Gene expression in the conversion of early-phase to late-phase long-term potentiation.
Changes in gene expression associated with different forms of synaptic plasticity in rat hippocampus were investigated. Microarray analysis revealed differential expression of hundreds of genes 30 min after synaptic or antidromic stimulation in different patterns. Results of selected genes were verified by LightCycler RT-PCR. Synaptic activation in a theta burst protocol, which induced long-term potentiation (LTP), increased the mRNA abundance of BDNF-exon 1, but antidromic stimulation in the presence of CNQX, APV, and MCPG (to block glutamatergic synapses) decreased the level of mRNA of this transcript, as did 1 Hz synaptic stimulation. The opposite regulation of this BDNF transcript after firing of the postsynaptic neuron, coincidently or uncorrelated with synaptic firing, is consistent with the effects of BDNF on synaptic transmission, suggesting possible involvement in strengthening and weakening CA1 synapses after correlated versus uncorrelated firing of the postsynaptic neurons with its synaptic inputs. Possible involvement of transcriptional regulation of BDNF in the conversion of early-phase LTP to late-phase LTP are discussed in the context of previous studies by Dudek & Fields (Proc. Natl. Acad. Sci. USA 99: 3962-3967) showing that this conversion can be induced by antidromic stimulation of CA1 neurons in the absence of excitatory synaptic activity.


In situ synthesis and properties of reduced graphene oxide/Bi nanocomposites: as an electroactive material for analysis of heavy metals.
An in situ modified Hummers method (without the use of any surfactants) has been used for the deposition of bismuth (Bi) nanoparticles onto the surface of reduced graphene oxide (RGO) sheets. The as-synthesized nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, transmission electron microscopy (TEM), thermogravimetry (TG) and differential scanning calorimetry (DSC). The morphology of the RGO/Bi nanocomposites provides a better choice as an electrode material for detection of heavy metal ions due to its better functional properties over the Bi film electrode. Trace analysis of heavy metal ions like Cd(+2), Pb(+2), Cu(+2) and Zn(+2) in water is carried out by stripping voltammetric analysis using RGO/Bi nanocomposite as an electrode material. The sensitivity and detection limit of the electrode were quantitatively estimated from the analysis. The three sigma detection limits at different deposition potential for Cd(2+), Pb(2+), Zn(2+) and Cu(2+) were obtained as 2.8, 0.55, 17 and 26μgL(-1), respectively. Copper detection using Bi-film electrode was a major challenge, which has been resolved using the RGO/Bi nanocomposite electrode.


Cardiac morphologic findings in patients with acute myocardial infarction treated with recombinant tissue plasminogen activator.
The hearts of 52 patients (aged 61 +/- 11 years, 34 men) who participated in the Thrombolysis in Myocardial Infarction (TIMI) Study and died from 5 hours to 260 days (median 2.7 days) after onset of chest pain were studied. One heart became available at cardiac transplantation. Of the 52 patients, 38 received recombinant tissue plasminogen activator (rt-PA) not followed by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Eight had PTCA, and 6 had CABG. The infarcts were hemorrhagic by gross inspection (with histologic confirmation) in 23 patients, nonhemorrhagic in 20, not visible grossly in 2 and, in 7, there was no myocardial necrosis by either gross or histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)


White Matter Injury After Subarachnoid Hemorrhage: Role of Blood-Brain Barrier Disruption and Matrix Metalloproteinase-9.
We recently observed early white matter injury after experimental subarachnoid hemorrhage (SAH), but the underlying mechanisms are uncertain. This study investigated the potential role of matrix metalloproteinase (MMP)-9 in blood-brain barrier (BBB) disruption and consequent white matter injury. SAH was induced by endovascular perforation in adult male mice. The following 3 experiments were devised: (1) mice underwent magnetic resonance imaging at 24 h after SAH and were euthanized to determine BBB disruption and MMP-9 activation in white matter; (2) to investigate the role of MMP-9 in BBB disruption, lesion volumes on magnetic resonance imaging were compared between wild-type (WT) and MMP-9 knockout (MMP-9-/-) mice at 24 h after SAH; (3) WT and MMP-9-/- mice underwent magnetic resonance imaging at 1 and 8 days after SAH to detect time-dependent changes in brain injury. Brains were used to investigate myelin integrity in white matter. In WT mice with SAH, white matter showed BBB disruption (albumin leakage) and T2 hyperintensity on magnetic resonance imaging. MMP-9 activity was elevated at 24 h after SAH. MMP-9-/- mice had less white matter T2 hyperintensity after SAH than WT mice. At 8 days after SAH, WT mice had decreased myelin integrity and MMP-9-/- mice developed less white matter injury. SAH causes BBB disruption and consequent injury in white matter. MMP-9 plays an important role in those pathologies and could be a therapeutic target for SAH-induced white matter injury.


Epidural analgesia inhibits the renin and aldosterone response to surgery.
Renin activity and aldosterone concentration in plasma and excretion of sodium and potassium in urine were measured during a period of 24 hours in 12 patients undergoing hysterectomy under general anaesthesia or epidural analgesia. Analgesia extended from T4 to S5 and was effective throughout the study. The normal stress-induced increase in plasma renin activity and aldosterone was inhibited by epidural analgesia. Urinary excretion of potassium was significantly lower in the epidural group, but sodium and water retention showed no difference between groups. It is concluded that neurogenic stimuli from the surgical area are important release mechanisms of the renin-aldosterone response to surgery. The results suggest that post-operative sodium retention is caused by factors other than the mineralocorticoid system.


Analysis of mutants disrupted in bacillithiol metabolism in Staphylococcus aureus.
Bacillithiol (BSH), an α-anomeric glycoside of l-cysteinyl-d-glucosaminyl-l-malate, is a major low molecular weight thiol found in low GC Gram-positive bacteria, such as Staphylococcus aureus. Like other low molecular weight thiols, BSH is likely involved in protection against a number of stresses. We examined S. aureus transposon mutants disrupted in each of the three genes associated with BSH biosynthesis. These mutants are sensitive to alkylating stress, oxidative stress, and metal stress indicating that BSH and BSH-dependent enzymes are involved in protection of S. aureus. We further demonstrate that BshB, a deacetylase involved in the second step of BSH biosynthesis, also acts as a BSH conjugate amidase and identify S. aureus USA 300 LAC 2626 as a BSH-S-transferase, which is able to conjugate chlorodinitrobenzene, cerulenin, and rifamycin to BSH.


Learning-Based Multimodal Image Registration for Prostate Cancer Radiation Therapy.
Computed tomography (CT) is widely used for dose planning in the radiotherapy of prostate cancer. However, CT has low tissue contrast, thus making manual contouring difficult. In contrast, magnetic resonance (MR) image provides high tissue contrast and is thus ideal for manual contouring. If MR image can be registered to CT image of the same patient, the contouring accuracy of CT could be substantially improved, which could eventually lead to high treatment efficacy. In this paper, we propose a learning-based approach for multimodal image registration. First, to fill the appearance gap between modalities, a structured random forest with auto-context model is learnt to synthesize MRI from CT and vice versa. Then, MRI-to-CT registration is steered in a dual manner of registering images with same appearances, i.e., (1) registering the synthesized CT with CT, and (2) also registering MRI with the synthesized MRI. Next, a dual-core deformation fusion framework is developed to iteratively and effectively combine these two registration results. Experiments on pelvic CT and MR images have shown the improved registration performance by our proposed method, compared with the existing non-learning based registration methods.


Cell Membrane Electropulsation: Chemical Analysis of Cell Membrane Modifications and Associated Transport Mechanisms.
The transport of substances across the cell membrane is complex because the main physiological role of the membrane is the control of the substances that would enter or exit the cells. Life would not be possible without this control. Cell electropulsation corresponds to the delivery of electric pulses to the cells and comprises cell electroporation and cell electropermeabilization. Cell electropulsation allows for the transport of non-permeant molecules across the membrane, bypassing the physiological limitations. In this chapter we discuss the changes occurring in the cell membrane during electroporation or electropermeabilization as they allow to understand which molecules can be transported as well as when and how their transport can occur. Electrophoretic or diffusive transports across the cell membrane can be distinguished. This understanding has a clear impact on the choice of the electrical parameters to be applied to the cells as well as on other aspects of the experimental protocols that have to be set to load the cells with non-permeant molecules.


Reductive amination of aldehyde 2,4-dinitrophenylhydrazones using cyanoborohydride for determination of selected carbonyl compounds in Port wines, table wines, and wine spirits.
Carbonyl compounds are mainly analysed by HPLC with ultraviolet detection after reaction with DNPH, yielding carbonyl-hydrazones. The presence of geometrical isomers whose relative abundance is dependent on the reaction condition introduces analytical errors and increases the complexity of the chromatograms. In this work, a simple, fast, and robust method for determining pyruvic acid, acetaldehyde, and α-ketobutyric acid in Port wines, dry table wines, and wine spirits by reductive amination of aldehyde 2,4-dinitrophenylhydrazones using cyanoborohydride followed by HPLC-DAD was developed, optimised and validated. The developed method was simple and showed good performance in several parameters such as linearity (0.025-200 mg/L), detection limits (0.0043-0.0097 mg/L), quantification (0.014-0.032 mg/L), precision (1.1-4.2 %) and accuracy (99.02 %). The method was applied to five different wine matrices, White, Tawny, and Ruby Port wines, white and red table wines, and wine spirits. The quantification of these carbonyl compounds simultaneously was achieved in Port wines for the first time.


Molecular hybridization used to design and synthesize neo-tanshinlactone derivatives as PD-1/PD-L1 inhibitors.
Four series of molecular hybrids (37 final products) of neo-tanshinlactone, a natural product extracted from Salvia miltiorrhiza Bunge, and known PD-1/PD-L1 interaction inhibitors were prepared as possible chemotherapeutic agents against triple negative breast cancer. Screening using a homogenous time-resolved fluorescence method resulted in three lead compounds (MZ52 IC50 74 ± 4 nM; MZ58 IC50 134 ± 17 nM; MZ61 IC50 225 ± 19 nM). With less T cell cytotoxicity and effects in activating CD8+ T cells in a T cell proliferation assay and a functionality experiment, MZ58 was selected as the best candidate for animal experiments. MZ58 exhibited antitumor effects in a subcutaneous transplantation tumor model as well as effects in reducing T cell exhaustion. In conclusion, after in vivo and in vitro experiments, we successfully acquired an effective candidate (MZ58) showing antitumor effects with low cytotoxicity toward T cells as well as the ability to activate CD8+ T cells and reduce T cell exhaustion.


Zygotic and somatic embryos of cucumber (Cucumis sativus L.) substantially differ in their levels of abscisic acid.
In this work we studied the changes in the level of abscisic acid (ABA) in the somatic embryos (SE) and in the diploid and triploid zygotic embryos (ZE) of the same cucumber line during embryogenesis and seed maturation. Different stages of seed development were selected according to days after pollination (DAP): 21, 24, 28, 35, 42 and 42 plus 14 days of storage for diploid ZE and 35 and 42 plus 14 days of storage for triploid ZE. SE were collected at five growth stages from globular to late cotyledonary. Quantitative analysis of ABA was performed using an enzyme linked immunosorbent assay (ELISA) test. Both types of embryos - somatic and zygotic - essentially differed in their levels of ABA, always being the highest for 2n ZE and lowest for SE. Although the concentration of ABA in ZE of the triploid line was higher when compared with the same DAP, when the comparison was based on embryo development, both the concentration and content of ABA was higher in the diploid line. The pattern of developmental changes in the level of ABA in the diploid ZE was consistent with that known for other species. An increase was observed during embryo development with a peak (51.1 µg g(-1) FW or 0.95 µg per embryo) at the final stage of embryo formation between 21 and 24 DAP. A sharp decrease in the ABA level then took place (more than 3-fold within 4 days) and was followed by a further reduction as the seed matured. The maximal and minimal values for ABA concentration differed about 35-fold. SE differed substantially from their zygotic counterparts not only in that the concentration of ABA was extremely low (0.005-0.011 µg g(-1) FW) but also that no significant changes occurred during embryo development and no peak of ABA concentration was observed. Other tissues of the ovule and ovary also contained ABA and could be a source of ABA for the embryo.


Effect of solvents on intra- and inter-molecular interactions of oligothiophenes.
Oligothiophenes have long been used as model compounds to understand the chemistry of polythiophenes. Herein, we have some quantum chemical calculations and intra- and inter-molecular interaction calculations of a series of oligothiophenes such as terthiophene, quintetthiophene, sevensthiophene, terthiophene-terthiophene, terthiophene-water, terthiophene-methanol, and terthiophene-chloroform performed by time-dependent density functional theory (TD-DFT), density functional theory (DFT), and Multiwfn: a multifunctional wavefunction analyzer. The UV-vis spectra, HOMO-LUMO energies, NBO analysis, MEP, molecular structures, and electronic properties were computed using DFT/TD-DFT at the level of B3LYP/6-31+ G (d,p) and described. The nature of molecular interactions between terthiophene and solvents like water, methanol, and chloroform were also investigated using non-covalent interaction index (NCI), reduced density gradient (RDG), localized orbital locator (LOL), and electron localization function (ELF) topological analyses. Besides, Fukui functions and energy of population density-of-states were computed using the same method. The calculation results show that there are some changes in the terthiophene with the addition of solvent to the medium. DFT calculations were performed using the Gaussian 09 software and GaussView 5.0 visulation program. Multiwfn software is used to calculate the reduced density gradient (RDG) scatterplots, non-covalent interactions (NCI), ELF, LOL, Fukui analysis, and energy of population density-of-states of oligothiophenes.


An epidemiological study of acne in female adults: results of a survey conducted in France.
Acne is usually perceived as a disease of teenagers, and most epidemiological studies have focused on adolescents. The primary objective was to investigate the prevalence of acne in a representative sample of French females. Information about skin type, life-style factors influencing acne and quality of life were also recorded. A self-administered questionnaire was sent to 4,000 adult women aged 25-40 years, after a validation test by three dermatologists. A definition of acne severity, according to questionnaire answers, was established before the questionnaire was sent out. A total of 3394 women completed the questionnaire of which 3,305 were useable. The data showed a prevalence of acne in 17% of the population, and physiological acne in 24%. Thus, the total acne prevalence was 41%. Forty-nine per cent of the acne patients had acne sequelae (scars and/or pigmented macules). Forty-one per cent of adult acne patients had not experienced acne during their adolescence. A premenstrual flare and stress was recorded as causing acne in 78% and 50%, respectively. Twenty-two per cent of acne subjects were currently receiving therapy. For most patients, acne did not severely impair their quality of life. This study shows a prevalence of acne in 41% of women in the general population. A high proportion of these acne cases are late onset acne.


University brand: A systematic literature review.
Despite its significant role, brand management is an oft-overlooked and challenging aspect in the development of academic institutions, especially in higher education context. Based on a systematic review of journal articles from various sources including ScienceDirect, Emerald Insight and SpringerLink during the 2000-2021 period, the authors of this paper seek to identify, evaluate, and analyze university brand. After careful consideration of academic publications based on their relevance for the research objectives, 43 articles have been included in this comprehensive and integrative review. Special attention is paid to the theories underlying brand management, brand positioning, brand identity of a higher education institution, marketing strategies, as well as implications for management, students, and staff. Moreover, some valuable lessons which a university can learn from a company in marketing are identified. Thereby, the competitive advantages of a university would be firmly enhanced. It is our hope that this paper will explore a new path for further research and provide another perspective for administrators, authors and practitioners in the area of university brand.


Ageing-resembling phenotype of long-term allogeneic hematopoietic cells recipients compared to their donors.
Ageing is a complex phenomenon that leads to decreased proliferative activity, loss of function of the cells, and cellular senescence. Senescence of the immune system exacerbates individual's immune response, both humoral and cellular but increases the frequency of infections. We hypothesized that physiological ageing of adaptive immune system occurs in recipients of allogeneic hematopoietic cells transplant (allo-HCT) at faster rate when compared to their respective donors since the small number of donor cells undergo immense proliferative stress restoring recipients hematopoiesis. We compared molecular characterizations of ageing between recipients and donors of allo-HCT: telomeric length and immunophenotypic changes in main lymphocyte subsets - CD4+, CD8+, CD19+, CD56+. Median telomeric length (TL) of CD8+ lymphocytes was significantly longer in donors compared to recipients (on average 2,1 kb and 1,7 kb respectively, p = 0,02). Similar trends were observed for CD4+ and CD19+ although the results did not reach statistical significance. We have also found trends in the immunophenotype between recipients and donors in the subpopulations of CD4+ (naïve and effector memory), CD8+ Eomes+ and B-lymphocytes (B1 and B2). Lower infection risk recipients had also a significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p = 0,04. Our data do not support the initial hypothesis of accelerated aging in the long term all-HCT recipients with the exception of the recipients lymphocytes (mainly CD8+) which present some molecular features, characteristic for physiological ageing (telomeric shortening, immunophenotype) when compared to their respective donors. However, a history of lower infection numbers in HCT recipients seems to be associated with increased percentage of NK cells. The history of GVHD seems not to affect the rate of ageing. Therefore, it is safe to conclude that the observed subtle differences between recipients' and donors' cells result mainly from the proliferative stress in the early period after allo-HCT and the difference between hosts' and recipients' microenvironments.


Biodistribution and pharmacokinetics of aerosol and intravenously administered DNA-polyethyleneimine complexes: optimization of pulmonary delivery and retention.
This report describes the time-dependent biodistribution of human p53 plasmid delivered in aerosol with polyethyleneimine in mice compared to the distribution of this material following intravenous injection. Area-under-the-curve values for p53 plasmid after inhalation were 2.8-fold greater than values after intravenous administration, despite the fact that the delivered aerosol dose was one-fifth the intravenous dose. After aerosol administration, pulmonary concentrations of p53 plasmid were high and other organs showed amounts not distinguishable from untreated control. High concentrations of p53 plasmid in the lungs remained with negligible reduction for at least 24 h. Shortly after intravenous injection, organs exhibited the following relative levels of exogenously administered p53: liver > spleen > blood > or = lungs > heart > kidney. These results demonstrate effective pulmonary delivery of DNA in complex with PEI by aerosol, without significant systemic dissemination. In contrast, intravenous administration caused a prompt systemic distribution of DNA with a shorter half-life of the administered gene in the lungs.


Endoscopic balloon dilatation as treatment of gastric outlet obstruction in infancy and childhood.
The application of balloon dilatation as treatment of gastric outlet obstruction is described. In two infants after inadequate pyloromyotomy and in an 11-year-old boy with surgical damage to the vagus, balloon dilatation was successful and considered a good alternative to surgery in these conditions.


Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.
We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications. NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS). Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001). In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.


Accurate determination for lipidomics based on LC-tandem-MS parameters modeling, prediction, and database: Monitoring the progression of hepatocellular carcinoma.
The unavailability of adequate lipid reference standards is a major challenge for accurate quantitative analysis of lipidomics. Based on the discovery of regularity and predictability for lipids in chromatography-mass spectrometry behaviors, "target compound-structure correlation-analytical parameter database" protocol and "modeling-prediction" strategy were carried out to calculate the relative coefficients of analytical parameters within each subclass. Then the relevant LC-tandem-MS parameters of unknown lipids were predicted and a quantification parameter database for 4081 lipids was established and validated. Reference standards-independent accurate determination for lipidomics was achieved with the parameter's database and applied to monitor the change of lipid metabolism in the plasma of whole course of health-hepatitis-cirrhosis-hepatocellular carcinoma (HCC). Combined Student's t test, orthogonal partial least squares discrimination analysis (OPLS-DA) and binary logistic regression-ROC analysis, lipid biomarkers for differentiating health from each disease and differentiating different stages of disease were identified and the pathogenesis of HCC was preliminarily clarified. The established methodology would shed light on comprehensive and accurate quantitative lipidomics and exploring the pathomechanism and potential therapeutic targets of HCC.


Susceptibility of South African Bulinus africanus populations to infection with Schistosoma haematobium.
The use of intermediate host snails of Schistosoma spp. which are insusceptible to infection has been proposed as a possible method of controlling schistosomiasis. The objective of this approach is to change the susceptibility of natural snail populations from being predominantly susceptible to a non-susceptible state, through the release of refractory snails into natural habitats. In an attempt to determine whether or not such refractory Bulinus africanus populations occur in eastern South Africa, F1 generation snails of populations from 8 different areas were exposed to miracidia hatched from eggs excreted in the urine of schoolchildren infected with Schistosoma haematobium in the Nelspruit district. The proportion of snails successfully infected ranged from 27 to 100%, which revealed considerable genetic heterogeneity amongst populations of the same snail species. One population from Natal could be regarded as partially refractory, while a laboratory population from Durban proved to be 100% susceptible. A completely refractory strain of B. africanus has not yet been identified.


Host Genetics But Not Commensal Microbiota Determines the Initial Development of Systemic Autoimmune Disease in BXD2 Mice.
To determine the extent to which the gut microbiome influences systemic autoimmunity in a mouse model of lupus. We generated germ-free (GF) lupus-prone BXD2 mice, which under normal conditions develop spontaneous germinal centers (GCs) and high titers of serum autoantibodies. GF status was confirmed by gut bacterial culture. The autoimmune phenotypes of 6- and 12-month-old gnotobiotic GF BXD2 mice and specific pathogen-free (SPF) BXD2 mice were compared. Serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay. Histologic sections of the mouse kidney and joints were evaluated. Flow cytometry was used to analyze GCs and age-associated B cells. CD4+ T cells were analyzed for PD-1+ICOS+ activated T cells, T follicular regulatory (Tfr) cells (Foxp3+CD25+ PD-1+CXCR5+), and PD-1+ICOS+ T cells expressing interleukin-17A (IL-17A) or interferon-γ (IFNγ) after stimulation with phorbol myristate acetate (PMA)/ionomycin. In 6-month-old mice, GF status did not affect splenomegaly, GC B cells, age-associated B cells, or serum autoantibody levels, except for IgG antihistone. GF BXD2 mice exhibited a significantly higher percentage of Tfr cells compared to their SPF counterparts (P < 0.05). At 12 months of age, however, GF BXD2 mice had significantly diminished IgG autoantibody levels and a lower percentage of GC B cells and age-associated B cells (P < 0.05). Following stimulation with PMA/ionomycin, PD-1+ICOS+ CD4+ T cells expressed significantly lower IL-17A, but not IFNγ, levels in GF BXD2 mice compared to SPF BXD2 mice (P < 0.01). SPF BXD2 mice and GF BXD2 mice developed equivalent renal and joint disease with no significant differences in severity. Our results suggest a model in which genetics plays a dominant role in determining the initial development of autoimmunity. In contrast, gut microbiomes may regulate the persistence of certain aspects of systemic autoimmunity.


Measurement of craving among gamers with internet gaming disorder using repeated presentations of game videos: a resting-state electroencephalography study.
Internet gaming disorder (IGD) is receiving increasing attention owing to its effects on daily living and psychological function. In this study, electroencephalography was used to compare neural activity triggered by repeated presentation of a stimulus in healthy controls (HCs) and those with IGD. A total of 42 adult men were categorized into two groups (IGD, n = 21) based on Y-IAT-K scores. Participants were required to watch repeated presentations of video games while wearing a head-mounted display, and the delta (D), theta (T), alpha (A), beta (B), and gamma (G) activities in the prefrontal (PF), central (C), and parieto-occipital (PO) regions were analyzed. The IGD group exhibited higher absolute powers of DC, DPO, TC, TPO, BC, and BPO than HCs. Among the IGD classification models, a neural network achieves the highest average accuracy of 93% (5-fold cross validation) and 84% (test). These findings may significantly contribute to a more comprehensive understanding of the neurological features associated with IGD and provide potential neurological markers that can be used to distinguish between individuals with IGD and HCs.


Introduction: Prison foodways. International and multidisciplinary perspectives.
The role of prison food for those in custody has long been either underestimated, or a narrow subject approached from the vantage point of nutritionists. This special issue on prison food, tackles extant knowledge gaps by highlighting the scope of interdisciplinary scholarship, and studies of prison foodways that operate at the intersection of several disciplines. As an introduction to this special issue, we highlight the symbolic role of food as an underestimated feature of the prison environment. For many prisoners, the restrictive detention conditions give food a greater significance than it has outside: food can, and does, condition life in prison and, in many respects, symbolises the custodial experience (Smith, 2002).


Adamantyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.
Adamantyl triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active both in in vitro and in in vivo pharmacodynamic models. The synthesis and structure-activity relationships of these inhibitors are presented.


Micronuclei frequency and renal function markers in gym members: The moderating role of supplement intake.
This research investigates the moderating role of dietary supplement intake in the relationship between MNi frequency and renal markers in gym members. A cross-sectional study was carried out with gym members of all sexes, between 20 and 59 years of age, with data on supplement use obtained via questionnaire. Renal markers (urea and creatinine) were assessed by blood collection. Buccal mucosa cells were collected to assess MNi frequency by buccal micronucleus cytome assay. Moderation was tested using multiple linear regression models by PROCESS macro for SPSS. Results showed significant interactions for supplement use (p = 0.001) and supplement type, ergogenic (p = 0.003) and sports food (p = 0.003), with MNi for urea. For creatinine, only supplement use showed interaction with MNi frequency (p = 0.048). In conclusion, supplement intake is a moderator in the relationship between MNi frequency and renal function markers in gym members.


Transcriptomic mechanisms for the promotion of cyanobacterial growth against eukaryotic microalgae by a ternary antibiotic mixture.
This study evaluated the responses of a mixed culture of two cyanobacterial species (Microcystis aeruginosa and Synechocystis sp.) and two eukaryotic microalgal species (Raphidocelis subcapitata and Tetradesmus obliquus) to a mixture of three frequently detected antibiotics (tetracycline, ciprofloxacin and sulfamethoxazole) at environmentally relevant exposure doses of 60-300 ng/L. Mixed antibiotics selectively stimulated (p < 0.05) the growth and photosynthetic activity as well as generated transcriptomic responses in cyanobacteria without disrupting co-existing eukaryotic microalgae. Mixed antibiotics stimulated the growth of M. aeruginosa through the regulation of genes related to ribosome, photosynthesis, redox homeostasis, quorum sensing and nutrient metabolism. The proportion of M. aeruginosa among the four phytoplankton species in the mixed-culture system was increased from 33% to 38-44% under antibiotic exposure, which promoted the dominance of M. aeruginosa. Up-regulation of carbon catabolism-related genes contributed to the increased growth of Synechocystis sp. under antibiotic exposure. Since the antibiotic-stimulated growth rate of Synechocystis sp. was still lower than that of M. aeruginosa, the proportion of Synechocystis sp. in the mixed-culture system remained stable. Synechocystis sp. was less adaptive to antibiotic exposure than M. aeruginosa, due to a lower number of up-regulated ribosomal genes and photosynthesis-related genes. Antibiotic exposure reduced the proportions of two eukaryotic microalgal species in the mixed-culture system through a selective promotion of cyanobacterial competitiveness against eukaryotic microalgae, which may facilitate the formation of cyanobacteria bloom.


Kinetic constants for the inhibition of eel and rabbit brain acetylcholinesterase by some organophosphates and carbamates of military significance.
The kinetics of the inhibition of eel and rabbit brain acetylcholinesterase by a number of organophosphates and carbamates has been studied. Five organophosphates (tabun, sarin, soman, GF, and VX) and two carbamates (neostigmine and physostigmine) were used. Small but significant differences have been found between the two enzyme preparations in both the dissociation constant and the rate constants for the irreversible step. The values of k2 ranged from 0.56 to 1.08 sec-1 for the eel enzyme and 0.19 to 0.73 sec-1 for the rabbit enzyme. Kd varied from 0.3 to 24.5 microM for the eel and 0.3 to 9.3 microM for the rabbit enzyme. The similarity between the enzymes is remarkable considering the differences in the species of origin.


Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.
Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.


Single- and two-step extraction and thin-layer detection procedures for benzoylecgonine (cocaine metabolite) alone or in combination with a wide variety of commonly abused drugs in urine screening programs.
Three extraction procedures for the detection of benzoylecgonine (a major metabolite of cocaine) in urine are presented. Each technique has its advantages, depending on the needs of a clinical operation. Procedures I and II involve the use of ion-exchange resin-loaded paper. Procedure I has a sensitivity of 1 microng/ml and requires 20 ml of urine, and is recommended when the aim is to test for the abuse of cocaine only. Procedure II is a two-step extraction method in which a wide variety of abused drugs are extracted by the first step and the benzoylecgonine left in the aqueous buffer phase is extracted in the second step. The sensitivity for benzoylecgonine using this procedure is 2 microng/ml and it requires 20-50 ml of urine. Procedure III involves the direct extraction of benzoylecgonine using 5 ml of urine and has a sensitivity of 0.5 microng/ml.


Direct Medical Costs of Incident Complications in Patients Newly Diagnosed With Type 2 Diabetes in China.
Reliable country-specific incidence and cost data on diabetes-related complications are essential inputs for the projections of the economic burden of diabetes. The aim of this study was to provide patient-level cost estimates of managing and treating complications in patients newly diagnosed with type 2 diabetes mellitus (T2DM) in China. Patients newly diagnosed with T2DM in the Tianjin Urban Employee Basic Medical Insurance Claims database between 2008 and 2015 were identified and followed up. The cumulative incidence and descriptive costs of certain macrovascular and microvascular complications were examined. A generalized estimating equations model was used to estimate the immediate- and long-term costs for the incident complication in quarterly intervals, controlling for demographics and the confounding effects of comorbid complications. A total of 114,847 newly diagnosed patients were identified (mean age 56.9 years, 45.5% women). After 7 years, 80.8% of the patients at risk had developed nephropathy and 75.7% had developed neuropathy. The immediate additional costs were highest for myocardial infarction during the quarterly interval that the complication first occurred (China yuan [CNY] 19,633), and the long-term costs were highest for stroke in the quarterly intervals of subsequent years (CNY 1087). The expected costs for all complications were calculated and presented as costs per quarterly interval and per year for different age and sex subgroups. Managing complications results in substantial costs to the Chinese healthcare system. Our study contributes towards quantifying the economic burden and supports the parametrization of economic models of diabetes in China.


Tango therapy for Parkinson's disease: Effects of rush elemental tango therapy.
Tango therapy is very effective by applying tango elements according to the clinical severity and status of a patient. Maximization of the clinical effects of tango therapy in patients with Parkinson's disease may be achieved by the proper prescription of tango elements according to the clinical status of a patient.


Disparate effects of catecholamines under stress conditions on endothelial glycocalyx injury: An in vitro model.
Geriatric trauma patients have high circulating norepinephrine (NE) levels but attenuated release of epinephrine (Epi) in response to increasing severity of injury. We hypothesized that NE and Epi have different effects on the endothelial and glycocalyx components of the vascular barrier following shock. Human umbilical vein endothelial cells (HUVEC) were treated with varying concentrations of NE or Epi and exposed to simulated shock conditions (HR). Relevant biomarkers were sampled to index glycocalyx injury and endothelial cell activation. NE was associated with significantly greater glycocalyx damage and endothelial activation/injury vs. Epi treatment groups. There were minimal changes in PAI-1 with either NE or Epi ± H/R. However NE ± H/R was associated with significantly higher tPA levels. NE favors a profibrinolytic state. Our study supports investigating liberal use of the anti-fibrinolytic agent tranexamic acid in the severely injured geriatric trauma patient.


Epicardial fat and incident heart failure with preserved ejection fraction in patients with coronary artery disease.
We aimed to determine, whether epicardial adipose tissue (EAT) as local source of inflammation, as well as its change over time, associates with the development of heart failure with preserved ejection fraction (HFpEF) in patients with coronary artery disease. We retrospectively included 379patients (aged 65.2 ± 11.7 years, 70.2%male) with coronary artery disease but without heart failure at baseline, undergoing clinical and echocardiographic assessment in 2010-2013 and receiving a second assessment in 2014-2018. EAT thickness was defined as space between the myocardium and the pericardium and indexed (EATi) by body surface area. Change in EATi was calculated as the difference of follow-up and baseline EATi. HFpEF was defined according to presence of dyspnea, elevated natriuretic peptides, and structural and/or functional alterations on echocardiography in accordance with current European Society of Cardiology guidelines. During a median follow-up of 4.3 years, 142patients (37.5%) developed HFpEF. Patients with onset of HFpEF had higher EATi at baseline (2.4 ± 1.3 vs. 1.9 ± 0.9 mm/m2, p = 0.001). In multivariable regression analysis, EATi associated with onset of HFpEF (1.25 [1.01-1.54], p = 0.04). Likewise, an increase in EATi over time was linked HFpEF development, independent of other risk factors and baseline EATi (1.39 [1.04-1.87], p = 0.03). EATi was significantly associated with follow-up b-type natriuretic peptide (BNP) levels (4.31[0.58-8.05], p = 0.024), but not with baseline BNP (2.24[-0.27-4.76], p = 0.08). EATi is associated with the development of HFpEF. The finding of changes in EATi altering the risk of HFpEF manifestation support the rationale for further research on epicardial fat modulation as a treatment target for HFpEF.


Salivary proteome patterns of individuals exposed to High Altitude.
Identification of molecular signatures having key roles in hypobaric hypoxia by analysing the salivary proteome. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being non-invasive. We employed qualitative proteomics approach to develop discriminatory biomarker signatures from human saliva exposed to hypobaric hypoxia. Salivary proteins were analyzed and compared between age-matched healthy subjects exposed to high altitude (∼13700 ft) for seven days (HAD7) with control subjects at sea level (Normoxia) by using 2-Dimensional gel electrophoresis/Mass Spectrometry approach. Several proteins with significant differential expression were found. The up-regulated proteins were apoptosis inducing factor-2, cystatin S, cystatin SN and carbonic anhydrase 6. The down regulated proteins were polymeric immunoglobulin receptor, alpha-enolase and prolactin-inducible protein. Further confirmation of the altered proteins such as alpha enolase, carbonic anhydrase 6, prolactin-inducible protein, apoptosis inducing factor 2, cystatin S and cystatin SN were performed using immunoblotting. The expression patterns of the selected proteins observed by immunoblot were in concurrence with 2-Dimesional gel electrophoresis results, therefore affirming the authenticity of the proteomic investigation. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of hypobaric hypoxia induced effects. It is highly feasible to turn these biomarkers into an applicable clinical test after large scale validation.


Early failure of a modern moderately cross-linked polyethylene acetabular liner.
Modern polyethylene components for total hip arthroplasty have shown excellent long-term wear properties. However, among 204 primary total hip arthroplasty procedures performed by one surgeon using the Exactech Connexion GXL Liner, we identified 5 cases of severe polyethylene wear and osteolysis which occurred within 5 years of the index surgery. Among the 5 cases, all patients had a size 36 head with an acetabular component from size 52 to 56 mm. All patients had a UCLA activity scale score of at least 6 at the time that the osteolysis was detected. The average wear rate was 0.265 mm ± 0.207 mm per year. This review of 5 cases of catastrophic early polyethylene wear demonstrates a concerning trend with the use of the Exactech Connexion GXL liner. Further investigation is warranted to evaluate material characteristics which may have caused this accelerated wear and to prevent recurrences of this complication in the future.


Synthesis of bis-diosgenin pyrazine dimers: new cephalostatin analogs.
A convenient synthesis for bis-diosgenin pyrazine dimers, cephalostatin analogues is reported. These symmetrical dimeric steroid-pyrazines were obtained by the classical condensation of alpha-amino ketones, the most efficient method for pyrazine ring construction.


Restoration by levamisole of rosette-forming cells inhibited by histamine, db-CAMP and adenosine.
Db-cAMP and adenosine in vitro markedly inhibited the E-rosette formation of peripheral T-cells of healthy subjects. Histamine in vitro also inhibited the E-rosette formation, but only in patients with allergic disorders. Levamisole in vitro significantly restored the E-rosette formation of T-cells inhibited by db-cAMP, adenosine and histamine.


A study of technetium-labelled sulphide colloid uptake by regional lymph nodes draining a tumour-bearing area.
With appropriate controls, experimental groups of inbred C3H mice bearing a syngeneic mammary carcinoma challenge in their right rear footpads were injected in both rear footpads with 99TcmASC. Mice were sacrificed 15 and 90 min after the labelled colloid injection. Popliteal and sacral lymph nodes were weighed and counted in a well scintillation counter. A marked inhibition of labelled colloid uptake was demonstrated in regional lymph nodes draining a tumour-bearing area. Rabbits bearing VX2 carcinoma in a forelimb received 99TcmASC into each front footpad. Depression of labelled colloid uptake by regional lymph nodes draining tumour was evident on gamma-camera scanning.


Expression of a truncated form of hHb1 hair keratin in human breast carcinomas.
Human hHb1 belongs to the type II hard keratin family and is physiologically expressed in hair shafts. In the present study, using specific 3' and 5' probes for hHb1, we established that breast carcinomas ectopically express a hHb1 5'-truncated mRNA, and that this transcript is restricted to malignant epithelial cells. Furthermore, an in vitro study indicated that it could be translated. We concluded that, in breast carcinomas, expression of truncated hHb1 is related to epithelial cell transformation. Because the hHb1 gene maps to 12q11-q13, a chromosome region known to present several breakpoints in solid tumours, we propose that the hHb1 gene might represent a target for such alterations.


In situ glomerular expression of activated NF-kappaB in human lupus nephritis and other non-proliferative proteinuric glomerulopathy.
Nuclear Factor-kappaB (NF-kappaB) has been suggested to play a role in the cellular and molecular mechanisms underlying glomerular injury. We investigated the potential role of NF-kappaB activation in the pathogenesis of glomerular injury in 31 patients with class III-V lupus nephritis (LN), 14 patients with non-proliferative proteinuric glomerulopathy and six normal controls. The expression of NF-kappaB subunits p65 and p50, and the NF-kappaB regulated proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) as well as CD68 and synaptopodin was examined by Southwestern histochemistry (SWH) or immunohistochemistry. In contrast to non-proliferative glomerulopathy and normal controls, NF-kappaB activation (both p65 and p50) was enhanced in glomerular endothelial, mesangial cells or infiltrating cells in class IV LN, along with upregulation of TNF-alpha, IL-1beta, IL-6 and ICAM-1 expression. Glomerular endothelial and mesangial activation of NF-kappaB and mesangial ICAM-1 expression correlated with disease activity and the level of glomerular macrophage infiltration. Podocyte NF-kappaB overactivation (predominantly p65) paralleled podocyte expression of TNF-alpha and IL-1beta in patients with LN and non-proliferative glomerulopathy. Podocyte staining scores of NF-kappaB and p65 were positively correlated with the severity of proteinuria in LN and non-proliferative glomerulopathy. These results suggest a pathogenic role for NF-kappaB in glomerular injury by multiple mechanisms.


Construction and Integrated Analysis of Competitive Endogenous Long Non-Coding RNA Network in Thoracic Aortic Dissection.
Long non-coding RNAs (lncRNAs) can act as a competitive endogenous RNA (ceRNA) to regulate gene expression by sequestering the microRNA (miRNA). However, the lncRNA-miRNA-mRNA ceRNA network in thoracic aortic dissection (TAD) has been rarely documented. Three Gene Expression Omnibus (GEO) datasets were used to detect differentially expressed mRNAs, miRNAs, and lncRNAs in TAD. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for the differentially expressed mRNAs. A protein-protein interaction network for differentially expressed mRNAs was also constructed, and hub genes were identified. We established a ceRNA network of TAD based on the differentially expressed miRNAs, mRNAs and lncRNAs, and verified our results using an independent dataset and quantitative real-time PCR (qRT-PCR). In TAD, 267 lncRNAs, 81 miRNAs, and 346 mRNAs were identified as differentially expressed. The established ceRNA network consisted of seven lncRNA nodes, three mRNA nodes, and three miRNA nodes, and the expression of miRNAs in TAD was opposite to that of lncRNAs and mRNAs. Subsequently, an independent GEO dataset and qRT-PCR were used to validate the expression of three mRNAs. In addition, the expression differences in SLC7A5, associated miRNA and lncRNA were verified. According to gene set enrichment analysis of SLC7A5, the most significant KEGG pathway was considerably enriched in spliceosome and pentose phosphate pathway. We established a novel ceRNA regulatory network in TAD, which provides valuable information for further research in the molecular mechanisms of TAD.


Justification of aggression against nurses: The effect of aggressor distress and nurse communication quality.
To explore the conditions that contribute to justification of aggression against nurses. A 2 (aggressor distress as reflected in stressful behaviour: high vs. low) × 2 (target nurse's communication quality as reflected in provision of information and expression of caring: high vs. low) factorial design. Communication quality was operationalized as caring for half the respondents and information provision for the other half. Data were collected online in 2018. Respondents (N = 305) were presented with one of the eight versions of a hypothetical vignette. Aggressor distress and caring were manipulated for half the participants and aggressor distress and information provision for the other half. After reading the vignette, respondents reported their attitudes towards the aggressor's behaviour and sense of warmth towards the target nurse. Additional data collected included trait empathy (a control variable), demographic variables and responses to a manipulation check. Data were analysed using the analyses of variance. The results show the main effects of aggressor distress and nurse communication quality on justification of aggression and sense of warmth towards the nurse. An interaction effect between aggressor distress and (poor) nurse information provision was found on justification of aggression. The results extend extant research on the causes of aggression against the nurses by highlighting a tendency to view certain circumstances as justifying such behaviour. The study explored conditions that increase the justification of aggression against nurses, from the perspective of a third party. The results show that aggressor's distress, as well as the attacked nurse's communication quality affect the justification of aggression. The results contribute to knowledge about the causes of aggression against nurses and highlight the need for healthcare policy and public education activities designed to undermine the view that aggression against nurses can be justified.


Benign papilloma on core biopsy requires surgical excision.
When a papillary lesion is identified on core biopsy of an impalpable breast lesion, standard practice involves excisional biopsy. Recent literature has questioned the need for surgical excision in patients with benign core biopsy and radiological concordance. Our aim was to assess whether surgical excision is required by targeting this concordant group in a large screen-detected population. A retrospective review of a prospectively collected database of all benign papillary core biopsies between February 1995 and September 2007 at North Western Breast Screen and Monash Breast Screen in Melbourne, Australia was performed. All patients had surgical excision, enabling correlation between core and final excisional biopsy results on all lesions. All histology reports were reviewed and the radiology was reassessed. During a 14-year period, 5783 core biopsies were performed from 633,163 screening mammograms. Eighty patients (0.01%) had benign papilloma on core biopsy, no patients had atypia on core biopsy, and all patients had benign radiological features. Of the 80 patients, 15 patients were found to have ductal carcinoma in situ (8) or invasive ductal carcinoma (7) on final pathology, yielding a 19% malignant rate. Core biopsy showing benign papillary lesion, even where radiology is also suggestive of a benign process, cannot exclude malignancy, and therefore surgical excision is required.


The diverse functional genes of maize rhizosphere microbiota assessed using shotgun metagenomics.
The geographical diversification in chemical, biological and physical properties of plant biospheres instigates heterogenicity in the proliferation of important soil microbiome. Controlling functions and structure of plant rhizosphere from a better understanding and prediction of a plant's immediate environment will help assess plant-microbe interplay, improve the productivity of plant ecosystems and improve plant response to adverse soil conditions. Here we characterized functional genes of the microbial community of maize rhizosphere using a culture-independent method. Our metadata showed microbial genes involved in nitrogen fixation, phosphate solubilization, quorum sensing molecules, trehalose, siderophore production, phenazine biosynthesis protein, daunorubicin resistance, acetoin, 1-aminocyclopropane-1-carboxylate deaminase, 4-hydroxybenzoate, disease control and stress-reducing genes (superoxidase dismutase, catalase, peroxidase, etc.). β-Diversity showed that there is a highly significant difference between most of the genes mined from rhizosphere soil samples and surrounding soils. The high relative abundance of stress-reducing genes mined from this study showed that the sampling sites harbor not only important plant-beneficial organisms but also a hotspot for developing bio-fertilizers. Nevertheless, since most of these organisms are unculturable, mapping cultivation strategies for their growth could make them readily available as bio-inoculants and possible biotechnological applications in the future. © 2020 Society of Chemical Industry.


Variation in severity of respiratory syncytial virus infections with subtype.
Two major subtypes of respiratory syncytial virus have been identified. This study assessed the hypothesis that A-subtype infections were more severe than B-subtype infections among the 157 infants hospitalized in two hospitals in Rochester, N.Y., during two winters. Severity was measured both by specific clinical observations and by a severity index that was derived empirically. Among all subjects, several clinical observations suggested that A-subtype infections were more severe. For example, mechanical ventilation was required in 12.6% of those with A-subtype compared with 1.6% of those with B-subtype infection (relative risk = 7.88; p = 0.01). Among high-risk infants (infants with underlying conditions or age 3 months or less at admission), carbon dioxide tension greater than 45 mm Hg was found in 37.0% of those with A-subtype compared with 12.0% of those with B-subtype infection (relative risk = 3.08; p = 0.04). In discrete multivariate (logit) analysis, effects of subtype (odds ratio = 6.59; p less than 0.01) on severity remained after adjustment for other statistically significant effects of age less than 3 months, underlying condition, and premature birth. The finding that A-subtype infections were more severe might have important implications for vaccine development, studies of the virulence of respiratory syncytial virus, clinical management (e.g., selection for antiviral therapy), and long-term prognosis.


Is zoonotic Plasmodium vivax malaria an obstacle for disease elimination?
The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern. Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species. In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax. This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda.


Cochlear Implant Infections and Outcomes: Experience From a Single Large Center.
To review our experience with cochlear implant infections over the past 5 years, the management strategy and to identify predictive factors that led to explantation. Retrospective record-base case series of cochlear implant infections. Tertiary otology and implant center. All patients who had cochlear implantation over a period of 5 years. None. To identify risk factors, rates and outcomes of cochlear implant infections, and to formulate strategies to develop clearer management protocols to prevent cochlear implant explantation. Of 704 implanted patients, 22 suffered a postoperative soft tissue infection (3%). Fifty-nine percent of these infected patients resulted in explantation, giving an explantation rate of 1.8% over the whole study population. One hundred percent of the infected implants identified as having either Staph. Aureus or Pseudomonas spp. as the single causative organism resulted in explantation. There is a high rate of explantation when infection is detected. Currently there is no clear consensus on medical management, such as choice of antibiotics or length of antibiotic course. A registry of cochlear implants would facilitate standard reporting methods for severity and type of infection, to be able to pool data across centers and form a more robust management protocol for cochlear implant infections.


Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.
Molecular events underlying progression of well-differentiated liposarcoma (WDLS) to dedifferentiated liposarcoma (DDLS) are poorly defined. This study sought to identify copy number alterations (CNA) associated with dedifferentiation of WDLS, with DDLS morphology, and with patient outcomes. Fifty-five WDLS and 52 DDLS were analyzed using Agilent 244K comparative genomic hybridization and Affymetrix U133A expression arrays. CNAs were identified by RAE analysis. Thirty-nine of the DDLS specimens were categorized morphologically by a single pathologist. Nine regions of CNA were identified as recurrent in DDLS but not WDLS; 79% of DDLS had at least one of these CNAs. Loss of the chromosome segment 11q23-24, the most common event, was observed only in DDLS that morphologically resembled the genomically complex sarcomas, undifferentiated pleomorphic sarcoma and myxofibrosarcoma. 11q23-24 loss was itself associated with increased genomic complexity in DDLS. Loss of 19q13, but not 11q23-24, was associated with poor prognosis. Median disease-specific survival was shorter for patients with19q13 loss (27 months) than for patients with diploid 19q13 (>90 months; P < 0.0025), and 19q13 loss was associated with local recurrence (HR, 2.86; P = 0.013). Common copy number losses were associated with transcriptional downregulation of potential tumor suppressors and adipogenesis-related genes (e.g., EI24 and CEBPA). Dedifferentiation of WDLS is associated with recurrent CNAs in 79% of tumors. In DDLS, loss of 11q23-24 is associated with genomic complexity and distinct morphology whereas loss of 19q13 predicts poor prognosis. CNAs in liposarcoma improve risk stratification for patients and will help identify potential tumor suppressors driving liposarcoma progression.


Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.
Thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dosing and fractionation remain unclear. The National Comprehensive Cancer Network guidelines have recommended either 45 Gy delivered twice daily (BID) or 60 to 70 Gy delivered once daily (QD). However, the current practice patterns among US radiation oncologists are unknown. We surveyed US radiation oncologists using an institutional review board-approved questionnaire. The questions covered demographic data, self-rated knowledge of key trials, and treatment recommendations. We received 309 responses from radiation oncologists. Of the 309 radiation oncologists, 60% preferred TRT QD and 76% acknowledged QD to be more common in their practice. The respondents in academic settings were more likely to endorse BID treatment by both preference (P = .001) and actual practice (P = .009). The concordance between preferring QD and administering QD in practice was 100%. In contrast, 40% of respondents who preferred BID actually administered QD more often. Also, 15% of physicians would be unwilling to switch from QD to BID and 3% would be unwilling to switch from BID to QD, even on patient request. Most respondents (88%) recommended a dose of 45 Gy for BID treatment. For QD treatment, the division was greater, with 54% recommending 60 Gy, 30% recommending 63 to 66 Gy, and 10% recommending 70 Gy. Substantial variation exists in how US radiation oncologists approach TRT dosing and fractionation for LS-SCLC. Three quarters of our respondents reported administering TRT QD most often. The most common doses were 60 Gy QD and 45 Gy BID. The results of the present survey have provided the most up-to-date information on US practice patterns for LS-SCLC.


Excess Ca(2+) does not alleviate but increases the toxicity of Hg(2+) to photosystem II in Synechocystis sp. (Cyanophyta).
This study demonstrated that excess Ca(2+) increased the toxicity of Hg(2+) to PSII of cyanobacterium Synechocystis sp. using fast rise chlorophyll fluorescence test. Excess Ca(2+) increased the inhibitory effect of Hg(2+) on O2 evolution. Exposure to Hg(2+) caused increase in functional antenna size (ABS/RC), trapping rate of reaction center (TR0/RC), dissipated energy flux per reaction center (DI0/RC) and maximum quantum yield of non-photochemical deexcitation ( [Formula: see text] ), indicating that some reaction centers were transformed to dissipation sinks under Hg(2+) stress. Hg(2+) stress slowed down electron transport on both donor side and acceptor side and caused accumulation of P680(+). Excess Ca(2+) intensified all the Hg(2+) toxic effects on PSII function and led to dysfunction of PSII. The number of reaction centers that were transformed into dissipation sinks increased with increasing Ca(2+) concentration.


Draft genome sequence data of Paenbacillus curdlanolyticus B-6 possessing a unique xylanolytic-cellulolytic multienzyme system.
Paenibacillus curdlanolyticus B-6 is a facultative anaerobic bacterium that efficiently produces a lignocellulolytic multienzyme complex. The whole genome of P. curdlanolyticus B-6 was sequenced on an Ion GeneStudio S5 system, which yielded 74 contigs with a total size of 4,875,097 bp, 4,473 protein-coding sequences, and a G+C content of 49.7%. The genome data have been deposited in DDBJ/ENA/GenBank under accession numbers BLWM01000001-BLWM01000074. Analyses of average nucleotide identities and phylogenetic relationships of 16S rRNA sequences of Paenibacillus species revealed that strain B-6 is most closely related to Paenibacillus xylaniclasticus TW1. P. curdlanolyticus B-6 should thus be reclassified as a strain of P. xylaniclasticus.


Cathepsin B expression is similar in African-American and Caucasian prostate cancer patients.
Increased incidence and mortality of prostate cancer (PCa) suggest that U.S. African-American men have more invasive cancer than Caucasian men. Invasive PCa requires several proteases, including the cysteine protease cathepsin B (CB), for degradation of basement membrane and extracellular matrix proteins prior to cancer cell migration across biological compartments. Our objective was to determine whether CB immunostaining patterns, in relation to clinical data, could distinguish invasive PCa in African-American and Caucasian patients. Fifty Gleason score 6/7 PCa cases were selected for similar clinical data with benign prostatic hyperplasia (BPH) samples as controls. Immunostainings were imaged directly from microscope slides to a computer using a digital camera. Data were quantified using Metamorph software, analyzed using the two-sample t-test and confirmed by multiple regression. Ratios of CB to its endogenous inhibitor stefin A (SA) immunostainings were greater in PCa than BPH, but were not significantly different in PCa of either race. The African-American patients did not show increased CB immunostaining, indicating that the contribution of this protease to invasiveness was similar in both races. When veterans received equal medical care at the Minneapolis Veterans Affairs Medical Center, African-American patients did not show increased PCa invasiveness. Our conclusion is supported by analysis of post-surgery serum total PSA levels and cancer cell invasion to margins/capsules, seminal vesicles and/or lymph nodes. Invasiveness of PCa does not appear to be race-dependent. The previous conclusion of race-based differences in PCa requires re-evaluation with respect to the role of proteases (such as CB, matrix metalloproteinase) in invasion and metastasis of cancer cells.


Brain structural changes in cannabis dependence: association with MAGL.
Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD. CD had lower fractional anisotropy than controls in white matter bundles innervating posterior cingulate and parietal cortex, basal ganglia, and temporal cortex. The CD group also had significantly less gray matter thickness and density in precuneus, relative to controls. Sibling-pair analysis found support for causal and graded liability effects of cannabis on precuneus structure. Spatial patterns of gray matter differences in CD were significantly associated with regional differences in monoacylglycerol lipase (MAGL) expression in postmortem brain tissue, such that regions with higher MAGL expression (but not fatty-acid amide hydrolase or FAAH) were more vulnerable to cortical thinning. In sum, chronic cannabis use is associated with structural differences in white and gray matter, which was most prominent in precuneus and associated white matter tracts. Regions with high MAGL expression, and therefore with potentially physiologically restricted endogenous cannabinoid signaling, may be more vulnerable to the effects of chronic cannabis use on cortical thickness.


Molecular docking analysis of apigenin and quercetin from ethylacetate fraction of Adansonia digitata with malaria-associated calcium transport protein: An in silico approach.
The investigation and knowledge of calcium handling mechanisms in the plasmodium has been considered as a potential biological target against malaria. This study deals with the evaluation of inhibitory activity of secondary metabolites of ethylacetate partitioned-fraction of Adansonia digitata stem bark extract on malaria-associated protein using in silico docking studies. Molecular docking and virtual screening was performed to understand the mechanism of ligand binding and to identify potent calcium transporter inhibitors. The stem bark extracts of A. digitata contains rich sources of phytochemicals. The secondary metabolites were determined by HPLC-DAD and HRGC-MS analysis. The major chemical constituent present in the ethylacetate partitioned-fraction of A. digitata stem bark extract were examined for their antiplasmodial activity and were also involved in docking study. The secondary metabolites, quercetin and apigenin inhibited the formation of β-hematin. The results showed that all the selected compounds in the A. digitata showed binding energy ranging between -6.5 kcal/mol and -7.1 kcal/mol. Among the two chemical constituents, apigenin has the highest docking score along with the highest number of hydrogen bonds formed when compared to quercetin. Analysis of the results suggests that apigenin and quercetin could act as an anti-malaria agent. Molecular docking analysis could lead to further development of potent calcium transporter inhibitors for the prevention and treatment of malaria and related conditions.


Felty syndrome: autoimmune neutropenia or immune-complex-mediated disease?
Immunofluorescence on polymorphonuclear cells (PMN) of patients with Felty syndrome (FS) revealed increased amounts of IgG, IgA, and IgM bound to the PMN surface compared with PMN of patients with rheumatoid arthritis alone. A positive correlation was found between the score for surface-bound immunoglobulins on FS-PMN and the results of the Clq binding assay in FS sera. After preincubation with sera from 20 patients with FS, immunofluorescence on PMN from healthy controls (HC) showed that these cells had bound IgG, IgA, and IgM. However F(ab')2 fragments of IgG from FS sera did not bind to PMN, although the antigen-binding reactivity of the F(ab')2 fragments was maintained as shown by control experiments. Immunoglobulins eluted from FS-PMN failed to bind to HC-PMN, whereas the corresponding IgG of patients with autoimmune neutropenia was bound. Gel filtration of FS sera on Sepharose 4B showed that the binding of IgG in FS sera to PMN did not coincide with the 7S peak but occurred mainly in fractions containing larger material. No binding of IgA and IgM to HC-PMN was found after incubation with FS sera pretreated with polyethylene glycol (PEG) to precipitate immune complexes. These results indicate that in sera of patients with FS the PMN-binding reactivity of IgG, IgA, and IgM is due to the binding of immune complexes containing these immunoglobulins and not to presence of autoantibodies directed to antigens on the neutrophil surface.


Medication overdose data analysis: a review of medication error reports in the FDA adverse event reporting system (FAERS).
drug overdose is a common type of medication error, which caused significant patient injuries and economic losses. To determine which drugs are reported most frequently in association with drug overdose, a comprehensive search was conducted in the FDA Adverse Event Reporting System (FAERS) database. The study also sought to determine the top 10 drugs reported with drug overdose. FAERS database was searched for drug overdose records submitted from the first quarter of 2017 to the fourth quarter of 2021. Descriptive analyses were conducted based on the total counts and percentages of reports associated with the drug. Subgroup analyses were performed on drugs of different pharmacological classifications. A total of 170,424 drug overdose reports were retrieved. The results revealed that antipyretics and analgesics took the highest risk for overdose, with 63,143 (37.05%) cases reported. Among them, opioids were associated with the most drug overdose events. The top 10 drug classes relating to drug overdose in FAERS were opioid analgesic, anilide antipyretic analgesic, 5-HT reuptake inhibitors, bronchodilators, monoclonal antibodies and antibody-drug conjugates, benzodiazepines, antipsychotics, GABA derivatives, antimanic agents, and propionic acid derivatives. to reduce the occurrence of drug overdose events, some methods could be considered including applying a pre-prescription review system, drug safety education, developing warning lists, etc.


Disruption of the primary salicylic acid hydroxylases in rice enhances broad-spectrum resistance against pathogens.
Salicylic acid (SA) is a crucial hormone involved in plant immunity. Rice (Oryza sativa) maintains high SA levels that are not induced by pathogens. However, the roles of SA in rice immunity and yield remain largely unknown. Here, we identified SA 5-hydroxylases 1 (OsS5H1) and 2 (OsS5H2) as the primary enzymes engaged in catalysing SA to 2,5-dihydroxybenzoic acid (2,5-DHBA) in rice. SA levels were significantly increased in the oss5h mutants, while they were dramatically decreased in the OsS5H1 and OsS5H2 overexpression lines. The mutants were resistant, whereas the overexpression lines were susceptible to Pyricularia oryzae and Xanthomonas oryzae pv. Oryzae. Moreover, the pathogen-associated molecular patterns-triggered immunity responses, including reactive oxygen species burst and callose deposition, were enhanced in all the mutants and compromised in the overexpression lines. Quantification of the agronomic traits of the oss5h mutants grown in the paddy fields demonstrated that the grain number per panicle was decreased as the SA levels increased; however, the tiller number and grain size were enhanced, resulting in no significant yield penalty. Collectively, we reveal that mildly increasing SA content in rice can confer broad-spectrum resistance without yield penalty and put new insights into the roles of SA in immunity and growth.


Nervous system effects of occupational manganese exposure on South African manganese mineworkers.
Occupational exposure to airborne manganese dust has been shown to produce adverse effects on the central nervous system. Four hundred and eighty-nine blue and white collar manganese mineworkers from South Africa were studied cross-sectionally to investigate the nervous system effects of medium to low occupational manganese exposures. The different facilities included underground mines, surface processing plants, and office locations. A job exposure matrix was constructed using routine occupational hygiene data. Exposure variables included years of service, a cumulative exposure index (CEI) and average intensity of exposure (AINT) across all jobs, and blood manganese. Endpoints included items from the Q16, WHO-NCTB, SPES, and Luria-Nebraska test batteries, and a brief clinical examination. Potential confounders and effect modifiers included age, level of education, past medical history including previous head injury, previous neurotoxic job exposures, tobacco use, alcohol use and home language. Associations were evaluated by multiple linear and logistic regression modeling. Average exposure intensity across all jobs was 0.21mg/m(3) manganese dust. Multivariate analyses showed that none of the symptom nor test results were associated with any measure of exposure including blood manganese, after adjustment for confounders. This relatively large null study indicates that manganese miners exposed on average across all jobs to MnO(2) at levels near the American Conference of Governmental Industrial Hygienists Threshold Limit Value (ACGIH TLV) are unlikely to have a subclinical neurotoxicity problem.


Hydrochemistry and quality appraisal of groundwater in Birr River Catchment, Central Blue Nile River Basin, using multivariate techniques and water quality indices.
Due to the continuous population growth and the expansion of industry and agriculture in Ethiopia, groundwater demand has been increasing to supplement the erratic surface water. Therefore, the availability of sufficient and clean groundwater should be appraised and tracked regularly to secure its multi-purposes. This work aims to assess the appropriateness of groundwater for drinking, and irrigation uses and identifies the key factors controlling groundwater quality in the Birr River Catchment (BRC), Blue Nile River Basin, Ethiopia. For this purpose, a total of 79 groundwater samples were assessed for physicochemical parameters. Major ion analysis, multivariate techniques (MCA, HCA, and PCA), and multi-hydrochemical indices were applied in the analysis of groundwater quality data. Hydrochemical analysis indicated that the principal cation and anion were Ca2+ and HCO3-, respectively. The spatial analysis of the major ions revealed a positive trend for Mg2+, Na+, K+, HCO3-, Cl-, and SO42- along the groundwater flow path from the upland to the Birr river valley. Conversely, Ca2+ shows a deleterious tendency along the groundwater flow direction. The aquifer has three principal hydrochemical facies: Ca-HCO3, Ca/Mg-HCO3, and Na-HCO3. The water quality analysis indicates that with the exception of TDS, Ca2+, Mg2+, and HCO3- in a few locations, most of the parameters analyzed are within the WHO allowable limits and are thus considered suitable for drinking water. The combined use of Gibbs and ionic ratio plots confirmed that silicate weathering was invariably prevailing in the region. The Chloro-Alkali Indices (CAIs) have indicated that cation exchange occurs in more than 85% of groundwater samples. However, there were indications of the influence of reverse ion exchange in the rest of the data. The MCA, PCA, and HCA disclosed that geo-genic sources accompanied by human activities mainly control the groundwater quality of the catchment. However, water quality assessment indices show that groundwater in the highest proportion of the catchment is suitable for human consumption and agricultural use.


Chronic ethanol ingestion alters xenobiotic absorption through the skin: potential role of oxidative stress.
Alcohol ingestion is correlated with several skin disorders and it has been proposed that changes in skin properties may be an early indicator of alcohol misuse. Topically applied ethanol is an effective transdermal penetration enhancer; however, little is known about the effects of chronic ethanol ingestion on skin. Rats were pair fed a diet containing 36% ethanol for twelve weeks. The animals were then switched to a non-ethanol diet and were monitored for up to four weeks. Non-invasive measurements for changes in dermal blood flow using laser Doppler velocimetry (LDV), damage to skin barrier via transepidermal water loss (TEWL) and changes in skin moisture content were obtained for the experimental duration. At 0, 1 day or 1, 2, 3, 4 weeks after alcohol removal rats were euthanized and their skin was analyzed for alcohol and aldehyde dehydrogenase, and lipid peroxidation. Transdermal penetration of the herbicide paraquat, industrial solvent dimethyl formamide (DMF), insect repellant N,N-diethyl-m-toluamide (DEET) and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was also determined. Transdermal absorption, LDV, TEWL, skin alcohol and aldehyde dehydrogenase, as well as lipid peroxidation significantly increased after continuous ethanol exposure (p<0.05). These factors remain elevated for up to four weeks after termination of ethanol consumption, showing that skin changes induced by alcohol are not immediately reversible and reflect fundamental changes in the skin itself. This work provides a starting point for examining the link between ethanol ingestion and skin disorders associated with alcohol use.


Transseptal occluder migration after transcatheter atrial septal aneurysm and double secondary septal defect correction: A case report.
We present a case of secondary atrial septal defect transcatheter correction attempt in a 72 years old male, complicated by the device migration. The occluder was captured, pulled down to the common femoral artery and retrieved through the arteriotomy site. Second attempt was successfully performed using combination of transesophageal echo (TEE) and sizing balloon to accurately measure the defect diameter. This case underscores the importance of TEE ultrasound, sizing balloon, and contrast fluoroscopy combination to achieve accurate device sizing. Our calculation approach significantly increased the success rate of the septal defect closure procedure and potentially reduced the risk of immediate and mid-term complications. Combination of measuring methods should be used in order to accurately assess the device diameter.


Modified technique of sphincteroplasty with the use of a specially prepared cannula.
A modified technique of sphincteroplasty with the use of a specially prepared cannula can exclude the pancreatic duct from the operative field by covering it with the posterior wall of the cannula. The use of the cannula can avoid some of the technical difficulties that may be encountered with operations involving the papilla of Vater. Our experience with 51 patients has been presented.


Alterations in amounts and covalent modifications of low-molecular-weight chromosomal proteins in Chinese hamster ovary cells during polyamine depletion.
The effect of polyamine depletion on phosphorylation and ADP-ribosylation of low-Mr chromosomal proteins was studied in intact, mutant Chinese hamster ovary cells (CHO-P22) devoid of ornithine decarboxylase activity. When starved of polyamines for 6 days, severe polyamine deficiency develops and the cells gradually stop growing. The rate of DNA synthesis was retarded to 16% of the control value and to 29% in density-inhibited cells. The synthesis of high-mobility-group (HMG) proteins was decreased by 65% in polyamine-depleted cells and by 40% in density-inhibited cells. The synthesis of core histones was decreased by 40% both in polyamine-depleted and density-inhibited cells. In polyamine-depleted cells the molar ratio of the higher-Mr HMG proteins (HMG 1 + 2) to the lower-Mr HMG proteins (HMG 14 + P) was about one-half of that found in cells grown in the presence of putrescine or in density-inhibited cells. In contrast to HMG proteins, no major differences were found in the content of core histones in these cell populations. In the perchloric acid-soluble fraction of nuclear proteins, 32P was incorporated mainly into histone H1, HMG P and a protein migrating more slowly than HMG 1 (protein P1). Specific changes in the 32P-labeling and migration of a number of protein bands, including histone H1, was observed in polyamine-depleted cells as compared to cells grown in the presence of putrescine or to density-inhibited cells. ADP-ribosylation experiments using [3H]adenosine showed a different pattern of label distribution; the higher-Mr HMG proteins from polyamine-depleted cells contained about one-half the amount of label found in the proteins from control cells. The lower-Mr HMG proteins and histone H1 were the preferentially labeled proteins in polyamine-depleted cells. Labeling of core histones with [32P]orthophosphate or [3H]adenosine did not differ markedly in the two cell populations. The results obtained using intact polyamine auxotrophic cells indicated that polyamine depletion is connected with more severe alterations in amounts and covalent modifications (phosphorylation and ADP-ribosylation) of HMG chromosomal proteins and histone H1 than core histones.


Changes in leaf water potential and CAM inSempervivum montanum andSedum album in response to water availability in the field.
The short term effects of irrigation on diurnal changes in Ψleaf and titratable acidity were examined both inSempervivum montanum and inSedum album, a facultative CAM plant, in the Spanish Pyrenees. InSemperivivum, Ψleaf responded rapidly to irrigation and, in both the control and irrigated plants, increased during the day and decreased during the night and early morning. By contrast, Ψleaf inSedum responded more slowly to irrigation and showed a decrease during the day and an increase in the period between evening and early morning. Under the conditions of the short-term experiments, changes in acid metabolism were not observed in either species following irrigation. The results suggest that transpirational water loss together with redistribution of water within the plant are more important than the osmotic concentration of malic acid in determining Ψleaf in both species and that daytime water loss is greater inSedum than inSempervivum.The effect of long-term water stress on Ψleaf and acid levels was also assessed in both species over a 3-week period. Both Ψleaf and acidification inSempervivum decreased over this time period but could, at least partially, be reversed by irrigation. InSedum, Ψleaf also declined but a more gradual reduction in acidification occurred than inSempervivum. Irrigation inSedum at least partially reversed the decline in Ψleaf but produced a complex pattern of acid metabolism. Nocturnal acidification in the irrigated plants was lower than in the non-irrigated control when preceded by a cool day but showed complete recovery following a hot day. It is suggested inSedum album that C3 photosynthesis during the preceding light period, as determined by light intensity and leaf temperature, may be important in determining the extent of nocturnal acidification under field conditions.


Vorinostat as a radiosensitizer for brain metastasis: a phase I clinical trial.
Perform a phase I study to evaluate the safety, and tolerability of vorinostat, an HDAC inhibitor, when combined with whole brain radiation treatment (WBRT) in patients with brain metastasis. A multi-institutional phase I clinical trial enrolled patients with a histological diagnosis of malignancy and radiographic evidence of brain metastasis. WBRT was 37.5 Gy in 2.5 Gy fractions delivered over 3 weeks. Vorinostat was administrated by mouth, once daily, Monday through Friday, concurrently with radiation treatment. The vorinostat dose was escalated from 200 to 400 mg daily using a 3+3 trial design. Seventeen patients were enrolled, 4 patients were excluded from the analysis due to either incorrect radiation dose (n = 1), or early treatment termination due to disease progression (n = 3). There were no treatment related grade 3 or higher toxicities in the 200 and 300 mg dose levels. In the 400 mg cohort there was a grade 3 pulmonary embolus and one death within 30 days of treatment. Both events were most likely related to disease progression rather than treatment; nonetheless, we conservatively classified the death as a dose limiting toxicity. We found Vorinostat administered with concurrent WBRT to be well tolerated to a dose of 300 mg once daily. This is the recommended dose for phase II study.


Additional Value of CH₄ Measurement in a Combined (13)C/H₂ Lactose Malabsorption Breath Test: A Retrospective Analysis.
The lactose hydrogen breath test is a commonly used, non-invasive method for the detection of lactose malabsorption and is based on an abnormal increase in breath hydrogen (H₂) excretion after an oral dose of lactose. We use a combined (13)C/H₂ lactose breath test that measures breath (13)CO₂ as a measure of lactose digestion in addition to H₂ and that has a better sensitivity and specificity than the standard test. The present retrospective study evaluated the results of 1051 (13)C/H₂ lactose breath tests to assess the impact on the diagnostic accuracy of measuring breath CH₄ in addition to H₂ and (13)CO₂. Based on the (13)C/H₂ breath test, 314 patients were diagnosed with lactase deficiency, 138 with lactose malabsorption or small bowel bacterial overgrowth (SIBO), and 599 with normal lactose digestion. Additional measurement of CH₄ further improved the accuracy of the test as 16% subjects with normal lactose digestion and no H₂-excretion were found to excrete CH₄. These subjects should have been classified as subjects with lactose malabsorption or SIBO. In conclusion, measuring CH₄-concentrations has an added value to the (13)C/H₂ breath test to identify methanogenic subjects with lactose malabsorption or SIBO.


Chemical excitability of axons: excitatory and inhibititory effects of putative neurotransmitters and modulators on frog sciatic nerves.
The microiontophoretic administration of putative neuromodulators (acetylcholine, norepinephrine, dopamine, 2-phenylethylamine, tryptamine, histamine) triggered firing or inhibited on-going activity in isolated frog sciatic nerves.


Anterior glottoplasty: the effect of inclusion of the vocal fold lamina propria to frequency elevation.
Anterior glottoplasty is a commonly used treatment for voice feminization. But it remains in dispute over whether to suture of the ligament as part of the procedure. This study aimed to explore the effect of inclusion of the vocal lamina propia. Anterior webs were created in 8 excised canine larynges by sutures placed at 10%, 20%, and 30% of the vocal fold length, respectively. The suture depth was divided into two groups: epithelium layer (Shallow Suture, SS group) and deep layers of vocal fold lamina propia (Deep Suture, DS group). For anterior webs between 0% and 30%, the frequency elevation ranged from 3% to 151% of the pre-web fundamental frequency (fo) in SS group and from 13% to 222% in DS group. No significance was found between two groups at three different sutures (p = .486 for suture at 10% of vocal fold length, 0.686 for 20%, 0.886 for 30%, respectively). The frequency in excised canine larynx increased continuously as the anterior glottic webs ranged from 0% to 30%. The inclusion of the vocal fold lamina propia does not affect the frequency elevation.


Hirschsprung disease presenting as sigmoid volvulus: a case report and review of the literature.
While sigmoid volvulus is commonly seen in older patients, it is rarely encountered in children and younger adults. Consequently, heightened awareness of this entity is required to avoid a delay in diagnosis. Among the pediatric and adult cases of colonic volvulus previously reported in the English literature, 23 of the affected individuals have also been diagnosed with Hirschsprung disease (HD). This report describes a 12-year-old male with a history of chronic constipation who presented with vomiting and abdominal distension and was found to have sigmoid volvulus with previously unrecognized HD. The case presentation is followed by a review of the literature describing colonic volvulus secondary to HD in children.


Selective inactivation of adrenomedullin over calcitonin gene-related peptide receptor function by the deletion of amino acids 14-20 of the mouse calcitonin-like receptor.
The receptors for the neuropeptide calcitonin (CT) gene-related peptide (CGRP) and the multifunctional peptide hormone adrenomedullin (AM) are calcitonin-like receptor (CLR)/receptor-activity-modifying protein (RAMP) 1 and CLR/RAMP2 heterodimers, respectively. Here, the amino acid sequence TRNKIMT, corresponding to the residues 14-20 of the N terminus of the mouse (m) CLR, was found to be required for a functional mCLR/RAMP2 AM receptor. The deletion of amino acids 14-20 (Delta14-20) or their substitution by alanine (14-20A) did not affect the heterodimerization of the mCLR with mRAMP1 or mRAMP2, and the levels of expression at the surface of transiently transfected COS-7 cells were not altered. In mRAMP1/mCLR- or mRAMP1/mCLR-(Delta14-20)-expressing cells CGRP stimulated cAMP formation with EC(50) values of 0.12 +/- 0.01 and 1.5 +/- 0.4 nm, respectively. In mRAMP2/mCLR-expressing cells the EC(50) of AM was 0.8 +/- 0.2 nm. However, in cells expressing mRAMP2/mCLR-(Delta14-20) up to 10(-6) m AM failed to stimulate cAMP production. In mRAMP2/mCLR-(14-20A) expressing cells the cAMP response to AM was minimally restored, and the EC(50) was >100 nm. In conclusion, the deletion of the amino acid sequence TRNKIMT of the extreme N terminus of the mCLR maintained CGRP receptor function of mRAMP1/receptor heterodimers, but AM no longer activated the mutant mCLR-(Delta14-20) in the presence of mRAMP2. The TRNKIMT sequence is required for normal mCLR/mRAMP2 association, and as a consequence, high affinity AM binding signaling the activation of adenylyl cyclase.


Resting Aortic Valve Area at Normal Transaortic Flow Rate Reflects True Valve Area in Suspected Low-Gradient Severe Aortic Stenosis.
This study sought to assess the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow, low-gradient aortic stenosis but normal resting transvalvular flow rate. SE may help to distinguish between true severe aortic stenosis and pseudosevere aortic stenosis in patients with low aortic valve area (AVA) and mean gradient. However, if rest flow rate is normal, then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi). Sixty-seven patients with suspected low-flow, low-gradient aortic stenosis who underwent SE were retrospectively studied. Following stratification by rest LVEF, SVi, and flow rate-using cutoffs of 50%, 35 ml/m(2), and 200 ml/s, respectively-we tested for significant changes in AVA during SE. Mean age was 77 ± 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 ± 0.12 cm(2); mean gradient: 27 ± 7 mm Hg; flow rate: 182 ± 37 ml/s; SVi: 32 ± 8 ml/m(2); and LVEF: 45 ± 15%. During SE, significant increases in AVA were observed regardless of resting LVEF and SVi state. In patients with rest flow rate ≥200 ml/s, AVA did not increase significantly during stress (rest AVA: 0.90 cm(2) vs. stress AVA: 0.97 cm(2); p = 0.11), and positive predictive value for confirming underlying true severe aortic stenosis was 84%. In adjusted analyses, rest flow rate was the only parameter associated with severe AS (odds ratio: 1.05, 95% confidence interval: 1.0 to 1.1; p = 0.002). Rest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS and unlikely to change significantly with SE. Flow normalization may only be required in patients with AVA <1 cm(2) and mean gradient <40 mm Hg when the rest flow rate is <200 ml/s.