Room-Temperature Wet Chemical Synthesis of Au NPs/TiH2/Nanocarved Ti Self-Supported Electrocatalysts for Highly Efficient H2 Generation.
Self-supported electrocatalysts are a new class of materials exhibiting high catalytic performance for various electrochemical processes and can be directly equipped in energy conversion devices. We present here, for the first time, sparse Au NPs self-supported on etched Ti (nanocarved Ti substrate self-supported with TiH2) as promising catalysts for the electrochemical generation of hydrogen (H2) in KOH solutions. Cleaned, as-polished Ti substrates were etched in highly concentrated sulfuric acid solutions without and with 0.1 M NH4F at room temperature for 15 min. These two etching processes yielded a thin layer of TiH2 (the corrosion product of the etching process) self-supported on nanocarved Ti substrates with different morphologies. While F--free etching process led to formation of parallel channels (average width: 200 nm), where each channel consists of an array of rounded cavities (average width: 150 nm), etching in the presence of F- yielded Ti surface carved with nanogrooves (average width: 100 nm) in parallel orientation. Au NPs were then grown in situ (self-supported) on such etched surfaces via immersion in a standard gold solution at room temperature without using stabilizers or reducing agents, producing Au NPs/TiH2/nanostructured Ti catalysts. These materials were characterized by scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDS), grazing incidence X-ray diffraction (GIXRD), and X-ray photoelectron spectroscopy (XPS). GIXRD confirmed the formation of Au2Ti phase, thus referring to strong chemical interaction between the supported Au NPs and the substrate surface (also evidenced from XPS) as well as a titanium hydride phase of chemical composition TiH2. Electrochemical measurements in 0.1 M KOH solution revealed outstanding hydrogen evolution reaction (HER) electrocatalytic activity for our synthesized catalysts, with Au NPs/TiH2/nanogrooved Ti catalyst being the best one among them. It exhibited fast kinetics for the HER with onset potentials as low as -22 mV vs. RHE, high exchange current density of 0.7 mA cm-2, and a Tafel slope of 113 mV dec-1. These HER electrochemical kinetic parameters are very close to those measured here for a commercial Pt/C catalyst (onset potential: -20 mV, Tafel slope: 110 mV dec-1, and exchange current density: 0.75 mA cm-2). The high catalytic activity of these materials was attributed to the catalytic impacts of both TiH2 phase and self-supported Au NPs (active sites for the catalytic reduction of water to H2), in addition to their nanostructured features which provide a large-surface area for the HER.


Mechanoregulation of cardiac myofibroblast differentiation: implications for cardiac fibrosis and therapy.
Cardiac myofibroblast differentiation, as one of the most important cellular responses to heart injury, plays a critical role in cardiac remodeling and failure. While biochemical cues for this have been extensively investigated, the role of mechanical cues, e.g., extracellular matrix stiffness and mechanical strain, has also been found to mediate cardiac myofibroblast differentiation. Cardiac fibroblasts in vivo are typically subjected to a specific spatiotemporally changed mechanical microenvironment. When exposed to abnormal mechanical conditions (e.g., increased extracellular matrix stiffness or strain), cardiac fibroblasts can undergo myofibroblast differentiation. To date, the impact of mechanical cues on cardiac myofibroblast differentiation has been studied both in vitro and in vivo. Most of the related in vitro research into this has been mainly undertaken in two-dimensional cell culture systems, although a few three-dimensional studies that exist revealed an important role of dimensionality. However, despite remarkable advances, the comprehensive mechanisms for mechanoregulation of cardiac myofibroblast differentiation remain elusive. In this review, we introduce important parameters for evaluating cardiac myofibroblast differentiation and then discuss the development of both in vitro (two and three dimensional) and in vivo studies on mechanoregulation of cardiac myofibroblast differentiation. An understanding of the development of cardiac myofibroblast differentiation in response to changing mechanical microenvironment will underlie potential targets for future therapy of cardiac fibrosis and failure.


Pronociceptive effects of spinal dynorphin promote cannabinoid-induced pain and antinociceptive tolerance.
Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. Response thresholds to non-noxious mechanical and noxious thermal stimuli were assessed. Antinociception was determined using the 52 degrees C tail-flick test. Mice received repeated WIN 55,212-2, its inactive enantiomer, WIN 55,212-3 or vehicle (i.th., bid, 5 days). WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced a time-related increased sensitivity to non-noxious and noxious stimuli. WIN 55,212-2, but not WIN 55,212-3 or vehicle, elicited a significant increase in lumbar spinal dynorphin content at treatment day 5. Increased sensitivity to mechanical and thermal stimuli produced by WIN 55,212-2 was reversed to baseline levels by i.th. MK-801 or dynorphin antiserum; control serum had no effect. WIN 55,212-2, but not WIN 55,212-3 or vehicle, produced dose-related antinociception and repeated administration resulted in antinociceptive tolerance. While MK-801 and dynorphin antiserum did not alter acute antinociception produced by WIN 55,212-2, these substances significantly blocked antinociceptive tolerance when given immediately prior to WIN 55,212-2 challenge on day 5. Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.


Conflicts of interest in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: associations with recommendations.
Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest. To investigate to what degree financial and non-financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources. We included studies comparing the association between conflicts of interest and favourable recommendations of drugs or devices (e.g. recommending a particular drug) in clinical guidelines, advisory committee reports, opinion pieces, or narrative reviews. Two review authors independently included studies, extracted data, and assessed risk of bias. When a meta-analysis was considered meaningful to synthesise our findings, we used random-effects models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), with RR > 1 indicating that documents (e.g. clinical guidelines) with conflicts of interest more often had favourable recommendations. We analysed associations for financial and non-financial conflicts of interest separately, and analysed the four types of documents both separately (pre-planned analyses) and combined (post hoc analysis). We included 21 studies analysing 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews. We received unpublished data from 11 studies; eight full data sets and three summary data sets. Fifteen studies had a risk of confounding, as they compared documents that may differ in other aspects than conflicts of interest (e.g. documents on different drugs used for different populations). The associations between financial conflicts of interest and favourable recommendations were: clinical guidelines, RR: 1.26, 95% CI: 0.93 to 1.69 (four studies of 86 clinical guidelines); advisory committee reports, RR: 1.20, 95% CI: 0.99 to 1.45 (four studies of 629 advisory committee reports); opinion pieces, RR: 2.62, 95% CI: 0.91 to 7.55 (four studies of 284 opinion pieces); and narrative reviews, RR: 1.20, 95% CI: 0.97 to 1.49 (four studies of 457 narrative reviews). An analysis combining all four document types supported these findings (RR: 1.26, 95% CI: 1.09 to 1.44). One study investigating specialty interests found that the association between including radiologist guideline authors and recommending routine breast cancer screening was RR: 2.10, 95% CI: 0.92 to 4.77 (12 clinical guidelines). We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.


Comparison of a preferred versus non-preferred waterpipe tobacco flavour: subjective experience, smoking behaviour and toxicant exposure.
One possible reason for the rapid proliferation of waterpipe (WP) smoking is the pervasive use of flavoured WP tobacco. To begin to understand the impact of WP tobacco flavours, the current study examined the impact of a preferred WP tobacco flavour compared with a non-preferred tobacco flavoured control on user's smoking behaviour, toxicant exposure and subjective smoking experience. Thirty-six current WP smokers completed two, 45-minute ad libitum smoking sessions (preferred flavour vs non-preferred tobacco flavour control) in a randomised cross-over design. Participants completed survey questionnaires assessing subjective smoking experience, exhaled carbon monoxide (eCO) testing, and provided blood samples for monitoring plasma nicotine. WP smoking topography was measured continuously throughout the smoking session. While participants reported an enhanced subjective smoking experience including greater interest in continued use, greater pleasure derived from smoking, increased liking and enjoyment, and willingness to continue use after smoking their preferred WP tobacco flavour (p values <0.05), no significant differences were observed in nicotine and carbon monoxide boost between flavour preparations. Greater average puff volume (p=0.018) was observed during the non-preferred flavour session. While not significant, measures of flow rate, interpuff interval (IPI), and total number of puffs were trending towards significance (p values <0.10), with decreased IPI and greater total number of puffs during the preferred flavour session. The current study is the first to examine flavours in WP smoking by measuring preferred versus control preparations to understand the impact on subjective experience, smoking behaviour and toxicant exposure. The pattern of results suggests that even this relatively minor manipulation resulted in significant changes in subjective experience. These results indicate a possible need for regulations restricting flavours in WP tobacco as with combustible cigarettes.


A functional model for G protein activation of the muscarinic K+ channel in guinea pig atrial myocytes. Spectral analysis of the effect of GTP on single-channel kinetics.
To elucidate the functional interaction between the active G protein subunit (GK*) and the cardiac muscarinic K+ (KACh) channel, the effect of intracellular GTP on the channel current fluctuation in the presence of 0.5 microM extracellular acetylcholine was examined in inside-out patches from guinea pig atrial myocytes using spectral analysis technique. The power density spectra of current fluctuations induced at various concentrations of GTP ([GTP]) were well fitted by the sum of two Lorentzian functions. Because the channel has one open state, the open-close transitions of the channel gate represented by the spectra could be described as C2<-->C1<-->O. As [GTP] was raised, the channel activity increased in a positive cooperative manner. The powers of the two Lorentzian components concomitantly increased, while the corner frequencies and the ratio of the powers at 0 Hz remained almost constant. This indicates that G protein activation did not affect the gating of each channel but mainly increased the number of functionally active channels in the patch to enhance the channel activity. Regulation of the number of functionally active channels could be described by a slow transition of the channel states, U (unavailable)<-->A (available), which is independent of the gating. The equilibrium of this slow transition was shifted by GTP from U to A. Monod-Wyman-Changeux's allosteric model for the channel state transition(U<-->A) could well describe the positive cooperative increase in the channel availability by GTP, assuming that, in the presence of saturating concentrations of ACh, [GK*] linearly increased as [GTP] was raised in our experimental range. The model indicates that the cardiac KACh channel could be described as a multimer composed of four or more functionally identical subunits, to each of which one GK* binds.


Identification of Molecules Responsible for Therapeutic Effects of Extracellular Vesicles Produced from iPSC-Derived MSCs on Sjo¨gren's Syndrome.
Recent research indicated that extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) are a promising alternative to MSCs for immunomodulatory therapy. However, the contents of MSC-EVs would change as their parent MSCs change, hence the therapeutic efficacy of MSC-derived EVs (MSC-EVs) would largely depend on donors, tissue sources and culture conditions of MSCs. To overcome limitations of tissue-derived MSCs, we previously used MSCs derived from human induced pluripotent stem cells (iMSCs) to produce EVs and demonstrated their therapeutic potential in a mouse model of secondary Sjo¨gren's Syndrome. Here, we further found that EVs from early-passage iMSCs had better immunomodulatory potency than EVs from late-passage iMSCs in TLR4-stimulated splenocytes and in a mouse model of primary Sjögren's syndrome. Comparative molecular profiling using proteomics and microRNA sequencing revealed distinctive molecular profiles of iMSC-EVs with or without immunomodulation capacity. Amongst them, manipulation of TGF-β1, miR-21 and miR-125b levels in iMSC-EVs significantly affected their immunosuppressive effects. These findings would help improve our understanding of the molecular mechanism underlying iMSC-EV-mediated immunomodulation and further provide strategies to improve regulatory function of EVs for the treatment of immune-mediated diseases.


On-line monitoring of microbial volatile metabolites by proton transfer reaction-mass spectrometry.
A method for analysis of volatile organic compounds (VOCs) from microbial cultures was established using proton transfer reaction-mass spectrometry (PTR-MS). A newly developed sampling system was coupled to a PTR-MS instrument to allow on-line monitoring of VOCs in the dynamic headspaces of microbial cultures. The novel PTR-MS method was evaluated for four reference organisms: Escherichia coli, Shigella flexneri, Salmonella enterica, and Candida tropicalis. Headspace VOCs in sampling bottles containing actively growing cultures and uninoculated culture medium controls were sequentially analyzed by PTR-MS. Characteristic marker ions were found for certain microbial cultures: C. tropicalis could be identified by several unique markers compared with the other three organisms, and E. coli and S. enterica were distinguishable from each other and from S. flexneri by specific marker ions, demonstrating the potential of this method to differentiate between even closely related microorganisms. Although the temporal profiles of some VOCs were similar to the growth dynamics of the microbial cultures, most VOCs showed a different temporal profile, characterized by constant or decreasing VOC levels or by single or multiple peaks over 24 h of incubation. These findings strongly indicate that the temporal evolution of VOC emissions during growth must be considered if characterization or differentiation based on microbial VOC emissions is attempted. Our study may help to establish the analysis of VOCs by on-line PTR-MS as a routine method in microbiology and as a tool for monitoring environmental and biotechnological processes.


Ipilimumab-Based Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events With Ipilimumab Monotherapy and Combination Therapy With Nivolumab.
Ipilimumab (Yervoy®) therapy improves outcomes in patients with resected stage III melanoma, and ipilimumab alone or combined with nivolumab (Opdivo®) does so in those with unresectable or metastatic melanoma. These immunotherapies are associated with immune-related adverse events (irAEs). With prompt recognition and appropriate management, serious sequelae or unnecessary treatment discontinuation can be prevented. . This article presents consensus statements to guide oncology nurses in the recognition and management of irAEs associated with ipilimumab and nivolumab. . Members of the Melanoma Nursing Initiative reviewed the current literature and clinical experience regarding nursing interventions related to irAEs associated with ipilimumab or ipilimumab and nivolumab therapy. . The care step pathways provided represent a proactive, evidence-based, and comprehensive plan to support optimal patient outcomes.


Welfare issues and potential solutions for laying hens in free range and organic production systems: A review based on literature and interviews.
In free-range and organic production systems, hens can make choices according to their needs and desires, which is in accordance with welfare definitions. Nonetheless, health and behavioral problems are also encountered in these systems. The aim of this article was to identify welfare challenges observed in these production systems in the EU and the most promising solutions to overcome these challenges. It is based on a review of published literature and research projects complemented by interviews with experts. We selected EU specific information for welfare problems, however, the selected literature regarding solutions is global. Free range use may increase the risk of infection by some bacteria, viruses and parasites. Preventive methods include avoiding contamination thanks to biosecurity measures and strengthening animals' natural defenses against these diseases which can be based on nutritional means with new diet components such as insect-derived products, probiotics and prebiotics. Phytotherapy and aromatherapy can be used as preventive and curative medicine and vaccines as alternatives to antibiotics and pesticides. Bone quality in pullets and hens prevents keel deviations and is favored by exercise in the outdoor range. Free range use also lead to higher exposure to variable weather conditions and predators, therefore shadow, fences and guard animals can be used to prevent heat stress and predation respectively. Granting a free range provides opportunities for the expression of many behaviors and yet many hens usually stay close to the house. Providing the birds with trees, shelters or attractive plants can increase range use. Small flock sizes, early experiences of enrichment and personality traits have also been found to enhance range use. Severe feather pecking can occur in free range production systems, although flocks using the outdoor area have better plumage than indoors. While many prevention strategies are facilitated in free range systems, the influence of genetics, prenatal and nutritional factors in free range hens still need to be investigated. This review provides information about practices that have been tested or still need to be explored and this information can be used by stakeholders and researchers to help them evaluate the applicability of these solutions for welfare improvement.


Multilocus sequence typing confirms synonymy but highlights differences between Candida albicans and Candida stellatoidea.
We used multi-locus sequence typing (MLST) to investigate 35 yeast isolates representing the two genome-sequenced strains plus the type strain of Candida albicans, four isolates originally identified as Candida stellatoidea type I and 28 representing type strains of other species now regarded as synonymous with C. albicans. DNA from all 32 C. albicans synonyms readily formed PCR products with the C. albicans MLST primer sets. Their sequences placed all of them within the existing C. albicans clade structure, represented by 1516 isolates. One isolate, originally received as Mycotorula sinensis, was resistant to flucytosine, but no other unusual susceptibilities were found to polyene, azole or echinocandin antifungal agents. The four isolates of C. stellatoidea type I coclustered with two other sucrose-negative isolates, originally identified as examples of Candida africana, in a group of strains highly distinct from the majority of C. albicans. Our results not only confirm the synonymity of all the isolates with C. albicans but also confirm an obvious genotypic difference in the case of C. stellatoidea type I.


Agglomeration Suppression of a Fe-Supported Catalyst and its Utilization for Low-Temperature Ammonia Synthesis in an Electric Field.
Fe-supported heterogeneous catalysts are used for various reactions, including ammonia synthesis, Fischer-Tropsch synthesis, and exhaust gas cleaning. For the practical use of Fe-supported catalysts, suppression of Fe particle agglomeration is the most important issue to be resolved. As described herein, we found that Al doping in an oxide support suppresses agglomeration of the supported Fe particle. Experimental and computational studies revealed two tradeoff Al doping effects: the Fe particle size decreased and remained without agglomeration by virtue of the anchoring effect of doped Al. Also, some Fe atoms anchored by Al cannot function as an active site because of bonding with oxygen atoms. Using an appropriate amount of Al doping is effective for increasing the number of active Fe sites and catalytic activity. This optimized catalyst showed high practical activity and stability for low-temperature ammonia synthesis in an electric field. The optimized catalyst of 12.5 wt % Fe/Ce0.4Al0.1Zr0.5O2-δ showed the highest ammonia synthesis rate (2.3 mmol g-1 h-1) achieved to date under mild conditions (464 K, 0.9 MPa) in an electric field among the Fe catalysts reported.


Maternal and perinatal outcomes of peruvian pregnant women in Chile: exploring the healthy immigrant effect.
To compare maternal and perinatal outcomes between Chilean and Peruvian pregnant women in Santiago, Chile, between January and July 2017. Analytical cross-sectional study of 1,578 Chilean and 318 Peruvian women who attended a clinical hospital in Santiago. We conducted a comparative analysis of maternal and perinatal variables by nationality. Crude and adjusted logistic models were carried out with a 95% confidence interval (95% CI). Peruvian pregnant women resided an average of 5.7 years in Chile, were older (28.1 ± 6.5 vs. 26.6 ± 6.5 years), had less unemployment (52.3% vs. 60.6%), were more likely to enter prenatal care (PC) late (OR: 2.17, 95% CI: 1.69-2.78) and had higher probability of having anemia (OR: 3.45, 95% CI: 2.13-5.56) associated with late entry to PC (adjusted OR: 0.43, 95% CI: 0.33-0.56). On the other hand, Chilean pregnant women were more likely to be obese upon entry to PC (OR: 2.48, 95% CI: 1.81-3.41) and at the time of delivery (OR: 2.03, 95% CI: 1.57-2.62). In addition, Chilean women had higher rates of gestational diabetes (GD) (OR: 2.12, 95% CI: 1.24-3.61), premature delivery (OR: 2.82, 95% CI: 1.59-5.01) and low birth weight (LBW) (OR: 3.10, 95% CI: 1.51-6.33). In the adjusted model, obesity was independently associated with GD (adjusted OR: 3.8, 95% CI: 2.44-6.18) and LBW (adjusted OR: 3.34, 95% CI: 2.33-4.85). The healthy immigrant effect was observed in pregnant Peruvian immigrants, mainly regarding the perinatal outcomes. It is necessary to promote early access to prenatal care and to stablish measures to prevent anemia and obesity, in order to avoid adverse maternal and perinatal outcomes in the studied population.


Post-traumatic stress disorder-related symptoms after intensive care.
To determine the incidence of Post Traumatic Stress Disorder (PTSD) related symptoms in a population of intensive care unit (ICU) admitted patients and the relationship between PTSD-related symptoms and memories of ICU. Adults consecutively admitted to an ICU of a University hospital during 1 year, who stayed in the ICU at least 3 days, were prospectively studied. A questionnaire (ICU memory tool) was administered to 84 patients 1 week after ICU discharge and to 63 of them after 3 months. Past medical history and clinical variables present during ICU stay were collected. At the 1st interview, 5 patients (5.9%) did not remember to have been in ICU. Of the remaining 79 patients (males 59.5%, median age 69 years, SAPS II 34, APACHE II 14 and ICU stay 5 days), 4 reported intrusive memories and none panic attacks. The Impact of Events Scale (IES), available in 3 of them, scored in medium/high levels. Only the median number of factual memories reported by the patients with and without intrusive memories was significantly different (4 interquartile range 2-5 vs 8 interquartile range 6-10; p=0.002). The patients with intrusive memories at the 1st interview did not report them at the 2nd interview. Two patients not having panic or intrusive memories at the 1st interview reported PTSD-related symptoms after 3 months. In a general ICU population, few patients (5%) have PTSD-related symptoms and those who present those symptoms report less factual memories of ICU stay.


Interferon-regulated Mx genes are not responsive to interleukin-1, tumor necrosis factor, and other cytokines.
Accumulation of Mx gene products in cells of patients and experimental animals has been recognized as a useful marker for detecting minute quantities of biologically active interferon (IFN). Goetschy et al. (J. Goetschy, H. Zeller, J. Content, and M. A. Horisberger, J. Virol. 63:2616-2622, 1989) reported that not only IFNs but also interleukin-1 (IL-1) and tumor necrosis factor (TNF) were potent inducers of the human Mx genes. However, we observed no Mx induction in cultured human fibroblasts or in human peripheral blood mononuclear cells treated with various concentrations of IL-1 alpha or TNF-alpha. Mx induction was found in the spleens of mice treated with TNF-alpha or IL-1 alpha, but this effect could be neutralized with antibodies to murine IFN-alpha/beta. Of the other cytokines that we tested (IL-2, IL-6, and granulocyte-macrophage colony-stimulating factor), only IL-2 induced the Mx genes in peripheral blood mononuclear cells, but antibodies to human IFN-beta efficiently neutralized this effect. Our results thus indicate that IFNs are the only cytokines with intrinsic Mx-inducing activity.


AMPK and PPARdelta agonists are exercise mimetics.
The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.


Myosin heavy chain kinase inactivated by Ca2+/calmodulin from aggregating cells of Dictyostelium discoideum.
Soluble myosin heavy chain kinases (MHC kinases) were partially purified from growth phase and aggregation-competent cells of Dictyostelium discoideum. In the aggregation-competent cells, two MHC kinases were distinguishable. One of these enzymes, called MHC kinase II, was inactivated by Ca2+ and calmodulin in a highly temperature-dependent reaction. A MHC kinase found in growth phase cells did not have these regulatory properties. Substrate specificities were analysed for MHC kinase II and for the MHC kinase from growth phase cells. Both enzymes phosphorylated threonine residues of the myosin heavy chains of D. discoideum and Physarum polycephalum. Phosphopeptide mapping of D. discoideum myosin and determination of the stoichiometry of its phosphorylation suggested the presence of two phosphorylation sites per heavy chain. Both sites were contained within a 38-kd chymotryptic fragment. The inactivation of MHC kinase II by Ca2+ plus calmodulin suggests this enzyme has a role in the regulation of myosin functions during the chemotactic response of a cell. The phosphorylated myosin had about one third the actin-activated Mg2+-ATPase activity of the non-phosphorylated myosin. Previous findings indicated that stimulation of D. discoideum cells with the chemo-attractant cAMP increases the cytoplasmic Ca2+ concentration. Under these conditions MHC kinase II might be inhibited and the dephosphorylated, more active form of myosin would accumulate.


Copper(I)-Catalyzed Cyanoperfluoroalkylation of Alkynes.
A highly chemoselective and regioselective copper-catalyzed radical cyanoperfluoroalkylation of alkynes is described. This three-component reaction directly uses commercially available alkynes, perfluoroalkyl iodides, and trimethylsilyl cyanide as the reaction partners and delivers a variety of perfluoroalkylated cyanoalkenes in good yields. Broad substrate scope and good functional group tolerance are observed. The perfluoroalkylated cyanoalkenes that are produced can be readily transformed into useful fluoroalkylated derivatives.


Circulating and utero-placental adaptations to chronic placental ischemia in the rat.
While utero-placental insufficiency is associated with adverse outcomes for both mother and fetus, many of the maternal-fetal adaptations during pregnancy in models of fetal compromise remain unclear. The purpose of this study was to determine if chronically reduced uterine perfusion pressure (RUPP) during days 14-19 of gestation alters feto-placental growth differentially from the cervical to ovarian ends of the uterus and generates metabolic adaptations such as increased blood lactate (BLa) concentrations and lactate transporter expression in the placenta. Fetal growth restriction was evident, placental efficiency (fetal weight/placental weight) decreased (4.7 ± 0.35 vs. 5.9 ± 0.30; P < 0.05) and fetal growth pattern within the uterus was altered in the RUPP compared to the normal pregnant (NP) rats. Blood lactate concentrations were increased (3.3 ± 0.3 vs. 2.1 ± 0.4 mmol/l; P < 0.05) in NP compared to virgin rats, and in RUPP compared to NP (5.0 ± 0.6 vs. 3.3 ± 0.3 mmol/l; P < 0.05). Lactate concentration was increased (10.0 ± 0.6 vs. 7.1 ± 0.8 mmol/l; P < 0.05) in the media from hypoxic compared to normoxic BeWo cells. No changes in expression of placental MCT1, 2, or 4 were observed between RUPP and NP rats. RUPP resulted in decreased plasma leptin (2.0 ± 0.3 vs. 3.1 ± 0.4; P < 0.05) but no change in IGF-1 compared to NP. The present data indicate chronic placental ischemia results in numerous endocrine and metabolic changes during late pregnancy in the rat and that the RUPP model has differential effects on fetal growth depending on uterine position.


Arginine deficiency in preconfluent intestinal Caco-2 cells modulates expression of proteins involved in proliferation, apoptosis, and heat shock response.
Arginine is classified as a conditionally essential amino acid required exogenously during catabolic disease states and periods of rapid growth, both characterized by increased arginine utilization. Arginine plays an important role in the intestine, where it is extensively metabolized, and enhances its immune-supportive function and mucosal repair. Cell proliferation is important for the latter process. This study aimed for a better molecular insight in the response to arginine deprivation/supplementation of preconfluent and 5-day-confluent, differentiated Caco-2 intestinal cells. The potential of citrulline to counteract the effects of arginine deprivation was investigated in preconfluent cells. 2-DE combined with MALDI-TOF-MS and the antibody microarray technology were applied. Evidence is provided that arginine deficiency modulates the protein expression profiles of preconfluent Caco-2 cells differently than that of postconfluent differentiated cells. In preconfluent cells, certain proteins changed in direct response to arginine deficiency, whereas other proteins did not, but instead responded during the recovery phase after an arginine/citrulline resupplementation. The protein changes suggest that arginine deprivation decreases cell proliferation and heat shock protein expression, and enhances the cells susceptibility to apoptosis. These processes are critical for proper cell function, and hence a state of arginine deficiency can be detrimental for intestinal cells which proliferate actively in vivo.


Catching a glimpse: Corona-life and its micro-politics in academia.
The spread of COVID-19 acutely challenges and affects not just economic markets, demographic statistics and healthcare systems, but indeed also the politics of organizing and becoming in a new everyday life of academia emerging in our homes. Through a collage of stories, snapshots, vignettes, photos and other reflections of everyday life, this collective contribution is catching a glimpse of corona-life and its micro-politics of multiple, often contradicting claims on practices as many of us live, work and care at home. It embodies concerns, dreams, anger, hope, numbness, passion and much more emerging amongst academics from across the world in response to the crisis. As such, this piece manifests a shared need to - together, apart - enact and explore constitutive relations of resistance, care and solidarity in these dis/organizing times of contested spaces, identities and agencies as we are living-working-caring at home during lockdowns.


Pilot test of brief instructions to improve the self-management of general food cravings.
To provide a preliminary investigation into the impact of brief online acceptance-based vs. control-based techniques to self-manage food cravings in women. Female participants (N = 151) were randomised to 'acceptance' or 'control' groups. Measures of general food cravings (primary outcome), and depression, anxiety and stress (secondary outcomes) were taken at baseline, two weeks and four weeks. Linear mixed models showed a significant group × time interaction, with food cravings significantly reduced in the thought-control group compared to the acceptance group over four weeks, along with a reduction in food consumption. Levels of depression, anxiety and stress decreased over the course of the study, but did not differ by group. These findings provide preliminary support for the acceptability of a minimal technique to self-manage food cravings without deleterious effects, and suggest that simple control-based techniques may be useful in non-clinical, real-world settings.


DOES AGE INFLUENCE IN ENDOSCOPIC THERAPEUTIC SUCCESS ON THE BILIARY TRACT?
Retrograde endoscopic cholangiopancreatography (ERCP) effectively treats biliary and pancreatic disorders. Its indications are limited and precise, since its misuse delays adequate treatment, increases costs and to patient´s adverse events. To compare clinical, radiological and exploratory characteristics in relation to therapeutic success in patients undergoing ERCP in relation to age. 421 patients who underwent the method were retrospectively studied; those who were not able to access the duodenal papilla were excluded. The patients were divided into two age groups: <60 years (group 1) and >60 years (group 2), and the variables of gender, examination indications, radiological findings, therapeutic success, diagnosis and the occurrence of immediate adverse events were analyzed. 177 patients were allocated to group 1 and 235 to group 2. The main indication found in both groups was choledocholithiasis. In group 2, the number of cases of acute cholangitis (p=0.001), biliary stenosis (p=0.002) and papilla cancer (p=0.046) was higher. In this group, urgent indication for ERCP was higher (p=0.042), as well as the diagnosis of biliary tract dilatation (p<0.001). The placement of prostheses was the most common procedure performed in both groups, but the greatest number of patients in absolute quantity occurred in group 2. In group 1, the success in catheterization and the chance of achieving clearing of the biliary tract was significantly higher in compared to group 2 (p=0.016, OR=2.1). The success of catheterization and complete clearance of the bile duct was significantly higher in the group of young patients.


Racial disparity in utilization of therapeutic modalities among multiple myeloma patients: a SEER-medicare analysis.
Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis. A total of 5338 MM patients were included with median 2.4-year follow-up. Within the first year of MM diagnosis, utilization of lenalidomide, bortezomib, SCT, and more than one novel agent increased over time while utilization of thalidomide decreased. There was significantly lower utilization of lenalidomide among African-Americans (P < 0.01), higher thalidomide use among Hispanics and Asians (P < 0.01), and lower bortezomib use among Asians (P < 0.01). Hispanics had the highest median number of days to first dose of bortezomib (P = 0.02) and the lowest utilization of SCT (P < 0.01). Hispanics and Asians were the only groups without notable increases in lenalidomide and bortezomib use, respectively. SCT utilization increased over time for all except African-Americans. SCT use within the first year after diagnosis was associated with better overall survival (HR 0.52; 95% CI: 0.4-0.68), while bortezomib use was associated with inferior survival (HR 1.14; 95% CI 1.02-1.28). We noted considerable variability in MM therapeutics utilization with seeming inequity for racial-ethnic minorities. These trends should be considered to eliminate drug access and utilization disparities and achieve equitable benefit of therapeutic advances across all races.


5-FU uptake in liver metastases after intravenous and intraperitoneal administration: an autoradiographic study in the rat.
To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO) administration. A total of 18 inbred rats with hepatic metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7), i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised autoradiographically and quantified by computer-based image analysis. After 20 minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours, 9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19 i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e. injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v. injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at any time point. When the calculations were based on average metastatic radioactivity of individual rats, the difference between i.v. and i.p.e. injected rats was still present at 2 hours. These results indicate that early tumour 5-FU uptake after intraperitoneal and intraportal administration may be inferior to that after intravenous injection. Deposition of the drug in the peritoneal cavity may, however, act as a slow release preparation giving continuous drug exposure for prolonged periods of time. These results suggest a role for combined intravenous and intraperitoneal adjuvant therapy.


Body weight affects ω-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial.
Guidelines for suggested intake of ω-3 polyunsaturated fatty acids (PUFAs) are limited in youth and rely primarily on age. However, body weight varies considerably within age classifications. The current analyses examined effects of body weight and body mass index (BMI) on fatty acid accumulation in 64 youth (7-14 years) with a diagnosed mood disorder in a double-blind randomized-controlled trial (2000mg ω-3 supplements or a control capsule) across 12 weeks. Weight and height were measured at the first study visit and EPA and DHA levels were determined using fasting blood samples obtained at both the first and end-of-study visits. In the ω-3 supplementation group, higher baseline body weight predicted less plasma accumulation of both EPA [B = -0.047, (95% CI = -0.077; -0.017), β = -0.54, p = 0.003] and DHA [B = -0.02, (95% CI = -0.034; -0.007), β = -0.52, p = 0.004]. Similarly, higher BMI percentile as well as BMI category (underweight, normal weight, overweight/obese) predicted less accumulation of EPA and DHA (ps≤0.01). Adherence to supplementation was negatively correlated with BMI percentile [B = -0.002 (95% CI = -0.004; 0.00), β = -0.44, p = 0.019], but did not meaningfully affect observed associations. As intended, the control supplement exerted no significant effect on plasma levels of relevant fatty acids regardless of youth body parameters. These data show strong linear relationships of both absolute body weight and BMI percentile with ω-3 PUFA accumulation in youth. A dose-response effect was observed across the BMI spectrum. Given increasing variability in weight within BMI percentile ranges as youth age, dosing based on absolute weight should be considered. Moreover, effects of weight should be incorporated into statistical models in studies examining clinical effects of ω-3 PUFAs in youth as well as adults, as weight-related differences in effects may contribute meaningfully to inconsistencies in the current literature. WHO International Clinical Trial Registry Platform NCT01341925 and NCT01507753.


Use of allele specificity of comigrating AFLP markers to align genetic maps from different potato genotypes.
The allele specificity of AFLP markers was assessed in five relatively unrelated potato genotypes. To this end, two diploid mapping populations of potato, F1SH x RH and F1AM x RH, were analysed using four and six AFLP primer combinations, respectively, recently applied to the analysis of the genetically well characterized backcross population BC_C x E. The AFLP profiles of the five parents revealed 733 AFLP markers and, when identical primer combinations were used, 131 comigrating AFLP markers were identified. After construction of five parental maps, the genomic positions of these comigrating AFLP markers were compared and 117 markers (89%) which targeted the same genomic region were assumed to be homologous. Of these putative homologues, 20 markers, each cloned from at least two genotypes, were sequenced and 19 sets of amplification products were shown to be nearly identical. The number of AFLP markers previously mapped in population BC_C x E ranged from three to eleven per chromosome, which allowed a reliable assessment of chromosome numbers from individual linkage groups obtained in populations F1SH x RH and F1AM x RH. The high incidence of corresponding AFLP alleles was confirmed by using an additional set of five primer combinations. The 733 AFLP markers localized provide a valuable reference collection for future mapping studies in potato. As a consequence AFLP analysis may replace more laborious locus-specific marker techniques.


[The determinants of the quality of life and pain of back pain patients].
Because of the changing life style of Koreans, we have witnessed an increase of patients with back pain. The development of medical knowledge and technology has resulted in more numerous and better treatment methods. However, the outcomes of diverse treatments have been examined by using a few medicine-oriented measures like pain. This study aims at identifying the factors that influence the outcomes of back pain treatments by using two outcome measures (e.g., quality of life and pain). We used the questionnaire survey method for data collection. The questionnaires contained 5 categories(treatment methods, clinical conditions, exercise, quality of life and, socio-demographic characteristics). We interviewed 188 back pain patients. We used the regression analysis method to predict the quality of life or pain. Surgery showed a statistically significant effect on the quality of life as well as pain. The illness period, age and exercise were turned out to be significant factors for both of the dependent variables. The social class and surgery methods showed a statistically significant effect solely on the quality of life. In choosing the surgical methods, doctors need to provide detailed explanations on the quality of life outcomes for each of the surgical methods to the patients.


Diagnostic accuracy of IgA anti-tissue transglutaminase in patients suspected of having coeliac disease in Iran.
As there are little data about the sensitivity of the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody test in the clinical practice setting, we evaluated the sensitivity of this serologic test in a group of patients who were suspected of having coeliac disease and had serologic testing performed at commercial laboratories. The study was performed at Poursina Hakim Research Institute in Isfahan-Iran. A total number of 350 consecutive patients were enrolled in our study. They were divided into 3 groups: classical mode of presentation, atypical mode of presentation and patients with non specific prolonged gastrointestinal symptoms. Upper gastrointestinal endoscopy, histopathologic examination of biopsies from the second part of duodenum and serologic evaluation were performed for every patient. Biopsy specimens were evaluated according to Marsh (1992, revised in 1997). The overall sensitivity and specificity of IgA anti-tTG antibody were 38% and 98%. The positive and negative predictive values for the anti-tTG antibodies were 57% and 96%, respectively. The sensitivity was 80% in patients with Marsh IIIC. In contrast to other reports suggesting a diagnostic accuracy of more than 90% for anti-tTG antibody in coeliac disease patients, our data showed that we are still far from an ideal screening serologic tool which can rely on the antibody test as the sole way of identifying patients with coeliac disease. This could result in many missed diagnoses, in particular in patients with lesser degrees of Marsh classification.


The risk factors for deep and superficial chest surgical-site infections after coronary artery bypass graft surgery are different.
We sought to determine risk factors for deep and superficial chest wound infections after coronary artery bypass graft surgery to develop predictive models. We retrospectively analyzed data collected on 1980 consecutive patients undergoing coronary artery bypass surgery at our institution between January 1, 1996, and June 30, 1999, by using the Society of Thoracic Surgery database. Independent risk factors for surgical-site infection were identified with multivariate logistic regression. There were 37 (1.9%) deep chest and 46 (2.3%) superficial chest surgical-site infections. Obese diabetic patients had a 7.7-fold increased risk of deep chest infections after controlling for intra-aortic balloon pump use (odds ratio, 3.1) and postoperative transfusion (odds ratio, 2.3). Independent risk factors for superficial surgical-site infections included obesity (odds ratio, 3.1), diabetes in persons 65 years of age or older (odds ratio, 2.7), and current smoking (odds ratio, 2.5). Use of antiplatelet drugs was associated with a lower risk of superficial infections (odds ratio, 0.4). Predicted operative mortality as a marker of severity of illness was not clearly predictive of deep or superficial surgical-site infection. Mortality in the year after the operation was increased in patients with deep chest infections compared with that seen in uninfected control subjects (8/37 [21.6%] vs 114/1612 [7.1%], P =.004) but not in patients with superficial chest infections (7/47 [15.2%] vs 114/1612 [7.1%], P =.075). Risk factors for deep and superficial chest surgical-site infections after coronary artery bypass surgery differ, suggesting different mechanisms of pathogenesis. Appropriate risk stratification models specific to these important outcomes must be developed.


Effects of human interferon and alpha-difluoromethylornithine on T47D cells.
The effect of human interferon (IFN) and alpha-difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of eukaryotic ornithine decarboxylase, on the rate of DNA synthesis and the increase of ornithine decarboxylase activity of T47D cells was examined. It was found that IFN or DFMO alone causes little or appreciable inhibition of the [3H]thymidine incorporation, respectively. Each of the drugs alone has a significant inhibitory effect on ornithine decarboxylase activity. Combination of the two drugs has a synergistic effect and eliminates completely the [3H]thymidine incorporation and the activity of ornithine decarboxylase. The biological implication of IFN and DFMO is discussed with regard to the regulation of ornithine decarboxylase activity and the antiproliferative effects of the two drugs.


BCR-ABL positive essential thrombocythaemia: a variant of chronic myelogerous leukaemia or a distinct clinical entity: a special case report.
A 37-year-old Malay man presented initially with the clinical picture of essential thrombocythaemia (ET) without the extreme leukocytosis, marked splenomegaly and low neutrophil alkaline phosphatase characteristic of chronic myelogenous leukaemia (CML). Bone marrow examination showed massive megakaryocytic hyperplasia; cytogenetic studies showed the presence of Philadelphia chromosome. The patient was treated with hydroxyurea that resulted in reduction in the platelet count. Seventeen months later, he presented with fever associated with tender massive splenomegaly. Bone marrow finding was consistent with chronic phase CML. The presence of a rearrangement involving the major breakpoint cluster region (M-bcr) on chromosome 22 was confirmed by reverse transcriptase-polymerase chain reaction. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, this patient who had Philadelphia chromosome underwent clinical transition to chronic phase CML17 months and blast crisis 29 months after presentation.


Physeal Sparing Approaches for MPFL Reconstruction.
To update and concepts for pediatric physeal-sparing patellofemoral stabilization surgery. Recent studies have demonstrated positive results in patellofemoral stabilization in pediatric populations with physeal-sparing techniques that limit the potential for physeal damage. Comprehensive analysis remains limited by population and technique heterogeneity. Physeal-sparing patellofemoral stabilization, most significantly through physeal-sparing reconstruction of the medial patellofemoral ligament complex remains a viable option for pediatric patients with recurrent patellofemoral instability.


Robotic Colonoscopy and Beyond: Insights into Modern Lower Gastrointestinal Endoscopy.
Lower gastrointestinal endoscopy is considered the gold standard for the diagnosis and removal of colonic polyps. Delays in colonoscopy following a positive fecal immunochemical test increase the likelihood of advanced adenomas and colorectal cancer (CRC) occurrence. However, patients may refuse to undergo conventional colonoscopy (CC) due to fear of possible risks and pain or discomfort. In this regard, patients undergoing CC frequently require sedation to better tolerate the procedure, increasing the risk of deep sedation or other complications related to sedation. Accordingly, the use of CC as a first-line screening strategy for CRC is hampered by patients' reluctance due to its invasiveness and anxiety about possible discomfort. To overcome the limitations of CC and improve patients' compliance, several studies have investigated the use of robotic colonoscopy (RC) both in experimental models and in vivo. Self-propelling robotic colonoscopes have proven to be promising thanks to their peculiar dexterity and adaptability to the shape of the lower gastrointestinal tract, allowing a virtually painless examination of the colon. In some instances, when alternatives to CC and RC are required, barium enema (BE), computed tomographic colonography (CTC), and colon capsule endoscopy (CCE) may be options. However, BE and CTC are limited by the need for subsequent investigations whenever suspicious lesions are found. In this narrative review, we discussed the current clinical applications of RC, CTC, and CCE, as well as the advantages and disadvantages of different endoscopic procedures, with a particular focus on RC.


Carnosine [corrected] increases efficiency of DOPA therapy of Parkinson's disease: a pilot study.
The addition of the neuropeptide carnosine (beta-alanyl-L-histidine) as a food additive to the basic protocol of Parkinson's disease treatment results in significant improvement of neurological symptoms, along with increase in red blood cell Cu/Zn-SOD and decrease in blood plasma protein carbonyls and lipid hydroperoxides, with no noticeable change in platelets MAO B activity. The combination of carnosine with basic therapy may be a useful way to increase efficiency of PD treatment.


V5/MT+ modulates spatio-temporal integration differently across and within hemifields: Causal evidence from TMS.
It is unclear how the brain reaches the correct balance between temporal and spatial processing necessary to perceive motion across space. Here, we tested whether visual motion area V5/MT + plays a causal role in Ternus illusion. Ternus displays can be perceived as showing either group motion or element motion and are empirically useful for dissociating temporal and spatial grouping across visual fields. Online single-pulse TMS was applied to observers during the presentation of Ternus displays, either within or across hemifields, over left V5/MT + or, respectively, a control site in the left somatosensory cortex, or an additional 'Sham' control condition. In the cross-hemifields condition, observers perceived more element motion with TMS over left V5/MT + than in either control condition. By contrast, in the within-hemifield condition, observers reported more group motion after left V5/MT + TMS. Our findings demonstrate a causal role of left V5/MT+ in the spatio-temporal grouping of Ternus apparent motion, and in maintaining the balance of spatio-temporal processing both within and across individual hemifields.


[First experiences with the trauma radiologic PACS project at the University of Innsbruck Department of Radiology].
Radiography in an emergency setting is a demanding task, in technical as well as in logistical terms. Rapid acquisition of high quality radiographs under difficult conditions, for example severely injured patients with multi-organ trauma is important. All image data and radiological reports must be transmitted to the trauma surgeon as soon as possible. To meet these needs with the promising means of modern X-ray technology, we decided to implement a completely digital X-ray division inside the new outpatient trauma department. In the setting of an outpatient emergency department digital radiography and PACS cannot be realised without problems. We present our first experience with the installation and 10 month filmless routine in the X-ray division for traumatology outpatients at the university of Innsbruck department of radiology.


Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group.
In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating physician can consider decreasing the frequency of or discontinuing zoledronic acid treatment. Denosumab can also be considered for the treatment of multiple myeloma-related bone disease, particularly in patients with renal impairment. Denosumab might prolong progression-free survival in patients with newly diagnosed multiple myeloma who have multiple myeloma-related bone disease and who are eligible for autologous stem-cell transplantation. Denosumab discontinuation is challenging due to the rebound effect. The Bone Working Group of the International Myeloma Working Group also found cement augmentation to be effective for painful vertebral compression fractures. Radiotherapy is recommended for uncontrolled pain, impeding or symptomatic spinal cord compression, or pathological fractures. Surgery should be used for the prevention and restoration of long-bone pathological fractures, vertebral column instability, and spinal cord compression with bone fragments within the spinal route.


The Use of Mobile Personal Health Records for Hemoglobin A1c Regulation in Patients With Diabetes: Retrospective Observational Study.
The effectiveness of personal health records (PHRs) in diabetes management has already been verified in several clinical trials; however, evidence of their effectiveness in real-world scenarios is also necessary. To provide solid real-world evidence, an analysis that is more accurate than the analyses solely based on patient-generated health data should be conducted. This study aimed to conduct a more accurate analysis of the effectiveness of using PHRs within electronic medical records (EMRs). The results of this study will provide precise real-world evidence of PHRs as a feasible diabetes management tool. We collected log data of the sugar function in the My Chart in My Hand version 2.0 (MCMH 2.0) app from Asan Medical Center (AMC), Seoul, Republic of Korea, between December 2015 and April 2018. The EMR data of MCMH 2.0 users from AMC were collected and integrated with the PHR data. We classified users according to whether they were continuous app users. We analyzed and compared their characteristics, patterns of hemoglobin A1c (HbA1c) levels, and the proportion of successful HbA1c control. The following confounders were adjusted for HbA1c pattern analysis and HbA1c regulation proportion comparison: age, sex, first HbA1c measurement, diabetes complications severity index score, sugar function data generation weeks, HbA1c measurement weeks before MCMH 2.0 start, and generated sugar function data count. The total number of MCMH 2.0 users was 64,932, with 7453 users having appropriate PHRs and diabetes criteria. The number of continuous and noncontinuous users was 133 and 7320, respectively. Compared with noncontinuous users, continuous users were younger (P<.001) and had a higher male proportion (P<.001). Furthermore, continuous users had more frequent HbA1c measurements (P=.007), shorter HbA1c measurement days (P=.04), and a shorter period between the first HbA1c measurement and MCMH 2.0 start (P<.001). Diabetes severity-related factors were not statistically significantly different between the two groups. Continuous users had a higher decrease in HbA1c (P=.02) and a higher proportion of regulation of HbA1c levels to the target level (P=.01). After adjusting the confounders, continuous users had more decline in HbA1c levels than noncontinuous users (P=.047). Of the users who had a first HbA1c measurement higher than 6.5% (111 continuous users and 5716 noncontinuous users), continuous users had better regulation of HbA1c levels with regard to the target level, 6.5%, which was statistically significant (P=.04). By integrating and analyzing patient- and clinically generated data, we demonstrated that the continuous use of PHRs improved diabetes management outcomes. In addition, the HbA1c reduction pattern was prominent in the PHR continuous user group. Although the continued use of PHRs has proven to be effective in managing diabetes, further evaluation of its effectiveness for various diseases and a study on PHR adherence are also required.


Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition.
In up to one-third of patients with acute myeloid leukemia, a C-terminal frame-shift mutation results in abnormal and abundant cytoplasmic accumulation of the usually nucleoli-bound protein nucleophosmin (NPM), and this is thought to function in cancer pathogenesis. Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8-mediated myeloid differentiation. Our data hence provide a potential explanation for the myeloid-specific involvement of cytoplasmic NPM in the leukemogenesis of a large subset of acute myeloid leukemia.


Muscle-specific protein expression in normal salivary glands and pleomorphic adenomas: an immunocytochemical study with biochemical confirmation.
Normal salivary gland myoepithelia are contractile cells with hybrid epithelial/myogenic ultrastructural features. It is known that these cells co-express the intermediate filaments cytokeratin, vimentin, and occasionally GFAP. This complex cytoskeletal immunophenotype is also reflected in multiple morphologic cell types of pleomorphic adenoma. At present, the myofilament complement of normal and neoplastic myoepithelium is not well defined. We have evaluated the expression of desmin and smooth and sarcomeric muscle actins in 11 normal salivary glands (six snap-frozen and five methacarn fixed) and 26 pleomorphic adenomas (11 snap-frozen and 15 methacarn fixed) by ABC-immunoperoxidase method. Two of 11 frozen pleomorphic adenomas contained the muscle-specific intermediate filament desmin, which is not found in the normal glands. This novel finding was confirmed by gel electrophoresis and immunoblot. Using specific antibodies, normal gland myoepithelial cells consistently contained muscle actin isoforms of the smooth muscle type but not sarcomeric muscle actins. Muscle actin expression by the neoplastic cells of pleomorphic adenoma was found in 13 of 26 tumors (six of 11 frozen tumors (desmin negative) and seven of 15 methacarn fixed tumors). In comparison to the normal myoepithelial cell, the transformed myoepithelial-like cells of pleomorphic adenoma are not always characterized by a muscle actin cytoskeleton. Expression of desmin intermediate filaments in pleomorphic adenomas appears to be a rare event that is independent of a muscle actin cytoskeleton.


Association of systolic blood pressure and pulse pressure with carotid intima thickness in elderly Japanese patients.
Many studies have demonstrated that increased carotid intima-media thickness (IMT) is related to future cardiovascular events and is influenced by cardiovascular risk factors such as sex, hypertension, diabetes, and hypercholesterolemia. Although aging is a well-known risk factor for an increase in carotid IMT, few studies have investigated which factors influence carotid IMT in the very elderly. In the present study, we investigated the relationship of pulse pressure (PP), blood pressure (BP), and its variability (six consecutive visits) with carotid IMT among 240 high-risk elderly in whom risk factors were managed clinically (average age was 79 ± 5 years). In the simple correlation, mean systolic BP (SBP) had a positive correlation with IMT and max IMT (P = .012 and P = .045), as did PP (P = .018 and P = .004), but did not diastolic BP or standard deviation of BP and coefficient of variation of BP. In multiple regression analyses, mean SBP and mean PP were each determinants of both IMT and max IMT, when each parameter was added separately to the regression model. We concluded that high SBP and wide PP still have an influence on increased carotid IMT in the very elderly Japanese patients.


Tyrosine kinase inhibition affects type 1 angiotensin II receptor internalization.
Growth factor receptors activate tyrosine kinases and undergo endocytosis. Recent data suggest that tyrosine kinase inhibition can affect growth factor receptor internalization. The type 1 angiotensin II receptor (AT1R) which is a G-protein-coupled receptor, also activates tyrosine kinases and undergoes endocytosis. Thus, we examined whether tyrosine kinase inhibition affected AT1R internalization. To verify protein tyrosine phosphorylation, both LLCPKCl4 cells expressing rabbit AT1R (LLCPKAT1R) and cultured rat mesangial cells (MSC) were treated with angiotensin II (Ang II) [1-100 nM] then solubilized and immunoprecipitated with antiphosphotyrosine antisera. Immunoblots of these samples demonstrated that Ang II stimulated protein tyrosine phosphorylation in both cell types. Losartan [1 microM], an AT1R antagonist, inhibited Ang II-stimulated protein tyrosine phosphorylation. LLCPKAT1R cells displayed specific 125I-Ang II binding at apical (AP) and basolateral (BL) membranes, and both AP and BL AT1R activated tyrosine phosphorylation. LLCPKAT1R cells, incubated with genistein (Gen) [200 microM] or tyrphostin B-48 (TB-48) [50 microM], were assayed for acid-resistant specific 125I-Ang II binding, a measure of Ang II internalization. Both Gen (n = 7) and TB-48 (n = 3) inhibited AP 125I-Ang II internalization (80+/-7% inhibition; p<0.025 vs. control). Neither compound affected BL internalization. TB-1, a non-tyrosine kinase-inhibiting tyrphostin, did not affect AP 125I-Ang II endocytosis (n = 3), suggesting that the TB-48 effect was specific for tyrosine kinase inhibition. Incubating MSC with Gen (n = 5) or herbimycin A [150 ng/ml] (n = 4) also inhibited MSC 125I-Ang II internalization (82+/-11% inhibition; p<0.005 vs. control). Thus, tyrosine kinase inhibition prevented Ang II internalization in MSC and selectively decreased AP Ang II internalization in LLCPKAT1R cells suggesting that AP AT1R in LLCPKAT1R cells and MSC AT1R have similar endocytic phenotypes, and tyrosine kinase activity may play a role in AT1R internalization.


Stress and vascular responses: oxidative stress and endothelial dysfunction in the insulin-resistant state.
Although insulin-resistant states have been associated with endothelial dysfunction due to increased vascular oxidative stress, the underlying mechanisms are pooly understood. Recent experimental evidence suggests that tetrahydrobiopterin (BH(4)), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS but also in controlling the formation of superoxide anion (O(2)(-)) in endothelial cells. Because insulin resistance has been suggested to be a significant contributing factor in the development of abnormal pteridine metabolism and endothelial dysfunction, we investigated pteridine content and NO/O(2)(-) production with the use of isolated thoracic aortas obtained from fructose-induced insulin-resistant rats. Under insulin-resistant conditions where BH(4) levels are suboptimal, the production of O(2)(-) by NOS leads to endothelial dysfunction. Furthermore, oral supplementation of BH(4) restores endothelial function and relieved oxidative tissue damage, at least in part, through activation of endothelial NOS (eNOS) in the aorta of insulin-resistant rats. These results indicate that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO due to enhanced formation of O(2)(-), which are caused by relative deficiency of BH(4) in vascular endothelial cells.


Transcranial Brain Sonography in Parkinson's Disease and Other Parkinsonian Disorders: a Hospital Study from Tuzla, Bosnia and Herzegovina.
Transcranial sonography (TCS) is a relatively new ultrasound modality which could display echogenicity of human brain tissue through the intact skull. TCS may be useful in differentiation of idiopathic Parkinson's disease (PD) from other parkinsonian disorders. Therefore, we studied different ultrasound markers by TCS in individuals with Parkinson's disease. We performed TCS in 44 patients with PD and 22 patients with other parkinsonian disorders. Echogenic sizes of the substantia nigra (SN) and the lentiform nuclei (LN), as well as the width of the third ventricle and the frontal horns of the lateral ventricle, were measured. We also analyzed the echogenicity of the brainstem raphe (BR). An unilateral hyperechogenic SN was observed in 31 (70%) patients with PD and only in 2 patients (9%) with other parkinsonian disorders (P<0.0001). Hyperechogenicity of the LN was no observed in patients with PD; however, it was present in 7 (32%) patients with other parkinsonian disorders (P=0.0002). Diameter of third ventricle (8.6+/-2.2 mm vs. 6.9+/-1.7mm, P=0.001), right (18.5+/-2.6 mm vs. 16.5+/-2.3 mm, P=0.003) and left frontal horn of lateral ventricle (19.0+/-3.7 mm vs. 16.2+/-2.6 mm, P=0.0006) was significantly wider in patients with other parkinsonian disorders compared with patients with PD. There was no difference in presence of hypoechogenic or interrupted BR in patients with PD and patients with other parkinsonian disorders (39% vs. 27%, P=0.4). TCS is a promising diagnostic technique and can be very helpful in differentiating between idiopathic Parkinson's disease and other parkinsonian disorders.


Two-dimensional crystals of photosystem II: biochemical characterization, cryoelectron microscopy and localization of the D1 and cytochrome b559 polypeptides.
Photosystem II (PS II) is a photosynthetic reaction center found in higher plants which has the unique ability to evolve oxygen from water. Several groups have formed two-dimensional PS II crystals or have isolated PS II complexes and studied them by electron microscopy and image analysis. The majority of these specimens have not been well characterized biochemically and have yielded relatively low resolution two-dimensional projection maps with a variety of unit cell sizes. We report the characterization of the polypeptide and lipid content of tubular crystals of PS II. The crystals contain the reaction center core polypeptides D1, D2, cytochrome b559, as well as the chlorophyll-binding polypeptides (CP) CP47, CP43, CP29, CP26, CP24, and CP22. The lipid composition was similar to the lipids found in the stacked portion of thylakoids. We also report a 2.0-nm resolution projection map determined by electron microscopy and image analysis of frozen, hydrated PS II crystals. This projection map includes information on the portion of the complex buried in the lipid bilayer. The unit cell is a dimer with unit vectors of 17.0 and 11.4 nm separated by an angle of 106.6 degrees. In addition, Fab fragments against D1 and cytochrome b559 were used to localize those two polypeptides, and thus the reaction center, within the PS II complex. The results indicate that D1 and cytochrome b559 are found within one of the heaviest densities of the monomeric unit.


Interview with a quality leader: Kent Bottles, MD, president of ICSI, on transforming care for the future. Interview by Susan V. White.
Kent Bottles, MD, President of the Institute for Clinical Systems Improvement (ICSI). Dr. Bottles is a board-certified pathologist who specialized in surgical and cyto-pathology. He earned a medical degree from Case Western Reserve University in Ohio. He has extensive experience in integrated healthcare delivery systems, research, academia, commercial laboratories, genomics, proteomics, and management of biotech start-up companies. Dr. Bottles was vice president and chief medical officer of the Iowa Health System. Before that, he served as president and CEO of Grand Rapids Medical Education and Research Center for Health Professions, a multi-institutional consortium of healthcare organizations, and as president of Genomics Repository and chief knowledge officer, Genomics Collaborative Inc. Dr. Bottles has extensive academic experience, serving as Professor and Acting Head, Department of Pathology and Laboratory Medicine at the University of Iowa. He was also the founding medical director of managed care plans for University of Iowa employees. Dr. Bottles has addressed topics ranging from quality and patient safety and disruptive technology to patient-physician relationships and the future of medicine. He has received numerous honors, including the Rodney T. West Literary Achievement Award for the most important article on medical management presented by the American College of Physician Executives. He has broad clinical experience with the University of Iowa and the San Francisco General Hospital, and has been a national leader in changing the practice of pathology and laboratory medicine to meet the challenges of managed care.


On the Use of Regression Calibration in a Complex Sampling Design With Application to the Hispanic Community Health Study/Study of Latinos.
Regression calibration is the most widely used method to adjust regression parameter estimates for covariate measurement error. Yet its application in the context of a complex sampling design, for which the common bootstrap variance estimator can be less straightforward, has been less studied. We propose 2 variance estimators for a multistage probability-based sampling design, a parametric and a resampling-based multiple imputation approach, where a latent mean exposure needed for regression calibration is the target of imputation. This work was motivated by the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) data from 2008 to 2011, for which relationships between several outcomes and diet, an error-prone self-reported exposure, are of interest. We assessed the relative performance of these variance estimation strategies in an extensive simulation study built on the HCHS/SOL data. We further illustrate the proposed estimators with an analysis of the cross-sectional association of dietary sodium intake with hypertension-related outcomes in a subsample of the HCHS/SOL cohort. We have provided guidelines for the application of regression models with regression-calibrated exposures. Practical considerations for implementation of these 2 variance estimators in the setting of a large multicenter study are also discussed. Code to replicate the presented results is available online.


CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated?
In chronic pancreatitis (CP), alterations in several genes have so far been described, but only small cohorts have been extensively investigated for all predisposing genes. 660 patients with idiopathic or hereditary CP and up to 1758 controls were enrolled. PRSS1, SPINK1 and CTRC were analysed by DNA sequencing, and cystic fibrosis transmembrane conductance regulator (CFTR) by melting curve analysis. Frequencies of CFTR variants p.R75Q, p.I148T, 5T-allele and p.E528E were comparable in patients and controls. We identified 103 CFTR variants, which represents a 2.7-fold risk increase (p<0.0001). Severe cystic fibrosis (CF)-causing variants increased the risk of developing CP 2.9-fold, and mild CF-causing variants 4.5-fold (p<0.0001 for both). Combined CF-causing variants increased CP risk 3.4-fold (p<0.0001), while non-CF-causing variants displayed a 1.5-fold over-representation in patients (p=0.14). CFTR compound heterozygous status with variant classes CF-causing severe and mild represented an OR of 16.1 (p<0.0001). Notably, only 9/660 (1.4%) patients were compound heterozygotes in this category. Trans-heterozygosity increased CP risk, with an OR of 38.7, with 43/660 (6.5%) patients and 3/1667 (0.2%) controls being trans-heterozygous (p<0.0001). Accumulation of CFTR variants in CP is less pronounced than reported previously, with ORs between 2.7 and 4.5. Only CF-causing variants reached statistical significance. Compound and trans-heterozygosity is an overt risk factor for the development of CP, but the number of CFTR compound heterozygotes in particular is rather low. In summary, the study demonstrates the complexity of genetic interactions in CP and a minor influence of CFTR alterations in CP development.


Selective excitation of surface plasmon modes propagating in Ag nanowires.
Surface plasmon modes propagating in metal nanowires are conveniently excited by focusing a laser beam on one extremity of the nanowire. We find that the precise positioning of the nanowire inside the focal region drastically influences the excitation efficiency of the different SPP modes sustained by the plasmonic waveguide. We demonstrate a spatially selective excitation of bound and leaky surface plasmon modes with excitation maps that strongly depend on the orientation of the incident linear polarization. We discuss this modal selection by considering the inhomogeneous distribution of the field components inside the focus. Our finding provides a way to discriminate the effective indices of the modes offering thus an increased coupling agility for future nanowire-based plasmonic architectures.


The current state of patient safety culture in Lebanese hospitals: a study at baseline.
The objective of this study is to conduct a baseline assessment of patient safety culture in Lebanese hospitals. The study adopted a cross-sectional research design and utilized the hospital survey on patient safety culture (HSOPSC). Sixty-eight Lebanese hospitals participated in the study (54% of all hospitals). A total of 6807 hospital employees participated in the study including hospital-employed physicians, nurses, clinical and non-clinical staff, and others. The HSOPSC measures 12 composites of patient safety culture. Two of the composites (frequency of events reported and overall perception of safety), in addition to questions on patient safety grade and number of events reported, are the four outcome variables. Survey respondents were primarily employed in medical and surgical units. The dimensions with the highest positive ratings were teamwork within units, hospital management support for patient safety, and organizational learning and continuous improvement, while those with lowest ratings included staffing and non-punitive response to error. Approximately 60% of respondents reported not completing any event reports in the past 12 months and over 70% gave their hospitals an 'excellent/very good' patient safety grade. Bivariate and multivariate analysis revealed significant differences across hospitals of different size and accreditation status. Study findings provide evidence that can be used by policy makers, managers and leaders who are able to create the culture and commitment needed to identify and solve underlying systemic causes related to patient safety.


Scalable collision detection using p-partition fronts on many-core processors.
We present a new parallel algorithm for collision detection using many-core computing platforms of CPUs or GPUs. Based on the notion of a $(p)$-partition front, our algorithm is able to evenly partition and distribute the workload of BVH traversal among multiple processing cores without the need for dynamic balancing, while minimizing the memory overhead inherent to the state-of-the-art parallel collision detection algorithms. We demonstrate the scalability of our algorithm on different benchmarking scenarios with and without using temporal coherence, including dynamic simulation of rigid bodies, cloth simulation, and random collision courses. In these experiments, we observe nearly linear performance improvement in terms of the number of processing cores on the CPUs and GPUs.


Low dose effect of bisphosphonates on hMSCs osteogenic response to titanium surface in vitro.
Since the 1980s, titanium (Ti) implants have been routinely used to replace missing teeth. This success is mainly due to the good biocompatibility of Ti and the phenomenon of osseointegration, with very early events at implant placement being important in determining good osseointegration. However, enhancing implant performance with coatings such as hydroxyapatite (HA) and calcium phosphate has proved largely unsuccessful. Human mesenchymal stem cells (hMSCs) are the first osteogenic cells to colonise implant surfaces and offer a target for enhancing osseointegration. We previously reported that small doses of bisphosphonate (BP) may play an integral role in enhancing hMSC proliferation and osteogenic differentiation. The aim of this study is to investigate whether small doses of bisphosphonates enhance proliferation and osteogenic differentiation of hMSCs on Ti surfaces, to enhance bone osseointegration and to accelerate wound healing around the implant surface. Our data suggests that treating cells with small doses of BP (100 nM & 10 nM) induces significant hMSC stimulation of osteogenic markers including calcium, collagen type I and ALP compared to control group on titanium surfaces (P < 0.05). In addition, cell proliferation and migration were significantly enhanced on titanium surfaces (P < 0.05).


Reconstruction of the Orbit and Anophthalmic Socket Using the Dermis Fat Graft: A Major Review.
To perform a comprehensive review of dermis fat graft (DFG) in socket reconstruction and illustrate the technical nuances and outcomes using a retrospective case review. A literature search of 143 texts was reviewed. A retrospective case series of 34 patients following primary or secondary DFG after enucleation at a single institution (2009-2019) was performed. Clinical outcomes were statistically analyzed. Variables investigated included age, sex, race, surgical indication, muscle reattachment, complications, motility, eyelid position, prosthesis fit, and need for additional surgery. The history of DFG, use in socket reconstruction, primary and secondary indications, and surgical techniques are described. Thirty-two adults and 2 pediatric cases of DFG were reviewed; 18.75% indications were primary and 81.25% were secondary. Good eyelid position was observed in 83.3% of patients with primary DFG versus 37.5% with secondary DFG (p = 0.07). Postoperative complications occurred in 58.8% of patients, were typically mild, and resolved with minimal or no intervention. No statistically significant differences were found between occurrence of any particular complication in primary versus secondary DFG placement (p = 0.36) or between primary and secondary DFG placement and the need for additional surgery (p = 1.0). Among the 67.7% patients who had implant exposure or extrusion as an indication for DFG, 39.1% required additional surgery within 2 years. Advanced age was not associated with higher complication rates (p = 0.12). DFG is an excellent option for socket reconstruction, particularly in cases involving pediatric patients, complicated orbits, history of multiple previous surgeries, and inflamed, contracted, or scarred sockets.


[The role of emotional-volitional traits in patients with ischemic heart disease in carrying out dietetic recommendations during long-term clinical observation].
The influence of subjective (individual) prerequisites on the possibility of long-term following anti-atherosclerotic diets by coronary patients was investigated. Basing on the examination of the patients they were divided into three groups: those who strictly kept the diet (I), patients who moderately violated the diet (II), and those who did not keep the diet at home (III). Specific psychological methods used in the study allowed differentiation of these groups of patients. A conclusion has been made on the relation between the capacity for keeping the diet and some psychological personality traits of coronary patients. The analysis of the results enabled the authors to reveal a complex of problems for prognosing the coronary patients' readiness to keep the diet at home. The data obtained may be conductive to a rise in the medicosocial adaptation of coronary patients to long-term diet therapy by means of directed psychotherapy.


Delayed dispersal and the costs and benefits of different routes to independent breeding in a cooperatively breeding bird.
Why sexually mature individuals stay in groups as nonreproductive subordinates is central to the evolution of sociality and cooperative breeding. To understand such delayed dispersal, its costs and benefits need to be compared with those of permanently leaving to float through the population. However, comprehensive comparisons, especially regarding differences in future breeding opportunities, are rare. Moreover, extraterritorial prospecting by philopatric individuals has generally been ignored, even though the factors underlying this route to independent breeding may differ from those of strict philopatry or floating. We use a comprehensive predictive framework to explore how various costs, benefits and intrinsic, environmental and social factors explain philopatry, prospecting, and floating in Seychelles warblers (Acrocephalus sechellensis). Not only floaters more likely obtained an independent breeding position before the next season than strictly philopatric individuals, but also suffered higher mortality. Prospecting yielded similar benefits to floating but lower mortality costs, suggesting that it is overall more beneficial than floating and strict philopatry. While prospecting is probably individual-driven, although limited by resource availability, floating likely results from eviction by unrelated breeders. Such differences in proximate and ultimate factors underlying each route to independent breeding highlight the need for simultaneous consideration when studying the evolution of delayed dispersal.


A Comprehensive Review of State Vision Screening Mandates for Schoolchildren in the United States.
Methods and frequency of vision screenings for school-aged children vary widely by state, and there has been no recent comparative analysis of state requirements. This analysis underscores the need for developing evidence-based criteria for vision screening in school-aged children across the United States. The purpose of this study was to conduct an updated comprehensive analysis of vision screening requirements for school-aged children in the United States. State laws pertaining to school-aged vision screening were obtained for each state. Additional information was obtained from each state's Department of Health and Education, through their websites or departmental representatives. A descriptive analysis was performed for states with data available. Forty-one states require vision screening for school-aged children to be conducted directly in schools or in the community. Screening is more commonly required in elementary school (n = 41) than in middle (n = 30) or high school (n = 19). Distance acuity is the most commonly required test (n = 41), followed by color vision (n = 11) and near vision (n = 10). Six states require a vision screening annually or every 2 years. Although most states require vision screening for some school-aged children, there is marked variation in screening methods and criteria, where the screening occurs, and grade levels that are screened. This lack of standardization and wide variation in state regulations point to a need for the development of evidence-based criteria for vision screening programs for school-aged children.


Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.
In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women. Isolated primary placental macrophages (Hofbauer cells [HCs]) were exposed to HIV-1BaL and/or interferon (IFN)-α, IFN-β, IFN-λ1, and RIG-I-like receptor (RLR) agonists. qRT-PCR, FACS, ELISA, Luminex, and Western blot analyses determined expression of activation markers, co-receptors, viral antigen, cytokines, antiviral genes, and host proteins. Early gestation HCs express higher levels of CCR5 and exhibit a more activated phenotype. Despite downregulation of CCR5, term HCs were more susceptible to HIV replication. Early gestation HCs displayed a more activated phenotype than term HCs and HIV exposure lead to the further up-regulation of T-cell co-stimulatory and MHC molecules. Limited HIV replication in early/mid gestation HCs was associated with increased secretion of anti-inflammatory cytokines, chemokines, and a more robust antiviral immune response. In contrast, term HCs were more susceptible to HIV replication, associated with dampening of IFN-induced STAT1 and STAT2 protein activation. Treatment of early/mid gestation and term HCs, with type I IFNs or RLR agonists reduced HIV replication, underscoring the importance of IFN and RLR signaling in inducing an antiviral state. Viral recognition and antiviral immunity in early gestation HCs may prevent in utero HIV infection, whereas diminished antiviral responses at term can facilitate transmission. Defining mechanisms and specific timing of vertical transmission are critical for the development of specific vaccines and antiviral therapeutics to prevent new HIV infections in children globally.


Two-incision approach for video-assisted thoracoscopic sleeve lobectomy treating the central lung cancer.
We review our experiences with video-assisted thoracoscopic surgery (VATS) sleeve lobectomy with bronchoplasty for nonsmall-cell lung cancer, using only two incisions. The aim of this study was to evaluate the technical feasibility and safety of surgical approach. From January 2013 to January 2014, we completed 15 cases of VATS sleeve lobectomy with bronchoplasty in our hospital. The patients underwent sleeve lobectomy with bronchoplasty at the following locations: right upper lobe (n = 4), right lower and middle lobes (n = 1), left lower lobe (n = 5), and left upper lobe (n = 6). The operation consisted of VATS anatomic sleeve lobectomy with bronchoplasty combined with systematic lymph node dissection, using only two incisions. The patients underwent sleeve lobectomy with bronchoplasty were no postoperative complications. Median operative time was 183 min; median bronchial anastomosis time was 39 min; median blood loss was 170 ml. Pathological examination showed 12 squamous cell carcinomas and 3 adenocarcinoma. Median postoperative chest tube drainage duration was 4.5 days, and median hospital stay was 6.9 days. Video-assisted thoracoscopic surgery sleeve lobectomy with bronchoplasty is a feasible and safe surgical approach, using only two incisions. This way of operation can promote the development of surgical technology.


[Evaluation of microbiological quality of seasoning purchased in the retail network].
The estimation of microbiological quality of seasoning purchased in the retail network was the aim of this work. The study included five kinds of seasoning manufactured by four Polish companies. Microbiological analysis of the material included: total count of mesophilic aerobic bacteria and their spores, count of yeast and moulds and occurrence of coliforms bacteria, E. coli, Salmonella sp. and S. aureus. The results showed that the total count of mesophilic aerobic bacteria was high (10(5) -10(6) cfu x g(-1)) in the most of estimated spices and bacteria occurred mainly as spores. The low titre of coliform reduced down to 10(-2)-10(-3), occurrence of E. coli it was stated in 20% of samples of spices. However no pathogenic bacteria (Salmonella sp., S. aureus) was detected. Contamination of seasoning by yeasts and moulds was low in majority of samples and only in two samples the count of moulds was higher than 10(3) cfu x g(-1) and not answered requirements. Moulds were mainly represented by Aspergillus sp. (A. glaucus, A. niger, A. flavus) and than by Penicillium sp. and Rhizopus sp. Microbiological quality of seasoning was differentiated in dependence on the manufacturer.


Global extent and drivers of mammal population declines in protected areas under illegal hunting pressure.
Illegal hunting is a persistent problem in many protected areas, but an overview of the extent of this problem and its impact on wildlife is lacking. We reviewed 40 years (1980-2020) of global research to examine the spatial distribution of research and socio-ecological factors influencing population decline within protected areas under illegal hunting pressure. From 81 papers reporting 988 species/site combinations, 294 mammal species were reported to have been illegally hunted from 155 protected areas across 48 countries. Research in illegal hunting has increased substantially during the review period and showed biases towards strictly protected areas and the African continent. Population declines were most frequent in countries with a low human development index, particularly in strict protected areas and for species with a body mass over 100 kg. Our results provide evidence that illegal hunting is most likely to cause declines of large-bodied species in protected areas of resource-poor countries regardless of protected area conservation status. Given the growing pressures of illegal hunting, increased investments in people's development and additional conservation efforts such as improving anti-poaching strategies and conservation resources in terms of improving funding and personnel directed at this problem are a growing priority.


The first James Kirk memorial lecture. What next in fractionated radiotherapy?
Models for predicting the total dose required to produce tolerable normal-tissue injury are becoming less empirical, more realistic, and more specific for different tissue reactions. The trend can be seen by the progression from the "cube root law", through Strandqvist's slope of 0.22, to NSD, TDF and CRE which have separate time and fraction number exponents, to the even better approximations which are now available. The dose-response formulae that can be used, with statistical legitimacy, to define the effect of fraction size (and number) include (1) the linear quadratic(LQ) model; (2) the two-component (TC) multi-target model; and (3) repair - misrepair models. The LQ model offers considerable convenience and requires only two parameters to be determined. The use of a new model often provides fresh insights. The LQ model has emphasized the difference between late and early normal-tissue dependence on dose per fraction which was first shown by exponents greater than the NSD slope of 0.24. Exponents of overall time, e.g. T0.11, yield the wrong shape of time curve, suggesting that most proliferation occurs early, although it really occurs after a delay depending on the turnover time of the tissue. The principles of better time factors are well known but actual values for human tissues are not well determined. Fortunately the time factors are usually small, especially for late reactions. Improved clinical results are being sought by hyperfractionation, by accelerated fractionation, or by continuous low dose rate irradiation as in interstitial implants. New clinical trials are investigating these approaches, which have been suggested by the accumulation of radiobiological data.


[Interaction of adhesion proteins with structural components of cytoskeleton in animal cells].
The short characteristic of cell adhesion molecules and the main components of cytoskeleton are submitted at the present review. Structural and functional peculiarities of these proteins are presented. On the basis of different sources an attempt to clarify the possible mechanism of the interaction of adhesion proteins cytoskeleton structure has been done. It is suggested that information about adhesion contacts is transmitted from the adhesion proteins to cytoskeleton structures that induces the transformation of the letter ones and promotes the cellular metabolic response.