Depolymerization of fucosylated chondroitin sulfate from sea cucumber, Pearsonothuria graeffei, via 60Co irradiation.
A method for depolymerization of a novel fucosylated chondroitin sulfate from Pearsonothuria graeffei (fCS-Pg) using (60)Co irradiation in water solution was developed in the current study. Fragments with varying molecular weights were obtained by (60)Co irradiation at different dosages and sample concentrations. The chemical compositions and structures of these fragments were further investigated using high-performance liquid chromatography (HPLC), infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Our results indicated that (60)Co irradiation induced depolymerization via selective breakage of glucuronic acid units in the fCS-Pg backbone, with no obvious influence on sulfated fucose branches under mild conditions. The recommended conditions for fCS-Pg degradation were 2-10% solution concentration and irradiation dosages of 10-50kGy. The anticoagulant activities of the low molecular weight fragments were additionally evaluated. Notably, anticoagulant activities were reduced with decreasing molecular weights. Compared to the native fCS-Pg, low molecular weight fragments displayed significantly decreased anticoagulant activities. Based on the collective findings, we propose that these fragments are potentially applicable as antithrombotic agents with reduced bleeding risk relative to native fCS-Pg.


Selection and demography drive range-wide patterns of MHC-DRB variation in mule deer.
Standing genetic variation is important especially in immune response-related genes because of threats to wild populations like the emergence of novel pathogens. Genetic variation at the major histocompatibility complex (MHC), which is crucial in activating the adaptive immune response, is influenced by both natural selection and historical population demography, and their relative roles can be difficult to disentangle. To provide insight into the influences of natural selection and demography on MHC evolution in large populations, we analyzed geographic patterns of variation at the MHC class II DRB exon 2 locus in mule deer (Odocoileus hemionus) using sequence data collected across their entire broad range. We identified 31 new MHC-DRB alleles which were phylogenetically similar to other cervid MHC alleles, and one allele that was shared with white-tailed deer (Odocoileus virginianus). We found evidence for selection on the MHC including high dN/dS ratios, positive neutrality tests, deviations from Hardy-Weinberg Equilibrium (HWE) and a stronger pattern of isolation-by-distance (IBD) than expected under neutrality. Historical demography also shaped variation at the MHC, as indicated by similar spatial patterns of variation between MHC and microsatellite loci and a lack of association between genetic variation at either locus type and environmental variables. Our results show that both natural selection and historical demography are important drivers in the evolution of the MHC in mule deer and work together to shape functional variation and the evolution of the adaptive immune response in large, well-connected populations.


Determination of nine hydroxylated polybrominated diphenyl ethers in water by precolumn derivatization-gas chromatography-mass spectrometry.
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs), acting as emerging endocrine disruptors, have aroused more and more concern recently. Produced from natural source or metabolism of PBDEs, OH-PBDEs are more toxic than their parent compounds. However, few analytical methods are available for sensitive determination of these compounds especially in water. In this study, a method of determination of nine OH-PBDEs in lake, reservoir, river and sewage treatment plant effluent was established using N,O-bis (trimethylsilyl) trifluoroacetamide (BSTFA) as derivatization reagent combined with gas chromatography-mass spectrometry (GC-MS). Optimal extraction solvent and derivatization factors such as the amount of BSTFA, time, temperature and dissolution solvent were determined experimentally. After extracted by hexane-dichloromethane (1:1, v/v), extracts were evaporated to almost dry, then BSTFA was added to the residue and heated at 90°C for 30min. The remains were dried under a stream of nitrogen and redissolved in hexane. The solution was separated in DB-35MS column, then determined by GC-MS in selected ion mode and full scan monitoring mode, and quantified by external standard method. The working curves were obtained using sample matrix in order to eliminate the matrix interference. Linear range was from 0.02μgL(-1) to 30μgL(-1). Limits of detection and quantification ranged from 0.0039μgL(-1) to 0.0220μgL(-1) and 0.0130μgL(-1) to 0.0733μgL(-1), respectively. Two different spiked levels were measured with 5 parallel tests for each level. The results indicated that the relative standard deviations were less than 14.08%. The method has been applied to lake water, reservoir water, river water and sewage treatment plant effluent. Five OH-PBDEs including 2'-OH-BDE3, 3'-OH-BDE7, 2'-OH-BDE28, 4'-OH-BDE17 and 5'-OH-BDE99 were detected in all the samples collected in Baoding, China. This method is simple, high sensitive, and suitable for simultaneous determination of nine OH-PBDEs in different environmental water.


Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation.
β-Adrenergic stimulation in heart leads to increased contractility and lusitropy via activation of protein kinase A (PKA). In the cardiac sarcomere, both cardiac myosin binding protein C (cMyBP-C) and troponin-I (cTnI) are prominent myofilament targets of PKA. Treatment of permeabilized myocardium with PKA induces enhanced myofilament length-dependent activation (LDA), the cellular basis of the Frank-Starling cardiac regulatory mechanism. It is not known, however, which of these targets mediates the altered LDA and to what extent. Here, we employed two genetic mouse models in which the three PKA sites in cMyBP-C were replaced with either phospho-mimic (DDD) or phospho-null (AAA) residues. AAA- or DDD-permeabilized myocytes (n = 12-17) were exchanged (~93%) for recombinant cTnI in which the two PKA sites were mutated to either phospho-mimic (DD) or phospho-null (AA) residues. Force-[Ca(2+)] relationships were determined at two sarcomere lengths (SL = 1.9 μm and SL = 2.3 μm). Data were fit to a modified Hill equation for each individual cell preparation at each SL. LDA was indexed as ΔEC50, the difference in [Ca(2+)] required to achieve 50% force activation at the two SLs. We found that PKA-mediated phosphorylation of cMyBP-C and cTnI each independently contribute to enhance myofilament length-dependent activation properties of the cardiac sarcomere, with relative contributions of ~67 and ~33% for cMyBP-C for cTnI, respectively. We conclude that β-adrenergic stimulation enhances the Frank-Starling regulatory mechanism predominantly via cMyBP-C PKA-mediated phosphorylation. We speculate that this molecular mechanism enhances cross-bridge formation at long SL while accelerating cross-bridge detachment and relaxation at short SLs.


Mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leucocytes.
Hydrocortisone (10 microgram/ml) greatly inhibits the prostaglandin release by rat peritoneal leucocytes phagocytosing killed bacteria. The inhibition, which occurs after an initial latency of 30 min, is completely reversed by either actinomycin D (0.5 microgram/ml) or cycloheximide (1 microgram/ml). Since these antibiotics are known inhibitors of DNA-dependent RNA synthesis and protein synthesis respectively, it appears that the mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leucocytes involves stimulation of transcription and induction of protein synthesis.


Contact sites between endoplasmic reticulum sheets and mitochondria regulate mitochondrial DNA replication and segregation.
Mitochondria are multifaceted organelles crucial for cellular homeostasis that contain their own genome. Mitochondrial DNA (mtDNA) replication is a spatially regulated process essential for the maintenance of mitochondrial function, its defect causing mitochondrial diseases. mtDNA replication occurs at endoplasmic reticulum (ER)-mitochondria contact sites and is affected by mitochondrial dynamics: The absence of mitochondrial fusion is associated with mtDNA depletion whereas loss of mitochondrial fission causes the aggregation of mtDNA within abnormal structures termed mitobulbs. Here, we show that contact sites between mitochondria and ER sheets, the ER structure associated with protein synthesis, regulate mtDNA replication and distribution within mitochondrial networks. DRP1 loss or mutation leads to modified ER sheets and alters the interaction between ER sheets and mitochondria, disrupting RRBP1-SYNJ2BP interaction. Importantly, mtDNA distribution and replication were rescued by promoting ER sheets-mitochondria contact sites. Our work identifies the role of ER sheet-mitochondria contact sites in regulating mtDNA replication and distribution.


The Evolving Landscape of Drug Therapies for Sickle Cell Disease.
Although sickle cell disease can be cured using allogeneic hematopoietic stem cell transplantation and possibly gene therapy and gene editing, these treatments remain unavailable to most patients. As understanding of the disease pathophysiology increases, progress is being made in developing drug therapies. Hydroxyurea, l-glutamine, crizanlizumab, and voxelotor are currently approved by the US Food and Drug Administration, with multiple others at various stages of testing. With the limited efficacy of individual agents, combinations of agents will likely be required for optimal outcomes. Clinical and surrogate endpoints, other than vaso-occlusive crisis, are increasingly being considered in the evaluation of novel drugs.


Targeted nanoparticles towards increased L cell stimulation as a strategy to improve oral peptide delivery in incretin-based diabetes treatment.
The delivery of therapeutic peptides via the oral route remains one of biggest challenges in the pharmaceutical industry. Recently, we have described an alternative improved drug delivery system for peptide delivery via the oral route, consisting of a lipidic nanocapsule. Despite the striking effects observed, it is still essential to develop strategies to strengthen the nanocarriers' glucagon-like peptide-1 (GLP-1) secretory effect of the nanocarrier and/or prolong its antidiabetic effect in vivo to facilitate its translation into the clinic. For this purpose, we developed and compared different fatty acid-targeted lipid and polymeric nanoparticles and evaluated the L cell stimulation induced by the nanocarriers in murine L cells in vitro and in normal healthy mice in vivo. We further examined the antidiabetic effect in vivo in an obese/diabetic mouse model induced by high-fat diet feeding and examined the effect of the oral administration frequency. Among the tested nanocarriers, only lipid-based nanocarriers that were surface-modified with DSPE-PEG2000 on the surface were able to significantly strengthen the biological effect of the nanocarriers. They increased endogenous GLP-1 levels up to 8-fold in vivo in normoglycemic mice. Moreover, they effectively prolonged the in vivo antidiabetic effect by normalizing the plasma glucose levels in obese/diabetic mice following long-term treatment (one month). Ultimately, the targeted nanocarriers were as effective when the administration frequency was reduced from once daily to once every other day.


The Unusual Cause of Cardiac Tamponade.
We present a previously healthy young man with cardiac tamponade. He underwent emergency pericardiocentesis. The pericardial fluid was exudative, and Salmonella sp. was grown on both pericardial and blood cultures. Further investigations revealed that this patient had classical Hodgkin lymphoma, which explains his immunocompromised state predisposing him to this infection. (Level of Difficulty: Advanced.).


The self-activated radical doping effects on the catalyzed surface of amorphous metal oxide films.
In this study, we propose a self-activated radical doping (SRD) method on the catalyzed surface of amorphous oxide film that can improve both the electrical characteristics and the stability of amorphous oxide films through oxidizing oxygen vacancy using hydroxyl radical which is a strong oxidizer. This SRD method, which uses UV irradiation and thermal hydrogen peroxide solution treatment, effectively decreased the amount of oxygen vacancies and facilitated self-passivation and doping effect by radical reaction with photo-activated oxygen defects. As a result, the SRD-treated amorphous indium-gallium-zinc oxide (a-IGZO) thin film transistors (TFTs) showed superior electrical performances compared with non-treated a-IGZO TFTs. The mobility increased from 9.1 to 17.5 cm2/Vs, on-off ratio increased from 8.9 × 107 to 7.96 × 109, and the threshold voltage shift of negative bias-illumination stress for 3600 secs under 5700 lux of white LED and negative bias-temperature stress at 50 °C decreased from 9.6 V to 4.6 V and from 2.4 V to 0.4 V, respectively.


Structural vaccinology approach to investigate the virulent and secretory proteins of Bacillus anthracis for devising anthrax next-generation vaccine.
Communicated by Ramaswamy H. Sarma.


A simple, quick and reliable method for TEM cross-section preparation of ceramic oxide films on thin metal substrates.
We present a preparation method of cross-sectional thin foils for transmission electron microscopy (TEM). Samples are 0.1-1 m thick ceramic oxide films (CeO2, CeO2-YBa2Cu3O7 and CeO2-ZrO2/YO2-YBa2Cu3O7) epitaxially grown on 30-100 m highly textured nickel substrates. This method includes gluing the sample between a copper oxide dummy and a silicon dummy, followed by mechanical polishing and conventional ion milling. TEM cross-sectional samples obtained with this selection of dummies are electron-transparent up to a few tens of m parallel to the film surface. Several layer structures were analyzed by TEM and the results are shown. The preparation technique described here can be applied to any type of oxide film deposited on thin metal substrates.


The 2005 Food Guide Pyramid: an opportunity lost?
Dietary quality has a vital role in the prevention of chronic disease. In 2005, the US Department of Agriculture released a new food guide, MyPyramid, because the previous pyramid was in substantial discordance with current scientific evidence. The US Department of Agriculture pyramids are the most visible source of US nutrition policy and dietary guidance and it is, therefore, imperative they provide scientifically derived recommendations for a healthy diet. Unfortunately, MyPyramid strays from much of the evidence generated through years of research and, in our opinion, fails to provide the public with clear information about healthy food choices. In this Review, we discuss the policy and process behind the development of MyPyramid, assess the current evidence linking diet to chronic diseases, including cardiovascular disease, cancer and diabetes, and suggest potential alternatives for dietary recommendations.


The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation.
Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent data implicate a critical function for hemoglobin and the erythrocyte in regulating the activity of NO in the vascular compartment. Intravascular hemolysis releases hemoglobin from the red blood cell into plasma (cell-free plasma hemoglobin), which is then able to scavenge endothelium-derived NO 600-fold faster than erythrocytic hemoglobin, thereby disrupting NO homeostasis. This may lead to vasoconstriction, decreased blood flow, platelet activation, increased endothelin-1 expression (ET-1), and end-organ injury, thus suggesting a novel mechanism of disease for hereditary and acquired hemolytic conditions such as sickle cell disease and cardiopulmonary bypass. Furthermore, therapy with NO gas inhalation or infusion of sodium nitrite during hemolysis may attenuate this disruption in vasomotor balance by oxidizing plasma cell-free hemoglobin, thereby preventing the consumption of endogenous NO and the associated pathophysiological changes. In addition to providing an NO scavenging role in the physiological regulation of NO-dependent vasodilation, hemoglobin and the erythrocyte may deliver NO as the hemoglobin deoxygenates. While this process has previously been ascribed to S-nitrosated hemoglobin, recent data from our laboratories suggest that deoxygenated hemoglobin reduces nitrite to NO and vasodilates the human circulation along the physiological oxygen gradient. This newly described role of hemoglobin as a nitrite reductase is discussed in the context of blood flow regulation, oxygen sensing, and nitrite-based therapeutics.


The reproducible observation of unstained embedded cellular material in thin sections: visualisation of an integral membrane protein by a new mode of imaging for STEM.
The contrast on micrographs obtained by conventional imaging in the conventional transmission electron microscope and in the scanning transmission electron microscope (STEM) (brightfield and darkfield) reflects mainly the variations of the mass-density and of the thickness of the specimen. The density differences in resin-embedded, unstained materials are too small to give enough contrast when compared to that produced by the surface perturbations introduced by sectioning. By darkfield imaging, therefore, this variable surface relief does not lead reproducibly to interpretable micrographs of high quality. Imaging by the ratio of elastically over inelastically scattered electrons in the STEM (Z-contrast) depends primarily on the atomic composition of the material. We present here the first experimental tests of theoretical predictions with thin sections; Z-contrast micrographs of septate junctions reveal the transmembrane proteins which are not visible in uranyl acetate stained sections viewed by conventional brightfield imaging.


Structural and functional relationships between epidermal Langerhans cells and dendritic cells.
Langerhans cells are dendritically shaped MHC-class II-bearing leukocytes which reside in the epidermis. During short-term culture, they develop into cells that are virtually indistinguishable from lymphoid dendritic cells with respect to morphology and phenotype, as well as function. It is hypothesized that Langerhans cells in situ represent immature precursors of dendritic cells.


Gilteritinib-induced severe immune-related enteritis: a possible case report.
Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a 'possible' cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.


Emotional intelligence in undergraduate medical students: a scoping review.
To perform a scoping review to determine what is known about emotional intelligence (EI) in undergraduate medical education (UME). Two main questions were asked: A. What medical student characteristics are associated with EI? Are there correlations with demographic or other factors? B. What research studies have been done on EI in UME? For example, is there evidence EI changes over time as a result of personal experiences? Should EI be used as an admission criterion? Can EI improve as a result of experiences or deliberate interventions? The authors searched four databases (PubMed, PsycInfo, Education Resources Information Center, and Web of Science) for all papers published up to and including December 2020. Two reviewers independently screened articles to determine if they met inclusion criteria. All authors extracted and analyzed data. A set of 1520 papers on the topic of emotional intelligence was identified, with 119 papers meeting inclusion criteria. Most studies were done at international locations with only 17 done at US medical schools. Seventy-five were cohort or cross-sectional studies. Study populations were mixed among the studies, with year of medical study, inclusion of other healthcare students, and participation rates among the inter-study differences noted. Numerous gaps in the literature on EI exist with several points being clear: (1) there is disagreement on the definition of EI, (2) it is undetermined whether EI is a trait or an ability, and (3) there is marked variability among the instruments used to measure EI. It is also becoming apparent that using EI determination may be helpful as a component of the admission process, higher EI is likely related to improved clinical reasoning, and higher EI contributes to more effective stress management.


Noncoding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability.
Most noncoding regions of the human genome do not harbor any annotated element and are even not marked with any epigenomic or protein binding signal. However, an overlooked aspect of their possible role in stabilizing 3D chromatin organization has not been extensively studied. To illuminate their structural importance, we started with the noncoding regions forming many 3D contacts (referred to as hubs) and performed a CRISPR library screening to identify dozens of hubs essential for cell viability. Hi-C and single-cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and affect the expressions of distal genes. This study revealed the 3D structural importance of noncoding loci that are not associated with any functional element, providing a previously unknown mechanistic understanding of disease-associated genetic variations (GVs). Furthermore, our analyses also suggest a possible approach to develop therapeutics targeting disease-specific noncoding regions that are critical for disease cell survival.


Fatal human herpes virus 6B myocarditis: Postmortem diagnosis of HHV-6B based on CD134+ T-cell tropism.
Human herpes virus 6 (HHV-6) is one of the most important pathogens of viral myocarditis, and is often responsible for sudden death in young adults. A 59-year-old immunocompetent man died of serious lymphocytic myocarditis, and his peripheral blood sample showed HHV-6 DNAemia. Recently, HHV-6 cell entry and reactivation have been suggested to be regulated by the expression of specific CD receptors on T lymphocytes. Here, we report a case of HHV-6 myocarditis diagnosed using an experimental method focused on this unique cell tropism. The interaction between HHV-6 and CD expression was assessed using an immunofluorescence assay. Colocalization between HHV-6B and CD134 was detected in lymphocytes infiltrating the myocardium, which was highly suggestive of an active HHV-6B infection and could be a useful criterion for postmortem diagnosis of HHV-6B myocarditis in the acute phase.


Downregulation of Brain Gα12 Attenuates Angiotensin II-Dependent Hypertension.
Angiotensin II (Ang II) activates central Angiotensin II type 1 receptors to increase blood pressure via multiple pathways. However, whether central Gα proteins contribute to Ang II-induced hypertension remains unknown. We hypothesized that Angiotensin II type 1 receptors couple with Gα12 and/or Gαq to produce sympatho-excitation and increase blood pressure and downregulation of these Gα-subunit proteins will attenuate Ang II-dependent hypertension. After chronic infusion of Ang II (s.c. 350 ng/kg/min) or vehicle for 2 weeks, Ang II evoked an increase in Gα12 expression, but not Gαq in the rostral ventrolateral medulla of Sprague-Dawley rats. In other studies, rats that received Ang II or vehicle infusion s.c. were simultaneously infused i.c.v. with a scrambled (SCR) or Gα12 oligodeoxynucleotide (ODN; 50 µg/day). Central Gα12 ODN infusion lowered mean blood pressure in Ang II infused rats compared with SCR ODN infusion (14-day peak; 133 ± 12 vs. 176 ± 11 mm Hg). Compared to the SCR ODN group, Ang II infused rats that received i.c.v. Gα12 ODN showed a greater increase in heart rate to atropine, an attenuated reduction in blood pressure to chlorisondamine, and an improved baroreflex sensitivity. In addition, central Gα12 and Gαq ODN pretreatment blunted the pressor response to an acute i.c.v. injection of Ang II (i.c.v., 200 ng). These findings suggest that central Gα12 protein signaling pathways play an important role in the development of chronic Ang II-dependent hypertension in rats.


Gene amplification in methotrexate-resistant mouse cells. V. Intact amplified units can be transferred to and amplified in methotrexate-sensitive mouse L cells.
Wild-type mouse LtAp20 cells were treated with calcium phosphate-precipitated DNA or chromosomes from two highly Methotrexate (MTX)-resistant mouse lymphoma cell lines--EL4/8 and EL4/11. Transfections with purified MTX-resistant DNA produced colonies of LtAp20 cells resistant to 3 X 10(-8) M MTX, at about eight times the frequency with which resistant colonies arose in control transfections. DNA transfectants contained multiple copies of the dihydrofolate reductase (dhfr) gene, but other sequences characteristic of the donor DNA could not be detected. Transfections using isolated chromosomes were twice as efficient as those using purified DNA. Unlike DNA transfectants, over 90% of all chromosome transfectants took up large stretches of donor DNA intact and contained DNA sequences characteristic of donor DNA. Of chromosome transfectants selected for resistance to high levels of MTX (1 mM), 70% amplified a unit of DNA which was indistinguishable from that present in the donor cell. The results showed that large fragments of chromosomes (as opposed to purified DNA) can be taken up to recipient cells without detectable alteration to the fine structure of the DNA they contain. The results also support the notion that all amplified units within a MTX-resistant cell have the same overall complex DNA structure.


Influence of copper on expression of nirS, norB and nosZ and the transcription and activity of NIR, NOR and N2 OR in the denitrifying soil bacteria Pseudomonas stutzeri.
Reduction of the potent greenhouse gas nitrous oxide (N(2)O) occurs in soil environments by the action of denitrifying bacteria possessing nitrous oxide reductase (N(2)OR), a dimeric copper (Cu)-dependent enzyme producing environmentally benign dinitrogen (N(2)). We examined the effects of increasing Cu concentrations on the transcription and activity of nitrite reductase (NIR), nitric oxide reductase (NOR) and N2 OR in Pseudomonas stutzeri grown anaerobically in solution over a 10-day period. Gas samples were taken on a daily basis and after 6 days, bacterial RNA was recovered to determine the expression of nirS, norB and nosZ encoding NIR, NOR and N(2)OR respectively. Results revealed that 0.05 mM Cu caused maximum conversion of N(2)O to N(2) via bacterial reduction of N(2)O. As soluble Cu generally makes up less than 0.001% of total soil Cu, extrapolation of 0.05 mg l(-l) soluble Cu would require soils to have a total concentration of Cu in the range of, 150-200 μg g(-1) to maximize the proportion of N(2)O reduced to N(2). Given that many intensively farmed agricultural soils are deficient in Cu in terms of plant nutrition, providing a sufficient concentration of biologically accessible Cu could provide a potentially useful microbial-based strategy of reducing agricultural N(2)O emissions.


Control of germ cell nuclear behaviour at fertilization by Tetrahymena intermediate filament protein.
Intermediate filament protein [relative molecular mass (Mr) 49,000 (49K)] from the ciliated protozoan Tetrahymena has been shown to resemble intermediate filament proteins from mammalian cells in several respects, and to have a possible role in the oral morphogenesis preceding binary fission in Tetrahymena. Here, based on immunofluorescence localization of the 49K protein in Tetrahymena during the early stages of conjugation, we suggest that the protein is involved in some nuclear events, such as the production of four haploid nuclei by prezygotic divisions (meiosis), selection of one of the four meiotic products, formation of the gametic pronucleus by the mitotic division of the selected meiotic product, transfer of the gametic pronucleus across a cell-cell junction, and zygote formation by pronuclear fusion.


Public wellbeing analytics framework using social media chatter data.
Public wellbeing has always been crucial. Many governments around the globe prioritize the impact of their decisions on public wellbeing. In this paper, we propose an end-to-end public wellbeing analytics framework designed to predict the public's wellbeing status and infer insights through the continuous analysis of social media content over several temporal events and across several locations. The proposed framework implements a novel distant supervision approach designed specifically to generate wellbeing-labeled datasets. In addition, it implements a wellbeing prediction model trained on contextualized sentence embeddings using BERT. Wellbeing predictions are visualized using several spatiotemporal analytics that can support decision-makers in gauging the impact of several government decisions and temporal events on the public, aiding in improving the decision-making process. Empirical experiments evaluate the effectiveness of the proposed distant supervision approach, the prediction model, and the utility of the produced analytics in gauging the public wellbeing status in a specific context.


The Effect of Crystal Defects on 3D High-Resolution Diffraction Peaks: A FFT-Based Method.
Forward modeling of diffraction peaks is a potential way to compare the results of theoretical mechanical simulations and experimental X-ray diffraction (XRD) data recorded during in situ experiments. As the input data are the strain or displacement field within a representative volume of the material containing dislocations, a computer-aided efficient and accurate method to generate these fields is necessary. With this aim, a current and promising numerical method is based on the use of the fast Fourier transform (FFT)-based method. However, classic FFT-based methods present some numerical artifacts due to the Gibbs phenomenon or "aliasing" and to "voxelization" effects. Here, we propose several improvements: first, a consistent discrete Green operator to remove "aliasing" effects; and second, a method to minimize the voxelization artifacts generated by dislocation loops inclined with respect to the computational grid. Then, we show the effect of these improvements on theoretical diffraction peaks.


Digestion of uncrushed leaf tissues by leaf-snipping larval Lepidoptera.
Cynodon dactylon (Poaceae) leaf pieces recovered from the frass of final-instar Paratrytone melane larvae (Lepidoptera: Hesperiidae) were composed of 14-22 percent crushed cells and 78-86 percent uncrushed cells, yet approximate digestibilities of soluble carbohydrates and protein averaged 78 and 88 percent, respectively. Therefore, nutrients from uncrushed cells were extracted by P. melane. The ability of P. melane and another leaf-snipping lepidopteran, Pseudaletia unipuncta (Noctuidae), to digest the contents of uncrushed bundle sheath and mesophyll cells in C. dactylon was examined with transmission electron microscopy. Organelles and plasma membranes were digested in the foreguts and midguts of both species. These findings suggest that nutrients in uncrushed leaf cells may be extracted through plasmodesmata and cell wall pores after membranes are digested. The generality of leaf-snipping, vis-a-vis leaf crushing, among larval Lepidoptera was assessed by surveying the mandible morphologies of 202 species. In 82 percent of the species surveyed only incisor regions were present. I conclude that leaf-snipping is a common mode of feeding among phytophagous Lepidoptera and that the digestion of cell contents is efficient despite the fact that few of the cells of ingested plant tissues are crushed.


Ultrastructure of the fetal rat anterior pituitary gland as term and during prolonged gestation.
The ultrastructure of the fetal rat anterior pituitary gland is described at term (day 22) and during experimentally prolonged gestation (days 23, 24, 25). The latter was achieved by daily subcutaneous injections of five mg progesterone to gravid females from the twentieth through the twenty-fourth day. Using morphological criteria for classifying pituitary cells (Moriarty, '73), six different types were observed: thyrotrophs, gonadotrophs, corticotrophs, mammotrophs, somatotrophs and non-granulated cells. During prolonged gestation (days 24 and 25 only), cells designated as corticotrophs revealed changes suggesting increased activity, i.e.,proliferation and dilation of the endoplasmic reticulum, dilated Golgi membranes and a redction of secretory granules. In addition, meconium staining , which is indicative of fetal distress, was also observed on days 24 and 25. The ultrastructural changes noted suggest an increased in corticotroph activity due to fetal hypoglycemia and hypoxia which are known to occur as a result of placental insufficiency during prolonged gestation (Roux et al., '64; Vorherr, '75; Thliveris, '76.


Evanescent wave fluorescence biosensor combined with DNA bio-barcode assay for platelet genotyping.
An evanescent wave fluorescence biosensor was combined with a DNA bio-barcode assay to resolve problems met in detection of poor biologic samples. Human platelet antigen (HPA) genotyping was used as a demonstrator. Our bio-barcode assay was based on magnetic carboxylatex particles and non-magnetic carboxylatex particles, both functionalized with oligonucleotides. It was assessed for detecting 84mer synthetic oligonucleotides as targets. The assay allows to specifically detect single nucleotide polymorphism with a detection limit of 2 pM of target nucleic acids. The fluorescence detection is achieved in 150 s.


Silent myocardial ischemia in patients undergoing peripheral vascular surgery: incidence and association with perioperative cardiac morbidity and mortality.
Atherosclerosis is a systemic disorder and coronary artery disease is highly prevalent in patients treated for lower-extremity obstructive vascular disease. Myocardial ischemia and infarction represent the most frequent and most clinically important complications of surgical procedures for lower-extremity revascularization. Despite attempts in several areas, no practical, sensitive, and specific method for identifying patients at highest risk for myocardial events postoperatively has been found before now. This study reports observations on a consecutive series of 50 patients who underwent continuous perioperative electrocardiographic monitoring with a microprocessor-based electrocardiographic ischemia monitor. Thirty-eight percent of the patients were found to have episodes of ischemia; most of these episodes were painless and would not otherwise have been recognized. Ischemia was most prominent in the postoperative rather than the preoperative or intraoperative phases. Tachycardia was often associated with ischemia. Significantly more cardiac-related morbidity and deaths occurred in patients who were documented to have silent myocardial ischemia. In fact, no cardiac events occurred in the 31 patients without ischemia (p less than 0.02). This type of ischemia monitoring represents a potential method for segregating patients at high risk for cardiac-related morbidity and death during lower-extremity revascularization.


Abdominal examination using pressure pain threshold algometer reflecting clinical characteristics of complementary and alternative medicine in Korea: A systematic review and a brief proposal.
A review was conducted to determine a pressure algometry measurement during abdominal examination that reflects clinical settings of traditional Korean medicine. After reviewing the previous studies, we have proposed a reference index, common posture and method for performing pressure algometry during abdominal examination. Keyword search using eight databases was performed. To identify the characteristics of pressure algometry during abdominal examination, keywords (e.g., abdomen, abdominal examination) were searched in national Korean databases, including Korean studies Information System (KISS), Research Information Sharing Service (RISS), and Oriental Medicine Advanced Searching Integrated System (OASIS). To examine the methods of measuring pressure pain threshold (PPT) with validity and reliability, combination keywords (e.g., PPT, pressure algometry, pressure pain, validity, reliability) were searched in Pubmed, Cochrane library, Google scholar, Ovid Embase, and China Knowledge Resource Integrated Database (CNKI). A total of 652 articles were identified, and 22 relevant articles were included. The following main indices are proposed as a standardized pressure algometry method during abdominal examination: unit of measurements, measuring tools, target locations, pressure area, pressure rate, posture of patients, and evaluators. Based on the results of the review combined with clinical practice, useful indices for pressure algometer during abdominal examination were derived (target location: CV 12, unit of measurement: MPa, pressure area: 4 cm2, pressure rate: 0.098 MPa/s, posture of patient: supine position, number, and intervals of measurement: three consecutive measurements at intervals of 30 seconds, 5 minutes rest prior to commencement). Postures and method sequence of pressure algometry during abdominal examination are also proposed. Using standardized indices, postures and method for abdominal examination in clinical settings will help make objective assessments.


Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.
Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD (HR = 1.31, P < 0.0001) than in patients with NASH (HR = 1.73, P < 0.0001) or HCV (HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease (MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT.


Development of a sensitive, multi-assay platform to monitor low levels of HBV DNA and pgRNA in patients with chronic hepatitis B virus infection.
HBV cure rates remain low despite prolonged nucleos(t)ide (NrtI) therapy, likely due to persistent residual viral replication and an inability to eliminate covalently closed circular DNA (cccDNA). Therapies with novel mechanisms of action against hepatitis B virus (HBV) are being explored with the goal of achieving sustained off-treatment response and a functional cure without requiring lifelong therapy. Recent studies have indicated that serum HBV DNA levels (a biomarker for viral replication) combined with serum pregenomic RNA (pgRNA) levels (a surrogate for intrahepatic cccDNA transcriptional activity), may provide a better prediction for the risk of liver-related complications. Current HBV DNA assays, such as the COBAS AmpliPrep/COBAS TaqMan HBV test v2.0, quantitate HBV DNA down to 20 IU/mL, but are not able to monitor loss of residual virus in patients on NrtI therapy. There are no commercially available assays approved to detect serum/plasma HBV pgRNA levels. We have developed a multi-assay panel of highly sensitive nucleic acid assays designed to monitor levels of HBV DNA, pgRNA and total nucleic acids (TNA, composite DNA + pgRNA) in clinical specimens and to monitor changes during treatment with new antiviral combination regimens.


Metastases to retroperitoneal or lateral pelvic lymph nodes indicated unfavorable survival and high pelvic recurrence rates in a cohort of 102 patients with low rectal adenocarcinoma.
The Japanese protocol considers metastases to retroperitoneal or lateral pelvic lymph nodes (RLPNs) as regional lymphatic dissemination in rectal adenocarcinoma patients and recommends total mesorectal excision (TME) plus retroperitoneal and lateral pelvic lymphadenectomy (RLPL). Western protocols consider RLPN metastases to indicate advanced disease. All outcomes were evaluated among a cohort of 102 rectal adenocarcinoma patients subjected to TME plus RLPL with a nerve-preserving technique. Chemoradiotherapy was delivered in patients with T3/T4 tumors or metastases to mesorectal nodes or RLPNs. Surgical mortality was 3.9%; surgical morbidity was 33.3%. Incidence of RLPN metastases was 17%. Pelvic recurrence was 14.5% in pT3/pT4 patients and 29.4% in patients with metastases to RLPNs. Survival at 50 months was 28.6% in patients with RLPN metastases versus 84.5% in patients without RLPN metastases (P < 0.0001). Survival at 50 months was 33.3% in TME stage II patients with RLPN metastases versus 97.1% in TME stage II patients without RLPN metastases (P < 0.0001), and 21.9% in TME stage III patients with RLPN metastases versus 68.9% in TME stage III patients without RLPN metastases (P = 0.0237). Patients who underwent RLPL had acceptable morbidity and mortality rates. Metastases to RLPNs indicated unfavorable survival and considerable pelvic recurrence rates.


Scalable Production of iPSC-Derived Human Neurons to Identify Tau-Lowering Compounds by High-Content Screening.
Lowering total tau levels is an attractive therapeutic strategy for Alzheimer's disease and other tauopathies. High-throughput screening in neurons derived from human induced pluripotent stem cells (iPSCs) is a powerful tool to identify tau-targeted therapeutics. However, such screens have been hampered by heterogeneous neuronal production, high cost and low yield, and multi-step differentiation procedures. We engineered an isogenic iPSC line that harbors an inducible neurogenin 2 transgene, a transcription factor that rapidly converts iPSCs to neurons, integrated at the AAVS1 locus. Using a simplified two-step protocol, we differentiated these iPSCs into cortical glutamatergic neurons with minimal well-to-well variability. We developed a robust high-content screening assay to identify tau-lowering compounds in LOPAC and identified adrenergic receptors agonists as a class of compounds that reduce endogenous human tau. These techniques enable the use of human neurons for high-throughput screening of drugs to treat neurodegenerative disease.


Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9/G NSCLC cells.
Gefitinib (Gef) provides clinical benefits to non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, acquired resistance (AR) is a major obstacle to effective Gef therapy. This study demonstrated that resveratrol (Res) could synergize with Gef to inhibit the proliferation of Gef-resistant NSCLC cells. The underlying mechanisms of synergism were investigated, and the results showed that cotreatment with Gef and Res could inhibit EGFR phosphorylation by increasing intracellular Gef accumulation through the impairment of Gef elimination from PC9/G cells. Consistently, CYP1A1 and ABCG2 expression were inhibited. Meanwhile, the cotreatment significantly induced cell apoptosis, autophagy, cell cycle arrest and senescence accompanied by increased expression of cleaved caspase-3, LC3B-II, p53 and p21. Further studies revealed that autophagy inhibition enhanced apoptosis and abrogated senescence while apoptosis inhibition had no notable effect on cell autophagy and senescence during cotreatment with Gef and Res. These results indicated that in addition to apoptosis, senescence promoted by autophagy contributes to the antiproliferation effect of combined Gef and Res on PC9/G cells. In conclusion, combined treatment with Gef and Res may represent a rational strategy to overcome AR in NSCLC cells.


Allozyme relationships among ten species of Rhodniini, showing paraphyly of Rhodnius including Psammolestes.
Genetic relationships among 10 species of bugs belonging to the tribe Rhodniini (Hemiptera: Reduviidae), including some important vectors of Chagas disease, were inferred from allozyme analysis of 12 enzyme loci (out of 21 enzyme systems examined), using agarose gel electrophoresis. These species formed two clusters: one comprising Rhodnius brethesi, R. ecuadoriensis, R. pallescens and R. pictipes; the other with Psammolestes tertius, Rhodnius domesticus and the Rhodnius prolixus group comprising R. nasutus, R. neglectus, R. prolixus and R. robustus. The resulting tree was [((R. ecuadoriensis, R. pallescens) R. brethesi) R. pictipes], [R. domesticus (P. tertius [(R. nasutus, R. neglectus) (R. prolixus, R. robustus)])]. Rhodnius nasutus and R. neglectus differed by only one locus, whereas no diagnostic loci were detected between R. prolixus and R. robustus (22 loci were analysed for these four species), despite considerable DNA sequence divergence between species in each of these pairs. Allozymes of the R. prolixus group showed greater similarity with Psammolestes tertius than with other Rhodnius spp., indicating that Rhodnius is paraphyletic and might include Psammolestes.


Characterization, evaluation of nutritional parameters of Radix isatidis protein and its antioxidant activity in D-galactose induced ageing mice.
Radix isatidis (Isatis indigotica Fort.) is an ancient medicinal herb, which has been applied to the prevention and treatment of influenza virus since ancient times. In recent years, the antioxidant activity of Radix isatidis has been widely concerned by researchers. Our previous studies have shown that Radix isatidis protein (RIP) has good antioxidant activity in vitro. In this study, the composition of the protein was characterized and its antioxidant activity in vivo was evaluated. The model of oxidative damage in mice was established by subcutaneous injection of D-galactose for 7 weeks. Commercially available kits were used to determine the content of protein and several oxidation indexes in different tissues of mice. The tissue samples were stained with hematoxylin and eosin (H&E) and the pathological changes were observed by optical microscope. The molecular weight of RIP was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The amino acid composition of RIP was determined by a non-derivative method developed by our research group. RIP significantly increased the activities of antioxidant enzymes such as SOD, CAT, GSH-Px and total antioxidant capability (TAOC) but decreased the MDA level in the serum, kidney and liver. H&E stained sections of liver and kidney revealed D-galactose could cause serious injury and RIP could substantially attenuate the injury. The analysis of SDS-PAGE showed that four bands with molecular weights of 19.2 kDa, 21.5 kDa, 24.8 kDa and 40.0 kDa were the main protein components of RIP. The results suggested that RIP had excellent antioxidant activity, which could be explored as a health-care product to retard aging and a good source of protein nutrition for human consumption.


Spectral domain optical coherence tomography findings of patients under treatment for pediatric acute lymphoblastic leukemia.
To investigate the use of spectral domain optical coherence tomography (SD-OCT) findings in pediatric acute lymphoblastic leukemia (ALL) patients. Children that were diagnosed with precursor B-cell ALL and classified as belonging to the medium-risk group for relapse were selected for this study. Individuals who were in continuous remission and on maintenance therapy were included in the study group. Cases that had central nervous system involvement were excluded. Age-matched, otherwise healthy children were selected for the control group. Each study participant underwent a comprehensive eye examination and SD-OCT evaluation. Thickness measurements were made within the retinal nerve fiber layer (RNFL), central macula, posterior polar, and peripapillary choroid. A total of 112 eyes of 56 children were included: 54 eyes in the study group and 58 in the control group. Compared to the control group, subfoveal and temporal choroidal thicknesses of the posterior pole were significantly thinner in the study group (P < 0.005). Similarly, peripapillary choroidal thicknesses were significantly thinner in most sectors of the study group (P < 0.005). There were no major differences between groups in terms of central macular thicknesses and overall RNFL thicknesses. Evidence of choroidal attenuation was found in this subgroup of pediatric ALL patients. Further studies are warranted to clarify the utility of SD-OCT in detecting subclinical ocular involvement and monitoring treatment response and risk of relapse in patients with pediatric leukemia.


Natural agglutinins to hidden membrane components in the bovine erythrocytes.
Digestion of bovine erythrocytes (BE) with trypsin (Tr) or chymotrypsin (CTr) revealed 'Tr and CTr specific' receptors respectively. These receptors reacted with all the isologous, including the autologous, sera. The titres of agglutinability varied for the Tr-digested BE from 1:2 to 1:64 and from zero to 1:128 for the CTr-digested BE. However, the variation between the members of monozygous twin pairs (MZ) in no case exceeded +/- 2 score units, the error limits. Agglutination of the CTr-digested BE gave with the PHA lectin very similar, (r = 0.964) results to that which was obtained with the isologous sera. The titre of agglutinins showed concordance in all the sera of MZ pairs when tested against the neuraminidase-digested human erythrocytes and the Tr or CTr-digested BE. Their variance due to differences varied between MZ pairs from 60.4 to 74.3%.


Purification and properties of the Ascaris pyruvate dehydrogenase complex.
The pyruvate dehyhdrogenase complex (pyruvate:lipoate oxidoreductase (decarboxylating and acceptor-acetylating), EC 188.8.131.52) has been isolated from Ascaris muscle mitochondria and purified to near homogeneity by differential centrifugation, (NH4)2SO4 fractionation and calcium phosphate gel-cellulose chromatography. It is similar in shape, size and physical characteristics to pyruvate dehydrogenase complexes isolated from mammalian sources. It has an absolute dependence on CoA, NAD+ and pyruvate for activity and is competitively inhibited by acetyl-CoA and NADH. However, much higher NADH/NAD+ ratios are necessary to inhibit activity, suggesting regulation by the more reduced state of the pyridine nucleotide pool in Ascaris mitochondria.


In vivo acute physiological stress induced by BHC on hemolymph biochemistry of Oziotelphusa senex senex, the Indian rice field crab.
Indian rice field crabs, exposed to a lethal concentration (LC50/24 h = 39 mg/l) of benzene hexachloride (BHC) to study acute toxic effects, showed changes in hemolymph glucose and protein. The effect of BHC resulted in hyperglycemia and hyperproteinemia.


Influence of Ca2+ and substance P on the (Ca Mg) ATPase (EC 184.108.40.206) activity of synaptosomes from different areas of rat brain.
The influence of SP in vitro on the (Ca Mg) ATPase activity of synaptosomes from cerebral cortex, hippocampus, midbrain and thalamus with hypothalamus of rats was studied. It was confirmed that SP increases the activity of the enzyme from hippocampus, midbrain and thalamus with hypothalamus. A condition of this stimulation is the maintenance of Ca2+ concentration between 1 and 2 X 10(-4) M. Ca2+ concentration above and below the optimal (0.2 mM), reduced the SP stimulation of (Ca Mg) ATPase activity.


A Scoping Review of the Literature on the Relationship Between Social and Structural Determinants of Health and Neurosurgical Outcomes.
In the present study, we performed a scoping review of the social and structural determinant of health (SSDOH)-related academic literature from neurosurgery. To identify the studies to include or consider for our systematic review, we worked with a medical librarian to develop detailed search strategies for each database. The search was limited to studies reported from January 1, 1990 to December 3, 2020. All reports retrieved from the database searches were exported and stored in EndNote X.9 bibliographic and reference manager (Clarivate, Philadelphia, Pennsylvania, USA). The reports were screened by title and abstract independently by two of the co-authors (G.G. and A.O.). Any disagreements between the 2 reviewers were resolved by a third reviewer, who was unaware of the decisions of the primary reviewers. The search resulted in 5940 studies. After exclusions during data extraction, 99 studies remained for the final analysis. From the 99 included studies, 6 social determinants were analyzed, with 3 studies evaluating the highest level of educational attainment, 14 studies evaluating gender, 52 studies evaluating race, and 41 studies evaluating economic stability. Studies referencing SSDOH were found in 8 subspecialties, with 40 studies in spine surgery, 4 studies in functional neurosurgery, 14 studies in vascular neurosurgery, 27 studies in cranial oncology, 5 studies in spinal oncology, 5 studies in pediatric neurosurgery, 1 study in trauma, and 3 studies in general/unspecified subspecialties. Research gaps included the remaining neurosurgical subspecialties and numerous other SSDOHs. These gaps should be areas of future study, with the goal of aligning research with new healthcare initiatives and ensuring consideration of SSDOHs.


A retrospective study of locally advanced cervical cancer cases treated with CT-based 3D-IGBT compared with 2D-IGBT.
To retrospectively review locally advanced cervical cancer (CC) cases treated with three-dimensional image-guided brachytherapy (3D-IGBT) and two-dimensional (2D)-IGBT. Patients with Stage IB-IVa CC who underwent intracavitary irradiation between 2007 and 2021 were divided into the 3D-IGBT and 2D-IGBT groups. Local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and gastrointestinal toxicity (G3 or more) were investigated at 2/3 years post-treatment. Seventy-one patients in the 2D-IGBT group from 2007 to 2016 and 61 patients in the 3D-IGBT group from 2016-2021 were included in the study. The median follow-up period was 72.7 (4.6-183.9) months in the 2D-IGBT group and 30.0 (4.2-70.5) months in the 3D-IGBT group. The median age was 65.0 (40-93) years in the 2D-IGBT group and 60.0 (28-87) years in the 3D-IGBT group, but there was no difference in FIGO stage, histology, or tumor size between the groups. In treatment, the median A point dose was 56.1 (40.0-74.0) Gy in the 2D-IGBT group and 64.0 (52.0-76.8) Gy in the 3D-IGBT group (P < 0.0001), and the proportion of patients who underwent chemotherapy more than five times was 54.3% in the 2D-IGBT group and 80.8% in the 3D-IGBT group (P = 0.0004). The 2/3-year LC, DMFS, PFS, and OS rates were 87.3%/85.5%, 77.4%/65.0%, 69.9%/59.9%, and 87.9%/77.9% in the 2D-IGBT group, and 94.2%/94.2%, 81.8%/81.8%, 80.5%/80.5%, and 91.6%/83.0% in the 3D-IGBT group, respectively. A significant difference was observed in PFS (P = 0.02). There was no difference in gastrointestinal toxicity, but there were four intestinal perforations in the patients from the 3D-IGBT group, three of whom had a history of bevacizumab treatment. The 2/3-year LC of the 3D-IGBT group was excellent and PFS also tended to improve. Care should be taken with concomitant use of bevacizumab after radiotherapy.


Clinical and primary evidence of silver diamine fluoride on root caries management.
Root caries is a growing problem for the worldwide aging population. Silver diamine fluoride (SDF) contains high concentrations of silver and fluoride ions, which prevents and arrests root caries, as well as dentin caries in the primary teeth of young children. Unlike other fluoride products that mainly reduce the formation of new carious lesions, 38% SDF is an effective agent that can efficiently arrest the carious process, remineralize the decayed dental tissues, and protect the tooth structure against the formation of new caries lesions. The use of SDF can result in more caries-resistant tooth structures. Despite these merits, its clinical disadvantages are the deep penetration of silver ions and sequential formation of silver compounds, which cause esthetic concern due to the discoloration and impaired efficacy of dentin bonding after using SDF. Thus, this narrative review, by addressing the primary experimental results and clinical applications of SDF on root caries, proposes management methods for root caries in conjunction with the application of SDF. We propose a two-visit treatment protocol to take advantage of the SDF application for root surface caries and utilize the discoloration caused by SDF.


Preventing hypoesthesia after a buccal plate fracture in a sagittal split procedure: A technical note.
If during a sagittal split osteotomy a buccal plate fracture occurs, it inevitably results in a time-consuming procedure with, in many cases, hypoesthesia of the mental region as a consequence of manipulation of the inferior alveolar nerve. We would like to present a novel technique to solve a (threatening) buccal plate fracture that is quick and easy to perform, and has thus far not resulted in hypoesthesia.


Nucleus of the solitary tract chemical stimulation induces extracellular norepinephrine release in the lateral and basolateral amygdala.
The NTS catecholaminergic neurons, activated by a variety of afferent stimuli, are ideally situated to coordinate afferent signaling to multiple brain regions. In particular, there is evidence that systemic epinephrine injections induce a significant increase of norepinephrine (NE) in the amygdala during enhanced memory, which can be disrupted by NTS chemical blockade or interruption of vagal afferents. The present experiment was conducted to obtain information about the levels of NE release induced by activation of the whole NTS, which projects to the lateral and basolateral amygdala. Therefore, we compared NE levels before and after general stimulation of the NTS and the amygdala in anesthetized rats, without any behavioral or vagal stimulation, to find out the degree of noradrenergic activation modulated by the NTS through all its projections to the lateral and basolateral amygdala, as well as the degree of noradrenergic activation which may occur locally in the amygdala through rapid and general activation of this structure.


Inhibition of forskolin-stimulated cAMP formation in vitro by paraoxon and chlorpyrifos oxon in cortical slices from neonatal, juvenile, and adult rats.
Parathion (PS) and chlorpyrifos (CPF) are organophosphorus insecticides, which elicit toxicity following biotransformation to the potent acetylcholinesterase inhibitors, paraoxon (PO) and chlorpyrifos oxon (CPO). Both oxons have also been shown to interact directly with muscarinic receptors coupled to inhibition of adenylyl cyclase. Immature animals are more sensitive than adults to the acute toxicity of PS and CPF but little is known regarding possible age-related differences in interactions between these toxicants and muscarinic receptors. We compared the inhibition of forskolin-stimulated cAMP formation by PO and CPO (1 nM-1 mM) in vitro in brain slices from 7-, 21-, and 90-day-old rats to the effects of well-known muscarinic agonists, carbachol and oxotremorine (100 microM). Both agonists inhibited cAMP formation in tissues from all age groups and both were more effective in adult and juvenile (20-26% inhibition) than in neonatal (12-13% inhibition) tissues. Atropine (10 microM) completely blocked agonist-induced inhibition in all cases. PO maximally inhibited (37-46%) cAMP formation similarly in tissues from all age groups, but atropine blocked those effects only partially and only in tissues from 7-day-old rats. CPO similarly inhibited cAMP formation across age groups (27-38%), but ATR was partially effective in tissues from all three age groups. Both oxons were markedly more potent in tissues from younger animals. We conclude that PO and CPO can directly inhibit cAMP formation through muscarinic receptor-dependent and independent mechanisms and that the developing nervous system may be more sensitive to these noncholinesterase actions.


Tobacco use is associated with increased rates of infection and revision surgery after primary superior labrum anterior and posterior repair.
Although the general health consequences of tobacco use have been well defined, the effects of perioperative tobacco use on arthroscopic shoulder procedures remain largely unknown. The purpose of this study is to use a national database to investigate the relationship between tobacco use and rates of superior labrum anterior and posterior (SLAP) repair failure and postoperative infection after primary SLAP repair compared with matched controls. A national private-payer insurance database was queried for patients who underwent arthroscopic primary SLAP from 2005-2012. These patients were divided into tobacco use and non-tobacco use cohorts using International Classification of Diseases, Ninth Revision coding. The non-tobacco use patients were then matched to the patients with coded tobacco use. Both cohorts were assessed for postoperative infection within 90 days and subsequent ipsilateral revision SLAP repair or biceps tenodesis within up to 7 years postoperatively. The incidences of revision SLAP repair or revision to a biceps tenodesis (P = .023) and postoperative infection (P = .034) were significantly higher in patients who used tobacco versus matched controls. SLAP repair in patients who use tobacco is associated with significantly increased rates of postoperative infection and revision SLAP repair or conversion to a biceps tenodesis.


Axonal transport of puromycin-sensitive aminopeptidase in rat sciatic nerves.
Axonal transport of puromycin-sensitive aminopeptidase (PSA), a putative neuropeptide degrading-enzyme which removes amino acid residues from the amino-terminal of neuropeptides, was examined in the proximal, middle, and distal segments of rat sciatic nerves using a double-ligation technique. The soluble fraction of each segment was partially purified by MonoQ column chromatography, and showed two peaks of aminopeptidase activity. One of the aminopeptidases was PSA. At 48 h after the ligations, a significant amount of the axonal transport of PSA activity was found in the proximal segment. Western blot analysis of the segments also showed that immunoreactive PSA in the proximal segment was 2.1-fold higher than that in the middle segment. Furthermore, the immunohistochemical analysis of the segments showed an increase of the immunoreactive PSA in the proximal segment in comparison with the enzyme in the distal segment, indicating that PSA is mainly transported by anterograde axonal flow. These results suggest that PSA plays a role in the metabolism of neuropeptides in nerve terminals or synaptic clefts.


Effect of the host genotype at a Porcine Reproductive and Respiratory Syndrome (PRRS) resistance marker on evolution of the modified-live PRRS vaccine virus in pigs.
Porcine reproductive and respiratory syndrome; Porcine reproductive and respiratory syndrome virus; PRRS; Whole genome sequencing; Quasispecies; WUR allele.


Effect of a National VHA Medical Scribe Pilot on Provider Productivity, Wait Times, and Patient Satisfaction in Cardiology and Orthopedics.
Section 507 of the VA MISSION Act of 2018 mandated a 2-year pilot study of medical scribes in the Veterans Health Administration (VHA), with 12 VA Medical Centers randomly selected to receive scribes in their emergency departments or high wait time specialty clinics (cardiology and orthopedics). The pilot began on June 30, 2020, and ended on July 1, 2022. Our objective was to evaluate the impact of medical scribes on provider productivity, wait times, and patient satisfaction in cardiology and orthopedics, as mandated by the MISSION Act. Cluster randomized trial, with intent-to-treat analysis using difference-in-differences regression. Veterans using 18 included VA Medical Centers (12 intervention and 6 comparison sites). Randomization into MISSION 507 medical scribe pilot. Provider productivity, wait times, and patient satisfaction per clinic-pay period. Randomization into the scribe pilot was associated with increases of 25.2 relative value units (RVUs) per full-time equivalent (FTE) (p < 0.001) and 8.5 visits per FTE (p = 0.002) in cardiology and increases of 17.3 RVUs per FTE (p = 0.001) and 12.5 visits per FTE (p = 0.001) in orthopedics. We found that the scribe pilot was associated with a decrease of 8.5 days in request to appointment day wait times (p < 0.001) in orthopedics, driven by a 5.7-day decrease in appointment made to appointment day wait times (p < 0.001), and observed no change in wait times in cardiology. We also observed no declines in patient satisfaction with randomization into the scribe pilot. Given the potential improvements in productivity and wait times with no change in patient satisfaction, our results suggest that scribes may be a useful tool to improve access to VHA care. However, participation in the pilot by sites and providers was voluntary, which could have implications for scalability and what effects could be expected if scribes were introduced to the care process without buy-in. Cost was not considered in this analysis but is an important factor for future implementation. ClinicalTrials.gov Identifier: NCT04154462.


The effects of different lookback periods on the sociodemographic structure of the study population and on the estimation of incidence rates: analyses with German claims data.
Defining incident cases has always been a challenging issue for researchers working with routine data. Lookback periods should enable researchers to identify and exclude recurrent cases and increase the accuracy of the incidence estimation. There are different recommendations for lookback periods depending on a disease entity of up to 10 years. Well-known drawbacks of the application of lookback periods are shorter remaining observation period in the dataset or smaller number of cases. The problem of selectivity of the remaining population after introducing lookback periods has not been considered in the literature until now. The analyses were performed with pseudonymized claims data of a German statutory health insurance fund with annual case numbers of about 2,1 million insured persons. Proportions of study population excluded due to the application of lookback periods are shown according to age, occupational qualification and income. Myocardial infarction and stroke were used to demonstrate changes in incidence rates after applying lookback periods of up to 5 years. Younger individuals show substantial dropouts after the application of lookback periods. Furthermore, there are selectivities regarding occupational qualification and income, which cannot be handled by age standardization. Due to selective dropouts of younger individuals, crude incidence rates of myocardial infarction and stroke increase after applying lookback periods. Depending on the income group, age-standardized incidence rates changed differentially, leading to a decrease and possible underestimation of the social gradient after applying lookback periods. Selectivity analyses regarding age and sociodemographic structure should be performed for the study population after applying lookback periods since the selectivity can affect the outcome especially in health care research. The selectivity effects might occur not only in claims data of one health insurance fund, but also in other longitudinal data with left- or right-censoring not covering the whole population. The effects may also apply to health care systems with a mix of public and private health insurance. A trade-off has to be considered between selectivity effects and eliminating recurrent events for more accuracy in the definition of incidence.


Effect of interferon and poly I: C on DNA fiber propagation in L 929 cells.
Autoradiographic analysis of DNA fiber replication was used to measure the rate of DNA propagation, the distances between initiation points of adjacent replicons and the direction of DNA propagation in L929 cells treated with either interferon or poly I: C, or untreated. Poly I:C ceased by 44% the rate of DNA propagation while the interferon had no effect. Poly I:C but not interferon reduced the mean distance between initiation points by 32%.


Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk.
UGT1A10 exhibits glucuronidating activity against metabolites of the tobacco smoke carcinogen, benzo(a)pyrene, and is expressed highly in numerous target tissues for tobacco-related cancers including the upper aerodigestive tract. The current study was conducted to determine the prevalence of genetic polymorphisms in the UGT1A10-specific region of the UDP-glucuronosyltransferase family 1A locus and their relationship with risk for orolaryngeal carcinoma. The authors analyzed UGT1A10-specific sequences in a population of black, white, and Asian individuals. Ten UGT1A10 alleles were identified by direct sequencing of UGT1A10 sequences amplified by polymerase chain reaction (PCR) using DNA purified from buccal cell swabs that were taken from individual subjects. In addition to three silent polymorphisms, three missense polymorphisms were found at codons 139 (Glu > Lys), 240 (Thr > Met), and 244 (Leu > Ile). Using PCR-restriction fragment length polymorphism analysis of buccal cell DNA, the prevalence of the UGT1A10(240Met) variant was less than 0.01% in whites and blacks. Similarly, the prevalence of both the UGT1A10(139Lys) and UGT1A10(244Ile) variants was less than 0.01% in whites but it was significantly higher (0.04 and 0.05, respectively, P < 0.01) in blacks. None of the missense UGT1A10 variants were found in any of the Asian individuals examined. In a case-control study of black individuals, a significant association with orolaryngeal carcinoma risk was found in persons with at least 1 UGT1A10(139Lys) allele (crude odds ratio, 0.29 [95% confidence interval, 0.10-0.81]; adjusted odds ratio, 0.20 [95% confidence interval, 0.05-0.87]). No association was observed for the codon 244 (Leu > Ile) polymorphism. The data from the current study show that the UGT1A10 gene has several low-frequency missense polymorphisms and that the codon 139 polymorphism is an independent risk factor for orolaryngeal carcinoma in blacks.


Food production in space from CO2 using microbial electrosynthesis.
The current food method in space is launching prepackaged food which is costly and unsustainable. Alternatives include growing crops and microalgae single cell protein (SCP) using artificial light photosynthesis, which are energy inefficient. Prepackaged food and microalgae food were compared to microbial electrosynthesis of acetic acid (MES-AA). Since the dominant cost of a space mission is the cost of launching mass, components of a system were converted to an equivalent mass, including power, heat rejection, and volume. Three-year roundtrip crewed missions were evaluated for the International Space Station, the Moon, and Mars. The average Equivalent System Mass (ESM) of MES-AA is 1.38x and 2.84x lower than prepackaged food and microalgae SCP, respectively. The expected electricity-to-calorie conversion efficiency of MES-AA is 19.8 %, consuming 3.45 kW to fully feed five astronauts; diets would realistically include multiple foods. MES-AA has a higher energy efficiency than any currently investigated resilient food in space. MES-AA can provide diet diversity at a lower cost than customarily storing prepackaged food or growing crops in space. Producing food while contributing to closed loop life support in space can contribute to reducing global catastrophic risk and is relevant in off-grid communities, like in rural Alaska.


Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear.
Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.


Renal Recovery and Mortality Risk among Patients with Hepatorenal Syndrome Receiving Chronic Maintenance Dialysis.
Kidney replacement therapy is controversial for patients with hepatorenal syndrome who may not be liver transplant candidates. Data surrounding the likelihood of recovery of kidney function and mortality after outpatient dialysis initiation in patients with dialysis-requiring hepatorenal syndrome could inform discussions between patients and providers. We performed a retrospective cohort study of patients with hepatorenal syndrome who were registered in the United States Renal Data System between 1996 and 2015 (n=7830) as receiving maintenance dialysis. We characterized patients with hepatorenal syndrome by recovery of kidney function using Fine and Gray models. We also examined hazard of recovery of kidney function and death among those with hepatorenal syndrome versus those with acute tubular necrosis (n=48,861) using adjusted Fine-Gray and Cox models, respectively. Of the patients with hepatorenal syndrome, 11% recovered kidney function. Those with higher likelihood of recovery were younger, non-Hispanic White, and had a history of alcohol use. Compared with patients with acute tubular necrosis, patients with hepatorenal syndrome as the attributed cause of kidney disease had a lower hazard of recovery (HR, 0.22; 95% CI, 0.21 to 0.24) and higher hazard of death within 1 year (HR, 3.10; 95% CI, 2.99 to 3.23) in fully adjusted models. Patients with hepatorenal syndrome receiving chronic maintenance dialysis had a lower likelihood of recovery of kidney function and higher mortality risk compared with patients with acute tubular necrosis. Among patients with hepatorenal syndrome, those most likely to recover kidney function were younger, had a history of alcohol use, and lacked comorbid conditions. These data may inform prognosis and discussions surrounding treatment options when patients with hepatorenal syndrome need chronic maintenance dialysis therapy.


Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities.
2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/micromol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were approximately 1-3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects ( approximately 50-400 revertants/micromol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at >or=1.9 microM). 4-A-2,6-DNBA was positive at 432 microM; the weakest effect was observed with 2,4,-DNBA (positive at >or=920 microM). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man.


[Pathophysiologic aspects of inflammatory and degenerative joint diseases].
Authors describe the physiological particularities of components of articular system (cartilage, synovialis, synovia, subchondral bone, ligamentous and neuromuscular apparatus). The essential resultant pathophysiological pattern in rheumatoid arthritis and osteoarthritis are demonstrated. Differences between temporary attendant synovitis in osteoarthritis and rheumatoid arthritis are pointed out.


Developmental distribution of platelet-derived growth factor in the mouse central nervous system.
Immunoblotting and immunohistochemical techniques have been used to characterize the developmental changes in the distribution and relative quantity of platelet-derived growth factor (PDGF), an important mitogen and growth regulator for glial (and possibly neuronal) cells. PDGF exists as a dimer of two chains, A and B, and antibodies which are relatively specific for one chain or the other can be used to localize PDGF isoforms during development. We have also studied the distribution of PDGF receptor beta subunit (PDGF-R beta)-like immunoreactivity using an antibody probe. All 3 isoforms of PDGF are found in neural structures during development, beginning at about the midpoint of embryogenesis. Immunoblotting studies confirm the presence of PDGF isoforms in brain during embryonic and postnatal development, with the distribution and relative abundance of each isoform appearing to be independently regulated. Similarly, immunoblotting studies have verified the relative abundance and specificity of PDGF receptor beta subunit. The immunohistochemical findings confirm and extend these biochemical observations. Each PDGF chain (A and B) has a discrete localization during nervous system development, and the immunohistochemical distribution of PDGF-R beta is distinct from each of the PDGF isoforms. PDGF A-chain (localized with an antibody to PDGF(AA) dimers) appears to be found in growth cones of developing neurons in mid-embryonic brain development. By 11.5 days post-conception (embryonic day 11.5, E11.5) to E12, PDGF isoforms are found in apparent neurons in the basal plate (future ventral horn) of spinal cord. PDGF-R beta-like immunoreactivity is localized to the boundary cap region of the developing spinal cord at the same age. Similarly, at E13.5, all 3 PDGF isoforms are found, to varying extents, within cells of the dorsal root ganglia and trigeminal ganglia. At the same developmental stage, PDGF receptor protein is most prevalent in the nerves accompanying these structures. By E15, both PDGF isoform and PDGF receptor beta subunit immunoreactivity have declined to near-background levels in the sensory ganglia, while in the spinal cord and developing forebrain, levels of all PDGF-related proteins remain high.


Neutrophil extracellular traps in acute coronary syndrome.
Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, which can cause heart failure, arrhythmia and even sudden death. It is the major cause of disability and death worldwide. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils activation and have various biological functions. NETs are closely related to the occurrence and development of ACS and also the subsequent damage after myocardial infarction. The mechanisms are complex and interdependent on various pathways, which require further exploration. This article reviewed the role and mechanism of NETs in ACS, thereby providing a valuable reference for the diagnosis and clinical treatment of ACS.


Pituitary adenylate cyclase-activating polypeptide ameliorates radiation-induced cardiac injury.
Radiation-induced heart disease (RIHD) is a common sequelae of thoracic irradiation. Currently, there is no effective prevention and treatment strategy. Oxidative stress is associated with the development of RIHD. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) has been defined as the multipotent properties of cytoprotective effect on its anti-apoptotic and antioxidant activities. Here, we set to investigate whether PACAP38 plays a role in attenuating RIHD. We established radiation-related cardiac injury models using 6MV X-ray based on H9C2 cardiomyocytes and male C57/BL6 mice which were pre-treated with PACAP38 prior to radiation exposure. PACAP38 protected mice from radiation-induced histological damage including myocardial apoptosis and fibrosis. Also, cell viability and colony-forming efficiency were enhanced and intracellular ROS generation was reduced in PACAP38 treated H9C2 cardiomyocytes exposed to radiation. Moreover, PACAP38 suppressed myocardial apoptosis and G2/M arrest through blunting the radiation-induced down-regulation of Bcl-2, CyclinB1 and CDC2, and inhibiting the up-regulation of Bax. Furthermore, irradiation resulted in activating of NRF2 and HO-1 expressions were further enhanced by PACAP38 in H9C2 cells and the protective effect of PACAP38 was partially blocked by NRF2 siRNA silencing. In summary, PACAP38 has the potential to effectively protect against acute radiation-induced cardiac injury and its cardioprotective effect involves upregulation of NRF2/HO-1-dependent signaling activation.


A masked negative self-esteem? Implicit and explicit self-esteem in patients with Narcissistic Personality Disorder.
The mask model of narcissism states that the narcissistic traits of patients with NPD are the result of a compensatory reaction to underlying ego fragility. This model assumes that high explicit self-esteem masks low implicit self-esteem. However, research on narcissism has predominantly focused on non-clinical participants and data derived from patients diagnosed with Narcissistic Personality Disorder (NPD) remain scarce. Therefore, the goal of the present study was to test the mask model hypothesis of narcissism among patients with NPD. Male patients with NPD were compared to patients with other PD's and healthy participants on implicit and explicit self-esteem. NPD patients did not differ in levels of explicit and implicit self-esteem compared to both the psychiatric and the healthy control group. Overall, the current study found no evidence in support of the mask model of narcissism among a clinical group. This implicates that it might not be relevant for clinicians to focus treatment of NPD on an underlying negative self-esteem.


Armed conflict and household food insecurity: evidence from war-torn Tigray, Ethiopia.
Exposure to armed conflicts result in strongly adverse and often irreversible short- and long-term effects which may transmit across generations. Armed conflicts directly cause food insecurity and starvation by disruption and destruction of food systems, reduce farming populations, destroying infrastructure, reducing resilience, and increasing vulnerabilities, disruptions in access to market, increasing food price or making goods and services unavailable altogether. The objective of the present study was to determine the status of household food insecurity in the armed conflict affected communities of Tigray in terms of Access, Experience and Hunger scale. Community-based cross-sectional study was conducted to assess impact of armed conflict on household food insecurity among households with children with under one year. FHI 360 and FAO guidelines were used to quantify household food insecurity and Household hunger status. Three-fourth of the households had anxiety about food supply and eat undesired monotonous diet due to lack of resources. Households were obliged to eat few kinds of foods, eat smaller meals, eat foods they do not want to eat, or went a whole day without eating any food. Household food insecurity access, food insecurity experience, and hunger scales significantly increased by 43.3 (95% CI: 41.9-44.7), 41.9 (95% CI: 40.5-43.3) and 32.5 (95% CI: 31.0-33.9) percentage points from the prewar period. Household food insecurity levels and household hunger status of the study communities was unacceptably high. The armed conflict has significant negative effect on food security in Tigray. It is recommended that the study communities need to be protected from the immediate and long-term consequences of conflict-induced household food insecurity.


Modeling Impact-induced Failure of Polysilicon MEMS: A Multi-scale Approach.
Failure of packaged polysilicon micro-electro-mechanical systems (MEMS) subjected to impacts involves phenomena occurring at several length-scales. In this paper we present a multi-scale finite element approach to properly allow for: (i) the propagation of stress waves inside the package; (ii) the dynamics of the whole MEMS; (iii) the spreading of micro-cracking in the failing part(s) of the sensor. Through Monte Carlo simulations, some effects of polysilicon micro-structure on the failure mode are elucidated.


Ring-shaped appearance in liver-specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers.
The aim was to clarify the features of contrast-enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers. Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide-band Doppler, 7/7), contrast-enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient. Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver-specific sonograms with a ring-shaped appearance--peripheral enhancement with a central non-enhanced area. Two of the three nodules showed decreased signal-intensity in the periphery on SPIO-enhanced MRI. The ring-shaped appearance on liver-specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.


Development and refinement of Rel@x:A training in hypnosis-derived communication for pediatric nurses to prevent procedural pain.
Studies in pediatric oncology have shown that hypnosis effectively reduces patients' pain and distress during painful procedures. This remains underutilized in the healthcare system due to the staff cost and availability of hypnotherapists. To develop the use of hypnosis-derived communication, we aimed to train nurses to use hypnosis-derived communication while they perform painful procedures. This study aimed to (1) develop a brief training in hypnosis-derived communication for pediatric nurses named Rel@x, (2) pretest the training with experienced pediatric oncology nurses, and (3) refine the training based on nurses' suggestions. The Rel@x training consists of two 4-h sessions: one related to relational aspects and another one presenting one of two selected hypnotic communication techniques ("pleasant place" or "magic glove"). Rel@x makes use of manuals, cue card reminders, visual aids, videos, and an e-learning platform. To refine Rel@x, a complete training cycle was conducted with seven female pediatric oncology nurses. A mixed method study with an evaluation questionnaire and a post-training focus group interview was conducted. Quantitative data showed that nurses overall positively rated the training program: relevance and acceptability (median average of 5.4/6); use of hypnotic communication (median average of 5.2/6); expected effects (median average of 5.4/6); program implementation (5.6/6). Two general themes emerged from the qualitative data: perceptions of hypnotic communication and the evaluation of the Rel@x training program. Based on nurses' suggestions, Rel@x was refined by adding more practical components, more time for practice, more time between the two sessions and additional tools (cue card reminders, keywords, virtual e-learning recap module). The use of hypnosis-derived communication during painful procedures and the Rel@x training were viewed favorably amongst pediatric nurses. Rel@x offers a complete training in hypnosis-derived communication for pediatric nurses. This training fosters the optimal use of hypnosis-derived communication during care and may significantly reduce children's procedural pain and distress.


Cone-beam computed tomography in pediatric dentistry, a retrospective observational study.
The aim of this study was to find the reasons for referral and their correlation with age, gender, field of view, and resolution for all patients under the age of 18 who underwent a cone-beam computed tomography (CBCT) scan between 1 May 2010 and 1 May 2012 in the dental out-patient clinic of the University Hospital Ghent. From the local CBCT database, 79 pediatric patients gave their consent. Subsequently age, gender, reason for referral, external or internal referral, field of view (FOV), and resolution data were collected. Descriptive and comparative statistical analysis was performed. There seemed to be a correlation between orthodontic referrals and female patients. The majority of patients referred for trauma follow-up were 12 years and older. Fourteen percent of referrals were for dento-alveolar trauma, 18 % for other dento-alveolar reasons, 4 % for developing dentition-generalized, 36 % for developing dentition-localized, 10 % for endodontics, 1 % for periodontics, 16 % for surgical applications, and 1 % was for the visualization of the TMJ. Eighty percent of the CBCTs were taken at a FOV 50 × 55 mm. Larger FOV was used for surgical planning or follow-up reasons. The majority of the CBCTs was taken at a resolution of 200 μm, while a resolution of 150 μm was used for endodontic issues. From these results, a classification system for referral was developed. From the present study, it can be concluded that a referral pattern could be detected which was correlated with gender, age group, FOV, and resolution. These results can help practitioners make the decision to refer for CBCT when extra three dimensional imaging is expected to have a benefit in therapeutic value for a pediatric or adolescent patient. This study can guide dental professionals referring pediatric and adolescent patients for CBCT.


Structural Effects on the Norrish Type I α-Bond Cleavage of Tropospherically Important Carbonyls.
Norrish Type I (NTI) α-bond cleavage is the dominant photolysis mechanism in small carbonyls and is an important source of radicals in the troposphere. In nonsymmetric species two cleavages are possible, NTIa and NTIb, forming larger and smaller alkyl radicals, respectively. For a data set of 20 small, atmospherically relevant carbonyls we predict NTIa and NTIb thresholds on the S0, S1, and T1 electronic states. The calculated NTIa T1 thresholds give a mean absolute deviation (MAD) of 5.8 kJ/mol with respect to the available experimental thresholds of five carbonyls. In addition, the intrinsic barrier heights to dissociation on the S0, S1, and T1 electronic states are predicted. We find RI-B2GP-PLYP/def2-TZVP calculations on S0 and unrestricted RI-B2GP-PLYP/def2-TZVP calculations on T1 give MADs of 6.1 kJ/mol for S0 asymptotic energies and 6.3 kJ/mol for S0 → T1 0-0 excitation energies, with respect to available experimental data. A composite method is used to determine S1 thresholds, with bt-STEOM-CCSD/cc-pVQZ calculation of vertical excitation energies and TD-RI-B3LYP/def2-TZVP calculations on S1, which achieves a MAD of 7.2 kJ/mol, with respect to experimental 0-0 excitation energies. Our calculations suggest, with the exception of bifunctional carbonyls and enones, NTI reactions on S1 are unlikely to be important at tropospherically relevant photolysis energies (<400 kJ/mol). In contrast, at these energies almost all possible NTI channels on T1 are open, and all barrierless S0 NTI dissociations are accessible. Our calculations allow a number of structural effects on both 0-0 excitation energies and intrinsic reaction barriers, on a given electronic state, to be elucidated and rationalized.


[Spontaneous bacterial peritonitis].
Since the beginning of the eighties systematic investigations broadened our knowledge about the clinical picture of spontaneous bacterial peritonitis very much. Important insights into epidemiology, pathogenesis, symptomatology, diagnosis and therapy of this disease, which is a frequent complication in patients with cirrhosis of the liver and ascites, could be gained. Actual research work primarily deals with questions of therapy and prophylaxis. Aim of this review is a comprehensive presentation of the different aspects of this disease on the basis of the present literature. As on the one side the clinical symptoms may be very little and on the other side the prognosis is very bad, it is extremely important to take this entity into the differential considerations to make an early diagnosis and to start an adequate therapy early.


Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study.
Ezetimibe has shown efficacy in the therapy of hypercholesterolemia in renal transplant patients. This is the first study investigating the effect of ezetimibe on renal function in kidney transplant recipients. Fifty-six patients with statin-resistant hypercholesterolemia (total cholesterol >200 mg/dl) after renal transplantation received additional ezetimibe therapy (10 mg/day) for 12 months. A group receiving statin therapy (n=28) served as controls in this prospective study. Total cholesterol and LDL cholesterol concentrations decreased significantly in the ezetimibe-treated patients but remained stable in the control group (delta total cholesterol: -24+/-49 mg/dl vs 19+/-49 mg/dl, P<0.01; delta LDL: -30+/-39 mg/dl vs -3+/-31 mg/dl, P<0.01). Mean creatinine clearance remained stable in ezetimibe-treated patients but decreased significantly in control group (delta Cockcroft-Gault: 0.9+/-7.3 ml/min vs - 4.8+/-12.8 ml/min, P=0.025; delta Modification of Diet in Renal Disease: -0.4+/-6.2 ml/min/1.73 m(2) vs 4.7+/-8.8 ml/min/1.73 m(2), P=0.033). The data of our prospective case-control study suggest that ezetimibe appears to ameliorate the decline of renal function after renal transplantation.