Electrophysiological correlates of predictive coding of auditory location in the perception of natural audiovisual events.
In many natural audiovisual events (e.g., a clap of the two hands), the visual signal precedes the sound and thus allows observers to predict when, where, and which sound will occur. Previous studies have reported that there are distinct neural correlates of temporal (when) versus phonetic/semantic (which) content on audiovisual integration. Here we examined the effect of visual prediction of auditory location (where) in audiovisual biological motion stimuli by varying the spatial congruency between the auditory and visual parts. Visual stimuli were presented centrally, whereas auditory stimuli were presented either centrally or at 90° azimuth. Typical sub-additive amplitude reductions (AV - V < A) were found for the auditory N1 and P2 for spatially congruent and incongruent conditions. The new finding is that this N1 suppression was greater for the spatially congruent stimuli. A very early audiovisual interaction was also found at 40-60 ms (P50) in the spatially congruent condition, while no effect of congruency was found on the suppression of the P2. This indicates that visual prediction of auditory location can be coded very early in auditory processing.


mcaGUI: microbial community analysis R-Graphical User Interface (GUI).
Microbial communities have an important role in natural ecosystems and have an impact on animal and human health. Intuitive graphic and analytical tools that can facilitate the study of these communities are in short supply. This article introduces Microbial Community Analysis GUI, a graphical user interface (GUI) for the R-programming language (R Development Core Team, 2010). With this application, researchers can input aligned and clustered sequence data to create custom abundance tables and perform analyses specific to their needs. This GUI provides a flexible modular platform, expandable to include other statistical tools for microbial community analysis in the future. The mcaGUI package and source are freely available as part of Bionconductor at http://www.bioconductor.org/packages/release/bioc/html/mcaGUI.html


Event-based prospective memory for poorly attended events.
In the most frequently used paradigm for studying event-based prospective memory (PM, Einstein & McDaniel, 1990), participants perform an ongoing task and are asked to perform an additional task when a particular stimulus (the PM cue) is presented. In this study three experiments examined how PM performance depends on stimulus selection, which is a major process involved in executive task control according to current theorizing. Participants made semantic judgments about a target word accompanied by two nontargets (distracters). The target was indicated by its spatial position (Experiment 1) or color (Experiment 2). The findings indicated that PM performance was much poorer when the PM cue was irrelevant to the ongoing task, in spite of the fact that nontargets were processed semantically as shown in Experiment 3.


Workplace Violence: An Extensive Issue for Nurses in Pakistan-: A Qualitative Investigation.
The objective of the present study was to examine the incidences of violence during nurses' careers and their impacts on their work life in the Islamic Republic of Pakistan. The current article highlights workplace violence toward nurses as a serious issue in Pakistan, which is almost an unexplored area as data are scarce. Individual interviews were conducted, applying a qualitative approach for getting the in-depth knowledge about the subject. Grounded theory method was used for data analysis and NVIVO-10 was used for information processing. Majority of the nurses experienced violence in the previous 6 months of their career. Nurses also confirmed that verbal abuse was witnessed and although experienced frequently, they did not report it, as they believed that reporting was useless and no action would be taken. Most nurses reported that due to violence, they experience stress, low work performance, low job satisfaction, high absenteeism, and high turnover intentions. The results illustrated a clear trend of an increasing number of violence incidents toward nurses. The findings of the present study possibly will assist hospital administration to manage and reduce violence at workplace.


Immunochemical detection of hepatic cocaine-protein adducts in mice.
Cocaine is capable of producing hepatic necrosis in laboratory animals and humans. Studies in mice indicate that N-oxidative metabolism of cocaine is required for hepatotoxicity and have suggested that toxicity may result from the adduction of proteins by cocaine-reactive metabolites. To aid in identifying protein targets for cocaine-reactive metabolites, an antibody was raised in rabbits immunized with cocaine linked via the tropane nitrogen to a carrier protein (bovine serum albumin). Hepatic proteins from cocaine-treated mice (ICR males, 50 mg of cocaine/kg of body weight, ip) and saline-treated controls were prepared from whole liver homogenate or following subcellular fractionation, and Western blot analyses of hepatic proteins using this antibody were conducted following one- and two-dimensional SDS-PAGE. Analysis of liver homogenate from cocaine-treated mice revealed major protein targets with approximate molecular masses of 20 kDa (pI = 6.0), 44 kDa (two proteins with pI's of 5.0 and 7.0), 52-54 kDa (pI = 4.5), and 64 kDa (pI = 5.5). These specific protein targets were shown to be localized in the mitochondria and microsomes. Several minor bands of immunoreactivity were also seen in mice treated with cocaine, but not in saline-treated controls. Pretreatment of mice with the P450 inhibitor SKF 525A diminished or eliminated the formation of these cocaine-protein adducts. Liver sections from cocaine-treated mice immunostained using the antibody indicated the presence of cocaine-adducted proteins in the centrilobular and midzonal regions of the lobule, corresponding to areas of hepatocyte swelling and necrosis. This study indicates that reactive metabolites from cocaine bind to discrete proteins in specific regions of the liver, consistent with a role for protein adduction in cocaine hepatotoxicity.


Traumatic brain injury, microglia, and Beta amyloid.
Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (Aβ). Data from both AD and TBI studies suggest that microglia play a central role in Aβ accumulation after TBI. This paper focuses on the current research on the role of microglia response to Aβ after TBI.


Population pharmacokinetics model and limited sampling strategy for intravenous vinorelbine derived from phase I clinical trials.
a) To characterize the pharmacokinetics of intravenous vinorelbine, b) to use a population analysis for the identification of patient covariates that might appreciably influence its disposition and c) to define a limited sampling strategy for further Bayesian estimation of individual pharmacokinetic parameters. All data were collected from 64 patients (99 courses) entered in three different phase I trials that have been previously reported. All patients received vinorelbine as a 20 min infusion with dose levels ranging from 20-45 mg m-2. The population pharmacokinetic model was built in a sequential manner on a subset of two-thirds of the data, starting with a covariate-free model then progressing to a covariate model using the nonlinear-mixed effect methodology. The remaining one-third of the data were used to validate several sparse sampling designs. A linear three-compartment model characterized vinorelbine blood concentrations (n=1228). Two primary pharmacokinetic parameters (total clearance and volume of distribution) were related to various combinations of covariates. The relationship for total clearance (CLtotal (l h-1)=29.2xBSAx(1-0.0090 Plt)+6.7xWt/Crs) was dependent on the patient's body surface area (BSA), weight (Wt), serum creatinine (Crs) and platelet count before administration (Plt). The optimal limited sampling strategy consisted of a combination of three measured blood concentrations; the first immediately before the end of infusion or 20 min later, the second at either 1 h, 3 h or 6 h and the third at 24 h after drug administration. A population pharmacokinetic model and a limited sampling strategy for intravenous vinorelbine have been developed. This is the first population analysis performed on the basis of a large phase I database that has identified clinical covariates influencing the disposition of i.v. vinorelbine. The model can be used to obtain accurate Bayesian estimates of pharmacokinetic parameters in situations where extensive pharmacokinetic sampling is not feasable.


High molecular weight of polysaccharides from Hericium erinaceus against amyloid beta-induced neurotoxicity.
Hericium erinaceus (HE) is a well-known mushroom in traditional Chinese food and medicine. HE extracts from the fruiting body and mycelia not only exhibit immunomodulatory, antimutagenic and antitumor activity but also have neuroprotective properties. Here, we purified HE polysaccharides (HEPS), composed of two high molecular weight polysaccharides (1.7 × 10(5) Da and 1.1 × 10(5) Da), and evaluated their protective effects on amyloid beta (Aβ)-induced neurotoxicity in rat pheochromocytoma PC12 cells. HEPS were prepared and purified using a 95 % ethanol extraction method. The components of HEPS were analyzed and the molecular weights of the polysaccharides were determined using high-pressure liquid chromatography (HPLC). The neuroprotective effects of the polysaccharides were evaluated through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and an MTT assay and by quantifying reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) of Aβ-induced neurotoxicity in cells. Our results showed that 250 μg/ml HEPS was harmless and promoted cell viability with 1.2 μM Aβ treatment. We observed that the free radical scavenging rate exceeded 90 % when the concentration of HEPS was higher than 1 mg/mL in cells. The HEPS decreased the production of ROS from 80 to 58 % in a dose-dependent manner. Cell pretreatment with 250 μg/mL HEPS significantly reduced Aβ-induced high MMPs from 74 to 51 % and 94 to 62 % at 24 and 48 h, respectively. Finally, 250 μg/mL of HEPS prevented Aβ-induced cell shrinkage and nuclear degradation of PC12 cells. Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons.


Variation of the Pseudomonas community structure on oak leaf lettuce during storage detected by culture-dependent and -independent methods.
The genus Pseudomonas plays an important role in the lettuce leaf microbiota and certain species can induce spoilage. The aim of this study was to investigate the occurrence and diversity of Pseudomonas spp. on oak leaf lettuce and to follow their community shift during a six day cold storage with culture-dependent and culture-independent methods. In total, 21 analysed partial Pseudomonas 16S rRNA gene sequences matched closely (> 98.3%) to the different reference strain sequences, which were distributed among 13 different phylogenetic groups or subgroups within the genus Pseudomonas. It could be shown that all detected Pseudomonas species belonged to the P. fluorescens lineage. In the culture-dependent analysis, 73% of the isolates at day 0 and 79% of the isolates at day 6 belonged to the P. fluorescens subgroup. The second most frequent group, with 12% of the isolates, was the P. koreensis subgroup. This subgroup was only detected at day 0. In the culture-independent analysis the P. fluorescens subgroup and P. extremaustralis could not be differentiated by RFLP. Both groups were most abundant and amounted to approximately 46% at day 0 and 79% at day 6. The phytopathogenic species P. salmonii, P. viridiflava and P. marginalis increased during storage. Both approaches identified the P. fluorescens group as the main phylogenetic group. The results of the present study suggest that pseudomonads found by plating methods indeed represent the most abundant part of the Pseudomonas community on oak leaf lettuce.


Paroxysmal nocturnal haemoglobinuria: nature's gene therapy?
The development of paroxysmal nocturnal haemoglobinuria (PNH) requires two coincident factors: somatic mutation of the PIG-A gene in one or more haemopoietic stem cells and an abnormal, hypoplastic bone marrow environment. When both of these conditions are met, the fledgling PNH clone may flourish. This review will discuss the pathophysiology of this disease, which has recently been elucidated in some detail.


Direct observation of a sub-Poissonian number distribution of atoms in an optical lattice.
We report single-site resolution in a lattice with tunneling between sites, allowing for an in situ study of stochastic losses. The ratio of the loss rate to the tunneling rate is seen to determine the number fluctuations, and the overall profile of the lattice. Sub-Poissonian number fluctuations are observed. Deriving the lattice beams from a microlens array results in perfect relative stability between beams.


Reactivity of organogermanium and organotin trihydrides.
The organogermanium and organotin trihydrides (TbbEH3) [E = Ge (3), Sn (7)] with the Tbb substituent were synthesized by hydride substitution (Tbb = 2,6-[CH(SiMe3)2]2-4-(t-Bu)C6H2). Deprotonation of the organoelement trihydrides 3 and 7 was studied in reaction with bases MeLi, BnK and LDA (Bn = benzyl, LDA = lithium diisopropylamide) to yield the deprotonation products (8-11) as lithium or potassium salts. Hydride abstraction from TbbSnH3 using the trityl salt [Ph3C][Al(OC{CF3}3)4] gives the salt [TbbSnH2][Al(OC{CF3}3)4] (12) which was stabilized by thf donor ligands [TbbSnH2(thf)2][Al(OC{CF3}3)4] (13). Tintrihydride 7 reacts with trialkylamine Et2MeN to give as the product of a reductive elimination of hydrogen the distannane (TbbSnH2)2 (14). Transfer of hydrogen was observed in reaction of trihydrides TbbEH3 (E = Ge, Sn) and Ar*GeH3 with N-heterocyclic carbene (NHC). The NHC adduct TbbSnH(iPrNHC) (15) was synthesized at rt and the germanium hydrides exhibit hydrogen transfer at higher temperatures to give Ar*GeH(MeNHC) (16) and TbbGeH(MeNHC) (17).


Blocking the IL-1β signalling pathway prevents chronic viral myocarditis and cardiac remodeling.
Coxsackieviruses of group B (CVB) are well-known causes of acute and chronic myocarditis. Chronic myocarditis can evolve into dilated cardiomyopathy (DCM) characterized by fibrosis and cardiac remodeling. Interleukin-1β (IL-1β) plays a decisive role in the induction of the inflammatory response as a consequence of viral replication. In this study, we analyzed the effects of IL-1β neutralization on the transition of acute to chronic myocarditis in a mouse model of CVB3 myocarditis. Mice were treated with an anti-murine IL-1β antibody as a surrogate for Canakinumab at different time points post CVB3 infection. Treatment was performed in the early phase (day 1-14 pi, day 3-14 pi) or at a later stage of myocarditis (day 14-28 pi). Subsequently, the hearts were examined histologically, immunohistochemically and by molecular biology. A significant reduction of viral replication, cardiac damage and inflammation was found after administration of the antibody in the early phase and in the later phase of infection. Furthermore, less collagen I deposition and a considerable reduction of fibrosis were found in antibody-treated mice. Using microarray analysis, a significant upregulation of various extracellular matrix and fibrosis-associated molecules was found in CVB3-infected mice, including TGF-β, TIMP-1 and MMP12, as well as diverse matricellular proteins, whereas, these molecules were significantly downregulated in all IL-1β antibody-treated infected mice. Neutralization of IL-1β at different stages of enteroviral infection prevents the development of chronic viral myocarditis by reducing inflammation, interstitial fibrosis and adverse cardiac remodeling. These findings are relevant for the treatment of patients with acute and chronic myocarditis.


Rationale for the clinical use of immunotoxins: monoclonal antibodies conjugated to ribosome-inactivating proteins.
The use of chemotherapeutic drugs in combination with bone marrow transplantation to treat cancer patients has markedly improved the disease-free survival and cure rate. Part of the tumor cells, however, can escape from therapy due to resistance. Tumor-specific delivery of toxins that do not interfere with conventional drugs and are not cell cycle dependent seems to be a reasonable approach to overcome this problem. Natural ribosome-inhibiting-proteins (RIPs) from plants, bacteria and fungi which are extremely toxic inhibitors of protein synthesis are isolated and coupled to monoclonal antibodies (MoAbs) and receptor-specific ligands, immunotoxins (ITs), to fulfil this purpose. ITs are very suitable to eliminate malignant cells in vitro and in vivo. RIPs contain two or three active sites: a binding site which can be absent in a part of the RIPs and can be replaced by the MoAb; a translocation site that facilitates transport into the cytosol after internalization, and a cytotoxic site that enzymatically inhibits protein synthesis. Binding site containing toxins induce strong nonspecific cytotoxicity when coupled to MoAbs. Recent developments in recombinant DNA techniques enable genetic elimination of the binding site to reduce nonspecific cytotoxicity of these toxins. In this review the structures and mechanisms of action of RIPs as well as factors that influence cytotoxicity of immunotoxins are discussed. Moreover the problems dealing with in vivo application of ITs such as blood clearance by instability of the IT and hepatic entrapment, and production of antibodies directed against MoAb and toxin are reviewed.


Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage.
Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed. Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional (133)Xenon) and regional (three-dimensional (99 m)Tc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml. Isovolemic hemodilution increased global cerebral blood flow from 52.25+/-10.12 to 58.56+/-11.73 ml * 100 g(-1) * min(-1) (p<0.05), but after hypervolemic hemodilution CBF returned to 51.38+/-11.34 ml * 100 g(-1) * min(-1). Global cerebral delivery rate of oxygen (CDRO(2)) decreased from 7.94+/-1.92 to 6.98+/-1.66 ml * 100 g(-1) * min(-1) (p<0.001) during isovolemic hemodilution and remained reduced, 6.77+/-1.60 ml * 100 g(-1) * min(-1) (p<0.001), after the hypervolemic hemodilution. As a test of the hemodilution effect on regional CDRO(2) an ischemic threshold was defined as the maximal amount of oxygen transported by a CBF of 10 ml * 100 g(-1) * min(-1) at a Hb 140 g/l which corresponds to a CDRO(2) of 1.83 ml * 100 g(-1) * min(-1). The brain volume with a CDRO(2) exceeding the ichemic threshold was 1300+/-236 ml before intervention. After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206+/-341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume remained reduced at 1228+/-347 ml (p<0.05). The present study of controlled isovolemic hemodilution demonstrated increased global CBF, but there was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO(2) remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH.


Sleep apnea syndrome: correction with surgical advancement of the mandible.
Mandibular retrognathism is occasionally associated with sleep apnea syndrome. Most cases of this disorder have, until now, been treated with permanent tracheotomies. One patient with this syndrome was treated with surgical advancement of the mandible with bilateral C osteotomies and iliac corticocancellous grafts. Complete reversal of the sleep apnea symptoms and return of the sleep EEG to normal resulted after surgery. Although further study needs to be done, mandibular advancement would appear to be a preferable alterantive to tracheotomy for such patients.


Validity and Reproducibility of a Dietary Questionnaire for Consumption Frequencies of Foods during Pregnancy in the Born in Guangzhou Cohort Study (BIGCS).
This study aimed to examine the reproducibility and validity of a new food frequency questionnaire (FFQ) used in a birth cohort study to estimate the usual consumption frequencies of foods during pregnancy. The reference measure was the average of three inconsecutive 24 h diet recalls (24 HR) administrated between two FFQs, and the reproducibility was measured by repeating the first FFQ (FFQ1) approximately eight weeks later (FFQ2). A total of 210 pregnant women from the Born in Guangzhou Cohort Study (BIGCS) with full data were included in the analysis. The Spearman's correlation coefficients of FFQ1 and FFQ2 ranged from 0.33 to 0.71. The intraclass correlation coefficients of the two FFQs ranged from 0.22 to 0.71. The Spearman's correlation coefficients of the 24 HR and FFQ2 ranged from 0.23 to 0.62. Cross-classification analysis showed 65.1% of participants were classified into same and contiguous quintiles, while only 3.2% were misclassified into the distant quintiles. Bland-Altman methods showed good agreement for most food groups across the range of frequencies between FFQ1 and FFQ2. Our findings indicated that the reproducibility and validity of the FFQ used in BIGCS for assessing the usual consumption frequencies of foods during pregnancy were acceptable.


A multiphase microscopic diffusion model for stratum corneum permeability. II. Estimation of physicochemical parameters, and application to a large permeability database.
The full parameterization for the stratum corneum biphasic microtransport model presented previously in this Journal [95:620-648 (2006)] is developed through a combination of fundamental transport theory and calibration with existing data. Of the five microscopic transport properties, four (D(cor), K(cor/w), D(lip), K(lip/w)) are developed from sources independent of the existing steady-state permeability database. The fifth parameter, k(trans) (the mass transfer coefficient for transbilayer hopping), is derived from a fit of the model to the permeability data according to a modified free surface area function of the form log(10) k(trans) = A-B x (MW)(1/3). Examination of the experimental data in terms of the two dimensionless groups, R and sigma, arising from the analysis leads to the conclusion that SC permeation for most compounds is dominated by the transcellular pathway regardless of their lipophilicity, a striking departure from recent skin permeability models. Overall fit of the developed model(s) to the permeability data is somewhat better than for the Potts-Guy equation and variants thereof; however, marked improvement is seen in the estimation of lag times and the related potential for predicting skin hydration effects and transient skin permeation profiles. Simple approximations to the full numerical solution are presented that allow the developed model(s) to be implemented on a spreadsheet.


Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.
Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).


Global Gleason grade groups in prostate cancer: concordance of biopsy and radical prostatectomy grades and predictors of upgrade and downgrade.
To evaluate concordance, upgrades and downgrades from biopsy to prostatectomy, and associated clincopathological parameters, using the recently proposed Gleason grade groups/International Society of Urologic Pathology (ISUP) grades. We evaluated 2529 patients who underwent biopsy and prostatectomy in our institution from 2005 to 2014. A global grade group (GR)/Gleason score (GS) was used. Factors associated with GR1/GS ≤6 upgrades and GR2/GS3 + 4 downgrades were analysed by multivariable logistic regression. The final GR/GS was identical with the biopsy GR/GS in 59.3% of cases, with the highest concordance for GR2 and GR5 and lowest for GR4. In GR1-5, identical grades were found in GR: (i) 47.6%, (ii) 73.6%, (iii) 52.8%, (iv) 21.4% and (v) 68.3%, respectively. Final GR was upgraded in 32.3% cases; in GR1-4: (i) 52.4%, (ii) 19.0%, (iii) 16.4% and (iv) 32.9%. Most frequent upgrades occurred from biopsy GR1 to prostatectomy GR2. A final GR downgrade was found in 8.3% cases. For individual GR2-5 the downgrades were found in GR: (i) 7.4%, (ii) 30.8%, (iii) 45.7% and (iv) 31.7%. Upgrades of biopsy GR1 were associated with: age ≥60 years, PSA density ≥0.2, ≥2 positive cores, ≥5% core tissue involvement and perineural invasion [area under receiver operating characteristic (ROC) curve 0.699]. Downgrades of biopsy GR2 correlated inversely with: age ≥60 years, PSA >10 ng/ml and ≥2 positive core (area under ROC curve 0.623). We found highest concordance for GR2 and GR5 and lowest for GR4. The baseline clinical variables associated with GR1 upgrades and GR2 downgrades may play a role in clinical decision-making.


Levator recession and minimal lateral tarsorrhaphy for the management of lagophthalmos and corneal exposure in facial palsy.
Recession of levator muscle can potentially decrease the severity of corneal exposure by reducing margin-reflex distance 1. The purpose of this study is evaluation of effects of levator recession on lagophthalmos in facial palsy. In a non-comparative case series of consecutive patients with exposure keratopathy due to facial paralysis between 2012 and 2017, levator recession was performed through lid crease incision. Small-size (⩽3 mm) lateral tarsorrhaphy was performed on a case-by-case basis for those with moderate-to-severe keratopathy. Preoperative and postoperative measurements of margin-reflex distance 1 and lagophthalmos were compared using paired t-test. Thirty-four patients (14 men and 20 women) were enrolled with an average age of 52.3 years. Mean follow-up was 13.3 months (range, 6-36 months). The most common etiology of facial paralysis was Bell's palsy (22 cases), followed by motor vehicle accident (8), parotid surgery (3), and brain tumor surgery (1). No additional procedure was performed for eight patients, while lateral tarsorrhaphy was performed in 26 cases. Mean margin-reflex distance 1 decreased from 5.0 ± 0.4 mm to 4.0 ± 0.5 mm (p < 0.001) and mean lagophthalmos decreased from 3.3 ± 0.9 mm to 1.8 ± 0.9 mm (p < 0.001). Subgroups of patients with additional lateral tarsorrhaphy and without tarsorrhaphy experienced the same amount of reduction in margin-reflex distance 1 and lagophthalmos. Recession of levator muscle was effective in reduction of margin-reflex distance 1 and lagophthalmos in facial palsy patients. This procedure can be added to the surgical armamentarium for management of patients with facial palsy and lagophthalmos.


Computational Models for Transplant Biomarker Discovery.
Translational medicine offers a rich promise for improved diagnostics and drug discovery for biomedical research in the field of transplantation, where continued unmet diagnostic and therapeutic needs persist. Current advent of genomics and proteomics profiling called "omics" provides new resources to develop novel biomarkers for clinical routine. Establishing such a marker system heavily depends on appropriate applications of computational algorithms and software, which are basically based on mathematical theories and models. Understanding these theories would help to apply appropriate algorithms to ensure biomarker systems successful. Here, we review the key advances in theories and mathematical models relevant to transplant biomarker developments. Advantages and limitations inherent inside these models are discussed. The principles of key -computational approaches for selecting efficiently the best subset of biomarkers from high--dimensional omics data are highlighted. Prediction models are also introduced, and the integration of multi-microarray data is also discussed. Appreciating these key advances would help to accelerate the development of clinically reliable biomarker systems.


Phagocytosis of codeveloping megakaryocytic progenitors by dendritic cells in culture with thrombopoietin and tumor necrosis factor-alpha and its possible role in hemophagocytic syndrome.
Tumor necrosis factor-alpha (TNF-alpha) and thrombopoietin (TPO) have been shown to induce the differentiation and proliferation of CD34+ cells toward dendritic cells (DCs) in the presence of multiacting cytokines. We hypothesized that the costimulation of TPO and TNF-alpha generates megakaryocytic progenitors and DCs together from human CD34+ cells and that the interaction of these cells may indicate a physiologic and/or a pathologic role of DCs in megakaryopoiesis. When highly purified human CD34+ cells were cultured for 7 days with TPO alone, the generated cells expressed megakaryocytic markers, such as CD41, CD42b, and CD61. The addition of TNF-alpha with TPO remarkably decreased the number of megakaryocytic progenitor cells without affecting the cell yield. Almost half of the cells thus generated expressed CD11c, and most of them were positive for CD4 and CD123. Furthermore, CD11c+ cells were found to capture damaged CD61+ cells and to induce autologous T-cell proliferation, although the cytokine productions were low. We also confirmed an engulfment of CD61+ cells and their fragment by CD11c+ cells in bone marrow cells from patients with hemophagocytic syndrome. These findings suggest that DCs generated under megakaryocytic and inflammatory stimuli are involved in megakaryopoiesis and the subsequent immune responses to self-antigens.


Interrelationship of hypertension, plasma lipids and atherosclerosis.
The relationship between hypertension and atherosclerosis has been illustrated by epidemiological, clinical and experimental observations. Typical atherosclerotic lesions develop in arterial wall when hypercholesterolaemia is present. Hypertension aggravates these lesions by causing vascular structural changes. In clinical studies, however, the correction of high blood pressure does not decrease the incidence of coronary heart disease. Several hypotheses have been formulated to account for this observation: one is that reversibility of the structural vascular changes induced by hypertension is not complete when the blood pressure is lowered; another is that antihypertensive drugs have a deleterious effect on the vascular wall.


Do older adults with chronic low back pain differ from younger adults in regards to baseline characteristics and prognosis?
Low back pain (LBP) in older adults is poorly understood because the vast majority of the LBP research has focused on the working aged population. The aim of this study was to compare older adults consulting with chronic LBP to middle aged and young adults consulting with chronic LBP, in terms of their baseline characteristics, and pain and disability outcomes over 1 year. Data were systematically collected as part of routine care in a secondary care spine clinic. At initial presentation patients answered a self-report questionnaire and underwent a physical examination. Patients older than 65 were classified as older adults and compared to middle aged (45-65 years old) and younger adults (17-44 years old) for 10 baseline characteristics. Pain intensity and disability were collected at 6 and 12 month follow-ups and compared between age groups. A total of 14,479 participants were included in the study. Of these 3087 (21%) patients were older adults, 6071 (42%) were middle aged and 5321 (37%) were young adults. At presentation older adults were statistically different to the middle aged and younger adults for most characteristics measured (e.g. less intense back pain, more leg pain and more depression); however, the differences were small. The change in pain and disability over 12 months did not differ between age groups. This study found small baseline differences in older people with chronic LBP compared to middle aged and younger adults. There were no associations between age groups and the clinical course. Small baseline differences exist in older people with chronic low back pain compared to middle aged and younger adults referred to secondary care for chronic low back pain. Older adults present with slightly less intense low back pain but slightly more intense leg pain. Changes in pain intensity and disability over a 12 month period were similar across all age groups.


Psoriasis day care centers.
With the rapidly mounting cost of medical care in hospitals, physicians must seek alternative forms of therapy for illnesses that could conceivably be treated by less confining methods. One appraoch to this problem is the Psoriasis Day Care Center, where psoriasis patients with extensive disease are treated during the day and allowed to return home at night. The advantages include reduced cost, accessibility for more patients, and superior therapeutic results. This day care center concept could be equally applicable to other diseases now routinely treated by complete hospitalization.


Personal health records: key adoption issues and implications for management.
Electronic Personal Health Records (PHRs) has been perceived as the tool to empower consumers to become active decision-makers of their healthcare instead of leaving the decision to providers. However, there has been the lack of enthusiasm and adoption of PHRs. This paper examines the current healthcare climate and attempts to understand the major challenges associated with PHRs adoption. The paper-based and fragmented healthcare system is no longer appropriate for the digital economy of the 21st century. The integrated health information technology system is the solution to transform clinical practice to consumer centric and information driven. Tools such as PHRs are means to an end that provide better, safer and more affordable healthcare for consumers. However, there has been little research conducted to demonstrate PHR's tangible value, despite the widespread perceived value of these technologies. Although survey data reveals that there is a lack of awareness among the public, consumers are receptive to this concept, especially when a physician recommends it. Key issues in adopting PHRs and strategies for successful implementation of PHRs are discussed.


The increase of treatment options at the end of life: impact on the social work role in an inpatient hospital setting.
Treatment choices for cancer patients are becoming increasingly complex as medicine advances and doctors are able to offer more treatment options at the end of life. Research data shows that 22% of all Medicare patients start a new chemotherapy regimen in the last month of life. In a study released in 2004, data showed treatment within two weeks of death has increased from 13.8% to 18.5% over a period of three years. Treatment options should be presented to ensure that the final treatment decision made is optimal and encompasses the patient's wishes, prognosis, financial barriers, and familial support. In this article we explore three case studies where patients and families were faced with the challenges of making treatment decisions at the end of life and the importance and impact of the social work role in the multidisciplinary team. An inpatient social worker can assume a leadership position to assist patients and families in navigating the health care system and with difficult treatment options.


Trained Innate Immunity as a Novel Mechanism Linking Infection and the Development of Atherosclerosis.
There is strong epidemiological evidence for an association between acute and chronic infections and the occurrence of atherosclerotic cardiovascular disease. The underlying pathophysiological mechanisms remain unclear. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. It has recently been established that monocytes/macrophages can develop a long-lasting proinflammatory phenotype after brief stimulation with micro-organisms or microbial products, which has been termed trained immunity. The aim of this study is to assess whether trained immunity mediates the link between infections and atherosclerotic cardiovascular disease. Brief exposure of monocytes to various micro-organisms results in the development of macrophages with a persistent proinflammatory phenotype: this represents a de facto nonspecific innate immune memory, which has been termed trained immunity. This is mediated by epigenetic reprogramming at the level of histone methylation and a profound rewiring of intracellular metabolism. Although this mechanism offers powerful protection against reinfection, trained macrophages display an atherogenic phenotype in terms of cytokine production and foam cell formation. Trained monocytes are present up to 3 months after experimental infection in humans. Moreover, a trained immunity phenotype is present in patients with established atherosclerosis. We propose that trained immunity provides the missing mechanistic link that explains the association between infections and atherosclerosis. Therefore, pharmacological modulation of trained immunity has the potential to prevent infection-related atherosclerotic cardiovascular disease in the future.


Quantitative and In-Depth Survey of the Isotopic Abundance Distribution Errors in Shotgun Proteomics.
Accuracy is an important metric when mass spectrometry (MS) is used in large-scale quantitative proteomics research. For MS-based quantification by extracting ion chromatogram (XIC), both the mass and intensity dimensions must be accurate. Although much research has focused on mass accuracy in recent years, less attention has been paid to intensity errors. Here, we investigated signal intensity measurement errors systematically and quantitatively using the natural properties of isotopic distributions. First, we defined a normalized isotopic abundance error model and presented its merits and demerits. Second, a comprehensive survey of the isotopic abundance errors using data sets with increasing sample complexities and concentrations was performed. We examined parameters such as error distribution, relationships between signal intensities within one isotopic cluster, and correlations between different peak errors in isotopic profiles. Our data demonstrated that the high resolution MS platforms might also generate large isotopic intensity measurement errors (approximately 20%). Meanwhile, this error can be reduced to less than 5% using a novel correction algorithm, which is based on the theoretical isotopic abundance distribution. Finally, a nonlinear relationship was observed as the abundance error decreased in isotopic profiles with higher intensity. Our findings are expected to provide insight into isotopic abundance recalibration in quantitative proteomics.


Primary omental torsion in a 9 year old girl: a case report.
Primary torsion of the omentus is an extremely unusual cause of acute abdomen in the pediatric population. This condition occurs from twist of the pedicle of the omental apron around its longer axis, leading to edema, ischaemia and necrosis. Here we present a rare case of a 9 year old girl referred by her general practitioner due to severe right lower quadrant abdominal pain with a presumed diagnosis of acute appendiceal inflammation. Surgical operation disclosed primary omental torsion. The infarcted segment was resected and the girl's clinical recovery was uneventful without any complication. The condition may mimic a variety of other causes of acute abdominal symptoms. In this case report, a presumed diagnosis of acute appendicitis urgently induced the decision of a surgical approach. Physicians involved in the acute pediatric care have to include this rare condition in the differential diagnosis of acute onset right-sided abdominal pain.


Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism.
Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143 +/- 31 on B and 151 +/- 34 nmol/l on C) than with the conventional twice (85 +/- 16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.


[Diagnosis of stroke due to cocaine and its complications].
INTRODUCTION. Cocaine is an independent cerebrovascular risk factor both for ischaemic and haemorrhagic events, above all among persons under 55 years of age. CASE REPORT. A case report of stroke due to the consumption of cocaine is used to review its pathophysiology and the complexity involved in the management and diagnosis of the associated complications. One of these complications reported in relation to the consumption of cocaine is vasospasm. This condition shares findings observed in ultrasound imaging studies with other conditions, such as early-onset post ischaemic hyperperfusion. Yet, there are important differences between the two as regards their treatment and prognosis. CONCLUSIONS. The consumption of cocaine is associated with cerebrovascular disease through a number of different mechanisms, which each give rise to different complications. By identifying these complications, correct management can be implemented.


Highway on-ramp control.
We study the phase transition on a highway induced by the fluctuations of on-ramp flow. The highway traffic is provided by a hydrodynamical model. We analyze the characteristics of perturbations to induce congestion near on ramp. The phase boundary is obtained. A scaling relation is revealed. We also analyze the time evolution of the local density profile. Conventional control mechanisms to regulate the on-ramp flow are examined. A control scheme is proposed to suppress the congestion.


Production of human immune interferon by recombinant mammalian cells cultivated on microcarriers.
Recombinant Chinese hamster ovary (rCHO) cells were cultivated on microcarriers for the production of human immune (Gamma) interferon. The effect of basal medium, serum, and microcarrier concentration on interferon production was investigated. The specific interferon productivity in the post-confluent stage was similar to that in the growth stage. Control of the pH results in a significant improvement in the volumetric interferon production. The volumetric production rate of interferon by these rCHO cells did not decrease after one month of cultivation on microcarriers.


[Role of autologous stem cell transplantation in the treatment of Hodgkin's lymphoma].
Among lymphomas, treatment of Hodgkin's disease (HD) allows the highest cure-rate. Radiotherapy (RT) represents first choice therapy in early stages, providing complete remission (CR) rate even superior to 90%. Chemotherapy (CHT) or, when indicated, the combined modality treatment (CHT + RT) is successful, in terms of long overall survival (> 10 yrs) in more than 60% of patients with advanced stage disease at onset. Considering all stages of disease at onset, about 75% of patients can be cured. However, the remaining 25% results resistant to the conventional approach (CHT +/- RT) or, mainly, relapses after first CR. For these poor prognosis patients, it has been assessed the possibility of inducing (or reinducing) a CR by using high dose CHT with stem cells rescue. Autologous stem cell transplantation (ASCT) consists in the administration of antiblastic drugs at so high dosages to require the consequent reinfusion of stem cells, preventively harvested and cryopreserved, thus dramatically decreasing the risk of a prolonged bone marrow aplasia. This procedure is currently performed as intensification treatment in selected cases of patients with advanced stage at onset, once in CR after first-line therapy. Therefore, the development of prognostic models aimed to define with higher sensibility and specificity patients at high risk of relapse and to be submitted to ASCT as consolidation therapy, is becoming of increasing interest.


Different electroclinical picture of generalized epilepsy in two families with 15q13.3 microdeletion.
15q.13.3 microdeletion has been described in a variety of neurodevelopmental disorders. Epilepsy appears to be a common feature and, specifically, the 15q13.3 microdeletion is found in about 1% of patients with idiopathic generalized epilepsy. Recently, absence seizures with intellectual disability (ID) have been reported in patients carrying this mutation. We describe two families in which several affected members carry a 15q13.3 microdeletion in a pattern suggestive of autosomal dominant inheritance. Their phenotype includes mainly absence epilepsy and mild ID, suggesting only similarities with genetic/idiopathic generalized epilepsies but not typical features. The importance of studying such families is crucial to broaden the phenotype and understand the long-term outcome of patients with this condition.


Internal mammarial lymphoscintigraphy with SPECT after ultrasound-guided injection of 99mTc-dextran.
Twenty-two women with stage II or III breast cancer were evaluated by SPECT to determine the number, size, three-dimensional localization and depth from skin surface of the internal mammary lymph nodes for accurate radiotherapy portal planning. The results were also compared with those of planar imaging (PI). Two-step injections of 99mTc-dextran were made under ultrasound guidance into the anterior sheath of the M. rectus abdominis first at the ablation side. 1.5 h thereafter an anterior planar view was obtained to evaluate cross drainage (13.6% was observed). Then, the second injection was done at the opposite side in the same manner. Planar and tomographic images were obtained 1.5 h after the second injection. Similar values were obtained for the depth from skin surface, distance from the midline and diameter of the lymph nodes with both PI and SPECT. The total number of nodes in 22 patients detected by SPECT was higher (138) than that from PI (129), the difference being statistically significant (0.005 greater than p greater than 0.0005).


Live Imaging of Chromosome Segregation during Meiosis in the Fission Yeast Schizosaccharomyces pombe.
This protocol describes the live observation of chromosome segregation during fission yeast meiosis. To visualize one chromosome of interest, the lac operator (lacO array) is integrated at its centromere-proximal locus, and the lac repressor (lacI)-GFP fusion protein is expressed in a haploid strain. This haploid strain, in which mCherry-tagged tubulin is also expressed exogenously to monitor meiotic progression, is crossed with a nonlabeled haploid strain to induce meiosis. GFP and mCherry signals in resulting zygotes are observed by a fluorescent microscopy during the progression of meiosis.


A new species of Schistura (Teleostei: Nemacheilidae) from the south-western lowlands of Sri Lanka.
Schistura scripta, new species, is described from Nakiyadeniya in the south-western lowlands of Sri Lanka. It can be distinguished from all other congeners from Sri Lankan and peninsular India by the combination of the following characters: an incomplete lateral line with 53-76 pores, ending beneath the dorsal-fin base or slightly beyond; 7-13 post-dorsal bars; 7½ branched dorsal-fin rays; absence of an axillary pelvic lobe; and absence of a suborbital flap.


Tam3 produces a suppressible allele of the DAG locus of Antirrhinum majus similar to Mu-suppressible alleles of maize.
Tam3 from Antirrhinum majus belongs to the Ac/Ds family of transposable elements. An allele of the DAG locus of Antirrhinum (dag::Tam3), which is required for chloroplast development and leaf palisade differentiation, has been generated by Tam3 insertion into the untranslated leader sequence of the gene. This allele gives rise to a cold-sensitive phenotype, where mutant tissue containing wild-type revertant somatic sections is observed in the leaves of plants grown at 15 degrees C, while leaves of plants grown at 25 degrees C appear near wild-type. The temperature sensitivity of dag::Tam3 results from expression of the DAG locus responding to the activity of the transposable element, the transposition of which is very sensitive to growing temperature. Genetic suppression of Tam3 transposition, using the STABILISER locus, also results in suppression of the dag mutant phenotype. dag::Tam3 represents a Tam3-suppressible allele similar to those described for Mu transposons in maize. Suppression of the dag mutant phenotype in response to element inactivation appears to result from use of an alternative promoter at the 3' end of the Tam3 element. The production of suppressible alleles by an Ac-like element is discussed in relation to the mutagenic potential of plant transposons in producing complex genetic diversity.


[Stigmatization in Employed Patients with Breast, Intestinal, Prostate and Lung Cancer].
Background The stigma of cancer patients can lead to far-reaching consequences, both for the individual and for the society. Quantitative studies on the stigmatization of cancer patients are scarce. The present study assessed the stigma of cancer patients in relation to their status of employment, and analyzes sociodemographic, disease and occupational predictors. Methods In a bicentric study, 858 patients with breast, bowel, lung or prostate cancer were included. Of these, n=305 were employed and entered into the analyses (age average 55 years, 43% female, 47% breast cancer). As a comparison group, a matched sample of non-employed persons (n=213) is used from our data set. In addition to questions on work and health aspects, stigmatization was measured using the SIS-D (Social Impact Scale). The data are evaluated uni- and multivariable. Results Employed persons with prostate or breast cancer are less stigmatized (p<0.01) than non-employed persons, with effects between d=0.35-0.97. The strongest influence on perceived stigma is the lack of support from the employer, further predictors are poor health, low mental workability and diagnosis of breast cancer (R2 of the final model=0.35). Conclusion The employment of cancer patients is associated with lesser perceived stigmatization. Occupational stigmatization depends above all on the work environment or the employer's supportive attitude.


Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells.
To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells. Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice. Preincubation of human CD34(+) progenitor cells with soluble JAM-A-Fc (sJAM-A-Fc) resulted in significantly decreased adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Human CD34(+) cells express JAM-A, as defined by flow cytometry and Western blot analysis. JAM-A mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates CD34(+) cell-induced reendothelialization in vitro. Pretreatment of human CD34(+) cells with sJAM-A-Fc resulted in increased neointima formation 3 weeks after endothelial denudation in the carotid arteries of nonobese diabetic/severe combined immunodeficient mice. These results indicate that the expression of JAM-A on CD34(+) cells mediates adhesion to the vascular wall after injury and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. Human CD34(+) cells express JAM-A, mediating their interaction with platelets and endothelial cells. Specifically, JAM-A expressed on human CD34(+) progenitor cells regulates their adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Moreover, it mediates differentiation of CD34(+) cells to endothelial progenitor cells and facilitates reendothelialization.


[Problems of premedication in pediatric gynecologic consultation hours].
It is reported about the behavior of 300 children, which were examined and treated gynecological after premedication, which was performed with Elroguil, Faustan, Lepinal, Myocuran, Sinophebin liqu. The sedative effect was not good in all cases. A premedication is not generally indicated, but in some of the cases the situation of examination is better.


Metronomic chemotherapy: Back to the future!
Angiogenesis is crucial for the growth of cancer. As such, it has become an established target to fight cancer. Metronomic chemotherapy-the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration, at close regular intervals, with no prolonged drug-free breaks-is a potential approach to control advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has the property to kill resistant cancer cells and/or to inhibit tumor growth while significantly reducing undesirable toxic side effects. Here, we will discuss potential mechanisms of action of metronomic chemotherapy and briefly review the data regarding the clinical experience with this kind of anticancer treatment. Based on recent insights in the various mechanisms of action, we will try to predict the potential new developments of metronomic chemotherapy in oncology.


Abandoned endoscopic procedures.
Intraoperatively, it may be prudent at times to abandon or defer the intended therapeutic procedure due to adverse prevailing conditions. A decision to abandon or defer an endoscopic procedure would necessarily result in less morbidity compared with conventional open surgery. A retrospective review of endoscopic procedures that were abandoned or deferred and subsequent patient outcomes were noted. Between January 1998 to May 2003, 48 procedures out of a total of 11,550 endoscopic surgical procedures had to be abandoned. Previously unsuspected intraabdominal malignancy was the cause in 32 patients. Anesthesia-related problems led to the decision in 6 patients. Coincidental tuberculosis and failure in accessing the target organ were the cause in two patients each. An ectopic gallbladder, an absent gallbladder, a pancreatic phlegmon, and a failure to achieve proper single-lung ventilation led to the decision in one patient each. In two patients, presence of dense intraabdominal adhesions that precluded further progress led the surgeon to abandon the surgery. The patients with intraabdominal malignancy were staged for their disease and treated accordingly. Nine patients without malignancy who had their operation deferred due to diverse reasons were operated on a later date, whereas 4 patients were lost to follow-up. The 9 patients who underwent operation at a later date are well on follow-up. Four patients with intraabdominal malignancy died, whereas the others are well in follow-up after being treated according to the stage of their disease. Certain adverse situation encountered intraoperatively may lead the surgeon to change the approach to surgery and abandon the procedure. He may consider operation at a suitable time later or consider a different treatment altogether. The morbidity consequent to such a decision is much less if the operative approach is an endoscopic one.


No Evidence for Association Between Norepinephrine Transporter-3081 (A/T) Polymorphism and Attention Deficit Hyperactivity Disorder in Iranian Population.
Attention Deficit Hyperactivity Disorder (ADHD) can lead to drastic problems for the patient and its worldwide prevalence is 5%-12%. It also has many comorbidities with other disorders, and the genetic contribution seems the most significant cause. The current study was conducted to investigate the association between norepinephrine transporter-3081 (A/T) polymorphisms and ADHD in Iranian population. Participants were chosen from children and adolescents diagnosed with ADHD referred to Imam Hoseyn Hospital. A child and adolescent psychiatrist confirmed the diagnosis using the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL) semi-structural interview. The control group was from pupils of schools in Tehran (capital city of Iran) who had no history or presence of psychiatric and medical complications. Also, a child and adolescent psychiatrist confirmed their health using the K-SADS-PL semi-structural interview. Genetic examinations were DNA distraction, Polymerase Chain Reaction (PCR), and Restricted Fragment Length Polymorphism (RFLP), which were conducted according to standard protocols. The statistical analysis was performed using chi-square and Fisher's exact test in SPSS version 21. The percentages of ADHD subtypes for combined, inattentive, and hyperactive/impulsive were 72.2%, 17.2%, and 11.9%, respectively. There was no significant association between norepinephrine transporter polymorphism and ADHD (P = 0.81). Moreover, no significant relationship was found between gender [male (P = 0.92) and female (P = 0.63)] and polymorphism. No significant association was found between subtypes of ADHD [combined (P = 0.46), inattentive (P = 0.41), hyperactive/impulsive (P = 0.32)] and polymorphism SCL6A2. This lack of association can also be seen in gender in every subtype. The results of the study show no significant association between norepinephrine transporter polymorphism SCL6A2 and ADHD.


Prenatal molecular diagnosis of β-thalassemia and sickle cell anemia in the Syrian population.
Our objective was to evaluate the prenatal diagnosis (PND) of β-thalassemia (β-thal) and sickle cell anemia in Syria. Mutations detected from blood of at-risk couples and 55 amniotic fluid samples collected at the second trimester of pregnancy (14-22 weeks' gestation) were characterized. Molecular screening and direct DNA sequencing of the HBB gene was carried out. DNA analyses showed 14 affected fetuses (25.45%), 32 (58.18%) carriers and eight (14.54%) normal fetuses. It appears that 20.0% of individuals carried the sickle cell anemia mutation and 80.0% carried the β-thal mutation. Thirteen different known mutations were detected in the fetuses. The most common mutations were: IVS-II-1 (G > A), codon 39 (C > T)], IVS-I-110 (G > A), IVS-I-1 (G > A) and IVS-I-5 (G > C). The Hb S [β6(A3)Glu → Val; HBB: c.20A > T] mutation was the only abnormal hemoglobin (Hb) that was found. The results point to a successful future for PND of β-thal and sickle cell anemia in Syria, using a rapid and accurate molecular method. We hope that this method will be used as a common application approach to decrease the incidence of β-thal major (β-TM).


SLC11A1 (formerly NRAMP1) and susceptibility to visceral leishmaniasis in The Sudan.
Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence and clinical phenotypes between ethnic groups in Sudan. In mice, innate susceptibility to Leishmania donovani, the etiological agent of VL, is controlled by Slc11a1 (formerly Nramp1). We therefore examined polymorphisms at SLC11A1 in 59 multicase families of VL from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis in ALLEGRO shows a significant linkage across SLC11A1 (Zlr scores 2.38-2.55; 0.008< or =P< or =0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5' polymorphisms in the promoter (P=0.0145), exon 3 (P=0.0037) and intron 4 (P=0.0049), and haplotypes formed by them (P=0.0089), but not for 3' polymorphisms at exon 15 or the 3'UTR. Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families was consistent with main effects contributed by the intron 4 469+14G/C polymorphism. Although the two alleles for 469+14G/C lie on haplotypes carrying different alleles for the functional promoter GTn polymorphism, the latter did not itself contribute separate main effects. Sequence analysis of 36 individuals failed to identify new putative functional polymorphisms in the coding region, intron 1, intron/exon boundaries, intron 4/exon 4a, or in the 3'UTR. One novel promoter polymorphism (-86G/A) was located within a putative nuclear factor kappa B binding site that could be functional. Further work will determine whether additional polymorphisms occur upstream in the promoter, which could be in linkage disequilibrium with the intron 4 polymorphism. These studies contribute to knowledge of the role of SLC11A1 in infectious disease.


Tuning Nonradiative Lifetimes via Molecular Aggregation.
We show that molecular aggregation can strongly influence the nonradiative decay (NRD) lifetime of an electronic excitation. As a demonstrative example, we consider a transition-dipole-dipole-interacting dimer whose monomers have harmonic potential energy surfaces (PESs). Depending on the position of the NRD channel (qnr), we find that the NRD lifetime (τnrdim) can exhibit a completely different dependence on the intermolecular-interaction strength. We observe that (i) for qnr near the Franck-Condon region, τnrdim increases with the interaction strength; (ii) for qnr near the minimum of the monomer excited PES, the intermolecular interaction has little influence on τnrdim; and (iii) for qnr near the classical turning point of the monomer nuclear dynamics, on the other side of the minimum, τnrdim decreases with the interaction strength. Our findings suggest design principles for molecular systems where a specific fluorescence quantum yield is desired.


Genomic epidemiology and transmission dynamics of recurrent Clostridioides difficile infection in Western Australia.
Recurrent cases of Clostridioides difficile infection (rCDI) remain one of the most common and serious challenges faced in the management of CDI. The accurate distinction between a relapse (caused by infection with the same strain) and reinfection (caused by a new strain) has implications for infection control and prevention, and patient therapy. Here, we used whole-genome sequencing to investigate the epidemiology of 94 C. difficile isolates from 38 patients with rCDI in Western Australia. The C. difficile strain population comprised 13 sequence types (STs) led by ST2 (PCR ribotype (RT) 014, 36.2%), ST8 (RT002, 19.1%) and ST34 (RT056, 11.7%). Among 38 patients, core genome SNP (cgSNP) typing found 27 strains (71%) from initial and recurring cases differed by ≤ 2 cgSNPs, suggesting a likely relapse of infection with the initial strain, while eight strains differed by ≥ 3 cgSNPs, suggesting reinfection. Almost half of patients with CDI relapse confirmed by WGS suffered episodes that occurred outside the widely used 8-week cut-off for defining rCDI. Several putative strain transmission events between epidemiologically unrelated patients were identified. Isolates of STs 2 and 34 from rCDI cases and environmental sources shared a recent evolutionary history, suggesting a possible common community reservoir. For some rCDI episodes caused by STs 2 and 231, within-host strain diversity was observed, characterised by loss/gain of moxifloxacin resistance. Genomics improves discrimination of relapse from reinfection and identifies putative strain transmission events among patients with rCDI. Current definitions of relapse and reinfection based on the timing of recurrence need to be reconsidered.


Hydrogen storage in a microporous metal-organic framework with exposed Mn2+ coordination sites.
Use of the tritopic bridging ligand 1,3,5-benzenetristetrazolate (BTT3-) enables formation of [Mn(DMF)6]3[(Mn4Cl)3(BTT)8(H2O)12]2.42DMF.11H2O.20CH3OH, featuring a porous metal-organic framework with a previously unknown cubic topology. Crystals of the compound remain intact upon desolvation and show a total H2 uptake of 6.9 wt % at 77 K and 90 bar, which at 60 g H2/L provides a storage density 85% of that of liquid hydrogen. The material exhibits a maximum isosteric heat of adsorption of 10.1 kJ/mol, the highest yet observed for a metal-organic framework. Neutron powder diffraction data demonstrate that this is directly related to H2 binding at coordinatively unsaturated Mn2+ centers within the framework.


The crystal structure of mouse LC3B in complex with the FYCO1 LIR reveals the importance of the flanking region of the LIR motif.
FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined. Structural analysis showed that the flanking sequences N-terminal and C-terminal to the LIR core sequence of FYCO1, as well as the tetrapeptide core sequence, were specifically recognized by LC3B and contributed to the binding. Moreover, comparisons of related structures revealed a conserved mechanism of FYCO1 recognition by different LC3 isoforms among different species.


Drought affects abortion of reproductive organs by exacerbating developmentally driven processes via expansive growth and hydraulics.
Abortion of reproductive organs is a major limiting factor of yield under water deficit, but is also a trait selected for by evolutionary processes. The youngest reproductive organs must be prone to abortion so older organs can finish their development in case of limited resources. Water deficit increases natural abortion via two developmentally driven processes, namely a signal from the first fertilized ovaries and a simultaneous arrest of the expansive growth of all ovaries at a precise stage. In maize (Zea mays) subjected to water deficits typically encountered in dryland agriculture, these developmental mechanisms account for 90% of drought-associated abortion and are irreversible 3 d after silk emergence. Consistently, transcripts and enzyme activities suggest that the molecular events associated with abortion affect expansive growth in silks whereas ovaries maintain a favourable carbon status. Abortion due to carbon starvation is only observed for severe drought scenarios occurring after silking. Both kinetic and genetic evidence indicates that vegetative and reproductive structures share a partly common hydraulic control of expansive growth. Hence, the control of expansive growth of reproductive structures probably has a prominent effect on abortion for mild water deficits occurring at flowering time, while carbon starvation dominates in severe post-flowering drought scenarios.


Coordination-Induced Emission from Tetraphenylethylene Units and Their Applications.
Thanks to the potential of aggregation-induced emission (AIE) phenomena, improved stabilities, and the good selectivity and sensitivity of the chemical responses exhibited by the products, coordination-driven self-assembly with tetraphenylethylene (TPE) units has recently received much attention and has been widely investigated for application in chemical sensors, cell imaging agents, light-harvesting systems, and others. Several reviews have emerged on the topics of AIE chemistry and aggregation-induced emission luminogen (AIEgen)-based supramolecular assembles, however, there is still a distinct lack of full overviews of emission enhancement from the viewpoint of metal-coordination effects. Thus, this minireview offers recent advances that have been made in the design and application of TPE-based metallacycles, metallacages, metal-organic frameworks (MOFs) and coordination polymers (CPs).


Oral warty dyskeratoma.
Warty dyskeratoma of the oral mucosa is a rare cause of solitary mouth lesions. Of the thirteen reported patients, only three have been described in the dermatologic literature. We now present an additional patient, and review both the medical and the dental literature on warty dyskeratoma. Various factors possibly related to its cause are discussed, including cigarette smoking, a heretofore largely unappreciated possibility.


Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.
Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.


A novel clinical prediction model of severity based on red cell distribution width, neutrophil-lymphocyte ratio and intra-abdominal pressure in acute pancreatitis in pregnancy.
Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value < 0.05). Our novel clinical prediction model was created by based on the above three risk factors and showed superior predictive power in primary cohort (AUC = 0.895) and validation cohort (AUC = 0.863). A nomogram for severe acute pancreatitis in pregnancy (SAPIP) was created based on the three indicators. The nomogram was well-calibrated. RDW, NLR and IAP were the independent risk factors of APIP. Our clinical prediction model of severity in APIP based on RDW, NLR and IAP with predictive evaluation is accurate and effective.


[Expressions of NLRP1 and NLRC4 inflammasomes in prostate cancer and their clinical value].
To explore the clinical value of the inflammasomes NLRP1 and NLRC4 in the diagnosis and treatment of PCa. Using immunohistochemical staining, we detected the expressions of the inflammasomes NLRP1 and NLRC4 and the inflammatory cytokines IL-18 and IL-1β in 54 cases of BPH and 58 cases of PCa treated in Pinghu First People's Hospital from January 2022 to May 2022. We analyzed the characteristics of their expressions in the two groups of patients and the correlation of NLRP1 and NLRC4 expressions with tPSA, fPSA and Gleason scores in the PCa patients. Based on the Cancer Genome Atlas dataset, we compared the expressions of NLRP1 and NLRC4 in different stages of PCa. The NLRP1 and NLRC4 expressions were significantly increased in the PCa patients (P < 0.001). The expression of NLRP1 was linearly correlated with those of IL-1β and IL-18 (P < 0.05), and so was the expression of NLRC4 with that of IL-18 (P < 0.05). The expressions of NLRP1 and NLRC4 were positively correlated with the Gleason scores of the PCa patients (P < 0.05), the former remarkably higher in T3 and T4 than in T1 (P > 0.05), and the latter markedly higher in T2, T3 and T4 than in T1 (P < 0.05). The inflammasomes NLRP1 and NLRC4 are highly expressed in PCa and facilitate tumorgenesis by promoting the maturation and release of the inflammatory cytokines IL-1β and IL-18, which indicates their important role in the progression of tumors and clinical value in the risk assessment and prognosis of PCa.


Effects of resistant starch and nonstarch polysaccharides on colonic luminal environment and genotoxin-induced apoptosis in the rat.
Fermentation of polysaccharides in the colon seems likely to regulate tumorigenesis but the mechanisms are unclear. A possible mechanism may be through facilitation of the acute apoptotic response to genotoxin-induced DNA damage. This study evaluated the effects of selected dietary polysaccharides, resistant starch (supplied as Hi-maize) and nonstarch polysaccharides (supplied as wheat bran and cellulose) on certain biological events relevant to protection against colon cancer (fecal bulk, pH, butyrate and apoptosis). Male Sprague-Dawley rats were fed the different experimental diets for a period of 4 weeks, after which a single azoxymethane injection was given to induce DNA damage; 6 h later the acute apoptotic response was measured. Other measures included short chain fatty acid (SCFA) levels, fecal bulk and pH. All wheat bran treatments significantly (P < 0.05) enhanced carcinogen-induced apoptosis in the distal colon, increased fecal bulk and butyrate levels and reduced fecal pH, when compared with rats fed NF or Cellulose diets. Total SCFA (P < 0.001, r = 0.496) and butyrate levels (P < 0.001, r = 0.353) in the feces correlated positively with the acute apoptotic response in distal colonic crypts. Resistant starch supplementation by this modest amount did not enhance carcinogen-induced apoptosis. While it did significantly increase bulk, SCFA and butyrate levels and lower pH, the magnitude of these effects was not as great as with wheat bran. These findings indicate that wheat bran is the most effective regulator of these biological events of relevance to protection against colon cancer. Assuming that the acute apoptotic response to genotoxic carcinogens acts to remove genetically damaged cells that might otherwise form mutated clones that progress to malignancy, we have identified an additional biological mechanism by which dietary polysaccharides provide protection.


Morphometrics and allometry of the larvae of five Characiformes species in the Paraíba do Sul River Basin.
The aim of this study was to analyse the morphology and allometry of larvae belonging to five potamodromous species. Five breeding species belonging to the order Characiformes [Salminus brasiliensis (Cuvier, 1816), Leporinus steindachneri, Eigenmann, 1907, Prochilodus lineatus (Valenciennes, 1837), Prochilodus vimboides (Kner,1859) and Brycon insignis, Steindachner, 1877] were used to obtain larvae samples during the pre-flexing, post-flexing, and juvenile developmental stages. When we observed the degree-hour (DH) amplitude time values, we found three developmental groups based on allometry and morphometrics within the period between the pre-flexing and post-flexing phases. Group 1 consists of the species S. brasiliensis and B. insignis, Group 2 consists of P. lineatus and P. vimboides, and Group 3 consists of L. steindachneri. Group 1 requires less development time and has more slender larvae. Group 2 has a moderate development time and larvae with a more rounded shape. Group 3 presents a greater development time and an intermediate larval morphology. It was possible to classify the larvae through cross-validated discriminant analyses based on seven morphometric variables with 90% accuracy in B. insignis, 83% in L. steindachneri, 91% in P. lineatus, 80% in P. vimboides, and 96% in S. brasiliensis. These results indicate larval characteristics that can be used for the taxonomic identification of the icthyoplankton.


Structure and Functional Properties of Antioxidant Nanoemulsions Prepared with Tea Polyphenols and Soybean Protein Isolate.
In this study, tea polyphenols (TP) was added to a soy protein isolate (SPI) to prepare nanoemulsions by ultra-high pressure homogenization (UHPH). The nanoemulsions were characterized by a confocal laser scanning electron microscopy, infrared spectroscopy, dynamic rheometer and size-potential analyzer. The effects of TP on the hydrophobicity, emulsifiability, particle size, potential and antioxidant capacity of the prepared nanoemulsions were investigated. The properties of the nanoemulsions with different concentrations of TP were analyzed. The results indicated that ultra-high pressure homogenization treatment contributed to the formation of the SPI-TP complex that showed higher antioxidant activity. The nanoemulsions with good emulsifying properties and high DPPH scavenging ability at the concentration of TP ranged from 0.15-0.20g / mL. Furthermore, nanoemulsions prepared in this way also had a uniform particle size. Therefore, this nanoemulsions exhibited a good potential to act as an efficient emulsifier.


Comparative modeling of the phosphatase and kinase domains of protein tyrosine phosphatase and insulin receptor kinase from Drosophila melanogaster (DPTP61fm), and a computational study of their mutual interactions.
The components and functions of the insulin receptor kinase signaling pathway have been conserved in a broad range of Metazoa ranging from mammals to insects and nematodes. There is a high degree of sequence homology and functional similarity between the human insulin receptor kinase (IRK) and the drosophila (Drosophila melanogaster) form (DIRK) of this enzyme. Similarly, a high degree of homology exists between human protein tyrosine phosphatase 1B (PTP1B) (which directly regulates IRK) and its drosophila counterpart DPTP61F (DPTP). However, genetic and biochemical studies have yet to demonstrate that DPTP61F acts in the DIRK pathway. Comparative structural modeling techniques using the known structures of human IRK and PTP1B as templates have yielded structures for the drosophila enzymes. The derived structures confirm that there is a high level of structural conservation at the tertiary level. Association of the DIRK and DPTP enzymes with each other was then investigated with a view to ascertaining whether DIRK might be a substrate of the DPTP. Evaluation of the interaction surfaces, including hydrophobic patch, shape, hydrogen bonding, and electrostatic compatibility, strongly suggested that the drosophila insulin receptor is a substrate of the DPTP. The interaction surfaces of the human and drosophila enzymes are structurally similar, although changes in critical residues modify possible electrostatic and hydrogen-bonding interactions. This suggests that in the mixed systems, DPTP-IRK or PTP1B-DIRK, the kinase domain will be a comparatively poor substrate for phosphatase activity when compared with the native systems.


Chorioretinitis sclopetaria caused by fishing line sinker.
A case of chorioretinitis sclopetaria caused by a grazing injury from a fishing line sinker was reported. A man was struck in his left orbit by the sinker, and immediately lost visual acuity. The sinker was removed, but funduscopy showed the typical appearance of chorioretinitis sclopetaria six months later. On fluorescein angiography, mottled background fluorescence appeared in a star-shaped scar. Fluorescein angiography, computed tomography, and roentgenography indicated that direct damage to the ciliary vessels was present.


[Phase III study of carboplatin in ovarian cancer].
A phase III study of carboplatin vs cisplatin in CAP regimen for ovarian cancer was conducted by a cooperative study group consisting of 22 institutions nationwide. The response rate for 23 cases allocated to carboplatin regimen group was 34.8% and 42.1% for 19 cases allocated to cisplatin regimen group. No significant difference was observed between these two regimens in response rates, and no significant differences were noted between the two regimens in each of the clinical toxicities and abnormalities in laboratory findings. Since the carboplatin regimen group did not require hydration, or the use diuretics or antiemetics, these results suggested that carboplatin is more useful in the treatment of ovarian cancer than cisplatin.


Assessment of Tuned Range Separated Exchange Functionals for Spectroscopies and Properties of Uranium Complexes.
The Kohn-Sham delocalization error (DE) is quantified in select uranium compounds for various functionals and shown to correlate with the magnitude of dative ligand donation into the 5f shell. Range separated exchange functionals are reparametrized to minimize the DE and analyzed for their spectroscopic predictive capabilities. Valence excitation spectra of occupied 5f systems exhibit noticeable improvement upon reparametrization, e.g. UCl6-, UCl62-, and UO2+. Less sensitivity to the reparameterization was observed for closed shell 5f systems and core excitation spectra. A general parametrization is proposed to perform well for valence excitation spectra with small DE.


Regression of liver fibrosis after curing chronic hepatitis C with oral antivirals in patients with and without HIV coinfection.
Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce in cured patients. All consecutive HCV-infected individuals treated with DAA at our institution were examined. Hepatic elastography was performed at baseline and at the time of SVR12. Liver fibrosis regression was defined as a shift from advanced fibrosis (Metavir F3-F4) to null-mild fibrosis (F0-F2) and/or a reduction greater than 30% kPa. AST to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores were calculated in parallel. A total of 260 patients were treated with DAA. All but 14 achieved SVR12 and represented the study population. HIV confection was present in 42%. At baseline, 57.2% had advanced liver fibrosis with a median of 11 kPa, FIB-4 of 2.4, and APRI of 0.95. At the time of SVR12, a median reduction of 2.1 kPa (P < 0.001) was recognized using elastography. A significant fibrosis regression was seen in 40%, being more frequent in patients with baseline advanced fibrosis than in those with null-mild fibrosis (52.3 vs. 22.5%; P < 0.001). Even so, 41.2% of patients with baseline F3-F4 kept within cirrhotic scores. In multivariable analysis, only baseline stiffness was significantly associated with the extent of liver fibrosis regression. HCV cure with DAA is associated with regression of liver fibrosis in most patients treated with DAA, as measured using elastography, FIB-4 and APRI. This benefit is more pronounced in patients with baseline advanced fibrosis and cirrhosis. The dynamics of liver fibrosis regression are not influenced by HIV coinfection.


Entrapment of Saccharomyces cerevisiae and 3T3 fibroblast cells into blue light cured hydrogels.
Hydrogels, containing yeast cells or fibroblast cells, were fabricated using blue light-induced polymerization technique. The cell-loaded prepolymer formulation was comprised of poly(ethyleneglycol) diacrylate (more than or equal to 50% v/v), 0.5 wt % Eosin Y and 0.5 wt % triethanolamine as the base oligomer, photo-initiator, and co-initiator, respectively. The two model cell lines, Saccharomyces cerevisiae and NIH 3T3 fibroblasts maintained high viability pre- and post-processing. Several bioassays have demonstrated the unaffected intracellular and extracellular activities of the cells entrapped within the hydrogels. Scanning electron microscopy confirmed the proliferation of S. cerevisiae cells that were entrapped and cultivated for 48 h in growth media, which validated the favorable microenvironment and nutrient transport in these gels. Upon entrapment, fibroblast cells remain viable upto 12 h, however they failed to attach within the crosslinked network, thus no further proliferation was observed. The tunable properties of this hydrogel system project it as a useful matrix for specialized biohybrids.


Endoscopic screening for gastric stump cancer--would it be beneficial? A hypothetical cohort study.
The incidence of gastric cancer is increased in the gastric stump. It has, therefore, been recommended that subjects who have undergone partial gastrectomy be screened by regular endoscopy. However, several factors make it very difficult to test, in a clinical trial, the efficacy of such screening. To solve this problem, known clinical observations on partial gastrectomy patients were applied to a hypothetical cohort of 100,000 German or American partial gastrectomy patients. In this way the possible benefits of regular endoscopic screening in such a population were predicted. Markov type of decision analysis was used on the hypothetical cohorts to see if yearly endoscopy significantly improved outcomes as compared with no endoscopic screening. Under the very liberal, but arbitrary, assumption that endoscopic screening could prevent death from gastric stump cancer in 80% of those diagnosed as having gastric stump cancer, 8.5% and 5.4% of German male and female gastrectomy patients, respectively, and 2.2% and 1.3% of American male and female gastrectomy patients, respectively, would benefit from screening. Lives of German men and women would be prolonged 10 and 13 yr, respectively, [11 and 15 yr for American men and women]. Life expectancy of the total male and female cohort would increase by 9 and 8 mo, respectively, [U.S.A: 2 and 2 mo]. Per 100 endoscopies invested, 6.4 and 4.3 [U.S.A.: 1.8 and 1.2] male and female life years would be gained. However, a sensitivity analysis shows the outcomes of the calculations to depend most on the rate of a 5-yr survival gained by endoscopy and surgery: as the postoperative 5-yr survival of gastric stump cancer patients falls below 80%, the benefit achieved by endoscopic screening becomes even less apparent. In American subjects who have undergone partial gastrectomy, the benefit of endoscopic screening would probably be too low to justify screening. Only in populations with high frequencies of gastric cancer may endoscopic screening be beneficial.


Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis.
Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.


Effect of Propofol and Desflurane on Immune Cell Populations in Breast Cancer Patients: A Randomized Trial.
Several factors can affect the perioperative immune function. We evaluated the effect of propofol and desflurane anesthesia on the surgery-induced immune perturbation in patients undergoing breast cancer surgery. The patients were randomly assigned to receive propofol (n = 20) or desflurane (n = 20) anesthesia. The total and differential white blood cell counts were determined with lymphocyte subpopulations before and 1 hr after anesthesia induction and at 24 hr postoperatively. Plasma concentrations of interleukin (IL)-2 and IL-4 were also measured. Both propofol and desflurane anesthesia preserved the IL-2/IL-4 and CD4(+)/CD8(+) T cell ratio. Leukocytes were lower in the propofol group than in the desflurane group at 1 hr after induction (median [quartiles], 4.98 [3.87-6.31] vs. 5.84 [5.18-7.94] 10(3)/µL) and 24 hr postoperatively (6.92 [5.54-6.86] vs. 7.62 [6.22-9.21] 10(3)/µL). NK cells significantly decreased 1 hr after induction in the propofol group (0.41 [0.34-0.53] to 0.25 [0.21-0.33] 10(3)/µL), but not in the desflurane group (0.33 [0.29-0.48] to 0.38 [0.30-0.56] 10(3)/µL). Our findings indicate that both propofol and desflurane anesthesia for breast cancer surgery induce a favorable immune response in terms of preservation of IL-2/IL-4 and CD4(+)/CD8(+) T cell ratio in the perioperative period. With respect to leukocytes and NK cells, desflurane anesthesia is associated with less adverse immune responses than propofol anesthesia during surgery for breast cancer. (Clinical trial registration at https://cris.nih.go.kr/cris number: KCT0000939).


Out of bounds? A critique of the new policies on hyperandrogenism in elite female athletes.
In May 2011, more than a decade after the International Association of Athletics Federations (IAAF) and the International Olympic Committee (IOC) abandoned sex testing, they devised new policies in response to the IAAF's treatment of Caster Semenya, the South African runner whose sex was challenged because of her spectacular win and powerful physique that fueled an international frenzy questioning her sex and legitimacy to compete as female. These policies claim that atypically high levels of endogenous testosterone in women (caused by various medical conditions) create an unfair advantage and must be regulated. Against the backdrop of Semenya's case and the scientific and historical complexity of "gender verification" in elite sports, we question the new policies on three grounds: (1) the underlying scientific assumptions; (2) the policymaking process; and (3) the potential to achieve fairness for female athletes. We find the policies in each of these domains significantly flawed and therefore argue they should be withdrawn.


Co-expression of CD40/CD40L on XG1 multiple myeloma cells promotes IL-6 autocrine function.
Multiple myeloma (MM) is characterized by uncontrolled proliferation of malignant plasma cells in the bone marrow and peripheral blood. Here, we found that CD40 and CD40L co-expressed on XG1 MM cells and the coordinated expression of CD40-CD40L was critical for production and autocrine IL-6 in XG1 cells. Furthermore, TNF-α enhanced the expression of both CD40 and CD40L expression on XG1 cells. We also found that persistent CD40L/CD40 signaling was required for the constitutive activation of NF-κB in the cells.


Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients.
Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42) (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain clearance of Abeta in animal models. We, therefore, treated macrophages of six AD patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake by AD macrophages was significantly lower in comparison to control macrophages and involved surface binding but no intracellular uptake. After treatment of macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of AD macrophages responsive to curcuminoids showed surface binding in untreated macrophages but co-localization with phalloidin in an intracellular compartment after treatment. Immunomodulation of the innate immune system by curcuminoids might be a safe approach to immune clearance of amyloidosis in AD brain.


Functional genomics in sarcoidosis--reduced or increased apoptosis?
A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signaling pathways. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in patients with acute onset sarcoidosis. We have performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HGU95A, Affymetrix) for RNA expression profiling from peripheral blood mononuclear cells from patients with acute pulmonary sarcoidosis and matched healthy controls. Twelve patients and 12 controls were assessed, mean age 36 +/- 12 and 33 +/- 10 years respectively. Results focus on apoptosis-related gene products. Group differences were assessed with the Mann-Whitney U-test. Seven patients had self-limited disease (all type I sarcoidosis) and 5 progressive disease requiring immunosuppression (all type II or III sarcoidosis). We found 53 of 112 (47%) apoptosis-related gene products dysregulated in sarcoidosis compared to controls. Particular growth factors, especially heparin-binding EGF-like GF, EGF, PDEGF, SISPDGF2 and VEGF, were upregulated in patients consistent with a pro-survival profile. The Bcl-2 family of genes also showed a net pro-survival profile in sarcoidosis patients. In contrast, alterations in the TNF-pathway were compatible with increased apoptosis signals in both, type I and type II/III sarcoidosis patients. Other cell death receptors were equally expressed, as were caspases and p53-associated genes. In contrast to patients with type I-sarcoidosis, patients with progressive type II or III disease showed an upregulation of NFKB and a leak of downregulation of inhibitor of apoptosis 1. Significant differences in the expression of apoptosis-related genes were found in peripheral blood of patients with acute onset sarcoidosis. Gene expression did not show a definite pattern that was suggestive of pro-survival or proapoptosis. However, the number of genes whose altered expression would be predicted to favour increased survival exceeded that of genes likely to reduce survival. Protein-based confirmation of the differences in the activity of apoptosis-pathways needs to be done in further studies.