High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma.
The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin's lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg(-1) day(-1) for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 +/- 13.3% versus 58.9 +/- 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite 'group II', denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.


Screening a natural product-based combinatorial library using FTICR mass spectrometry.
This manuscript reports the use of Fourier transform ion cyclotron resonance mass spectrometry to screen a combinatorially generated natural product-based library for binding affinity to bovine carbonic anhydrase II (bCAII). The fungal natural product 3-chloro-4-hydroxyphenylacetamide was the library template, with 11 secondary amide analogues of this template constituting the combinatorial library. 2-(3-Chloro-4-hydroxyphenyl)-N-(4-sulfamoylphenethyl)acetamide (compound 11) of this library was identified as a tight binding inhibitor of bCAII, by detection of a noncovalent complex corresponding to [bCAII+11] in the mass spectrum. A competitive bCAII enzyme binding assay validated the mass spectrometry screening result. The equilibrium dissociation constant (K(i)) for 11 was measured as 77.4 nM. Preliminary structure-activity investigations of the bioactive natural product analogue are also reported.


Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs.
Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants.


Can villous atrophy be induced by chronic alcohol consumption?
A 43-year-old man presented with loose stools, abdominal pain and a weight loss of 15 kg. Investigations revealed a pancreatic insufficiency and an enteropathy with villous atrophy. Coeliaki was suspected. In spite of treatment with a gluten-free diet in hospital the patient did not improve and the villous atrophy remained unchanged. Other causes than coeliaki to villous atrophy were ruled out. The patient had a heavy consumption of alcohol and after prolonged abstinence the patient gained weight, the pain disappeared and the stools were normalized. The jejunal biopsy was now normal. This case report raises the possibility that enteropathy and villous atrophy may be causally related to alcohol overconsumption.


Diagnosing cystic fibrosis-related diabetes: current methods and challenges.
Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.


Melatonin action in tumor skeletal muscle cells: an ultrastructural study.
Melatonin (Mel), or N-acetyl-5-methoxytryptamine, is a circadian hormone that can diffuse through all the biological membranes thanks to its amphiphilic structure, also overcoming the blood-brain barrier and placenta. Although Mel has been reported to exhibit strong antioxidant properties in healthy tissues, studies carried out on tumor cultures gave a different picture of its action, often describing Mel as effective to trigger the cell death of tumor cells by enhancing oxidative stress. Based on this premise, here Mel effect was investigated using a tumor cell line representative of the human alveolar rhabdomyosarcoma (ARMS), the most frequent soft tissue sarcoma affecting childhood. For this purpose, Mel was given either dissolved in ethanol (EtOH) or dimethyl sulfoxide (DMSO) at different concentrations and time exposures. Cell viability assays and ultrastructural observations demonstrated that Mel was able to induce a dose- and time-dependent cell death independently on the dissolution solvent. Microscopy analyses highlighted the presence of various apoptotic and necrotic patterns correlating with the increasing Mel dose and time of exposure. These findings suggest that Mel, triggering apoptosis in ARMS cells, could be considered as a promising drug for future multitargeted therapies.


Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset.
Since the discovery of T helper type 1 and type 2 effector T cell subsets 20 years ago, inducible regulatory T cells and interleukin 17 (IL-17)-producing T helper cells have been added to the 'portfolio' of helper T cells. It is unclear how many more effector T cell subsets there may be and to what degree their characteristics are fixed or flexible. Here we show that transforming growth factor-beta, a cytokine at the center of the differentiation of IL-17-producing T helper cells and inducible regulatory T cells, 'reprograms' T helper type 2 cells to lose their characteristic profile and switch to IL-9 secretion or, in combination with IL-4, drives the differentiation of 'T(H)-9' cells directly. Thus, transforming growth factor-beta constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways.


Life-threatening postoperative pulmonary complications in patients with previous amiodarone pulmonary toxicity undergoing cardiothoracic operations.
Amiodarone therapy for cardiac arrhythmias is increasingly being recognized to be associated with pulmonary toxicity. In this report, we describe the case histories of four patients with previously diagnosed amiodarone pulmonary toxicity in whom the adult respiratory distress syndrome developed after cardiothoracic operations for malignant ventricular arrhythmias. Three patients underwent endocardial resection (two died), and a fourth patient had implantation of an automatic defibrillator unit. Radiographic changes and results of pulmonary function testing are evaluated during initial toxicity and preoperatively. These four patients (mean amiodarone dosage of 420 mg/day for 20 months) are compared to 13 other patients undergoing cardiothoracic operations with prior amiodarone treatment (one patient with preoperative pulmonary toxicity) in whom life-threatening postoperative pulmonary complications did not develop (mean dosage of 550 mg/day for 10 months). Mean preoperative serum amiodarone levels for the four patients were 1.5 micrograms/ml. In the two patients who died, desethylamiodarone levels were 510 and 4,400 micrograms/gm in pulmonary tissue. Histologic examination showed "honeycomb" appearance of the lung with prominent septae, alveolar foamy macrophages, and hyperplasia of alveolar lining cells, consistent with amiodarone pulmonary toxicity. Causes including pump-oxygenator time, oxygen toxicity, anesthetic agents, congestive heart failure, and pulmonary infection superimposed on amiodarone pulmonary toxicity are discussed with a review of the literature.


Leprosy scenario in southern part of Dakshina Kannada district, Karnataka, after 16 years of control work.
This article examines the changes that occurred in epidemiological indices over a period of 16 years following the introduction of MDT in Ullal town, south of Mangalore city, having a population of 130,000. The analysis indicates that new case-detection rates and prevalence rates showed a declining trend due to shorter duration of treatment with MDT. There was a ten-fold reduction in the prevalence rate during the first 6 years, from 23 in 1987 (230 cases) to 2.76 per 10,000 (29 cases) at the end of 16 years. The number of nmultibacillary cases among the newly detected cases showed a downtrend (from 28 cases in 1987 to 5 in 2001). The number of newly detected cases presenting with single lesion also showed a declining trend.


Cell cycle progression score improves risk stratification in prostate cancer patients with adverse pathology after radical prostatectomy.
To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.


In vitro activities of free and lipid formulations of amphotericin B and nystatin against clinical isolates of Coccidioides immitis at various saprobic stages.
We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis.


Lipoxin receptor agonist, may be a potential treatment for hemorrhagic shock-induced acute lung injury.
The main pathogenesis of acute lung injury induced by hemorrhagic shock is increasingly recognized as an inflammatory process. BML-111, a lipoxin receptor agonist, has been demonstrated to promote acute inflammatory resolution by reduction of pro-inflammatory cytokines, attenuation of neutrophilic infiltration, and increasing macrophage phagocytosis of apoptotic neutrophils. Meanwhile, lipoxins and lipoxin analogues have been reported to play pro-resolving and anti-inflammatory effects in many disease models including cerebral ischemia, dorsal air pouch, peritonitis, and so on. Therefore, we hypothesize that BML-111 may be implicated in pathogenesis of hemorrhagic shock-induced acute lung injury.


Influence of implantations of extended depth-of-focus on standard automated perimetry.
This prospective study aimed to investigate the influence of an extended depth-of-focus intraocular lens (EDOF IOL) on standard automated perimetry. Ninety eyes of 90 patients who had undergone cataract surgery from February 2018 to December 2018 were included. No patients had any diseases that might affect the visual field. ZMB00 (+ 4.00 D add), ZXR00V (+ 1.75 D add), and ZCB00V (Johnson & Johnson Surgical Vision, Santa Ana, CA, USA) were used as multifocal, EDOF, and monofocal IOLs, respectively. Humphrey Visual Field 10-2 testing was performed 2-3 months after cataract surgery, acceptable reliability indices were measured, and mean deviation (MD), pattern standard deviation (PSD), foveal sensitivity and mean sensitivity (MS) were compared. Seventy-one eyes (ZXR00V: 24 eyes, ZMB00: 25 eyes, ZCB00V: 22 eyes) were used for the analyses. The MD and MS of the EDOF and monofocal groups were significantly higher than those of the multifocal group (P < 0.0051). However, the MD and MS of the EDOF and monofocal groups were not different (P > 0.23). The PSD and foveal sensitivity were not different among the groups. In non-glaucomatous patients, the MD and MS of the EDOF IOL were comparable to those of the monofocal IOL and better than those of the multifocal IOL.


Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids.
The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.


Influence of post-training intrahippocampally applied oxotremorine on the consolidation of a brightness discrimination.
The posttraining intrahippocampal injection of oxotremorine revealed an improvement of the retention performance in a brightness discrimination task. The oxotremorine effect seemed to be dependent on distinct variables of training and was restricted to rats exhibiting a good acquisition performance. Scopolamine impaired the retention performance of animals with few training errors. The role of hippocampal cholinergic synapses for consolidation was discussed.


Cryopreservation of the blood stages of Plasmodium falciparum and Plasmodium vivax for in vivo studies.
Cryopreservation in Alsevers-glycerol of the blood stages of Plasmodium falciparum (5 strains) and P. vivax (2 strains) indicated that parasite infectivity for Aotus was retained for more than 1,100 days.


Development and validation of a scalable next-generation sequencing system for assessing relevant somatic variants in solid tumors.
Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.


The role of PI 3-kinase in the UVB-induced expression of c-fos.
The role of the PI 3-kinase signaling pathway in UVB-induced c-fos gene expression was investigated in a human keratinocyte cell line, HaCaT. The enzymatic activity of PI 3-kinase was increased threefold by 250 J/m(2) UVB. Inhibition of PI 3-kinase activity, via expression of a mutant p85 subunit or treatment with wortmannin, resulted in decreased levels of c-fos promoter activity and c-fos protein. Two members of the PI 3-kinase signaling pathway, Akt and GSK-3beta, were also found to affect c-fos transactivation. Expression of dominant negative Akt or wild-type GSK-3beta significantly inhibited UVB-induced c-fos promoter activity. In addition, when GSK-3beta activity was inhibited by lithium chloride, both c-fos promoter activity and protein levels increased. These results demonstrate that both Akt activation and GSK-3beta inactivation are required in the UVB-induction of c-fos. Our results demonstrate for the first time that UVB induction of c-fos is in part mediated by the PI 3-kinase signaling pathway in the HaCaT cell line. By identifying the multiple signaling pathways that are induced by UVB and contribute to the induction of c-fos expression, more drug targets may be identified to aid attempts to prevent and treat skin cancer.


Sexual dimorphism of the metacarpals in contemporary Cretans: Are there differences with mainland Greeks?
Sex in the adult skeleton can usually be reliably determined through an assessment of features found on the pelvis and cranium. In the lack of these elements it is necessary to elaborate other methods to establish sex in skeletonised remains recovered in forensic cases. Standards for other bones (e.g. humerus, metacarpals and metatarsals) have already been established for the Greek population. The aim of this study is to determine whether the standards for metacarpals provided from a study on the Athens collection are representative of a modern Cretan population. Using a digital caliper we took 7 measurements on each one of the left and right metacarpal bones of 108 adult individuals from a modern collection from Crete. Totally twenty formulae for left and right bones created from the Athens collection were used to sex the sample of this study. The overall classification accuracy obtained for our sample was very close to the cross-validated accuracy reported by the authors. However, looking at the classification accuracy for males and females, a consistent trend for low classification rates in females was observed. New formulae were developed for the Cretan sample yielding up to 85% classification accuracy. This study clearly indicates that the standards for metacarpals developed from the Athens collection are not appropriate for application in forensic cases for the island of Crete as they do not represent the local population efficiently. This may hold true for other regions of Greece thus great caution should be taken when applying these standards. Obviously more research is needed to confirm these results.


Atomic-Scale Engineering of Abrupt Interface for Direct Spin Contact of Ferromagnetic Semiconductor with Silicon.
Control and manipulation of the spin of conduction electrons in industrial semiconductors such as silicon are suggested as an operating principle for a new generation of spintronic devices. Coherent injection of spin-polarized carriers into Si is a key to this novel technology. It is contingent on our ability to engineer flawless interfaces of Si with a spin injector to prevent spin-flip scattering. The unique properties of the ferromagnetic semiconductor EuO make it a prospective spin injector into silicon. Recent advances in the epitaxial integration of EuO with Si bring the manufacturing of a direct spin contact within reach. Here we employ transmission electron microscopy to study the interface EuO/Si with atomic-scale resolution. We report techniques for interface control on a submonolayer scale through surface reconstruction. Thus we prevent formation of alien phases and imperfections detrimental to spin injection. This development opens a new avenue for semiconductor spintronics.


Recent Advances in Water-Soluble Vitamins Delivery Systems Prepared by Mechanical Processes (Electrospinning and Spray-Drying Techniques) for Food and Nutraceuticals Applications-A Review.
Water-soluble vitamins are essential micronutrients in diets and crucial to biochemical functions in human body physiology. These vitamins are essential for healthy diets and have a preventive role against diseases. However, their limitations associated with high sensitivity against external conditions (temperature, light, pH, moisture, oxygen) can lead to degradation during processing and storage. In this context, microencapsulation may overcome these conditions, protecting a biomolecule's bioavailability, stability, and effectiveness of delivery. This technique has been used to produce delivery systems based on polymeric agents that surround the active compounds. The present review focuses on the most relevant topics of water-soluble vitamin encapsulation using promising methods to produce delivery vehicles-electrohydrodynamic (electrospinning and electrospraying) and spray-drying techniques. An overview of the suitable structures produced by these processes is provided. The review introduces the general principles of the methods, advantages, disadvantages, and involved parameters. A brief list of the used physicochemical techniques for the systems' characterization is discussed in this review. Electrospinning and spray-drying techniques are the focus of this investigation in order to guarantee vitamins' bioaccessibility and bioavailability. Recent studies and the main encapsulating agents used for these micronutrients in both processes applied to functional food and nutraceutical areas are highlighted in this review.


Systemic neutrophil migration and rapid consumption of neutrophils in the spleen.
The systemic migration of neutrophils is not fully understood. In this study, we purified neutrophils from rat peripheral blood and labeled them with [51Cr] sodium chromate. The labeled cells were injected into the tail veins of rats, and were traced. Neutrophils were rapidly trapped in the liver and the spleen within 6 h. The migration ratios of neutrophils in the lung and the gut were lower compared with those in the liver and the spleen. Interestingly, migrated cells into the spleen were rapidly phagocytosed by monocytes/macrophages. Therefore, accumulation of intact neutrophils in the spleen may be difficult to measure.


The calcium agonist Bay K 8644 stimulates secretion from a pituitary cell line.
The dihydropyridine calcium agonist Bay K 8644 acts in a dose-dependent manner to increase prolactin secretion from the GH4C1 pituitary cell line. Enhanced secretion was observed at agonist concentrations as low as 10 nM. In the continued presence of Bay K 8644 secretion remained elevated for at least 30 min. The effect of the agonist was Ca2+-dependent and competitively antagonized by dihydropyridine antagonists. Apparently Bay K 8644 acts at the dihydropyridine binding site associated with GH4C1 Ca2+ channels to enhance Ca2+ influx and stimulate secretion from these cells. This is the first report demonstrating that the newly discovered Ca2+ agonist can, by itself, stimulate secretion from a cell.


Clovoxamine kinetics in an early clinical trial.
Elimination kinetics of the new antidepressant clovoxamine were determined in a preliminary clinical trial in 10 depressed patients. When final oral doses of 50 mg clovoxamine fumarate were given, the mean peak steady-state plasma concentration was about 60 ng/ml after 3 hr. Clovoxamine elimination proceeded by an apparent single-phasic, first-order decline with a mean t1/2 of 9.5 +/- 2.8 hr. One subject had an unusually long t1/2 (31.5 hr) and had correspondingly high clovoxamine plasma concentrations. The mean apparent volume of distribution (Vd) calculated from oral dosage was 19.5 +/- 6 l/kg, but one atypical subject had an apparent Vd of 96 l/kg. The mean apparent oral clearance was 25.5 +/- 12.5 ml/min/kg. These parameters should be of assistance in planning dosage regimens and monitoring therapeutic blood levels according to kinetic principles. Atypical clovoxamine kinetics can be associated with abnormally high or low blood levels and could therefore lead to variability in clinical response.


Effect of excitatory amino acids on gamma-aminobutyric acid release from frog horizontal cells.
The effects of excitatory amino acids, analogues and K on [3H]gamma-aminobutyric acid [3H]GABA) release from horizontal cells of the isolated superfused frog retina were studied. Exposure of the retina to medium containing high concentrations (25-100 mM) of KCl increased the release of [3H]GABA to a maximum which was 40 times the spontaneous resting release. The K-evoked release of [3H]GABA was almost abolished in high-Mg/low-Ca medium. Glutamate, aspartate, kainate and quisqualate also stimulated the release of [3H]GABA from horizontal cells, the maximum evoked release being similar to that produced by KCl. The release of [3H]GABA evoked by glutamate, aspartate, kainate and quisqualate was abolished in high-Mg/low-Ca medium and by Na-free medium. The evoked releases of [3H]GABA were not reduced by tetrodotoxin. N-Methyl-D-aspartate (NMDA) at concentrations up to 10 mM had virtually no effect on [3H]GABA release from horizontal cells. In Mg-free medium, NMDA stimulated [3H]GABA release, but the maximum release was only 10% of that produced by other agonists. Mg-free medium did not significantly affect the evoked release of [3H]GABA by other agonists. NMDA apparently possessed affinity for the kainate receptor, because in normal medium it antagonized the effects of kainate but not glutamate, aspartate or quisqualate. The non-selective antagonist of excitatory amino acids, (+/-)-cis-2,3-piperidine dicarboxylic acid (PDA) antagonized the action of glutamate, aspartate, kainate and quisqualate on horizontal cell [3H]GABA release. D(-)-2-Amino-4-phosphonobutyrate (APB) and D-gamma-glutamylglycine (D-gamma-GG) antagonized the actions of kainate on horizontal cell [3H]GABA release at concentrations which had little affect on quisqualate-evoked responses. Approximate estimates of pA2 values (Schild, 1947) showed that the specificity and potency of the antagonists was low. Nevertheless, the retinal 'non-NMDA' receptors can probably be subdivided into kainate and quisqualate types. Glutamate diethylester (GDEE) did not affect the action of any agonist. We conclude that glutamate (and aspartate) probably stimulate the release of [3H]GABA from frog horizontal cells by activating receptors of the non-NMDA type. This activation may trigger the opening of tetrodotoxin-insensitive Na channels, resulting in the depolarization of the cell membrane and an increase in the conductance of voltage-sensitive Ca-channels. An influx of Ca ions would then trigger the release of [3H]GABA. Our results are not consistent with previous suggestions that GABA release from horizontal cells involves an outwardly directed transport process.


OF4949, new inhibitors of aminopeptidase B. IV. Effects of OF4949 and its derivatives on enzyme systems.
OF4949-I and II inhibited aminopeptidase B from Ehrlich ascites carcinoma in a competitive way and the Ki value for both against L-arginine-beta-naphthylamide was 8 X 10(-9) M. Inhibition by I and II of various exopeptidases and endopeptidases was examined. OF4949-I and II both strongly inhibited leucine aminopeptidase and enkephalin-degrading aminopeptidase; I also inhibited enkephalinase B. The inhibitory effects of various derivatives of I and II on aminopeptidase B activity, showed that the terminal amino and carboxamide groups are essential for activity.


Complete Genome Sequence of an Acinetobacter Strain Harboring the NDM-1 Gene.
The NDM-1 gene is a significant public health concern. Acinetobacter is one of the most prevalent opportunistic pathogens causing recent nosocomial infections with NDM-1, and drug-resistant strains pose serious threats to public health worldwide. Herein, we present the genomic sequence of Acinetobacter calcoaceticus subsp. anitratus XM1570, a multidrug-resistant isolate that carries the blaNDM-1 gene.


Self-complementary peptides for the formation of collagen-like triple helical supramolecules.
Collagen is acknowledged as one of the most prominent biomaterials on account of its high biocompatibility and biostability. The development of artificial collagens to replace the animal-derived collagens presents a challenge in the formation of safer and highly functionalized biomaterials. Here, a novel peptide-based system for obtaining collagen-like supramolecules via a spontaneous self-assembling process is described. The designed collagen-like peptides are self-complementary trimers in which each of the 24-mer peptide strands is tethered by two cystine knots forming a staggered arrangement. Their self-assembling ability in aqueous solution was analyzed by circular dichroism, ultrafiltration, and laser diffraction particle size estimation. The obtained results indicate that the staggered trimers form large supramolecular architectures through intermolecular triple helix-formation.


Defining parameters for peripheral laser angioplasty.
In vitro studies are reported using a Pulsed Dye laser at wavelengths of 440, 480, 504, 560 and 590 nm, to vaporise multiple samples of yellow, fibrous and calcified plaque. The threshold for crater production at 440 nm was 5 mJ/pulse and at 590 nm 65 mJ/pulse. Crater depth was significantly deeper at the short wavelengths (440, 480 and 504 nm) than at the longer (560 and 590 nm). Light microscopy confirmed the absence of thermal damage associated with continuous wave lasers. Electron microscopy revealed smooth-contoured craters and no disruption of subcellular elements at the crater margin. Samples of thrombus- and atheroma-occluded human femoral artery were successfully recanalised at the 480 nm wavelength with atraumatic spherical-tipped and modified spherical tipped optical fibres. The advantages of pulsed laser energy in peripheral vessel recanalisation are discussed.


Force, membrane potential and cytoplasmic Ca2+ responses to cyclic nucleotides in rat anococcygeus muscle.
Simultaneous recordings of membrane potential and force, and cytoplasmic calcium ([Ca2+]i) and force were made in rat anococcygeus to determine whether membrane hyperpolarisation plays a role in cyclic nucleotide-induced relaxation. In the presence of phenylephrine (0.2 microM), which evoked sustained contraction, an elevation in [Ca2+]i, and depolarisation, nitroprusside (5 microM) caused 96+/-3% relaxation, 77+/-3% decrease in suprabasal [Ca2+]i, and 16+/-2 mV hyperpolarisation. Forskolin (1 microM) caused 98+/-1% relaxation, 92+/-2% decrease in suprabasal [Ca2+]i, and 18+/-1 mV hyperpolarisation. These responses persisted in the presence of a variety of K+ channel blockers or in ouabain. The decrease in [Ca2+]i preceded the commencement of relaxation whereas the onset of hyperpolarisation lagged behind. Thus, cyclic nucleotide-mediated relaxation in rat anococcygeus is not dependent on hyperpolarisation mediated by the opening of K+ channels. Rather, it is suggested that the decrease in [Ca2+]i gives rise to hyperpolarisation, which reflects a decline in the Ca2+ dependent conductance(s) activated by phenylephrine.


Posterior retroperitoneal versus transperitoneal laparoscopic adrenalectomy in adults: results from the EUROCRINE® surgical registry.
This study aims to compare posterior retroperitoneal laparoscopic adrenalectomy (PRLA) and laparoscopic transperitoneal adrenalectomy (LTA) in adults using pan-European data as conflicting results have been published regarding length of hospital stay, institutional volume, and morbidity. This retrospective cohort study analyzed data from the surgical registry EUROCRINE®. All patients undergoing PRLA and TLA for adrenal tumours and registered between 2015 and 2020 were included and compared for morbidity, length of hospital stay, and conversion to open surgery. A total of 2660 patients from 11 different countries and 69 different hospitals were analyzed and 1696 LTA were compared to 964 PRLA. Length of hospital stay was shorter after RPLA, with less patients (N = 434, 45.5%, vs N = 1094, 65.0%, p < 0.001) staying more than 2 days. In total, 96 patients (3.6%) developed a complication Clavien-Dindo grade 2 or higher. No statistical difference was found between both study groups. After propensity score matching, length of hospital stay was shorter after PRLA (> 2 days 45.2% vs 63.0%, p < 0.001). After multivariable logistic regression, factors associated with morbidity were age (OR 1.03), male sex (OR 1.52), and conversion to open surgery (OR 5.73). This study presents the largest retrospective observational analysis comparing LTA and PRLA. Our findings confirm the shorter length of hospital stay after PRLA. Both techniques are safe leading to comparable morbidity and conversion rates.


Supramolecular Biocomposite Hydrogels Formed by Cellulose and Host-Guest Polymers Assisted by Calcium Ion Complexes.
Hydrogels are biocompatible polymer networks; however, they have the disadvantage of having poor mechanical properties. Herein, the mechanical properties of host-guest hydrogels were increased by adding a filler and incorporating other noncovalent interactions. Cellulose was added as a filler to the hydrogels to afford a composite. Citric acid-modified cellulose (CAC) with many carboxyl groups was used instead of conventional cellulose. The preparation began with mixing an acrylamide-based αCD host polymer (p-αCD) and a dodecanoic acid guest polymer (p-AADA) to form supramolecular hydrogels (p-αCD/p-AADA). However, when CAC was directly added to p-αCD/p-AADA to form biocomposite hydrogels (p-αCD/p-AADA/CAC), it showed weaker mechanical properties than p-αCD/p-AADA itself. This was caused by the strong intramolecular hydrogen bonding (H-bonding) within the CAC, which prevented the CAC reinforcing p-αCD/p-AADA in p-αCD/p-AADA/CAC. Then, calcium chloride solution (CaCl2) was used to form calcium ion (Ca2+) complexes between the CAC and p-αCD/p-AADA. This approach successfully created supramolecular biocomposite hydrogels assisted by Ca2+ complexes (p-αCD/p-AADA/CAC/Ca2+) with improved mechanical properties relative to p-αCD/p-AADA hydrogels; the toughness was increased 6-fold, from 1 to 6 MJ/m3. The mechanical properties were improved because of the disruption of the intramolecular H-bonding within the CAC by Ca2+ and subsequent complex formation between the carboxyl groups of CAC and p-AADA. This mechanism is a new approach for improving the mechanical properties of hydrogels that can be broadly applied as biomaterials.


Neurocognitive deficits in HIV-positive patients-two case reports: Revising current AANTF guidelines in view of recent revelation of new neurocognitive symptoms.
Certain organic antecedents such as fever, weight loss, diarrhoea and systemic infections often present with neurocognitive deficits (NCDs). However, routine HIV screening is not done in such cases. HIV can present with psychiatric and neurocognitive symptoms as highlighted in the two cases given below.Case 1, a housewife, had been exhibiting altered behaviour following a low-grade fever over the past 3 weeks, associated with muttering to self, talking irrelevantly, would wander away from home, had decreased sleep, loss of appetite, and neglected self-care. She had displayed impulsivity by jumping into a well. On admission, the patient was mute, lethargic and the cerebrospinal fluid (CSF) tested positive for cryptococcus. Her human immunodeficiency virus (HIV) status was positive.Case 2, a housewife, presented with one-month history of muttering to self, increased irritability, aggressive on minimal provocation, decreased sleep, loss of appetite, and suspiciousness towards family members. On provisional diagnosis of schizophrenia, the patient was started on low-dose antipsychotic drugs, which showed minimal improvement. There was a distinct slowness in her movements and she progressively lost weight. Routine investigations were normal but her HIV status was positive.It has recently come to light that HIV infection also presents with subtle manifestations of the central nervous system (CNS), which are distinct from NCD and, if harnessed, could enhance diagnostic sensitivity and reduce the 'asymptomatic period'. Hence HIV testing is recommended in such cases.


Immunohistological analysis on distribution of smooth muscle tissues in livers of various vertebrates with attention to different liver architectures.
The liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having non-periportal bile ducts). The former is detectable from the hagfish, which is the most ancestral vertebrate, to tetrapod livers whereas many actinopterygian livers have the latter. The aim of the present study is to reveal the distribution of smooth muscle tissue in livers of various vertebrates with attention to their architectures. Smooth muscle was immunohistochemically compared in hepatic blood vessels and bile ducts of various vertebrates, using an anti-alpha-smooth muscle actin (ASMA) antibody. Smooth muscle was noted in the gallbladder and hepatic artery in all vertebrates, including the hagfish. Bile ducts having ASMA-positive smooth muscles were absent in the hagfish, but detected in the Chondrichthyes and conserved in actinopterygians with or without portal triads during the evolution of vertebrates. In tetrapods having portal triads, reptiles had a tendency to have strongly ASMA-positive biliary smooth muscle tissues whereas other tetrapods had bile ducts with poor smooth muscle tissues. Although the hagfish livers never had ASMA-positive smooth muscle tissue in the walls of portal and central veins, it was observed in discontinuous distributions or not observed in portal veins and central veins of chondrichthyans and actinopterygians. By contrast, in most tetrapods, ASMA-positive smooth muscle tissue was detectable in portal veins, which supported the adjacent endothelial cells as a circular layer. Central veins did not consistently have smooth muscle tissue in these groups. The hagfish liver may retain more ancestral characteristics than other vertebrates in terms of smooth muscle distribution in the vascular and biliary systems. Actinopterygians might have a different mechanism of bile transport from tetrapods from their smooth muscle distribution in intrahepatic bile ducts. The circular smooth muscle distribution in portal veins might be a characteristic acquired by tetrapods.


Thermal enhancement of bleomycin-induced tumour growth delay: the effect of dose fractionation.
The influence of hyperthermia on bleomycin-induced growth delay of a syngeneic murine carcinoma has been studied in both simultaneous and sequential schedules for single and multi-fraction drug dose. The results reveal thermal potentiation of drug-induced growth delay if treatment is given simultaneously. This observed potentiation is independent of single or multi-fraction drug administration. Sequential pre-heating treatment resulted in only additive growth rate depression for single and two-fraction drug doses. However, when the drug dose was given in three fractions a significant thermal potentiation was observed for both simultaneous and sequential schedules.


Increased rf power absorption in MR imaging due to rf coupling between body coil and surface coil.
Fears have been voiced that excessive tissue heating could occur in the event that first, a surface coil is placed with its axis parallel to the transmitting rf field leading to a maximal coupling of the two coils and second, the decoupling circuit of the surface coil breaks down. To avoid an rf coupling of the transmitting body coil to the receive-only surface coil, conventionally applied surface coils are equipped with an active electronic rf decoupling circuit. In extensive worst-case experiments on phantoms we have shown that no tissue heating occurs for surface coils which are equipped with semiconductor varicap diodes for tuning and matching. These coils should be safe for patient applications even if the decoupling circuit fails. Surface coils equipped with mechanically variable capacitors are generally passively decoupled. To simulate the worst-case situation phantom experiments were performed in which a surface coil of this type having no passive decoupling circuit was coupled to the transmitter coil by its geometric position. Theoretical calculations, in agreement with the experimental results achieved during a 15-min measurement in a 1.5-T MRI whole-body imager, show that a significant rf power deposition in the tissue underneath the coil wire occurs, leading typically to a local specific absorption rate of 24 W/kg and a local temperature rise of 5.2 degrees C.


[Frequency of coercive measures as a quality indicator for psychiatric hospitals?]
The percentage of patients subjected to coercive measures has been proposed as 1 of 10 quality indicators for psychiatric inpatient treatment by the German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN). Internationally, there are similar recommendations and corresponding reporting systems. The registry of coercive measures of psychiatric hospitals in Baden-Württemberg that was established in 2015, yields the possibility to examine the appropriateness of this indicator, based on raw data of 108,863 cases in 2016. This study investigated how the indicator is influenced by patient variables and characteristics of hospital structure. The percentage of cases exposed to coercive measures was strongly (r = 0.6) correlated with the percentage of involuntarily treated cases. With respect to the latter, hospitals varied widely with a range from 0.7% up to 24.1%. Specialized wards serving patients outside the catchment area with a high number of coercive measures also had a strong influence on the results of a benchmarking comparison. The indicator is a good instrument for longitudinal evaluation of an institution; however, due to a high number of known and unknown confounding factors, it is inappropriate for the purpose of comparing psychiatric hospitals.


Preparation and encapsulation techniques of chitosan microsphere for enhanced bioavailability of natural antioxidants.
Reactive oxygen species (ROS), induced by medical and life irradiation, have led to diverse diseases. Natural antioxidants (NAs) have been widely used to protect the body from the harmful effects of ROS. NAs have biocompatible properties but their bioavailability in the body is very low. This article discusses possible solutions to improve the bioavailability using several preparation and encapsulation techniques for microspheres using chitosan as a carrier. The first is the emulsion technique that controls particle size (0.5-1000 μm) according to the speed (RPM) of the agitator. The second technique discussed is spray drying-a very simple method that can control particle size (5-5000 μm) according to the nozzle size and discharge pressure. The third is the extrusion technique, which can control particle size (250-2500 μm) according to the syringe pore size. These techniques have enormous potential for use as drug delivery systems (DDS) in the functional food and biomedical field industries.


Cross-level group density interactions on mental health for cultural, but not economic, components of social class.
The ethnic density literature links mental health to ethnic minority status in one's neighbourhood. This design has also been applied to other identities, including sexual and political minorities, but surprisingly little attention has been paid to class-based identities. We use a Bourdieusian framework to examine whether a 'class density' association with mental health can be found for economic capital - people's material assets - and cultural capital - symbolic signifiers of class, such as tastes and interests. Multi-level regression with post-stratification was used to make area-level estimates of cultural and economic capital for each middle super output area in Wales, using data from the National Survey for Wales 2017/18 (N = 11,381). These estimates were linked to independent individual-level data from the 2018/19 edition of the same survey (N = 4058) and mixed effects models containing individual-level capital, area-level capital, and their interaction were fitted, predicting whether respondents reported a mental health problem. Models were fitted unadjusted, adjusted for age and gender; for the other form of capital on the individual and area levels; and for the other capital's cross-level interaction. Multiple imputation was used to account for missing data. For cultural capital, a cross-level interaction was found where area-level cultural capital was protective in respondents reporting higher levels of individual-level cultural capital, but a risk factor for mental health problems in those with low individual-level cultural capital (odds ratio = 0.83, CI95% = 0.75-0.93). No such relationship was found for economic capital (odds ratio = 0.96, CI95% = 0.88-1.06). These results remained robust in adjusted models. The presence of a class density association with mental health for cultural capital but not economic capital suggests that symbolic signifiers of class, more than material aspects, activate class identities and drive group density phenomena. There are implications for planning policy, mental health, and political leadership.


Synthesis Folate-linked Chitosan-coated Quetiapine/BSA Nano-Carriers as the Efficient Targeted Anti-Cancer Drug Delivery System.
Quetiapine (QTP) has been known to suppress cancer progression in patients suffering from mental disorders. This study aimed to produce the folate-linked chitosan-coated quetiapine/BSA nano-carriers (FCQB-NCs) and evaluate their antioxidant, apoptotic, and anti-metastatic potentials on prostate, pancreas, colon, and breast cancer cell lines. The FCQB-NCs were designed, produced, and characterized using DLS, FESEM, FTIR, and Zeta potential techniques. The nano-carriers antioxidant activity was studied by applying ABTS, DPPH, and FRAP assays. The FCQB-NCs' cytotoxicity and apoptotic/metastatic properties were evaluated utilizing MTT assay and qPCR-based analysis for measuring the apoptotic (Nf-KB)/metastatic (MMP2, MMP9, and MMP13) gene expression, respectively. The AO/PI fluorescent cell staining, DAPI staining, and scratch assay methods were conducted to verify the apoptotic and anti-metastatic activities of FCQB-NCs. The 51-nm FCQB-NCs (PDI = 0.26) exhibited antioxidant activity and selectively decreased the MDA-MB-231 cancer cells' viability by inducing Nf-KB overexpression, which caused the apoptosis pathway activation. Moreover, the FCQB-NCs suppressed the MDA-MB-231 cells' metastatic activity by down-regulating the MMP2, MMP9, and MMP13 gene expression, verified by detecting the decreased migration rate. The FCQB-NCs selectively induced apoptosis and suppressed metastasis in the human breast cancer cell line, which can be attributed to the stepwise release of QTP in two primary (extra-cellular release) and secondary (intra-cellular release) phases. The efficient selective cytotoxic impact of FCQB-NCs can be due to the novel stepwise release mechanism of the FCQB-NCs based on the two-phase entrapment of QTP by BSA and chitosan molecules. Therefore, FCQB-NCs have the potential to be used as an efficient selective anti-breast cancer.


Lysergylpeptides in the course of peptide ergot alkaloid formation.
Radioactive d-lysergyl-Val-Leu-OMe, d-lysergyl-Val-Val-OMe and d-lysergyl-Val-Val-Pro-OMe were synthetized according to the dicyclohexylcarbodiimide/1-hydroxybenzotriazole procedure. These compounds are not used by intact mycelium of Claviceps as immediate precursors for cyclolalkaloid biosynthesis.


Public legitimacy of healthcare resource allocation committees: lessons learned from assessing an Israeli case study.
The National Health Insurance Law enacted in 1995 stipulates a list of health services to which all Israeli residents are entitled. For the past 20 years, the list has been updated annually, as a function of a predetermined budget, according to recommendations from the Public National Advisory Committee (PNAC), which evaluates and prioritizes candidate technologies. We assessed the legitimacy of this resource-allocation process as reflected in Israeli public discourse and its congruence with the accountability for reasonableness (A4R) framework. A qualitative analysis of public discourse documents (articles in the print media, court rulings and parliamentary debates (N = 119) was conducted to assess the perceived legitimacy by the Israeli public of the PNAC. Further content analysis of these documents and semi-structured interviews with stakeholders (N = 70) revealed the mainstays and threats to its legitimacy. Based on these data sources, on governmental documents specifying PNAC's procedures, and on data from participant observations, we assessed its congruence with A4R's four conditions: publicity, relevance, revision and appeals, regulation. The PNAC enjoys ongoing support for its legitimacy in Israeli public discourse, which stem from its perceived professional focus and transparency. These strengths are consistent with the A4R's emphasis on the publicity and the relevance conditions. The three major threats to PNAC's legitimacy pertain to: (1) the composition of the committee; (2) its operating procedures; (3) its guiding principles. These perceived shortcomings are also consistent with incongruencies between PNAC's work model and A4R. These findings thus further support the empirical validity of the A4R. The analysis of the fit between the PNAC and A4R points to refinements in all four conditions that could make the A4R a more precise evaluative framework. Concurrently, it highlights areas that the PNAC should improve to increase its legitimacy, such as incorporating cost-effectiveness analyses and including patient representatives in the decision-making process. Hebrew and Arabic abstracts for this article are available as an additional file.


Baroreceptor reflexes in conscious guinea-pigs are unaffected by depletion of cardiovascular substance P nerves.
Adult guinea-pigs were injected with doses of capsaicin increasing from 10 mg/kg to 400 mg/kg over 6-days. The guinea-pigs were supplied with indwelling arterial cannulae 14 days later and the next day cardiovascular function was assessed in the conscious animals. Resting blood pressures and heart rates were recorded and then baroreceptor reflex function was evaluated by recording the changes in heart period which were evoked by blood pressure responses to injections of phenylephrine and glyceryl trinitrate. Substance P was measured by radioimmunoassay and its localization examined by immunohistochemistry. The capsaicin treatment caused a substantial reduction in substance P levels in vascular and cardiac nerves. However, there were no changes in resting heart rate, blood pressure or baroreceptor sensitivity. It is concluded that the widespread substance P nerves associated with the heart and blood vessels are not necessary for baroreceptor reflex function. Their role or roles remain unknown.


Systematic Review: Impact of Social Determinants of Health on the Management and Prognosis of Gallstone Disease.
Due to its prevalence, gallstone disease is a major public health issue. It affects diverse patient populations across various socioeconomic levels. Socioeconomic and geographic deprivation may impact both morbidity and mortality associated with digestive diseases, such as biliary tract disease. The aim of this systematic review was to review the available data on the impact of socioeconomic determinants and geographic factors on gallstone disease and its complications. This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The MEDLINE and Web of Science databases were searched by two investigators to retrieve studies about the impact of income, insurance status, hospital status, education level, living areas, and deprivation indices on gallstone disease. Thirty-seven studies were selected for this review. Socially disadvantaged populations appear to be more frequently affected by complicated or severe forms of gallstone disease. The prognosis of biliary tract disease is poor in these populations regardless of patient status, and increased morbidity and mortality were observed for acute cholangitis or subsequent cholecystectomy. Limited or delayed access and low-quality therapeutic interventions could be among the potential causes for this poor prognosis. This systematic review suggests that socioeconomic determinants impact the management of gallstone disease. Enhanced knowledge of these parameters could contribute to improved public health policies to manage these diseases.


Increased expression of ZBP-89 and its prognostic significance in hepatocellular carcinoma.
ZBP-89 plays a role in cell growth and death. Its expression in hepatocellular carcinoma (HCC) is not well documented. This study aimed to analyse ZBP-89 expression in HCC. We examined ZBP-89 expression in five HCC cell lines and 182 HCC tissue samples by reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunofluorescence staining. Our results showed that the expression of ZBP-89 was higher in HCC than adjacent non-tumour liver, at both mRNA and protein levels. ZBP-89 was localized in the nucleus in most HCC tissue samples, but was found in the cytoplasm in 11.5% of cases. Patient survival in those tumours showing high ZBP-89 expression was better than in those with low expression. High ZBP-89 expression tended to be more common in World Health Organization (WHO) grade I than grades II-IV HCC. There was a significant association between HBV positivity and high ZBP-89 expression. Colony formation was reduced dramatically in those HCC cell lines in which ZBP-89 overexpression was demonstrated; this appeared to correlate with increased apoptosis, inferred by finding elevated levels of cleaved poly(ADP-ribose)polymerases (PARP), the probable mechanisms for which may involve increased p53 or p21 expression. ZBP-89 has anti-tumour properties and is a potential biomarker for prognosis of HCC.


Fear-conditioned respiration and its association to cardiac reactivity.
This study aimed to investigate ventilatory correlates of conditioned fear responses. Respiratory, end-tidal carbon dioxide pressure (PetCO(2)) and heart rate changes were studied in a differential fear-conditioning paradigm. Forty-two participants viewed pictures of faces. One picture (CS+) was followed by a human scream (US) during the acquisition phase, but not in a subsequent extinction phase. Conditioning of PetCO(2) (decrease), respiratory cycle time (decrease) and inspiratory duty time (increase) was established and subsequently extinguished. When participants were clustered according to their conditioned PetCO(2) responses during acquisition, only a group showing a conditioned decrease in PetCO(2) showed also a differential cardiac acceleration, a decrease in expiratory duration and an increase in inspiratory duty time in response to the CS+. These results suggest that preparation for defensive action is characterized by a tendency towards hyperventilation and cardiac acceleration.


Improving the accuracy of maternal mortality and pregnancy related death.
Comparing abortion-related death and pregnancy-related death remains difficult due to the limitations within the Abortion Mortality Surveillance System and the International Statistical Classification of Diseases and Related Health Problems (ICD). These methods lack a systematic and comprehensive method of collecting complete records regarding abortion outcomes in each state and fail to properly identify longitudinal cause of death related to induced abortion. This article seeks to analyze the current method of comparing abortion-related death with pregnancy-related death and provide solutions to improve data collection regarding these subjects.


Pharmacokinetics of solifenacin in pediatric populations with overactive bladder or neurogenic detrusor overactivity.
The aim of this investigation was to characterize and compare the pharmacokinetics (PK) of the antimuscarinic drug solifenacin in pediatric patients with overactive bladder (OAB) or neurogenic detrusor overactivity (NDO) utilizing data from three phase III trials. LION was a placebo-controlled, 12-week trial in children (5-<12 years) and adolescents (12-<18 years) with OAB. MONKEY and MARMOSET were open-label, 52-week trials in children and adolescents or younger children (6 months-<5 years), respectively, with NDO. During the trials, solifenacin doses could be titrated to weight-adjusted pediatric equivalent doses (PEDs) of 2.5, 5, 7.5, or 10 mg day-1 . Nonlinear mixed effects modeling was used to develop population PK models to characterize the PK in patients with either OAB or NDO. Overall, 194 children and adolescents received solifenacin. At the time of PK sampling, the majority (119/164 [72.6%] patients) were receiving PED10 once daily. All population models included first-order oral absorption, a lag time, and interindividual variability. PK analysis showed that apparent clearance was similar in both patient populations. Mean apparent oral plasma clearance (CL/F), apparent volume of distribution during the terminal phase (Vz /F), and terminal half-life (t1/2 ) were higher in adolescents than in children, but median time to maximum plasma concentration (tmax ) was similar. Dose-normalized exposure results were similar for both younger and older patients with OAB or NDO. In conclusion, population PK modeling was used to successfully characterize solifenacin PK in pediatric patients with OAB or NDO. Similar solifenacin PK characteristics were observed in both populations.


Residual postmyocardial infarction ventricular septal defect repair through right atrium with right thoracotomy on beating heart technique.
The incidence of residual opening after repair of postmyocardial infarction ventricular septal defect (VSD) was reported to be 10% to 25%. Redo surgery with remedial sternotomy is more complex than primary surgery and is consequently associated with higher mortality and morbidity due to the myocardial and patent coronary grafts injury during pericardial dissection. A 59-year-old female patient had coronary artery bypass grafting and closure of post myocardial infarction ventricular septal defect with patch 10 months earlier in a different cardiac center. She was admitted to the hospital for severe congestive heart failure. She was operated because of the residual opening after repair of post myocardial infarction ventricular septal defect. Post myocardial infarction ventricular septal defect closure was performed through the right atrium by on-pump beating heart technique via the right thoracotomy. Closure of post myocardial infarction ventricular septal defect with this technique offers an alternative and safe approach to repair of the residual VSD when the coronary bypass grafts are patent.


Degranulation of brain mast cells in young albino rats.
Quantitative measurements were made of brain mast cell (MC) degranulation in juvenile albino rats. Neither acute nor chronic intraperitoneal injections of Compound 48/80 (C 48/80) evoked any clear degranulation. Fifteen to thirty minutes after the injection of either C 48/80 or physiological saline into the right anterior thalamus, frank degranulation in the leptomeninges and some degranulation in the parenchyma were evident. The injected sides contained about twice as much degranulated cells as the noninjected sides. In a second experiment, animals were killed 10, 100, 1000, and 10,000 min after a single 10-microliters injection of C 48/80 into the anterior thalamus. Although about 40% of the leptomeningeal and 20% of the parenchymal MCs were degranulated within 10 min, more than 50% of the MCs in both areas were degranulated within 100 min after the injection. More extensive degranulation was evident at both times within the parenchyma of the injected sides. Degranulated MCs were not obvious after this period although nuclei surrounded by sparse granules (in the parenchyma) or by fused, globular metachromatic material (in the leptomeninges or their ventricular processes) were still discernable 7 days later. The implications of brain mast cell degranulation for psychoneuroimmunology are considered.


Involvement of METTL3/m6Adenosine and TGFβ/Smad3 signaling on Tenon's fibroblasts and in a rabbit model of glaucoma surgery.
Glaucoma filtration surgery (GFS) is a classic operation for the treatment of glaucoma, which is the second leading cause of blindness, and scar formation caused by excessive human Tenon's capsule fibroblasts (HTFs) activation is responsible for surgery failure. However, the mechanism underlying excessive HTFs activation is largely unknown. Studies have revealed that N6-methyladenosine (m6A), which is one of the most common posttranscriptional modifications, plays an important role in multiple types of cellular processes. First, we isolated and identified primary HTFs and found that transforming growth factor-β1 (TGF-β1) enhanced cell viability and promoted cell proliferation and extracellular matrix (ECM) deposition in HTFs. We subsequently found that TGF-β1 elevated the quantity of m6A and promoted the expression of m6A "writers", in the process from DNA to RNA, adenylate was methylated at the sixth N position by methylases methyltransferase-like 3 (METTL3). Furthermore, we demonstrated that METTL3 repression inhibited the promotion of cell viability, proliferation and ECM deposition in HTFs treated with TGF-β1. We then illustrated that increased METTL3 played a role by promoting Smad3 in TGF-β1-induced HTFs. We subsequently demonstrated that the METTL3/Smad3 regulatory axis was aberrantly expressed in the rabbit model of GFS. Thus, our study reveals that METTL3 indeed plays a role in modulating Smad3 in TGF-β1-induced HTFs and further provides novel theoretical strategies based on METTL3 for the inhibition of scar formation after GFS.


Stereotactic MRI in DYT1 dystonia: focal signal abnormalities in the basal ganglia do not contraindicate deep brain stimulation.
To study stereotactic magnetic resonance imaging (MRI) features of the basal ganglia in DYT1 primary dystonia. Twenty-five genetically confirmed DYT1 dystonia patients (age range, 8-66 years; mean age, 22 years) underwent brain MRI under general anesthesia at the time of globus pallidus internus (GPi) deep brain stimulation (DBS) surgery. MR images were retrospectively reviewed for signal intensity alterations. Clinical improvement of patients was assessed by comparing pre- and postoperative Burke-Fahn-Marsden Dystonia Rating Scale scores. Seventeen patients out of 25 (68%) exhibited T(1)-weighted hypointense/T(2)-weighted hyperintense signal abnormalities in the putamen and globus pallidus on MR images. Signals were isointense with cerebrospinal fluid in all sequences. The mean volume of focal signal abnormalities was 15 mm(3) (maximum, 154.5 mm(3)). The total volume of focal signal abnormalities in the basal ganglia was correlated with the duration of the disease (p = 0.01). Although clinical outcome did not differ as a function of the presence of focal signal abnormalities overall, patients with signals within the GPi tended to show lesser improvement (p = 0.04). T(1)-hypointense/T(2)-hyperintense signal abnormalities are common findings in the putamen and globus pallidus of DYT1 patients but do not contraindicate DBS. However, their presence within the GPi may reduce the efficacy of DBS treatment.


Effect of water content on transient nonequilibrium NAPL-gas mass transfer during soil vapor extraction.
The effect of water content on the volatilization of nonaqueous phase liquid (NAPL) in unsaturated soils was characterized by one-dimensional venting experiments conducted to evaluate the lumped mass transfer coefficient. An empirical correlation based upon the modified Sherwood number, Peclet number, and normalized mean grain size was used to estimate initial lumped mass transfer coefficients over a range of water content. The effects of water content on the soil vapor extraction SVE process have been investigated through experimentation and mathematical modeling. The experimental results indicated that a rate-limited NAPL-gas mass transfer occurred in water-wet soils. A severe mass transfer limitation was observed at 61.0% water saturation where the normalized effluent gas concentrations fell below 1.0 almost immediately, declined exponentially from the initiation of venting, and showed long tailing. This result was attributed to the reduction of interfacial area between the NAPL and mobile gas phases due to the increased water content. A transient mathematical model describing the change of the lumped mass transfer coefficient was used. Simulations showed that the nonequilibrium mass transfer process could be characterized by the exponent beta, a parameter which described the reduction of the specific area available for NAPL volatilization. The nonequilibrium mass transfer limitations were controlled by the soil mean grain size and pore gas velocity, were well described by beta values below 1.0 at low water saturation, and were well predicted with beta values greater than 1.0 at high water saturation.


Evidence for the existence of a low spin complex in acidic methemoglobin: its structure and formation.
By means of electron spin resonance and magneto-optical rotation, specific low spin complexes in acidic methemoglobin are obtained. The formation of these complexes is explained by a specific stereochemical arrangement of the distal histidine in the absence of allosteric effectors inducing the formation of a low spin ligand at room temperature. At low temperature, however, the distal histidine is directly bound to the heme iron. As the formation of the low spin complexes depends on allosteric effectors it is suggested that via the distal histidine the affinity of heme iron ligands is modified.


Studies on lipase-catalyzed asymmetric synthesis of (S)-(hydroxymethyl)glutamic acid (HMG).
(S)-(Hydroxymethyl)glutamic acid was successfully synthesized in total 12 % yield over eight steps from tris(hydroxymethyl)aminomethane hydrochloride (Tris·HCl), employing lipase TL-induced enantioselective acetylation of a prochiral 1,3-diol as the key step.


Phosphorylation of an ethylene response factor by MPK3/MPK6 mediates negative feedback regulation of pathogen-induced ethylene biosynthesis in Arabidopsis.
Plants under pathogen attack produce high levels of the gaseous phytohormone ethylene to induce plant defense responses via the ethylene signaling pathway. The 1-aminocyclopropane-1-carboxylate synthase (ACS) is a critical rate-limiting enzyme of ethylene biosynthesis. Transcriptional and post-translational upregulation of ACS2 and ACS6 by the mitogen-activated protein kinases MPK3 and MPK6 are previously shown to be crucial for pathogen-induced ethylene biosynthesis in Arabidopsis. Here, we report that the fungal pathogen Botrytis cinerea-induced ethylene biosynthesis in Arabidopsis is under the negative feedback regulation by ethylene signaling pathway. The ethylene response factor ERF1A is further found to act downstream of ethylene signaling to negatively regulate the B. cinerea-induced ethylene biosynthesis via indirectly suppressing the expression of ACS2 and ACS6. Interestingly, ERF1A is shown to also upregulate defensin genes directly and therefore promote Arabidopsis resistance to B. cinerea. Furthermore, ERF1A is identified to be a substrate of MPK3 and MPK6, which phosphoactivate ERF1A to enhance its functions in suppressing ethylene biosynthesis and inducing defensin gene expression. Taken together, our data reveal that ERF1A and its phosphorylation by MPK3/MPK6 not only mediate the negative-feedback regulation of the B. cinerea-induced ethylene biosynthesis, but also upregulate defensin gene expression to increase Arabidopsis resistance to B. cinerea.


Association of TIM-3 expression with glucose metabolism in Jurkat T cells.
T cell activation is associated with increase in glycolysis and glutaminolysis. T cell immunoglobulin and mucin domain containing protein-3 (TIM-3), a T cell surface molecule, downregulates T cell activation and leads to insufficient immunity in cancer and chronic infection. TIM-3 regulates T cell activation possibly through alterations in metabolism; however, the relationship between TIM-3 expression and T cell metabolic changes has not been well studied. We investigated the association between TIM-3 expression and metabolic changes by analyzing glucose metabolism, glutamine metabolism, and mitochondrial function in TIM-3 overexpressing or knockout Jurkat T cell lines relative to their control cell lines. Glucose uptake and consumption, and lactate release were downregulated by TIM-3 expression but upregulated by TIM-3 knockout. Concomitantly, the expression of the glucose transporter, Glut1, but not Glut2, 3, or 4 was altered by TIM-3 expression. However, TIM-3 expression alone could not account for the change in glutamine consumption, glutamate release, and mitochondrial mass, ROS production or membrane potential in these cell lines. Our results show the association of TIM-3 expression with T cell glucose metabolism. These results are significant in chronic infections and cancers where it is necessary to control TIM-3 expressing T cells.


Essential Role of Sptan1 in Cochlear Hair Cell Morphology and Function Via Focal Adhesion Signaling.
Hearing loss is the most common human sensory deficit. Hearing relies on stereocilia, inserted into the cuticular plate of hair cells (HCs), where they play an important role in the perception of sound and its transmission. Although numerous genes have been associated with hearing loss, the function of many hair cell genes has yet to be elucidated. Herein, we focused on nonerythroid spectrin αII (SPTAN1), abundant in the cuticular plate, surrounding the rootlets of stereocilia and along the plasma membrane. Interestingly, mice with HC-specific Sptan1 knockout exhibited rapid deafness, abnormal formation of stereocilia and cuticular plates, and loss of HCs from middle and apical turns of the cochlea during early postnatal stages. Additionally, Sptan1 deficiency led to the decreased spreading of House Ear Institute-Organ of Corti 1 cells, and induced abnormal formation of focal adhesions and integrin signaling in mouse HCs. Altogether, our findings highlight SPTAN1 as a critical molecule for HC stereocilia morphology and auditory function via regulation of focal adhesion signaling.


In vitro activity of second and third generation cephalosporins against ampicillin susceptible and resistant haemophilus influenzae.
One hundred seventy-five clinical isolates of Haemophilus influenzae (including 74 beta-lactamase-producing strains) were examined for susceptibility to ampicillin, cefonicid, cefamandole, cefuroxime and cefotaxime. Cefonicid and cefamandole exhibited similar activity against ampicillin-susceptible strains (MIC90 = 0.2 mg/l for both antibiotics); cefuroxime was slightly less active (MIC90 = 0.01 mg/l). However, cefonicid, cefuroxime and cefotaxime were all more active against beta-lactamase-producing H. influenzae than cefamandole (MIC90 = 1.0 mg/l for cefonicid, MIC90 = 2.0 mg/l for cefuroxime, MIC90 = 0.01 mg/l for cefotaxime, MIC90 = 5.0 mg/l for cefamandole). One hundred twenty-five of the 175 isolates were also tested for susceptibility to cefonicid and cefamandole by disc diffusion technique and a plot of zone diameter vs. MIC was analyzed for the beta-lactamase-producing strains.


The effectiveness of technology-based strategies to promote engagement with digital interventions: a systematic review protocol.
Digital interventions provide effective and potentially cost-effective models for improving health outcomes as they deliver health information and services that are widely disseminated, confidential, and can be tailored to needs of the individual user. Digital interventions have been used successfully for health promotion, mental health, and for enabling self-management of long-term conditions. However, their effectiveness is limited by low usage rates, with non-engagement a major challenge. Hence, it is crucial to find effective strategies to increase user engagement with digital interventions. This systematic review will aim to evaluate the effectiveness of technology-based strategies to promote engagement with digital interventions. We will follow Cochrane Collaboration guidelines on systematic review methodology. The search strategy will be executed across seven e-databases (including MEDLINE, EMBASE, PsycINFO, CINAHL) using the concepts "digital intervention" and "engagement", limited by study type (randomized controlled trial). Grey literature and reference lists of included studies will be searched. Titles and abstracts will be independently screened by 2 authors. Then the full text of potentially eligible papers will be obtained and double screened. Data from eligible papers will be extracted by 1 author and checked for accuracy by another author. Bias will be assessed using the Cochrane bias assessment tool. Narrative synthesis will report on all included studies, and where appropriate, data will be pooled using meta-analysis. All findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Sources of heterogeneity will be further investigated if required. Our research is in progress. The final draft of the systematic review is being written and will be submitted before the end of 2015. The review findings will inform researchers and digital intervention providers about optimal use of technology-based strategies to promote engagement with digital interventions. PROSPERO International Prospective Register of Systematic Reviews: CRD42014010164; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014010164#.VTZmmiFViko (Archived by WebCite at http://www.webcitation.org/6XxQC8fT8).


Cancer Pain, Anxiety, and Depression in Admitted Patients at a Tertiary Care Hospital: A Prospective Observational Study.
Pain is the most common symptom in admitted cancer patients. The association between the severity of cancer pain and distress symptoms such as depression and anxiety is a subject of research. The aim is to study the prevalence of pain, anxiety, and depression in admitted cancer patients and determine the association between pain and anxiety and depression at a tertiary cancer care institute. This was prospective observational study. We enrolled 393 cancer inpatients prospectively after written informed consent. Their disease details, presence, severity, and character of pain were recorded. Numerical Pain Scale was used for pain scores, self-reporting Hospital Anxiety and Depression Scale for anxiety and depression. Normal data were analyzed with parametric, nonnormal with nonparametric methods, and categorical with the Chi-square test. The prevalence of moderate-to-severe pain was 41.5%, anxiety 20.3%, and depression 24.8%. Proportion of patients with anxiety and depression was 9.2% and 17.7% in patients with no pain; about 32.8% and 36.7% with severe pain, respectively (P < 0.000). In patients with no depression 6% had anxiety; with depression 44.9% had anxiety (P < 0.000). Odd's ratio to have anxiety and depression was 4.44 (95% confidence interval [CI] 2.0318-9.7024) and 2.92 (95% CI 1.5739-5.4186), respectively, in patients with pain as compared to no pain (P < 0.00). There was a positive correlation between pain, anxiety, and depression scores. There is strong association between the presence and severity of pain and distress symptoms such as anxiety and depression in admitted cancer patients.


Mask communication: The development of the face covering as a semiotic resource through government public health posters in England and Wales.
This paper will explore the multi-modal semiotic properties of a selection of key public health information posters issued by the UK Westminster government on the use of masks and face coverings during the first year of the COVID-19 pandemic. Using multi-modal critical discourse analysis, we show how the posters featuring masks sustained consistent government-led branding, while drawing upon what we describe as "synthetic personalisation" to manage the orientation of the crisis as the pandemic progressed. Through this analysis, the article will highlight the possible contribution of these posters to an environment characterised by political confusion and enabling of a relatively widespread rejection of mask-wearing as a public health responsibility. Examining this within a broader decline in trust in government, we suggest the various attempts to produce a positive message about mask-wearing contributed instead to the appropriation of masks as symbols of individual alignment within a contested political field.


Optical coherence tomography morphologic grading of macular commotio retinae and its association with anatomic and visual outcomes.
To investigate the morphologic characteristics of macular commotio retinae using spectral-domain optical coherence tomography (SDOCT) and develop a grading system for traumatic photoreceptor damage. Retrospective, observational case series. setting: Seoul National University Bundang Hospital. patients: Forty-nine patients with macular commotio retinae, examined by SDOCT within 7 days of the initial traumatic event. observations: A 4-step grading system was based on the morphology revealed by SDOCT. Best-corrected visual acuity (BCVA) and structural integrity of the 3 photoreceptor layers (cone outer segment tips [COST], inner/outer segment [IS-OS] junction, external limiting membrane [ELM]) were evaluated at baseline, at 1 month, and at the final visit. Visual and anatomic outcomes at 1 month and at the final visit were compared among subgroups. main outcome measures: The severity of photoreceptor damage as revealed by SDOCT and BCVA. The following 4 distinct photoreceptor morphologic features were observed: increase in IS-OS junction reflectivity with the disappearance of the thin hyporeflective optical space (n = 8, grade 1), COST defect only (n = 5, grade 2), COST and IS-OS junction defects (n = 16, grade 3), and COST, IS-OS junction, and ELM defects (n = 20, grade 4). Eyes with higher grades at baseline had significantly worse visual (final BCVA, P = .002) and anatomic outcomes (complete photoreceptor recovery, P < .001). The number of disrupted photoreceptor layers, as determined using SDOCT images, can be used to grade macular commotio retinae. This system may be useful in documenting the baseline severity of photoreceptor damage and in predicting visual and anatomic outcomes.


Species and gender differences in the formation of an active metabolite of a substituted 2,4-thiazolidinedione insulin sensitizer.
1. The metabolism of a substituted 2,4-thiazolidinedione (P1) with dual PPARalpha/gamma activity was evaluated in male and female rats, dogs and monkeys. A para-hydroxylated metabolite (M1) with potent PPARgamma-selective agonist, was a major circulating drug-related component in female rats, dogs and monkeys, but not in male rats (M1-to-P1 exposure ratio of <1, 3-5, 5 and 5-11 in male rat, monkey, female rat, and dog, respectively). 2. M1 (%) formed in vitro (5, 53, 57-65, 67 and 67% in male rat, monkey, female rat, dog, and human liver microsomes, respectively), rank ordered with M1 (%) formed in vivo (24-45, 53-57, 78, 75-85%, for male rat, monkey, female rat and dog, respectively, after oral administration of P1). 3. The plasma clearance of M1 was higher in male rats (32 ml min(-1) kg(-1) compared with 6, 7 and 2 ml min(-1) kg(-1) in female rat, male monkey and male dogs, respectively). 4. The low amounts of M1 observed in male rats, with the appearance of products of the cleavage of the propyl group between the phenyl groups was probably due to the presence of the sex-specific CYP2C11, which cleaves P1 at the propyl bridge. None of the CYPs present in female rats cleaved P1 at this site and M1 was only produced by CYP2C6. In humans, only CYP2C8 and the polymorphic CYP2C19 produced M1.


[Treatment of tuberculosis. Current standards].
The treatment of drug-sensitive tuberculosis consists of 2 months of isoniazid, rifampin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampin. These drugs are well tolerated and cure rate are above 95 %. In contrast the treatment of drug-resistent tuberculosis is difficult, mostly due to side effects of the drugs used under these circumstances. Therefore, any treatment of drug-resistant tuberculosis has to be done by experts.


Blood pressure lowering and potassium conservation by triamterene-hydrochlorothiazide and amiloride-hydrochlorothiazide in hypertension.
Effects of once-daily doses of 50 mg triamterene with 25 mg hydrochlorothiazide and 5 mg amiloride with 50 mg hydrochlorothiazide were compared in a randomized, multicenter study of 84 adult subjects with mild to moderate hypertension (diastolic blood pressure 90 to 114 mm Hg). After a 3-wk placebo lead-in period, the subjects entered a 6-wk treatment period. The two drug regimens were compared with respect to antihypertensive effects and effects on serum potassium and magnesium levels during the final week of drug therapy, with the use of the last week of placebo therapy as a covariate. Both drug regimens substantially reduced mean supine systolic and diastolic blood pressures to well within normal limits; there was no significant difference the two groups. Twenty-four of the 41 subjects receiving triamterene-hydrochlorothiazide (59%) and 29 of the 43 patients receiving amiloride-hydrochlorothiazide (67%) had diastolic blood pressure less than 90 mm Hg at week 9. Five subjects receiving amiloride-hydrochlorothiazide (12%) and two subjects receiving triamterene-hydrochlorothiazide (5%) had hypokalemia (serum potassium level less than 3.5 mEq/l) at week 9. The average decrease in serum potassium levels during amiloride-hydrochlorothiazide therapy (-0.33 +/- 0.08 mEq/l) was greater than that after triamterene-hydrochlorothiazide (- 0.08 +/- 0.07 mEq/l). Serum magnesium levels were not changed by either regimen. Weight loss was greater in the amiloride-hydrochlorothiazide group than in the triamterene-hydrochlorothiazide group.(ABSTRACT TRUNCATED AT 250 WORDS)


Injury of the Internal Carotid Artery During Endoscopic Skull Base Surgery: Prevention and Management Protocol.
Injury of the internal carotid artery during endoscopic endonasal skull base surgery is a feared and perilous scenario. This article discusses perioperative strategies to prevent or manage an internal carotid artery injury to optimize outcomes. Meticulous preoperative planning is crucial in preventing its occurrence and minimizing its consequences. An effective plan of action relies on a well-prepared protocol, availability of proper instruments and devices, and an experienced multidisciplinary team. Intraoperative control of hemorrhage and stabilization of the patient's cardiovascular status is followed by an angiography and endovascular treatment whenever possible. Close clinical and radiologic monitoring of the patient prevents early and late complications.


Asymptomatic right atrial leiomyosarcoma with tricuspid valve obstruction in a young female patient.
Primary cardiac leiomyosarcomas of the heart are rare tumors usually diagnosed post-mortem. Like other sarcomas located in the heart, it causes symptoms by obstruction or occlusion of cardiac cavities, local invasion, embolization or by systemic manifestations. We present an unusual case of a previously healthy young female patient who was accidentally diagnosed with a cardiac tumor of unknown origin during routine physical examination in May 1997. Until a few days prior to elective cardiac surgery for diagnostic purposes in June 1997, no clinical symptoms were present. To our surprise, a primary right atrial leiomyosarcoma was found which almost completely occluded the right atrium and destroyed the tricuspid valve. Despite the combination of surgical removal and adjuvant chemotherapy the patient died 3 weeks after the operation due to progressive tumor disease and development of congestive heart failure and lung embolism.


Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.
Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.


Localization of glucoamylase genes of Saccharomyces cerevisiae by pulsed field gel electrophoresis.
The chromosomal locations of four glucoamylase-specifying genes in the yeast Saccharomyces cerevisiae have been determined. Chromosomes were separated by pulsed field gel electrophoresis and blots were probed with radiolabelled STA2 and marker DNA from specific yeast chromosomes. The three genes encoding extracellular glucoamylases, STA1 (DEX2), STA2 (DEX1) and STA3 (DEX3) are located on chromosomes IV, II and XIV, respectively. SGA, specifying the sporulation-specific glucoamylase, was positioned on chromosome IX.


Circadian gene expression in the murine larynx.
Symptoms of airway diseases are often associated with specific times of the day. For example, midnight worsening of cough is a frequent complaint of patients with laryngitis and bronchitis. We speculate that these symptoms are under the control of the circadian clock, and the clock genes in the airway epithelium play some important roles. In the present study, we tried to prove the time specific expressions of clock oscillating genes in the murine larynx. Adult wild-type C57/Bl6 mice and mCry1(-/-)mCry2(-/-) mutant mice were used for this study. We employed immunohistochemistry and/or Northern blotting for examining the circadian expression of mPer1, mPer2, C/EBPbeta, HNF3beta, and MUC5b. The expression of mPer2 mRNA showed a strong day-night expression difference, which was abolished after the lesion of the suprachiasmatic nucleus, and in mCry1(-/-)mCry2(-/-) mutant mice. mPER1 and mPER2 proteins both showed very similar expression profiles in the epithelium and submucosal glands with a peak in the evening and a trough in the early morning. Other nuclear proteins such as C/EBPbeta and HNF3beta did not show the rhythms. MUC5b protein showed circadian oscillation in the laryngeal submucosal gland. In this study, we confirmed the existence of a local laryngeal clock which is controlled by the central clock in the suprachiasmatic nucleus. MUC5b protein in the submucosal mucous gland also showed circadian rhythm. We consider that these rhythmic expressions may cause the time specific symptoms among laryngeal diseases.


A pilot study evaluating chemotherapy tolerability for breast cancer patients who have received prior treatment and chest radiation for Hodgkin Lymphoma.
Women treated with chest radiation for Hodgkin lymphoma (HL) have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. This small retrospective study identified 15 patients, noting that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. Women treated for Hodgkin lymphoma (HL) with chest radiation have significantly higher risk of developing breast cancer, and little is known about how these patients tolerate chemotherapy for breast cancer. Women with breast cancer diagnosed from 1986-2015 after radiation for HL were identified from hospitals and clinics in St. Paul and Minneapolis, Minnesota. Patient, tumor and treatment characteristics, and clinical outcomes were abstracted from medical records and summarized using descriptive statistics. Chemotherapy was defined as tolerated if all scheduled doses and cycles were completed without deviation from the initial plan, with lack of grade 3 or higher toxicity attributable to chemotherapy in categories including blood, cardiac, gastrointestinal, fatigue and pain. Forty-two patients with breast cancer and prior radiation for HL were identified, 15 of which received chemotherapy for breast cancer. We noted 75% tolerability of taxane-based and 100% tolerability of anthracycline-based chemotherapy, suggesting that most patients with prior radiation for HL tolerate chemotherapy for breast cancer. A subset of patients (N = 7) in this study were also treated with chemotherapy for HL prior to breast cancer diagnosis, and 86% (6 of 7) also tolerated chemotherapy for breast cancer. Treatment of breast cancer is strongly influenced by prior treatment of HL. Although this study was small and did not meet statistical significance, the data suggest that these patients tolerate proposed chemotherapy regimens for breast cancer in rates similar to those without prior HL and therapeutic radiation. Larger studies comparing specific chemotherapy dosing schedules are needed to address this complicated population.


Incidence ofFusaria and occurrence of selected Fusarium mycotoxins on Lolium spp. in Germany.
Test plantings with varieties ofLolium multiflorum andL perenne were harvested 4 to 7 times a year in 1991 and 1992. Samples were checked for the presence ofFusaria, the mycotoxins zearalenone, T-2 toxin, and diacetoxyscirpenol (DAS). Spectrum of species and the incidence ofFusaria and fusariotoxins are discussed in relation to the influencing factors site, variety ofLolium, harvesting time and year. Depending on these factors, 41 % to 100 % of the samples wereFusarium positive. Differences in infestation with Fusarium among varieties ofLolium perenne were dependent on location and did not correlate with yield. The six species ofFusarium pathogenic toLolium spp. (F. graminearum, F. culmorum, F. avenaceum, F. oxysporum, F. solani, and F. acuminatum) totaled 35.7 % of all the isolated strains. 14 species could be isolated fromLolium samples (descending frequency):F. culmorum, F. sambucinum, F. equiseti, F. acuminatum, F. semitectum, F. oxysporum, F. subglutinans, F. avenaceum, F. sporotrichioides, F. proliferatum, F. tricinctum, F. anthophilum, F. dimerum and F. graminearum. For the detection ofFusaria a promising new immunological method is presented. It is based on the genus specific production of exopolysaccharides byFusarium species.Mycotoxin contents in grass ranged from 0.01 to 4.75 ppm for zearalenone with 67 % positive samples and 0.3 % samples above 1 ppm, 0.04 to 2.78 ppm for T-2 toxin with 25 % positive samples and 2.8 % samples above 1 ppm, and 0.003 to 0.06 for DAS with 21.6 % positive samples. In silages, no T-2 toxin was detectable. IsolatedFusarium strains were checked for the ability to produce the mycotoxins zearalenone, T-2 toxin and DAS in culture. Most of the strains were positive for at least one of the toxins.


Decreased platelet cytochrome c oxidase activity is accompanied by increased blood lactate concentration during exercise in patients with Alzheimer disease.
Increasing evidence indicates that mitochondrial dysfunction occurs in the central nervous system as well as in the peripheral tissues from Alzheimer's disease (AD) patients. We have recently shown that mitochondrial cytochrome c oxidase (COX) activity is significantly reduced in brain and platelets from AD patients compared to controls. In the present study we investigated whether impaired COX activity could have functional consequences on energy metabolism. Blood lactate concentration was monitored at rest and during incremental exercise in 22 AD patients in whom COX activity in platelets was decreased compared to controls (35.7 +/- 11.4 vs 48.4 +/- 1.4 nmol/min/mg, P < 0.01). In both resting and exercising conditions, blood lactate was significantly higher in AD patients than in controls. Although the magnitude of exercise-related lactate accumulation was not different between the two groups, an anticipated anaerobic lactate threshold during the incremental forearm exercise was found in AD patients (50% of maximal voluntary contraction MVC compared to 60% in controls). COX activity was inversely related to lactate at a significant level for resting condition (r = -0.65) and borderline for anaerobic threshold exercise level. These results support the hypothesis of a systemic impairment of the mitochondrial function in AD and indicate that decreased COX activity could have functional consequences on metabolism.