In vitro immune response of cells of various lymphoid tissues in (NZB X NZW)F1 mice: evidence for abnormality of the mesenteric lymph node cells.
Autoimmune-prone (NZB X NZW)F1 (B/W) mice have been shown to have a variety of immunologic perturbations. However, most studies have been performed with spleen cells. By using the Mishell-Dutton culture system, we examined the in vitro immune response of the various lymphoid tissue to determine whether an imbalance at a selective lymphoid site may exist in B/W mice. It was shown that the ability of mesenteric lymph node (MLN) cells of B/W mice to generate plaque-forming cells (PFC) in response to sheep red blood cells was consistently less than that of the spleen cells. This relationship held true in the aged mice. In contrast, the ability of the MLN cells of other strains not prone to develop autoimmunity to generate PFC was higher than that of the spleen cells. No significant difference in the mitogenic response of the lymphoid cells from various lymphoid tissue in the young B/W mice was seen, as compared with normal lymphoid cells from control mice. However, it was demonstrated that a relative decrease of B cells and immunoregulatory Lyt-123+ cells in the MLN in the B/W mice occurred early in life, and it was concluded that this abnormality may account for the low PFC response observed.


Composite keratohyaline granules in striate keratoderma.
The gross, light microscopic, and ultrastructural findings in a 55 year old man was striate keratoderma are presented. There was no family history of the disease. The lesions developed in his late teens and early adult years, and consisted of progressively worsening, raised, hyperkeratotic, linear plaques on the palm and volar surface of the third and fifth fingers bilaterally. There were also painful callosities on both heels, and thick, raised plaques on the heels and lateral plantar surfaces. The epidermis was papillomatous and acanthotic, with marked orthokeratosis, minimal parakeratosis, and a very thickened granular layer. No epidermolysis was seen. Electron microscopy showed increased tonofibrils in the stratum spinosum arranged in wavy, parallel bundles and a granular layer in which normal Odland bodies were present. However, the keratohyaline granules were large, with rounded borders and a striped, alternating, dark and light content characteristic of composite granules. There was diminished contact of the granules with tonofibrils. The transition to the stratum corneum was abrupt. The ultrastructural and genetic features of keratodermas, with special emphasis on the striate type, are reviewed.


Effect of Resistance Training on Blood Pressure and Autonomic Responses in Treated Hypertensives.
Trevizani, GA, Seixas, MB, Benchimol-Barbosa, PR, Vianna, JM, da Silva, LP, and Nadal, J. Effect of resistance training on blood pressure and autonomic responses in treated hypertensives. J Strength Cond Res 32(5): 1462-1470, 2018-This study evaluated the effect of resistance training (RT) on heart rate variability (HRV) and on blood pressure (BP) responses to acute and short-term exposure in treated hypertensive (HT) subjects. Twenty-one men participated in the study, 8 HT under drug treatment regimen and achieving adequate BP control before inclusion and 13 normotensive (NT). The RT protocol consisted of 12 sessions with eight exercises (leg extension, leg press, leg curl, bench press, seated row, triceps push-down, seated calf flexion, and seated arm curl) performed for two sets of 15-20 repetitions with 50% of one repetition maximum with 2-minute rest intervals in between sets, 3×/week. Heartbeat measurements were taken before and after RT, and BP was measured at the beginning and at the end of each session after 10-minute rest. The repeated measures analysis of variance (effect: group vs. training) evaluated BP and HRV responses. Effect size (ES) calculation measured the magnitude of the RT effect on these variables. There was a statistically significant reduction in postexercise systolic BP in both groups (p = 0.040), without significant change in resting BP along RT (p = 0.159). Regarding HRV, it was observed a reduced sympathetic-vagal balance (training interaction vs. group: p = 0.058, ES = -0.83) in HT subjects. Resistance training promotes a significant acute reduction of BP in the HT and NT groups and provides a slight benefit of cardiac autonomic balance in the HT.


Comparative functional analysis of full-length and N-terminal fragments of phytochrome C, D and E in red light-induced signaling.
Phytochromes (phy) C, D and E are involved in the regulation of red/far-red light-induced photomorphogenesis of Arabidopsis thaliana, but only limited data are available on the mode of action and biological function of these lesser studied phytochrome species. We fused N-terminal fragments or full-length PHYC, D and E to YELLOW FLUORESCENT PROTEIN (YFP), and analyzed the function, stability and intracellular distribution of these fusion proteins in planta. The activity of the constitutively nuclear-localized homodimers of N-terminal fragments was comparable with that of full-length PHYC, D, E-YFP, and resulted in the regulation of various red light-induced photomorphogenic responses in the studied genetic backgrounds. PHYE-YFP was active in the absence of phyB and phyD, and PHYE-YFP controlled responses, as well as accumulation, of the fusion protein in the nuclei, was saturated at low fluence rates of red light and did not require functional FAR-RED ELONGATED HYPOCOTYL1 (FHY-1) and FHY-1-like proteins. Our data suggest that PHYC-YFP, PHYD-YFP and PHYE-YFP fusion proteins, as well as their truncated N-terminal derivatives, are biologically active in the modulation of red light-regulated photomorphogenesis. We propose that PHYE-YFP can function as a homodimer and that low-fluence red light-induced translocation of phyE and phyA into the nuclei is mediated by different molecular mechanisms.


Short-term cell-attachment rates: a surface-sensitive test of cell-substrate compatibility.
Mechanisms of cell deposition from a sessile liquid phase and adherence to various plastic substrates have been investigated by measurement of short-term (less than 120 min) cell-attachment rates. Sigmoidal attachment-rate curves were fit with a three-parameter variant of a logistic equation to quantify parameters related to initial rate and equilibrium-adherence. For substrates on which cell adhesion was low, initial rates were estimated from slopes of linear best-fit equations. Average variations in adherence parameters for three cell lines, MDCK (epithelioid), VERO, and AHL-1 (fibroblastic) to tissue-culture grade polystyrene dishes were less than 10% (standard-error-of-mean/mean X 100) over extended periods of more than two months, so that attachment measurements could be repetitively applied with the same cell stocks continuously subcultured in the laboratory. Developed techniques were applied to a variety of plastics and the results tabulated. Comparison of adherence parameters for ionomer and polyethylene films, both with and without adsorbed fetal-bovine-serum proteins, demonstrated that surface carboxyl groups were important in protein adsorption and cellular adherence. Attachment rates of MDCK to polystyrene were dependent on starting cell number whereas equilibrium adherence did not vary significantly over a wide range of inoculum concentrations. It was concluded from theoretical considerations that initial rates of MDCK attachment were sensitive to and dependent on electrostatic barriers to formation of close substrate contacts whereas equilibrium-adherence levels were controlled by short-range forces such as interfacial energies and formation of receptor-ligand complexes.


"Real-world" analysis of battery longevity of implantable cardioverter-defibrillators: an in-depth analysis of a prospective defibrillator database.
There is a lack of evidence regarding contemporary implantable cardioverter-defibrillator (ICD) battery longevity. Our aim was to assess battery longevity in ICDs in a real-world setting. Retrospective cross-sectional single center study of a prospectively collected database of consecutive patients who underwent ICD implantation from January 2010 to December 2015. Clinical data and battery longevity of all manufacturers were collected. A total of 351 patients (84.6% males, mean age of 61 ± 12 years) were included in the study (292 VVI; 6 VDD; 53 DDD). All manufacturers (Abbott, Biotronik, Boston, Medtronic and Microport) were equally represented in the study (p = 0.110). Median battery longevity was 10.8 years (11 years for VVI and 8.5 for DDD). After a follow-up time of 5 years, 98% of VVI and DDD were still in service (vs. industry-projected longevity of 98%). During this time, 89 patients (25.4%) underwent device replacement - 69 patients (77.5%) due to battery depletion, 6 patients due to infection, 3 patients due to dysfunction and 13 patients due to upgrade to CRT-D. Patients with Medtronic or Biotronik ICDs had a greater probability of being replaced earlier due to battery depletion (Biotronik HR 6.87, 95% CI 2.54-18.58, p < 0.001; Medtronic HR 6.08, 95% CI 2.45-15.06 p < 0.001). VVI and DDD ICD battery longevity matched industry-projected longevity after 5 years of follow-up. Medtronic and Biotronik ICDs appeared to have an earlier battery depletion. Further randomized studies are required to ensure optimal care.


Liver stem cells: from preface to advancements.
Liver is a major metabolic organ of the body and is known to comprise of two epithelial cell lineages, namely, hepatocytes and cholangiocytes which are known to originate from hepatoblasts during fetal developing stages. Upon acute injury, the hepatocytes and cholangiocytes undergo cellular division to compensate the loss, however, chronic damage may suppress this proliferative ability and as a consequence hepatic and extra-hepatic stem cells may contribute for liver regeneration. Facultative liver stem cells (oval cells) may emerge, proliferate and contribute in replacing damaged hepatic cells. Similarly, bone marrow and mesenchymal stem cells are also known for contributing in liver regeneration having their ability of self renewal and differentiation. However, a closer look is still required to bridge the existing knowledge gaps between functionality and limitations. Thereby, we have discussed the detailed mechanistic insights of both hepatic and extra-hepatic stem cells including, stem/progenitor cells, adult/fetal hepatocytes, oval cells, bone marrow and mesenchymal stem cells. We have also focused on few in vitro and in vivo studies elucidating therapeutic applications and challenges related to the liver stem cells. We believe that such conversations may provide invaluable contribution for realistic advancement in the state of therapeutic stem-cell transplantation.


[Experimental basis for possible tumors induction in descendants after placental transmission of chrysotile asbestos fibers].
Experiments on white outbred rats helped to establish placental transmission of chrysotile asbestos fibers from mother to fetus with reliable increased incidence of neoplasma in first generation, mainly of respiratory malignancies. Chronic exposure to chrysotile asbestos damaged peripheral lymphocytes and did not affect red bone marrow. Extrapolating the experimental data on placental transmission of chrysotile asbestos to children requires epidemiologic research.


Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study.
New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen.


Control of vitamin B 6 biosynthesis in Escherichia coli.
Pyridoxineless mutants of Escherichia coli B which specifically require pyridoxal or pyridoxamine for growth can be divided into classes according to their growth responses in enriched media. Members of the slowest growing class synthesize vitamin B(6) at the fastest rates when starved for pyridoxal in glycerol minimal medium. After 80 min of synthesis at 4 x 10(-10) moles of vitamin B(6) per mg of cells per hr, the rate increases four- to fivefold and continues at the new rate for several hours. The shift to the new rate is prevented by chloramphenicol, thus suggesting that a derepression mechanism exists to control vitamin B(6) synthesis in addition to the previously discovered feedback control.


A Golgi study of the early postnatal development of the visual cortex of the hooded rat.
Although neuroanatomical plasticity has been demonstrated in the rat visual cortex, no systematic data on the dendritic development of the area are available. In the present study, the visual cortex of hooded rats at 1, 3, 5, 7, 10 and 15 postnatal days of age (P1-P15) was impregnated with the rapid Golgi method. The cortex was divided into the superficial layers, II-IV, and the middle layer V. At P1, pyramidal neurons had apical shafts and the beginning of the apical terminal arch. Analysis of both basilar and oblique dendritic number showed that pyramidal neurons of the middle layer developed more quickly than those in the superficial layers. The number of lower order basilar dendritic branches reached asymptote over the examined time period, whereas the higher order branches were still increasing in number but at a decelerating rate by P15. Dendrites at all ages exhibited varicosities which were especially prominent on the thin dendritic branches of the earlier ages. Some thin, filamentous processes, termed protospines, were found on dendrites and cell bodies at P1 to P5. They seemed to decrease by P7, when a few mature spines appeared. Spines increased in number on days P10 and P15. A comparison of the data from this study with quantified Golgi studies in adult rats indicates that by P10 and P15 the number of basilar branches is in the range seen in the adult.


The genetics of vascular complications in diabetes mellitus.
Prospective identification of which individuals with diabetes mellitus (DM) are at greatest risk for developing cardiovascular disease (CVD) complications would have considerable public health importance by allowing the allocation of limited resources to be focused on those individuals who would most benefit from aggressive intervention. Over the past 20 years genetic disease association studies have demonstrated that polymorphisms at specific genetic loci may identify those individuals at greatest risk for developing CVD in the setting of DM. This article reviews the evidence accumulated to date on four polymorphic loci with the aim of explaining how these polymorphisms modify the risk for CVD in DM by modifying the functional activity of a specific gene. Use of the knowledge of these genetic differences among individuals in targeting drug therapy (pharmacogenomics) is also discussed.


Spoof polariton enhanced modal density of states in planar nanostructured metallic cavities.
Spoof surface modes on nanostructured metallic surfaces are known to have tailorable dispersion dependent on the geometric characteristics of the periodic pattern. Here we examine the spoof plasmon dispersion on an isolated grating and a grating-planar mirror cavity configuration. The spoof polariton dispersion in the cavity is obtained using the scattering matrix approach, and the related differential modal density of states is introduced to obtain the mode dispersion and classify the cavity polariton modes. The grating-mirror cavity geometry is an example of periodically nanostructured metals above a planar ground plane. The properties discussed here are relevant for applications ranging from thin electromagnetic perfect absorbers to near-field radiative heat transfer.


Primary caregivers of cancer patients in the palliative phase: a path analysis of variables influencing their burden.
Research has shown that several variables influence the burden of primary caregivers of cancer patients staying at home in the palliative phase, but the associations between these variables have hardly been explored. The aim of this study was to examine the associations of theory-driven variables with the caregivers' burden by means of path analysis. The sample consisted of 96 caregivers of cancer patients in the palliative phase staying at home recruited from a hospital trust in Norway. The dimensions of burden from the Caregiver Reaction Assessment, namely self esteem, lack of family support, impact on finances, and impact on daily schedule, were used as the dependent variable. The following independent variables were tested in the models: the patients' levels of pain, fatigue, and nausea; and the caregivers' physical quality of life, anxiety and depression, and social support. The Partial Least Squares approach to structural equation modelling was used for the path analysis. Model 1 shows the direct associations between the independent variables and the dependent variable, explaining 16% of the variance in caregiver burden. Model 1 supports the finding that only caregivers' depression has a direct significant association with caregiver burden, and shows further that the effects of the other independent variables on burden are mediated through depression. In Model 2, anxiety and depression are mediating factors between three other independent variables and caregiver burden, and 12% of the variance is explained. Model 2 supports none of the independent variables as antecedents of burden. Testing of the models suggested that caregivers' depression was the main factor associated with caregiver burden, but also an important mediator of indirect associations of indirect associations of caregivers' anxiety and physical health.


Spectral Knowledge (SK-UTALCA): Software for Exploratory Analysis of High-Resolution Spectral Reflectance Data on Plant Breeding.
This article describes public, free software that provides efficient exploratory analysis of high-resolution spectral reflectance data. Spectral reflectance data can suffer from problems such as poor signal to noise ratios in various wavebands or invalid measurements due to changes in incoming solar radiation or operator fatigue leading to poor orientation of sensors. Thus, exploratory data analysis is essential to identify appropriate data for further analyses. This software overcomes the problem that analysis tools such as Excel are cumbersome to use for the high number of wavelengths and samples typically acquired in these studies. The software, Spectral Knowledge (SK-UTALCA), was initially developed for plant breeding, but it is also suitable for other studies such as precision agriculture, crop protection, ecophysiology plant nutrition, and soil fertility. Various spectral reflectance indices (SRIs) are often used to relate crop characteristics to spectral data and the software is loaded with 255 SRIs which can be applied quickly to the data. This article describes the architecture and functions of SK-UTALCA and the features of the data that led to the development of each of its modules.


Pulp cell response to the application of silver diamine fluoride and potassium iodide on caries-like demineralized dentin.
To investigate the response of pulp cells to the application of silver diamine fluoride (SDF) and potassium iodide (KI) on demineralized dentin. The occlusal surfaces of human dentin discs (0.4 mm thick) with similar permeability were subjected to an artificial caries protocol, and then the discs were adapted into artificial pulp chambers. MDPC-23 cells were seeded on the healthy pulp dentin surface, while the demineralized surface was treated with SDF, KI, SDF + KI, or hydrogen peroxide (positive control-PC) (n = 8). The negative control (NC) received ultrapure water. After 24 h, cell viability (alamarBlue) and morphology (SEM) were evaluated. The extracts were then applied to new MDPC-23 cells seeded in culture plates to assess their viability and the formation of mineralized nodules (MN; Alizarin Red) after seven days. The data were analyzed using one-way analysis of variance/Tukey or Games-Howell tests (α = 5%). SDF and PC significantly reduced the viability of cells seeded on discs (45.6% and 71.0%, respectively). Only cells treated with SDF or PC detached from the dentin substrate, while the remaining cells showed altered morphology. Cells in contact with extracts showed less reduction in viability, but it was still more toxic compared to NC. Only PC reduced MN deposition. SDF + KI or KI alone did not affect the cell response. SDF applied alone showed a mild to moderate transdentinal cytotoxic effect on pulp cells. However, the combination of SDF + KI reduced the cytotoxic effects. Both materials used alone or in combination did not affect the mineralization ability of pulp cells. Besides improving esthetic results, associating potassium iodide with silver diamine fluoride may reduce the transdentinal cytotoxic effects of this cariostatic agent on pulp cells.


New trends in the development of transcription factor decoy (TFD) pharmacotherapy.
Many recent published observations firmly demonstrate that one of the ways to study and artificially modulate gene expression at the transcriptional level is offered by the "transcription factor decoy" (TFD) strategy. This experimental approach is based on the competition for trans-acting factors between endogenous cis-elements present within regulatory regions of target genes and exogenously added DNA sequences (the DNA-based drug) mimicking the specific cis-elements. The objective of this molecular intervention is to cause a decrease of the interactions of trans-factors with the target genomic cis-elements, leading to alteration of transcription. The characterisation of the biological activity of the designed decoy molecules is routinely assessed by molecular technologies, such as electrophoretic mobility gel shift assay (EMSA), competitive DNase I footprinting, in vitro transcription. New advances in this field employ biospecific interaction analysis (BIA) based on surface plasmon resonance (SPR) and biosensor technology. With respect to the design of the decoy biomolecules, in addition to double-stranded DNA/DNA hybrids, cross-linking between two DNA molecules either via photocrosslinking or by the introduction of a covalently linked, non-nucleotide bridge has been reported. Furthermore, RNA decoys have been described able to bind transcription factors via aptameric interactions. In addition, circular decoys assuming a dumbbell configuration or single-stranded decoys with intramolecular palindromic sequences have also been described. Decoy molecules were also produced by polymerase-chain reaction (PCR). More recently, peptide nucleic acids-DNA chimeras have been shown to exhibit decoy activity and high level of stability. This variety of decoy biomolecules facilitate the establishment of suitable delivery approaches, including pressure-mediated transfer, electrically enhanced transfer, biolistic bombardment, cationic liposomes, hemagglutinating virus of Japan (HVJ)-liposomes, microsphere-aided delivery, nano-particles, peptide-mediated delivery, steroid mediated gene transfer, and red-blood cells.


The major cholesterol metabolite cholestane-3β,5α,6β-triol functions as an endogenous neuroprotectant.
Overstimulation of NMDA-type glutamate receptors is believed to be responsible for neuronal death of the CNS in various disorders, including cerebral and spinal cord ischemia. However, the intrinsic and physiological mechanisms of modulation of these receptors are essentially unknown. Here we report that cholestane-3β,5α,6β-triol (triol), a major metabolite of cholesterol, is an endogenous neuroprotectant and protects against neuronal injury both in vitro and in vivo via negative modulation of NMDA receptors. Treatment of cultured neurons with triol protects against glutamate-induced neurotoxicity, and administration of triol significantly decreases neuronal injury after spinal cord ischemia in rabbits and transient focal cerebral ischemia in rats. An inducible elevation of triol is associated with ischemic preconditioning and subsequent neuroprotection in the spinal cord of rabbits. This neuroprotection is effectively abolished by preadministration of a specific inhibitor of triol synthesis. Physiological concentrations of triol attenuate [Ca(2+)]i induced by glutamate and decrease inward NMDA-mediated currents in cultured cortical neurons and HEK-293 cells transiently transfected with NR1/NR2B NMDA receptors. Saturable binding of [(3)H]triol to cerebellar granule neurons and displacement of [(3)H]MK-801 binding to NMDA receptors by triol suggest that direct blockade of NMDA receptors may underlie the neuroprotective properties. Our findings suggest that the naturally occurring oxysterol, the major cholesterol metabolite triol, functions as an endogenous neuroprotectant in vivo, which may provide novel insights into understanding and developing potential therapeutics for disorders in the CNS.


Identification and characterization of a novel RNA binding protein that associates with the 5'-untranslated region of the chloroplast psbA mRNA.
Binding of proteins to chloroplast-encoded mRNAs has been shown to be an essential part of chloroplast gene expression. Four nuclear-encoded proteins (38, 47, 55, and 60 kDa) have been identified that bind to the 5'-untranslated region of the Chlamydomonas reinhardtii psbA mRNA with high affinity and specificity. We have cloned a cDNA that represents the 38 kDa protein (RB38) and show that it encodes a novel RNA binding protein that is primarily localized within the chloroplast stroma. RB38 contains four 70 amino acid repeats with a high percentage of basic amino acids, as well as an amino-terminal extension predicted to act as a chloroplast import sequence. We demonstrate that the 38 kDa precursor protein is imported into isolated chloroplasts and interacts with high specificity to uridine-rich regions within the 5'-untranslated region of the psbA mRNA. While database searches have identified hypothetical proteins from several other eukaryotic species with high sequence similarity to the deduced amino acid sequence of RB38, no proteins with homology to RB38 have been biochemically characterized. Bioinformatic analysis of the RB38 sequence, together with structure analysis using circular dichroism and protein modeling, suggests that the 70 amino acid repeats within RB38 are similar in fold to previously identified RNA binding motifs, despite limited sequence homology.


Up and away: ontogenic transference as a pathway for aerial dispersal of microplastics.
Microplastics (MPs) are ubiquitous pollutants found in marine, freshwater and terrestrial ecosystems. With so many MPs in aquatic systems, it is inevitable that they will be ingested by aquatic organisms and be transferred up through the food chain. However, to date, no study has considered whether MPs can be transmitted by means of ontogenic transference, i.e. between life stages that use different habitats. Here, we determine whether fluorescent polystyrene beads could transfer between Culex mosquito life stages and, particularly, could move into the flying adult stage. We show for the first time that MPs can be transferred ontogenically from a feeding (larva) into a non-feeding (pupa) life stage and subsequently into the adult terrestrial life stage. However, transference is dependent on particle size, with smaller 2 µm MPs transferring readily into pupae and adult stages, while 15 µm MPs transferred at a significantly reduced rate. MPs appear to accumulate in the Malpighian tubule renal excretion system. The transfer of MPs to the adults represents a potential aerial pathway to contamination of new environments. Thus, any organism that feeds on terrestrial life phases of freshwater insects could be impacted by MPs found in aquatic ecosystems.


CMV DNA levels and CMV gB subtypes in ART-naive HAART-treated patients: a 2-year follow-up study in The Netherlands.
In the pre-HAART period, HIV-1 patients were greatly at risk for cytomegalovirus (CMV) disease. In HAART-treated patients, the incidence of CMV disease has decreased dramatically and the timing and presentation of CMV infection may be different. Also the relevance of different CMV genotypes is part of debate. A total of 132 antiretroviral naive patients starting HAART were selected for a 2-year follow-up study in the Netherlands. In 105 (80%) patients, CMV DNA were less than 100 copies/ml in all plasma samples during follow-up. In 27 (20%) patients, a detectable CMV load was found during follow-up. In seven patients, the initial decrease in HIV-1 loads during HAART was accompanied by an increase in CMV loads. Of 1348 plasma samples, only 50 (3.7%) samples were positive with a CMV load more of than 100 copies/ml plasma. CMV loads more than 1000 copies/ml were found only in samples with CD4 levels less than 250 x 10 cells/l and with detectable HIV-1 loads. CMV glycoprotein B (gB) typing was possible in 19 patients. Among these patients, including four patients with triple CMV infection and seven patients with double infection, the most prevalent genotype was gB3 (16x) followed by gB2 (9x), gB1 (5x) and gB4 (4x). CMV disease during HAART is very unlikely as soon as the HIV-1 viral load becomes undetectable (<50 copies/ml) and/or CD4 cell levels are restored to more than 250 x 10 cells/l. Within Dutch HAART treated patients, infection with CMV gB3 is most prevalent, but also double or triple infection with other CMV gB strains are common.


Use of Bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma.
Differentiating Spitz nevus from malignant melanoma is difficult and controversial. Despite helpful lists of differential diagnostic features, uncertainty about the diagnosis often provokes some to stain the tumor for MIB-1 antibody to Ki-67 and measure the proliferation index (PI) of the tumor. Of the many reports about MIB-1 PI in Spitz nevi and melanoma, none have consolidated the information to provide guidelines for the predictive probability that a lesion is a Spitz nevus, given that the MIB-1 PI falls into a certain interval. The present study used previously published data and exponential and gamma probability density functions to model statistical distributions of PI, respectively, in Spitz nevi and melanomas and Bayes rule to estimate the predictive probability that a lesion is a Spitz nevus, given an observed PI. Results indicate that PIs more than 10% favor a melanoma diagnosis and PIs less than 2%, Spitz nevus. PI values between 2% and 10% yield various predictive values for Spitz nevus, depending on the a priori probability that the lesion is a Spitz nevus. The algorithm tabulates guidelines for the predictive probabilities of Spitz nevus given an observed PI.


FcRH1: an activation coreceptor on human B cells.
B-cell activation and differentiation is regulated through the coordinated function of a dynamic array of cell surface receptors. At different stages in their differentiation, human B cells may express one or more members of a large family of immunoglobulin Fc receptor homologs (FcRH) with regulatory potential. Among these newly identified transmembrane molecules, FcRH1 is unique in having 2 immunoreceptor tyrosine-based activation motif (ITAM)-like motifs in its intracellular domain. Here we used the Fab fragments of new monoclonal anti-FcRH1 antibodies and mRNA analysis to evaluate FcRH1 expression and function during B-cell differentiation. FcRH1 expression begins in pre-B cells, reaches peak levels on naive B cells, and is down-regulated after B cells are activated to begin to form germinal centers. This FcRH1 down-regulation coincides with dramatic enlargement of the pre-germinal center cells, cell cycle entry, and other overt signs of activation that include CD80 and CD86 up-regulation and immunoglobulin D (IgD) down-regulation. In vitro analysis indicates that ligation of FcRH1 leads to its tyrosine phosphorylation and to modest B-cell activation and proliferation. Concomitant FcRH1 ligation enhances B-cell antigen receptor (BCR)-induced Ca(2+) mobilization and proliferation. FcRH1 thus has the potential to serve as an activating coreceptor on B cells.


Bowel cleansing methods prior to CT colonography.
To compare the cleansing effect, ease of preparation and side-effects of two cleansing regimens containing either polyethylene glycol solution (PEG) or phospho-soda (Na-P) solution prior to CT colonography in a prospective, randomized, radiologist-blinded design. Fifty persons were randomized to receive either a PEG preparation or a Na-P preparation prior to CT colonography. On axial 2D images, the rectum, the sigmoid, the descending, the transverse and the cecum/ascending colon were scored semiquantitatively as to cleanness by two radiologists blinded to the bowel preparation regimen. Quality scores in the two groups were compared. Ease of preparation and side-effects were assessed by a questionnaire. The overall quality of the bowel preparation with the Na-P preparation was better than with the PEG preparation with significantly better cleansing scores for the rectum, the sigmoid, the descending and the transverse colon. The Na-P preparation was significantly better tolerated than the PEG preparation with significantly less nausea and significantly less fecal incontinence. The quality of the bowel preparation was better with the Na-P preparation than with the PEG preparation prior to CT colonography. Moreover, the Na-P preparation was better tolerated and with fewer side-effects.


Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children.
In conditions associated with insulin resistance, insulin-like growth factor binding protein-I (IGFBP-I) levels have been shown to correlate inversely with insulin levels. Puberty is associated with insulin resistance and thus provides a model for comparing the relationship of IGFBP-I to both insulin levels and measures of insulin sensitivity. Our study population consisted of 104 healthy pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity (Si) assessed by the modified minimal model of Bergman, which employs a frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I levels were significantly higher in boys than in pubertally matched girls (P < 0.01). There was a strong positive correlation between IGFBP-I levels and Si (r = 0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF-I are important predictors of IGFBP-I levels in pubertal children. It is possible that insulin-mediated suppression of IGFBP-I in obese children may increase free IGF-I levels and thus contribute to somatic growth. The same mechanism may operate in pubertal children, where insulin resistance and growth acceleration occur simultaneously.


Ontogeny of the production of an estrogen-regulated eosinophil chemotactic factor in the rat uterus.
The ontogeny of an estrogen-induced eosinophil chemotactic activity in the uterus after estrogen administration and its regulation by progesterone was studied in neonatal rats at 3, 7, 10, and 13 days of age. These results were compared with the increase in peroxidase activity and the secretion of complement component C3 by the uterus. No chemotactic activity was observed in animals younger than 14 days, and after this age the estrogen regulation of the response was also prevented by the co-administration of progesterone. The secretion of complement C3 appeared earlier, at 10 days of age. It was also observed that the uterus of 3-7-day-old rats responded to estrogen by increasing the secretion of two proteins of 36 and 110 kDa. No further regulation or synthesis was observed with increasing age for these two proteins.


Patterns of alcohol consumption and risk of falls in older adults: a prospective cohort study.
Falls are a major health problem in older adults, but their relationship with alcohol consumption in this population remains unclear. In a cohort with 2170 older adults followed up for 3.3 years, both moderate drinking and the Mediterranean drinking pattern were associated with a lower risk of falls and injurious falls. This study aims to examine the association between certain patterns of alcohol consumption, including the Mediterranean drinking pattern (MDP), and the risk of falls in older adults. A prospective cohort with 2170 community-dwelling individuals aged ≥60 years was recruited in Spain in 2008-2010 and followed up through 2012. At baseline, participants reported alcohol consumption and, at the end of follow-up, their falls during the previous year. The MDP was defined as moderate alcohol consumption (threshold between moderate and heavy intake was 40 g/day for men and 24 g/day for women) with preference for wine and drinking only with meals. Analyses were conducted with negative binomial or logistic regression, as appropriate, and adjusted for the main confounders. Compared with never drinkers, the number of falls was lower in moderate drinkers (incidence rate ratio (95% confidence interval), 0.79 (0.63-0.99)) and drinkers with MDP (0.73 (0.56-0.96)). Also, moderate drinkers and those with MDP showed a lower risk of ≥2 falls (odds ratio (95% confidence interval), 0.58 (0.38-0.88) and 0.56 (0.34-0.93), respectively) and of falls requiring medical care (0.67 (0.46-0.96) and 0.61 (0.39-0.96), respectively). Both moderate drinking and the MDP were associated with a lower risk of falls and injurious falls in older adults. However, sound advice on alcohol consumption should balance risks and benefits.


Dual X-ray absorptiometry of hip, heel ultrasound, and densitometry of fingers can discriminate male patients with hip fracture from control subjects: a comparison of four different methods.
Few studies have examined different bone densitometry techniques to determine male hip fracture risk. We conducted a case-control study of 31 noninstitutionalized men, mean age 77 yr, with a first hip fracture and compared the results with 68 randomly selected age-matched control subjects. The methods used were dual X-ray absorptiometry (DXA) of the proximal femur, quantitative ultrasound (QUS) of the heel and fingers, and radiographic absorptiometry of the fingers. Case patients had significantly lower values (4-17%; p < 0.01) for all methods. The odds ratios for every SD reduction in bone values were 4.8 (95% confidence interval [CI]: 2.3-9.9) for DXA of the femoral neck, 2.2 (95% CI: 1.2-3.9) for QUS of the heel, 2.0 (95% CI: 1.2-3.3) for QUS of the phalanges, and 3.1 (95% CI: 1.5-6.6) for radiographic absorptiometry of the phalanges. The results indicate a strong capability of DXA of the femoral neck to distinguish between men with a first hip fracture and control subjects. Furthermore, ultrasound of the heel and fingers as well as radiographic absorptiometry proved capable of discriminating men with hip fractures from control subjects.


Methamphetamine Use and Cardiovascular Disease.
While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and accidents, the leading cause of death in methamphetamine users is cardiovascular disease, because of significant effects of methamphetamine on vasoconstriction, pulmonary hypertension, atherosclerotic plaque formation, cardiac arrhythmias, and cardiomyopathy. In this review, we examine the current literature on methamphetamine-induced changes in cardiovascular health, discuss the potential mechanisms regulating these varied effects, and highlight our deficiencies in understanding how to treat methamphetamine-associated cardiovascular dysfunction.


[Malignant vulvar soft tissue myoepithelioma].
The authors describe a case of malignant vulvar soft tissue myoepithelioma in a 41-year-old woman. Microscopically, epithelioid and spindle cells were located in the myxoid stroma. Tumor cells co-expressed pan-cytokeratin, EMA, and cytokeratin 18, vimentin, protein S100, and smooth muscle actin. The tumor was found to have a very high proliferative activity (Ki-67 was as high as 80%). The disease was fulminant with a fatal outcome 4 months after the occurrence of the first symptoms of the tumor.


[Aneurysm of the aorto-coronary venous bypass. Apropos of a case disclosed by a pre-sternal mass and a review of the literature].
A 61 year old man was admitted with a pulsatile pre-sternal swelling ten years after saphenous vein coronary-artery bypass grafting. The precise diagnosis of this vascular tumor was not established despite various investigations. At reoperation, an aneurysm of the saphenous vein graft, eroding the sternum, was found. This rare complication of saphenous vein coronary artery bypass grafting is described and a review of the literature is presented. Reoperation is mandatory for this uncommon alteration of the saphenous vein graft.


Gradient of rigidity in the lamellipodia of migrating cells revealed by atomic force microscopy.
Changes in mechanical properties of the cytoplasm have been implicated in cell motility, but there is little information about these properties in specific regions of the cell at specific stages of the cell migration process. Fish epidermal keratocytes with their stable shape and steady motion represent an ideal system to elucidate temporal and spatial dynamics of the mechanical state of the cytoplasm. As the shape of the cell does not change during motion and actin network in the lamellipodia is nearly stationary with respect to the substrate, the spatial changes in the direction from the front to the rear of the cell reflect temporal changes in the actin network after its assembly at the leading edge. We have utilized atomic force microscopy to determine the rigidity of fish keratocyte lamellipodia as a function of time/distance from the leading edge. Although vertical thickness remained nearly constant throughout the lamellipodia, the rigidity exhibited a gradual but significant decrease from the front to the rear of the lamellipodia. The rigidity profile resembled closely the actin density profile, suggesting that the dynamics of rigidity are due to actin depolymerization. The decrease of rigidity may play a role in facilitating the contraction of the actin-myosin network at the lamellipodium/cell body transition zone.


Dual functions of highly potent graphene derivative-poly-L-lysine composites to inhibit bacteria and support human cells.
Dual-function poly(L-lysine) (PLL) composites that function as antibacterial agents and promote the growth of human cell culture have been sought by researchers for a long period. In this paper, we report the preparation of new graphene derivative-PLL composites via electrostatic interactions and covalent bonding between graphene derivatives and PLL. The resulting composites were characterized by infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. The novel dual function of PLL composites, specifically antibacterial activity and biocompatibility with human cells [human adipose-derived stem cells and non-small-cell lung carcinoma cells (A549)], was carefully investigated. Graphene-DS-PLL composites composed of 4-carboxylic acid benzene diazonium salt (DS) generated more anionic carboxylic acid groups to bind to cationic PLLs, forming the most potent antibacterial agent among PLL and PLL composites with high biocompatibility with human cell culture. This dual functionality can be used to inhibit bacterial growth while enhancing human cell growth.


Complementary LEEM and eV-TEM for imaging and spectroscopy.
Transmission electron microscopy at very low energy is a promising way to avoid damaging delicate biological samples with the incident electrons, a known problem in conventional transmission electron microscopy. For imaging in the 0-30 eV range, we added a second electron source to a low energy electron microscopy (LEEM) setup, enabling imaging and spectroscopy in both transmission and reflection mode at nanometer (nm) resolution. The latter is experimentally demonstrated for free-standing graphene. Exemplary eV-TEM micrographs of gold nanoparticles suspended on graphene and of DNA origami rectangles on graphene oxide further establish the capabilities of the technique. The long and short axes of the DNA origami rectangles are discernable even after an hour of illumination with low energy electrons. In combination with recent developments in 2D membranes, allowing for versatile sample preparation, eV-TEM is paving the way to damage-free imaging of biological samples at nm resolution.


Toxic effects of selenium on growing swine fed corn-soybean meal diets.
A total of 96 crossbred pigs received various levels of sodium selenite to determine the effect of dietary selenium (Se) on growing swine fed corn-soybean meal diets. Levels of supplemental Se were 0, 4, 8, 12, 16 and 20 micrograms/g. There were linear decreases (P less than .01) in both gain and feed intake with increasing levels of dietary Se. Feed/gain increased numerically as dietary Se increased. Hair Se increased quadratically (P less than .01) and blood Se increased linearly (P less than .01) with increasing level of dietary Se. Cell volume and hemoglobin were not affected by dietary treatment. Increasing dietary Se significantly increased glutathione peroxidase (GSH-Px), glutamic-oxalacetic transaminase (GOT). and glutamic-pyruvic transaminase (GPT). External signs of selenosis were noted in some pigs fed 12 or 20 micrograms/g of Se. The toxic level of Se in a corn-soybean meal diet for crossbred pigs appears to be between 4 and 8 micrograms/g. Of variables studied, growth rate was the most sensitive indicator of chronic selenosis in swine.


Preoperative Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Perioperative Liver-Related Complications Following Liver Resection for Colorectal Cancer Metastases.
There are limited data on the potential role of preoperative non-invasive markers, specifically the aspartate-to-alanine aminotransferase ratio and the aspartate aminotransferase-to-platelet ratio index, in predicting perioperative liver-related complications after hepatectomy for colorectal cancer metastases. Patients undergoing liver resection for colorectal cancer metastases in a European institution during 2003-2010 were retrospectively enrolled. Relevant data, such as neoadjuvant chemotherapy, preoperative liver function tests, and perioperative complications, were collected from medical records. The nontumorous liver parenchyma in the surgical specimens of 31 patients was re-evaluated. Overall, 215 patients were included. In total, 40% underwent neoadjuvant chemotherapy and 47% major resection, while 47% had perioperative complications (6% liver-related). In multivariate regression analysis, the aspartate aminotransferase-to-platelet ratio index was independently associated with liver-related complications (odds ratio: 1.149, p = 0.003) and perioperative liver failure (odds ratio: 1.155, p = 0.012). The latter was also true in the subcohort of patients with neoadjuvant chemotherapy (odds ratio: 1.157, p = 0.004) but not in those without such therapy (p = 0.062). The aspartate-to-alanine aminotransferase ratio was not related to liver-related complications (p = 0.929). The area under the receiver operating characteristics curve for the aspartate aminotransferase-to-platelet ratio index as a predictor of liver-related complications was 0.857 (p = 0.008) in patients with neoadjuvant chemotherapy. Increasing aspartate aminotransferase-to-platelet ratio index was observed with an increase in degrees of sinusoidal obstruction syndrome (p = 0.01) but not for fibrosis (p = 0.175) or steatosis (p = 0.173) in the nontumorous liver in surgical specimens. The preoperative aspartate aminotransferase-to-platelet ratio index, but not the aspartate-to-alanine aminotransferase ratio, predicts perioperative liver-related complications following hepatectomy due to colorectal cancer metastases, in particular after neoadjuvant chemotherapy. The aspartate aminotransferase-to-platelet ratio index is related to sinusoidal obstruction syndrome in the nontumorous liver.


The SOIL-N/WEKU model system--a GIS-supported tool for the assessment and management of diffuse nitrogen leaching at the scale of river basins.
The SOIL-N/WEKU model system was developed to estimate groundwater-borne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out in the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) for a macroscale study river basin in Germany (the Uecker basin, ca. 2,400 km2) and a mesoscale study catchment area in Denmark (the Gjern basin, ca. 200 km2). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwater-borne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparison with observed groundwater-borne riverine nitrogen loads showed a very good agreement, proving the key role nitrogen retention in groundwater plays in the two catchment areas.


A Privacy-Preserving Mobile and Fog Computing Framework to Trace and Prevent COVID-19 Community Transmission.
To slow down the spread of COVID-19, governments worldwide are trying to identify infected people, and contain the virus by enforcing isolation, and quarantine. However, it is difficult to trace people who came into contact with an infected person, which causes widespread community transmission, and mass infection. To address this problem, we develop an e-government Privacy-Preserving Mobile, and Fog computing framework entitled PPMF that can trace infected, and suspected cases nationwide. We use personal mobile devices with contact tracing app, and two types of stationary fog nodes, named Automatic Risk Checkers (ARC), and Suspected User Data Uploader Node (SUDUN), to trace community transmission alongside maintaining user data privacy. Each user's mobile device receives a Unique Encrypted Reference Code (UERC) when registering on the central application. The mobile device, and the central application both generate Rotational Unique Encrypted Reference Code (RUERC), which broadcasted using the Bluetooth Low Energy (BLE) technology. The ARCs are placed at the entry points of buildings, which can immediately detect if there are positive or suspected cases nearby. If any confirmed case is found, the ARCs broadcast pre-cautionary messages to nearby people without revealing the identity of the infected person. The SUDUNs are placed at the health centers that report test results to the central cloud application. The reported data is later used to map between infected, and suspected cases. Therefore, using our proposed PPMF framework, governments can let organizations continue their economic activities without complete lockdown.


Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins.
Enhanced prostaglandin production during fungal infection could be an important factor in promoting fungal colonization and chronic infection. Host cells are one source of prostaglandins; however, another potential source of prostaglandins is the fungal pathogen itself. Our objective was to determine if the pathogenic yeasts Cryptococcus neoformans and Candida albicans produce prostaglandins and, if so, to begin to define the role of these bioactive lipids in yeast biology and disease pathogenesis. C. neoformans and C. albicans both secreted prostaglandins de novo or via conversion of exogenous arachidonic acid. Treatment with cyclooxygenase inhibitors dramatically reduced the viability of the yeast and the production of prostaglandins, suggesting that an essential cyclooxygenase like enzyme may be responsible for fungal prostaglandin production. A PGE series lipid was purified from both C. albicans and C. neoformans and was biologically active on both fungal and mammalian cells. Fungal PGE(x) and synthetic PGE(2) enhanced the yeast-to-hypha transition in C. albicans. Furthermore, in mammalian cells, fungal PGE(x) down-modulated chemokine production, tumor necrosis factor alpha production, and splenocyte proliferation while up-regulating interleukin 10 production. These are all activities previously documented for mammalian PGE(2). Thus, eicosanoids are produced by pathogenic fungi, are critical for growth of the fungi, and can modulate host immune functions. The discovery that pathogenic fungi produce and respond to immunomodulatory eicosanoids reveals a virulence mechanism that has potentially great implications for understanding the mechanisms of chronic fungal infection, immune deviation, and fungi as disease cofactors.


Syndesmotic disruption in low fibular fractures associated with deltoid ligament injury.
Low fibular fractures that were associated with deltoid ligament disruption and inferior tibiofibular syndesmotic disruption were studied. All of the patients had a Type B Weber fibular fracture associated with a deltoid ligament injury. It was difficult to detect the syndesmosis disruption on the initial assessment of the anteroposterior and mortise radiographs obtained preoperatively because there was no obvious talar shift on the plain radiograph. Careful evaluation of the plain radiograph and determination of all the recommended measurements were necessary to diagnose the syndesmotic disruption. However, the syndesmotic disruption was easily recognizable on axial computed tomography scans when comparing the injured and the noninjured sides. Axial computed tomography scans also showed a shallow incisura fibularis in all patients and in three cases it revealed anterior fibular subluxation that was not appreciated on the plain radiographs obtained preoperatively. On the basis of the current study using the level of the fibular fracture as a guideline for application of the syndesmotic screw as suggested by some authors may not be accurate. There are several factors that should be considered including the depth of the incisura fibularis, posterior malleolus fractures, deltoid ligament injury, and subluxation of the fibula. The surgeon's impression in the operating room of syndesmosis stability should be considered as the best guideline in the application of syndesmosis fixation rather than depending on the level of the fibular fracture.


Prenatal methylazoxymethanol acetate alters behavior and brain NGF levels in young rats: a possible correlation with the development of schizophrenia-like deficits.
It has been hypothesized that a deleterious key contribution to schizophrenia (SZ) development is a failure of migration and setting of young neurons into their appropriate cortical target sites, particularly in the entorhinal cortex (EC). To test this hypothesis in an animal model, we injected, in pregnant rats, on gestational day (GD) 9, or 10, or 11, or 12, the antimitotic compound methylazoxymethanolacetate (MAM) known to cause EC neuronal loss. We investigated whether or not EC disruption during prenatal development is able to affect behavior, including memory and learning, and brain nerve growth factor (NGF). Prenatally MAM treated young rats didn't display gross behavioral changes in social interaction, open-field and novel object investigation tests. By contrast, GD11 and GD12 MAM treated rats had a retardation in passive avoidance acquisition, while, in GD12 animals, pain sensitivity was reduced. GD12 animals also showed increased NGF in the EC and remaining cortex. MAM treated animals showed no changes in paw NGF or substance P levels suggesting that the altered nociceptive response is not related to local downregulation of these two molecules. The possibility that these behavioral and biochemical alterations might be associated with the onset of SZ is discussed.


Regulation of native Kv1.3 channels by cAMP-dependent protein phosphorylation.
We present evidence that activity of native Kv1.3 channels in human T lymphocytes can be increased by inhibiting phosphatases [using okadaic acid (OA)] or by activating protein kinase A (PKA). OA increased the maximal conductance (Gmax) by 40% and shifted the voltage dependence of activation and inactivation, resulting in a significant increase in window current around the normal membrane potential. PKA inhibition [using the PKA inhibitor peptide PKI-(5-24)] decreased Gmax by 43%, whereas PKA activation [by the Sp diastereomer of adenosine 3',5'-cyclic monophosphothioate (Sp-cAMPS)] increased Gmax by 60% and shifted the inactivation curve, producing an increase in the window current. These results are consistent with our previously published work using cell-attached patches but differ from some studies of Kv1.3. Because we previously reported a similar upregulation by protein kinase C (PKC) activation in these cells, we tested whether the PKA and PKC effects were additive. Our results suggest that PKC-dependent phosphorylation acts as a master switch, inasmuch as calphostin C greatly inhibited the current even after Sp-cAMPS, OA, or PKC activation was used to increase protein phosphorylation. Inasmuch as phosphorylation by both kinases (phorbol ester followed by Sp-cAMPS) abrogated the effects of either kinase alone, our results support the view that Kv1.3 is regulated in a complex manner by serine/threonine phosphorylation.


Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer.
Aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second-line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty-two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy-eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma interaction. Plasma levels of biomarkers at baseline and at pre-dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a ±30% change from baseline to pre-dose 3 (adjusted P < .001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end-products binding protein, insulin-like growth factor-binding protein 1, interleukin-8, kallikrein 5, pulmonary surfactant-associated protein D, tissue inhibitor of metalloproteinases 1, tenascin-C, and tumor necrosis factor receptor 2. None correlated with progression-free survival or maximum tumor shrinkage. Pre-dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.


A brief review of current scientific evidence involving aromatherapy use for nausea and vomiting.
The objective of this study was to compile existing scientific evidence regarding the effects of essential oils (EOs) administered via inhalation for the alleviation of nausea and vomiting. CINAHL, PubMed, and EBSCO Host and Science Direct databases were searched for articles related to the use of EOs and/or aromatherapy for nausea and vomiting. Only articles using English as a language of publication were included. Eligible articles included all forms of evidence (nonexperimental, experimental, case report). Interventions were limited to the use of EOs by inhalation of their vapors to treat symptoms of nausea and vomiting in various conditions regardless of age group. Studies where the intervention did not utilize EOs or were concerned with only alcohol inhalation and trials that combined the use of aromatherapy with other treatments (massage, relaxations, or acupressure) were excluded. Five (5) articles met the inclusion criteria encompassing trials with 328 respondents. Their results suggest that the inhaled vapor of peppermint or ginger essential oils not only reduced the incidence and severity of nausea and vomiting but also decreased antiemetic requirements and consequently improved patient satisfaction. However, a definitive conclusion could not be drawn due to methodological flaws in the existing research articles and an acute lack of additional research in this area. The existing evidence is encouraging but yet not compelling. Hence, further well-designed large trials are needed before confirmation of EOs effectiveness in treating nausea and vomiting can be strongly substantiated.


Appearance concerns and psychological distress among HIV-infected individuals with injection drug use histories: prospective analyses.
Morphologic alterations in body composition are common among HIV-infected individuals, and these changes are associated with increased appearance concerns. Previous cross-sectional data indicate that appearance concerns among HIV-infected individuals are related to increased levels of psychological distress. However, to date, no known prospective data have been published on these relationships. The purpose of the current study was to address the temporal prediction of appearance concerns on depression and anxiety severity. Data were culled from a prospective, randomized controlled trial of cognitive behavioral therapy for depression and medication adherence in individuals with a history of injection drug use (IDU). Participants were 89 HIV-infected individuals who were randomized to either a cognitive behavioral therapy or treatment as usual condition. Linear mixed-level modeling revealed elevated levels of appearance concerns were prospectively related to increased depression and anxiety, as rated by both clinician-administered and self-report measures. Appearance concerns among depressed, IDU, HIV-infected individuals are associated with changes in psychological distress. Psychosocial interventions should consider the role of appearance as it relates to psychological functioning.


Pediatric Calvarial Bone Thickness in Patients With and Without Aural Atresia.
To compare temporal bone thickness along a three-dimensional arc of potential osseointegrated implant sites for bone-anchored hearing aids in children with and without aural atresia using computed tomographic imaging (CT). Retrospective case review. Tertiary children's hospital. Children with or without aural atresia aged less than 11 years who had a temporal bone CT. Calvarial bone volume on CT was rendered in three-dimensional and thickness was reconstructed and measured at up to 12 defined sites along an arc of recommended implant sites. Determining whether a majority of observed potential implant sites have 2, 3, or 4 mm of bone thickness while controlling for age differences and atresia status. A total of 40 atretic (from 34 patients) and 34 control (from 34 patients) temporal bones were compared using CT. Likelihood ratio tests indicated that diagnosis did not have a statistically significant effect on whether patients reached thresholds of 2, 3, or 4 mm at most observed sites (p = 0.781, 0.773, and 0.529, respectively) when adjusting for age. For all children measured, 93% had >50% of measured points greater than or equal to 2 mm thick. Most children had greater than 2 mm of temporal bone thickness at >50% of the sites measured regardless of age or atresia diagnosis. The likelihood of reaching 4 mm of thickness at most sites improves with age. In unilateral patients, there was not a significant difference in thickness between affected and unaffected sides. There was also no significant difference in thickness when comparing patients with atresia to those without.


Risk factors for hepatocellular carcinoma in a cohort infected with hepatitis B or C.
The incidence of hepatocellular carcinoma (HCC) has increased in Australia in recent decades, a large and growing proportion of which occurs among a population chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, risk factors for HCC among these high-risk groups require further characterization. We conducted a population-based cohort study using HBV and HCV cases notified to the New South Wales Health Department between 2000 and 2007. These were linked to cause of death data, HIV/AIDS notifications, and hospital records. Proportional hazards regression was used to identify significant risk factors for developing HCC. A total of 242 and 339 HCC cases were linked to HBV (n = 43 892) and HCV (n = 83 817) notifications, respectively. For both HBV and HCV groups, being male and increasing age were significantly associated with risk of HCC. Increasing comorbidity score indicated high risk, while living outside urban areas was associated with lower risk. Hazard ratios for males were two to three times those of females. For both HBV and HCV groups, cirrhosis, alcoholic liver disease, and the interaction between the two were associated with significantly and considerably elevated risk. This large population-based study confirms known risk factors for HCC. The association with older age highlights the potential impact of HBV and HCV screening of at-risk groups and early clinical assessment. Additional research is required to evaluate the impact of improving antiviral therapy on HCC risk.


Large-scale albuminuria screen for nephropathy models in chemically induced mouse mutants.
Phenotype-driven screening of a great pool of randomly mutant mice and subsequent selection of animals showing symptoms equivalent to human kidney diseases may result in the generation of novel suitable models for the study of the pathomechanisms and the identification of genes involved in kidney dysfunction. We carried out a large-scale analysis of ethylnitrosourea (ENU)-induced mouse mutants for albuminuria by using qualitative SDS-polyacrylamide gel electrophoresis. The primary albuminuria screen preceded the comprehensive phenotypic mutation analysis in a part of the mice of the Munich ENU project to avoid loss of mutant animals as a consequence of prolonged suffering from severe nephropathy. The primary screen detected six confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations and no variant in 48 G3 pedigrees screened for recessive mutations. Further breeding experiments resulted in two lines showing a low phenotypic penetrance of albuminuria. The secondary albuminuria screen was carried out in mutant lines which were established in the Munich ENU project without preceding primary albuminuria analysis. Two lines showing increased plasma urea levels were chosen to clarify if severe kidney lesions are involved in the abnormal phenotype. This analysis revealed severe albuminuria in mice which are affected by a recessive mutation leading to increased plasma urea and cholesterol levels. Thus, the phenotypic selection of ENU-induced mutants according to the parameter proteinuria in principle demonstrates the feasibility to identify nephropathy phenotypes in ENU-mutagenized mice.


Catalytic asymmetric hydroxylative dearomatization of 2-naphthols: synthesis of lacinilene derivatives.
An enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished using a N,N'-dioxide-scandium(iii) complex catalyst. Various substituted ortho-quinols could be obtained in high yields (up to 99%) and enantioselectivities (up to 95 : 5 er). This methodology could be applied in the synthesis of bioactive lacinilenes in a gram-scale reaction. Based on the experimental investigations and previous work, a possible catalytic model was proposed.


Changing climates of conflict: A social network experiment in 56 schools.
Theories of human behavior suggest that individuals attend to the behavior of certain people in their community to understand what is socially normative and adjust their own behavior in response. An experiment tested these theories by randomizing an anticonflict intervention across 56 schools with 24,191 students. After comprehensively measuring every school's social network, randomly selected seed groups of 20-32 students from randomly selected schools were assigned to an intervention that encouraged their public stance against conflict at school. Compared with control schools, disciplinary reports of student conflict at treatment schools were reduced by 25% over 1 year. The effect was stronger when the seed group contained more "social referent" students who, as network measures reveal, attract more student attention. Network analyses of peer-to-peer influence show that social referents spread perceptions of conflict as less socially normative.


Ultrasonographic and clinical evaluation of additional contribution of kinesiotaping to tendon and nerve gliding exercises in the treatment of carpal tunnel syndrome
Background and aim: This study aims to ultrasonographically and clinically evaluate the additive contribution of kinesiotaping to tendon and nerve gliding exercises in the treatment of mild or moderate carpal tunnel syndrome (CTS). Materials and methods: Thirty-eight wrists of patients (n = 21) with CTS were randomized into two groups as the intervention group (n = 19) and the control group (n = 19). Tendon and nerve gliding exercises were given to both groups. In the intervention group, additional kinesiotaping was performed three times with 5-day intervals. Functional assessments were performed with the Boston Carpal Tunnel Syndrome Questionnaire and the Moberg pick-up test. Hand grip and pinch strength were evaluated. Cross-section area (CSA) of the median nerve was measured by ultrasonography. All assessments were performed at baseline and at 3 and 6 weeks after treatment. Results: In the intervention group, there was a significant improvement in all clinical assessments and in the CSA of the median nerve at the level of proximal carpal bones. In the control group, a significant improvement was detected in all clinical parameters except grip strength and ultrasonographic measurements. There was no significant difference in the clinical and ultrasonographic findings between the groups at 6 weeks. Conclusion: Kinesiotaping may provide a positive contribution to ultrasonographic and clinical outcomes in the treatment of mild or moderate CTS in the short term.


Hyperbaric oxygen combined with hydrogen-rich saline protects against acute lung injury.
This study sought to investigate therapeutic effects of hydrogen-rich saline (HRS) combined with hyperbaric oxygen (HBO2) in an experimental rat model of acute lung injury (ALI). Forty male Sprague-Dawley rats were randomly divided into sham, LPS, LPS + HBO2, LPS + HRS, and LPS + HBO2 + HRS groups. After an intratracheal injection of LPS-induced ALI, the rats were given a single-agent HBO2 or HRS or HBO2 + HRS treatment. The treatments were continued for three days in this experimental rat model of ALI. At the end of experiment, the lung pathological, inflammatory factors, and cell apoptosis in the pulmonary tissue were detected by Tunel method and cell apoptosis rate was calculated accordingly. In the groups treated with HBO2 + HRS, pulmonary pathological data, wet-dry weight ratio, and inflammatory factors of pulmonary tissues and alveolar lavage fluid were significantly superior to those of the sham group (p≺0.05). Cell apoptosis detection revealed that no single agent treatment of HRS or HBO2, or combination treatment, could alleviate all cell apoptosis. HRS combined with HBO2 treatment was superior to single treatment (p≺0.05). HRS or HBO2 single treatment could decrease inflammatory cytokines release in lung tissue, reduce the accumulation of oxidative products and alleviate apoptosis of pulmonary cells, then lead to positive therapeutic effects on ALI induced by LPS. Furthermore, HBO2 combined with HRS treatment presented a synergy effect on cell apoptosis decrease and a decline in inflammatory cytokine release and related inflammatory product generation, compared with a single treatment.


The mode of delivery and content of communication strategies used in mandatory and non-mandatory biosimilar transitions: a systematic review with meta-analysis.
Effective patient-provider communication is crucial to promote shared decision-making. However, it is unclear how to explain treatment changes to ensure patient acceptance, such as when transitioning from a bio-originator to a biosimilar. This review investigates communication strategies used to educate patients on transitioning to biosimilars and explores whether the willingness to transition and treatment persistence differs for the delivery (verbal or written) and the amount of information provided. MEDLINE, Embase, Scopus, and relevant conference databases were systematically searched. Communication strategies from 33 studies (88% observational cohort studies) published from 2012 to 2020 were synthesized and willingness to transition, persistence, and subjective adverse events explored. Patients only received information verbally in 11 studies. The remaining 22 studies also provided written information. Cost-saving was the main reason provided for the transition. Patients were most willing to transition when receiving written and verbal information (χ2 = 5.83, p = .02) or written information that only addressed a few (3-5) concerns (χ2 = 16.08, p < .001). There was no significant difference for persistence or subjective adverse events (p's > .05). Few randomized controlled trials have been conducted. Available data shows more willingness to transition when patients received written and verbal information. Initial documents should contain basic information and consultations or telephone calls used to address concerns.


A taxonomic study of the Aeromonas hydrophila-Aeromonas punctata group.
A total of 203 characters has been determined for 68 strains of Aeromonas belonging to the Aeromonas hydrophila-A. punctata group. The results have been subjected to computer analysis using the coefficient of Jaccard-Sneath and the strains clustered by the method of aggregation according to the variance. The 68 strains can be divided into two well-segregated classes on the basis of 59 variable characters, of which seven are of diagnostic value. The two classes are considered as two separate species. The first one (42 strains) is assigned to the type species of the genus, A. hydrophila, and it appears that the species name, A. punctata, is an illegitimate synonym for A. hydrophila. The second (26 strains) constitutes a new species for which the name A. sobria sp. nov. is proposed. The type strain of this new species has been deposited under the reference CIP7433 (our strain 208).


Human T-cell epitopes of the latex allergen Hev b 5 in health care workers.
Latex allergy affects health care workers as a high-risk cohort. Hev b 5 is a major latex allergen reacting with serum IgE from 92% of latex-allergic health care workers. Because CD4(+) T-cell recognition is central to the specific immune response to allergens, identification of dominant T-cell epitopes is important for the development of specific immunotherapy for latex allergy. Our purpose was to map T-cell epitopes of Hev b 5 in health care workers. Six latex-allergic health care workers (grade 3 to 4 enzyme allergosorbent test score) were studied. Peripheral blood latex specific 3-week T-cell lines were generated and screened for proliferative response to overlapping 20-mer peptides of Hev b 5. Supernatants collected at 48 hours were analyzed by ELISA for IL-5 and IFN-gamma. Dot immunoblotting with use of recombinant Hev b 5/maltose-binding protein indicated serum-specific IgE in 5 of 6 patients. T-cell reactivity to one or more Hev b 5 peptides was identified in these 5 donors, but not in the sixth. Hev b 5 (46-65) induced T-cell proliferation in all 5 donors. Hev b 5 (109-128) stimulated T cells from 3 of these patients. Proliferative responses were accompanied by substantial IL-5 secretion and minimal IFN-gamma, indicating a T(H)2-predominant cytokine profile. Five of 6 latex-allergic patients demonstrated T-cell responsiveness to Hev b 5 consistent with a major T-cell reactive latex allergen. Two T-cell immunodominant regions of Hev b 5 were identified, and reactivity to these sites was associated with strong IL-5 but minimal IFN-gamma production.


FastProject: a tool for low-dimensional analysis of single-cell RNA-Seq data.
A key challenge in the emerging field of single-cell RNA-Seq is to characterize phenotypic diversity between cells and visualize this information in an informative manner. A common technique when dealing with high-dimensional data is to project the data to 2 or 3 dimensions for visualization. However, there are a variety of methods to achieve this result and once projected, it can be difficult to ascribe biological significance to the observed features. Additionally, when analyzing single-cell data, the relationship between cells can be obscured by technical confounders such as variable gene capture rates. To aid in the analysis and interpretation of single-cell RNA-Seq data, we have developed FastProject, a software tool which analyzes a gene expression matrix and produces a dynamic output report in which two-dimensional projections of the data can be explored. Annotated gene sets (referred to as gene 'signatures') are incorporated so that features in the projections can be understood in relation to the biological processes they might represent. FastProject provides a novel method of scoring each cell against a gene signature so as to minimize the effect of missed transcripts as well as a method to rank signature-projection pairings so that meaningful associations can be quickly identified. Additionally, FastProject is written with a modular architecture and designed to serve as a platform for incorporating and comparing new projection methods and gene selection algorithms. Here we present FastProject, a software package for two-dimensional visualization of single cell data, which utilizes a plethora of projection methods and provides a way to systematically investigate the biological relevance of these low dimensional representations by incorporating domain knowledge.


THE EFFECT OF IRON LIMITATION ON THE PHOTOPHYSIOLOGY OF PHAEOCYSTIS ANTARCTICA (PRYMNESIOPHYCEAE) AND FRAGILARIOPSIS CYLINDRUS (BACILLARIOPHYCEAE) UNDER DYNAMIC IRRADIANCE(1).
The effects of iron limitation on photoacclimation to dynamic irradiance were studied in Phaeocystis antarctica G. Karst. and Fragilariopsis cylindrus (Grunow) W. Krieg. in terms of growth rate, photosynthetic parameters, pigment composition, and fluorescence characteristics. Under dynamic light conditions mimicking vertical mixing below the euphotic zone, P. antarctica displayed higher growth rates than F. cylindrus both under iron (Fe)-replete and Fe-limiting conditions. Both species showed xanthophyll de-epoxidation that was accompanied by low levels of nonphotochemical quenching (NPQ) during the irradiance maximum of the light cycle. The potential for NPQ at light levels corresponding to full sunlight was substantial in both species and increased under Fe limitation in F. cylindrus. Although the decline in Fv /Fm under Fe limitation was similar in both species, the accompanying decrease in the maximum rate of photosynthesis and growth rate was much stronger in F. cylindrus. Analysis of the electron transport rates through PSII and on to carbon (C) fixation revealed a large potential for photoprotective cyclic electron transport (CET) in F. cylindrus, particularly under Fe limitation. Probably, CET aided the photoprotection in F. cylindrus, but it also reduced photosynthetic efficiency at higher light intensities. P. antarctica, on the other hand, was able to efficiently use electrons flowing through PSII for C fixation at all light levels, particularly under Fe limitation. Thus, Fe limitation enhanced the photophysiological differences between P. antarctica and diatoms, supporting field observations where P. antarctica is found to dominate deeply mixed water columns, whereas diatoms dominate shallower mixed layers.


A video questionnaire identifies upper airway abnormalities in preschool children with reported wheeze.
Accurate characterisation of subjects is essential to interpret data from studies investigating preschool wheezing. To assess whether a video questionnaire (VQ) identifies upper airway abnormalities in preschool children with reported wheeze. Forty three children (median age 17 months, range 3-58) undergoing fibreoptic bronchoscopy for clinical investigation of troublesome noisy breathing at a tertiary centre were studied. Parents were shown a VQ with four clips (wheeze, stridor, and two other upper respiratory noises) and chose the clip(s) resembling their child's main symptom. Doctor observed symptoms, parental reported symptoms, and symptoms identified on VQ were related to bronchoscopy. Thirty subjects had wheeze as the main symptom: 19 had doctor observed wheeze (DOW) and 11 had parental reported wheeze (RW). Parents of two of the subjects with RW identified wheeze alone on VQ and both had normal bronchoscopic findings. Five of the remaining nine subjects with RW had upper airway abnormalities at bronchoscopy. Parents of six subjects with RW identified a noise other than wheeze on VQ; four of these had upper airway abnormalities. Parents of two subjects with RW did not identify a noise on VQ; one had upper airway abnormalities. Of the 19 with DOW, nine parents identified wheeze alone on VQ, and all had a normal upper airway. Parents of nine subjects with DOW identified a noise other than wheeze as an equal or only symptom, (no noise identified in one), and five had upper airway abnormalities. A VQ helps to identify upper airway abnormalities in preschool children with a history of wheezing.


An interpretive review of lymphoma of the stomach.
Lymphoma of the stomach may exist as a primary lesion or as a manifestation of generalized or systemic lymphoma. The primary lesions constitute approximately 3 per cent of all malignant lesions of the stomach and outnumber all other types of non-epithelial malignant lesions. The cause is not known. Gross characteristics often resemble carcinoma, and like carcinoma, the primary lesion may affect other structures by direct extension, may seed to peritoneal surfaces, may metastasize to lymph nodes near or far, and may be borne by the blood to liver, lung or bone. Diagnosis begins with clinical suspicion by the physician, is supported by the results of roentogenographic and gastroscopic studies, and is finally established by a positive study of biopsy specimens obtained with or without laparotomy. Improvements in both gastroscopic instruments and their use promise to increase greatly the accuracy of preoperative diagnosis. Pseudolymphoma of the stomach, a rare type of inflammatory lesion, may, on occasion, offer a difficult differential diagnosis from that of lymphoma. The clinical approach to the lesion, whether the diagnosis is histologically proved or not, is the same as for suspected carcinoma. A laparotomy is usually necessary to determine the possibility of surgical cure, unless distant spread or systemic involvement can be established by other means, such as a distant lymph node containing the disease or a positive needle biopsy of the liver. When a cure seems possible, resection is favored by most surgeons, even though it entails total gastrectomy or multiple organ resection. Opinion is divided as to whether or not a curative resection should be followed routinely by irradiation, although irradiation is generally favored by palliation of lesions not amenable to resection. Transgastroscopic biopsy and gastroscopic follow-up study may permit radiation to be tested as the only form of treatment of favorable lesions. At the present time, chemotherapy should be reserved for lesions not controlled by operation or irradiation. Stage for stage, the outlook for lymphoma of the stomach is about twice as favorable as that for carcinoma. No generally accepted classification of lymphoma exists as yet. Correlations between prognosis and microscopic characteristics are not close, except for the generally favorable outlook for lymphocytic lymphoma.


Flemish experience using the Advanta V12 stent-graft for the treatment of iliac artery occlusive disease.
The aim of this study was to evaluate the technical feasibility and safety of implanting a polytetrafluoroethylene (PTFE) covered balloon expandable stent to treat iliac artery stenoses and occlusions. Additionally, the primary patency and clinical and hemodynamic efficacy at 1 year were analysed. This nonrandomized, prospective study involved patients with claudication and iliac artery occlusive disease at 2 participating centres. Patients with suitable lesions determined by clinical examination, ankle-brachial indices (ABIs), colour-flow duplex ultrasound (CFDU), magnetic resonance angiogram (MRA) and confirmed with biplanar digital subtraction angiography (DSA) were treated with PTFE-covered stainless steel stents. Procedural and 30-day periprocedural complications were recorded prospectively. According to in-hospital standards, follow-up with clinical ischemia category determination, ABI and CFDU was performed at 1, 6 and 12 months to determine treatment efficacy and primary limb patency. In total, 91 limbs were treated in 65 patients (51 male; mean age 65 years). Stent-graft deployment was successful in 91 (100%) limbs. There were no limbs with residual stenosis >30%. There were no procedural or 30-day complications. The clinical ischemia category distribution improved significantly at 1, 6 and 12 months. The mean ABI rose significantly from 0.59 before treatment to 0.98, 0.98 and 0.99 at 1, 6 and 12 months after the procedure. Primary limb patency at 1-year was 91.1% Implantation of Advanta V12 PTFE-covered stent for iliac occlusive disease shows to be safe and feasible with excellent clinical results at 1 year in the investigated patient cohort.


Transcription and cancer.
The normal growth, development and function of an organism requires precise and co-ordinated control of gene expression. A major part of this control is exerted by regulating messenger RNA (mRNA) production and involves complex interactions between an array of transcriptionally active proteins and specific regulatory DNA sequences. The combination of such proteins and DNA sequences is specific for given gene or group of genes in a particular cell type and the proteins regulating the same gene may vary between cell types. In addition the expression or activity of these regulatory proteins may be modified depending on the state of differentiation of a cell or in response to an external stimulus. Thus, the differentiation of embryonic cells into diverse tissues is achieved and the mature structure and function of the organism is maintained. This review focusses on the role of perturbations of these transcriptional controls in neoplasia. Deregulation of transcription may result in the failure to express genes responsible for cellular differentiation, or alternatively, in the transcription of genes involved in cell division, through the inappropriate expression or activation of positively acting transcription factors and nuclear oncogenes. Whether the biochemical abnormalities that lead to the disordered growth and differentiation of a malignant tumour affect cell surface receptors, membrane or cytoplasmic signalling proteins or nuclear transcription factors, the end result is the inappropriate expression of some genes and failure to express others. Current research is starting to elucidate which of the elements of this complicated system are important in neoplasia.


Ordinal Distance Metric Learning for Image Ranking.
Recently, distance metric learning (DML) has attracted much attention in image retrieval, but most previous methods only work for image classification and clustering tasks. In this brief, we focus on designing ordinal DML algorithms for image ranking tasks, by which the rank levels among the images can be well measured. We first present a linear ordinal Mahalanobis DML model that tries to preserve both the local geometry information and the ordinal relationship of the data. Then, we develop a nonlinear DML method by kernelizing the above model, considering of real-world image data with nonlinear structures. To further improve the ranking performance, we finally derive a multiple kernel DML approach inspired by the idea of multiple-kernel learning that performs different kernel operators on different kinds of image features. Extensive experiments on four benchmarks demonstrate the power of the proposed algorithms against some related state-of-the-art methods.


Zingiber officinale Roscoe (Ginger) as a Complementary Option for Clinical Treatment of Endometriosis: An Experimental Study in Rats.
Endometriosis was induced (autotransplant) in Wistar rats. After 21 days, the rats were randomly divided into two groups (16 female rats each). Control group was forced-fed 0.9% sodium chloride solution, and the ginger group was forced-fed 0.5 mg/100 g of Zingiber officinale Roscoe fresh extract, both by gavage, for 14 days, in addition to their normal diet. After that, an anesthetic dose (ketamine/xylazine) was administered until euthanasia. Peritoneal lavage fluid was collected to evaluate tumor necrosis factor (TNF)-α and interleukin (IL)-6, and autotransplant was measured and excised to evaluate histology. The final mean volumes were larger in the control group (120.92 mm3 ± 78.91) than in the ginger group (40.50 mm3 ± 19.57) (P = .01). The endometriosis foci increased in the control group from 45.10 mm3 ± 29.96 at 21 days postimplantation to 120.92 mm3 ± 78.91 on the day of euthanasia (P = .02). In the ginger group, a slight increase was observed from 38.43 mm3 ± 19.96 to 40.50 mm3 ± 19.57, without statistical difference (P = .83). In addition, a greater increase in growth of the endometriosis foci was found when compared with the control (75.81 mm3 ± 58.95) and ginger groups (2.07 mm3 ± 18.87) (P = .004). No difference was found in TNF-α (P = .51) and in IL-6 (P = .12). The degree of lesion atrophy was higher in the ginger group (1 ± 0.92) than in the control group (2.25 ± 1.16) (P = .03). The ginger extract reduced and atrophied autotransplanted endometriosis foci, but did not reduce IL-6 and TNF-α in the peritoneal lavage fluid.


Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure.
We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells' inflammatory phenotype may impact obesity and its complications.


Human platelet alloantigen systems in three Chinese ethnic populations.
Knowledge of the prevalence of human platelet antigens (HPA) in different populations is important for effective diagnosis and management of immune-mediated platelet disorders. The purpose of this study was to determine HPA gene frequencies in the majority Han ethnic population of China and in ethnic She and Tajik minority populations. Using PCR sequence specific primers, HPA- 1, -2, -3, -4, -5, and -6, we determined genotypes for ethnic Han, She, and Tajik blood donors. HPA gene frequencies for Chinese Han were found to be similar to those of She, reflecting the historic affinities of these two populations. HPA gene frequencies for Tajik were closer to those for Caucasians than to Chinese Han, She, or other Asian populations, reflecting their disparate origin and historic geographic isolation. HPA gene frequencies in these Chinese populations reflect their historic origins. Knowledge of these findings may be used to better understand and treat immune-mediated platelet disorders in these populations.


Two new species of Xiphocephalus in Eleodes tricostata and Eleodes fusiformis (Coleoptera: Tenebrionidae: Eleodini) from the sandhills of western Nebraska.
Xiphocephalus triplogemmatus n. sp. and Xiphocephalus quadratogemmatus n. sp. (Apicomplexa: Eugregarinida) are described from Eleodes tricostata and Eleodes fusiformis (Coleoptera: Tenebrionidae), respectively, collected from Keith County in the sandhills of western Nebraska. Gamonts can be diagnosed with some confidence based on relative size and shape of the deutomerite, but these taxa are distinguished by differences in oocyst size, shape, and residuua number. Together with Xiphocephalus ellisi from Eleodes opacus in the same region, X. triplogemmatus and X. quadratogemmatus form a distinct Nearctic xiphocephalid group that is morphologically distinct from groups that occur in the Palearctic, Ethiopian, and Oriental regions.


Cross-reactivity between related sequences found in Acinetobacter sp., Pseudomonas aeruginosa, myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis.
To investigate the possible role of molecular mimicry to bacterial components in multiple sclerosis (MS) pathogenesis we examined antibody responses to mimicry peptide sequences of Acinetobacter, Pseudomonas aeruginosa and myelin components. Antibodies to mimicry peptides from Acinetobacter (p<0.001), P. aeruginosa (p<0.001), myelin basic protein (MBP) (p<0.001) and myelin oligodendrocyte glycoprotein (MOG) (p<0.001) were significantly elevated in MS patients compared to controls. Antisera against MBP (residues 110-124) reacted with both Acinetobacter and Pseudomonas peptides from 4- and gamma-carboxymuconolactone decarboxylase, respectively. MOG (residues 43-57) antisera reacted with Acinetobacter peptide from 3-oxo-adipate-CoA-transferase subunit A. The role of these bacteria in MS is unclear but demonstrates that molecular mimicry is not restricted to viruses suggesting bacterial infections could play a role in MS pathogenesis. Further work is required to evaluate the relevance of these cross-reactive antibodies to the neuropathology of MS.


S-adenosyl-L-methionine co-administration prevents the ethanol-elicited dissociation of hepatic mitochondrial ribosomes in male rats.
Chronic ethanol feeding to male rats has been shown to result in decreased mitochondrial translation, depressed respiratory complex levels and mitochondrial respiration rates. In addition, ethanol consumption has been shown to result in an increased dissociation of mitoribosomes. S-adenosyl-L-methionine (SAM) is required for the assembly and subsequent stability of mitoribosomes and is depleted during chronic ethanol feeding. The ability of dietary SAM co-administration to prevent these ethanol-elicited lesions was investigated. Male Sprague-Dawley rats were fed a nutritionally adequate liquid diet with ethanol comprising 36% of the calories according to a pair-fed design for 28 days. For some animals, SAM was supplemented in the diet at 200 mg/l. Liver mitochondria were prepared and mitoribosomes isolated. Respiration rates, ATP levels, respiratory complex levels, and the extent of mitoribosome dissociation were determined. Twenty-eight days of ethanol feeding were found to result in decreased SAM content, depressed respiration, and increased mitoribosome dissociation. No changes in mitochondrial protein content; levels of respiratory complexes I, III, and V; complex I activities; and ATP levels were detected. Co-administration of SAM in the diet was found to prevent ethanol-induced SAM depletion, respiration decreases and mitoribosome dissociation. Taken together, these findings suggest (1) that mitoribosome dissociation precedes respiratory complex depressions in alcoholic animals and (2) that dietary supplementation of SAM prevents some of the early mitochondrial lesions associated with chronic ethanol consumption.