[Peculiarities of cytokine status in patients with vitiligo and stress in anamnesis].
The aim of our study was to investigate the content of some proinflammatory cytokines (IL-2, IL-6) in the serum of patients with vitiligo and stress in anamnesis. Cytokine levels in serum were measured in 50 patients with vitiligo (20 men and 30 women aged from 18 to 65 years old.) All the patients were divided according to anamnesis (27 patients with stress in anamnesis and 23 patients, where the onset of the disease was not preceded by stress). Patients of both groups were similar in terms of shape (according to T. Fitzpatrick classification) and in terms of the dermatosis stages. Concomitant autoimmune or inflammatory diseases of the skin in our vitiligo patients were not observed. The cytokines in the blood serum of vitiligo patients were determined by ELISA using the corresponding monoclonal antibodies. Student's t-test was used for evaluation of statistical significance of received results (p < 0.05 was considered as a statistically significant). Content of IL-2 in the serum of patients with vitiligo, in which stress was not preceded dermatosis, was significantly higher than that in healthy individuals (25,5 ± 7,6 vs 10,5 ± 3,6 pg/ml, p < 0,05). But the same parameter in patients with stress in anamnesis was significantly lower than those in healthy individuals (3,5 ± 1,5 vs 10,5 ± 3,6 pg/l, p < 0.05). Changes in the content of IL-6 in the serum of vitiligo patients was a similar to changes in IL-2 content, and the most significant this indicator was in patients with generalized and progressive stage of the disease. Data on increased concentrations of IL-6 agree with the majority of studies conducted earlier. For a complete analysis of our results on the reduction of the cytokines (IL-2, IL-6) content in patients with a stress in anamnesis, that will allow to identify the most effective ways to treat patients with this pathology (including their cytokine status), further research is necessary.


Cross species expression analysis of innate immune response.
The innate immune response is the first line of host defense against infections. This system employs a number of different types of cells, which in turn activate different sets of genes. Microarray studies of human and mouse cells infected with various pathogens identified hundreds of differentially expressed genes. However, combining these datasets to identify common and unique response patterns remained a challenge. We developed methods based on probabilistic graphical models to combine expression experiments across species, cells, and pathogens. Our method analyzes homologous genes in different species concurrently overcoming problems related to noise and orthology assignments. Using our method, we identified both core immune response genes and genes that are activated in macrophages in both human and mouse but not in dendritic cells, and vice versa. Our results shed light on immune response mechanisms and on the differences between various types of cells that are used to fight infecting bacteria. For supporting website, see www.cs.cmu.edu/-lyongu/pub/immune/.


Psoriasis and phenotype of patients with early inflammatory back pain.
Psoriasis is an important clinical feature in spondyloarthritis. However, the influence of psoriasis on the clinical, functional and imaging features of patients with inflammatory back pain (IBP) related to spondyloarthritis is not known. To determine the prevalence of psoriasis and its impact in patients with recent IBP suggestive of spondyloarthritis. The prevalence of psoriasis was determined in 692 patients (mean age 33.3±8.5 years, 53.8% female, 58.3% human leucocyte antigen B27 positive) included in the DESIR cohort. Demographic characteristics, imaging features and blood tests of patients with and without psoriasis were compared. The prevalence of psoriasis was 16.6%. Patients with rather than without psoriasis more often presented with enthesitis (59.1% vs 47.5%; p=0.02) and had more active disease (BASDAI 4.8±1.8 vs 4.4±2.0; p=0.05) and poorer functional status (BASFI 3.6±2.2 vs 3.0±2.3; p=0.006; SF-36 (physical function) 61.9±24.4 vs 66.9±24.9; p=0.04). Patients with psoriasis showed higher levels of C-reactive protein (p=0.02), total cholesterol (p=0.01) and triglycerides (p=0.02). The two groups did not differ in structural changes as assessed by standard x-rays or MRI at the spinal and sacroiliac levels. However, ultrasonography of the Achilles tendon revealed psoriasis associated with bone erosions (p=0.0003) and abnormal vascularisation (p=0.04). Multivariate regression analysis revealed BASFI score (p=0.03), cholesterol level (p=0.02), dactylitis (p=0.0006) and family history of psoriasis (p<0.0001) as independent predictors of psoriasis. In patients with recent IBP suggestive of spondyloarthritis, psoriasis is associated with active axial disease and frequent concomitant enthesopathy and dactylitis.


Biochemical characterization of the water-soluble squalene synthase from Methylococcus capsulatus and the functional analyses of its two DXXD(E)D motifs and the highly conserved aromatic amino acid residues.
Information regarding squalene synthases (SQSs) from prokaryotes is scarce. We aimed to characterize the SQS from Methylococcus capsulatus. We studied its reaction mechanism by kinetic analysis and evaluated the structure of the substrate/inhibitor-binding sites via homology modeling. The cloned M. capsulatus SQS was expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid column chromatography. Interestingly, M. capsulatus SQS was water-soluble and did not require any detergent for its higher activity, unlike other SQSs studied previously; supplementation of any type of detergent inhibited enzyme activity. The specific activity and the kinetic values (Km and kcat ) for the substrate farnesyl diphosphate and NADPH are reported. The substrate analog farnesyl methylenediphosphonate showed potent inhibition toward the enzyme. We prepared the site-specific mutants directed at potential active-site residues (58) DXX(61) E(62) D (S1 site) and (213) DXX(216) D(217) D (S2 site), which were assumed to be involved in the binding of the substrate farnesyl diphosphate through the Mg(2+) ion. We first demonstrated that the S1 site and the two basic residues (R55 and K212) were responsible for the binding of farnesyl diphosphate. Furthermore, we examined the catalytic roles of the highly conserved aromatic residues and demonstrated that the Y164 residue abstracts the proton of cation 5, which is produced during the first half-reaction (Scheme 1), to afford presqualene diphosphate, and that the W224 residue stabilizes the intermediary cation 5 via the cation-π interaction. Furthermore, we confirm for the first time that the F32 and the Y51 residues also stabilize the carbocation intermediate(s) generated during the second half-reaction.


[The predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis/dermatomyositis].
To analyze the predictive factors and the unfavourable prognostic factors of interstitial lung disease (ILD) in patients with polymyositis (PM)/dermatomyositis (DM). The clinical data were collected from 87 inpatients with DM or PM, who were admitted to Shanghai Changhai Hospital from January 1997 to November 2006. The patients were divided into an ILD group and a non-ILD group. The clinical feature, incidence and prognosis of ILD were retrospectively analyzed. The clinical and laboratory data were analyzed by using the SPSS 13.0 software. The t-test and rank-sum test were used, depending on the measurement data. The enumeration data were analyzed with chi-square test. Logistic regression and Kaplan-Meier survival curve were used to analyze the correlative and prognostic factors of interstitial lung disease (ILD) in patients with PM/DM. The incidence and mortality of ILD in PM/DM patients were 46% (40/87) and 40% (16/40), respectively. Compared with the non-ILD group, the age in the ILD group was markedly older [(54 +/- 13) years vs (45 +/- 18) years], and the percentages of fever (21/40 vs 7/47, chi2 = 14.00, P < 0.01), dysphagia (16/40 vs 8/47, chi2 = 5.71, P < 0.05), arthralgia (26/40 vs 9/47, chi2 = 18.89, P<0.01), Gottron's rash (14/40 vs 2/47, chi2 = 13.61, P <0.01) and heart impairment (26/40 vs 14/47, chi2 = 10.28, P <0.01) were significantly higher in the ILD group. The levels ofLDH [(472 +/- 285) IU vs (310 +/- 238) IU, t =2.86, P<0.01], ESR [(44 +/- 24) mm/1 h vs (26 +/- 24) mm/l h, t = 3.19, P <0.01] and immunoglobulin G [(18 +/- 9) g/L vs (14 +/- 5) g/L, t = 2.31, P <0.05] were statistically different between the two groups. By multivariate nonparametric logistic regression analysis, Gottron's rash, arthralgia, fever, and > or = 40 years of age were identified as predictors with relative risk ratio of 12.048, 7.812, 6.329 and 5.236 respectively. The unfavourable prognostic factors of ILD were Gottron' s rash (chi2 = 5.35, P <0.05), cardiac impairment (chi2 = 5.68, P < 0.05) and pulmonary fibrosis (chi2 = 5.42, P <0.05) by survival analysis. The occurrence of ILD in PM/ DM patients was closely correlated to Gottron's rash, age > or = 40 years, arthralgia and fever. Gottron's rash, heart impairment and pulmonary fibrosis were poor prognosis factors of PM/DM patients complicated with ILD.


Phycocyanin synthesis and degradation in the blue-green bacterium Anacystis nidulans.
Cellular content and rates of synthesis of the apoprotein subunits of phycocyanin in Anacystis nidulans cultures undergoing, and recovering from, nitrate starvation were measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total and immunoprecipitable soluble proteins. Results indicated that (i) nitrate starvation provokes coordinate degradation of apoprotein subunits: (ii) de novo synthesis of these subunits is selectively depressed during starvation; (iii) nitrate restoration provokes coordinate increases in the rates of synthesis of these subunits, although maximal rates are not achieved for 6 to 10 h after readdition of nitrate; and (iv) illumination affects both relative and absolute rates of apoprotein formation.


In self-defense: Reappraisal buffers the negative impact of low procedural fairness on performance.
Contrary to an often-found result in the organizational justice literature, we suggest that there may be circumstances under which organization members will not perform poorly in response to being on the receiving end of low procedural fairness. To explain the theoretical mechanism, we integrate the group engagement model of justice with the emotion regulation perspective. Specifically, we argue that the detrimental effect of lower procedural fairness on performance is attenuated when individuals engage in reappraisal. Moreover, this is the case because reappraisal makes lower procedural fairness less likely to undermine self-perceived standing in the organization. Three experiments and a multisource survey among employees reveal support for these predictions. This research contributes to the organizational justice literature by showing that reappraisal can help maintain performance when people have experienced low procedural fairness, extending the typical finding that low procedural fairness undermines performance. Theoretical and practical implications, limitations, and suggestions for future research are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Investing in public health: barriers and possible solutions.
Health care is a less important determinant of health than behaviour and the environment but paradoxically, spending on health in most countries suggests the opposite. What determines these health policy and funding decisions, and might there be ways to increase investment in public health? Published papers, reviews and reports on the cost-effectiveness of public health interventions and barriers to investment in public health were reviewed. There is evidence to support investment in public health. Many public health interventions have been shown to save money, and some have cost-effectiveness ratios better than or equivalent to health care interventions. Despite this, there are recognized barriers to investing in public health. These barriers include the greater requirements for cost-effectiveness sometimes placed on public health interventions, the belief that in the long run prevention may cost more than treatment, the timeframes required for some public health interventions, the 'identifiable victim effect', the influence of interest groups, and the reality that evidence alone does not drive health policy. Investment in public health has the potential to deliver improved health outcomes. Strategies to address the barriers and increase investment in public health are suggested.


Glycosmis pentaphylla (Rutaceae): A Natural Candidate for the Isolation of Potential Bioactive Arborine and Skimmianine Compounds for Controlling Multidrug-Resistant Staphylococcus aureus.
Several multidrug-resistant organisms have emerged, which increases the threat to public health around the world and a limited number of therapeutics were available to counteract these issues. Thus, researchers are trying to find out novel antimicrobials to overcome multidrug-resistant issues. The present study aimed to isolate antibacterial principles against the clinical isolates of multidrug-resistant (MDR) Staphylococcus aureus from the ethyl acetate extract of Gycosmis pentaphylla. The isolation and structural characterization of bioactive compounds were carried out using various chromatographic techniques (TLC, column, HPLC, and LC-MS) and spectral studies such as FT-IR, CHNS analysis, 1H-NMR, and 13C-NMR. The antimicrobial potential of isolated compounds was assessed according to the standard methods. The isolated compounds were identified as arborine and skimmianine, which exhibited a significant antibacterial effect with the lowest MIC and MBC values against MDR S. aureus and in vitro kinetic and protein leakage assays supported the antimicrobial activity. Significant morphological changes such as uneven cell surfaces and morphology, cell shrinkage, and cell membrane damages were observed in the MDR S. aureus upon the treatment of arborine and skimmianine. The present investigation concludes that the isolated arborine and skimmianine compounds from G. pentaphylla harbor a strong antibacterial activity against MDR S. aureus and may be used as alternative natural drugs in the treatment of MDR S. aureus.


Health visitors know the benefits of breastfeeding.
I find it astonishing that the article promoting health visiting (careers, May 4) should portray formula feeding as normal in its accompanying photograph. This undermines the individual woman's choice to breastfeed. It also reinforces the societal norm of formula feeding.


Microdevice to capture colon crypts for in vitro studies.
There is a need in biological research for tools designed to manipulate the environment surrounding microscopic regions of tissue. In the current work, a device for the oriented capture of an important and under-studied tissue, the colon crypt, has been designed and tested. The objective of this work is to create a BioMEMs device for biological assays of living colonic crypts. The end goal will be to subject the polarized tissue to user-controlled fluidic microenvironments in a manner that recapitulates the in vivo state. Crypt surrogates, polymeric structures of similar dimensions and shape to isolated colon crypts, were used in the initial design and testing of the device. Successful capture of crypt surrogates was accomplished on a simple device composed of an array of micron-scale capture sites that enabled individual structures to be captured with high efficiency (92+/-3%) in an ordered and properly oriented fashion. The device was then evaluated using colon crypts isolated from a murine animal model. The capture efficiency attained using the fixed biologic sample was 37+/-5% due to the increased variability of the colon crypts compared with the surrogate structures, yet 94+/-3% of the captured crypts were properly oriented. A simple approach to plug the remaining capture sites in the array was performed using inert glass beads. Blockage of unfilled capture sites is an important feature to establish a chemical gradient across the arrayed crypts. A chemical concentration gradient (Cluminal/Cbasal>10) was demonstrated across the arrayed crypts for over 8 h. Finally unfixed colon crypts were demonstrated to be effectively captured by the micromesh array and to remain viable on the capture sites at 5 h after mouse sacrifice. The present study demonstrates the feasibility and potential for rationally microengineered technologies to address the specific needs of the biologic researcher.


Self-doping of molecular quantum-dot cellular automata: mixed valence zwitterions.
Molecular quantum-dot cellular automata (QCA) is a promising paradigm for realizing molecular electronics. In molecular QCA, binary information is encoded in the distribution of intramolecular charge, and Coulomb interactions between neighboring molecules combine to create long-range correlations in charge distribution that can be exploited for signal transfer and computation. Appropriate mixed-valence species are promising candidates for single-molecule device operation. A complication arises because many mixed-valence compounds are ions and the associated counterions can potentially disrupt the correct flow of information through the circuit. We suggest a self-doping mechanism which incorporates the counterion covalently into the structure of a neutral molecular cell, thus producing a zwitterionic mixed-valence complex. The counterion is located at the geometrical center of the QCA molecule and bound to the working dots via covalent bonds, thus avoiding counterion effects that bias the system toward one binary information state or the other. We investigate the feasibility of using multiply charged anion (MCA) boron clusters, specifically closo-borate dianion, as building blocks. A first principle calculation shows that neutral, bistable, and switchable QCA molecules are possible. The self-doping mechanism is confirmed by molecular orbital analysis, which shows that MCA counterions can be stabilized by the electrostatic interaction between negatively charged counterions and positively charged working dots.


Ionization energy thresholds of microhydrated adenine and its tautomers.
In the present work the vertical and adiabatic ionization energy thresholds (IET) of adenine, and its amino and imino tautomers complexed with 1-3 water molecules are presented. The vertical and adiabatic IETs have been calculated at the B3LYP and P3 levels of theory, using the standard 6-31++G(d,p) basis set. The results show that there is hardly any effect of microhydration on the vertical DeltaIET of adenine, which is at odds with the experimental values determined by Kim et al. (J. Phys. Chem. 1996, 100, 7933). In an attempt to assign the experimental DeltaIET values, calculations have been performed on the microhydrated amino and imino tautomers of adenine. Vertical DeltaIET calculations and adiabatic DeltaIET calculations on adenine N7H tautomers complexed with water are in better agreement with the experimental results than are calculations involving the canonical (N9H) form of adenine.


Gapmer Antisense Oligonucleotides Targeting 5S Ribosomal RNA Can Reduce Mature 5S Ribosomal RNA by Two Mechanisms.
In this study, we demonstrate that 5S ribosomal RNA (rRNA), a highly structured and protein-bound RNA, is quite difficult to reduce with antisense oligonucleotides (ASOs). However, we found a single accessible site that was targetable with a high-affinity complementary ASO. The ASO appeared to bind to the site, recruit RNaseH1, and cause degradation of the 5S RNA. Intriguingly, we also observed that the same ASO induced an accumulation of pre-5S RNA, which may contribute to reduced levels of mature 5S rRNA. As expected, ASO mediated reduction of 5S RNA, and modest inhibition of processing of pre-5S RNA resulted in nucleolar toxicity. However, the toxicity induced was minimal compared with actinomycin D, consistent with its modest effects on pre-5S rRNA. Mechanistically, we show that the accumulation of pre-5S rRNA required ASO hybridization to the cognate rRNA sequence but was independent of RNaseH1 activity. We found that Ro60 and La, proteins known to bind misprocessed RNAs, likely sequester the ASO-pre-5S rRNA species and block RNaseH1 activity, thus identifying another example of competitive mechanisms mediated by proteins that compete with RNaseH1 for binding to ASO-RNA heteroduplexes.


Mechanism of superoxide dismutase loss from human sperm cells during cryopreservation.
Earlier studies on human sperm cryodamage have shown that plasma membrane stress is the primary process and that phospholipid peroxidation in cryopreserved samples is not inhibited by addition of antioxidants. One consistent effect of cryopreservation is loss of enzymatic activity of the peroxidation defense enzyme, superoxide dismutase (SOD). To clarify this aspect of the freeze-thaw process and to develop a more complete resolution of the reactions leading to cryodamage, we sought to identify which of the two most probable mechanisms, loss of enzyme protein from the cells of denaturation of the protein, operates. If the first operates, cellular enzymatic activity and enzyme protein as identified by immunocytochemistry should give a linear correlation. If the second operates, there should be no correlation. In this study, five individual samples were analyzed before and after cryopreservation for immunoreactive Cu/Zn SOD and cell intactness by flow cytometry, for SOD enzymatic activity by a highly sensitive fluorimetric method, and for motility characteristics by Hamilton-Thorn motility analyzer. Fresh samples were obtained by the "swim-up" method and had > 95% intact cells with > 78% motile cells. After freeze-thaw, about half the cells were intact. SOD enzymatic activity was determined on Triton X-100 cell extracts, a method that removes all enzymatic activity from the cell structure, and compared with immunoreactive SOD in the cells as determined by indirect immunofluorescence mean intensities. Residual immunofluorescence was observed in the cells after Triton X-100 treatment; if this was taken into account, a close linear correlation between SOD enzyme activity and SOD immunoreactivity was obtained (r = 0.90; P = 0.00014). There was no correlation between SOD enzyme activity ratios for cryopreserved and fresh cells and fraction of intact cells after freeze-thaw. We conclude that loss of SOD protein from the subset of cells undergoing acute membrane damage is the most probable primary mechanism of SOD enzymatic activity loss from the sample and that resistance to cryodamage and SOD activity in any given cell are quite independent of one another.


The interaction between the infant and the environment: the importance of mother-child contact after delivery.
Birth is more than just the physical beginning of a new life--it is also the start of the psychosocial development of the newborn infant together with its family. Immediately after delivery parents and infants can start to exchange signals that maybe are of major importance for this development. The early post partum period has been regarded to have great potentials and especially the mother has been regarded to play a very powerful role, whereas the infant's contribution has been accorded little discussion. The individual reactive capacity of the newborn baby and its influence on the environment can be illustrated in a number of ways. In recent years studies of fetal movements have been made by means of ultra sound registration and it has been discussed whether these are precursors of later behavior in the neonate-infant. The transition at birth can be considered either to be continuous or dis-continuous, the outcome of this discussion has great bearing on the importance of early neonate-environment interactions. Short and long term outcome of different routine care procedures around the time of delivery and transition are controversial subjects. Although several studies support the importance of early post delivery interaction, other studies do not seem to find correlations between early experiences and later developmental outcome measurements. In this paper several of these aspects will be discussed, examples from the literature given and possible clinical applications suggested, as well as their impact on the care of healthy and sick newborns and their families.


Reinforced self-assembly of hexa-peri-hexabenzocoronenes by hydrogen bonds: from microscopic aggregates to macroscopic fluorescent organogels.
Hexa-peri-hexabenzocoronene derivatives (HBCs) that have hydrogen-bonding functionalities (either amido or ureido groups) adjacent to the aromatic cores have been synthesized to study the effects of intracolumnar hydrogen bonds on the self-assembly behavior of HBCs. The hydrogen bonds effectively increased the aggregation tendency of these compounds in solution. In the bulk state, the typical columnar supramolecular arrangement of HBCs was either stabilized substantially (1 a, 1 b, 2 a, and 2 b), or suppressed by dominant hydrogen-bonding interactions (3). For some of the compounds (1 a, 2 a, and 2 b), the supramolecular arrangement adopted in the liquid-crystalline state was even retained after annealing, presumably owing to the reinforcement of the pi-stacking interactions by the hydrogen bonds. Additionally, the combined effect of the hydrogen bonds and pi-stacking of the aromatic moieties led to the formation of fluorescent organogels, whereby some derivatives were further investigated as novel low molecular-mass organic gelators (LMOGs).


The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway.
VHL is part of an SCF related E3-ubiquitin ligase complex with 'gatekeeper' function in renal carcinoma. However, no mutations have been identified in VHL interacting proteins in wild type VHL tumors. We previously reported that the TRC8 gene was interrupted by a t(3;8) translocation in a family with hereditary renal and non-medullary thyroid cancer. TRC8 encodes a multi-membrane spanning protein containing a RING-H2 finger with in vitro ubiquitin ligase activity. We isolated the Drosophila homologue, DTrc8, and studied its function by genetic manipulations and a yeast 2-hybrid screen. Human and Drosophila TRC8 proteins localize to the endoplasmic reticulum. Loss of either DTrc8 or DVhl resulted in an identical ventral midline defect. Direct interaction between DTrc8 and DVhl was confirmed by GST-pulldown and co-immunoprecipitation experiments. CSN-5/JAB1 is a component of the COP9 signalosome, recently shown to regulate SCF function. We found that DTrc8 physically interacts with CSN-5 and that human JAB1 localization is dependent on VHL mutant status. Lastly, overexpression of DTrc8 inhibited growth consistent with its presumed role as a tumor suppressor gene. Thus, VHL, TRC8, and JAB1 appear to be linked both physically and functionally and all three may participate in the development of kidney cancer.


Elimination of trachoma from Morocco: a historical review.
Since the 1950s, the Kingdom of Morocco has been and remains one of the pioneers in the fight against trachoma, a disease that has completely disappeared in the majority of its national territory, but some endemic pockets have persisted and pose a health risk, particularly for children and women. Morocco finds itself today, thanks to years of joint efforts, at the forefront of the world stage of the fight against trachoma. The country has demonstrated through its experience the effectiveness and relevance of the "SAFE" strategy - an extensive programme designed to tackle trachoma and its complications. The strategy is complex in its implementation and requires the synergy of a set of actors dedicated to specific activities, whether medico-surgical management activities aimed at setting up a physical project for local development, or information and awareness-raising activities. The key to the long-term success of eliminating blinding trachoma was not only to link distribution of drugs to the entire project area for several years to reduce substantially the reservoir of human- to-human transmission, but also to ensure permanence. In addition, services that provide quality palpebral surgery and especially repeat treatment campaigns with antibiotics, as well as health education campaigns and the promotion of personal and collective hygiene have generated sustainable changes in the living environment of receiving populations.


Why is SCA12 different from other SCAs?
Spinocerebellar ataxia type 12 (SCA12), now described in European-American and Asian (Indian) pedigrees, is unique among the SCAs from clinical, pathological, and molecular perspectives. Clinically, the distinguishing feature is early and prominent action tremor with variability in other signs. Pathologically, brain MRIs also suggest variability, with prominent cortical as well as cerebellar atrophy. Genetically, SCA12 is caused by a CAG repeat expansion that does not encode polyglutamine; we speculate that the mutation may affect expression of the gene PPP2R2B, which encodes a brain-specific regulatory subunit of the protein phosphatase PP2A.


Functional activities and psychosocial factors in the rehabilitation of patients with low back pain.
A four-week rehabilitation programme for back patients, focusing on functional activities and psychosocial factors in the demands of work and daily living, was evaluated. The programme is a combination of training of functional activities and increased psychological knowledge, body awareness and coping. A total of 40 patients with lumbago or lumbago ischias participated in the program and were compared with a matched control group. The results showed that the patients had significantly more ergonomic and psychosocial problems in their working environment than did the controls. A significant reduction in ratings of low back pain was noted in patients compared with controls after rehabilitation. Increased functional ability and physical fitness were shown in the patient group after rehabilitation. Significantly more patients than controls returned to work after the rehabilitation.


Ultrathin cross-linked nanoparticle membranes.
The fabrication of functional nanostructured materials for sensing, encapsulation and delivery requires practical approaches to self-assembly on multiple length scales and the synthesis of tough yet permeable structures. Here, the self-assembly of functionalized, photoluminescent nanoparticles at liquid interfaces, followed by cross-linking of the associated ligands, affords robust membranes that maintain their integrity even when they are removed from the interface. These composite membranes, nanometers in thickness, are elastic yet permeable and have potential applications involving controlled permeability and diffusion. Cadmium selenide (CdSe) nanoparticles are used, since their inherent photoluminescence offers a direct way to probe the spatial organization of the particles. Functionalized ligands attached to the nanoparticles provide an effective means to stabilize the interfacial assembly by cross-linking. The concepts shown are adaptable to other type of nanoparticles, ligands, and solvent combinations.


Proinflammatory Dietary Intake Relates to Pain Sensitivity in Chronic Nonspecific Low Back Pain: A Case-Control Study.
Nonspecific chronic low back pain (nCLBP) has been associated with nutrition. Yet, it is not clear how nutritional factors and nCLBP relate to one another. Therefore, the aim of the present study was to investigate differences in diet quality and dietary intake levels between nCLBP patients and healthy controls (HCs) and explore the association between nutritional factors and pain sensitivity in nCLBP. In this case-control study, 106 participants (ie, n = 53 nCLBP and n = 53 HCs) were recruited and completed a 3-day food diary to assess their dietary intake, which allowed to generate individual diet quality scores (ie, the Healthy Eating Index-2015 and Dietary Inflammatory Index). Additionally, each participant underwent an experimental pain assessment (quantitative sensory testing) and filled out self-reported pain questionnaires. Compared to HCs, the nCLBP group showed significantly lower diet quality, higher inflammatory scores, and a lower intake of total protein, total fat, dietary fiber, omega-3 fatty acids, vitamin B6, vitamin A, beta-carotene, vitamin E, and magnesium. Pain sensitivity mainly showed a negative correlation with nutritional intakes known for anti-inflammatory properties (ie, vitamins E, D, A, B6, B12, and zinc). Interestingly, total fat, cholesterol, saturated, and monounsaturated fat intakes were found to be inversely associated with pain sensitivity. Overall, patients with nCLBP have a lower diet quality, eat more proinflammatory, have less intake of nutrients known for their anti-inflammatory and antioxidative properties, and drink less water compared to HCs. Accordingly, pain sensitivity was mainly found to be positively associated with proinflammatory dietary intake. PERSPECTIVE: This study emphasizes the association between a proinflammatory diet and nCLBP. Among nCLBP patients, positive association between increased pain sensitivity and the proinflammatory potential of a diet, highlighting the potential for individualized pain management strategies and leading to the development of novel therapeutic methods.


Viral hepatitis in patients infected with human immunodeficiency virus.
From 1992 to 1995 we studied 232 (69% male, 87% Caucasian) anti-human immunodeficiency virus (anti-HIV) positive Brazilian patients, through a questionnaire; HIV had been acquired sexually by 50%, from blood by 32%, sexually and/or from blood by 16.4% and by an unknown route by 1.7%. Intravenous drug use was reported by 29%; it was the most important risk factor for HIV transmission. The alanine aminotransferase quotient (qALT) was >1 for 40% of the patients, 93.6% had anti-hepatitis A virus antibody, 5.3% presented hepatitis B surface antigen, 44% were anti-hepatitis B core antigen positive and 53.8% were anti-hepatitis C virus (anti-HCV) positive. The anti-HCV test showed a significant association with qALT>1. Patients for whom the probable HIV transmission route was blood had a 10.8 times greater risk of being anti-HCV positive than patients infected by other routes. Among 30 patients submitted to liver biopsy, 18 presented chronic hepatitis.


Management of a dentigerous cyst in a child with hereditary angioedema.
The purpose of this paper was to report the case of an 8-year-old girl with hereditary angioedema (HAE) who underwent 2 oral surgeries for removal of a dentigerous cyst without any significant episode of angioedema. One week after routine radiographic examination revealed an odontogenic cyst, short-term prophylactic therapy (Danazol 600 mg/day) was initiated to avoid an angioedema attack. The cyst was carefully removed under general anesthesia without life-threatening complications. Postoperative prophylactic therapy also was performed. Histopathological exam confirmed the diagnosis of a dentigerous cyst. Nine months after surgery, the cyst recurred and it was successfully removed once more under general anesthesia. The same prophylactic therapy was used, this time with fresh frozen plasma. The case presented showed that the oral management of a pediatric patient with HAE is a high-risk procedure. It can be performed successfully, however, when the involved health professionals are aware of both the risks and preventive strategies.


Malignant lymphoma in a renal transplant recipient presenting as a solitary pulmonary nodule.
Malignant lymphoma is the second most common type of tumor in renal transplant recipients. The commonest site is the central nervous system, which is involved in about 50% of the cases. This report described a 45-year-old female cadaveric renal transplant recipient, who presented with upper respiratory tract infection. Her chest radiograph showed a solitary pulmonary nodule. Open lung biopsy revealed a poorly differentiated malignant lymphoma of the histiocytic type. This case emphasizes the often atypical presentation of lymphoma in immunosuppressed patients.


Telomere length: is the future in our "ends"?
Telomeres, repetitive nucleotide sequences located at the end of each chromosome, play the important function of preserving chromosome stability and preventing molecular contact with neighboring chromosomes. Albeit the concept that telomere length may be a marker of health and disease seems hence counterintuitive, the translation of this clear-cut concept from the bench to the beside has appeared so far less straightforward. In particular, controversial evidence has emerged so far about the fact that telomere length may actually predict morbidity and mortality across many clinical settings. This uncertainty is actually due to a kaleidoscope of biological and technical factors, including preanalytical issues (e.g., sample matrix), poor standardization of techniques used for their assessment, and dependence of telomere structure upon genetics, epigenetics, environment and behavioral attitudes, which may be present at a variable extent in various physiological or pathological conditions. Therefore, although it is now undeniable that our future is largely in our "hands" (i.e., genotype, diet, exposure to environmental factors and so forth), larger and more solid evidence will be necessary before concluding that the future is also written in our (chromosome) "ends".


Flexible Polyimide Aerogels with Dodecane Links in the Backbone Structure.
Polyimide aerogels using 1,12-dodecyldiamine (DADD), 3,3'-dimethylbenzidine (DMBZ), and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA) and cross linked using 1,3,5-triaminophenoxybenzene (TAB) were synthesized. Substitution of the aromatic diamine, DMBZ, with varying amounts of the aliphatic diamine, DADD, increases the flexibility in the backbone structure of the prepared aerogel. These aerogels are also lightweight, low density, have a low dielectric constant, and high modulus. Their overall properties (density, shrinkage, porosity, dielectric constant, water uptake, and modulus) and potential use as a conformal substrate for lightweight, high-performance antennas are discussed.


Photoelectron detachment and solvated electron dynamics of the cobalt(III) and iron(III) oxalato complexes.
The photochemical redox reaction kinetics of [M(III)(C(2)O(4))(3)](3-) [M = Co, Fe] complexes have been reexamined and studied by time-resolved spectroscopy. The redox mechanisms of the two systems, Co and Fe, were found to be similar to each other, and solvated electrons were observed immediately after 266/267 nm photoexcitation. A reaction mechanism is proposed that involves photoelectron detachment as a primary process. The charge-transfer bands for both complexes, which had been attributed to ligand to metal charge-transfer (LMCT) transitions previously, are reassigned to charge transfer to solvent (CTTS) transitions.


Interactive effects of gender and sexual orientation on cortical thickness, surface area and gray matter volume: a structural brain MRI study.
Testosterone is thought to play a crucial role in sexual differentiation of the brain, and sexual orientation is programmed into our brain structures even when we are still fetuses. Although gender and sexual orientation differences have been shown respectively in many brain structures, the mechanism underlying the sexual differentiation of the brain is still unknown. The study is to investigate the interactive effects of gender and sexual orientation on cerebral structures in homosexual and heterosexual people. Sexual orientation was evaluated by the Kinsey scale. We collected structural magnetic resonance image (MRI) data of local cortical thickness, surface area, and gray matter volume in all the subjects (29 homosexual and 29 heterosexual men, 17 homosexual and 17 heterosexual women). Statistical maps were generated using a general linear model (GLM) using FreeSurfer's Query, Design, Estimate, Contrast (QDEC) interface. We had sexual orientation and gender as 2 discrete factors with 2 levels, allowing for the generation of the interaction between sexual orientation and gender: homosexual women and heterosexual men versus heterosexual women and homosexual men. Coordinates were in Talairach space. All the cluster sizes were calculated with a P value of 0.01. Results revealed interactions concerning the area and gray matter volume between the factors of sexual orientation and gender. Regarding the thickness, an interaction was not found in any regions of the clusters. Regarding the area, an interaction was found in region of left middle temporal lobe, inferior temporal lobe, lateral occipital lobe, fusiform [(-58.1, -38.6, -14.7), maximum vertex-wise (MV) log10(P) =3.30, cluster size (CS) =1,286.90 mm2], and left rostral middle frontal lobe, pars opercularis, caudal middle frontal lobe [(-37.3, 23.6, 24.8), MV log10(P) =2.92, CS =1,194.40 mm2]. Regarding the gray matter volume, an interaction was found in the region of the left pars opercularis (inferior frontal gyrus) [(-42.9, 6.3, 18.5), MV log10(P) =1.31, CS =526.79 mm2]. The present study extends our understandings of how structural features differ in homosexual men, heterosexual men, homosexual women, and heterosexual women. Furthermore, it highlights the interactions between sexual orientation and gender in the left inferior frontal gyrus, bilateral temporal lobe, and the right rostral anterior cingulate cortex, which are suggested to play a critical role in the sexual differentiation of the human brain.


Combining 4D pharmacophore generation and multidimensional QSAR: modeling ligand binding to the bradykinin B2 receptor.
We recently reported the development of two receptor-modeling concepts (software Quasar and Raptor) based on multidimensional quantitative structure-activity relationships (QSAR) and allowing for the explicit simulation of induced fit. As the identification of the bioactive configuration of ligand molecules in such studies is all but unambiguous, each compound may be represented by an ensemble of different conformations, orientations, stereoisomers, and protonation states, leading to a 4D data set. In this account, we present a novel technology (software Symposar) allowed to automatically generate a 4D pharmacophore as input for multidimensional QSAR. Symposar aligns ligands utilizing fuzzylike 2D-subfeature mapping and, subsequently, a Monte Carlo search on a 3D similarity grid. The two-step concept (4D pharmacophore generation and quantification of ligand binding by multidimensional QSAR) was applied to 186 compounds binding to the bradykinin B2 receptor. The prediction of their binding affinity by means of the Quasar and Raptor technologies allowed for consensus scoring and generated topologically and quantitatively consistent receptor models. These converged at a cross-validated r2 of 0.752 and 0.815 and yielded a predictive r2 of 0.784 and 0.853 for a test set (for Quasar and Raptor, respectively).


Chimeric Antigen Receptor T Cells in Glioblastoma-Current Concepts and Promising Future.
Glioblastoma (GBM) is a highly aggressive primary brain tumor that is largely refractory to treatment and, therefore, invariably relapses. GBM patients have a median overall survival of 15 months and, given this devastating prognosis, there is a high need for therapy improvement. One of the therapeutic approaches currently tested in GBM is chimeric antigen receptor (CAR)-T cell therapy. CAR-T cells are genetically altered T cells that are redirected to eliminate tumor cells in a highly specific manner. There are several challenges to CAR-T cell therapy in solid tumors such as GBM, including restricted trafficking and penetration of tumor tissue, a highly immunosuppressive tumor microenvironment (TME), as well as heterogeneous antigen expression and antigen loss. In addition, CAR-T cells have limitations concerning safety, toxicity, and the manufacturing process. To date, CAR-T cells directed against several target antigens in GBM including interleukin-13 receptor alpha 2 (IL-13Rα2), epidermal growth factor receptor variant III (EGFRvIII), human epidermal growth factor receptor 2 (HER2), and ephrin type-A receptor 2 (EphA2) have been tested in preclinical and clinical studies. These studies demonstrated that CAR-T cell therapy is a feasible option in GBM with at least transient responses and acceptable adverse effects. Further improvements in CAR-T cells regarding their efficacy, flexibility, and safety could render them a promising therapy option in GBM.


Evaluation of body development, fat mass and lipid profile in rats fed with high-PUFA and -MUFA diets, after neonatal malnutrition.
Neonatal malnutrition is associated with several features of the metabolic syndrome, later in life. Although the recovery of malnutrition was studied with different high-fat diets, few studies compare the effects of enriched vegetable oil diets, containing PUFA and MUFA, after weaning. Our aim was to evaluate the recovery with soya oil- or rapeseed oil-enriched diet, after malnutrition in rats whose mothers were food restricted (FR) during lactation. Dams were 50 % FR and compared to standard diet-fed dams (control, C). At 21 d, FR offspring had a lower body mass and length. After weaning C and FR offspring were fed a diet containing 7 % soya oil (7 %sC and 7 %sFR), or supplemented with 19 % soya oil (19 %sC or 19 %sFR) or 19 % rapeseed oil (19 %cC or 19 %cFR). The normal animals fed enriched vegetable oil diets had more visceral fat mass, but lower serum TAG and higher HDL-cholesterol. The 19 %FR groups showed significantly less food intake and body development compared to the 7 %sFR, and the same pattern was observed when this group was compared to the C groups. Absolute and relative mass of vital organs and body were lower in the FR groups. Visceral fat depot was lower in 19 %FR than 7 %FR and C groups. Serum glucose, albumin, TAG, cholesterol, leptin and triiodothyronine did not show significant changes. However, 19 %FR groups showed higher HDL-cholesterol and the 19 %sFR group showed lower serum thyroxine. The data suggest that a higher vegetable oil diet in the recovery of neonatal malnutrition ameliorates some features of the metabolic syndrome later in life.


[Anti-proliferative and antiviral effects of human alpha-interferon on tumor cells].
Antiproliferative and antiviral activities of a type alpha human leukocytic interferon on several heteroploidic cell lines: HeLa, HEp-2, and T-10, a cell line of malignant origin (glioblastoma) were investigated, as compared to subcultures of human embryo fibroblasts. The tumor cell multiplication rate decreased proportionally to the amount of interferon in the culture medium. The highest interferon concentration used in our experiments (1,000 mu/ml) induced a decrease of the normal cell multiplication rate (human embryo fibroblasts). The same amount of interferon had a cytotoxic effect against the T-10 cells, but this phenomenon is reversible if the interferon is excluded after 24 h from the culture medium. There was no quantitative relation between the magnitude of the antiviral and of the cytotoxic effects of the type alpha human interferon on the tested cellular substrates.


Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor.
Proliferation of endometrium is dependent on sex steroid hormones, but specific growth factors are likely to play an important role in regulating this process. A number of cytokines and growth factors are synthesized in the endometrium in response to sex steroid hormones and act to regulate endometrial function. Endometrial cells produce interleukin-8 (IL-8) both in vivo and in vitro. We hypothesized that IL-8, a neutrophil chemoattractant/activating factor and a potent angiogenic agent that has been shown to stimulate growth in other cell types, may directly stimulate proliferation of endometrial cells. We first investigated the effect of IL-8 and mouse antihuman-IL-8 neutralizing antibody on endometrial stromal cell proliferation using both a colorimetric assay and thymidine uptake. We then investigated the modulation of endometrial stromal cell IL-8 production and proliferation by antisense oligonucleotides specific for IL-8. There was a concentration-dependent increase of cell proliferation with IL-8 (2-fold at 1 ng/mL; P < 0.01 between control and concentrations above 0.01 ng/mL) and a concentration-dependent inhibition of cell proliferation with anti-IL-8 antibody (to 30% of the control at 1 microg/mL; P < 0.01 between control and concentrations above 0.1 microg/mL). IL-8 antisense oligonucleotide treatment decreased IL-8 production by endometrial stromal cells in culture as well as cell proliferation when it is compared with scrambled (nonsense) oligonucleotide treatment (P < 0.01). Addition of IL-8 (1 ng/mL) reversed the proliferation inhibitory effect of IL-8 antisense oligonucleotides. We propose that IL-8 may act as an autocrine growth factor in the endometrium, and suggest that it may also play a role in the pathogenesis of endometriosis.


Steroid hormone interactions with target cells: cross talk between membrane and nuclear pathways.
The biological effects of steroid hormones are mediated by receptors associated with the plasma membrane as well as located inside of target cells. This perspective focuses on recent advances in our understanding of the integration that occurs between membrane-associated rapid signaling events and various changes in gene transcription that modulate the function and phenotype of steroid-responsive cells. Three frequently studied members of the steroid hormone receptor superfamily, the estrogen receptors, the thyroid hormone receptors, and the vitamin D receptors, are included to illustrate the emerging concepts. Each of these hormones has been conclusively shown to function at multiple subcellular sites leading to a continuum of signals intimately linked by intracellular cross talk. Understanding the molecular mechanisms by which these steroid hormones and their receptors transduce cellular signals will allow us to create new pharmacologic therapies aimed at treatment of a variety of human diseases affecting the cardiovascular system, the reproductive system, the skeletal system, the nervous system, the mammary gland, and many others.


Case Report: Disseminated Talaromyces marneffei Infection in a Patient With Chronic Mucocutaneous Candidiasis and a Novel STAT1 Gain-of-Function Mutation.
Chronic mucocutaneous candidiasis (CMC) is a disorder of recurrent or persistent chronic noninvasive symptomatic infections of the skin, nails and mucous membranes. This disorder is primarily caused by Candida albicans. Many factors, including primary immunodeficiencies, can make a host more susceptible to CMC. Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations are the most common genetic etiologies of CMC. We describe a case of CMC with disseminated Talaromyces marneffei infection caused by a new pathogenic Y287N mutation at amino acid 287 in the coiled-coiled domain of STAT1, which was identified using whole-exome sequencing. Position 287 might be a hot spot for missense mutations because several amino acid substitutions were found there. Flow cytometry suggested that the Y287N mutation might reduce the expression of IL-17 of Th17 cells in peripheral blood mononuclear cells stimulated by phorbol myristate acetate and ionomycin. The STAT1 Y287N GOF mutation may be the direct cause of recurrent cutaneous and mucosal candidiasis, including the T. marneffei infection in this patient.


Tetrahymena as a Unicellular Model Eukaryote: Genetic and Genomic Tools.
Tetrahymena thermophila is a ciliate model organism whose study has led to important discoveries and insights into both conserved and divergent biological processes. In this review, we describe the tools for the use of Tetrahymena as a model eukaryote, including an overview of its life cycle, orientation to its evolutionary roots, and methodological approaches to forward and reverse genetics. Recent genomic tools have expanded Tetrahymena's utility as a genetic model system. With the unique advantages that Tetrahymena provide, we argue that it will continue to be a model organism of choice.


Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial.
Delirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma. We undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989. Between Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI -1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug. These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients. National Institute for Health Research.


The neural basis of defensive behaviour evolution in Peromyscus mice.
Evading imminent predator threat is critical for survival. Effective defensive strategies can vary, even between closely related species. However, the neural basis of such species-specific behaviours is still poorly understood. Here we find that two sister species of deer mice (genus Peromyscus) show different responses to the same looming stimulus: P. maniculatus, which occupy densely vegetated habitats, predominantly dart to escape, while the open field specialist, P. polionotus, pause their movement. This difference arises from species-specific escape thresholds, is largely context-independent, and can be triggered by both visual and auditory threat stimuli. Using immunohistochemistry and electrophysiological recordings, we find that although visual threat activates the superior colliculus in both species, the role of the dorsal periaqueductal gray (dPAG) in driving behaviour differs. While dPAG activity scales with running speed and involves both excitatory and inhibitory neurons in P. maniculatus, the dPAG is largely silent in P. polionotus, even when darting is triggered. Moreover, optogenetic activation of excitatory dPAG neurons reliably elicits darting behaviour in P. maniculatus but not P. polionotus. Together, we trace the evolution of species-specific escape thresholds to a central circuit node, downstream of peripheral sensory neurons, localizing an ecologically relevant behavioural difference to a specific region of the complex mammalian brain.


Effects of Topical Antiseptic Solutions Used During Total Knee Arthroplasty on Suture Tensile Strength.
Irrigating a surgical wound with an antiseptic solution is commonly performed while suturing following a total knee arthroplasty (TKA) to help prevent wound complications. The purpose of this study was to: 1) evaluate the mean load to failure of different sutures, and 2) compare the mean load to failure of the sutures after soaking in four different antiseptic solutions. Load-to-failure tests were conducted on four sets of comparable sutures (eight sutures) from two different companies Ethicon Inc. (Somerville, New Jersey) and Covidien (Mansfield, Massachusetts). The four suture types included: 1) non-absorbable braided polyethylene, 2) absorbable braided glycolide or lactide polymer, 3) absorbable monofilament polydioxanone or polyglyconate, and 4) absorbable monofilament polyglecaprone or gylcomer. Sutures were tested for tensile strength at baseline (i.e., no solution; n=5 per suture), and were then soaked for five minutes in one of four different antiseptic solutions: 0.125% sodium hypochlorite, 4% chlorhexidine gluconate, 10% povidone-iodine, and a 1:1 ratio of 3% hydrogen peroxide and sterile water. Effects of the different solutions on individual sutures were assessed with analysis of variance, and pairwise comparison tests were performed with post-hoc Tukey tests. For the controls, the mean failure loads for the type 1 sutures were 118.5 N and 120.3 N, for the type 2 sutures, 145.8 N and 155.4 N, the type 3 sutures, 103.8 N and 162.2 N, and the type 4 sutures, 86.9 N and 87.7 N. After being soaked in sodium hypochlorite, the mean failure load decreased for one of the type 2 sutures (mean difference, -12.8 N;p=0.003), while the other type 2 suture had a decreased failure load after soaking in povidone-iodine (mean difference, -10.3 N;p=0.041) and hydrogen peroxide (mean difference, -14.6 N;p=0.001). A type 1 suture had an increased load to failure after soaking in povidone-iodine (mean difference, 13.2 N;p<0.0001) and hydrogen peroxide (mean difference, 10.5 N;p<0.0001). Certain sutures may have changes in their breaking point depending on what type of antiseptic solution is used for wound irrigation, but due to the small magnitude of change, this may not necessarily be clinically relevant.


Plasmonic hot-electron reconfigurable photodetector based on phase-change material Sb2S3.
Hot-carrier based photodetectors and enhanced by surface plasmons (SPs) hot-electron injection into semiconductors, are drawing significant attention. This photodetecting strategy yields to narrowband photoresponse while enabling photodetection at sub-bandgap energies of the semiconductor materials. In this work, we analyze the design of a reconfigurable photodetector based on a metal-semiconductor (MS) configuration with interdigitated dual-comb Au electrodes deposited on the semiconducting Sb2S3 phase-change material. The reconfigurability of the device relies on the changes of refractive index between the amorphous and crystalline phases of Sb2S3 that entail a modulation of the properties of the SPs generated at the dual-comb Au electrodes. An exhaustive numerical study has been realized on the Au grating parameters formed by the dual-comb electrodes, and on the SP order with the purpose of optimizing the absorption of the device, and thus, the responsivity of the photodetector. The optimized photodetector layout proposed here enables tunable narrowband photodetection from the O telecom band (λ = 1310 nm) to the C telecom band (λ = 1550 nm).


Establishment and intra-/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation.
A reactive oxygen species (ROS) assay was previously developed for photosafety evaluation of pharmaceuticals, and the present multi-center study aimed to establish and validate a standard protocol for ROS assay. In three participating laboratories, two standards and 42 coded chemicals, including 23 phototoxins and 19 nonphototoxic drugs/chemicals, were assessed by the ROS assay according to the standardized protocol. Most phototoxins tended to generate singlet oxygen and/or superoxide under UV-vis exposure, but nonphototoxic chemicals were less photoreactive. In the ROS assay on quinine (200 µm), a typical phototoxic drug, the intra- and inter-day precisions (coefficient of variation; CV) were found to be 1.5-7.4% and 1.7-9.3%, respectively. The inter-laboratory CV for quinine averaged 15.4% for singlet oxygen and 17.0% for superoxide. The ROS assay on 42 coded chemicals (200 µm) provided no false negative predictions upon previously defined criteria as compared with the in vitro/in vivo phototoxicity, although several false positives appeared. Outcomes from the validation study were indicative of satisfactory transferability, intra- and inter-laboratory variability, and predictive capacity of the ROS assay.


The isothiocyanate complex of triphenylborane forms an unusual coordination polymer with [K(18-crown-6)](+), both in the solid state and in solution.
The title salt, (1,4,7,10,13,16-hexaoxacyclooctadecane-kappa(6)O)[(isothiocyanato)triphenylborato-kappaS]potassium(I), [K(C(19)H(15)BNS)(C(12)H(24)O(6))] or [K(SCNBPh(3))(18-crown-6)], where 18-crown-6 is 1,4,7,10,13,16-hexaoxacyclooctadecane and [SCNBPh(3)](-) is the (isothiocyanato)triphenylborate anion, exhibits a supramolecular structure that is best described as a helical coordination polymer or molecular screw. This unusual supramolecular structure is based on a framework in which the SCN(-) ion bridges the chelated K(+) ion and the B atom of BPh(3) in a micro(2) fashion. The X-ray crystal structure of the title salt has been determined at 100 (1) and 293 (2) K. The K(+) ion exhibits axial ligation by the S atom of the [SCNBPh(3)](-) anion, with a K-S distance of 3.2617 (17) A (100 K). The trans-axial ligand is an unexpected eta(2)-bound C=C bond of a phenyl group (meta- and para-C atoms) that belongs to the BPh(3) moiety of a neighboring molecule. The K-C bond distances span the range 3.099 (3)-3.310 (3) A (100 K) and are apparently retained in CDCl(3) solution (as evidenced by (13)C NMR spectroscopy). By virtue of the latter interaction, the supramolecular structure is a helical coordination polymer, with the helix axis parallel to the b axis of the unit cell. IR spectroscopy and semi-empirical molecular orbital (AM1) calculations have been used to investigate further the electronic structure of the [SCNBPh(3)](-) ion.


Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy: a morphological and immunohistochemical study.
The maternal circulation to the human placenta is not fully established until 10-12 weeks of pregnancy. During the first trimester the intervillous space is filled by a clear fluid, in part derived from secretions from the endometrial glands via openings in the basal plate. The aim was to determine the activity of the glands throughout the first trimester, and to identify components of the secretions. Samples of human decidua basalis from 5-14 weeks gestational age were examined by transmission electron microscopy and immunohistochemically. An archival collection of placenta-in-situ samples was also reviewed. The thickness of the endometrium beneath the implantation site reduced from approximately 5 mm at 6 weeks to 1 mm at 14 weeks of gestation. The glandular epithelium also transformed from tall columnar cells, packed with secretory organelles, to a low cuboidal layer over this period. The lumens of the glands were always filled with precipitated secretions, and communications with the intervillous space could be traced until at least 10 weeks. The glandular epithelium reacted strongly for leukaemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, transforming growth factor beta, alpha tocopherol transfer protein, MUC-1 and glycodelin, and weakly for lactoferrin. As gestation advanced uterine natural killer cells became closely approximated to the basal surface of the epithelium. These cells were also immunopositive for epidermal growth factor. Morphologically the endometrial glands are best developed and most active during early human pregnancy. The glands gradually regress over the first trimester, but still communicate with the intervillous space until at least 10 weeks. Hence, they could provide an important source of nutrients, growth factors and cytokines for the feto-placental unit. The endometrium may therefore play a greater role in regulating placental growth and differentiation post-implantation than previously appreciated.


Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle.
Adult skeletal muscle undergoes adaptation in response to endurance exercise, including fast-to-slow fiber type transformation and enhanced angiogenesis. The purpose of this study was to determine the temporal and spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately twofold increase in capillary density and capillary-to-fiber ratio in plantaris muscle as measured by indirect immunofluorescence with an antibody against the endothelial cell marker CD31 (466 +/- 16 capillaries/mm2 and 0.95 +/- 0.04 capillaries/fiber in sedentary control mice vs. 909 +/- 55 capillaries/mm2 and 1.70 +/- 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A significant increase in capillary-to-fiber ratio was present at day 7 with increased concentration of vascular endothelial growth factor (VEGF) in the muscle, before a significant increase in percentage of type IIa myofibers, suggesting that exercise-induced angiogenesis occurs first, followed by fiber type transformation. Further analysis with simultaneous staining of endothelial cells and isoforms of myosin heavy chains (MHCs) showed that the increase in capillary contact manifested transiently in type IIb + IId/x fibers at the time (day 7) of significant increase in total capillary density. These findings suggest that endurance training induces angiogenesis in a subpopulation of type IIb + IId/x fibers before switching to type IIa fibers.


Chemical Composition, Antifungal and Insecticidal Activities of the Essential Oils from Tunisian Clinopodium Nepeta Subsp. nepeta and Clinopodium Nepeta Subsp. Glandulosum.
The present investigation was focused on the study of the chemical composition variability and biological activities of the essential oils from Clinopodium nepeta subsp. nepeta and subsp. glandulosum. Essential oils extraction was performed using hydrodistillation and the separation of the constituents was carried out by gas chromatography coupled with mass spectrometry (GC-MS). Antifungal activities were tested against Aspergillus flavus, Aspergillus terreus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, and Candida albicans. Toxicity and repellency were evaluated against the stored product pests Tribolium confusum and Sitophilus zeamais. Both essential oils were characterized by a high content of oxygenated monoterpenes. Piperitone ranks first in the subspecies nepeta and piperitenone oxide is the dominant constituent in the subspecies glandulosum. All tested samples displayed noteworthy antifungal properties, with the highest activity observed for the essential oil of C. nepeta subsp. glandulosum, collected in Béni-M'tir, against T. mentagrophytes (MIC = 40 µg/mL). The essential oil samples of C. nepeta subsp. glandulosum were strongly repellent to the insect species (PR > 80%, after 2h) and highly toxic to S. zeamais reaching 97.5%-100% mortality after 24 h of exposure. In conclusion, this study showed considerable intra-specific changes in the quality of C. nepeta essential oils, which is reflected in different rates of antifungal and insecticidal activity.


DNA base composition, DNA-DNA homology and long-chain fatty acid studies on streptococcus thermophilus and Streptococcus salivarius.
DNA base composition, DNA-DNA homology and long-chain fatty acid studies were performed on Streptococcus thermophilus and Streptococcus salivarius. These species possess similar mol % G + C values (about 37 to 41), long-chain fatty acid profiles and belong to a single DNA homology group. On the basis of the present and earlier studies it is proposed that Streptococcus thermophilus (Orla-Jensen) be reclassified as Streptococcus salivarius subsp. thermophilus comb. nov.


Prognostic and clinical significance of metastasis-associated gene 1 overexpression in solid cancers: A meta-analysis.
In the past 2 decades, metastasis-associated gene 1 (MTA1) has attracted attention for its close association with cancer progression and its roles in chromatin remodeling processes, making it a central gene in cancer. The present meta-analysis was performed to assess MTA1 expression in solid tumors. This analysis identified studies that evaluated the relationship between MTA1 expression and clinical characteristics or prognosis of patients with solid tumors via the PubMed, Cochrane Library, and Embase electronic databases. Fixed-effect and random-effect meta-analytical techniques were used to correlate MTA1 expression with outcome measures. The outcome variables are shown as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Analysis of 40 cohort studies involving 4564 cancer patients revealed a significant association of MTA1 overexpression with tumor patient age (>50 vs. <50 years: combined OR 0.73, 95% CI 0.57-0.94), tumor grade (G3/4 vs. G1/2: combined OR 1.94, 95% CI 1.48-2.53), tumor size (>3 cm vs. <3 cm: combined OR 2.35, 95% CI 1.73-3.19), T stage (T3/4 vs. T1/2: combined OR 2.11, 95% CI 1.74-2.56), lymph node metastasis (yes vs. no: combined OR 2.92, 95% CI 2.26-3.75), distant metastasis (yes vs. no: combined OR 2.26, 95% CI 1.42-3.59), TNM stage (III/IV vs. I/II: combined OR 2.50, 95% CI 1.84-3.38), vascular invasion (yes vs. no: combined OR 2.26, 95% CI 1.92-3.56), and poor overall survival time (HR 1.83; 95% CI: 1.53-2.20; P = .000). Our analyses demonstrate that MTA1 was an effective predictor of a worse prognosis in tumor patients. Moreover, MTA1 may play important role in tumor progression and outcome, and targeting MTA1 may be a new strategy for anti-cancer therapy.


Crocodile tears and thread test of lacrimation.
Patients with incomplete recovery from peripheral facial paralysis often complain of eye-watering while eating (crocodile tears or gustolacrimal reflex). In 55 patients (22 completely recovered from peripheral facial paralysis, 23 incompletely recovered, and ten with hemifacial spasm), lacrimation was monitored by the thread test (a modification of the Schirmer test) during taste stimulation. In the 22 patients with complete recovery, the results of the thread test did not differ before and after a sweet-sour candy was given (taste stimulation). All the patients with incomplete recovery showed either synkinesis or contracture. Lacrimation on the side of the lesion was high even before taste stimulation. After taste stimulation, a rapid and definite increase in lacrimation was observed. The results show that in patients with synkinesis and incomplete recovery after peripheral facial paralysis, the misdirected regeneration of the injured nerve fiber often occurs from the gustatory nerve to the lacrimal nerve, as well as between motor fibers.


EGF does not enhance corneal epithelial cell motility.
Although it is well known that epidermal growth factor (EGF) accelerates corneal epithelial wound healing by stimulating mitosis, it is also believed that EGF may directly stimulate the motility of individual corneal epithelial cells. We employed three different experimental methods to determine if EGF does indeed enhance the motility of corneal epithelial cells (independent of mitotic effects). First, the effects of EGF on the motility of tissue-cultured rat and rabbit corneal epithelial cells were investigated by a Boyden chamber assay. In rat corneal epithelium, these effects were further investigated by a second method, the agarose drop assay. Both assay techniques demonstrated no increase in corneal epithelial cell motility in the presence of EGF. These findings were corroborated by a third method which consisted of measuring the closure rate of epithelial wounds in organ-cultured rat corneas in the presence and absence of EGF, while concurrently arresting mitosis with colchicine. The wound closure rate before addition of any drug was 0.46 +/- 0.03 mm2/hr. The wound closure rate with EGF (50 ng/ml) was 0.55 +/- 0.03 mm2/hr, significantly (P less than 0.005) more rapid than the drug-free controls. However, when EGF (50 ng/ml) and colchicine (40 micrograms/ml) were used simultaneously, the acceleration of wound closure by EGF was completely negated by the presence of colchicine, resulting in a wound closure rate (0.46 +/- 0.06 mm2/hr) that did not differ significantly (P greater than 0.50) from that of the drug-free control.(ABSTRACT TRUNCATED AT 250 WORDS)


Genomic dark matter: the reliability of short read mapping illustrated by the genome mappability score.
Genome resequencing and short read mapping are two of the primary tools of genomics and are used for many important applications. The current state-of-the-art in mapping uses the quality values and mapping quality scores to evaluate the reliability of the mapping. These attributes, however, are assigned to individual reads and do not directly measure the problematic repeats across the genome. Here, we present the Genome Mappability Score (GMS) as a novel measure of the complexity of resequencing a genome. The GMS is a weighted probability that any read could be unambiguously mapped to a given position and thus measures the overall composition of the genome itself. We have developed the Genome Mappability Analyzer to compute the GMS of every position in a genome. It leverages the parallelism of cloud computing to analyze large genomes, and enabled us to identify the 5-14% of the human, mouse, fly and yeast genomes that are difficult to analyze with short reads. We examined the accuracy of the widely used BWA/SAMtools polymorphism discovery pipeline in the context of the GMS, and found discovery errors are dominated by false negatives, especially in regions with poor GMS. These errors are fundamental to the mapping process and cannot be overcome by increasing coverage. As such, the GMS should be considered in every resequencing project to pinpoint the 'dark matter' of the genome, including of known clinically relevant variations in these regions. The source code and profiles of several model organisms are available at http://gma-bio.sourceforge.net


The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan.
Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan. Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance. Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function. The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.


Back to the future for wound care?
The European Renaissance was a time of enormous change and rapid progress in the arts, sciences, and medicine. A glimpse of wound care in the last phase of the European Renaissance is provided by the analysis of work by Wilhelm Fabry, the "father of German surgery," as provided in his book De Combustionibus ("Burns") which details his range of treatments for the burn wound, as well as his approach to the later problems of scarring and contracture. We describe some of the historic events which may have stimulated Fabry's writings, in particular, the influences passed down from the medical school of Padua which thereby advanced the cause of wound care and surgery. Finally, we briefly explore the potential of such an approach to the works of our medical forefathers.


Posterior crossbites in children.
Posterior crossbite, the most common malocclusion in young children, can be caused by a variety of skeletal, muscular, or dental factors. This condition produces insufficient maxillary arch width and is frequently associated with various oral sucking and postural habits. If left untreated, this problem can result in adverse skeletal growth changes. Various mechanical treatment modalities designed to expand the posterior maxillary arch width are available to correct this problem. The appropriate treatment method depends on the patient's age and level of cooperation as well as the determined etiology of the constriction.


A Diels-Alder super diene breaking benzene into C2H2 and C4H4 units.
Cyclic polyene with six carbon atoms (benzene) is very stable, whereas cyclic polyene with four carbon atoms (cyclobutadiene) is extremely unstable. The electron-withdrawing pentafluorophenyl group of a substituted cyclobutadiene lowers the energy of the lowest unoccupied molecular orbital, greatly increasing its reactivity as a diene in Diels-Alder reactions with acetylene, ethylene and even benzene. Here we show that the reaction with benzene occurs cleanly at the relatively low temperature of 120 °C and results in the formal fragmentation of benzene into C2H2 and C4H4 units, via a unique Diels-Alder/retro-Diels-Alder reaction. This is a new example of the rare case where breaking the C-C bond of benzene is possible with no activation by a transition metal.


Ultraviolet light suppresses IFN-gamma-induced IL-7 gene expression in murine keratinocytes by interfering with IFN regulatory factors.
UV light is a potent stimulus for keratinocytes to release several cytokines. Recently, UV light was shown to inhibit keratinocyte release of IL-7, a growth factor for dendritic epidermal T cells. Since to date IL-7 is the only keratinocyte-derived cytokine down-regulated by UV light, we addressed the molecular mechanisms involved. IFN-gamma treatment of the murine keratinocyte cell line Pam 212 resulted in an up-regulation of IL-7 mRNA, while IL-7 transcripts were suppressed in cells exposed to UV before IFN-gamma. Because IFN-gamma induces IL-7 via activation of an IFN-stimulated response element (ISRE) located in the 5' upstream region of the IL-7 gene, bandshift assays were performed using the ISRE sequence from the IL-7 gene. Nuclear extracts from untreated cells revealed two bands, a slower migrating band identified by supershift analysis as IFN regulatory factor-2 (IRF-2), a transcriptional repressor, and a more rapidly migrating band identified as IRF-1, a transcriptional activator. IFN-gamma significantly induced IRF-1 binding, whereas UV treatment plus IFN-gamma decreased IRF-1 binding, suggesting that UV light suppresses IFN-gamma-induced expression of IL-7 by interfering with IRF-1. Chloramphenicol transferase assay confirmed functional relevance, showing that the minimal promoter sequence for the ISRE explicitly responded to IFN-gamma, which was suppressed by UV irradiation. Northern blot analysis using an IRF-1 cDNA probe revealed that UV light reduced IFN-gamma-induced IRF-1 mRNA. This study demonstrates that UV light can inhibit cytokine activities by interference with transcriptional activators. This newly described ability of UV light may contribute to its immunosuppressive properties.


Physical activity compliance: differences between overweight/obese and normal-weight adults.
Comparisons of physical activity measured by accelerometers in overweight/obese adults and their normal-weight counterparts are limited. Compliance with the 2002 Institute of Medicine (IOM) exercise recommendations for 60 minutes of moderate-intensity exercise daily has not been reported. The purpose of this study was to compare physical activity, as measured by accelerometers, in overweight/obese adults vs. normal-weight controls and to assess compliance with recommendations for physical activity by the IOM in 2002 and by the Centers for Disease Control and Prevention and American College of Sports Medicine in 1995 for 30 minutes of moderate-intensity activity, preferably all days of the week. Sixty-two overweight/obese subjects, BMI > or = 25, included 31 adults, 12 men and 19 women, 25 to 69 years old, and their normal-weight controls, BMI 18.5 to 24.9, matched for gender, age, and height. Body composition was assessed using DXA. Physical activity was measured with Actigraph accelerometers (MTI, Fort Walton Beach, FL) worn by each participant for 7 consecutive days. Accelerometry data indicated that overweight/obese adults recorded approximately 60 counts per minute less per day and spent 21 minutes less engaged in moderate or greater intensity activity than their normal-weight counterparts. Although 71% to 94% of those studied met 1995 recommendations, only 13% of overweight/obese subjects and 26% of normal-weight participants met 2002 exercise recommendations. These results suggest that daily minutes spent in moderate-intensity activity or greater are associated with weight status and that the 2002 IOM recommendations may be difficult to meet even for normal-weight individuals.


BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining.
The 16q23 locus has been recently suggested in both breast and prostate cancer to contain a gene involved in disease progression. The breast cancer antiestrogen resistance 1 (BCAR1) gene, located at 16q23, contributes to many cellular processes including migration and survival, and interacts in vitro with the growth factor receptor EGFR and the metastasis suppressor KAI1. BCAR1, EGFR, and KAI1 expression was studied by immunohistochemistry on a tissue microarray containing 100 localized prostate cancers (LPC), 15 hormone refractory prostate cancers (HRPC), and 15 lymph node metastasis (LNM). Forty eight of the LPC were also analyzed for 16q23 LOH status using microsatellite markers. BCAR1 staining was present in 25% of LPC, associated with higher Gleason score, and in 60% and 80% of, respectively, LNM and HRPC. BCAR1 expression was inversely correlated with 16q23 LOH status (P < 0.001), and was associated with high EGFR staining (P < 0.02), and negative KAI1 expression (P < 0.01). BCAR1 expression in LPC seems to be regulated at least in part by genetic events. The increased expression of BCAR1 with disease progression suggests a potential interest for both prognosis and treatment.


An analytical study on the identification of N-linked glycosylation sites using machine learning model.
N-linked is the most common type of glycosylation which plays a significant role in identifying various diseases such as type I diabetes and cancer and helps in drug development. Most of the proteins cannot perform their biological and psychological functionalities without undergoing such modification. Therefore, it is essential to identify such sites by computational techniques because of experimental limitations. This study aims to analyze and synthesize the progress to discover N-linked places using machine learning methods. It also explores the performance of currently available tools to predict such sites. Almost seventy research articles published in recognized journals of the N-linked glycosylation field have shortlisted after the rigorous filtering process. The findings of the studies have been reported based on multiple aspects: publication channel, feature set construction method, training algorithm, and performance evaluation. Moreover, a literature survey has developed a taxonomy of N-linked sequence identification. Our study focuses on the performance evaluation criteria, and the importance of N-linked glycosylation motivates us to discover resources that use computational methods instead of the experimental method due to its limitations.


Multimodal fiber source for nonlinear microscopy based on a dissipative soliton laser.
Recent developments in high energy femtosecond fiber lasers have enabled robust and lower-cost sources for multiphoton-fluorescence and harmonic-generation imaging. However, picosecond pulses are better suited for Raman scattering microscopy, so the ideal multimodal source for nonlinear microcopy needs to provide both durations. Here we present spectral compression of a high-power femtosecond fiber laser as a route to producing transform-limited picosecond pulses. These pulses pump a fiber optical parametric oscillator to yield a robust fiber source capable of providing the synchronized picosecond pulse trains needed for Raman scattering microscopy. Thus, this system can be used as a multimodal platform for nonlinear microscopy techniques.


Tissue oxygen perfusion and pressure ulcer healing.
Diabetes mellitus is known to retard wound healing. This study of 35 subjects with pressure ulcers found that carbon dioxide levels were negatively correlated to healing rates. Transcutaneous oxygen levels of peri ulcer was not statistically significantly related to healing rates.


Seroprevalence of zoonoses in a Cree community (Canada).
Cree trappers and hunters are at risk for contracting infectious diseases conveyed by wildlife. We performed a study in a Cree community (Canada) to determine the seroprevalence of 8 zoonotic infections among hunters and trappers for evidence of exposure to Trichinella sp., Toxoplasma gondii, Toxocara canis, Echinococcus granulosus, Leptospira sp., Coxiella burnetii, Francisella tularensis, and Sin Nombre virus. A total of 50 participants (28 women and 22 men) were included in this study. Results indicate no or infrequent exposure to the Sin Nombre virus (0%) and 3 of the 4 parasites investigated (0-4%). Exposure to T. gondii (10%) and some bacteria appeared to be more prevalent (range, 4-18%). Overall, seropositivity was related to fishing, hunting, and trapping activities. Physicians should be aware of these infections in this population, particularly Q fever, tularemia, and leptospirosis.


Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, including binge drinking: a population-based study.
Alcohol consumption is postulated to be a risk factor for pancreatic cancer (PCA), but clarification of degree of risk related to consumption characteristics is lacking. We examined the association between alcohol consumption and PCA in a population-based case-control study (532 cases, 1,701 controls) in the San Francisco Bay Area. Population-based controls were frequency-matched by sex, age within 5-year categories and county of residence to cases identified by the cancer registry's rapid case ascertainment. Detailed alcohol consumption data, including binge drinking (>or=5 drinks/day), were collected during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using adjusted unconditional logistic regression. Depending on dose, duration, and pattern of drinking, ORs were increased 1.5- to 6-fold among men but not women. In men, ORs increased with increasing overall alcohol consumption (22-35 drinks/week OR = 2.2, 95% CI = 1.1-4.0; >or=35 drinks/week OR = 2.6, 95% CI = 1.3-5.1, p-trend = 0.04). Most notable were effects with a history of binge drinking (OR = 3.5, 95% CI = 1.6-7.5) including increased number of drinks per day (p-trend = 0.002), and increased years of binge drinking (p-trend = 0.0006). In fully adjusted models that included smoking and other confounders, ORs for binge drinking in men were somewhat higher than in age-adjusted models. Results from our detailed analyses provide support for heavy alcohol consumption (including binge drinking) as a risk factor for PCA in men.


How Compassionate Abilities Influence the Experience of Loneliness and Quality of Life of People with and without Chronic Physical Disease?
The current study aimed to test whether individuals with and without a chronic physical disease differ in levels of compassionate abilities, loneliness and quality of life (QoL); and to examine whether loneliness mediated the impact of self-compassion and of receiving compassion from others in physical, psychological, and social QoL. In this cross-sectional study, individuals with (n = 278) and without (n = 455) physical chronic disease were recruited through an online self-report protocol. The Compassionate Attributes and Engagement Scale, the UCLA Loneliness Scale, and the World Health Organization's QoL-BREF were used. Individuals with a chronic physical disease diagnosis reported lower compassionate abilities and QoL, as well as higher levels of loneliness, when compared to participants without a diagnosis. For both samples, compassionate abilities were negatively linked to loneliness, and positively linked to QoL. Path analysis results indicated that compassionate abilities have a direct effect on loneliness, which explains individuals' perceived QoL. Results highlight the crucial role of self-compassion skills and the ability to perceive others as compassionate, in loneliness and QoL, both in individuals with and without a chronic physical disease. These findings seem to have important research and clinical implications.


Profiling of long non-coding RNAs identifies LINC00958 and LINC01296 as candidate oncogenes in bladder cancer.
Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as a critical component in bladder cancer (BC) and lncRNAs have been associated with BC development and progression although their overall expression and functional significance is still unclear. The aim of our study was to identify novel lncRNAs with a functional role in BC carcinogenesis. RNA-sequencing was used to identify aberrantly expressed lncRNAs in 8 normal and 72 BC samples. We identified 89 lncRNAs that were significantly dys-regulated in BC. Five lncRNAs; LINC00958, LINC01296, LINC00355, LNC-CMC1-1 and LNC-ALX1-2 were selected for further analyses. Silencing of LINC00958 or LINC01296 in vitro reduced both cell viability and migration. Knock-down of LINC00958 also affected invasion and resistance to anoikis. These cellular effects could be linked to direct/indirect regulation of protein coding mRNAs involved in cell death/survival, proliferation and cellular movement. Finally, we showed that LINC00958 binds proteins involved in regulation and initiation of translation and in post-transcriptional modification of RNA, including Metadherin, which has previously been associated with BC. Our analyses identified novel lncRNAs in BC that likely act as oncogenic drivers contributing to an aggressive cancerous phenotype likely through interaction with proteins involved in initiation of translation and/or post-transcriptional modification of RNA.


The wisent (Bison bonasus, Bovidae) as an intermediate host of three Sarcocystis species (Apicomplexa: Sarcocystidae) of cattle.
Sarocysts were found in muscle tissue of a wisent (Bison bonasus) which was born and kept in Germany. Light microscopic and TEM examination revealed all the three named species known from cattle: Sarcocystis cruzi ("thin-walled", with longer hair-like villar protrusions of the primary cyst wall); S. hirsuta ("thick-walled", with tongue-like protrusions of the cyst wall arising with very short and narrow stalklets from the surface of the cyst and containing rows of electron-dense granules in the core); and S. hominis ("thick-walled", with finger-like protrusions of the cyst wall not constricted at their base and containing few or no electron-dense granules). So far, only S. cruzi was known to occur in Bison bison in North America. The findings in the wisent strikingly support a modified conception of the intermediate host specificity in Bovinae. In this connection the identity of S. cruzi and S. poephagicanis is suggested as well as that of S. hirsuta and S. poephagi.


Neuropsychological Tests for Monitoring Delirium Severity in Elderly Patients.
The authors identified neuropsychological tests appropriate for use in monitoring delirium severity in elderly patients. Ten elderly patients were administered a battery of tests while they were delirious and later during their recovery. All of the measures showed significant improvement across the two occasions (P < 0.05). Examination of components of variance suggests that modified versions of the Forward Digit Span, Similarities, or Oral Sentence Spelling tests or a combination of Forward Digit Span and Similarities or Oral Sentence Spelling are likely to be most effective in monitoring delirium severity.


Somatization, sensitization, and functional dyspepsia.
Functional dysepsia (FD) is defined as persistent or recurrent pain or discomfort centered in the upper abdomen without evidence of organic disease likely to explain the symptoms. Visceral hypersensitivity, motor dysfunction, and impaired gastric accommodation are found in some patients with FD, and psychological factors like chronic stress, attention and perception bias are also likely to play a part in the symptom formation. There is considerable overlap of non-specific symptoms like fatigue, headache, abdominal discomfort, muscle pain, and sleep disturbance in patients with different functional disorders, in this article exemplified by FD, fibromyalgia, and chronic fatigue syndrome. This overlap of symptoms indicates a common underlying sensitization process, leading to somatization.


A synthetic 'essentialome' for axenic culturing of 'Candidatus Liberibacter asiaticus'.
'Candidatus Liberibacter asiaticus' (CLas) is associated with the devastating citrus 'greening' disease. All attempts to achieve axenic growth and complete Koch's postulates with CLas have failed to date, at best yielding complex cocultures with very low CLas titers detectable only by PCR. Reductive genome evolution has rendered all pathogenic 'Ca. Liberibacter' spp. deficient in multiple key biosynthetic, metabolic and structural pathways that are highly unlikely to be rescued in vitro by media supplementation alone. By contrast, Liberibacter crescens (Lcr) is axenically cultured and its genome is both syntenic and highly similar to CLas. Our objective is to achieve replicative axenic growth of CLas via addition of missing culturability-related Lcr genes. Bioinformatic analyses identified 405 unique ORFs in Lcr but missing (or truncated) in all 24 sequenced CLas strains. Site-directed mutagenesis confirmed and extended published EZ-Tn5 mutagenesis data, allowing elimination of 310 of these 405 genes as nonessential, leaving 95 experimentally validated Lcr genes as essential for CLas growth in axenic culture. Experimental conditions for conjugation of large GFP-expressing plasmids from Escherichia coli to Lcr were successfully established for the first time, providing a practical method for transfer of large groups of 'essential' Lcr genes to CLas.


Papillary renal cell carcinoma radiographically mimicking massive calcification.
A 53-year-old male was referred to the Department of Urology, Hokkaido Kouseiren Kutchan Kousei Hospital for a left renal mass incidentally found by computed tomography. The tumor was 29 mm in diameter and showed ring-like calcification and heterogeneous enhancement by the contrast medium. The patient underwent left partial nephrectomy after the diagnosis of left renal cell carcinoma. Contrary to the radiographic finding, there was no palpable calcified lesion in the macroscopic specimen. Histopathologically, the tumor showed features of papillary renal cell carcinoma with massive psammoma bodies which might have been the cause for mimicking radiographic calcification.


Immunohistochemical findings in primary fallopian tube cancer. Case report.
Primary fallopian tube carcinoma is a rare malignancy, representing about 1% of female genital tract malignancies. We present a case report and compare the medical performance with accessible data from the literature as well as present immunohistochemical analysis of estrogen, progesterone, and proliferative together with basic cytokeratin reactions. We found that immunohistochemical expression of ER-beta was dominant over ER-alpha which encourages further evaluations to be performed on a larger number of samples, especially taking into account the very scant progesterone receptor expression we noted. On the basis of the course of disease under study, etiological problems and the possibility of clinical misdiagnosis have been discussed. The low prevalence rate and lack of clear symptoms of this type of carcinoma makes the final clinical diagnosis almost impossible without an intraoperative histopathological study. Multicenter studies are needed to improve the understanding of possible risk factors.