CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues.
Intraepithelial T lymphocytes have been reported as being functional in the growth of epithelial cells and also in the discrimination of aberrant cells, whereas their function against colon adenocarcinoma cells is obscure. The phenotype of colon intraepithelial T lymphocytes has been found in patients with inflammatory bowel diseases but not in patients with colon adenocarcinoma. In this study, we investigated cell surface markers of tumor-infiltrating T lymphocytes of adenocarcinoma of the colon and rectum at various grades of differentiation and intraepithelial T lymphocytes of adjacent normal colon by enzyme immunostaining. Among intraepithelial T lymphocytes of the normal colon, CD8-and TCRgammadelta-positive T lymphocytes were predominant as described. In contrast, tumor-infiltrating T lymphocytes of well-moderately differentiated adenocarcinoma of the colon and rectum were predominantly CD4- and TCRalphabeta-positive. The decrease of TCRgammadelta-positive T lymphocytes and the increase of CD4 and TCRalphabeta-positive T lymphocytes in adenocarcinoma tissues of the colon and rectum suggests that an alteration of the local immune system participates in the formation of adenoma and/or adenocarcinoma of the colon and rectum, resulting in infiltration of CD4-positive T lymphocytes that have certain activity against transformed cells.


Diethylstilbestrol counteracts barbiturate narcosis and hypothermia in male mice.
Treatment with DES one hour prior to pentobarbital injection resulted in diminution of the narcotic sleep and hypothermia usually found after pentobarbital (50 mg/kg 1) injection in male mice. The effect was biphasic: significantly countered relative to saline pretreated controls at low (.001-.10 mg/kg 1) and at high (10-50 mg/kg -1) DES doses only. Giving DES alone did not change core body temperature compared to saline injected controls, at either 25 degrees C or at 33 degrees C. At 33 degrees C, neither PeB narcosis nor body temperature loss was significantly inhibited by DES. Possible cytoplasmic, nonsex differentiated bases for these estrogen effects on barbiturate action in the brain is discussed.


Regulation of blood vessel versus lymphatic vessel growth in the cornea.
In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea. Micropellets loaded with high-dose (80 ng) or low-dose (12.5 ng) basic fibroblast growth factor (bFGF) were placed in BALB/c corneas. Angiogenic responses were analyzed by immunohistochemistry to quantify blood neovessels (BVs) and lymphatic neovessels (LVs) to 3 weeks after implantation. Areas covered by BV and LV were calculated and expressed as a percentage of the total corneal area (percentage BV and percentage LV). Hemangiogenesis (HA) and lymphangiogenesis (LA) were also assessed after antibody blockade of VEGFR-2 or VEGFR-3 Although high-dose bFGF stimulation induced a more potent angiogenic response, the relative LV (RLV=percentage LV/percentage BV x 100) was nearly identical with high- and low-doses of bFGF. Delayed LA responses induced 3 weeks after implantation of high-dose bFGF resulted in a lymphatic vessel-dominant phenotype. Interestingly, the blockade of VEGFR-2 significantly suppressed BV and LV. However, the blockade of VEGFR-3 inhibited only LV (P=0.0002) without concurrent inhibition of BV (P=0.79), thereby resulting in a blood vessel-dominant phenotype An HA-dominant corneal phenotype can be obtained in BALB/c mice 2 weeks after implantation of an 80-ng bFGF micropellet with VEGFR-3 blockade. Alternatively, an LA-dominant corneal phenotype can be obtained 3 weeks after implantation of an 80-ng bFGF micropellet without supplementary modulating agents. These models will be useful in evaluating the differential contribution of BV and LV to a variety of corneal abnormalities, including transplant rejection, wound healing and microbial keratitis.


Multi-omic Characterization of Intraspecies Variation in Laboratory and Natural Environments.
Investigation of microbial communities has led to many advances in our understanding of ecosystem function, whether that ecosystem is a subglacial lake or the human gut. Within these communities, much emphasis has been placed on interspecific variation and between-species relationships. However, with current advances in sequencing technology resulting in both the reduction in sequencing costs and the rise of shotgun metagenomic sequencing, the importance of intraspecific variation and within-species relationships is becoming realized. Our group conducts multi-omic analyses to understand how spatial structure and resource availability influence diversification within a species and the potential for long-term coexistence of multiple ecotypes within a microbial community. Here, we present examples of ecotypic variation observed in the lab and in the wild, current challenges faced when investigating intraspecies diversity, and future developments that we expect to define the field over the next 5 years.


Helix-coil stability constants for the naturally occurring amino acids in water. 15 Arginine parameters from random poly(hydroxybutylglutamine-co-L-arginine).
Water-soluble copolymers containing L-arginine and N5-(4-hydroxybutyl)-L-glutamine were prepared by copolymerization of the N-carboxy-alpha-amino acid anhydrides of Ndelta-tert-butyloxycarbonyl-L-ornithine and gamma-benzyl L-glutamate, followed by aminolysis with 4-amino-1-butanol, by removal of the tert-butyloxycarbonyl protecting group, and by treatment with O-methylisourea. The copolymers were fractionated and characterized, and the thermally induced helix-coil transitions of these copolymers were studied in water at neutral pH in the presence and in the absence of KCl. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-arginine) in aqueous solution were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The computed values of s indicate that L-arginine is a weak helix-making residue at low temperature and a weak helix-breaking residue at high temperature in aqueous solution. The results were found to be in good agreement with those obtained earlier in conformational analyses of arginyl residues in proteins.


Inhibitory effects of castration in an orthotopic model of androgen-independent prostate cancer can be mimicked and enhanced by angiogenesis inhibition.
Today, the most important treatment of advanced prostate cancer is castration; unfortunately, however, the long-term effect of this therapy is insufficient. Recent studies suggest that castration-induced prostate involution could be caused by primary effects in the prostate vasculature; therefore, we examined if antivascular treatments could mimic the effects of castration. Androgen-independent AT-1 prostate cancer cells were grown inside the ventral prostate in adult rats. Tumor-bearing animals were treated with an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor signaling, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine (ZD6474, AstraZeneca, Södertälje, Sweden), and short-term effects (after 3 days) were compared with those induced by castration. Castration caused decreased vascular density in the normal tissue surrounding the tumor and consequently increased tumor hypoxia and apoptosis, and moderately decreased tumor growth. ZD6474 treatment resulted in decreased tumor vascular density accompanied by increased tumor hypoxia, apoptosis, and decreased tumor growth, suggesting that castration and antiangiogenic therapy work through similar mechanisms. Interestingly, castration or ZD6474 alone worked by reducing vascular density in the surrounding normal tissue and ZD6474 also in the tumor. Combined treatment with castration + ZD6474 was more effective than castration and ZD6474 alone in inducing tumor hypoxia, apoptosis, necrosis, and decreasing tumor vascular density. These findings show that a drug that targets the vasculature in the tumor and in the surrounding ventral prostate lobe could mimic and even enhance the effects of castration. Our present findings thus suggest that castration + ZD6474 could be a particularly effective way to treat prostate tumors.


The Reaction of Thiyl Radical with Methyl Linoleate: Completing the Picture.
Cis lipids can be converted by thiols and free radicals into trans lipids, which are therefore a valuable tell-tale for free radical activity in the cell's lipidome. Our previous studies have shown that polyunsaturated lipids are isomerized by alkanethiyl radicals (S•) in a cycle propagated by reversible double-bond addition and terminated by radical H-abstraction from the lipid. A critical flaw in this picture has long been that the reported lipid abstraction rate from radiolysis studies is faster than addition-isomerization, implying that the "cycle" must be terminating faster than it is propagating! Herein, we resolved this longstanding puzzle by combining a detailed product analysis, with reinvestigation of the time-resolved kinetics, DFT calculations of the indicated pathways, and reformulation of the radical-stasis equations. We have determined thiol-coupled products in dilute solutions arise mainly from addition to the inside position of the bisallylic group, followed by rapid intramolecular H• transfer, yielding allylic radicals (LZZ + S• ⇄ SL• → SL'•) that are slowly reduced by thiol (SL'• + SH → SL'H + S•). The first-order grow-in rate of the L-H• signal (kexp280nm) may therefore be dominated by the addition-H-translocation rather than slower direct H•-abstraction. Steady-state kinetic analysis of the new mechanism is consistent with products and the rates and trends for polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and mixtures, with and without physiological [O2]. Implications of this new paradigm for the thiol-ene reactivity fall in an interdisciplinary research area spanning from synthetic applications to metabolomics.


Magnetic Co@g-C3N4 Core-Shells on rGO Sheets for Momentum Transfer with Catalytic Activity toward Continuous-Flow Hydrogen Generation.
Magnetic core-shell structures provide abundant opportunities for the construction of multifunctional composites. In this article, magnetic core-shells were fabricated with Co nanoparticles (NPs) as cores and g-C3N4 as shells. In the fabrication process, the Co@g-C3N4 core-shells were anchored onto the rGO nanosheets to form a Co@g-C3N4-rGO composite (CNG-I). For hydrogen generation from the hydrolysis of NaBH4 or NH3BH3, the Co NP cores act as catalytic active sites. The g-C3N4 shells protect Co NPs cores from aggregating or growing. The connection between Co NPs and rGO was strengthened by the g-C3N4 shells to prevent them from leaching or flowing away. The g-C3N4 shells also work as a cocatalyst for hydrogen generation. The magnetism of Co NPs and the shape of rGO nanosheets achieve effective momentum transfer in the external magnetic field. In the batch reactor, a higher catalytic activity was obtained for CNG-I in self-stirring mode than in magneton stirring mode. In the continuous-flow process, stable hydrogen generation was carried out with CNG-I being fixed and propelled by the external magnetic field. The separation film is unnecessary because of magnetic momentum transfer. This idea of the composite design and magnetic momentum transfer will be useful for the development of both hydrogen generation and multifunctional composite materials.


Restoration of Normal Prothrombin Time/International Normalized Ratio With Fresh Frozen Plasma in Hypocoagulable Patients.
Fresh frozen plasma (FFP) is an effective reversal agent for hypocoagulable patients. Its proven efficacy continues to prompt its usage as both a prophylactic and a therapeutic therapy. Although published guidelines encouraging the appropriate administration of FFP exist, overutilization continues. The purpose of these ex vivo studies was to determine the effects of succeeding volumes of FFP supplementation on hypocoagulable plasma prothrombin time/international normalized ratio (PT/INR). By analyzing the decline in PT/INR with varying volumes of FFP, a minimal required volume of FFP could be identified representing the optimal volume to administer while still providing therapeutic effect. A total of 497 plasma samples were screened for elevated PT/INR values and 50 samples were selected for inclusion in this experiment. The initial PTs/INRs ranged from 12.5 to 43.4 seconds/1.42 to 4.91. Subsequent declines in PT/INR values were analyzed following addition of 50, 100, and 150 µL of FFP to a fixed volume of 250 µL of plasma (26.4 ± 5.318 seconds/2.99 ± 0.603, 13.3 ± 1.077 seconds/1.51 ± 0.122, 11.2 ± 0.712 seconds/1.27 ± 0.081, and 10.3 ± 0.533 seconds/1.16 ± 0.06, respectively). A nonlinear relationship between decline in INR values and percentage of FFP supplementation was demonstrated. The greatest effect on INR was obtained after supplementation with 50 µL (49%). Doubling and tripling the volume of FFP lead to significantly lower declines in INR (16% and 8%, respectively). Analysis of variance indicated a statistical significance with subsequent volume supplementation of FFP, but marginal clinical benefits exist between the PTs/INRs obtainable with increased FFP volume administration.


Induced and repressed genes after irradiation sensitizing by pentoxyphylline.
Aim in cancer therapy is to increase the therapeutic ratio eliminating the disease while minimizing toxicity to normal tissues. Radiation therapy is a main component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX) have been evaluated to improve radiotherapy. Commonly, cells respond to radiation by the activation of specific early and late response genes as well as by inhibition of genes, which are expressed under normal conditions. A display of the genetic distinctions at the level of transcription is given here to characterize the molecular events underlying the radiosensitizing mechanisms. The method of suppression subtractive hybridization allows the visualization of both induced and repressed genes in irradiated cells compared with cells sensitized immediately after irradiation. The genes were isolated by cDNA-cloning, differential analysis and sequence similarity search. Genes involved in protein synthesis, metabolism, proteolysis and transcriptional regulation were detected. It is important that genes like KIAA280, which were only known as unidentified EST sequences before without function, but inaccessible by array technology were recovered as functional genes. Database searches for PTX-induced genes detected a human mRNA completely unknown. In case of suppressed genes, we detected several mRNAs; one thereof shows homology to a hypothetical protein possibly involved in signal transduction. A further mRNA encodes the protein BM036 supposed to associate with the E2F transcription factor. A hypothetical protein H41 was detected, which may repress the Her-2/neu receptor influencing breast cancer, gliomas and prostate tumors. Radiation combined with PTX may lead to a better prognosis by down regulation of the Her-2/neu, which will be proven by clinical studies in the near future.


Peer effects on risk behaviour: the importance of group identity.
This paper investigates whether and to what extent group identity plays a role in peer effects on risk behaviour. We run a laboratory experiment in which different levels of group identity are induced through different matching protocols (random or based on individual painting preferences) and the possibility to interact with group members via an online chat in a group task. Risk behaviour is measured by using the Bomb Risk Elicitation Task and peer influence is introduced by giving subjects feedback regarding group members' previous decisions. We find that subjects are affected by their peers when taking decisions and that group identity influences the magnitude of peer effects: painting preferences matching significantly reduces the heterogeneity in risk behaviour compared with random matching. On the other hand, introducing a group task has no significant effect on behaviour, possibly because interaction does not always contribute to enhancing group identity. Finally, relative riskiness within the group matters and individuals whose peers are riskier than they are take on average riskier decisions, even when controlling for regression to the mean.


Application of ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry for the characterization of organic aerosol: Searching for naphthenic acids.
Naphthenic acids (NAs) are naturally occurring constituents of hydrocarbon deposits (petroleum, oil sands bitumen, and crude oils), and present in any facilities that extract, process or use crude oil or bitumen for manufacturing. In the Athabasca oil sands region (AOSR) of Alberta, Canada, this diverse group of saturated acyclic, monocyclic, and polycyclic carboxylic acids is present in bitumen and in tailing ponds. Little is known about the occurrence of residual oil sands derived organic material, including NAs, in atmospheric particulate matter (PM). This work describes the optimization of an ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS) method to characterize and identify classical NAs in atmospheric PM. Under the optimum conditions, analysis of the Sigma-Aldrich technical NA STD Mix showed the absence of saturated fatty acids, while branched and cyclic NAs isomers with carbon number ranged between 10 and 30, and Z families between 0 and -12 were detected. Higher molecular weight NAs representing compounds with carbon number ranging between 30 and 40 were identified in the analyzed PM samples collected in AOSR. In contrast, isomeric branched acyclic NAs were not detected in the background (PM-R) samples collected far from AOSR. Except for fatty acids (Z=0), other Z homologues were also not detectable or present at very low concentration in the analysed PM-R samples. Preliminary examination of NA profiles showed that the composition of NAs in PM collected in close proximity to surface mining operations is predominantly "refractory" high molecular weight branched NAs, differing from that collected closer to upgraders and tailings ponds. It is suspected that dust released from the mine faces and dry tailings in the AOSR are sources of NAs to atmosphere. Further samples should be examined to confirm findings. This preliminary study presents, to our knowledge, the first direct identification of branched acyclic and cyclic NAs in atmospheric PM.


Resolving fine structures of the electric double layer of electrochemical interfaces in ionic liquids with an AFM tip modification strategy.
We report enhanced force detection selectivity based on Coulombic interactions through AFM tip modification for probing fine structures of the electric double layer (EDL) in ionic liquids. When AFM tips anchored with alkylthiol molecular layers having end groups with different charge states (e.g., -CH3, -COO(-), and -NH3(+)) are employed, Coulombic interactions between the tip and a specified layering structure are intensified or diminished depending on the polarities of the tip and the layering species. Systematic potential-dependent measurements of force curves with careful inspection of layered features and thickness analysis allows the fine structure of the EDL at the Au(111)-OMIPF6 interface to be resolved at the subionic level. The enhanced force detection selectivity provides a basis for thoroughly understanding the EDL in ionic liquids.


Degradation of oxamic acid using dimensionally stable anodes (DSA) based on a mixture of RuO2 and IrO2 nanoparticles.
Dimensionally stable anodes (DSA) have been widely used to degrade organic compounds because these surfaces promote the electrogeneration of active chlorine species in the bulk of the solution, as well as in the vicinity of the anode when NaCl is used as supporting electrolyte. In this work, the nanoparticles synthesis of IrO2 and RuO2 was performed to obtain two types of DSA electrodes named Class I and II to degrade oxamic acid. For Class I and II DSA, the nanoparticles used were synthesized separately and in the same reaction medium, respectively. Electrolysis were carried out in an open cylindrical cell without division at 25 °C, DSAs were used as anodes and a stainless-steel electrode as cathode, both elements have a geometric area of 2.8 cm2 immersed in 0.05 mol L-1 of NaCl or Na2SO4 and a current density of 3 mA cm-2 was applied for 6 h. Active chlorine species generated in the absence of oxamic acid in NaCl were also detected and quantified through ion chromatography. In Na2SO4 there was no degradation of the compound, but in NaCl the oxamic acid concentration reaching 85% with Class I DSA. The same tendency is observed in mineralization, in which Class I DSA allowed reaching a CO2 transformation close to 73%. The difference in the results occurs because with Class I DSA, more hypochlorite is generated than with Class II and therefore there is a larger amount of oxidizing species in the solution that enables the degradation and mineralization of oxamic acid.


Monoamine oxidases and related amine oxidases as phase I enzymes in the metabolism of xenobiotics.
To date most of the interest in oxidative metabolism of xenobiotics has been devoted to the role of the microsomal cytochrome P-450 system and to establish the basis for classifying and naming P450 enzymes. The contribution of amine oxidases to the metabolism of xenobiotics has been largely neglected, with the exception of the contribution of monoamine oxidases (MAOs) to the metabolism of exogenous tyramine and the studies of the "cheese effect" produced as the result of ingestion of large amounts of tyramine-containing foods under particular conditions. A review of the involvement of the mitochondrial MAOs in drug metabolism was published in 1988. Since that time, considerable additional evidence has appeared in the literature to support the contribution of MAOs to drug metabolism. In addition, the involvement of other amine oxidases in the metabolism of foreign compounds has been established. A second review on the contribution of amine oxidases to the metabolism of xenobiotics was therefore published in 1994. On an arbitrary basis, the heterogeneous class of amine oxidases can be divided into two types according to their prosthetic group: the flavineadenine dinucleotide (FAD)-dependent amine oxidases (Monoamine Oxidase and Polyamine Oxidase) and the amine oxidases not containing FAD (Semicarbazide-sensitive amine oxidases). In this overview, the contributions of these two types in xenobiotic metabolism are considered separately.


C1 CAGE detects transcription start sites and enhancer activity at single-cell resolution.
Single-cell transcriptomic profiling is a powerful tool to explore cellular heterogeneity. However, most of these methods focus on the 3'-end of polyadenylated transcripts and provide only a partial view of the transcriptome. We introduce C1 CAGE, a method for the detection of transcript 5'-ends with an original sample multiplexing strategy in the C1TM microfluidic system. We first quantifiy the performance of C1 CAGE and find it as accurate and sensitive as other methods in the C1 system. We then use it to profile promoter and enhancer activities in the cellular response to TGF-β of lung cancer cells and discover subpopulations of cells differing in their response. We also describe enhancer RNA dynamics revealing transcriptional bursts in subsets of cells with transcripts arising from either strand in a mutually exclusive manner, validated using single molecule fluorescence in situ hybridization.


Autodisplay of the La/SSB protein on LPS-free E. coli for the diagnosis of Sjögren's syndrome.
The objective of this study was to present an immunoassay for the diagnosis of Sjögren's syndrome based on the autodisplayed La/SSB protein on the outer membrane of intact E. coli (strain UT-5600) and LPS-free E. coli (ClearColi™). As the first step, an autodisplay vector (pCK002) was transfected into intact E. coli and LPS-free E. coli for comparison of efficiency of autdisplay of La/SSB. The maximal level of La/SSB expression was estimated to be similar for LPS-free E. coli and intact E. coli at different optimal induction periods. Intact E. coli was found to grow twofold faster than LPS-free E. coli, and the maximal level of expression for LPS-free E. coli was obtained with a longer induction period. When the zeta potential was measured, both intact E. coli and LPS-free E. coli showed negative values, and the autodisplay of negatively charged La/SSB protein (pI<7) on the outer membrane of intact E. coli and LPS-free E. coli resulted in a slight change in zeta potential values. E. coli with autodisplayed La/SSB protein was used for an immunoassay of anti-La/SSB antibodies for the diagnosis of Sjögren's syndrome. The surface of E. coli with the autodisplayed antigen was modified with rabbit serum and papain to prevent false positive signals because of nonspecific binding of unrelated antibodies from human serum. LPS-free E. coli with autodisplayed La/SSB protein yielded sensitivity and selectivity of 81.6% and 78.6%, respectively. The Bland-Altman test showed that the immunoassays based on LPS-free E. coli and intact E. coli with autodisplayed La/SSB protein were statistically equivalent to a clinical immunoassay for detection of anti-La/SSB antibodies (confidence coefficient 95%).


Habit-specific locus of control scales for drinking, smoking, and eating.
The internal consistencies of three habit-specific locus of control scales measuring drinking, smoking, and eating behavior were evaluated using coefficient alpha. The three scales, along with Rotter's 1-E scale, were administered to 202 undergraduate students. Estimates indicated the scales showed reasonably high internal consistency. Scores on the smoking and drinking scales had the lowest correlations with scores on Rotter's generalized measure. Mean drinking scale scores were lower than those for smoking and eating, suggesting that people judge drinking to be under more personal control. The implications of habit-specific expectancies, particularly with regard to habit disorders, are discussed.


A mathematical model of cell movement and clustering due to chemotaxis.
This paper presents a numerical method for modelling cell migration and aggregation due to chemotaxis where the cell is attracted towards the direction in which the concentration of a chemical signal is increasing. In the model presented here, each cell is represented by a system of springs connected together at node points on the cell's membrane and on the boundary of the cell's nucleus. The nodes located on a cell's membrane are subject to a force which is proportional to the gradient of the concentration of the chemical signal which mimics the behaviour of the chemical receptors in the cell's membrane. In particular, the model developed here will consider what happens when two (or more) cells collide and how their membranes connect to each other to form clusters of cells. The methods described in this paper will be illustrated with a number of typical examples simulating cells moving in response to a chemical signal and how they combine to form clusters.


IL-2/Anti-IL-2 Complex Attenuates Inflammation and BBB Disruption in Mice Subjected to Traumatic Brain Injury.
Traumatic brain injury (TBI) induces the excessive inflammation and disruption of blood-brain barrier, both of which are partially mediated by the activation of microglia and release of inflammatory cytokines. Previous reports showed that administration of regulatory T cells (Tregs) could suppress inflammation and promote neurological function recovery, and that the IL-2/anti-IL-2 complex (IL-2C) could increase the number of Tregs. Thus, we hypothesized that IL-2C-mediated expansion of Tregs would be beneficial in mice subjected to TBI. In this study, mice received an intraperitoneal injection of IL-2C for three consecutive days. We observed that IL-2C dose-dependently increased Tregs without affecting the populations of CD4, CD8, or natural killer cells. IL-2C could improve the neurological recovery and reduce brain edema, tissue loss, neutrophils infiltration, and tight junction proteins degradation. Furthermore, this complex could also reduce the expression of CD16/32, IL-1β, or TNF-α, and elevate the expression of CD206, arginase 1, or TGF-β. These results suggest that IL-2C could be a potential therapeutic method to alleviate excessive inflammation and maintain blood vessel stability after TBI.


Oral Sweet's syndrome occurring in ulcerative colitis.
A man aged 78 years presented with a 3-week history of tender mouth ulceration associated with arthralgia and weight loss. He had ulcerative colitis that was diagnosed 10 years previously which was well controlled on adalimumab 40 mg fortnightly. Biochemical and haematological investigations showed raised inflammatory markers (CRP 105) and a marked neutrophilia (10). On examination, the patient had severe oral ulceration involving the anterior tongue and lips. In addition, on cutaneous examination had tender erythematous nodules involving the forehead. Histology from a diagnostic punch biopsy showed marked dermal oedema with an inflammatory infiltrate consisting of neutrophils. Our working diagnosis was therefore oral Sweet's syndrome. The patient was then started on oral prednisolone and later received colchicine which led to a complete resolution of symptoms.


Ultraviolet spectrometer and polarimeter for the Solar Maximum Mission.
The detailed optical design of the Solar Maximum Mission-Ultraviolet Spectrometer and Polarimeter is discussed in conjunction with the scientific objectives that led to the design. The instrument consists of a 1.8-m effective focal length aplanatic Gregorian telescope followed by a 1-m Ebert spectrometer. The design of the Stokes polarimeter is also discussed.


First autochthonous case of canine visceral leishmaniasis in Rondônia, Brazil, a region with no history of visceral leishmaniasis.
This report describes the first autochthonous case of canine visceral leishmaniasis in Rondônia, northern Brazil. A canine resident of the municipality of Cacoal, with clinical signs and symptoms of visceral leishmaniasis, was treated by a veterinarian. Samples were analyzed by a reference laboratory. Dual-path platform (DPP) assay, indirect immunofluorescence technique (IIT), enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), isolation in a culture medium, and direct parasitological analysis were performed. DPP assay, IIT, and ELISA revealed positive results for Leishmania; PCR identified the species as Leishmania infantum. Based on the clinical presentation and test results, canine visceral leishmaniasis was diagnosed.


Quality of Decision Support in Computerized Provider Order Entry: Systematic Literature Review.
Computerized decision support systems have raised a lot of hopes and expectations in the field of order entry. Although there are numerous studies reporting positive impacts, concerns are increasingly high about alert fatigue and effective impacts of these systems. One of the root causes of fatigue alert reported is the low clinical relevance of these alerts. The objective of this systematic review was to assess the reported positive predictive value (PPV), as a proxy to clinical relevance, of decision support systems in computerized provider order entry (CPOE). A systematic search of the scientific literature published between February 2009 and March 2015 on CPOE, clinical decision support systems, and the predictive value associated with alert fatigue was conducted using PubMed database. Inclusion criteria were as follows: English language, full text available (free or pay for access), assessed medication, direct or indirect level of predictive value, sensitivity, or specificity. When possible with the information provided, PPV was calculated or evaluated. Additive queries on PubMed retrieved 928 candidate papers. Of these, 376 were eligible based on abstract. Finally, 26 studies qualified for a full-text review, and 17 provided enough information for the study objectives. An additional 4 papers were added from the references of the reviewed papers. The results demonstrate massive variations in PPVs ranging from 8% to 83% according to the object of the decision support, with most results between 20% and 40%. The best results were observed when patients' characteristics, such as comorbidity or laboratory test results, were taken into account. There was also an important variation in sensitivity, ranging from 38% to 91%. There is increasing reporting of alerts override in CPOE decision support. Several causes are discussed in the literature, the most important one being the clinical relevance of alerts. In this paper, we tried to assess formally the clinical relevance of alerts, using a near-strong proxy, which is the PPV of alerts, or any way to express it such as the rate of true and false positive alerts. In doing this literature review, three inferences were drawn. First, very few papers report direct or enough indirect elements that support the use or the computation of PPV, which is a gold standard for all diagnostic tools in medicine and should be systematically reported for decision support. Second, the PPV varies a lot according to the typology of decision support, so that overall rates are not useful, but must be reported by the type of alert. Finally, in general, the PPVs are below or near 50%, which can be considered as very low.


Chemoprophylaxis for venous thromboembolism prevention: concerns regarding efficacy and ethics.
Chemoprophylaxis has been recommended for plastic surgery patients judged to be at increased risk for venous thromboembolism. Several investigators have encountered this complication in patients despite anticoagulation therapy. An increased rate of complications related to postoperative bleeding has been reported. This article examines the efficacy and safety of this intervention, along with ethical considerations, in an attempt to determine whether any benefits of chemoprophylaxis justify the additional risks. The statistical methods and conclusion of the Venous Thromboembolism Prevention Study are challenged. Other preventative measures that do not cause negative side effects are discussed as safer alternatives.


Impact of cirrhosis on the neuropsychological test performance of alcoholics.
Alcoholics and nonalcoholics with biopsy-proven cirrhosis were compared to each other and to a normal control group on a comprehensive battery of neuropsychological tests. No systematic differences were found between the two liver disease groups. These results indicate that a history of alcoholism does not substantially contribute to the manifest neuropsychological deficits beyond that due to a coexistent hepatic encephalopathy.


[Changes of motor function in patients with cerebral palsy during the treatment using the intensive neurophysiological rehabilitation system].
Changes in gross motor function during the intensive neurophysiological rehabilitation were studied in 61 patients, aged from 2 to 15 years, with spastic forms of cerebral palsy. All patients were examined before and at the end of a two-week course of treatment using the Gross Motor Function Measurement GMFM-66 Item Sets test to calculate motor development scores. Statistical analysis indicates a significant increase in the level of motor development of children after treatment from 45.1 to 47.6 (p > 0.01). The most significant progress was noted in patients at level II of Gross Motor Function Classification System. The score of motor development has increased from 66.2 to 69.6 (p < 0.01). The results suggest the effectiveness of the Intensive Neurophysiological Rehabilitation System for the improvement of gross motor functions in patients with cerebral palsy. It is necessary to continue this study according to the requirements of evidence-based medicine.


Henoch-Schönlein purpura in rheumatoid arthritis.
This is the first report of Henoch-Schönlein purpura associated with permanent joint damage due to rheumatoid arthritis, which was observed in 3 of the 10 adults we treated for Henoch-Schönlein purpura since 1974. Each of 3 women had been admitted with palpable purpura of the lower extremities. The diagnosis was based on various findings including arthralgia, stiffness, and/or swelling of the joints, and on the results of radiographic, immunofluorescence and other studies. Renal biopsy revealed slight mesangial proliferation in 2 of the patients. The nephropathy did not deteriorate following discharge. However, bilateral swelling of the wrists with destructive joint changes was subsequently observed on radiographs in all patients. Since 2 patients showed positivity for human leukocyte antigen DR4, this antigen may have been a genetic factor in the joint disease in these patients.


A comparison of three models for the diffusion of oxygen in electrolyte solutions.
Diffusion of oxygen through aqueous solutions is of great importance in biological systems. In this work, three models for the diffusion of oxygen through aqueous salt solutions are compared. One model uses mole fraction as the driving force (Fick's Law) and another uses chemical potential. The third model uses the gradient in oxygen activity as the driving force. This new model was chosen because of the availability of oxygen electrodes which directly measure oxygen activity in aqueous solution. These models have been used to reevaluate the technique of measuring O(2) diffusivities. We show that Pick's Law diffusion coefficients do not vary strongly with salt concentration as was erroneously reported in the literature. In addition, we compare the predicted O(2) fluxes of the three models over a wide range in O(2) concentrations. For oxygen concentrations of biological interest, the three models give identical predictions of the flux.


Alteration of alpha1-adrenoceptor subtypes in aortas of 12-month-old spontaneously hypertensive rats.
Alterations in alpha1-adrenoceptor subtypes in aortas from 12-month-old spontaneously hypertensive rats (SHR) were studied in functional studies and RNase protection assays. The norepinephrine-induced contraction, including maximum response and pD2 values, was not significantly different between the SHR and age-matched Kyoto Wistar (WKY) rats. The pA2 values of the alpha1D-adrenoceptor subtype-selective antagonist BMY7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)dec ane-7,9-dionedihydrochloride) were increased from 8.10 +/- 0.12 in WKY rats to 8.45 +/- 0.13 in SHR (P < 0.05). The pA2 values of the alpha1A-adrenoceptor subtype-selective antagonist RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dim ethyl-1H-indole-3-ethanamine hydrochloride) were reduced from 8.52 +/- 0.20 in WKY rats to 7.82 +/- 0.18 in SHR (P < 0.05), whereas the pA2 values of the alpha1A/alpha1D-adrenoceptor subtype-selective antagonist WB4101 (2-(2,6-dimethoxphenoxyethyl)-aminomethyl-1,4 benzodioxane) were not significantly different between WKY rats and SHR (9.05 +/- 0.22 versus 9.27 +/- 0.15, P > 0.05). Preincubation of preparations in 50 microM chloroethylclonidine for 30 min irreversibly inhibited the norepinephrine-induced response more profoundly in aortas from SHR than in aortas from WKY rats. The results of RNase protection assays showed that mRNAs for alpha1A- and alpha1B-adrenoceptor subtypes were decreased and that mRNA for the alpha1D-adrenoceptor subtype was increased in aortas from SHR compared with WKY rats. The results suggested that the alpha1A-adrenoceptor subtype was decreased and the alpha1D-adrenoceptor subtype was increased in aortas of 12-month-old SHR.


A modified tunnel technique to treat multiple gingival recessions: Case Series.
This case series reports a modified tunnel technique with connective tissue graft for the root coverage of multiple Miller Class I, II, and III gingival recessions. The modified approach presents an innovative suture technique to improve the stability and position of the graft. Ten patients with multiple gingival recessions (n=85 teeth) received surgical root coverage treatment. The gingival recession height and width were measured and presented as median, minimum, and maximum values. The percentage of the root coverage after at least 12 months expressed the treatment effectiveness. The Shapiro-Wilk test evaluated the normality; pared Wilcoxon test determined the exact P-value for the differences in the height of the gingival recession before and after surgical treatment (α = 0.05). An average of 97.9% (± 5.6%, p < 0.0001) root coverage after treatment occurred, and 73 out of 85 recessions presented complete root coverage after 12 months. Treatment of Miller class I and II gingival recessions resulted in root coverage higher than 99 and class III higher than 95% (p < 0.0001). The presented case series report the efficacy of a modified surgical technique promoting more than 95% of root coverage after 12 months in multiple Miller Class I, II, and III gingival recessions. Well-designed blind randomized controlled trials are needed to validate the proposed technique.


In Vitro and In Vivo Assessment of the Efficacy of Bromoageliferin, an Alkaloid Isolated from the Sponge Agelas dilatata, against Pseudomonas aeruginosa.
The pyrrole-imidazoles, a group of alkaloids commonly found in marine sponges belonging to the genus Agelas, display a wide range of biological activities. Herein, we report the first chemical study of the secondary metabolites of the sponge A. dilatata from the coastal area of the Yucatan Peninsula (Mexico). In this study, we isolated eight known alkaloids from an organic extract of the sponge. We used NMR and MS analysis and comparison with existing databases to characterize the alkaloids: ageliferin (1), bromoageliferin (2), dibromoageliferin (3), sceptrin (4), nakamuric acid (5), 4-bromo-1H-pyrrole-2-carboxylic acid (6), 4,5-dibromopyrrole-2-carboxylic acid (7) and 3,7-dimethylisoguanine (8). We also evaluated, for the first time, the activity of these alkaloids against the most problematic multidrug-resistant (MDR) pathogens, i.e., the Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Bromoageliferin (2) displayed significant activity against P. aeruginosa. Comparison of the antibacterial activity of ageliferins 1-3 (of similar structure) against P. aeruginosa revealed some relationship between structure and activity. Furthermore, in in vitro assays, 2 inhibited growth and biofilm production in clinical strains of P. aeruginosa. Moreover, 2 increased the survival time in an in vivo Galleria mellonella model of infection. The findings confirm bromoageliferin (2) as a potential lead for designing new antibacterial drugs.


[The local and sensual conditions of delay of voice breaking in adolescent boys].
Disorders of voice breaking in adolescent boys (mutational dysphonia) could be a result of local, hormonal, neuropsychiatric or sensual factors. The aim of this paper was the voice assessment of three subjects with incomplete mutation with particular additional factors, disturbing hearing, voice and speech: like hearing loss, hyperfunctional childhood dysphonia and speech dysfluency. Diagnostics included complete phoniatric examination with perceptive estimation, videostroboscopy and acoustic voice analysis, done before and after treatment. Rehabilitation process results were well seen in perceptive and objective voice analysis except significant improvement of fundamental frequency average. Analysis of incomplete mutation etiological factors need special attention due to coexist with another voice, speech and hearing disorders, which undergo with high tension of voice organ muscles or with the lack of phonation auditory feedback.


Double Balloon Cervical Ripening Catheter for Control of Massive Hemorrhage in a Cervical Ectopic Pregnancy.
Cervical pregnancy can be complicated by perfuse vaginal bleeding. Mechanical compression directed at tamponing the cervical vessels can control hemostasis. There are several types of balloon catheters that have been described for cervical compression. However use of a double balloon catheter is a novel approach for cervical tamponade, as one balloon is positioned below the external cervical os and the second balloon is situated above in the internal cervical os. This compresses the cervix from internal os to external os between the two balloons, forming a "cervical sandwich." We describe this method of cervical tamponade using a silicone double balloon cervical ripening catheter that rapidly controlled hemorrhage in a patient that failed conservative management with methotrexate.


Social Determinants of Health: An Evaluation of Risk Factors Associated With Inpatient Presentations in the United States.
Social Determinants of Health (SDoH) are socioeconomic indicators that directly or indirectly impact individual and community health outcomes. The distribution of most of these indicators within communities can be traced to public policies. These public policies often lead to diverse inequities with varying impacts on communities across the country. The inequities that arise because of specific public policies can be associated with increased risk factors and poor health outcomes among communities at high risk for these indicators. This study examined inpatient hospitalization and SDoH indicators that put individuals at risk of poor health outcomes. We utilized the National Inpatient Sample (NIS) databases 2012-2014 and 2016-2017 through the Healthcare Cost and Utilization Project (HCUP). The NIS datasets are de-identified to ensure patients' privacy. The HCUP-NIS dataset is a well-established sizable all-payer inpatient dataset for national estimates. It includes primary, secondary inpatient diagnoses as well as demographic information. SDoH indicators were identified using the International Classification of Diseases (ICD), versions 9 and 10 diagnosis codes. The relationship between SDoH indicators such as housing, psychosocial, healthcare access, upbringing, unemployment, social factors, gender, race, income, region, payer, age group, mortality, and severity was evaluated in a regression analysis. A total of 3,002,557 (2012-2014) and 1,254,899 (2016-2017) cases were included in this study. Mental diseases (p < 0.001) were high between 2012-2014 (OR 18.8, 95% CI 18.20-19.42) and 2016-2017 (OR 4.11, 95% CI 3.99-4.23). Native Americans had odds of presentation (p < 0.001) with SDoH indicator between 2012-2014 (OR 1.15, 95% CI 1.12-1.18) and 2016-2017 (OR 1.75, 95% CI 1.70-1.79). The odds of presentation among long income group were high compared to other income categories (p < 0.001) between 2012-2014 (OR 1.15, 95% CI 1.15-1.16) and 2016-2017 (OR 1.26, 95% CI 1.28-1.32). In conclusion, disparities, severity, and mortality risk at presentation were high among minority communities, males, and low-income demographics across all regions of United States.


Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin.
Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.


Age as a factor in the complication rate after removal of unerupted/impacted third molars at the time of mandibular sagittal split osteotomy.
This study was designed to investigate the effect that the presence of an unerupted third molar has on the mandibular sagittal split osteotomy (SSO). One operator performed 139 SSOs (70 right side and 69 left side) in 70 patients during a period of 6 months. Data related to gender, age, presence or absence of unerupted third molar teeth, split difficulty during SSO, fracture complications of the segment, neurovascular bundle involvement at surgery, removal of unerupted third molar teeth, and the postoperative recovery of nerve function were recorded. The SSOs evaluated as technically difficult were significantly more prevalent in mandibles with unerupted third molar teeth. All fractures (4) occurred in the younger age group (<20 years) with unerupted third molars present at the time of surgery. Although inferior alveolar nerve recovery was slower in the patients in whom the unerupted third molar teeth were present at the time of surgery due to increased frequency of neurovascular bundle manipulation, the recovery rates at 1 year were equal. The presence of unerupted third molar teeth increases the degree of difficulty of the SSO. Fracture of proximal and/or distal segments during SSO tend to occur more frequently in the younger age group (<20 years) with an unerupted third molar present.


Neonatal blood pressures.
Arterial blood pressures were taken by the Doppler ultrasound method in 134 unselected mature neonates (birthweights 2,600-3,900 grams) who were managed in the same manner after birth. Blood pressures were measured at 3-5, 10 and 30 minutes of life and, if indicated, intermittently during the next 24-48 h. Left and right arm pressures were identical or differed by only 1-2 mm Hg. Lower than normal blood pressures were found in 4 groups of infants: those born by cesarean section, those recovering from intrauterine asphyxia, those exposed to maternal anti-hypertensive therapy, and those whose mothers received thiopental within four minutes of delivery. Return of the low pressures to within the normal range was fastest following thiopental induction in the absence of fetal asphyxia and slowest after antihypertensive therapy.


Air blast-induced evaporative water loss from human dentine, in vitro.
Short air blasts are commonly used to test for dentine sensitivity but their mechanism of action is poorly understood. In this study, evaporative water loss of teeth in vitro was measured under spontaneous conditions and during air blasts from three-way dental air syringes. Air blasts induced a 15-30-fold increase in evaporative water loss, which varied inversely with distance from the tooth and directly with air temperature. As water evaporation occurs readily across smear layers, which greatly impede bulk fluid movement, the use of air blasts may overestimate dentine sensitivity. Sustained air blasts may remove enough fluid from the pulp-dentine complex to cause disruption of odontoblasts and changes in pulpal blood flow.


Does the media (also) keep the score? Media-based exposure to the Russian-Ukrainian war and mental health in Portugal.
The Russian-Ukrainian war (RUW) is responsible for extensive individual suffering and a socio-economic impact on the world and is reshaping global affairs. Many studies have focused on direct exposure to conflict and several public health policies have been devised. Nonetheless, indirect exposure through media has received minimal attention and there is limited evidence that mental health symptoms and disorders may arise as a result. We explored the role of voluntary or involuntary media-based exposure to the RUW on individuals' mental health including stress symptoms, coping strategies, daily functioning, and worries across demographic variables. In our sample, subjects with involuntary and higher amount of exposure seem to have higher stress symptoms. Also, those who had previous ruminations on war issues could be at risk of developing more post-traumatic stress symptoms. Therefore, media appears to be a conduit that spreads negative consequences of community trauma beyond directly affected communities.


Risk factors of ocular hypertension and glaucoma. The Casteldaccia Eye Study.
A case-control study was planned as a part of the Casteldaccia Eye Study in order to investigate about risk factors of ocular hypertension and glaucoma. Cases were 44 subjects with glaucoma or intraocular pressure of 24 mm Hg or more. Controls were 220 subjects with intraocular pressure of 20 mm Hg or less and no signs of glaucoma. A number of environmental, behavioral, systemic and ocular variables were studied. Among the others we investigated the following: sunlight exposure, smoking, alcohol intake, pregnancies, systemic hypertension, diabetes, use of corticosteroids, refractive status, anterior chamber depth, lens nuclear sclerosis, iris color and texture. After univariate analysis the use of ocular corticosteroids and antibiotics, myopia, shallow anterior chamber and myopic macular degeneration were associated with ocular hypertension or glaucoma. However, the logistic regression showed that only the use of ocular corticosteroids (odds ratio = 7.79) and the myopia (odds ratio = 5.56) were independently associated.


Singular self-preserving regimes of coagulation processes.
The late stages of the time evolution of disperse systems when either coagulation alone governs the temporal changes of particle mass spectra or simultaneous condensation complicates the evolution process are studied under the assumption that the condensation efficiencies and coagulation kernels are homogeneous functions of the particle masses, with gamma and lambda being their homogeneity exponents, respectively. In considering the asymptotic behavior of the particle mass distributions the renormalization-group approach is applied to three types of coagulating systems: free coagulating systems in which coagulation alone is responsible for disperse particle growth; source-enhanced coagulating systems, where an external spacially uniform source permanently adds fresh small particles, with the particle production being a power function of time; and coagulating-condensing systems in which a condensation process accompanies the coagulation growth of disperse particles. The particle mass distributions of the form N(A)(g,t)=A(t)psi(gB(t)) are shown to describe the asymptotic regimes of particle growth in all the three types of coagulating systems (g is the particle mass). The functions A(t) and B(t) are normally power functions of time whose power exponents are found for all possible regimes of coagulation and condensation as the functions of lambda and gamma. The equations for the universality function psi(x) are formulated. It is shown that in many cases psi(x) proportional, variant x(-sigma) (sigma > 1) at small x, i.e., the particle mass distributions are singular. The power exponent sigma is expressed in terms of lambda and gamma. Two exactly soluble models illustrate the general theoretical consideration.


Biobjective Optimization Algorithms Using Neumann Series Expansion for Engineering Design.
In this paper, two novel algorithms are designed for solving biobjective optimization engineering problems. In order to obtain the optimal solutions of the biobjective optimization problems in a fast and accurate manner, the algorithms, which have combined Newton's method with Neumann series expansion as well as the weighted sum method, are applied to deal with two objectives, and the Pareto optimal front is achieved through adjusting weighted factors. Theoretical analysis and numerical examples demonstrate the validity and effectiveness of the proposed algorithms. Moreover, an effective biobjective optimization strategy, which is based upon the two algorithms and the surrogate model method, is developed for engineering problems. The effectiveness of the optimization strategy is proved by its application to the optimal design of the dummy head structure in the car crash experiments.


Inhibition of O-linked N-acetylglucosamine transferase activity in PC12 cells - A molecular mechanism of organophosphate flame retardants developmental neurotoxicity.
Organophosphate flame retardants (OPFRs), as alternatives of brominated flame retardants, can cause neurodevelopmental effects similar to organophosphate pesticides. However, the molecular mechanisms underlying the toxicity remain elusive. O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) regulates numerous neural processes through the O-GlcNAcylation modification of nuclear and cytoplasmic proteins. In this study, we aimed to investigate the molecular mechanisms accounting for the developmental neurotoxicity of OPFRs by identifying potential targets of OPFRs and the attendant effects. Twelve OPFRs were evaluated for inhibition of OGT activity using an electrochemical biosensor. Their potency differed with substituent groups. The alkyl group substituted OPFRs had no inhibitory effect. Instead, the six OPFRs substituted with aromatic or chlorinated alkyl groups inhibited OGT activity significantly, with tri-m-cresyl phosphate (TCrP) being the strongest. The six OPFRs (0-100 μM exposure) also inhibited OGT activity in PC12 cells and decreased protein O-GlcNAcylation level. Inhibition of OGT by OPFRs might be involved in the subsequent toxic effects, including intracellular reactive oxygen species (ROS), calcium level, as well as cell proliferation and autophagy. Molecular docking of the OGT/OPFR complexes provided rationales for the difference in their structure-dependent inhibition potency. Our findings may provide a new biological target of OPFRs in their neurotoxicological actions, which might be a major molecular mechanism of OPFRs developmental neurotoxicity.


CT-based radiomic phenotypes of lung adenocarcinoma: a preliminary comparative analysis with targeted next-generation sequencing.
This study aimed to explore the relationship between computed tomography (CT)-based radiomic phenotypes and genomic profiles, including expression of programmed cell death-ligand 1 (PD-L1) and the 10 major genes, such as epidermal growth factor receptor (EGFR), tumor protein 53 (TP53), and Kirsten rat sarcoma viral oncogene (KRAS), in patients with lung adenocarcinoma (LUAD). In total, 288 consecutive patients with pathologically confirmed LUAD were enrolled in this retrospective study. Radiomic features were extracted from preoperative CT images, and targeted genomic data were profiled through next-generation sequencing. PD-L1 expression was assessed by immunohistochemistry staining (chi-square test or Fisher's exact test for categorical data and the Kruskal-Wallis test for continuous data). A total of 1,013 radiomic features were obtained from each patient's CT images. Consensus clustering was used to cluster patients on the basis of radiomic features. The 288 patients were classified according to consensus clustering into four radiomic phenotypes: Cluster 1 (n = 11) involving mainly large solid masses with a maximum diameter of 5.1 ± 2.0 cm; Clusters 2 and 3 involving mainly part-solid and solid masses with maximum diameters of 2.1 ± 1.4 cm and 2.1 ± 0.9 cm, respectively; and Cluster 4 involving mostly small ground-glass opacity lesions with a maximum diameter of 1.0 ± 0.9 cm. Differences in maximum diameter, PD-L1 expression, and TP53, EGFR, BRAF, ROS1, and ERBB2 mutations among the four clusters were statistically significant. Regarding targeted therapy and immunotherapy, EGFR mutations were highest in Cluster 2 (73.1%); PD-L1 expression was highest in Cluster 1 (45.5%). Our findings provide evidence that CT-based radiomic phenotypes could non-invasively identify LUADs with different molecular characteristics, showing the potential to provide personalized treatment decision-making support for LUAD patients.


Characteristics and predictors of infusion-related reactions to rituximab in patients with B-cell non-Hodgkin lymphoma.
This retrospective study aimed to assess the characteristics and predictors of infusion-related reactions (IRRs) to rituximab in patients with B-cell non-Hodgkin lymphoma (B-NHL). The medical records of adult patients with B-NHL who received their first cycle of rituximab from August 2020 to August 2022 were reviewed. IRRs were defined as any signs experienced by patients during rituximab infusion and graded according to the Common Terminology Criteria for Adverse Events. During the study period, 334 patients were included; among them, 100 patients (30%) developed IRRs (mean age 54.7 (SD 13.2) years). Of the reported IRRs, 90% were grade II reactions, and 10% were grade III reactions. The multivariate analysis identified indolent lymphoma [OR 1.90, p = 0.025], no hydrocortisone as premedication [OR 3.03, p = 0.029], thrombocytopenia [OR 2.55, p = 0.009], and absolute lymphocyte count ≥ 2000 lymphocytes/microL [OR 1.74, p = 0.045] as independent predictors for IRRs.


Effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisations for cardiovascular disease, cerebrovascular disease and pneumonia in the elderly.
Annual circulation of influenza virus coincides with a peak in cardiovascular and pneumonia mortality/morbidity. This study aimed to determine the effectiveness of MF59-adjuvanted subunit influenza vaccine in preventing hospitalisation due to acute coronary syndrome (ACS), cerebrovascular accident (CVA) and pneumonia in the elderly. Three case-control studies were performed during the 2004-2005 influenza season in three health districts in Valencia, Spain (total elderly [>64 years of age] population: n=105,454). Controls were patients admitted for an acute surgical process or trauma within 10 days of case admission. In total, 159 patients were hospitalised for ACS, 148 for CVA and 242 for pneumonia. The risk of hospitalisation after the start of the influenza season was significantly lower in vaccinated patients compared with non-vaccinated patients (adjusted odds ratios: 0.13 [P=0.013] for ACS; 0.07 [P=0.007] for CVA; 0.31 [P=0.005] for pneumonia). During peak virus circulation, vaccination with MF59-adjuvanted subunit influenza vaccine was associated with an 87% relative risk reduction in hospitalisation for ACS, 93% for CVA, and 69% for pneumonia.


Dynamical Study of the Dissociative Chemisorption of CHD3 on Pd(111).
The specific reaction parameter (SRP) approach to density functional theory has been shown to model reactions of polyatomic molecules with metal surfaces important for heterogeneous catalysis in the industry with chemical accuracy. However, transferability of the SRP functional among systems in which methane interacts with group 10 metals remains unclear for methane + Pd(111). Therefore, in this work, predictions have been made for the reaction of CHD3 on Pd(111) using Born-Oppenheimer molecular dynamics while also performing a rough comparison with experimental data for CH4 + Pd(111) obtained for lower incidence energies. Hopefully, future experiments can test the transferability of the SRP functional among group 10 metals also for Pd(111). We found that the reactivity of CHD3 on Pd(111) is intermediate between and similar to either Pt(111) or Ni(111), depending on the incidence energy and the initial vibrational state distribution. This is surprising because the barrier height and experiments performed at lower incidence energies than investigated here suggest that the reactivity of Pd(111) should be similar to that of Pt(111) only. The relative decrease in the reactivity of Pd(111) at high incidence energies is attributed to site specificity of the reaction and to dynamical effects such as the bobsled effect and energy transfer from methane to the surface.


Erdosteine protection against cigarette smoking-induced functional antiprotease deficiency in human bronchiolo-alveolar structures.
Cigarette smoke reduces the elastase inhibitory capacity (EIC) of alpha 1-antitrypsin by an oxidative process and thus may promote the pathogenetic bases for the development of pulmonary emphysema. The present study was performed with the aim to evaluate the protective activity of erdosteine, a novel thiol derivative endowed with reducing properties, against the functional inactivation of alpha 1-AT induced by smoke. For the purpose, a double-blind study was carried out on 24 healthy smokers divided into two groups orally treated with placebo or erdosteine 900 mg/day for one month. The antigenic and functional alpha 1-AT was measured in bronchoalveolar (BAL) fluids and sera before and shortly after the last treatment. The findings indicate that the loss of EIC of alpha 1-AT in BAL fluids can be partially prevented by pharmacological treatment. In this regard, it is reasonable to hypothesize that the reestablishment of the oxidant-antioxidant balance in favor of the antioxidants would be useful as a therapeutic strategy to arrest or at least delay the emphysematous process.


Low-dose spiral CT: application to surface-rendered three-dimensional imaging of central airways.
The purpose of this work was to assess the utility of low-dose spiral CT for three-dimensional imaging of the central airways. Spiral CT was performed in 15 patients using two tube currents (50 and 240 mA), producing 30 CT data sets. Surface-rendered virtual bronchoscopy (VB) and shaded surface display (SSD) images were assessed by three radiologists for image quality. The radiologists were also asked to compare 15 matched pairs each of 50 and 240 mA VB and SSD images, blindly select the 240 mA image, and record differences in diagnostic quality between the matched images. No significant difference in image quality was noted with 50 or 240 mA. Only 51.1% of 240 mA SSD and 51.1% of 240 mA VB images were correctly identified. Differences in diagnostic quality, noted in 84.4% of SSD and 33% of VB image pairs, were not ascribed to image noise. Image quality of surface-rendered three-dimensional images of the central airways is preserved using a lower tube current.


Gene fusion and overlapping reading frames in the mammalian genes for 4E-BP3 and MASK.
4E-BP3 is a member of the eukaryotic initiation factor (eIF) 4F-binding protein family of translational repressors. eIF4E-binding proteins (4E-BPs) inhibit translation initiation by sequestering eIF4E, the cap-binding protein, from eIF4G thus preventing ribosome recruitment to the mRNA. Previous analysis of 4E-BP3 expression uncovered an 8.5-kb mRNA variant of unknown origin. To study this splice variant, we determined the structure of the genomic locus encoding human 4E-BP3 (EIF4EBP3). EIF4EBP3 is located on human chromosome 5q31.3 and comprises three exons (A, B, and C) and two introns. Exon B contains the region of the open reading frame responsible for eIF4E binding. GenBank searches revealed multiple expressed sequence tags originating from the alternative splicing of exon B with unidentified upstream exons. Further studies revealed that the 8.5-kb transcript arises from the fusion of EIF4EBP3 with the mammalian homologue of Drosophila MASK (multiple ankyrin repeats, single KH domain), which is crucial for photoreceptor differentiation, cell survival, and proliferation. Surprisingly, the open reading frame of the MASK-BP3 transcript is different from that of 4E-BP3, which indicates that exon B is translated using an alternative reading frame. A gene fusion similar to that of MASK and EIF4EBP3 has been reported only once in mammals for the UEV1-Kua transcript. The use of an alternative reading frame is also very rare, having been described for two loci, INK4a/ARF and XLalphas/ALEX. The simultaneous exploitation of both mechanisms underscores the flexibility of mammalian genomes and has important implications for the functional analysis of 4E-BP3 and MASK. Interestingly, both eIF4E and MASK are downstream effectors of the Ras/MAPK pathway, which provides a rationale for the MASK-BP3 fusion in mammals.


Three-dimensional rotating flow of carbon nanotubes with Darcy-Forchheimer porous medium.
Here we are concerned with the Darcy-Forchheimer three-dimensional flow of carbon nanotubes in a rotating frame. Flow is generated by stretching of the surface. Xue model is adopted for nanofluid transport mechanism. Results for single wall carbon nanotubes (SWCNTs) and multi wall carbon nanotubes are achieved and compared. Flow saturating porous space obeys Darcy-Forchheimer expression. Boundary layer approximations are invoked to simplify governing partial differential system. Optimal homotopy analysis method (OHAM) is utilized for solutions of governing model. The optimal values of auxiliary parameters are computed. Plots have been displayed in order to analyze how the velocities and temperature fields get affected by various flow parameters. Skin-friction coefficients and local Nusselt number are presented through numerical data for both SWCNTs and MWCNTs. Moreover the skin-friction coefficients and local Nusselt number are enhanced for larger values of nanoparticles volume fraction.


VARIABLE SELECTION ON EUROSTA'S GALL SIZE. II. A PATH ANALYSIS OF THE ECOLOGICAL FACTORS BEHIND SELECTION.
We examined phenotypic selection exerted by natural enemies on the gall-making fly Eurosta solidaginis in an extensive field study of 16 populations, spanning four generations. Gall-makers that induce small galls are vulnerable to the attack of Eurytoma gigantea. This imposes upward directional selection on gall size. Insectivorous birds, predominantly the downy woodpecker, are more likely to attack larvae that induce large galls than small ones, and this imposes downward directional selection. We used path analysis to explore the relative contributions of these natural enemies to the net directional selection on gall size. The path models further examined several ecological factors that influence selection intensity through their effects on parasitoid and bird attack rates. Net directional selection varied more strongly with E. gigantea attack than bird attack. Competitive interactions among birds and the three parasitoid species, including E. gigantea, were evidenced by low winter bird attack rates in fields where a high proportion of galls contained the overwintering parasitoids. Eurytoma gigantea attack was heavier in fields where mean gall size was small and bird attack heavier in fields where mean gall size was large. Neither birds nor E. gigantea showed simple density-dependent attack. Data suggested a form of frequency-dependent attack by birds but not by E. gigantea.


Fabrication of an inexpensive and high efficiency microphotoreactor using CO2 laser technique for photocatalytic water treatment applications.
In this study, a micro-photoreactor with catalyst-immobilized micro-channels was designed and fabricated using CO2 laser as a simple and inexpensive technique. The micro-photoreactor is composed of an array of micro-channels, a quartz plate, and an array of UV-LEDs. The micro-channels with the dimension of 400 µm width, 50 µm depth, and 80 cm length were inscribed on a flat plate of poly(methyl methacrylate) (PMMA). The illuminated specific surface area for the designed micro-reactor was calculated to be 25000 m(-1). To examine the performance of miniaturized photoreactor, the photocatalytic degradation of 4-Nitrophenol as a refractory pollutant was investigated. The effects of operational variables on the performance of micro-photoreactor were studied. Higher photocatalytic degradation is obtained for low flow rates, high light intensities, long micro-channels lengths, and low inlet concentrations. Also, the performance of micro-photoreactor was examined in the presence of different types of TiO2 catalysts with an average particle size between 5 and 27 nm (such as P25, PC500, Merck, and UV100) and textile dyes with different chemical structures (such as Acid Orange 7, Acid Violet 19, Basic Red 46, Methyl Orange, and Malachite Green). Finally, the reusability of miniaturized photoreactor was evaluated and the results showed satisfactory stability and reusability for the designed micro-reactor in the photocatalytic degradation of organic pollutants.


Non-climacteric fruit development and ripening regulation: 'the phytohormones show'.
Fruit ripening involves numerous physiological, structural, and metabolic changes that result in the formation of edible fruits. This process is controlled at different molecular levels, with essential roles for phytohormones, transcription factors, and epigenetic modifications. Fleshy fruits are classified as either climacteric or non-climacteric species. Climacteric fruits are characterized by a burst in respiration and ethylene production at the onset of ripening, while regulation of non-climacteric fruit ripening has been commonly attributed to abscisic acid (ABA). However, there is controversy as to whether mechanisms regulating fruit ripening are shared between non-climacteric species, and to what extent other hormones contribute alongside ABA. In this review, we summarize classic and recent studies on the accumulation profile and role of ABA and other important hormones in the regulation of non-climacteric fruit development and ripening, as well as their crosstalk, paying special attention to the two main non-climacteric plant models, strawberry and grape. We highlight both the common and different roles of these regulators in these two crops, and discuss the importance of the transcriptional and environmental regulation of fruit ripening, as well as the need to optimize genetic transformation methodologies to facilitate gene functional analyses.


Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation.
Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.


Quantifying the urban environment: a scale measure of urbanicity outperforms the urban-rural dichotomy.
The rapid urbanization of the developing world has important consequences for human health. Although several authorities have called for better research on the relationships between urbanicity and health, most researchers still use a poor measurement of urbanicity, the urban-rural dichotomy. Our goal was to construct a scale of urbanicity using community level data from the Cebu Longitudinal Health and Nutrition Survey. We used established scale development methods to validate the new measure and tested its performance against the dichotomy. The new scale illustrated misclassification by the urban-rural dichotomy, and was able to detect differences in urbanicity, both between communities and across time, that were not apparent before. Furthermore, using a continuous measure of urbanicity allowed for better illustrations of the relationships between urbanicity and health. The new scale is a better measure of urbanicity than the traditionally used urban-rural dichotomy.


Anti-inflammatory treatments for chronic diseases: a review.
Inflammation is viewed as one of the major causes for the development of different diseases like cancer, cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, asthma, and CNS related diseases such as depression and parkinson's disease; and this fervent phenomenon provides space for understanding different inflammatory markers. Increasing evidences have elucidated the outcome of inflammatory pathways dysregulation resulting in many symptoms of chronic diseases. The detection of transcription factors such as nuclear factor kappa-B (NF-κB), STAT and their gene products such as COX-2, cytokines, chemokines and chemokine receptors has laid molecular foundation for the important role of inflammation in chronic diseases in which the NF-κB is reported as a major mediator which makes a possible way for the development of new therapeutic approaches using synthetic and natural compounds that might eventually decrease the prevalence of these diseases. Even if many inflammatory markers like TNF-α, IL-1, IL-6, IL-8 and C-reactive protein (CRP) are reported to be the major key factors with proved role in several inflammatory diseases, IL-1 and TNF-α are the important cytokines that can induce the expression of NF-κB which is the potential target in these inflammatory diseases. This review aims to explore and summarize that how some drugs and natural compounds show their modulatory activity in inflammatory pathways and chronic inflammatory markers in these inflammatory diseases.


Mycoflora Associated With Pyrethrum Seed and the Integration of Seed Steam Treatment Into Foliar Disease Management Strategies.
A complex of foliar diseases can affect pyrethrum in Australia, but those of greatest importance are ray blight, caused by Stagonosporopsis tanaceti, and tan spot, caused primarily by Didymella tanaceti. Isolation of fungi from pyrethrum seed lots produced over 15 years resulted in recovery of six known pathogens: S. tanaceti, D. tanaceti, Alternaria tenuissima, Colletotrichum tanaceti, Stemphylium botryosum, and Botrytis cinerea. The incidence of S. tanaceti and D. tanaceti isolated from seed varied between 0.9 and 19.5% (mean = 7.7%) and 0 and 24.1% (mean = 5.3%) among years, respectively. Commercial heat treatment of pyrethrum seed via steaming reduced the incidence of D. tanaceti from 10.9 to 0.06% and the incidence of S. tanaceti from 24.6% to nondetectable levels (<0.18%). In a second experiment, both species were reduced to nondetectable levels (<0.20%) from their initial incidences of 22.4 and 2.4%, respectively. In a field study in 2013, colonization of pyrethrum foliage by S. tanaceti was reduced from 21.1 to 14.3% in early winter when heat-treated seed was planted. However, isolation frequency of D. tanaceti was not affected significantly by seed treatment in this year. In a related experiment in 2015, the isolation frequency of D. tanaceti in plots planted from heat-treated seed depended on both prior application of an industry-standard fungicide program and proximity to another pyrethrum field in autumn. The fungus was recovered at a similar frequency in fungicide-treated and nontreated plots located near other pyrethrum fields (13.8 versus 16.3%, respectively), whereas recovery of the pathogen was reduced by fungicide applications in geographically remote pyrethrum fields (6.7 versus 1.4%, respectively). However, these differences in isolation frequency of D. tanaceti in autumn did not obviate the need for later fungicide applications to suppress foliar disease intensity in spring or flower yield in summer, independent of the proximity to other pyrethrum fields. This study suggests that steam treatment of seed can delay development of the foliar disease complex on pyrethrum, although an extremely low level of remaining infected seed or exogenous sources of inoculum necessitates the use of foliar fungicide applications in spring.


Yolk sac and allied tumours of the ovary.
A review is presented of the histological appearances of 38 yolk sac tumours of the ovary and four so-called embryonal carcinomas together with the associated clinical features. It is suggested that these neoplasms belong to a single taxonomic group of embryonal ovarian tumours differing only in the concomitant types of differentiation. One yolk sac tumour occurred in an individual of 46 XY chromosome constitution and another in a patient with a gonadoblastoma in the contralateral ovary. The value of post-operative serial assays of serum AFP is stressed.


A model of GAG/MIP-2/CXCR2 interfaces and its functional effects.
MIP-2/CXCL2 is a murine chemokine related to human chemokines that possesses the Glu-Leu-Arg (ELR) activation motif and activates CXCR2 for neutrophil chemotaxis. We determined the structure of MIP-2 to 1.9 Å resolution and created a model with its murine receptor CXCR2 based on the coordinates of human CXCR4. Chemokine-induced migration of cells through specific G-protein coupled receptors is regulated by glycosaminoglycans (GAGs) that oligomerize chemokines. MIP-2 GAG-binding residues were identified that interact with heparin disaccharide I-S by NMR spectroscopy. A model GAG/MIP-2/CXCR2 complex that supports a 2:2 complex between chemokine and receptor was created. Mutants of these disaccharide-binding residues were made and tested for heparin binding, in vitro neutrophil chemotaxis, and in vivo neutrophil recruitment to the mouse peritoneum and lung. The mutants have a 10-fold decrease in neutrophil chemotaxis in vitro. There is no difference in neutrophil recruitment between wild-type MIP-2 and mutants in the peritoneum, but all activity of the mutants is lost in the lung, supporting the concept that GAG regulation of chemokines is tissue-dependent.


Higher levels of IL-6, CD4 turnover and Treg frequency are already present before cART in HIV-infected subjects with later low CD4 recovery.
Immunological characterization of HIV-infected subjects with low CD4-recovery (LR-subjects) has been extensively performed after a variable period of combined antiretroviral therapy (cART). We now explore immunological alterations present before the cART onset. In a case-control study, we selected pre-cART samples of HIV-subjects with and without low CD4-recovery after cART (n = 21 per group). CD4 T-cell activation, senescence and exhaustion related markers were not found specifically altered before cART initiation. On the other hand, we found that LR-subjects before cART already showed increased levels of IL6 (p = 0.009) and increased frequencies of Ki67+CD4+ T-cells (p = 0.026), CD45RA-CD27+CD4+ T-cells (p = 0.008) and Treg (p = 0.001), as well as increased expression of CD95 and CD127 on CD4 T-cells (p = 0.016; p = 0.032, respectively). These parameters characterize the immunological damage in LR-subjects before the cART onset and could be associated to the mechanisms hindering the subsequent CD4 recovery.


Cloning and characterization of a basic phospholipase A2 homologue from Micrurus corallinus (coral snake) venom gland.
During the cloning of abundant cDNAs expressed in the Micrurus corallinus coral snake venom gland, several putative toxins, including a phospholipase A2 homologue cDNA (clone V2), were identified. The V2 cDNA clone codes for a potential coral snake toxin with a signal peptide of 27 amino acid residues plus a predicted mature protein with 119 amino acid residues. The deduced protein is highly similar to known phospholipases A2, with seven deduced S-S bridges at the same conserved positions. This protein was expressed in Escherichia coli as a His-tagged protein that allowed the rapid purification of the recombinant protein. This protein was used to generate antibodies, which recognized the recombinant protein in Western blot. This antiserum was used to screen a large number of venoms, showing a ubiquitous distribution of immunorelated proteins in all elapidic venoms but not in the viperidic Bothrops jararaca venom. This is the first description of a complete primary structure of a phospholipase A2 homologue deduced by cDNA cloning from a coral snake.


On the Spontaneous Build-Up of Voltage between Dissimilar Metals Under High Relative Humidity Conditions.
Certain metals can surprisingly build-up charge spontaneously, when exposed to high relative humidity (RH), although they need to be isolated from the ground. We have explored this phenomenon, building on former experimental knowledge and carrying out additional experiments, to identify the parameters that could enhance this charging. We used many types of metals with different characteristics under different RH and temperature conditions. While some metals were unaffected by high RH, others, like zinc and stainless steel, did acquire charge, when RH was >60%, and charged a capacitor to a voltage of 1 V. For the first time, we also performed outdoors experiments, showing this phenomenon is also valid under similar natural ambient humid conditions. If these results can be scaled up, it may lead to the development of practical applications for regions and times of high RH conditions.


Right Heart Failure Management: Focus on Mechanical Support Options.
Millions of American adults suffer from right heart failure (RHF), a condition associated with high rates of hospitalization, organ failure, and death. There is a multitude of etiologies and mechanisms that lead to RHF, often in a feedforward spiral of decline. The management of advanced cases of RHF can be particularly difficult. For patients who are refractory to the medical optimization of volume status, hemodynamic and pharmacologic support, and rhythm control, mechanical therapies may be warranted. Currently available mechanical assist devices for RHF include venoarterial extracorporeal oxygenation and right ventricular assist devices, both surgical and percutaneous. Each advanced therapy has its own potential advantages and limitations, and often is appropriate in different clinical contexts. In this review, the authors describe the pathophysiology and medical therapies for RHF and then focus on the different types of advanced therapies that currently exist to help inform medical decision-making for this complicated patient cohort.


Therapy-related myelodysplastic syndrome/acute leukemia after multiple myeloma in the era of novel agents.
Survival for patients with multiple myeloma has increased. Both melphalan and lenalidomide are associated with subsequent development of myelodysplasia. We reviewed the cases of all patients with multiple myeloma who had subsequent development of myelodysplastic syndrome (MDS) or acute non-lymphoblastic leukemia (ANLL) during a 12-year period in three centers. Of 55 patients identified, two received only lenalidomide before myelodysplasia developed. The median time between the diagnoses of multiple myeloma and MDS/ANLL was 52.7 months. Median survival after the diagnosis of MDS or ANLL was 6.7 months. Treatment of MDS comprised allogeneic stem cell transplant in eight patients (median survival, 219 days; one patient alive at 624 days) and a hypomethylating agent in 21 patients (response of stable or better in five patients). Myelodysplasia remains a devastating complication of therapy for multiple myeloma, with short survival and poor response rates to available modalities.


Gastroenteropancreatic neuroendocrine tumour arising in Meckel's diverticulum coexisting with colon adenocarcinoma.
Although colon cancer is the third most common cause of cancer-related death worldwide, the prevalence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) remains rare. To date, very few cases of GEP-NETs within Meckel's diverticulum and synchronous colorectal cancer have been reported. Although the coexistence of these two tumour types is uncommon, it is important to be aware of their disease patterns. We present a rare case of a patient with an intestinal GEP-NET arising in Meckel's diverticulum coexisting with metastatic colon adenocarcinoma, and we discuss the clinical manifestations and the diagnostic procedures and treatment modalities used. This case report underlines the importance of being aware of this particular coexistence, as well as the unlikely metastatic spread of GEP-NETs and the importance of a multidisciplinary approach to cancer treatment. Finally, individualizing the treatment according to the stages of the primaries will result in durable cancer control, particularly in synchronous double malignancy.


[Th1/Th2 cytokines and its clinical significance in obstructive sleep apnea hypopnea syndrome children without allergic rhinitis and asthma].
To analyze Th1 and Th2 immune balance related cytokines and clinical significance in obstructive sleep apnea hypopnea syndrome children without allergic rhinitis and asthma. Collected 91 cases of obstructive sleep apnea hypopnea syndrome children with obstructive level data, and measured the serum Th1 cytokine TNF-beta and IFN-gamma, Th2 cytokines IL-4 and IL-5 levels. One hundred and five normal children were enrolled for the same detection of serum cytokines. Non-allergic rhinitis and asthma children serum levels of IFN-gamma was lower than control group children, the difference was statistically significant (P < 0. 01). Other cytokines (TNF-beta, IL-4 and IL-5) were no significant difference with the control group. Th1 and Th2 immune response was imbalance in non-allergic rhinitis and asthma obstructive sleep apnea hypopnea syndrome children. The decline in Th1 cell-mediated protective immune response cells may cause disease.


Phytochemical, proximate, antioxidant and free radical scavenging evaluations of Calliandria surinamensis.
The flower pigment of Calliandria suninamensis is used folklorically as a colorant and a dye. The crude powdered sample and methanolic extract of the plant were subjected to phytochemical, proximate analysis and antioxidant activities. Parameters like moisture content, ash values and extractive values were determined. The methanolic extract was evaluated for its antioxidant/free radical scavenging activities using standard experimental procedures. The result of the study indicated the presence of copious amount of phenolics and anthocyanidins. The antioxidant activity of Calliandria surinamensis showed a significant free radical activity. Its action was comparable to standard antioxidants like gallic acid and tocopherol (vitamin E). The proximate analysis gave 3.40 +/- 0.02 g, 4.15 +/- 0.01 g, 1.38 +/- 0.13 g and 5.20 +/- 0.03 g as moisture content, ash value, acid insoluble ash and alcohol extractives, respectively. This study gives scientific justification of the plant as antioxidant and free radical scavenger.


Prostaglandins and activation of AC/cAMP prevents anoikis in IEC-18.
Recent data indicates that chronic inflammation of the intestine such as Crohn's or ulcerative colitis puts those individuals at heightened risk for colorectal adenocarcinoma. In this study, we examine the effect of the inflammatory mediator PGE(2) and associated signalling on detachment-induced cell death (anoikis) in intestinal epithelial cells. Treatment of detached IEC-18 with 0.01-0.05 microM PGE(2) increased cell viability as well as induced aggregation. As EP4 prostaglandin receptors on IEC are coupled to adenylate cyclase, we next treated cells with agents that promote cAMP signalling (Forskolin, dbcAMP, and etazolate), all of which promoted IEC aggregation as well as survival. We next treated detached IECs with specific inhibitors of adenylate cyclase or PKA, which accelerated anoikis. To explore the mechanism of cell-cell adhesion, we next treated detached IECs with an anti-E-cadherin blocking antibody which dispersed aggregates induced by dbcAMP, and an adenovirus expressing a dominant negative E-cadherin (EcadDeltaEC) prevented aggregate formation. Interestingly EcadDeltaEC prevented aggregation of IEC induced by dbcAMP but did not significantly reduce viability. This suggests that cAMP signalling is important in both aggregate formation and promoting viability but these are distinct events. Taken together, these data support a mechanism whereby elevated PGE(2) levels characteristic of colitis prevent anoikis by activating an AC-, cAMP-, and PKA-dependent signalling pathway. The delay of apoptosis by PGE(2) may be one mechanism by which inflammation may contribute to carcinogenesis.


Awake craniotomy for brain tumor: indications, technique and benefits.
Increasing interest in the quality of life of patients after treatment of brain tumors has led to the exploration of methods that can improve intraoperative assessment of neurological status to avoid neurological deficits. The only method that can provide assessment of all eloquent areas of cerebral cortex and white matter is brain mapping during awake craniotomy. This method helps ensure that the quality of life and the neuro-oncological result of treatment are not compromised. Apart from the medical aspects of awake surgery, its economic issues are also favorable. Here, we review the main aspects of awake brain tumor surgery. Neurosurgical, neuropsychological, neurophysiological and anesthetic issues are briefly discussed.


MICA/B and ULBP1 NKG2D ligands are independent predictors of good prognosis in cervical cancer.
NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer. Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients. MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer. High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.


[The laparoscopic approach to the polycystic liver and adnexal cysts].
Having re-examined the nosographic data acquired on the subject of hepatic polycystosis and uterine adnexal cysts, the authors report the results of their experience. On the basis of the evaluation of these results (no laparotomic conversion, no postoperative complications, reduced hospital stay), which are comparable to those reported in the literature, the authors conclude that the modern technology may be used to advantage in all cases where laparoscopic surgery is not difficult, does not require numerous tests and does not entail a high risk of complications.


Congenital fusion of jaw and ankyloblepharon filiforme adnatum: malformation and multiple systems anomaly.
Congenital fusion of jaw and its association with ankyloblepharon filiforme adnatum is reported but is a quite rare congenital benign anomaly. It may be unilateral or bilateral and can present with a single system or multiple systems involvement. This report concentrates on describing the clinical features of above disease, likely aetiological causes, and embryogenesis with classification, diagnostic, and, treatment modality, anesthesia problems and review of literature.


Perceptions of television violence: effects of programme genre and type of violence on viewers' judgements of violent portrayals.
This paper reports two studies which examined the mediating effects of programme genre and physical form of violence on viewers' perceptions of violent TV portrayals. In Expt 1, a panel of British viewers saw portrayals from five programme genres: British crime-drama series, US crime-drama series, westerns, science-fiction series and cartoons which feature either fights or shootings. In Expt. 2, the same viewers rated portrayals from British crime-drama and westerns which featured four types of violence, fist-fights, shootings, stabbings and explosions. All scenes were rated along eight unipolar scales. Panel members also completed four subscales of a personal hostility inventory. Results showed that both fictional setting and physical form had significant effects on viewers' perceptions of televised violence. British crime-drama portrayals, and portrayals that featured shootings and stabbings, were rated as most violent and disturbing. Also, there were strong differences between viewers with different self-reported propensities towards either verbal or physical aggression. More physically aggressive individuals tended to perceive physical unarmed violence as less violent than did more verbally aggressive types.