Modulation by alloxan of glucagon and insulin secretion in the isolated perfused rat pancreas.
The acute in vitro effect of alloxan on glucagon and insulin secretion from the isolated perfused rat pancreas was examined. Alloxan alone produced transient insulin secretion. Pretreatment with alloxan attenuated both the stimulatory effect of glucose on insulin secretion and the inhibitory effect of glucose on glucagon secretion. Exposure to alloxan in varying doses either partially or completely inhibited insulin secretion induced by arginine in the presence or absence of glucose. On the contrary, pretreatment with alloxan produced complex effects on arginine-induced glucagon secretion. In the absence of glucose, the response of glucagon to arginine infusion was lower in the pancreas exposed to alloxan than in the control experiment. In the presence of glucose, however, an apparently augmented response of glucagon to arginine was observed after exposure to higher doses of alloxan, suggesting an impaired inhibitory effect of glucose on arginine-induced glucagon secretion. These effects of pretreatment with alloxan on glucagon secretion can not be explained by earlier or simultaneous insulin secretion. Therefore, we conclude that alloxan acts not only on beta-cells, but also directly on alpha-cells, although the latter are less sensitive to this agent.


Molecular analysis of the major MHC recombinational hot spot located within the G7c gene of the murine class III region that is involved in disease susceptibility.
Recombination within the MHC does not occur at random, but crossovers are clustered in hot spots. We previously described a recombinational hotspot within the 50-kb Hsp70.3-G7 interval in the class III region of the mouse MHC. The parental haplotypes of recombinants with crossovers in this region represent the majority of the laboratory haplotypes (a, b, d, dx, k, m, p, px, q, s, and u). Using microsatellite markers and sequence-based nucleotide polymorphisms, the breakpoint intervals of 30 recombinants were mapped to a 5-kb-long interval within the G7c gene adjacent to G7a. Recombination within the G7c hot spot does not appear to be restricted to certain haplotypes. Sequence motifs that had been suggested to be associated with site-restricted meiotic recombination were absent in the vicinity of the G7c hot spot, and hence, these sequence motifs are no prerequisite for meiotic recombination. The G7c hot spot resides in a region to which a number of disease susceptibility loci have been mapped, including susceptibility to cleft palate, experimental autoimmune allergic orchitis, and chemically induced alveolar lung tumors. The exact localization of crossovers in recombinants that have been used in functional studies is important for mapping susceptibility genes and limits the number of candidate genes.


The association of adolescent spinal-pain-related absenteeism with early adulthood work absenteeism: A six-year follow-up data from a population-based cohort.
Objectives Spinal (ie, back and neck) pain often develops as early as during adolescence and can set a trajectory for later life. However, whether early-life spinal-pain-related behavioral responses of missing school/work are predictive of future work absenteeism is yet unknown. We assessed the association of adolescent spinal-pain-related work or school absenteeism with early adulthood work absenteeism in a prospective population-based cohort. Methods Six year follow-up data from the Western Australian Pregnancy Cohort (Raine) study were used (N=476; with a 54% response rate). At age 17, participants reported spinal pain (using the Nordic questionnaire) and adolescent spinal-pain-related work/school absenteeism (with a single item question). Annual total and health-related work absenteeism was assessed with the Health and Work Performance questionnaire distributed in four quarterly text messages during the 23rd year of age. We modelled the association of adolescent spinal-pain-related absenteeism with work absenteeism during early adulthood, using negative binomial regression adjusting for sex, occupation and comorbidities. Results Participants with adolescent low-back or neck pain with work/school absenteeism reported higher total work absenteeism in early adulthood [148.7, standard deviation (SD) 243.4 hours/year], than those without pain [43.7 (SD 95.2) hours/year); incidence rate ratio 3.4 (95% CI 1.2-9.2)]. Comparable findings were found when considering low-back and neck separately, and when considering health-related absenteeism. Conclusions We found a more than three-fold higher risk of work absenteeism in early adulthood among those with adolescent spinal-pain-related absenteeism, compared to those without. These findings suggest that, to keep a sustainable workforce, pain prevention and management should focus on pain-related behaviors as early as in adolescence.


Is talk cheap? Correspondence between self-attributions about changes in drinking and longitudinal changes in drinking during the 2019 coronavirus pandemic.
There are concerns that the coronavirus disease 2019 (COVID-19) pandemic may increase drinking, but most accounts to date are cross-sectional studies of self-attributions about alcohol-related impacts and the accuracy of those perceptions has not been investigated. The current study examined the correspondence between self-attributions of pandemic-related changes in drinking and longitudinally-measured changes in drinking and alcohol-related consequences in a sample of emerging adults. In an existing ongoing longitudinal study on alcohol misuse (≥1 heavy episodic drinking day/month) in emerging adults, 473 individuals (Mage = 23.8; 41.7% male) received a supplemental assessment from June 17th to July 1st, 2020, during public health restrictions in Ontario, Canada. These intrapandemic data were matched to the most recent assessment prior to the pandemic (~8 months earlier). Self-attributions about changes in drinking were assessed globally (i.e., increases/decreases/no change) and with higher resolution questions clarifying the magnitude of changes. Global self-attributions about changes in drinking substantively paralleled longitudinal changes in weekly drinking days (DD). In the longitudinal data, individuals' who self-reported increases in drinking exhibited significant increases; individuals' who self-reported decreases exhibited significant decreases; and individuals who self-reported no change exhibited nonsignificant changes. Higher resolution items likewise revealed longitudinal patterns of weekly drinking that were substantively consistent with self-attributions. Heavy DD and alcohol-related consequences exhibited similar patterns, but only individuals who self-reported large increases in drinking exhibited increases on these outcomes. Individuals who reported large increases in drinking also exhibited significant increases in depression and posttraumatic stress disorder symptoms. Self-attributions about drinking closely corresponded to longitudinal changes in drinking, supporting the validity of self-attributions in population-level surveys, particularly in young adults. Notably, a subgroup was identified that exhibited pronounced increases for all alcohol-related outcomes and concurrent increases in internalizing psychopathology.


Upregulation of nuclear factor-related kappa B suggests a disorder of transcriptional regulation in minimal change nephrotic syndrome.
Immune mechanisms underlying the pathophysiology of idiopathic nephrotic syndrome, the most frequent glomerular disease in children, are believed to involve a systemic disorder of T cell function and cell mediated immunity. How these perturbations take place remains unclear. We report here that NFRKB, a member of the chromatin remodeling complex, is upregulated in MCNS relapse, mainly in CD4+T cells and B cells and undergo post-translational modifications including sumoylation. We showed that NFRKB was highly expressed in nuclear compartment during the relapse, while it was restricted to cytoplasm in remission. NFRKB induced the activation of AP1 signaling pathway by upregulating the expression of c-jun. We showed that NFRKB promotes hypomethylation of genomic DNA, suggesting its implication in regulation of gene expression by enhancing the binding of transcription factors through chromatin remodeling. These results suggest for the first time that NFRKB may be involved in the disorders of transcriptional regulation commonly observed in MCNS relapse.


Epigenetic and genetic diagnosis of Silver-Russell syndrome.
Silver-Russell syndrome (SRS) is a congenital imprinting disorder characterized by intrauterine and postnatal growth restriction and further characteristic features. SRS is genetically heterogenous: 7-10% of patients carry a maternal uniparental disomy of chromosome 7; >38% show a hypomethylation in imprinting control region 1 in 11p15; and a further class of mutations are copy number variations affecting different chromosomes, but mainly 11p15 and 7. The diagnostic work-up should thus aim to detect these three molecular subtypes. Numerous techniques are currently applied in genetic SRS testing, but none of them covers all known (epi)mutations, and they should therefore be used synergistically. However, future next-generation sequencing approaches will allow a comprehensive analysis of all types of alterations in SRS.


Translational machinery of the chaetognath Spadella cephaloptera: a transcriptomic approach to the analysis of cytosolic ribosomal protein genes and their expression.
Chaetognaths, or arrow worms, are small marine, bilaterally symmetrical metazoans. The objective of this study was to analyse ribosomal protein (RP) coding sequences from a published collection of expressed sequence tags (ESTs) from a chaetognath (Spadella cephaloptera) and to use them in phylogenetic studies. This analysis has allowed us to determine the complete primary structures of 23 out of 32 RPs from the small ribosomal subunit (SSU) and 32 out of 47 RPs from the large ribosomal subunit (LSU). Ten proteins are partially determined and 14 proteins are missing. Phylogenetic analyses of concatenated RPs from six animals (chaetognath, echinoderm, mammalian, insect, mollusc and sponge) and one fungal taxa do not resolve the chaetognath phylogenetic position, although each mega-sequence comprises approximately 5,000 amino acid residues. This is probably due to the extremely biased base composition and to the high evolutionary rates in chaetognaths. However, the analysis of chaetognath RP genes revealed three unique features in the animal Kingdom. First, whereas generally in animals one RP appeared to have a single type of mRNA, two or more genes are generally transcribed for one RP type in chaetognath. Second, cDNAs with complete 5'-ends encoding a given protein sequence can be divided in two sub-groups according to a short region in their 5'-ends: two novel and highly conserved elements have been identified (5'-TAATTGAGTAGTTT-3' and 5'-TATTAAGTACTAC-3') which could correspond to different transcription factor binding sites on paralog RP genes. And, third, the overall number of deduced paralogous RPs is very high compared to those published for other animals. These results suggest that in chaetognaths the deleterious effects of the presence of paralogous RPs, such as apoptosis or cancer are avoided, and also that in each protein family, some of the members could have tissue-specific and extra-ribosomal functions. These results are congruent with the hypotheses of an allopolyploid origin of this phylum and of a ribosome heterogeneity.


Role of atrial tissue remodeling on rotor dynamics: an in vitro study.
The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.


Women's positive perception of transvaginal NOTES surgery.
Two decades ago, minimally invasive surgery (MIS) was introduced and led to a revolution in modern surgery. Currently MIS procedures are the standard of care for many surgical interventions and patients often seek out surgeons with special training in MIS. Today, natural orifice transluminal endoscopic surgery (NOTES) appears to be on the threshold of another such revolution. We surmise that its advantages are similar to those of other MIS procedures, but there are no associated abdominal wall complications as there are no abdominal incisions. To date, there is no data evaluating women's perceptions of such a procedure and their willingness to consent to this type of surgical approach. We surveyed 100 women who were given a written description of MIS and NOTES surgery along with a 10-question survey exploring their concerns and opinions regarding transvaginal surgery. The majority of women (68%) indicated that they would want a transvaginal procedure in the future because of decreased risk of hernia and decreased operative pain (90 and 93%, respectively), while only 39% were concerned with the improved cosmesis of NOTES surgery. Of the women polled, nulliparous women and those under age 45 years were significantly more often concerned with how transvaginal surgery may affect healthy sexual life and fertility issues (p < 0.05). Of the women who would not prefer transvaginal surgery, a significant number indicated concerns over infectious issues (p < 0.05). Our study shows that there is considerable public interest in NOTES surgery and women would be receptive to this new surgical technique. Our study highlights a strong need for early reporting of outcomes data to enlighten ourselves, and our patients, about this exciting new technology.


A temperature-triggered triplex bistable switch in a hybrid multifunctional material: [(CH2)4N(CH2)4]2[MnBr4].
Bistable optical-electrical duplex switches represent a class of highly desirable intelligent materials because of their potential applications in the fields of next-generation flexible devices. However, controllable photoelectric switchable materials with high-performance dielectric-switching and optical-switching properties are still scarce, with triplex bistable switches being rarely reported. Herein, a novel optoelectronic triple-functional organic-inorganic material, 5-azonia-spiro[4,4]nonane tetrabromomanganese (1, [ASN]2[MnBr4], ASN = (CH2)4N(CH2)4), which undergoes a reversible solid-state phase transition around 327 K and exhibits a recognizable second harmonic generation (SHG) effect between SHG-on and SHG-off states, has been successfully synthesized and grown as block crystals. Intriguingly, the bromine-doped crystal can exhibit intense green luminescence with a high quantum yield of 13.07% under UV excitation, extending its application in the field of photoelectric seamless integration and/or flexible multifunctional devices.


Precursor cells in mouse islets generate new beta-cells in vivo during aging and after islet injury.
Whereas it is believed that the pancreatic duct contains endocrine precursors, the presence of insulin progenitor cells residing in islets remain controversial. We tested whether pancreatic islets of adult mice contain precursor beta-cells that initiate insulin synthesis during aging and after islet injury. We used bigenic mice in which the activation of an inducible form of Cre recombinase by a one-time pulse of tamoxifen results in the permanent expression of a floxed human placental alkaline phosphatase (PLAP) gene in 30% of pancreatic beta-cells. If islets contain PLAP(-) precursor cells that differentiate into beta-cells (PLAP(-)IN(+)), a decrease in the percentage of PLAP(+)IN(+) cells per total number of IN(+) cells would occur. Conversely, if islets contain PLAP(+)IN(-) precursors that initiate synthesis of insulin, the percentage of PLAP(+)IN(+) cells would increase. Confocal microscope analysis revealed that the percentage of PLAP(+)IN(+) cells in islets increased from 30 to 45% at 6 months and to 60% at 12 months. The augmentation in the level of PLAP in islets with time was confirmed by real-time PCR. Our studies also demonstrate that the percentage of PLAP(+)IN(+) cells in islets increased after islet injury and identified putative precursors in islets. We postulate that PLAP(+)IN(-) precursors differentiate into insulin-positive cells that participate in a slow renewal of the beta-cell mass during aging and replenish beta-cells eliminated by injury.


Plant litter chemistry and microbial priming regulate the accrual, composition and stability of soil carbon in invaded ecosystems.
Soil carbon (C) sequestration, as an ecosystem property, may be strongly influenced by invasive plants capable of depositing disproportionately high quantities of chemically distinct litter that disrupt ecosystem processes. However, a mechanistic understanding of the processes that regulate soil C storage in invaded ecosystems remains surprisingly elusive. Here, we studied the impact of the invasion of two noxious nonnative species, Polygonum cuspidatum, which produces recalcitrant litter, and Pueraria lobata, which produces labile litter, on the quantity, molecular composition, and stability of C in the soils they invade. Compared with an adjacent noninvaded old-field, P. cuspidatum-invaded soils exhibited a 26% increase in C, partially through selective preservation of plant polymers. Despite receiving a 22% higher litter input, P. lobata-invaded Pinus stands exhibited a 28% decrease in soil C and a twofold decrease in plant biomarkers, indicating microbial priming of native soil C. The stability of C exhibited an opposite trend: the proportion of C that was resistant to oxidation was 21% lower in P. cuspidatum-invaded soils and 50% higher in P. lobata-invaded soils. Our results highlight the capacity of invasive plants to feed back to climate change by destabilizing native soil C stocks and indicate that environments that promote the biochemical decomposition of plant litter would enhance the long-term storage of soil C. Further, our study highlights the concurrent influence of dominant plant species on both selective preservation and humification of soil organic matter.


Burden in caregivers of adults with epilepsy in Asian families.
The literature on caregiver burden tends to focus on children and teenagers with epilepsy and less on adults. As caregiving is a dynamic, complex process across the trajectories, this study aims to examine the factors associated with caregiving burden in those caring for adults with epilepsy. This is a cross-sectional, survey-based study in which participants responded to questionnairesregarding perceived burden (ZBI), quality of life (IEQoL), psychological distress (DASS-21), family functioning (FAD) and perceived social support (MSPSS). Additional measures include socio-demographics and clinical characteristics of the care-recipient. A total of 111 caregivers participated, of whom 72.1% were females, 55% parents, 59.5% Chinese, 51.4% unemployed and 46.0% with tertiary education.Approximately half (42.3%) reported mild-to-moderate levels of burden (mean ZBI score 29.93, SD 16.09).Furthermore, multiple regression analysisidentified10 predictors of caregiver burden, namely family functioning, weekly caregiving hours, number of caregivers per family, attitude towards epilepsy, family support, caregivers' gender, personal income and as well as care-recipients' age of onset, seizure frequency and ADL dependency (F(10, 85) = 11.37, p < 0.001). Stepwise regression highlighted family functioning as the main predictor (β = 0.299, p < 0.001). The total ZBI score was positively correlated with caregivers' reported levels of depression (r = 0.549, p < 0.001), anxiety (r = 0.599, p < 0.001) and stress (r = 0.576, p < 0.001) subscales in DASS-21, and negatively correlated with IEQoL (r=-0.637, p < 0.001). This study shows that caregivers' burden is highly associated with the family system (family functioning, support and number of caregivers), besides demographics, psychosocial and clinical characteristics. Future research is required to learn how to support this sub-group of caregivers within the family system.


A method for fixing and paraffin embedding tissue to retain the natural fluorescence of reporter proteins.
Green fluorescent protein (GFP) and its derivatives are routinely employed as surrogate markers for gene expression and lineage tracing in genetically engineered mice. Tissues from these mice are commonly formalin fixed and paraffin embedded (FFPE) for histological studies. However, this results in inactivation of the natural fluorescence of these proteins, requiring their detection by immunological techniques. Here we present an ethanol fixation protocol that allows for the direct visualization of the natural fluorescence of reporter proteins while maintaining excellent tissue histology. We demonstrate the utility of this method for visualizing green and red fluorescent proteins in a wide range of murine tissues using both cytoplasmic and membrane-localized fluorescent reporter proteins. Tissues fixed by this method also allow for immunohistochemical studies, providing a single method to visualize the natural fluorescence of reporter proteins with subsequent detection of cellular proteins.


Somatomedin production in the neonatal rat.
The hormonal stimulus to rat fetal and neonatal somatic and skeletal growth has been investigated by a study of ciruclating somatomedin (SM), growth hormone (GH) and insulin levels in rats from 21 days in utero to 40 days of post natal life. Somatomedin activity could not be detected in the serum of fetal rats in which circulating GH and insulin levels were high. In early post natal life GH and insulin levels remained high but gradually declined reaching normal adult levels at 19 days and 40 days respectively. Somatomedin activity was measurable only at low levels until 11 days after birth and thereafter remained steady throughout the time period studied. These studies suggest that somatomedin alone is not responsible for the rapid growth of the rat in early neonatal life and it is suggested that insulin may also be active as a growth factor in this period.


[Novel insights into the glomerular structure].
In recent years, significant progress has been made in understanding the structure and pathomechanisms of the glomerulus of the kidney. Some of these more recent advances and open questions are discussed in this review: 1.) The functioning of the glomerular filter still remains incompletely understood, although the microanatomy and molecular biology of the glomerular filter has been investigated in great detail. 2.) Vascular endothelial growth factor (VEGF) has been shown to mediate spacial clues that are essential for the polarized distribution of the cells within the glomerulus. 3.) A novel theory of the subpodocyte space offers a novel explanation for the flux of VEGF from the podocytes against the bulk flow of the filtrate to the glomerular endothelial cells. 4.) Novel transgenic mouse models have enabled us to investigate the functional role not only of podocytes but more recently also of parietal cells which might serve as an intrarenal progenitor cell population. 5.) Parietal cells play a so far under-recognized role in various glomerular diseases. In rapid progressive glomerulonephritis, cellular crescents originate predominantly from parietal cells.


Global transcriptional analysis of nitrogen fixation and ammonium repression in root-associated Pseudomonas stutzeri A1501.
Biological nitrogen fixation is highly controlled at the transcriptional level by regulatory networks that respond to the availability of fixed nitrogen. In many diazotrophs, addition of excess ammonium in the growth medium results in immediate repression of nif gene transcription. Although the regulatory cascades that control the transcription of the nif genes in proteobacteria have been well investigated, there are limited data on the kinetics of ammonium-dependent repression of nitrogen fixation. Here we report a global transcriptional profiling analysis of nitrogen fixation and ammonium repression in Pseudomonas stutzeri A1501, a root-associated and nitrogen-fixing bacterium. A total of 166 genes, including those coding for the global nitrogen regulation (Ntr) and Nif-specific regulatory proteins, were upregulated under nitrogen fixation conditions but rapidly downregulated as early as 10 min after ammonium shock. Among these nitrogen fixation-inducible genes, 95 have orthologs in each of Azoarcus sp. BH72 and Azotobacter vinelandii AvoP. In particular, a 49-kb expression island containing nif and other associated genes was markedly downregulated by ammonium shock. Further functional characterization of pnfA, a new NifA-sigma54-dependent gene chromosomally linked to nifHDK, is reported. This gene encodes a protein product with an amino acid sequence similar to that of five hypothetical proteins found only in diazotrophic strains. No noticeable differences in the transcription of nifHDK were detected between the wild type strain and pnfA mutant. However, the mutant strain exhibited a significant decrease in nitrogenase activity under microaerobic conditions and lost its ability to use nitrate as a terminal electron acceptor for the support of nitrogen fixation under anaerobic conditions. Based on our results, we conclude that transcriptional regulation of nif gene expression in A1501 is mediated by the nif-specific and ntr gene regulatory systems. Furthermore, microarray and mutational analyses revealed that many genes of unknown function may play some essential roles in controlling the expression or activity of nitrogenase. The findings presented here establish the foundation for further studies on the physiological function of nitrogen fixation-inducible genes.


The use of social media in assessing the impact of war on cetaceans.
War has always brought millions of silent non-human victims but the scale of this suffering is often either unknown, neglected or difficult to quantify. Further, the complexities associated with long-term and large-scale monitoring of marine species make it difficult to assess the impacts of war and the mortality of cetaceans resulting from warfare has not been investigated. Here we propose the use of a modified form of citizen science, namely gathering the information from social media. Dolphin stranding is such a poignant incident for most people, that the probability of eyewitness posting information on social media appears high. We test this idea by collecting data on cetacean strandings along the Black Sea published on the Internet over the three months of Russia's invasion of Ukraine in 2022. We also validate this method with a small-scale scientific study on cetacean mortality during the same period of time, conducted in 'Tuzlivski lymany' Nature National Park in Ukraine. Our dual approach has produced similar results, indicating a dramatic increase in cetacean mortality due to war operations in the Black Sea. We advocate the future use of social media to bridge the knowledge gap on the impacts of war on animals, in particular cetaceans.


Temperature-Dependent Deicing Properties of Electrostatically Anchored Branched Brush Layers of Poly(ethylene oxide).
The hydration water of hydrophilic polymers freezes at subzero temperatures. The adsorption of such polymers will result in a hydrophilic surface layer that strongly binds water. Provided this interfacial hydration water remains liquidlike at subzero temperatures, its presence could possibly reduce ice adhesion, in particular, if the liquidlike layer is thicker than or comparable to the surface roughness. To explore this idea, a diblock copolymer, having one branched bottle-brush block of poly(ethylene oxide) and one linear cationic block, was electrostatically anchored on flat silica surfaces. The shear ice adhesion strength on such polymer-coated surfaces was investigated down to -25 °C using a homebuilt device. In addition, the temperature dependence of the ice adhesion on surfaces coated with only the cationic block, only the branched bottle-brush block, and with linear poly(ethylene oxide) was investigated. Significant ice adhesion reduction, in particular, at temperatures above -15 °C, was observed on silica surfaces coated with the electrostatically anchored diblock copolymer. Differential scanning calorimetry measurements on bulk polymer solutions demonstrate different thermal transitions of water interacting with branched and linear poly(ethylene oxide) (with hydration water melting points of about -18 and -10 °C, respectively). This difference is consistent with the low shear ice adhesion strength measured on surfaces carrying branched bottle-brush structured poly(ethylene oxide) at -10 °C, whereas no significant adhesion reduction was obtained with linear poly(ethylene oxide) at this temperature. We propose a lubrication effect of the hydration water bound to the branched bottle-brush structured poly(ethylene oxide), which, in the bulk, does not freeze until -18 °C.


Well-aligned Vertically Oriented ZnO Nanorod Arrays and their Application in Inverted Small Molecule Solar Cells.
This manuscript describes how to design and fabricate efficient inverted solar cells, which are based on a two-dimensional conjugated small molecule (SMPV1) and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM), by utilizing ZnO nanorods (NRs) grown on a high quality Al-doped ZnO (AZO) seed layer. The inverted SMPV1:PC71BM solar cells with ZnO NRs that grew on both a sputtered and sol-gel processed AZO seed layer are fabricated. Compared with the AZO thin film prepared by the sol-gel method, the sputtered AZO thin film exhibits better crystallization and lower surface roughness, according to X-ray diffraction (XRD) and atomic force microscope (AFM) measurements. The orientation of the ZnO NRs grown on a sputtered AZO seed layer shows better vertical alignment, which is beneficial for the deposition of the subsequent active layer, forming better surface morphologies. Generally, the surface morphology of the active layer mainly dominates the fill factor (FF) of the devices. Consequently, the well-aligned ZnO NRs can be used to improve the carrier collection of the active layer and to increase the FF of the solar cells. Moreover, as an anti-reflection structure, it can also be utilized to enhance the light harvesting of the absorption layer, with the power conversion efficiency (PCE) of solar cells reaching 6.01%, higher than the sol-gel based solar cells with an efficiency of 4.74%.


Development and Validation of a Nomogram for Differentiating Combined Hepatocellular Cholangiocarcinoma From Intrahepatic Cholangiocarcinoma.
To establish a nomogram based on preoperative laboratory study variables using least absolute shrinkage and selection operator (LASSO) regression for differentiating combined hepatocellular cholangiocarcinoma (cHCC) from intrahepatic cholangiocarcinoma (iCCA). We performed a retrospective analysis of iCCA and cHCC patients who underwent liver resection. Blood signatures were established using LASSO regression, and then, the clinical risk factors based on the multivariate logistic regression and blood signatures were combined to establish a nomogram for a differential preoperative diagnosis between iCCA and cHCC. The differential accuracy ability of the nomogram was determined by Harrell's index (C-index) and decision curve analysis, and the results were validated using a validation set. Furthermore, patients were categorized into two groups according to the optimal cut-off values of the nomogram-based scores, and their survival differences were assessed using Kaplan-Meier curves. A total of 587 patients who underwent curative liver resection for iCCA or cHCC between January 2008 and December 2017 at West China Hospital were enrolled in this study. The cHCC score was based on the personalized levels of the seven laboratory study variables. On multivariate logistic analysis, the independent factors for distinguishing cHCC were age, sex, biliary duct stones, and portal hypertension, all of which were incorporated into the nomogram combined with the cHCC-score. The nomogram had a good discriminating capability, with a C-index of 0.796 (95% CI, 0.752-0.840). The calibration plot for distinguishing cHCC from iCCA showed optimal agreement between the nomogram prediction and actual observation in the training and validation sets. The decision curves indicated significant clinical usefulness. The nomogram showed good accuracy for the differential diagnosis between iCCA and cHCC preoperatively, and therapeutic decisions would improve if it was applied in clinical practice.


Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma.
Osteosarcoma is the most frequent primary malignant tumor of bone with a high propensity for metastasis. We have previously showed that ezrin expression is necessary for metastatic behavior in a murine model of osteosarcoma (K7M2). In this study, we found that a mechanism of ezrin-related metastatic behavior is linked to an Akt-dependent mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (S6K1)/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) pathway. Suppression of ezrin expression either by antisense transfection or by small interfering RNAs or disruption of ezrin function by transfection of a dominant-negative ezrin-T567A mutant led to decreased expression and decreased phosphorylation of both S6K1 and 4E-BP1. Proteosomal inhibition by MG132 reversed antisense-mediated decrease of S6K1 and 4E-BP1 protein expression, but failed to affect the effect of ezrin on phosphorylation of S6K1 and 4E-BP1. Blockade of the mTOR pathway with rapamycin or its analog, cell cycle inhibitor-779 led to significant inhibition of experimental lung metastasis in vivo. These results suggest that blocking the mTOR/S6K1/4E-BP1 pathway may be an appropriate target for strategies to reduce tumor cell metastasis.


[A study on serum level and urinary excretion of fosfomycin-Na in man with special reference to pharmacokinetic analysis (author's transl)].
FOM-Na was investigated on its distribution after a continuous intravenous drip infusion in 3 healthy adult volunteers, and its serum levels and urinary excretion were pharmacokinetically analyzed, while the excreted substance into urine was also analyzed with GC/MS. The results obtained are summarized as follows: 1. The distribution volume of FOM-Na in one-compartment open model was 0.183 L/kg, half life in human body 1.66 hours and renal clearance 0.0737 L/hr/kg. 2. With these pharmacokinetic constants, the mean values following various doses demonstrated almost equal irrespective of its dosage schedule, keeping an almost constant level in each individual tested. 3. The area under serum level-time curve was approximately 216 microgram.hr/ml per 1 g (potency), and increased in proportion to an infused dose within the range of 1 approximately 6 g (potency). Three consecutive administrations showed no trend of accumulation of the agent in the serum. 4. Urinary excretion of the agent was found to be very fast, and its recovery rate from urine within 10 approximately 11 hours after the completion of an i. v. drip infusion was approximately 95 approximately 99%. 5. As a result of GC/MS on the substance excreted into urine, it was noted that FOM-Na was not metabolized in human body and excreted into urine in its original form. 6. There was seen no specific change in electrocardiogram during and/or after an intravenous drip infusion in 1 hour of 2 g (potency) FOM-Na dissolved in a 300 ml 5% glucose solution.


Dynamics of amino acid utilization in Phaeobacter inhibens DSM 17395.
Time-resolved utilization of multiple amino acids by Phaeobacter inhibens DSM 17395 was studied during growth with casamino acids. The 15 detected amino acids could be grouped according to depletion rate into four different categories, i.e. from rapid (category I) to nondepletion (category IV). Upon entry into stationary growth phase, amino acids of category I (e.g. glutamate) were (almost) completely depleted, while those of categories II (e.g. leucine) and III (e.g. serine) were further consumed at varying rates and to different extents. Thus, cultures entered stationary growth phase despite the ample presence of organic nutrients, i.e. under nonlimiting conditions. Integrated proteomic and metabolomic analysis identified 1747 proteins and 94 intracellular metabolites. Of these, 180 proteins and 86 metabolites displayed altered abundance levels during growth. Most strikingly, abundance and activity profiles of alanine dehydrogenase concomitantly increased with the onset of enhanced alanine utilization during transition into stationary growth phase. Most enzymes of amino acid and central metabolism, however, displayed unaltered abundances across exponential and stationary growth phases. In contrast, metabolites of the Entner-Doudoroff pathway and gluconeogenesis as well as cellular fatty acids increased markedly in abundance in early stationary growth phase.


Effect of elevated intraocular pressure on endothelin-1 in a rat model of glaucoma.
The role of endothelin-1 (ET-1) a potent vasoactive peptide, in glaucoma pathogenesis is receiving increasing attention, particularly in astroglial activation in optic nerve damage. Our laboratory has also shown that ET-1 treatment causes proliferation of cultured human optic nerve head astrocytes to possibly initiate astrogliosis. ET-1 is distributed in retina, optic nerve, and ciliary epithelium, however the effects of elevated intraocular pressure (IOP) (as seen in glaucoma) on ET-1 and ET(B) receptors are not clearly understood. In the present study, the levels of immunoreactive ET-1 (ir-ET-1) in aqueous humour (AH) and optic nerve head (ONH) were determined in the Morrison elevated IOP model of glaucoma. Additionally in the ONH of these rats, immunohistochemical analyses of ET(B) receptors and glial fibrillary acidic protein (GFAP; a marker for astroglial cells and for astrogliosis) were performed. There was 2- to 2.5-fold increase in AH ir-ET-1 levels for rats subjected to elevated IOP, compared to their respective controls. In the Morrison rat model of glaucoma, elevated IOP increased optic nerve ir-ET-1 with concomitant increases in ir-ET(B) and ir-GFAP labelling (possibly indicative of astrogliosis and hypertrophy). As seen in brain astrocytes subjected to neurotrauma, the present findings are suggestive of ET-1's role in astroglial activation, particularly in response to elevated IOP in glaucoma.


Diuretics in acute kidney injury.
In an acute care setting, diuretics are often prescribed to maintain or increase urine output in patients presenting with acute kidney injury (AKI). The rationale behind giving diuretics is that they may protect the kidney from ischemic injury by maintaining a nonoliguric state. There have been many studies both supporting and criticizing diuretic use in AKI for improving overall patient outcomes. A systematic review of the literature was conducted to evaluate the role of diuretics including osmotics, loop diuretics, and nesiritide in modifying AKI. There was no evidence to suggest that the use of loop diuretics in AKI reduces mortality, the need for dialysis, the number of dialysis sessions, or length of Intensive Care Unit/hospital stay or that it increases the recovery of renal function. There is no benefit for the use of mannitol as an osmotic diuretic over hydration in rhabdomyolysis. In contrast, mannitol was found to cause more harm and to induce nephropathy. Nesiritide did not improve renal function in patients with decompensated heart failure and mild chronic renal insufficiency. Nesiritide may be effective in the prevention of AKI when applied in lower doses for a prolonged period of time in patients with mild to moderate renal insufficiency. Diuretics have been shown to be ineffective in the prevention of AKI or for improving outcomes once AKI occurs. At best, diuretics can help decrease symptoms of pulmonary edema secondary to volume overload.


Establishment of DNA-DNA Interactions by the Cohesin Ring.
The ring-shaped structural maintenance of chromosome (SMC) complexes are multi-subunit ATPases that topologically encircle DNA. SMC rings make vital contributions to numerous chromosomal functions, including mitotic chromosome condensation, sister chromatid cohesion, DNA repair, and transcriptional regulation. They are thought to do so by establishing interactions between more than one DNA. Here, we demonstrate DNA-DNA tethering by the purified fission yeast cohesin complex. DNA-bound cohesin efficiently and topologically captures a second DNA, but only if that is single-stranded DNA (ssDNA). Like initial double-stranded DNA (dsDNA) embrace, second ssDNA capture is ATP-dependent, and it strictly requires the cohesin loader complex. Second-ssDNA capture is relatively labile but is converted into stable dsDNA-dsDNA cohesion through DNA synthesis. Our study illustrates second-DNA capture by an SMC complex and provides a molecular model for the establishment of sister chromatid cohesion.


Superior oxygen and glucose supply in perfusion cell cultures compared to static cell cultures demonstrated by simulations using the finite element method.
Oxygen and glucose supply is one of the important factors for the growth and viability of the cells in cultivation of tissues, e.g., spheroid, multilayered cells, and three-dimensional tissue construct. In this study, we used finite element methods to simulate the flow profile as well as oxygen and glucose supply to the multilayered cells in a microwell array chip for static and perfusion cultures. The simulation results indicated that oxygen supply is more crucial than glucose supply in both static and perfusion cultures, and that the oxygen supply through the wall of the perfusion culture chip is important in perfusion cultures. Glucose concentrations decline with time in static cultures, whereas they can be maintained at a constant level over time in perfusion cultures. The simulation of perfusion cultures indicated that the important parameters for glucose supply are the flow rate of the perfusion medium and the length of the cell culture chamber. In a perfusion culture chip made of oxygen-permeable materials, e.g., polydimethylsiloxane, oxygen is hardly supplied via the perfusion medium, but mainly supplied through the walls of the perfusion culture chip. The simulation of perfusion cultures indicated that the important parameters for oxygen supply are the thickness of the flow channel and the oxygen permeability of the walls of the channel, i.e., the type of material and the thickness of the wall.


Ocean acidification: effects of pH on 45Ca uptake by lobster branchiostegites.
Gill chambers of the Atlantic lobster, Homarus americanus, possess three structures that are involved with respiration and ion regulation: gill filaments, epipodites, and branchiostegites. This paper describes ion transport mechanisms present in the plasma membranes of branchiostegite epithelial cells and the effects of pH on the uptake of 45Ca by these processes. Partially purified membrane vesicles (PPMV) of branchiostegite cells were produced by a homogenization/centrifugation method that has previously been used to define ion transport processes in both crab and lobster gill tissues. In the present study, lobster branchiostegite PPMV 45Ca uptake was highest at pH 8.5 and lowest at pH values between 6.0 and 7.0 (p < 0.02). At pH 8.0, 45Ca uptake was a biphasic process consisting of a saturable process at low [Ca] and a linear process at higher [Ca]. At pH 6.0, 45Ca uptake was only a linear process and paralleled linear uptake at pH 8.0. A valinomycin/K+-induced membrane potential (PD, inside negative) doubled 45Ca uptake at pH 7.0 above that in the absence of a PD (p < 0.05). An induced PD at pH 8.0 did not significantly (p > 0.05) affect 45Ca uptake observed in the absence of a PD, but was threefold greater than uptake at pH 7.0 in the absence of a PD (p < 0.05). Amiloride (2 mM) did not affect 45Ca uptake at pH 8.0, but 2 mM amiloride + 100 µM verapamil reduced uptake by approximately 50%. In the presence of both 2 mM amiloride + 100 µM verapamil, 15 s 45Ca influx at pH 8.5 was a hyperbolic function of [Ca] (0.1-5 mM) (Km = 4.2 ± 0.3 mM; Jmax = 9792 ± 439 pmol/mg protein × 15 s). 45Ca influxes at pH 7.5 under the same conditions were also hyperbolic with Km = 8.3 ± 1.4 mM; Jmax = 10732 ± 1250 pmol/mg protein × 15 s. Km values were significantly different (p < 0.05), but Jmax values were not (p > 0.05). These results suggest that 45Ca uptake by lobster branchiostegites may have occurred by the combination of diffusion through a verapamil-inhibited calcium channel and carrier-mediated transport by amiloride-insensitive, electroneutral, 1Ca2+/2H+ antiporters. Decreased pH, as might occur during ocean acidification, did not appear to modify calcium diffusion through the channels, but protons acted as competitive inhibitors of calcium transport by carrier-mediated antiport. Decreased calcium uptake with continued ocean acidification may significantly affect calcification processes during periodic molting, potentially influencing mortality.


Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.
Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma. Netherlands Trial Register [ NTR4243 , 11 October 2013].


Hyperadrenocorticism of calorie restriction contributes to its anti-inflammatory action in mice.
Calorie restriction (CR), which lengthens lifespan in many species, is associated with moderate hyperadrenocorticism and attenuated inflammation. Given the anti-inflammatory action of glucocorticoids, we tested the hypothesis that the hyperadrenocorticism of CR contributes to its attenuated inflammatory response. We used a corticotropin-releasing-hormone knockout (CRHKO) mouse, which is glucocorticoid insufficient. There were four controls groups: CRHKO mice and wild-type (WT) littermates fed either ad libitum (AL) or CR (60% of AL food intake), and three experimental groups: (a) AL-fed CRHKO mice given corticosterone (CORT) in their drinking water titrated to match the integrated 24-hr plasma CORT levels of AL-fed WT mice, (b) CR-fed CRHKO mice given CORT to match the 24-hr CORT levels of AL-fed WT mice, and (c) CR-fed CHRKO mice given CORT to match the 24-hr CORT levels of CR-fed WT mice. Inflammation was measured volumetrically as footpad edema induced by carrageenan injection. As previously observed, CR attenuated footpad edema in WT mice. This attenuation was significantly blocked in CORT-deficient CR-fed CRHKO mice. Replacement of CORT in CR-fed CRHKO mice to the elevated levels observed in CR-fed WT mice, but not to the levels observed in AL-fed WT mice, restored the anti-inflammatory effect of CR. These results indicate that the hyperadrenocorticism of CR contributes to the anti-inflammatory action of CR, which may in turn contribute to its life-extending actions.


Infrared analysis of urinary stones: a trial of automated identification.
A Search algorithm included in the Opus software of Bruker (Germany) was evaluated for analysis of urinary stones. Three reference libraries containing respectively 85 (single components), 1,059 (binary mixtures) and 4,565 (ternary mixture) digitized spectra were created and used to identify unknown spectra (n=320), applying the automatic procedure. Identification of the major component was correct in 83% of cases but the percentage of identification significantly decreased for the second and the third components. In cases of identification of the two first components, quantitative assessment was correct within tolerance limits +/- 15%. The computer results are judged unsatisfactory with regard to pathology because computer-aided identification is not sufficiently sensitive and specific to differentiate species with similar spectral pattern, even for the identification of main component, and also to detect minor components. It can be of assistance to guide spectral analysis, but it cannot replace human identification.


ESR and TL investigations on gamma irradiated linden (Tilia vulgaris).
Electron spin resonance (ESR) and thermoluminescence (TL) signals induced by gamma irradiation in linden (Tilia vulgaris) were studied for detection and dosimetric purposes. Before irradiation, linden leaf samples exhibit one singlet ESR signal centred at g = 2.0088. Besides this central signal, in spectra of irradiated linden samples, two weak satellite signals situated about 3 mT left (g = 2.0267) and right (g = 1.9883) were observed. Dose-response curves for the left satellite signal and the central single signal were constructed, and it was found that both of these curves can be described best by the combination of two exponential saturation functions. Variable temperature and fading studies at room temperature showed that the radiation-induced radicals in linden leaf samples are very sensitive to temperature. The stabilities of the left satellite (g = 2.0267) and the central single (g = 2.0088) signal at room temperature over a storage period of 126 days turned out to be best described by a sum of two first-order decay functions. The kinetic features of the left satellite signal were studied over the temperature range of 313-373 K. The results indicate that the isothermal decay curves of the left satellite ESR signal also proved to be best fitted by the combination of two first-order decay functions. Fading and annealing studies suggested the existence of two different radiation-induced free radical species. At the same time, Arrhenius plots evidenced two different kinetic regimes with two different activation energies. TL investigation of polyminerals from the linden samples allowed to discriminate clearly between irradiated and unirradiated samples even 75 days after irradiation.


Analysis of human UDP-glucose dehydrogenase gene promoter: identification of an Sp1 binding site crucial for the expression of the large transcript.
UDP-glucose dehydrogenase (UGDH) catalyzes the conversion of UDP-glucose to UDP-glucuronic acid, which is required in liver for the excretion of toxic compounds, and for the biosynthesis of complex carbohydrates, such as hyaluronan, in many cell types. Analysis of a human EST database, as well as the results of a 5'-RACE experiment, have revealed the presence of two transcription start sites approximately 160 bp apart in the human UGDH gene confirming previous Northern hybridization results. To delineate the regions in the UGDH promoter required for regulating the expression of the gene, in particular the synthesis of the large transcript, serial deletions of the 2.1-kb UGDH promoter region were constructed and their activities determined by the firefly luciferase reporter gene assay. Our results indicate that the region from nucleotide position -486 to -632 relative to the start of the small transcript contains positive regulatory elements that contribute to gene expression. Mithramycin A, an inhibitor of transcription factor Sp1, abrogates the promoter activity, suggesting the involvement of this specific protein in UGDH expression. By using site-directed mutagenesis, we analyzed the functional contribution of three putative Sp1 binding elements within this region. A mutation at position -564 demonstrated that this site serves as an enhancing element in both HepG2 and HeLa cells. The complex formation pattern revealed by an electrophoretic mobility shift assay as well as an anti-Sp1 antibody-mediated supershift assay confirmed the identity of this GC box as an Sp1 binding motif. Our results thus identify an alternative transcription start site on the UGDH promoter, and locate the cis-element that greatly enhances the basal transcriptional activity of UGDH gene.


Implementation Science for the Environment.
The establishment of the field of implementation science was motivated by the understanding that medical and health research alone is insufficient to generate better health outcomes. With strong support from funding agencies for medical research, implementation science promotes the application of a structured framework or model in the implementation of research-based results, specifically evidence-based practices (EBPs). Furthermore, explicit consideration is given to the context of EBP implementation (i.e., socio-economic, political, cultural, and institutional factors that could affect the implementation process). Finally, implementation is monitored in a robust and rigorous way. Today, the field of implementation science supports conferences and professional societies as well as one dedicated journal and numerous others with related content. The goal of these various activities is to reduce the estimated, average "bench to bedside" time lag of 17 years for uptake of EBPs from health research into routine practice. Despite similar time lags and impediments to uptake in the environmental domain, a parallel field of implementation science for the environment has not (yet) emerged. Although some parallels in needs and opportunities can easily be drawn between the health and environmental domains, a detailed mapping exercise is needed to understand which aspects of implementation science could be applied in the environmental domain either directly or in a modified form. This would allow an accelerated development of implementation science for the environment.


Explaining the Early Development and Health of Teen Mothers' Children.
The transmission of social disadvantage from teenage mothers to their children is well established, but when and why do these disparities emerge in the early life course? Using nationally representative data from the Early Childhood Longitudinal Study-Birth Cohort, this study investigated the relationship between teen childbearing and children's cognition, behavior, and health from infancy through preschool. Developmental disparities between teenage mothers' children and others were largely nonexistent at 9 months but accumulated with age. Having a teenage mother predicted compromised development across several domains by age 4½. Our conceptual model expected preexisting disadvantage, ongoing resource disadvantage, and compromised parenting quality to explain the association between teen childbearing and child outcomes. Preexisting social disadvantage accounted for much of this relationship. Financial, social, and material resources in the child's household partially or fully explained each of the remaining significant relationships between teenage childbearing and child outcomes. Parenting quality explained a smaller proportion of these relationships than did resources, and these factors' influences were largely independent. Because children of teenage mothers with a modest set of resources were not predicted to have compromised development, resources provided in early childhood may have the potential to reduce developmental disparities for teenage mothers' children.


[On informing in-patients, and the problem of hospitalism (author's transl)].
Sixty-seven in-patients, admitted to neurological or surgical wards of an acute hospital, were repeatedly interviewed during an average stay of 15 days to test their need for information about their illness, their satisfaction with information received and their knowledge about their illness. Parallel to these interviews psychometric tests were performed on the second, seventh and penultimate day of the hospital stay, in the evening, to assess the extent of any disturbance in their subjective condition. Independent of the initial state, there were consistently less favourable results in those patient groups which (using several indicators) had a deficit in subjective information. These group-specific differences were in part statistically significant. An intervening influence of 12 personality dimensions was not definitely established. These findings support the hypothesis that deficient instruction and information of in-patients represents an important stress component which in the majority of these patients can give rise to an objectifiable psychosocial hospitalism.


Post-traumatic stress disorder among bank employee victims of robbery.
Post-traumatic stress disorder (PTSD) in the occupational context, especially following workplace robbery, is still under-investigated. To evaluate PTSD incidence and risk factors among bank employee victims of robbery voluntarily joining an employer-sponsored post-robbery support programme. The programme entailed a structured support interview with robbery victims within 15 days of the robbery and a follow-up psychological assessment 45 days after. A self-reported questionnaire on personal variables and robbery characteristics was administered to participants at the first support session (T1). Interviews on employees' psychophysical health and their opinion about the support programme were administered individually at follow-up (T2). The Impact of Event Scale (IES) was administered both at T1 and T2. There were 383 participants. At T2, 13% of subjects had an IES score >34, a cut-off suggestive of PTSD. In a multi-variate model, feelings of helplessness and terror during the robbery and the number of previous robberies were associated with a PTSD diagnosis. After including IES score at T1, other variables lost statistical significance. Our findings showed that PTSD is common among employee victims of workplace robbery. Our results also suggest the importance of subjective variables, such as personal perception of robbery severity and early emotional reaction, in identifying people at higher risk of developing PTSD.


Core-Shell Gold Nanorod@Zirconium-Based Metal-Organic Framework Composites as in Situ Size-Selective Raman Probes.
Nanoparticle encapsulation inside zirconium-based metal-organic frameworks (NP@MOF) is hard to control, and the resulting materials often have nonuniform morphologies with NPs on the external surface of MOFs and NP aggregates inside the MOFs. In this work, we report the controlled encapsulation of gold nanorods (AuNRs) by a scu-topology Zr-MOF, via a room-temperature MOF assembly. This is achieved by functionalizing the AuNRs with poly(ethylene glycol) surface ligands, allowing them to retain colloidal stability in the precursor solution and to seed the MOF growth. Using this approach, we achieve core-shell yields exceeding 99%, tuning the MOF particle size via the solution concentration of AuNRs. The functionality of AuNR@MOFs is demonstrated by using the AuNRs as embedded probes for selective surface-enhanced Raman spectroscopy (SERS). The AuNR@MOFs are able to both take-up or block molecules from the pores, thereby facilitating highly selective sensing at the AuNR ends. This proof-of-principle study serves to present both the outstanding level of control in the synthesis and the high potential for AuNR@Zr-MOF composites for SERS.


Deep learning-based diagnosis of stifle joint diseases in dogs.
In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.


GAS6-AXL Inhibition by AVB-500 Overcomes Resistance to Paclitaxel in Endometrial Cancer by Decreasing Tumor Cell Glycolysis.
Chemotherapy is often ineffective in advanced-stage and aggressive histologic subtypes of endometrial cancer. Overexpression of the receptor tyrosine kinase AXL has been found to be associated with therapeutic resistance, metastasis, and poor prognosis. However, the mechanism of how inhibition of AXL improves response to chemotherapy is still largely unknown. Thus, we aimed to determine whether treatment with AVB-500, a selective inhibitor of GAS6-AXL, improves endometrial cancer cell sensitivity to chemotherapy particularly through metabolic changes. We found that both GAS6 and AXL expression were higher by immunohistochemistry in patient tumors with a poor response to chemotherapy compared with tumors with a good response to chemotherapy. We showed that chemotherapy-resistant endometrial cancer cells (ARK1, uterine serous carcinoma and PUC198, grade 3 endometrioid adenocarcinoma) had improved sensitivity and synergy with paclitaxel and carboplatin when treated in combination with AVB-500. We also found that in vivo intraperitoneal models with ARK1 and PUC198 cells had decreased tumor burden when treated with AVB-500 + paclitaxel compared with paclitaxel alone. Treatment with AVB-500 + paclitaxel decreased AKT signaling, which resulted in a decrease in basal glycolysis. Finally, multiple glycolytic metabolites were lower in the tumors treated with AVB-500 + paclitaxel than in tumors treated with paclitaxel alone. Our study provides strong preclinical rationale for combining AVB-500 with paclitaxel in aggressive endometrial cancer models.


Beyond expectations: disease duration and psychological burden in psoriatic arthritis.
This study aims to investigate the relationship between disease duration and psychological burden in PsA and to identify the risk factors associated with psychological distress. Patients with PsA who met CASPAR classification criteria enrolled by Turkish League Against Rheumatism (TLAR)-Network. Patients were categorized into three groups based on disease duration: early stage (< 5 years), middle stage (≥ 5, < 10 years), and late stage (≥ 10 years). All patients underwent clinical and laboratory assessment using standardized protocol and case report forms. The associations between psychological variables and clinical parameters were assessed by a multivariate analysis. Of the 1113 patients with PsA (63.9% female), 564 (%50.7) had high risk for depression and 263 (%23.6) for anxiety. The risk of psychological burden was similar across all PsA groups, and patients with a higher risk of depression and anxiety also experienced greater disease activity, poorer quality of life, and physical disability. Multivariate logistic regression revealed that female gender (OR = 1.52), PsAQoL (OR = 1.13), HAQ (OR = 1.99), FiRST score (OR = 1.14), unemployment/retired (OR = 1.48) and PASI head score (OR = 1.41) were factors that influenced the risk of depression, whereas the current or past enthesitis (OR = 1.45), PsAQoL (OR = 1.19), and FiRST score (OR = 1.26) were factors that influenced the risk of anxiety. PsA patients can experience a comparable level of psychological burden throughout the course of their disease. Several socio-demographic and disease-related factors may contribute to mental disorders in PsA. In the present era of personalized treatment for PsA, evaluating psychiatric distress can guide tailored interventions that improve overall well-being and reduce disease burden.


Lysine oxidation by growing pigs receiving diets containing free and protein-bound lysine.
Knowledge of amino acid availability in feedstuffs is central to accurate diet formulation. Dietary lysine oxidation was evaluated as a means of predicting dietary lysine availability. Growing pigs (30 kg) were offered control (1.43% lysine), free lysine-supplemented soybean meal-, or cottonseed meal-supplemented diets. Supplemented diets provided equivalent total lysine (approximately 24.2 g/d at 30 kg BW) but availabilities of lysine, determined by slope-ratio assay, in the free lysine, soybean meal, and cottonseed meal were 100, 90, and 30%, respectively. Feed was offered in eight equally spaced meals per day to achieve three times maintenance energy intake. Following a meal containing L-[U-14C]lysine (1 mu Ci/kg BW), lysine oxidation, as 14CO2 expired, was lower (P < .05) for the control diet but not different between the other three diets, contrary to the hypothesis. Lysine oxidation following an intravenous bolus dose was lowest (P < .05) for pigs fed the control, highest (P < .05) for pigs fed the cottonseed diet, and intermediate (P < .05) for pigs fed the free lysine-supplemented diet (27.1, 80.2, and 47.5, dpm/kg x 10(-2), respectively). Plasma lysine concentration was lower (P < .05) and lysine specific radioactivity tended to be higher (P < .10) following a meal containing cottonseed than following a meal containing free lysine, indicating that the lysine pool was smaller in pigs receiving the cottonseed-meal diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Anomic suicides on rise during recently emerging crises: revisiting Durkheim's model.
Suicide is a global public health issue, with behavior differing across genders, age groups, places, and sociopolitical settings. Emile Durkheim characterized anomic suicide as occurring when social standards fail, resulting in purposelessness and directionlessness. Young people who are experiencing social issues are in danger, even if they do not voice suicidal ideas. Prevention interventions should target these people by strengthening resilience, minimizing social dysregulation stress, and fostering the development of life skills, coping resources, and social support. Anomic suicide has important psychological and societal implications, emphasizing the importance of fostering social cohesion and assisting persons experiencing purposelessness or a lack of direction in life.


Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM.
The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.


Male partners of women with provoked vestibulodynia: attributions for pain and their implications for dyadic adjustment, sexual satisfaction, and psychological distress.
Provoked vestibulodynia is a female genital pain condition that results in sexual dysfunction and impacts negatively on the couple. Although patients' causal attributions have been linked to worse psychosexual outcomes, no study has documented the male partners' perspective of this distressing problem and its potential influence on their psychosexual adaptation. To identify whether male partners' attributions for vestibulodynia are possible predictors of their dyadic adjustment, sexual functioning, sexual satisfaction, and psychological distress, as well as of women's pain and sexual functioning. Thirty-eight women with vestibulodynia first completed measures of pain intensity and sexual functioning. Male partners responded to mailed questionnaires assessing their own attributions for genital pain as well as their psychological distress, relationship adjustment, sexual functioning, and sexual satisfaction. Women completed the McGill-Melzack Pain Questionnaire (MPQ) and the Female Sexual Function Index (FSFI). Attributions of male partners were measured using an adapted version of the Attributional Style Questionnaire (ASQ)-Partner Version. Men also filled out the Brief Symptom Inventory (BSI), the Dyadic Adjustment Scale (DAS), the Sexual History Form (SHF), and the Global Measure of Sexual Satisfaction (GMSEX). All four negative attribution dimensions and higher levels of women's pain intensity successfully predicted increased psychological distress in male partners. Higher levels of both internal and global attributions were associated with men's poorer dyadic adjustment, whereas global and stable attributions were related to their lower sexual satisfaction. Attributions failed to significantly predict sexual functioning in male partners and women's pain and sexual functioning. Evaluation and treatment of sexual pain problems should involve both partners and should explore the role of negative attributions.


Laparoscopic versus open radical cystectomy in the treatment of locally advanced T3 and T4 bladder cancer: Perioperative and Mid-term oncological outcomes.
In this study, we aim to compare the perioperative and midterm oncological outcomes in patients with advanced bladder cancer and those who had laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). We retrospectively reviewed medical records of patients who underwent LRC or ORC in a single center between 2008 and 2014 with a pathological diagnosis of pT3 and pT4 bladder cancer. Thirty-five and 39 patients were included in the study as part of the LRC and ORC groups, respectively. There was no statistically significant difference between the two groups in terms of disease-free survival (LRC, 39.8±4.86 months; ORC, 45.47±8.92 months, P=0.896). Average estimated blood loss and length of hospitalization were significantly less in the LRC group. The overall survival rates of patients at 1, 2, and 3 years were 73%, 46%, and 46% in the ORC group and 78%, 65%, and 40% in the LRC group, respectively, and there was no statistically significant difference between the two groups. One patient in the ORC group experienced rectal injury in the form of a serosal tear, which was repaired primarily without any postoperative sequelae. There were no conversions in the laparoscopic group. Similarly, in 1 patient, rectal serosal tear was repaired preoperatively. Our study showed that LRC provides midterm oncological outcomes similar to ORC in the treatment of locally advanced T3 and T4 bladder cancer. However, long-term oncological and functional outcomes are required.


Comparative mapping reveals quantitative trait loci that affect spawning time in coho salmon (Oncorhynchus kisutch).
Spawning time in salmonids is a sex-limited quantitative trait that can be modified by selection. In rainbow trout (Oncorhynchus mykiss), various quantitative trait loci (QTL) that affect the expression of this trait have been discovered. In this study, we describe four microsatellite loci associated with two possible spawning time QTL regions in coho salmon (Oncorhynchus kisutch). The four loci were identified in females from two populations (early and late spawners) produced by divergent selection from the same base population. Three of the loci (OmyFGT34TUF, One2ASC and One19ASC) that were strongly associated with spawning time in coho salmon (p < 0.0002) were previously associated with QTL for the same trait in rainbow trout; a fourth loci (Oki10) with a suggestive association (p = 0.00035) mapped 10 cM from locus OmyFGT34TUF in rainbow trout. The changes in allelic frequency observed after three generations of selection were greater than expected because of genetic drift. This work shows that comparing information from closely-related species is a valid strategy for identifying QTLs for marker-assisted selection in species whose genomes are poorly characterized or lack a saturated genetic map.


Improving visual search in instruction manuals using pictograms.
Instruction manuals provide important messages about the proper use of a product. They should communicate in such a way that they facilitate users' searches for specific information. Despite the increasing research interest in visual search, there is a lack of empirical knowledge concerning the role of pictograms in search performance during the browsing of a manual's pages. This study investigates how the inclusion of pictograms improves the search for the target information. Furthermore, it examines whether this search process is influenced by the visual similarity between the pictograms and the searched for information. On the basis of eye-tracking measurements, as objective indicators of the participants' visual attention, it was found that pictograms can be a useful element of search strategy. Another interesting finding was that boldface highlighting is a more effective method for improving user experience in information seeking, rather than the similarity between the pictorial and adjacent textual information. Implications for designing effective user manuals are discussed. Practitioner Summary: Users often view instruction manuals with the aim of finding specific information. We used eye-tracking technology to examine different manual pages in order to improve the user's visual search for target information. The results indicate that the use of pictograms and bold highlighting of relevant information facilitate the search process.


Carbon dioxide adsorption by physisorption and chemisorption interactions in piperazine-grafted Ni2(dobdc) (dobdc = 1,4-dioxido-2,5-benzenedicarboxylate).
The metal-organic framework Ni(2)(dobdc) (CPO-27-Ni, where dobdc = 1,4-dioxido-2,5-benzenedicarboxylate) has been post-synthetically modified with piperazine (pip) - a known 'accelerator' to improve the kinetics of CO(2) uptake in alkanolamine solvents for chemical absorption - and the impact of the modification on the CO(2) uptake and selectivity over N(2) has been probed. While the modified framework, Ni(2)(dobdc)(pip)(0.5) (pip-CPO-27-Ni), exhibits a lower uptake of CO(2) compared with the non-grafted material, the selectivity for CO(2) over N(2) at 25 °C and at pressures pertinent to post-combustion flue gas capture (0.1-0.15 bar) is enhanced. Mechanistically, the interaction between the CO(2) molecules and the free amine sites in pip-CPO-27-Ni occurs via physisorption and chemisorption interactions, in which CO(2) binds to the framework with an isosteric heat of adsorption (-Q(st)) of 40.5 kJ mol(-1) at very low coverage (P = 0.033 mbar), followed by binding at a higher heat of adsorption (-Q(st) = 46.2 kJ mol(-1) at P = 3.55 mbar). Pure water adsorption isotherms revealed a two-step mechanism for uptake in CPO-27-Ni, consistent with adsorption into the first and second hydration spheres of Ni(2+) followed by subsequent uptake via physisorption into the pores. Additional steric hindrance in pip-CPO-27-Ni results in a single step only. The working capacity over multiple cycles was also investigated using a temperature swing adsorption process which revealed reversible CO(2) adsorption and desorption of 10 wt% over 10 cycles.


Multiple Sclerosis-Minimizing Errors in Radiological Diagnosis.
Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions. Incorrect diagnosis poses a significant risk to patients, it may lead to delays in management, increased morbidity, and also adds to the financial cost. The aim of this study was to highlight strategies for the efficient differentiation of multiple sclerosis from other diseases which may masquerade as MS clinico-radiologically. A systematic literature review was conducted through online databases including PubMed and Medline. Relevant publications on radiological aspects of multiple sclerosis, white matter diseases and mimickers of Multiple sclerosis were included in the analysis. Common mimickers of MS include small vessel disease, acute disseminated encephalomyelitis, neuromyelitis optica, anti-MOG encephalomyelitis, vasculitis, and CADASIL. Contrast-enhanced MRI study performed using MS protocol on high strength MRI system evaluated following a structured protocol along with clinical correlation is effective in differentiating MS from its mimickers. Contrast-enhanced MRI performed on a high strength scanner using MS protocol with structured protocol for evaluation along, with a better collaboration between radiologists and clinicians may help in minimizing errors in diagnosis of multiple sclerosis.


Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydrophilic and hydrophobic polymers.
The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material.


Intrahousehold discrepancy regarding food insecurity within intermarried couples of Vietnamese wives and Korean husbands in South Korea.
Our previous studies have demonstrated the inadequate nutritional status of Vietnamese female marriage immigrants in Korea. Major possible reasons include food insecurity due to economic problems as well as a lack of adjustment to unfamiliar Korean foods and limited access to Vietnamese foods; however, no study has investigated food insecurity among such intermarried couples. This study was performed to investigate the prevalence of food insecurity in Korean-husband-Vietnamese-wife couples and to determine whether they exhibit an intrahousehold discrepancy regarding food insecurity. A cross-sectional analysis of the Cohort of Intermarried Women in Korea study was performed with 84 intermarried couples. Among the 84 Vietnamese immigrants, 48.8% and 41.7% had food insecurity due to economic problems and a lack of foods appealing to their appetite, respectively. There was a marked discrepancy in reporting food insecurity between Vietnamese wives (22.6-38.1%) and their Korean husbands (6.0-15.5%). Vietnamese wives were five and two times more food-insecure due to economic problems and no foods appealing to their appetite, respectively, than their Korean spouses. A follow-up study is needed to investigate the causes of this discrepancy and ways of reducing food insecurity among female marriage immigrants living in low-income, rural communities.


Development of a porcine hard-to-heal wound model: evaluation of a bromelain-based enzymatic debriding agent.
We describe the development of a novel porcine eschar model and compare the debridement efficacy of various concentrations of a novel bromelain-based enzymatic agent with collagenase. Full thickness excisional wounds were created on pigs and injected intradermally with various doses of doxorubicin. Wounds were monitored for a period of 46 days for the development of eschar and wound closure. After determining the optimal concentration and dose of doxorubicin resulting in non-healing eschars, these conditions were used to create additional wounds on another set of animals. The resulting eschars were treated with various concentrations of a novel bromelain-based enzymatic agent (EscharEx-02) or collagenase. The primary endpoint was greater than 95% removal of the central eschar. Consistent eschars composed of two distinct areas (a central area of exudate and slough representing the hard-to-heal wound bed, and a peripheral area of full-thickness mummified necrosis) were seen after injection of doxorubicin (0.5 ml/cm2 of stock solution 0.75mg/ml) at one and six days after wound creation. Complete removal of the central eschar was achieved in all wounds after five and eight treatments with 5% and 2% EscharEx-02 respectively. Complete removal of the central eschar with collagenase was achieved in 0% and 82% of the wounds after 10 and 16 treatments respectively. We describe a porcine model for creating eschars similar to hard-to-heal wounds in humans. A novel bromelain-based enzymatic debridement agent was more effective than a commercially available collagenase in removing eschars in this wound model.


Relationship between calcific tendinopathy and rotator cuff tear on shoulder magnetic resonance imaging: case-controlled comparison.
To determine the frequency of rotator cuff tear on the shoulder magnetic resonance imaging (MRI) of patients with rotator cuff calcific tendinopathy and the relationship between rotator cuff tear and calcific tendinopathy. In this retrospective case control study, 137 patients with calcific tendinopathy and 137 control group patients without calcific tendinopathy with shoulder pain, whose age, sex, and shoulder laterality values were matched, were compared in terms of rotator cuff tears on their shoulder MRI images. The frequency of rotator cuff tear was found to be significantly higher in the control group (37.2%) compared to the calcific tendinopathy group (23.4%) (p < 0.01). Partial thickness was 81.3% in the calcific tendinopathy group and 70.6% in the control group, and no significant difference was observed between the two groups in terms of the size of the rotator cuff tear (p > 0.05). In the calcific tendinopathy group, there was no significant relationship between the localisation of calcification and the rotator cuff tear, and only in 4.4% of the participants were calcification and tear at the same location on the same tendon (p > 0.05, r = 0.04). The patients with calcific tendinopathy, who had been admitted with shoulder pain, did not demonstrate an increased risk of rotator cuff tear based on their MRI compared to patients with shoulder pain without calcific tendinopathy. No significant relationship was determined between calcific tendinopathy and rotator cuff tear.


Microwave absorption by normal and tumor cells.
Energy levels exist in mammalian cells which result in the absorption of microwaves between 66 and 76 gigahertz. Many of these energy levels occur when water molecules associate with the various chemical groups of macromolecules. The absorption spectra of cells between 66 and 76 gigahertz, therefore, is determined by the structure of in vivo water lattices, and these seem to reflect indirectly the structural makeup of macromolecules or macromolecular complexes. Tumor cells absorb 66-, 68-, and 70-gigahertz microwaves less strongly and 69-, 72-, and 75-gigahertz microwaves more strongly than normal cells. These differences in the strength of attenuation at each frequency suggest that either the ratio of RNA to DNA or the relative number of certain types of chemical groups in tumor cells is different from that in normal cells.


Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart.
The effect of rigorous swim training (6 h day-1, 5 days week-1 for an average of 191 h) on mitochondrial respiratory function was investigated in rat heart subjected to in vivo ischaemia reperfusion (I-R). Mitochondria was isolated from the risk region of the left ventricle subjected to 60 min occlusion of the main left coronary artery followed by 30 min reperfusion. Heart weight and heart-to-body weight ratio was increased by 21 and 28% (P < 0.01), respectively, in the trained (T, n = 15) vs. control rats (C, n = 20). I-R per se showed minimal effect on heart mitochondria regardless of training status. In sham, state 4 respiration rate was 26 and 32% (P < 0.05) lower in T vs. C rats, using malate-pyruvate (M-P) and 2-oxoglutarate (OG) as substrates, respectively. Training also reduced state 3 respiration by 28% (M-P) and 50% (OG) (P < 0.01). The respiratory control index (RCI) was unaltered in T with M-P, but decreased with OG (P < 0.01). In vitro exposure to superoxide radicals severely reduced state 4 and 3 respiration and RCI, but T hearts showed greater reductions of state 4 and 3 rates than C. Mitochondria from T hearts also revealed a greater state 4 inhibition by H2O2 and HO. compared with C. A lower glutathione content and a higher gamma-glutamyl transpeptidase activity (P < 0.05) was observed in T vs. C. It is concluded that rigorous swim training impairs heart mitochondrial function, making them more susceptible to in vivo and in vitro oxidative stress, and that this damaging effect may be related to a diminished glutathione reserve.


Fiber-based source for multiplex-CARS microscopy based on degenerate four-wave mixing.
We present a fiber-based laser source for multiplex coherent anti-Stokes Raman scattering (CARS) microscopy. This source is very compact and potentially alignment-free. The corresponding pump and Stokes pulses for the CARS process are generated by degenerate four-wave mixing (FWM) in photonic-crystal fibers. In addition, an ytterbium-doped fiber laser emitting spectrally narrow 100 ps pulses at 1035 nm wavelength serves as pump for the FWM frequency conversion. The FWM process delivers narrow-band pulses at 648 nm and drives a continuum-like spectrum ranging from 700 to 820 nm. With the presented source vibrational resonances with energies between 1200 cm-1 and 3200 cm-1 can be accessed with a resolution of 10 cm-1. Additionally, the temporal characteristics of the FWM output have been investigated by a cross-correlation setup, revealing the suitability of the emitted pulses for CARS microscopy. This work marks a significant step towards a simple and powerful all-fiber, maintenance-free multiplex-CARS source for real-world applications outside a laboratory environment.


In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.
The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and efficacy of rivastigmine in adolescents with Down syndrome: a preliminary 20-week, open-label study.
Individuals with Down syndrome (DS) exhibit a cholinergic deficiency similar to that found in Alzheimer's disease. Cholinesterase inhibitors, used to treat Alzheimer's disease, may improve cognitive function in individuals with DS. This is the first investigation of the safety and efficacy of rivastigmine (an acetyl and butyryl cholinesterase inhibitor) on specific cognitive domains in pediatric DS. Eleven subjects with DS (ages 10-17 years) were treated with a liquid formulation of rivastigmine. Four subjects experienced no adverse events (AEs). Seven subjects reported AEs that were mild, transient and consistent with adverse events typically noted with cholinesterase inhibitors. Significant improvements were found in overall adaptive function (Vineland Adaptive Behavior Scales and Clinician's Interview-Based Impression of Change), attention (Leiter Attention Sustained tests A and B), memory (NEPSY: Narrative and Immediate Memory for Names subtests) and language (Test of Verbal Expression and Reasoning and Clinical Evaluation of Language Fundamentals-Preschool) domains. Improved language performance was found across all functional levels. These results underscore the need for larger, controlled studies employing a carefully constructed test battery capable of measuring the full scope of performance across multiple domains and a wide range of functional levels.


Median sternotomy and multiple lung resections for metastatic sarcomas.
In the attempt to apply salvage surgery to the majority of patients with pulmonary tumour relapse, we have adopted a new treatment plan consisting of early bilateral lung exploration and resection through median sternotomy in all cases of sarcoma with resectable lung metastases, including synchronous or previously resected ones. The present paper summarizes the early results achieved with this technique in 56 consecutive patients treated between 1985 and 1988. Perioperative mortality was zero, and morbidity negligible. Occult contralateral metastases were resected in about one third of subjects with monolateral clinical lesions. Overall actuarial survival from first pulmonary resection is 51% at 2 years and 35% at 3 years. A slightly more favourable trend is evident for solitary lesions but the difference is not statistically significant. No difference in survival is observed in relation to the initial disease-free interval or to the histological type. The majority of relapses occurred within 6 months of sternotomy (23/35) and were confined to the lungs (21/35). Ten of these 21 patients with pulmonary relapse have undergone further resection and 5 of them are alive, with a median survival of 28 months. Present results are encouraging as far as resectability and early recurrence rate are concerned. Median sternotomy appears a most valuable therapeutic approach to pulmonary metastases from sarcomas, being safe and effective in local control of disease, and compatible with further surgical management of pulmonary recurrences.


Depression and reduced natural killer cytotoxicity: a longitudinal study of depressed patients and control subjects.
Cross-sectional studies have demonstrated that natural killer (NK) cell activity is reduced in depression. To extend these observations and examine further the association between severity of depressive symptoms and values of NK activity, this study used a longitudinal case-control design and assessed NK cytotoxicity at intake and at follow-up 6 months after discharge from the hospital in depressed patients and control subjects. From acute hospitalization to follow-up, depression scores significantly (P < 0.01) decreased following treatment in the depressed patients but did not change in the control subjects. NK activity significantly (P < 0.05) increased from intake to follow-up in the depressives while lytic activity did not change in the controls. At intake NK activity was significantly (P < 0.01) reduced in the depressed patients as compared to values in the controls, while at follow-up cytotoxicity was similar between the two groups. These longitudinal data suggest that a reduction of NK cytotoxicity is temporally associated with the state of acute depression.


A systematic benchmarking of computational vibrational spectroscopy with DFTB3: Normal mode analysis and fast Fourier transform dipole autocorrelation function.
Computational vibrational spectroscopy serves as an important tool in the interpretation of experimental infrared (IR) spectra. In this article, we present a systematic benchmarking study of DFTB3 with two different computational vibrational spectroscopic methods, based on either normal mode analysis (NMA) or fast Fourier transform dipole autocorrelation function (FT-DAC). The results were compared with experimental data and theoretical calculations with B3LYP/cc-pVTZ. The empirical scaling factors for DFTB3/NMA, DFTB3-freq/NMA, and DFTB3/FT-DAC methods are 0.9993, 1.0059, and 0.9982, respectively. We also demonstrate the significance of anharmonicity and conformational sampling in vibrational spectroscopic calculations on flexible molecules. As expected, DFTB3/FT-DAC predicted the anharmonic vibrational peaks more accurately than DFTB3/NMA and NMA spectra are highly dependent on the initial structures. The potential limitations of DFTB3 for vibrational spectroscopic calculations and the challenges in assigning the FT-DAC spectral peaks were noted. DFTB3/FT-DAC is expected to serve as a promising technique in computational spectroscopy in complex biomolecular systems. © 2018 Wiley Periodicals, Inc.