, RT-PCR and Southern analyses identified that three genes (Contig4901_s_at, HU03D17U_s_at, and Contig7061_s_at), were deleted in the rpr1 mutant. These three genes mapped to chromosome 4(4H) bin 5 and co-segregated with the rpr1-mediated susceptible phenotype. The loss of resistance was presumed to be due to a mutation in one or more of these genes. However, the possibility exists that there are other genes within the deletions, which are not represented on the Barley1 GeneChip. The Rpr1 gene was not required for Rpg5- and rpg4-mediated stem rust resistance, indicating that it shows specificity to the Rpg1-mediated resistance pathway.


The influence of different food and drink on tics in Tourette syndrome.
Tourette syndrome (TS) is characterized by waxing and waning motor and vocal tics. Because standard medication often remains unsatisfactory, many patients seek alternative medicine. The aim of this study was to increase experience about the influence of food and drinks in TS. A standardized questionnaire was sent to 887 people recruited from our Tourette outpatient clinic and the German TS self-aid group. Respondents should assess whether 32 different foods influenced their tics. Two hundred twenty-four questionnaires could be used for analyses. A significant positive correlation (tic deterioration) was found for caffeine- and theine-containing drinks such as coke (p<0.001), coffee (p<0.001) and black tea (p<0.001) as well as for preserving agents (p<0.001), refined sugar (p<0.001) and sweeteners (p<0.001). A significant negative correlation (tic improvement) was not found. Results from this first survey investigating the influence of special foods and drinks on tics demonstrated that 34% and 47% of responders, respectively, assessed that coffee and coke deteriorate tics. It, therefore, can be speculated that caffeine may further stimulate an already overactive dopaminergic system in TS and thus increases tics. However, from these preliminary data, no further general recommendations regarding special diets and food restrictions can be made.


The relationship between microbial carbon and the resource quality of soil carbon.
The biological health of soil is an important aspect of soil quality because of the many critical functions performed by organisms in soil. Various indicators of soil quality have been proposed, but measurements of microbial biomass are most commonly used. During decomposition of plant residues in soil the relative intensities of the O-alkyl-C signal decreases and the alkyl-C signal increases in nuclear magnetic resonance (NMR) spectra. This leads to the suggestion that the alkyl-C to O-alkyl-C ratio of a soil may indicate the degree of decomposition. Consequently, the overall resource quality of soil C as a substrate for heterotrophic microorganisms may be inversely related to the alkyl-C to O-alkyl-C ratio. Our hypothesis is that a relationship exists between the size of the soil microbial community (microbial biomass) and the quality of soil carbon as a resource for microorganisms. New data have been combined with previously published data to show that there was a significant, negative correlation between the biomass C to total C (Cmic, to Corg) ratio and the alkyl-C to O-alkyl-C ratio (p < 0.01), which supports our hypothesis.


Effects of appetite, BMI, food form and flavor on mastication: almonds as a test food.
To investigate the effects of appetitive sensations, body mass index (BMI) and physical/sensory properties of food (almonds) on masticatory indices and resultant pre-swallowing particle sizes. Twelve lean (BMI=22.2+/-0.3) and 12 obese (BMI=34.3+/-0.6) adults. After collecting appetitive ratings, electromyographic recordings were used to assess participants' microstructure of eating for five almond products (raw, dry unsalted roasted, natural sliced, roasted salted and honey roasted) under fasted and satiated conditions. Duplicate samples were masticated to the point of deglutition and then were expectorated and size sorted. No statistically significant effects of BMI were detected for any of the mastication measures. Maximum and mean bite forces were greater under the fasted condition. Sliced almonds required lower bite force than did the other almond varieties. The pre-swallowing particle sizes were significantly greater for the sliced almonds than all other varieties. Both the number of chews and mastication time were negatively correlated with particle size. There were no significant effects of almond form or flavor on particle size. These results do not support differences in masticatory performance between lean and obese individuals, nor effects of sensory properties. Instead, the physical form of foods as well as an individuals' appetitive state may have a greater influence on masticatory behavior. The health implications of these observations warrant further investigation.


Organic aerosols associated with the generation of reactive oxygen species (ROS) by water-soluble PM2.5.
We compare the relative toxicity of various organic aerosol (OA) components identified by an aerosol mass spectrometer (AMS) based on their ability to generate reactive oxygen species (ROS). Ambient fine aerosols were collected from urban (three in Atlanta, GA and one in Birmingham, AL) and rural (Yorkville, GA and Centerville, AL) sites in the Southeastern United States. The ROS generating capability of the water-soluble fraction of the particles was measured by the dithiothreitol (DTT) assay. Water-soluble PM extracts were further separated into the hydrophobic and hydrophilic fractions using a C-18 column, and both fractions were analyzed for DTT activity and water-soluble metals. Organic aerosol composition was measured at selected sites using a high-resolution time-of-flight AMS. Positive matrix factorization of the AMS spectra resolved the organic aerosol into isoprene-derived OA (Isop_OA), hydrocarbon-like OA (HOA), less-oxidized oxygenated OA, (LO-OOA), more-oxidized OOA (MO-OOA), cooking OA (COA), and biomass burning OA (BBOA). The association of the DTT activity of water-soluble PM2.5 (WS_DTT) with these factors was investigated by linear regression techniques. BBOA and MO-OOA were most consistently linked with WS_DTT, with intrinsic water-soluble activities of 151 ± 20 and 36 ± 22 pmol/min/μg, respectively. Although less toxic, MO-OOA was most widespread, contributing to WS_DTT activity at all sites and during all seasons. WS_DTT activity was least associated with biogenic secondary organic aerosol. The OA components contributing to WS_DTT were humic-like substances (HULIS), which are abundantly emitted in biomass burning (BBOA) and include highly oxidized OA from multiple sources (MO-OOA). Overall, OA contributed approximately 60% to the WS_DTT activity, with the remaining probably from water-soluble metals, which were mostly associated with the hydrophilic WS_DTT fraction.


Analysis of Laboratory-Evolved Flavin-Dependent Halogenases Affords a Computational Model for Predicting Halogenase Site Selectivity.
Flavin-dependent halogenases (FDHs) catalyze selective halogenation of electron-rich aromatic compounds without the need for harsh oxidants required by conventional oxidative halogenation reactions. Predictive models for halogenase site selectivity could greatly improve their utility for chemical synthesis. Toward this end, we analyzed the structures and selectivity of three halogenase variants evolved to halogenate tryptamine with orthogonal selectivity. Crystal structures and reversion mutations revealed key residues involved in altering halogenase selectivity. Density functional theory calculations and molecular dynamics simulations are both consistent with hypohalous acid as the active halogenating species in FDH catalysis. This model was used to accurately predict the site selectivity of halogenase variants toward different synthetic substrates, providing a valuable tool for implementing halogenases in biocatalysis efforts.


Schwann cell mitosis in response to regenerating peripheral axons in vivo.
Schwann cell mitosis has been demonstrated in chronically denervated cat tibial nerves re-innervated by axons regenerating from the proximal stump of a coapted peroneal nerve. Thymidine incorporation rose above baseline levels at the axon front, with no detectable increase in more distal regions occupied by denervated Schwann cells. Schwann cells therefore enter S phase upon the arrival of a regenerating axon in vivo as previously described in tissue culture. Intraneural treatment of the denervated distal stump with Mitomycin C prior to re-innervation delayed the subsequent appearance of myelin formation. This supports the notion that axonally stimulated division of Schwann cells is a prerequisite for myelination during nerve regeneration. Axonal advancement was also retarded by drug treatment, possibly because of a reduced level of trophic support provided by the compromised Schwann cells. A comparable absence of myelin and poor re-innervation was found in chemically untreated distal stumps that had been maintained in the denervated state for prolonged periods when Schwann cell columns are known to undergo progressive atrophy. These observations suggest that nerve repair should be delayed for limited periods if efficacious regeneration is desired.


The experience of neurofibromatosis type I originating from pterygopalatine fossa and salivary gland.
One patient of neurofibromatosis type I originating from the pterygopalatine fossa and salivary gland underwent surgery in our department. At the outset, the case was misdiagnosed as arising from salivary gland tumors, and surgery was immediately performed. The tumor was entered directly, which induced ferocious bleeding. The subsequent hemostasis with tamponade and compression caused intracranial venous sinus thrombosis, which induced irreversible intracranial complications and finally resulted in death. The experience regarding the diagnosis and treatment of the case was retrospectively reviewed and shared in this article.


Optimum pressfit and proximal stress transfer with an improved modular design in total hip arthroplasty.
Femoral stem pressfit fixation depends on optimal proximal fit and stress transfer for long-term function. Newer modular designs offer improvements that enhance proximal-distal sizing, anatomical canal fill in the proximal metaphysis, and better stress transfer resulting from more intimate cortical contact. The Infinity modular femoral stem has the unique advantage of very proximal loading and gains fixation with a flexible stem that allows matching the variables of anteversion and proximal metaphyseal bow.


Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10.
The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies.


Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial.
The risks and benefits of adding fludarabine to a 2-Gy total body irradiation (TBI) nonmyeloablative regimen are unknown. For this reason, we conducted a prospective randomized trial comparing 2-Gy TBI alone, or in combination with 90 mg/m(2) fludarabine (FLU/TBI), before transplantation of peripheral blood stem cells from HLA-matched related donors. Eighty-five patients with hematological malignancies were randomized to be conditioned with TBI alone (n = 44) or FLU/TBI (n = 41). All patients had initial engraftment. Two graft rejections were observed, both in the TBI group. Infection rates, nonrelapse mortality, and graft-versus-host disease (GVHD) were similar between groups. Three-year overall survival was lower in the TBI group (54% versus 65%; hazard ratio [HR], .57; P = .09), with higher incidences of relapse/progression (55% versus 40%; HR, .55; P = .06), relapse-related mortality (37% versus 28%; HR, .53; P = .09), and a lower progression-free survival (36% versus 53%; HR, .56; P = .05). Median donor T cell chimerism levels were significantly lower in the TBI group at days 28 (61% versus 90%; P < .0001) and 84 (68% versus 92%; P < .0001), as was NK cell chimerism on day 28 (75% versus 96%; P = .0005). In conclusion, this randomized trial demonstrates the importance of fludarabine in augmenting the graft-versus-tumor effect by ensuring prompt and durable high-level donor engraftment early after transplantation.


[Levels of lipid peroxidation products and activity of antiradical defense enzymes in blood of patients with Bechterew disease].
To study lipid peroxidation (LPO) in Bechterev's disease (BD) treated with antiinflammatory and antioxidant drugs. LPO was estimated in 75 BD patients before medication and during this treatment. 30 healthy volunteers served control. Levels of LPO products was high but activity of antioxidant defense enzymes low in BD patients. Antiinflammatory drugs meloxicam, indometacin and an antioxidant drug triovit depressed LPO activity, improve the patients' condition and results of functional tests.


Renal tubular acidosis: practical guides to diagnosis and treatment.
The syndrome of renal tubular acidosis in some one of its various forms should be suspected when an infant or child has failure to thrive, metabolic acidosis, constipation, diarrhea, vomiting, anorexia, polyuria, or dehydration in infancy. Confirmatory biochemical findings include an inappropriately high urinary pH, inadequate acid excretion and/or abnormal tubular reabsorption of filtered bicarbonate. Growth can be normal when there is sustained correction of the metabolic acidosis through appropriate alkaline therapy.


Cognitive decline monitoring through a web-based application.
Cognitive decline usually begins after individuals reach maturity, which is more evident in late adulthood. Rapid and constant cognitive screenings allow early detection of cognitive decline and motivate individuals to participate in prevention interventions. Due to accelerated technological advances, cognitive screening and training are now available to the layperson using electronic devices connected to the internet. Large datasets generated by these platforms provide a unique opportunity to explore cognitive development throughout life and across multiple naturalistic environments. However, such data collection mechanisms must be validated. This study aimed to determine whether the data gathered by commercial visuospatial and phonological working memory tests (CogniFit Inc., San Francisco, USA) confirm the well-established argument that age predicts cognitive decline. Data from 3,212 participants (2,238 females) who were 45 years old or older were analyzed. A linear regression analysis explored the relationship between age and working memory while controlling for gender, sleep quality, and physical activity (variables that are known to affect working memory). We found that age negatively predicts working memory. Furthermore, there was an interaction between age and gender for visuospatial working memory, indicating that although male participants significantly outperformed females, the relationship between age and working memory differs for females and males. Our results suggest that the computerized assessment of visuospatial and phonological working memory is sensible enough to predict cognitive functions in aging. Suggestions for improving the sensitivity of self-reports are discussed. Further studies must explore the nature of gender effects on cognitive aging.