Association between tax on sugar sweetened beverages and soft drink consumption in adults in Mexico: open cohort longitudinal analysis of Health Workers Cohort Study.
To examine changes in categories of soft drink consumption in a cohort of Mexican adults, three years after the implementation of the sugar sweetened beverage tax. Open cohort longitudinal analysis. Three waves of the Health Workers Cohort Study, Mexico, spanning 2004 to 2018. 1770 people aged 19 years or older with information on drinks consumption available in at least one of the three cohort waves. Change in probability of belonging to one of four categories of soft drinks consumption (non, low, medium, high) after the tax was implemented. Heterogeneity of associations by income and education was also assessed. Before the implementation of the tax, more than 50% of the participants were medium and high consumers of soft drinks and less than 10% were in the non-consumer category. After the tax was implemented, 43% of the population was categorised as medium or high consumers and the prevalence of non-consumers increased to 14%. Three years after implementation of the tax on 1 January 2014, the probability of being a non-consumer of soft drinks increased by 4.7 (95% confidence interval 0.3 to 9.1) percentage points and that of being a low consumer increased by 8.3 (0.6 to 16.0) percentage points compared with the pre-tax period. Conversely, the probability of being in the medium and high levels of soft drinks consumption decreased by 6.8 (0.5 to 13.2) percentage points and 6.1 (0.4 to 11.9) percentage points, respectively. No significant heterogeneity of the tax across income levels was observed, but stronger effects of the tax were seen in participants with secondary school education or higher, compared with those with elementary school or less. The Mexican sugar sweetened beverage tax was associated with a reduction in the probability of consuming soft drinks in this cohort of employees from a healthcare provider. The results cannot be extrapolated to the Mexican population, but they suggest that three years after implementation, the tax had helped to increase the proportion of people who do not consume soft drinks while decreasing the proportion of high and medium consumers.


Living with renal failure.
In this interpretive study, the experience of patients living with chronic renal failure was studied. Within the framework of Heideggerian phenomenology, a hermeneutic analysis revealed three themes and one constitutive pattern. The three themes were: taking on a new understanding of Being, maintaining hope and dwelling in dialysis. The constitutive pattern was " The Meaning of Technology." The findings provide an understanding of living with renal failure that argues against the traditional understanding of noncompliant behaviors. The study makes visible the meaning of technology in the lives of renal patients and highlights the need for nurses to sustain meaningful human connections with patients.


Cholera and pertussis toxins increase acidification of endocytic vesicles without altering ion conductances.
Acidification of endocytic vesicles, driven by the vacuolar H+ pump, is affected by parallel ion transporters. Because adenosine 3',5'-cyclic monophosphate (cAMP) and heterotrimeric G proteins may alter ion transporters, I tested whether cholera and pertussis toxins affected acidification of rat liver endosomes. Fluorescein-labeled dextran-loaded "10-min" endosomes from cholera toxin-treated rats exhibited ATP-dependent rates of acidification in the presence and absence of Cl- or K+ that were approximately 60-120% (P < 0.05) faster than rates from control endosomes. This increase was greater for "older" "20-min" endosomes and less for 'early" "2-min" endosomes. Ion transport functions of 10-min and 20-min toxin-exposed endosomes were similar to those of 2-min control endosomes. Cholera toxin also increased ATP-dependent steady-state intravesicular H+ concentration by 38-218% (P < 0.05). Pertussis toxin increased endosome acidification rates by 20-54% (P < 0.05). Both toxins increased liver cAMP content, and endosomes prepared from perfused livers exposed to 0.75 mM dibutyryl cAMP exhibited similar increases in acidification rates. These studies indicate that both cholera and pertussis toxins markedly alter the function of rat liver endosomes. The mechanism is unlikely to reflect major changes in vesicle ion transporters but rather may indicate either an increase in the number of H+ pumps per endosome and/or changes in fusion, remodeling, and maturation of early endocytic vesicles in response to cAMP.


Detection of Specific Volatile Organic Compounds in Tribolium castaneum (Herbst) by Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry.
The red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), is a major storage pest that could lead to a wide range of damage. Its secretions have a significant impact on the quality of stored grain and food, leading to serious food safety problems such as grain spoilage and food carcinogenesis. This study investigates new detection techniques for grain storage pests to improve grain insect detection in China. The primary volatile organic chemicals (VOCs) in these secretions are identified using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). The specific VOCs that are unique to T. castaneum are selected as criteria for determining the presence of T. castaneum in the granary. To obtain more specific VOCs, experiments were designed for the analysis of T. castaneum samples under different extraction times, two types of SPME fibers and two GC-MS devices of different manufacturers. The experimental results showed that 12 VOCs were detected at relatively high levels, seven of which were common and which were not detected in other grains and grain insects. The seven compounds are 1-pentadecene, 2-methyl-p-benzoquinone, 2-ethyl-p-benzoquinone, 1-hexadecene, cis-9-tetradecen-1-ol, m-cresol and paeonol. These seven compounds can be used as volatile markers to identify the presence of T. castaneum, which could serve as a research foundation for the creation of new techniques for T. castaneum monitoring.


Nonamorphism in flufenamic acid and a new record for a polymorphic compound with solved structures.
The unprecedented polymorphism of the non-steroidal anti-inflammatory drug (NSAID) flufenamic acid (FFA) is described here. Nine polymorphs were accessed through the use of polymer-induced heteronucleation (PIHn) and solid-solid transformation at low temperature. Structural elucidation of six of these forms, in addition to the two previously known forms, makes FFA indisputably octamorphic. Although the structure of at least one other form of FFA remains elusive, the occurrence of most of these polymorphs under one crystallization condition through PIHn illustrates that a fine interplay exists among the kinetic factors that lead to phase selection in this NSAID.


Fear sensitivity and the psychological profile of patients with psychogenic nonepileptic seizures.
Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon for both patients and their physicians. Recent work has begun to focus on the possible psychological underpinnings of this diagnosis, but few studies have focused on specific emotional pathologies. This study sought to investigate the impact of a specific emotional measure: self-reported fear sensitivity. Three patient groups (patients with PNES, patients with epilepsy, and healthy volunteers) were administered the Modified Fear Survey Schedule, along with other neuropsychological batteries. As expected, the PNES and epilepsy cohorts demonstrated elevated levels of depression, anxiety, and comorbid psychiatric conditions. The PNES group independently exhibited a statistically significant higher level of fear sensitivity compared with both patients with epilepsy and healthy volunteers. This fear-specific trait was independent of other comorbid psychological factors or psychiatric conditions. These results suggest that patients with PNES exhibit disproportionately elevated fear sensitivity on self-report measures when compared with patients with epilepsy. This finding may reflect an elevated internal "setpoint" for appraising the intensity of emotional settings.


Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on (TRO) Approach.
This manuscript describes a protocol for detecting transcription termination defect in vivo. The strand-specific TRO protocol using BrUTP described here is a powerful experimental approach for analyzing the transcription termination defect under physiological conditions. Like the traditional TRO assay, it relies on the presence of a transcriptionally active polymerase beyond the 3' end of the gene as an indicator of a transcription termination defect1. It overcomes two major problems encountered with the traditional TRO assay. First, it can detect if the polymerase reading through the termination signal is the one that initiated transcription from the promoter-proximal region, or if it is simply representing a pervasively transcribing polymerase that initiated non-specifically from somewhere in the body or the 3' end of the gene. Secondly, it can distinguish if the transcriptionally active polymerase signal beyond the terminator region is truly the readthrough sense mRNA transcribing polymerase or a terminator-initiated non-coding anti-sense RNA signal. Briefly, the protocol involves permeabilizing the exponentially growing yeast cells, allowing the transcripts that initiated in vivo to elongate in the presence of the BrUTP nucleotide, purifying BrUTP-labelled RNA by the affinity approach, reverse transcribing the purified nascent RNA and amplifying the cDNA using strand-specific primers flanking the promoter and the terminator regions of the gene2.


The Use of Trichostatin A during Pluripotent Stem Cell Generation Does Not Affect MHC Expression Level.
Pluripotent stem cells (PSCs) are considered as a potent tool for use in regenerative medicine. Highly efficient generation of PSCs through chromatin modulators such as trichostatin A (TSA) might change their MHC molecule expression profile. The efficiency of PSC generation and their immunogenicity is major obstacles for clinical use. Hence, we aim to investigate whether the use of TSA during PSC generation affects MHC expression level. Three PSC lines were generated by iPSCs, NT-ESCs, and IVF-ESCs' reprogramming methods from B6D2F1 mouse embryonic fibroblast cells. Established PSC lines were characterized by alkaline phosphatase assay (ALP) and immunocytochemistry. Their chromosome fidelity was checked by karyotyping. The expression level of pluripotent genes (oct4, nanog, sox2, klf4), HDACs (hdac1, hdac2, and hdac3), and immune-related genes (including Qa-1, Qa-2, H2kb, H2kd, H2db, H2db, CIITA, H2-IE-βb, H2-IE-βd) in iPSC and ESC lines were assessed by real-time PCR analysis. The presence of MHC molecules on the surface of pluripotent stem cells was also checked by flow cytometry technique. Significant increase of pluripotency markers, oct4, nanog, sox2, and klf4, was observed in 100 nM TSA-treated samples. 100 nM TSA induced significant upregulation of H2db in generated iPSCs. H2-IE-βd was remarkably downregulated in 50 and 100 nM TSA-treated iPSC lines. The expression level of other immune-related genes was not greatly affected by TSA in iPSC and NT-ESC lines. It is concluded that the use of short-term and low concentration of TSA during reprogramming in PSC generation procedure significantly increases PSC generation efficiency, but do not affect the MHC expression in established cell lines, which is in the benefit of cell transplantation in regenerative medicine.


Prostate cancer mortality risk in relation to working underground in the Wismut cohort study of German uranium miners, 1970-2003.
A recent study and comprehensive literature review has indicated that mining could be protective against prostate cancer. This indication has been explored further here by analysing prostate cancer mortality in the German 'Wismut' uranium miner cohort, which has detailed information on the number of days worked underground. An historical cohort study of 58 987 male mine workers with retrospective follow-up before 1999 and prospective follow-up since 1999. Uranium mine workers employed during the period 1970-1990 in the regions of Saxony and Thuringia, Germany, contributing 1.42 million person-years of follow-up ending in 2003. Simple standardised mortality ratio (SMR) analyses were applied to assess differences between the national and cohort prostate cancer mortality rates and complemented by refined analyses done entirely within the cohort. The internal comparisons applied Poisson regression excess relative prostate cancer mortality risk model with background stratification by age and calendar year and a whole range of possible explanatory covariables that included days worked underground and years worked at high physical activity with γ radiation treated as a confounder. The analysis is based on miner data for 263 prostate cancer deaths. The overall SMR was 0.85 (95% CI 0.75 to 0.95). A linear excess relative risk model with the number of years worked at high physical activity and the number of days worked underground as explanatory covariables provided a statistically significant fit when compared with the background model (p=0.039). Results (with 95% CIs) for the excess relative risk per day worked underground indicated a statistically significant (p=0.0096) small protective effect of -5.59 (-9.81 to -1.36) ×10(-5). Evidence is provided from the German Wismut cohort in support of a protective effect from working underground on prostate cancer mortality risk.


[The surgeon as a prognostic factor in the treatment of cancer of the rectum].
The study of prognostic factors in neoplastic rectal surgery is enriched with a new element, namely, the role of the surgeon. The aim of this study was to evaluate whether this was true of our own experience. We selected 118 patients with rectal cancer operated on with a radical intent by two different surgeons and analyzed factors such as sex, age, Dukes' stage, histological type, tumour length, differentiation and type of operation. We studied these factors by univariate and multivariate analysis in relation to local and distant recurrence and survival. We found statistically significant correlations between distant recurrence and tumour stage, differentiation and surgeon, but between local recurrence and tumour stage only. Multivariate analysis showed statistically significant correlations between distant recurrence and tumour stage and differentiation, but between local recurrence and tumour stage only. As regards survival, we found statistically significant differences in relation to stage, histological type, and differentiation. The role of the surgeon appeared to be important when there are differences in experience, training and specialization.


Validation of a motor skills performance theory with applications for dental education.
While several investigations assessing applications of contemporary motor learning theory to preclinic laboratory instruction have been successful, they provide only indirect and incomplete validation of theoretical constructs. This study's purpose was to further evaluate the validity of salient constructs through the use of a validation technique called verbal self-reporting, and to describe applications for dental education. Subjects were videotaped completing a preparation. Later, the tape was replayed and a structured interview used to stimulate recall of mental processes that occurred during the preparation. Transcribed self-reports were classified by two calibrated raters into categories corresponding to the constructs of interest. Results confirm many of the constructs' characteristics. Subjects reported that they a) defined the desired outcome in detail before beginning production; b) defined performance strategies that would be useful for different aspects of the preparation; c) constantly generated knowledge of results during the course of production in order to directly assess the adequacy of the product; and d) generated knowledge of performance as an indirect assessment of product acceptability especially when visual access was impeded. These results support previous applications of the theory to dentistry and have important implications for the improvement of instruction in preclinic laboratory courses.


Current venues of care and related costs for the chronically critically ill.
The chronically critically ill (CCI) patient population is characterized by a prolonged need for high cost medical interventions, a high 1-year mortality rate, and a very high demand for post acute care services. The best characterized CCI patient population is patients on prolonged mechanical ventilation (PMV). This review will focus on the current knowledge of costs and care venues for the care of this patient population. The PMV population suffers from a prolonged length of acute care hospital stay, median hospital costs 3-4 times the cost of short-term ventilator patients, frequent care venue changes during the course of illness, a small likelihood of discharge to the home environment, yet a hospital mortality that does not differ significantly from the short-term ventilated patient group. The PMV population is projected to double in size by the year 2020. Given the dramatic comparative acute care cost burden of PMV patients, the societal implications for managing both the care burden and the costs of care are staggering. Strategies to improve the efficiency in healthcare for this patient population will be essential. Limitations to the existing care models in the United States will be identified with a focus on our current research deficiencies, which limit healthcare providers and administrators in providing patient focused care for this patient population.


Rapid domain wall motion in permalloy nanowires excited by a spin-polarized current applied perpendicular to the nanowire.
We study domain wall dynamics in Permalloy nanowires excited by alternating spin-polarized current applied perpendicular to the nanowire. Spin torque ferromagnetic resonance measurements reveal that domain wall oscillations at a pinning site in the nanowire can be excited with velocities as high as 800 m/s at current densities below 10{7} A/cm{2}.


Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression: In vitro and in vivo studies.
Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the scratch-wound assay and transwell invasion assay. Cell cycle and apoptosis were evaluated by flow cytometry, and the associated proteins were examined by western blotting. The mRNA and protein expression levels related to the Shh pathway were measured by quantitative PCR, western blotting, and immunofluorescence staining. The xenograft murine model was carried out to evaluate the anticancer effect of metformin on medulloblastoma in vivo. Metformin inhibited proliferation and metastasis of the Shh subgroup MB cell line, and the inhibitory effect on proliferation was related to apoptosis and the block of the cell cycle at the G0/G1 phase. Animal experiments showed that metformin inhibits medulloblastoma growth in vivo. Moreover, metformin decreased mRNA and protein expression levels of the Shh pathway, and this effect was reversed by the AMP-activated protein kinase (AMPK) siRNA. Furthermore, the pro-apoptotic and cell cycle arrest effects of metformin on Daoy cells could be reversed by the Shh pathway activators. Our findings demonstrated that metformin could inhibit medulloblastoma progression in vitro and in vivo, and this effect was associated with AMPK-mediated inhibition of the Shh signaling pathway in vitro studies.


Nail psoriasis treated with pulsed dye laser.
Nail changes are present in about 50% of psoriasis patients and tend to be refractory to conventional treatments. Pulsed dye laser has emerged as an alternative therapy. Our aim is to evaluate the efficacy of pulsed dye laser in nail psoriasis and the impact of treatment on quality of life. Fourteen patients were treated in monthly sessions for three months. The outcome assesment was made by the Nail Psoriasis Severity Index (NAPSI). The median improvement in the scores of the overall NAPSI, nail bed NAPSI, and nail matrix NAPSI were 44.2% (P = 0.002), 50% (P = 0.033) and 65.1% (P = 0.024), respectively.


Antiviral effects of interferon-stimulated genes in bats.
The interferon pathway is the first line of defense in viral infection in all mammals, and its induction stimulates broad expression of interferon-stimulated genes (ISGs). In mice and also humans, the antiviral function of ISGs has been extensively studied. As an important viral reservoir in nature, bats can coexist with a variety of pathogenic viruses without overt signs of disease, yet only limited data are available for the role of ISGs in bats. There are multiple species of bats and work has begun deciphering the differences and similarities between ISG function of human/mouse and different bat species. This review summarizes the current knowledge of conserved and bat-specific-ISGs and their known antiviral effector functions.


Automated Tecan programming for bioanalytical sample preparation with EZTecan.
This paper reports the first successful automated Tecan (Tecan US, Research Triangle Park, NC) programming for bioanalytical sample analysis with an in-house developed software, called EZTecan. Based on the sample run list in the Watson Laboratory Information Management System (InnaPhase Corp., Philadelphia, PA), EZTecan can generate a Tecan program for bioanalytical sample preparation, including sample transfer, sample dilution, extraction, and reconstitution. Many built-in functions for EZTecan ensure the flexibility, quality, and efficiency of the liquid handling. It takes about 90 min to prepare two 96-well plates from sample transfer to reconstitution. Analytical results shown good inter- and intra-assay accuracy and precision, which meet the +/-15% Good Laboratory Performance acceptance criteria. With EZTecan, bioanalysts can prepare samples without writing a single line of Tecan program.


Proteins, lipids, and water in the gas phase.
Evidence from mass-spectrometry experiments and molecular dynamics simulations suggests that it is possible to transfer proteins, or in general biomolecular aggregates, from solution to the gas-phase without grave impact on the structure. If correct, this allows interpretation of such experiments as a probe of physiological behavior. Here, we survey recent experimental results from mass spectrometry and ion-mobility spectroscopy and combine this with observations based on molecular dynamics simulation, in order to give a comprehensive overview of the state of the art in gas-phase studies. We introduce a new concept in protein structure analysis by determining the fraction of the theoretical possible numbers of hydrogen bonds that are formed in solution and in the gas-phase. In solution on average 43% of the hydrogen bonds is realized, while in vacuo this fraction increases to 56%. The hydrogen bonds stabilizing the secondary structure (α-helices, β-sheets) are maintained to a large degree, with additional hydrogen bonds occurring when side chains make new hydrogen bonds to rest of the protein rather than to solvent. This indicates that proteins that are transported to the gas phase in a native-like manner in many cases will be kinetically trapped in near-physiological structures. Simulation results for lipid- and detergent-aggregates and lipid-coated (membrane) proteins in the gas phase are discussed, which in general point to the conclusion that encapsulating proteins in "something" aids in the conservation of native-like structure. Isolated solvated micelles of cetyl-tetraammonium bromide quickly turn into reverse micelles whereas dodecyl phosphocholine micelles undergo much slower conversions, and do not quite reach a reverse micelle conformation within 100 ns.


Protective antigen as a correlative marker for anthrax in animal models.
The most aggressive form of anthrax results from inhalation of airborne spores of Bacillus anthracis and usually progresses unnoticed in the early stages because of unspecific symptoms. The only reliable marker of anthrax is development of bacteremia, which increases with disease progress. Rapid diagnosis of anthrax is imperative for efficient treatment and cure. Herein we demonstrate that the presence and level of a bacterial antigen, the protective antigen (PA), a component of B. anthracis toxins, in host sera can serve as a reliable marker of infection. This was tested in two animal models of inhalation anthrax, rabbits and guinea pigs infected by intranasal instillation of Vollum spores. In both models, we demonstrated qualitative and quantitative correlations between levels of bacteremia and PA concentrations in the sera of sick animals. The average time to death in infected animals was about 16 h after the appearance of bacteremia, leaving a small therapeutic window. As the time required for immunodetection of PA can be very short, the use of this marker will be beneficial for faster diagnosis and treatment of inhalation anthrax.


Identification of estrogenic compounds in oil sands process waters by effect directed analysis.
Using effect directed analysis, the presence of estrogenic components in untreated and biologically treated oil sands process water (OSPW) was detected with the yeast estrogenic screening assay after fractionation with solid phase extraction followed by reversed phase high performance liquid chromatography. Comparison of the composition, as determined by electrospray ionization combined with high-resolution linear trap quadropole (LTQ)-Orbitrap Velos Pro hybrid mass spectrometry (negative ion) of selected estrogenic and nonestrogenic fractions identified compounds that were uniquely present in the estrogenic samples, biologically treated and untreated. Of the 30 most abundant compounds, there were 14 possible nonaromatic structures and 16 possible aromatic structures. Based on the published literature, the latter are the most likely to cause estrogenicity and were O2, O3 and O4 C17 to C20 compounds with double bond equivalents between 6 and 10 and chemical formulas similar to estrone- and estradiol-like compounds. This study shows exact formulas and masses of possible estrogenic compounds in OSPW. These findings will help to focus study on the most environmentally significant components in OSPW.


An on-line method for evaluation of the in vitro pulsatile pressure drop and regurgitative characteristics of prosthetic heart valves.
An on-line digital method is described for analyzing the pressure drop and regurgitative characteristics of prosthetic heart valves in a pulse duplicator system. The method is based on the Apple II microcomputer system but could be modified to be used with most microcomputers currently available. The digital data collection system is synchronized with the pulse duplicator system, and is programmed to collect the relevant pressure (upstream and downstream) and volumetric flow data for 10 cardiac cycles at a given time. The system is relatively easy to use and gives the scientist a fair amount of flexibility in terms of data collection, storage, and analysis. The on-line method has been used with the pulse duplicator of the Georgia Institute of Technology for the past 3 years.


Analytical and clinical validation of a custom 15-gene next-generation sequencing panel for the evaluation of circulating tumor DNA mutations in patients with advanced non-small-cell lung cancer.
This is a pilot proof-of-concept study to evaluate the utility of a custom 15-gene circulating tumor DNA (ctDNA) panel as a potential companion molecular next-generation sequencing (NGS) assay for identifying somatic single nucleotide variants and indels in non-small-cell lung cancer (NSCLC) patients. The custom panel covers the hotspot mutations in EGFR, KRAS, NRAS, BRAF, PIK3CA, ERBB2, MET, KIT, PDGFRA, ALK, ROS1, RET, NTRK1, NTRK2 and NTRK3 genes which serve as biomarkers for guiding treatment decisions in NSCLC patients. The custom 15-gene ctDNA NGS panel was designed using ArcherDX Assay Designer. A total of 20 ng or 50 ng input ctDNA was used to construct the libraries. The analytical performance was evaluated using reference standards at different allellic frequencies (0.1%, 1%, 5% and parental). The clinical performance was evaluated using plasma samples collected from 10 treatment naïve advanced stage III or IV NSCLC patients who were tested for tissue EGFR mutations. The bioinformatics analysis was performed using the proprietary Archer Analysis Software. For the analytical validation, we achieved 100% sensitivity and specificity for the detection of known mutations in the reference standards. The limit of detection was 1% allelic frequency. Clinical validation showed that the clinical sensitivity and specificity of the assay for detecting EGFR mutation were 83.3% and 100% respectively. In addition, the NGS panel also detected other mutations of uncertain significance in 6 out of 10 patients. This preliminary analysis showed that the custom 15-gene ctDNA NGS panel demonstrated good analytical and clinical performances for the EGFR mutation. Further studies incorporating the validation of other candidate gene mutations are warranted.


[Treatment of tuberculous meningitis: marker of cure].
A 49-year-old male with tuberculous meningitis was reported. When admitted to our hospital with mild right hemiparesis, he was alert but he developed disorientation 7 days later. A diagnosis of tuberculous meningitis was reached because of elevated levels of adenosine-deaminase at 19.6U/liter in the cerebrospinal fluid. MRI showed a marked enhancement in the basal cisterns and an enhanced intraparenchymal lesion in the brainstem. Chronological changes of MRI findings did not closely correlate with the clinical course. Slight meningeal enhancement on MRI seems to remain for a long time without active tuberculous meningitis, and absence of the meningeal enhancement on MRI is not necessarily appropriate as a marker of cure of tuberculous meningitis.


Simple absorbing-state transition.
We study a simple reaction-diffusion process that exhibits a phase transition to an absorbing phase in its steady state. We characterize the universal properties of the transition by computing the associated critical exponents. We suggest that the exclusion constraint between particles may change the universality class of the transition even though the density is asymptotically low at the transition. This is surprising as no segregation or jamming phenomena are in play since we are dealing with a single species diffusing without drift.


Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute myocardial infarction.
The objective of this study was to determine whether two novel rapid bedside assays for whole-blood detection of cardiac troponin T and creatine kinase (CK)-MB mass/myoglobin could rule out or rule in acute myocardial infarction in patients with acute chest pain. Ninety-two patients with chest pain <12 h prior to admission were investigated. No difference in the cumulative sensitivity of the TropT test and the CARDIAC STATus test (CK-MB mass and myoglobin in combination) was found 6 h after admission (94 vs. 97%). The cumulative positive predictive value of the TropT test and CARDIAC STATus test 6 h after admission was 97 and 76%, respectively. The negative predictive value was 97% for the TropT test and 98% for the CARDIAC STATus test at this time point. Our data show that the rapid assays provide diagnostic as well as prognostic information shortly after admission.


Research in haemophilia B--approaching the request for high evidence levels in a rare disease.
Payers in European countries request studies with high levels of evidence for decision making also for rare diseases like haemophilia B (HB). The objective of the study was to determine the status quo of current studies in HB regarding the overall level of evidence generated. The methods used for performing the study were systematic literature research in EMBASE and MEDLINE, search terms 'HB' and 'factor IX' (FIX). The inclusion criteria were journal articles (JA), conference abstracts (CA), English language, published between January 2009 and March 2013, studies only; screening of titles, abstracts, full texts subsequently. ClinicalTrials.gov search: unpublished registered trials (RT) concerning HB or FIX. The analysis was performed on research topic, sponsor, recruitment status and study design. Screening of 1639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was subject of 21 studies (60.0%) and 29 CA (46.8%). Seven studies focused on various aspects of HB, six on haemophilia studies with separate HB data. Screening of 173 hits from ClinicalTrials.gov yielded 42 RT. Overall, 32 RT (76.2%) related to FIX. Measurement of health-related quality of life (HRQoL) was identified in none of these studies, four CA (6.5%), four RT (9.5%). Randomized study design was found in one study (2.9%), four RT (9.5%). Three studies (8.6%) and seven RT (16.7%) were prospective, observational and comparative. The majority of published clinical studies do not meet payers' expectations for evidence. Therefore, clinical investigation concepts addressing randomization, outcomes research including HRQoL and comparison of therapy options should be discussed. Refined statistical methods and exploitation of complementary real-life data sources may fill current evidence gaps concerning rare diseases.


Impact of Modern Drug Therapy on Surgery: Crohn's Disease.
A significant number of patients with Crohn's disease needs to undergo surgery, and many of these patients are under modern drug treatment. These drugs may influence the rate of perioperative complications. This may have an impact on the chosen surgical strategy. This review considers clinical studies and guidelines on the effect of modern drug treatment on surgical complication rates and surgical strategy in patients with Crohn's disease. Steroids above a certain dose significantly influence perioperative complications and should therefore be tapered down before performing elective surgery. Anti-TNF-alpha drugs are associated with perioperative complications, and therefore a safe interval between drug intake and surgery should be adhered to. The data on newer biologicals is scarce and conflicting; thus, it seems prudent to wait at least for one dosing interval before operating. In the emergency setting, patients undergoing bowel resection while on the above medications without an adequate interval to the last medication dose should generally get a resectional or diverting stoma. Modern drug treatment influences the surgical strategy in patients with Crohn's disease.


Interaction of substituted aromatic compounds with graphene.
We have modeled the adsorption of various substituted derivatives of benzene on a graphene sheet, using a first-principles density functional theory-local density approximation method. The presence of functional groups can significantly alter the overall magnitude of pi-pi interactions between the adsorbed molecules and graphene by giving rise to strong medium-range interactions involving pi-orbitals of the substituents. When the substituents can simultaneously permit the formation of hydrogen bonds between adsorbed molecules, it is possible to evaluate the relative contributions of hydrogen bonding and pi-based interactions to the overall adsorption. Adsorption of individual molecules and hydrogen-bonded aggregates reflects a hierarchical balance of the different interactions that determine the overall energy of adsorption.


Efficacy of sulfadoxin pyrimethamine for uncomplicated Plasmodium falciparum malaria in a small sample of Sudanese children.
A prospective clinical trial was carried out to determine in vivo efficacy of sulfadoxine/pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in children in New Halfa. Forty patients were enrolled; 31 completed the 28-day follow-up. Six (19.4%) patients showed recurrence of parasitaemia during follow-up, while the rest (80.6%) cleared the parasites and responded fully to treatment. All the failures were late treatment failures. Parasite genotyping showed that 1 (16.7%) of the 6 cases of late parasitaemia was due to reinfection while the rest (83.4%) were due to true recrudescence. During the follow-up period 22.6% of patients showed gametocytaemia. The high level of treatment failure as well as gametocytaemia necessitates the introduction of artesunate in this combination therapy.


Darbufelone, a novel anti-inflammatory drug, induces growth inhibition of lung cancer cells both in vitro and in vivo.
Inflammation plays a crucial role in the development of lung cancer. Accumulated studies have proved that non-steroidal anti-inflammatory drugs (NSAIDs) which block inflammation by their actions on arachidonic acid (AA) metabolism have a potential role in cancer chemotherapy and chemoprevention. The aim of our study was to investigate whether darbufelone, a novel anti-inflammatory drug, has anticancer effects in lung cancer. Human non-small cell lung cancer cell lines were treated with darbufelone at various doses and time points for analysis of cell viability, cell cycle, and apoptosis in vitro. The in vivo effect of darbufelone was assessed in Lewis lung carcinoma mice model. Darbufelone inhibited the proliferation of non-small cell lung cancer cell lines in a dose-dependent manner, and induced cell cycle arrest at G0/G1 phase through up-regulation of p27 expression. Treatment with darbufelone also induced apoptosis by activating caspase-3 and caspase-8. Lewis lung carcinoma growth was also significantly inhibited by darbufelone treatment at daily dose of 80 mg/kg. Taken together, these studies suggested that darbufelone, an anti-inflammation drug, might represent a novel therapeutic approach for lung cancer treatment.


Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells.
Nuclear inclusions formed by the aggregation of a polyalanine expansion mutant of the nuclear poly(A)-binding protein (PABPN1) is a hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant autosomal disease in which patients exhibit progressive difficulty of swallowing and eyelid elevation, starting around the age of 50. At present, there is no specific treatment to reduce the aggregate burden in patients. However, in cell culture models of OPMD, reduction of protein aggregation can be achieved by ectopic expression of HSP70. As gene transfer may not be the most effective means to elevate HSP70 levels, we tested four pharmacological agents for their ability to induce HSP70, recruit both HSP70 and HSC70 into the cell nucleus and reduce mutant PABPN1 aggregation in a HeLa cell culture model. We show here that exposure to moderate levels of ZnSO4, 8-hydroxyquinoline, ibuprofen and indomethacin produced a robust stress response resulting in the induction of HSP70 in HeLa cells expressing the mutant PABPN1 as a green fluorescent protein (GFP) fusion protein. Both HSP70 and the constitutive chaperone HSC70 localized in the nucleus of cells treated with any one of the four agents. This stress response was similar to what was observed following hyperthermia. All four agents also caused a significant reduction in the cellular burden of protein aggregates, as was judged by confocal microscopy and solubility changes of the aggregates. A concomitant reduction of cell death in drug-treated mutant PABPN1 expressing cells was also observed.


Photoperiodic Programming of the SCN and Its Role in Photoperiodic Output.
Though the seasonal response of organisms to changing day lengths is a phenomenon that has been scientifically reported for nearly a century, significant questions remain about how photoperiod is encoded and effected neurobiologically. In mammals, early work identified the master circadian clock, the suprachiasmatic nuclei (SCN), as a tentative encoder of photoperiodic information. Here, we provide an overview of research on the SCN as a coordinator of photoperiodic responses, the intercellular coupling changes that accompany that coordination, as well as the SCN's role in a putative brain network controlling photoperiodic input and output. Lastly, we discuss the importance of photoperiodic research in the context of tangible benefits to human health that have been realized through this research as well as challenges that remain.


Case report: The gait deviation index may predict neurotherapeutic effects of FES-assisted gait training in children with cerebral palsy.
Children with cerebral palsy (CP) show progressive loss of ambulatory function characterized by kinematic deviations at the hip, knee, and ankle. Functional electrical stimulation (FES) can lead to more typical lower limb kinematics during walking by eliciting appropriately timed muscle contractions. FES-assisted walking interventions have shown mixed to positive results in improving lower limb kinematics through immediate correction of gait during the application of FES, or long-term, persisting effects of non-FES-assisted gait improvements following multi-week FES-assisted gait training, at the absence of stimulation, i.e., neurotherapeutic effects. It is unknown, however, if children with CP will demonstrate a neurotherapeutic response following FES-assisted gait training because of the CP population's heterogeneity in gait deviations and responses to FES. Identifying the neurotherapeutic responders is, therefore, important to optimize the training interventions to those that have higher probability of benefiting from the intervention. The purpose of this case study was to investigate the relationship between immediate and neurotherapeutic effects of FES-assisted walking to identify responders to a FES-assisted gait training protocol. The primary outcome was Gait Deviation Index (GDI) and secondary outcome was root mean squared error (RMSE) of the lower extremity joint angles in the sagittal plane between participants with CP and a typically developing (TD) dataset. Potential indicators were defined as immediate improvements from baseline during FES-assisted walking followed by neurotherapeutic improvements at the end of training. Gait analysis of two adolescent female participants with spastic diplegia (Gross Motor Function Classification System level II and III) was conducted at the start and end of a 12-week FES-assisted treadmill training protocol. Participant 1 had scissoring crouch gait, while participant 2 had jump gait. The GDI showed both immediate (presence of FES) and neurotherapeutic (absence of FES after training period) improvements from baseline in our two participants. Joint angle RMSE showed mixed trends between immediate and neurotherapeutic changes from baseline. The GDI warrants investigation in a larger sample to determine if it can be used to identify responders to FES-assisted gait training.


Contingency management of exercise by chronic schizophrenics.
Research on the control and maintenance of exercise by chronic schizophrenics has been relatively neglected, despite widespread knowledge of the adverse consequences of sedentary living. The present study evaluated the effects of simple contingency-management procedures designed to encourage exercising by two psychotic residents living in a sheltered group home. For both subjects, the ABAB experimental analysis demonstrated the effectiveness of the intervention. Improved levels of exercise were maintained at follow-up and the contingency-management system was implemented as a regular part of the group home's rehabilitation program for all residents.


Pseudoelastic behaviour of a natural material is achieved via reversible changes in protein backbone conformation.
The egg capsules of marine prosobranch gastropods, commonly know as whelks, function as a protective encapsulant for whelk embryos in wave-swept marine environments. The proteinaceous sheets comprising the wall of whelk egg capsules (WEC) exhibit long-range reversible extensibility with a hysteresis of up to 50 per cent, previously suggested to result from reversible changes in the structure of the constituent protein building blocks. Here, we further investigate the structural changes of the WEC biopolymer at various hierarchical levels using several different time-resolved in situ approaches. We find strong evidence in these biological polymers for a strain-induced reversible transition from an ordered conformational phase to a largely disordered one that leads to the characteristic reversible hysteretic behaviour, which is reminiscent of the pseudoelastic behaviour in some metallic alloys. On the basis of these results, we generate a simple numerical model incorporating a worm-like chain equation to explain the phase transition behaviour of the WEC at the molecular level.


Histamine-selective H3 receptor ligands and cognitive functions: an overview.
This review presents a link between histamine and cognition and provides an overview on the effect of histamine and selective ligands of histamine receptors on experimental models for learning, memory and cognitive functions, with a special focus on recently developed H(3) receptor ligands. Studies suggest a tremendous potential for H(3) antagonists in cognitive function disorders.


Redefining the Anatomic Boundaries for Safe Dissection of the Skin Paddle in a Gracilis Myofasciocutaneous Free Flap: An Indocyanine Green Cadaveric Injection Study.
The gracilis free flap remains a versatile option in the reconstructive ladder. The flap itself can be harvested with or without a skin paddle. The gracilis myocutaneous free flap, however, is known for partial skin flap necrosis, especially in the distal one-third of the skin island. The gracilis myofasciocutaneous flap has been previously described as a technique to improve perfusion to the skin by harvesting surrounding deep fascia in a pedicled flap. However, limitations to this study required injection of multiple pedicles to demonstrate its perfusion. We demonstrate a novel technique using a cadaveric model that shows perfusion through injection via a single dominant pedicle (medial circumflex) with a large cutaneous paddle (average 770 cm2) with included deep fascia, using indocyanine green and near-infrared imaging. For comparison, we are also able to confirm the lack of perfusion to the distal cutaneous paddle when the fascia is not harvested, correlating with previous findings and ink injection studies. This novel technique is versatile, relatively inexpensive, and can demonstrate perfusion patterns via perforasomes that were otherwise not possible from previous techniques. Additionally, real-time imaging is possible, helping to elucidate the sequence of flow into the flap and potentially predict areas of flap necrosis.


Multivariate morphotaxonomy in the identification of adult females of the Simulium damnosum Theobald complex (Diptera: Simuliidae) in the Onchocerciasis Control Programme area of West Africa.
Adult female Simulium damnosum s.l. flies obtained in nine countries of the Onchocerciasis Control Programme were examined for 14 morphological characters with the aim of selecting specific characters to identify the main species that form the complex. Two approaches were used, the first involved discriminant function analysis of the species groups using all the characters which were both qualitative (the colour of the fore coxa, the antennae, the wing tuft, the arculus, the ninth abdominal tergite setae and the scutellar setae) and quantitative (the lengths of thorax, antenna, and femur, tibia and first basitarsus of both the fore and hind legs) in nature. The second sought colour characters unique to the S. damnosum subcomplex and to S. yahense, to separate them from the rest, and progressively applied discriminant analyses in the dichotomous stepwise manner to within the subcomplex level. The combination of pale arculus and pale antennae with pale or dark fore coxae were unique to the S. damnosum subcomplex, whilst those of black arculus together with wholly dark or mixed ninth abdominal tergite setae and scutellar setae were unique to S. yahense. Further discrimination was achieved between subcomplexes and species by entering the qualitative and quantitative characters into discriminant function analysis. The two schemes were both successful at separating the main species subcomplexes of the S. damnosum complex, with 90-100% correct classification. Within the subcomplex level, correct identification of sibling species was 85-100% successful.(ABSTRACT TRUNCATED AT 250 WORDS)


Recent Progress in Protein S-Nitrosylation in Phytohormone Signaling.
The free radical nitric oxide (NO) is a critical regulator in modulation of wide range of growth and developmental processes as well as environmental responses in plants. In most cases, NO interacts with plant hormones to regulate these processes. It is clear that NO might work through either transcriptional or post-translational level. The redox-based post-translational modification S-nitrosylation has been recognized as a NO-dependent regulatory mechanism in recent years. In general, S-nitrosylation can be understood as a product of reversible reaction where NO moiety group covalently attaches to thiol of cysteine residue resulting in the formation of S-nitrosothiol in target proteins. Recently, the crosstalk between S-nitrosylation and phytohormones has been emerging. Furthermore, several proteins involved in plant hormone signaling have been reported to undergo S-nitrosylation, which might subsequently mediate plant growth and defense response. In this review, we focus on the recent processes in protein S-nitrosylation in phytohormone signaling. In addition, both importance and challenges of future work on protein S-nitrosylation in plant hormone network are also highlighted.


Convergent evidence for the effectiveness of interpersonal skill training for dental students.
The Florida Interpersonal Skills Training (FIST) program for dental students has been evolving for five years. This current paper describes the development and current status of the FIST program and several pieces of evidence that indicate that the program is having its desired effect. This evidence includes (1) demonstration of short-term change in the chairside behavior of students exposed to FIST, (2) more favorable patient perceptions of dentists who behave in accordance with FIST principles (an analog study), (3) student evaluation of the course employing FIST, and (4) practicing dentists' and auxiliaries' evaluation of the usefulness of the course content. It is concluded both that the course seems to be effective and that the evaluation procedures used are both practical and useful.


Cerebral circulatory changes during migraine headache with aura.
Many authors report alterations of cephalic (both intracranial and extracranial) blood flow and vascular responsiveness in patients with migraine. In the majority of reports, rCBF has been decreased during the prodromal phase and increased during and immediately after the headache phase of migraine attacks. Abnormal vascular responsiveness has been demonstrated, not only during each attack, but also between attacks. Pharmacological and therapeutic evidence that many vasoactive agents induce, prevent or abolish attacks of migraine headache are consonant with the close relationships that exist between vascular abnormalities and the pathogenesis of migraine with aura. This is particularly true of the marked therapeutic effectiveness of calcium entry blockers, which are effective in the prophylaxis of migraine, and sumatriptan, which has direct vasoconstrictive effects, with relief of the headache, which lends strong support to a vascular hypothesis.


Clarifying differences in definitions between ASHA policy documents and the authors in "the critical shortage of speech-language pathologists in the public school setting: features of the work environment that affect recruitment and retention".
The January 2007 issue of Language, Speech, and Hearing Services in Schools includes an article by D. Edgar and L. Rosa-Lugo entitled "The Critical Shortage of Speech-Language Pathologists in the Public School Setting: Features of the Work Environment That Affect Recruitment and Retention." In their article, the authors cite the American Speech-Language-Hearing Association (ASHA) policy document "A Workload Analysis Approach for Establishing Speech-Language Caseload Standards in Schools: Guidelines" (ASHA, 2002) and include the term workload in their survey instrument and study results. However, their definition of workload differs from the definition in ASHA policy documents. In addition, they provide some information from the ASHA Technical Report on workload (ASHA, 2002) that may be misconstrued out of context. The purpose of this letter is to reduce the possibility of any misunderstanding on the part of readers by highlighting the differences in definitions between the authors' work and ASHA policy documents and by providing context for information from the policy document. D. Edgar and L. Rosa-Lugo should be commended for conducting research related to the successful recruitment and retention of qualified speech-language pathologists in schools. Hopefully, these comments will contribute to those discussions by clarifying important points.


Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy.
The electrodiagnosis of polyneuropathy (PNP) may benefit from examination using near-nerve needle technique (NNT) and from inclusion of distal nerves. This study compared the diagnostic utility of distal nerve conduction studies (NCS) and NNT recording. Bilateral NNT and surface recording of the sural nerve and surface recording of the dorsal sural and medial plantar nerves were prospectively done in 91 patients with clinically suspected PNP. Distal NCS were additionally done in 37 healthy controls. Diagnostic reference standard was the final clinical diagnosis retrieved from the patients medical records after 1-4years. The clinical follow-up diagnosis confirmed PNP in 68 patients. Equally high sensitivities of the dorsal sural (72%), medial plantar (75%), and sural nerve with NNT recording (77%) were seen, while the sensitivity of conventional surface recording of the sural nerve was lower (60%). Sural NCS with both NNT and surface recording and dorsal sural NCS showed high specificities (85-95%) and positive predictive values (94-98%), while a lower specificity was seen for the medial plantar nerve (68%). NCS of distal nerves, especially the dorsal sural nerve, have high diagnostic power equalling sural NNT recording. The electrodiagnostic evaluation of patients with suspected PNP benefits from NCS of distal nerves.


A Cloud-Based Metabolite and Chemical Prioritization System for the Biology/Disease-Driven Human Proteome Project.
Targeted metabolomics and biochemical studies complement the ongoing investigations led by the Human Proteome Organization (HUPO) Biology/Disease-Driven Human Proteome Project (B/D-HPP). However, it is challenging to identify and prioritize metabolite and chemical targets. Literature-mining-based approaches have been proposed for target proteomics studies, but text mining methods for metabolite and chemical prioritization are hindered by a large number of synonyms and nonstandardized names of each entity. In this study, we developed a cloud-based literature mining and summarization platform that maps metabolites and chemicals in the literature to unique identifiers and summarizes the copublication trends of metabolites/chemicals and B/D-HPP topics using Protein Universal Reference Publication-Originated Search Engine (PURPOSE) scores. We successfully prioritized metabolites and chemicals associated with the B/D-HPP targeted fields and validated the results by checking against expert-curated associations and enrichment analyses. Compared with existing algorithms, our system achieved better precision and recall in retrieving chemicals related to B/D-HPP focused areas. Our cloud-based platform enables queries on all biological terms in multiple species, which will contribute to B/D-HPP and targeted metabolomics/chemical studies.


Myopathy with thick filament (myosin) loss following prolonged paralysis with vecuronium during steroid treatment.
A 20-year-old female hospitalized with status asthmaticus was treated with bronchodilators, antibiotics, and high-dose corticosteroids, and was paralyzed with vecuronium for 10 days to facilitate mechanical ventilation. When this was discontinued, she was found to have a flaccid quadriplegia with areflexia and 4-fold elevation in serum creatine kinase. A muscle biopsy showed extensive loss of thick (myosin) myofilaments, sometimes in core-like distribution, with relative preservation of thin (actin) filaments and Z-discs. Muscle strength returned to normal after 2 months. The pathological lesion in this patient's muscle fibers resemble those in rats treated with high doses of corticosteroids following denervation.


Solid-phase synthesis of three-armed star-shaped peptoids and their hierarchical self-assembly.
Due to the branched structure feature and unique properties, a variety of star-shaped polymers have been designed and synthesized. Despite those advances, solid-phase synthesis of star-shaped sequence-defined synthetic polymers that exhibit hierarchical self-assembly remains a significant challenge. Hence, we present an effective strategy for the solid-phase synthesis of three-armed star-shaped peptoids, in which ethylenediamine was used as the centric star pivot. Based on the sequence of monomer addition, a series of AA'A''-type and ABB'-type peptoids were synthesized and characterized by UPLC-MS (ultrahigh performance liquid chromatography-mass spectrometry). By taking advantage of the easy-synthesis and large side-chain diversity, we synthesized star-shaped peptoids with tunable functions. We further demonstrated the aqueous self-assembly of some representative peptoids into biomimetic nanomaterials with well-defined hierarchical structures, such as nanofibers and nanotubes. These results indicate that star-shaped peptoids offer the potential in self-assembly of biomimetic nanomaterials with tunable chemistries and functions.


ANP concentrations during interchanging DDD-VVI pacing modes in patients with retrograde ventriculoatrial conduction.
The main reason for the pacemaker syndrome during VVI pacing is the existence of ventriculoatrial conduction (V-AC). Twenty-five patients with a permanent DDD pacemaker and ventriculoatrial conduction were included in the study. IN those patients the hemodynamic changes were evaluated in relation to ANP plasma concentration changes during different modes of pacing. After a resting period of 30 minutes in the supine position ANP plasma concentration and blood pressure were evaluated: a) under DDD atrioventricular pacing at 90/min and for 30 minutes and b) under VVI pacing at 90/min and for 30 minutes. A decrease of systolic blood pressure by 12.77% (P < 0.0001) and diastolic blood pressure by 10.50% (P < 0.0001) was noticed during VVI pacing. ANP was increased during VVI pacing by 215.95% (P < 0.0001). It was observed that the acute transition from DDD to VVI pacing leads to a 3-fold increase in the levels of plasma ANP; this may be partially responsible for the pathogenesis of the haemodynamic changes during VVI pacing mediated through the direct hypotensive effect in addition to the coincidence of atrial and ventricular contraction. This study also proves the role of the increased systolic stress of atrial myocardium for the increased ANP secretion.


Systematic review and meta-analysis of the prevalence of cognitive impairment no dementia in the first year post-stroke.
Increasing attention is being paid to interventions for cognitive impairment (CI) post-stroke, including for CI that does not meet dementia criteria. The aim of this paper was to conduct a systematic review and meta-analysis of the prevalence of cognitive impairment no dementia (CIND) within one year post-stroke. Pubmed, EMBASE and PsychInfo were searched for papers published in English in 1995-2017. Included studies were population or hospital-based cohort studies for first-ever/recurrent stroke, assessing CIND using standardised criteria at 1-12 months post-stroke. Abstracts were screened, followed by full text review of potentially relevant articles. Data were extracted using a standard form, and study quality was appraised using the Crowe Critical Appraisal Tool. A pooled prevalence of CIND with 95% confidence intervals (CI) was estimated using random-effects meta-analysis. Heterogeneity was measured using the I2 statistic. A total of 7000 abstracts were screened, followed by 1028 full text articles. Twenty-three articles were included in the systematic review, and 21 in the meta-analysis. The pooled CIND prevalence was 38% [95% CI = 32-43%] (I2=92.5%, p < 0.01). Study quality emerged as one source of heterogeneity. The five studies with the highest quality scores had no heterogeneity (I2=0%, p = 0.99), with a similar pooled prevalence (39%, 95%CI = 35-42%). Other sources of heterogeneity were stroke type, inclusion of pre-stroke CI, and age at assessment time.Discussion and conclusion: Meta-analysis of available studies indicates that in the first year post-stroke, 4 in 10 patients display a level of cognitive impairment that does not meet the criteria for dementia.


[Comparative antihistamine and anti-allergic effects of various antihistamine preparations].
To compare antihistaminic and antiallergic activity of antihistaminic drugs of the latest generation (ebastin, cetirisine, fexofenadine, loratadine) and antihistaminic drugs of the first generation (clemastin) in the same patients with pollenosis. Skin prick-titration with 10-dilution histamine and specific allergen, provocative nasal titration with 2-dilution histamine and allergen before and after a single intake of H1-antagonists were made in 30 patients in stable clinical remission of pollenosis during maximal antihistamine activity of the above drugs. Systemic administration of the known H1-antagonists suppresses histamine sensitivity of both skin and nasal mucosa in the same degree. Drugs with more potent antihistaminic activity (fexofenadin and cetirisin) inhibited allergen-induced reactions more effectively. The order of the tested drugs by suppression of allergen-provoked skin and nasal reactions (by lowering antiallergic activity) is the following: fexofenadin and cetirisin > ebastin and loratadin > clemastin. The above drugs of the latest generation seem to posses antiallergic activity not only due to antihistaminic effect but also due to other mechanisms. Different suppressive action of H1-antagonists reflects also individual sensitivity to different drugs. The factor of individual sensitivity of the patients to a pharmacological action of the drug may be crucial in the selection of the most effective medicine for each patient. This is confirmed by the data of individual sensitivity of the patient to antihistaminic and antiallergic action of H1-antagonists. The illustrated method may be helpful for individual selection of H1-antagonists for treatment of patients with allergic diseases.


Covid-19 association with anterior uveitis (post-covid acute anterior uveitis).
The Covid-19 outbreak in Wuhan on 31st December 2019 soon became a pandemic. Ocular manifestations in post covid patients have been widely reported. Anterior uveitis is a common form of intraocular inflammation observed on a daily basis by Ophthalmologists. Diagnosis of AAU is relatively simple but identification of its etiology is difficult, specifically with Covid-19. Post Covid-19 AAU is not reported in Pakistan yet. The patient in the given case is investigated thoroughly, no possible cause of AAU is identified. The patient was managed for uveitis.


Molecular mechanisms of liver injury and hepatocarcinogenesis: focusing on the role of stress-activated MAPK.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Short-term prognosis of patients with HCC has improved recently due to advances in early diagnosis and treatment, but long-term prognosis is still unsatisfactory. Therefore, obtaining a further understanding of the molecular carcinogenic mechanisms and the unique pathogenic biology of HCC is important. The most characteristic process in hepatocarcinogenesis is underlying chronic liver injury, which leads to repeated cycles of hepatocyte death, inflammation, and compensatory proliferation and subsequently provides a mitogenic and mutagenic environment leading to the development of HCC. Recent in vivo studies have shown that the stress-activated mitogen-activated protein kinase (MAPK) cascade converging on c-Jun NH(2)-terminal kinase (JNK) and p38 plays a central role in these processes, and it has attracted considerable attention as a therapeutic target. However, JNK and p38 have complex functions and a wide range of cellular effects. In addition, crosstalk with each other and the nuclear factor-kappaB pathway further complicate these functions. A full understanding is essential to bring these observations into clinical settings. In this paper, we discuss the latest findings regarding the mechanisms of liver injury and hepatocarcinogenesis focusing on the role of the stress-activated MAPK pathway.


Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress.
While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR) protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT), increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.


Utility of anti-WI-1 serological testing in the diagnosis of blastomycosis in Wisconsin residents.
WI-1, a 120-kD protein found in the outer cell wall of Blastomyces dermatitidis, has been purified, labeled with 125I, and used as a target in a radioimmunoassay (RIA). In an assessment of the usefulness of anti-WI-1 serology in the diagnosis of blastomycosis, the RIA was used to test four panels of sera from residents of Wisconsin, a state in which blastomycosis is endemic. Twenty-four (75%) of 32 patients whose blastomycosis had been reported to the Wisconsin Division of Health had at least one serum sample positive for antibody to WI-1; 25 (93%) of 27 serum samples obtained from these patients within 60 days of diagnosis were positive. In an effort to simulate clinical practice, 132 serum samples were assayed from another 107 patients in whom blastomycosis was being considered as a cause of illness. The result was positive for at least one sample from 83% of the 23 patients with confirmed blastomycosis and from 5% of the 84 patients from whom the fungus was not documented. Serum samples from another five patients with blastomycosis identified during investigation of a 1990 outbreak in Oconto Falls, Wisconsin, also gave a positive result, whereas none of the serum specimens from 57 healthy family members or neighbors did so. Only three (0.56%) of 535 serum samples from random blood donors residing in two counties with a high annual incidence of blastomycosis were positive for antibody to WI-1. Modification of the RIA so that IgM rather than IgG antibody was detected did not enhance diagnostic sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)


[Echographic features in the diagnosis of renal abscess].
The Authors emphasize sonographic aspects of Renal Abscess in early phase and in proclaimed disease. The advent of the sonography and its extensive use marked an inversion of tendency in Perinephric Abscess evolution. So it is possible to point out small Abscesses and in early phase. Leukocytes tags Scintiscan and CT can confirm the diagnostic tentative.


Design of exchange-correlation functionals through the correlation factor approach.
The correlation factor model is developed in which the spherically averaged exchange-correlation hole of Kohn-Sham theory is factorized into an exchange hole model and a correlation factor. The exchange hole model reproduces the exact exchange energy per particle. The correlation factor is constructed in such a manner that the exchange-correlation energy correctly reduces to exact exchange in the high density and rapidly varying limits. Four different correlation factor models are presented which satisfy varying sets of physical constraints. Three models are free from empirical adjustments to experimental data, while one correlation factor model draws on one empirical parameter. The correlation factor models are derived in detail and the resulting exchange-correlation holes are analyzed. Furthermore, the exchange-correlation energies obtained from the correlation factor models are employed to calculate total energies, atomization energies, and barrier heights. It is shown that accurate, non-empirical functionals can be constructed building on exact exchange. Avenues for further improvements are outlined as well.


Aortic valve replacement in elderly patients.
The results for 62 consecutive patients aged 70 or more given aortic valve replacement (A.V.R.) between 1970 and 1982 are reported. All the patients were in the New York Heart Association (N.Y.H.A.) functional class III (29%) or IV (71%); 54.8% had angina and 30.6% had experienced syncope. Forty patients had aortic stenosis (A.S.), 10 had aortic regurgitation and 12 had mixed aortic valve disease. The operative myocardial infarction rate was 6.4%. Tilting disk valves were used. Eighty percent of the patients were anticoagulated with Warfarin whilst twenty percent received only antiplatelet drugs. All the patients were followed up for a mean period of 26 months; late mortality was 22.6% with 4.8% cardiac deaths. The thromboembolic rate was 1.6% and the disinsertion rate was 3.2%. Cerebral stroke was fatal in 3 cases in anticoagulated patients but the mechanism of the accident was not known. At the termination of the study 93% of surviving patients were in N.Y.H.A. class I or II. No patient was in class IV. The probability of five year survival is 71% for the entire group.


The management of thyroid cancer in adults: a review of new guidelines.
The management of thyroid cancer has been facilitated by the recent publication of the Guidelines for the management of thyroid cancer in adults under the auspices of the British Thyroid Association and the Royal College of Physicians. This is a consensus document that has been developed by a number of key investigators in the field. The central tenet of the guidelines is that thyroid cancer is a disease which requires specialist care from a multidisciplinary team, including an endocrinologist, nuclear medicine physician, thyroid surgeon and endocrine pathologist. The guidelines are comprehensive and detailed, covering differentiated (papillary and follicular) and medullary cancer of the thyroid. They have been written in sections aimed at thyroid cancer specialists, primary care physicians, patients and their families. The guidelines are greatly welcomed and represent a major step forwards in the co-ordination of specialist care for thyroid cancer in the UK.


Psychiatric emergencies in prehospital emergency medical systems: a prospective comparison of two urban settings.
Psychiatric emergency situations (PES) are of high importance to the German prehospital physician-based emergency medical system. So far, however, no prospective studies regarding the incidence of PES have been performed, neither have effects of training programs on diagnostic and therapeutic accuracy been studied. The protocols of two emergency medical services (EMS) were collected and analyzed prospectively. Emergency physicians (EPs) in Kaiserslautern (KL) attended a standardized educational program and underwent daily supervision. EPs in Homburg (HOM) had not been informed about the study. In KL, sociodemographic variables were collected. An investigator who was not involved in the individual EMS mission assessed the correct classification of PES. Among all calls for an EP, 11.8% were classified as PES. There was no difference between the two centers. Correct classification of PES in KL was significantly higher than that in HOM (94.3% vs. 80.6%). Documentation of suicidal behavior was deficient in both centers. EPs in KL gave verbal crisis intervention significantly more often, administered less medication overall, and dispensed more specific drugs in psychotic disorders and significantly less drugs in substance abuse disorders. Patients were more often treated at the scene and were less often transported to a hospital. Some sociodemographic variables were associated with psychiatric morbidity of treatment. Accounting for 12% of all missions, psychiatric emergencies are a frequent reason for calls for EPs, equaling trauma-related and neurological emergencies. The most frequent reasons for calls were alcohol intoxication, states of agitation and suicidal behavior. The diagnostic and therapeutic accuracy of EPs may be improved with a concise standardized teaching program.


Bead Based Proteome Enrichment Enhances Features of the Protein Elution Plate (PEP) for Functional Proteomic Profiling.
A novel functional proteomics technology called PEP(Protein Elution Plate) was developed to separate complex proteomes from natural sources and analyze protein functions systematically. The technology takes advantage of the powerful resolution of two-dimensional gel electrophoresis (2-D Gels). The modification of electrophoretic conditions in combination with a high-resolution protein elution plate supports the recovery of functionally active proteins. As 2DE(2-Dimensional Electrophoresis) resolution can be limited by protein load, we investigated the use of bead based enrichment technologies, called AlbuVoid™ and KinaSorb™ to determine their effect on the proteomic features which can be generated from the PEP platform. Using a variety of substrates and enzyme activity assays, we report on the benefits of combining bead based enrichment to improve the signal report and the features generated for Hexokinase, Protein Kinase, Protease, and Alkaline Phosphatase activities. As a result, the PEP technology allows systematic analysis of large enzyme families and can build a comprehensive picture of protein function from a complex proteome, providing biological insights that could otherwise not be observed if only protein abundances were analyzed.


Pressurised fluid extraction (PFE) as an alternative general method for the determination of pesticide residues in rape seed.
A pressurised fluid extraction (PFE) multi-method has been developed for the determination of pesticide residues in rape seed. The method was validated for 25 different pesticides and metabolites. The reliability and efficiency of PFE for extracting pesticide residues from rape seed was investigated. The traditional extraction solvent, hexane saturated with acetonitrile, was used at elevated temperature and pressure. With increased temperature, the extraction kinetics were improved but at the same time more co-extractives were obtained in the form of lipids. When 1 g of rape seed was extracted at temperatures from 60 degrees C to 150 degrees C, the lipid content extracted was found to be as high as 17-26%. An additional clean-up step was therefore required and lipid co-extractives were effectively removed by gel permeation chromatography. The interpretation of the chromatograms and the quantification of the results were satisfactorily improved by the removal of interfering lipids. The developed method was used to extract vinclozolin and iprodione from incurred samples, resulting in a concentration in accordance with the results using conventional liquid-liquid extraction (LLE) between hexane and acetonitrile and also supercritical fluid extraction (SFE) using carbon dioxide. The results of the present study suggest that PEE is a good alternative extraction technique for the determination of pesticide residues in oil seed. Despite the necessity for a lipid-removal clean-up step, the PFE technique facilitated the extraction process by faster extractions and the possibility of automated analysis.


Genus Microlithosia (Lepidoptera, Erebidae, Arctiinae) in Laos, with the description of a new species.
Microlithosia Daniel, 1954 from Laos is reviewed. A new species, Microlithosia laosana Bayarsaikhan Bae, n. sp., is described along with two newly recorded species, M. umbripuncta (de Joannis, 1928) and M. nanlingica Dubatolov, Kishida Wang, 2012. Illustrations of adults and male genitalia are provided. The checklist of the genus is updated.


Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights.
The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COVID-19 severity and mortality, and accumulating evidence suggests that IBTs may favorably alter the clinical course of SARS-CoV-2 infection due to their inherent mechanisms of action. Further research into prognostic variables associated with various antidiabetic treatment regimens, and in particular the IBT, in patients with T2DM affected by the COVID-19 pandemic is therefore warranted.


Older adults in Emergency Department: management by clinical severity at triage.
The elderly are involved in an ever-increasing proportion of Emergency Department (ED) visits, consuming a large share of the available resources. The aim of this study was to assess elderly individuals' demand for ED hospital care, in terms of the management process and outcomes by level of urgency at triage. The design was a retrospective cohort study. Details on ED attendance were drawn from the 2010 dataset of the Local Health Agency n°18 (n=18,648) in the Veneto Region, North-East Italy and the participants were resident seniors seen at the ED aged 65 or more. At triage on arrival, their priority was most often (in 38.63% of cases) considered non-urgent (white triage tag - Wt). In the majority of these cases, the elderly patients were self-referred, although about 1 in 5 of them had been referred by their General Practitioners. The consumption of resources for specialist visit and routine X-rays is higher for non-urgent patients. Injuries, requests for specialist examinations and musculoskeletal disorders account for a large proportion of the reasons why elderly people classified as Wt at triage had gone to the ED. Our findings show that older patients have high rates of non-urgent ED attendance, especially for minor traumatic events or requests to see a specialist. This picture emphasizes the need to develop new organizational models for delivering care to meet the most common health care needs of this special frail population.


Role of N-6 and N-3 fatty acids in the dietary treatment of metabolic disorders.
The impetus to examine the effects on n-3 PUFA was generated from epidemiologic studies of a traditional population largely dependent on the marine environment. These studies and clinical interventions support a recommendation to increase the consumption of n-3 fatty acids, particularly in communities that currently have a low n-3 fatty acid intake. If we are to be guided by the diet of other traditional hunter-gatherer populations, dependent on both terrestrial and marine sources of food, it is clear that we may need to reappraise the importance of long chain PUFA of the n-6 series such as arachidonic acid. Recent studies on such populations indicate that elevated arachidonic acid levels, when associated with elevated n-3 PUFA, are likely not to be harmful to health.


A broad variety of antigens contribute to the pathogenesis of atherosclerosis: how to neutralize noxious reactions in the host.
Atherosclerosis is an inflammatory disease characterized by lipid accumulation as well as vascular injury due to a massive infiltration of immune cells in the endothelial wall. Microbial and self- antigens are responsible for a persistent activation of immune and non-immune cells, thus leading to a condition of arterial chronic inflammation with plaque formation and rupture in complicated cases. In particular, the effects of bacteria, viruses and their toxic products as well as of glycated lipoproteins will be illustrated with special reference to the main inflammatory pathways triggered by a persistent antigenic load in the host. Taking into consideration this broad variety of antigens implicated in the pathogenesis of atherosclerosis, therapeutic approaches such as antibiotics, dietary intervention and immune therapies will be discussed.


Energy functions in de novo protein design: current challenges and future prospects.
In the past decade, a concerted effort to successfully capture specific tertiary packing interactions produced specific three-dimensional structures for many de novo designed proteins that are validated by nuclear magnetic resonance and/or X-ray crystallographic techniques. However, the success rate of computational design remains low. In this review, we provide an overview of experimentally validated, de novo designed proteins and compare four available programs, RosettaDesign, EGAD, Liang-Grishin, and RosettaDesign-SR, by assessing designed sequences computationally. Computational assessment includes the recovery of native sequences, the calculation of sizes of hydrophobic patches and total solvent-accessible surface area, and the prediction of structural properties such as intrinsic disorder, secondary structures, and three-dimensional structures. This computational assessment, together with a recent community-wide experiment in assessing scoring functions for interface design, suggests that the next-generation protein-design scoring function will come from the right balance of complementary interaction terms. Such balance may be found when more negative experimental data become available as part of a training set.


Clinical and urodynamic effects of norfenefrine in women with stress incontinence.
20 women with stress incontinence were treated with an alpha-adrenoceptor stimulating agent norfenefrine (Nevadral Retard) for 3 months. The mean dose administered was 60 mg given in slow-release tablets. Significant beneficial effect on the symptom and the 'sign' of stress incontinence was found as well as a significant increase in the maximum urethral closure pressure. 7 patients (35%) became subjectively and objectively continent. Only minor side effects were observed during treatment.


Effect of gender on endothelium-dependent dilation to bradykinin in human adipose microvessels.
We examined the influence of gender and climacteric status, two coronary risk factors, on bradykinin (BK)-induced dilation in adipose arterioles from men and women of different ages [premenopausal women (Pre-W), postmenopausal women (Post-W), and similar aged men (Y-M and O-M), respectively]. We examined the responses from both omental (more closely associated with coronary disease) and subcutaneous fat. Tissues were obtained at surgery and cannulated (60 mmHg) for measurement of internal diameter. In vessels from omental tissue, dilation to BK was more sensitive in Pre-W than other groups, whereas in vessels from subcutaneous tissue, sensitivity to BK was greater in both Pre-W and Post-W compared with Y-M and O-M. Maximal dilation was similar among groups. Indomethacin (Indo; 10(-5) M) alone had no effect on dilation to BK in any groups, but Indo and N(omega)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) reduced dilation to BK in Pre-W more than in Y-M. L-NAME increased dilation to BK in subcutaneous fat from Y-M but had no effect in Post-W and O-M. Indo- and L-NAME-resistant dilation in all vessels was markedly reduced by 30 mM KCl. There was no difference in sodium nitroprusside-induced dilation among groups. We conclude that gender and climacteric state contribute to mechanisms of microvascular regulation in humans. Functional vascular differences in visceral and subcutaneous fat may underlie the proposed differential influence of these tissues on cardiovascular risk.


Mouse mammary tumor virus (MMTV), a retrovirus that exploits the immune system. Genetics of susceptibility to MMTV infection.
All animals, including humans, show differential susceptibility to infection with viruses. Study of the genetics of susceptibility or resistance to specific pathogens is most easily studied in inbred mice. We have been using mouse mammary tumor virus (MMTV), a retrovirus that causes mammary tumors in mice, to study virus/host interactions. These studies have focused on understanding the mechanisms that determine genetic susceptibility to MMTV-induced mammary tumors, the regulation of virus gene expression in vivo and how the virus is transmitted between different cell types. We have found that some endogenous MMTVs are only expressed in lymphoid tissue and that a single base pair change in the long terminal repeat of MMTV determines whether the virus is expressed in mammary gland. This expression in lymphoid cells is necessary for the infectious cycle of MMTV, and both T and B cells express and shed MMTV. Infected lymphocytes are required not only for the initial introduction of MMTV to the mammary gland, but also for virus spread at later times. Without this virus spread, mammary tumorigenesis is dramatically reduced. Mammary tumor incidence is also affected by the genetic background of the mouse and at least one gene that affects infection of both lymphocytes and mammary cells has not yet been identified. The results obtained from these studies will greatly increase our understanding of the genetic mechanisms that viruses use to infect their hosts and how genetic resistance to such viruses in the hosts occurs.


Periprocedural ischaemia during recanalisation of chronic total coronary occlusions: the influence of the transcollateral retrograde approach.
Percutaneous coronary intervention for chronic total coronary occlusions (CTO) becomes increasingly more complex with the transcollateral retrograde approach. This study assesses the effect of the retrograde approach on markers of ischaemia and clinical events. Four hundred and ninety-two consecutive procedures in 392 patients were prospectively evaluated. Before and within 18-24 hours after the PCI creatine kinase (CK) and cardiac troponin I (cTnI) were obtained. A CK increase of greater than three times the upper limit of normal (ULN) was considered a periprocedural MI. Patients with initially elevated cTnI were excluded. In 106 patients with a retrograde wire passage of the septal collaterals, the incidence of a CK or TnI increase was higher as compared to the antegrade group. Patients with septal dilatation or passage of a dilatation catheter (Corsair) showed the highest cTnI. There was no difference in cardiac death or cerebral complications between the groups with antegrade and retrograde approach within the first 30 days. Complex retrograde recanalisation procedures for CTOs lead to an increased periprocedural ischaemic burden, most likely due to obstruction of the collateral pathway, and to the increased plaque burden of complex lesions treated with the retrograde approach.


Effects of consciousness on human brain waves following binocular rivalry.
When the two eyes of an observer are exposed to conflicting stimuli, they enter into binocular rivalry and the two possible percepts will alternate in dominance. We investigated neural activity and its time course following binocular rivalry by measuring human event-related brain potentials to transitions from rivalrous to non-rivalrous stimulation. When these changes did not entail a change in conscious perception they elicited a markedly attenuated N1 component and a delayed and attenuated P3 peak as compared to percept-incompatible changes and non-rivalrous control conditions. These results suggest that in humans binocular rivalry is resolved at latest in extrastriate visual areas.


Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling.
Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçet's disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-beta, which was detected in 39% of Behçet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-beta were monitored prospectively. IFN-beta was shown to be present for 6-12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçet's and uveitis patient sera were compared to sera from normal controls. Sera from Behçet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis.


Comparison of High-flow Nasal Cannula (HFNC) and Conventional Oxygen Therapy in Obese Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis.
High-flow nasal cannula (HFNC), a new method for postoperative oxygenation, has increasingly received attention during postoperative care. However, its importance for obese patients undergoing cardiac surgery remains controversial. This systematic review and meta-analysis compared and evaluated HFNC and conventional oxygen therapy (COT) in this patient group. Literature was retrieved by searching eight public databases. Randomized controlled trials (RCTs) were selected. RevMan 5.3 was used to analyze the results and any potential bias. The primary outcome included atelectasis score at 24 h postoperatively. The secondary outcomes included PaO2/FiO2 (ratio), dyspnea score at 24 h postoperatively, intensive care unit (ICU) length of stay, and reintubation. The search strategy yielded 382 studies after duplicates were removed. Finally, 3 RCTs with a total of 526 patients were included in the present study. Compared with COT, there was no significant difference in atelectasis score, dyspnea score, reintubation, and ICU length of stay. For obese patients undergoing cardiac surgery, postoperative use of HFNC can maintain patient's oxygenation. Additional clinical studies are needed to investigate the role of HFNC in this patient group.


The feasibility of dose escalation with three-dimensional conformal radiotherapy in patients with prostatic carcinoma.
To evaluate the acute morbidity, late toxicity, and response to treatment in patients with prostate cancer treated on a phase I dose-escalation study with three-dimensional conformal radiotherapy. A group of 432 patients with stages T1c-T3 prostate cancer were treated with three-dimensional conformal radiotherapy targeting the prostate and seminal vesicles, but effectively excluding the surrounding normal tissue structures from the high-dose volume. A minimum tumor dose of 64.8 to 66.6 Gy was given to 89 patients (20%), 70.2 Gy to 199 patients (46%), 75.6 Gy to 98 patients (23%), and 81.0 Gy to 46 patients (11%). Treatment was well tolerated, and the acute toxicities and long-term complications observed were of minimal severity (grade 1 or 2) regardless of dose. Acute grade 2 rectal symptoms were observed in 15% of patients, whereas 40% developed grade 2 urinary symptoms. Among patients who received from 64.8 to 70.2 Gy, the 2-year actuarial likelihood of grade 2 late toxicity was 2% for rectal and 1% for urinary complications, compared to 11% and 5%, respectively, for those treated with doses ranging from 75.6 to 81 Gy. Only three patients (0.7%) have so far developed severe (grade 3 or 4) late urethral or rectal complications. The rate of prostate-specific antigen normalization from abnormal pretreatment levels to a value of < or = 1.0 ng/mL was used as an endpoint to evaluate the initial response to treatment. When the analysis was restricted to patients with pretreatment prostate-specific antigen levels of < or = 20 ng/mL, patients who received 70.2 Gy had a significantly higher rate of prostate-specific antigen normalization than patients who received 64.8 to 66.6 Gy. Evaluation of the prostate-specific antigen response at 75.6 Gy and 81.0 Gy was not possible because of the short follow-up time in many of these patients. Three-dimensional conformal radiotherapy technique has made it possible safely to escalate radiation doses to unprecedented levels in patients with prostatic cancer. Preliminary evidence for an improved initial prostate-specific antigen response with higher doses indicates a potential for an improved therapeutic ratio with the three-dimensional conformal radiotherapy approach.


Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy.
Patients with convexity and parasagittal (CPS) meningiomas treated with stereotactic radiosurgery (SRS) have been shown to be at risk for posttreatment symptomatic peritumoral edema (SPTE). We sought to analyze the pattern of this complication and compare it with the SPTE experienced in our patients treated with fractionated stereotactic radiotherapy. From January 2003 to October 2005, 32 patients with CPS meningiomas were treated. Thirty patients with a total of 38 lesions had sufficient follow-up for analysis. Group A (n = 14) patients were treated with single fraction SRS, and Group B (n = 16) patients were treated with fractionated stereotactic radiotherapy. The lesion volume was different between the two groups with the Group B median volume (7.46 cm) being larger than that for Group A (2.84 cm) (P = 0.0008). Conversely age, follow-up, sex, prior surgical events, number of lesions, tumor location, and atypical histology did not differ between these groups. The median marginal dose for patients in Group A was 14 Gy (range, 12.5-18 Gy). For Group B, six patients received a median marginal dose of 50.4 Gy in 28 fractions, and 10 patients received a marginal dose of 25 Gy in five fractions. Seven of the 30 patients treated in this series developed posttreatment SPTE. The incidence of SPTE in Group A (six of 14 patients) was significantly higher than that in Group B (one of 16 patients) (P = 0.031). The median time to onset of SPTE in the six patients in Group A was 4 months. In Group B, one patient had onset of SPTE in 3 months. On univariate analysis, larger tumor volume (P = 0.0014) and tumor margin dose >14 Gy in patients undergoing SRS (P = 0.031) was associated with onset of SPTE. Age, previous surgery, and tumor location were not associated with onset of SPTE. Despite larger lesion volumes, fractionated stereotactic radiotherapy is associated with less risk of posttreatment SPTE than SRS for patients with CPS meningiomas in our series. For patients treated with SRS, smaller volume and dose <14 Gy seems to be safe. Longer follow-up will be required to compare late complications and tumor control rates in these patients.