Effects of Cross-Training on Medical Teams' Teamwork and Collaboration: Use of Simulation.
Previous research in the US Navy demonstrated that cross-training enhances teamwork and interpersonal collaboration. Limited data exists on cross-training effectiveness in medical education. This research aimed to assess whether cross-training would have similar effects on medical teams. A multidisciplinary pair of resident participants-consisting of one physician and one pharmacist-was randomly assigned to cross-training or current training condition. The training experience involved one video-based content module (training a pharmacist's task of pharmacokinetic dosing and a physician's task of intubation) and one simulation-based practice scenario (collaborative treatment of an unstable critically ill simulated patient). Interprofessional pairs randomized to cross-training condition participated in both the content module and practice scenario in the alternative professional role whereas pairs randomized to current training condition participated in their own professional role. Pairs also participated in pre- and post- training assessment scenarios in their own professional role. Teamwork and interprofessionalism were measured immediately following assessment scenarios. Knowledge assessments were conducted at the start and end of the scenario sequence. Multidisciplinary pairs experiencing cross-training showed a significant improvement in teamwork (increased by 6.11% vs. 3.24%, p < 0.05). All participants demonstrated significant improvement in knowledge scores (increase of 14% cross-training, p < 0.05, and increase of 13.9% control, p < 0.05). Our project suggests that cross-training can improve teamwork in interprofessional medical teams.


Is it advantageous for Atlantic salmon to be triploid at lower temperatures?
Marine organisms living at low temperatures tend to have larger genomes and larger cells which suggest that these traits can be beneficial in colder environments. In fish, triploidy (three complete sets of chromosomes) can be induced experimentally following fertilization, which provides a model system to investigate the hypothesis that larger cells and genomes offers a physiological advantage at low temperatures. We tested this hypothesis by measuring metabolic rates and swimming performance of diploid and triploid Atlantic salmon (Salmo salar) post smolts acclimated to 3 or 10.5 °C. At 10.5 °C, triploids had significantly lower maximum metabolic rates which resulted in a lower aerobic scope compared to diploids. In addition, triploids initiated ram ventilation at lower swimming speeds, providing further evidence of a reduced capacity to meet oxygen demands during strenuous activity at 10.5 °C. However, at 3 °C, metabolic rates and critical swimming speeds were similar between both ploidies, and as expected substantially lower than at 10.5 °C. Therefore, triploidy in colder environments did not provide any advantage over diploidy in terms of metabolic rate traits or swimming performance in Atlantic salmon. We therefore conclude that traits, other than aerobic scope and swimming performance, contribute to the trend for increased cell and genome size in marine ectotherms living in cold environments.


Comparing the analytical performance of three SARS-CoV-2 molecular diagnostic assays.
In December 2019, a novel coronavirus (SARS-CoV-2) was first isolated from Wuhan city, China and within three months, the global community was challenged with a devastating pandemic. The rapid spread of the virus challenged diagnostic laboratories to rapidly develop molecular diagnostic methods. As SARS CoV-2 assays became available for testing on existing molecular platforms, laboratories devoted unprecedented energy and resources into evaluating the analytical performance of the new tests and in some cases developed their own diagnostic assays under FDA-EUA guidance. This study compares the validation of three different molecular assays at the Johns Hopkins Molecular Virology laboratory: the RealStar® SARS-CoV-2 RT-PCR, ePlex® SARS-CoV-2, and the CDC COVID-19 RT-PCR tests. Overall, our studies indicate a comparable analytical performance of the three assays for the detection of SARS-CoV-2.


Circadian Metabolomics in Time and Space.
Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various "omics"-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine "omics" approach for studying metabolism, and "circadian metabolomics" (i.e., studying the 24-h metabolome) has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal.


Invited review: molecular adaptations in mammalian hibernators: unique adaptations or generalized responses?
Hibernators are unique among mammals in their ability to attain, withstand, and reverse low body temperatures. Hibernators repeatedly cycle between body temperatures near zero during torpor and 37 degrees C during euthermy. How do these mammals maintain cardiac function, cell integrity, blood fluidity, and energetic balance during their prolonged periods at low body temperature and avoid damage when they rewarm? Hibernation is often considered an example of a unique adaptation for low-temperature function in mammals. Although such adaptation is apparent at the level of whole animal physiology, it is surprisingly difficult to demonstrate clear examples of adaptations at the cellular and biochemical levels that improve function in the cold and are unique to hibernators. Instead of adaptation for improved function in the cold, the key molecular adaptations of hibernation may be to exploit the cold to depress most aspects of biochemical function and then rewarm without damage to restore optimal function of all systems. These capabilities are likely due to novel regulation of biochemical pathways shared by all mammals, including humans.


Copy-number variations, noncoding sequences, and human phenotypes.
Whereas single-nucleotide polymorphisms and their role in predisposition to disease have been studied extensively, the analysis of structural variants--genomic changes such as insertions, deletions, inversions, duplications, and translocations--is still in its infancy. Changes in copy number, also known as copy-number variations (CNVs), constitute one such group of these structural variants. CNVs are structural genomic variants that arise from deletions (loss) or duplications (gain), and as a consequence result in a copy-number change of the respective genomic region. CNVs may include entire genes or regions of transcribed sequence, or, indeed, comprise only nontranscribed sequences. Whereas the duplication or deletion of a gene can be expected to have an effect on gene dosage, the consequences of CNVs in nontranscribed sequences are less obvious. Here we review CNVs that involve regulatory nontranscribed regions of the genome, describe the associated human phenotypes, and discuss possible disease mechanisms.


Noble-Collip Drum Trauma Induces Disseminated Intravascular Coagulation But Not Acute Coagulopathy of Trauma-Shock.
There are two opposing possibilities for the main pathogenesis of trauma-induced coagulopathy: an acute coagulopathy of trauma shock and disseminated intravascular coagulation with the fibrinolytic phenotype. The objective of this study was to clarify the main pathogenesis of trauma-induced coagulopathy using a rat model of Noble-Collip drum trauma. Eighteen rats were divided into the control, trauma 0, and trauma 30 groups. The trauma 0 and 30 groups were exposed to Noble-Collip drum trauma. Blood samples were drawn without, immediately after, and 30 min after Noble-Collip drum trauma in the control, trauma 0, and trauma 30 groups, respectively. Coagulation and fibrinolysis markers were measured. Thrombin generation was assessed according to a calibrated automated thrombogram. Spontaneous thrombin bursts resulting from circulating procoagulants were observed in the nonstimulated thrombin generation assay immediately after trauma. Soluble fibrin levels (a marker of thrombin generation in the systemic circulation) were 50-fold greater in the trauma groups than in the control group. The resultant coagulation activation consumed platelets, coagulation factors, and antithrombin. Endogenous thrombin potential and factor II ratio were significantly negatively correlated with antithrombin levels, suggesting insufficient control of thrombin generation by antithrombin. High levels of active tissue-type plasminogen activator induced hyperfibrin(ogen)olysis. Soluble thrombomodulin increased significantly. However, activated protein C levels did not change. The systemic thrombin generation accelerated by insufficient antithrombin control leads to the consumption of platelets and coagulation factors associated with hyperfibrin(ogen)olysis. These changes are collectively termed disseminated intravascular coagulation with the fibrinolytic phenotype.


Total synthesis of (+/-)-flustramines A and C, (+/-)-flustramide A, and (-)- and (+)-debromoflustramines A.
Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.


Early risk pathways to physical versus relational peer aggression: The interplay of externalizing behavior and corporal punishment varies by child sex.
Children who aggress against their peers may use physical or relational forms, yet little research has looked at early childhood risk factors and characteristics that uniquely predict high levels of relational versus physical aggression in preadolescence. Accordingly, the main aim of our study was to link early corporal punishment and externalizing behavior to children's physical and relational peer aggression during preadolescence and to examine how these pathways differed by sex. Participants were 193, 3-year-old boys (39%) and girls who were reassessed following the transition to kindergarten (5.5 years) and preadolescence (10.5 years). A series of autoregressive, cross-lagged path analyses were conducted to examine the relationships between child externalizing problems and corporal punishment at ages 3 and 5.5 years, and their association with physical and relational aggression at age 10.5. Multiple group analysis was used to determine whether pathways differed by sex. Three developmental pathways were identified: (i) direct associations between stable childhood externalizing problems and later physical aggression; (ii) a direct pathway from early corporal punishment to preadolescent relational and physical peer aggression; and (iii) an indirect pathway from early corporal punishment to later physical aggression via continuing externalizing problems in middle childhood. Child sex moderated the nature of these pathways, as well as the direction of association between risk and outcome variables. These data advance our understanding of the etiology of distinct forms of peer aggression and highlight the potential for more efficacious prevention and intervention efforts in the early childhood years.


Variation in normal mood state influences sensitivity to dynamic changes in emotional expression.
Normal social functioning depends on the ability to efficiently and accurately detect when someone's facial expression changes to convey positive or negative emotion. While observer mood state has been shown to influence emotion recognition, how variations in normal mood might influence sensitivity to the dynamic emergence of expressions has not yet been addressed. To investigate this, we modified an existing face-morphing paradigm in which a central face gradually changes from neutral to expressive (angry, sad, happy, surprised). Our sample comprised healthy young adults, and current mood state was measured using the PANAS-X. Participants pressed a key as soon as they (1) noticed a physical change in expression (perceptual sensitivity-novel task element), and (2) could clearly conceptualize which expression was emerging (conceptual sensitivity). A final unspeeded response required participants to explicitly label the expression as a measure of recognition accuracy. We measured the percentage morph (expression intensity) at which a perceptual and conceptual change was detected, where greater intensity equates to poorer sensitivity. Increased positive mood reduced perceptual and conceptual sensitivity to angry and sad expressions only (a mood incongruency effect). Of particular interest, increased negative mood decreased conceptual sensitivity for all expressions, but had limited impact on perceptual sensitivity. Thus, heightened negative mood is particularly detrimental for effectively decoding someone else's mood change. This may reflect greater introspection and consumption of attentional resources directed toward the negative self, leaving fewer resources to process emotional signals conveyed by others. This could have important consequences for human social interaction.


MeCAT--comparing relative quantification of alpha lactalbumin using both molecular and elemental mass spectrometry.
Chemical tagging with stable isotopes is one of the best established methods for the quantification of proteins using mass spectrometry, especially in non-proliferating cells and tissue. The absolute quantification of proteins is still a challenge. Metal-coded affinity tagging (MeCAT), used to label proteins and peptides with lanthanide ions, allows both, relative and absolute, quantitative determination. MeCAT loaded with lanthanide ions allows the use of inductively coupled plasma mass spectrometry (ICP-MS) enabling very accurate and sensitive quantification of peptides and proteins based on the metal ion signal. Furthermore, multiplex assays are possible that are not limited to 4- or 8-plex analyses when using different lanthanides. Naturally, different lanthanides also lead to different molecular masses for the same labelled peptides which can be distinguished easily. This enables the relative quantification in electrospray MS based on the relative signal intensities of the differentially labelled peptides. We have studied MeCAT labelled peptides, using LC/ESI-MS and LC/ESI-MS/MS with infrared multiphoton dissociation (IRMPD) to show that both the molecular masses and the specific fragments resulting from the MS/MS experiments can be used for relative quantification. The results are compared with high performance liquid chromatography (HPLC)/ICP-MS and direct ICP-MS analysis as standard methods. We show that the ESI and IRMPD based methods deliver quantitative results comparable to ICP-MS.


Role of Chemical Biology in Tuberculosis Drug Discovery and Diagnosis.
The use of chemical techniques to study biological systems (often referred to currently as chemical biology) has become a powerful tool for both drug discovery and the development of novel diagnostic strategies. In tuberculosis, such tools have been applied to identifying drug targets from hit compounds, matching high-throughput screening hits against large numbers of isolated protein targets and identifying classes of enzymes with important functions. Metabolites unique to mycobacteria have provided important starting points for the development of innovative tools. For example, the unique biology of trehalose has provided both novel diagnostic strategies as well as probes of in vivo biological processes that are difficult to study any other way. Other mycobacterial metabolites are potentially valuable starting points and have the potential to illuminate new aspects of mycobacterial pathogenesis.


Pagano-Levin Candida test medium: evaluation using vaginal samples.
Since 1958 pagano-Levin medium (PLM) has been used as an aid in the identification of Candida albicans. However, no statistical analysis of its effectiveness based on large number of random human specimens has been reported. The present study compared PLM (now called Candida test) with Sabouraud's plus antimicrobials and Littman's ox-gall agar without antimicrobials. Of 500 random vaginal samples 24.8 were true positives, 71.9% were true negatives, 2.2% were false positives, and 1.2% were false negatives on PLM. If only samples identified as C. albicans were considered, 95.4% were true positives and 4.6% were false negatives. PLM did not inhibit C. albicans from the vagina. No one medium was found superior to the others for the purpose of isolating and identifying C. albicans. Of the five strains of C. parapsilosis, the only other Candida species isolated, all the samples grew on PLM but most were inhibited on Sabouraud's medium plus antimicrobials.


In vivo canine study of three different coatings applied to p64 flow-diverter stents: initial biocompatibility study.
Flow-diverter stents (FDSs) have revolutionised the treatment of intracranial aneurysms. However, associated dual antiplatelet treatment is mandatory. We investigated the biocompatibility of three proprietary antithrombogenic coatings applied to FDSs. After Institutional Animal Care and Use Committee approval, four domestic juvenile female dogs (weight 19.9 ± 0.9 kg, mean ± standard deviation) were commenced on three different oral antiplatelet regimes: no medication (n = 1), acetylsalicylic acid (n = 2), and acetylsalicylic acid and clopidogrel (n = 1). Four p64 FDSs were randomly implanted into the subclavian, common carotid, and external carotid arteries of each dog, including both uncoated p64 stents and p64 stents coated with three different antithrombogenic hydrophilic coating (HPC). Angiography and histological examinations were performed. Wilcoxon/Kruskal-Wallis and ANOVA were used with p value < 0.05 considered as significant. Minimal inflammatory cell infiltration and no device-associated granulomatous cell inflammation were observed. No significant difference in adventitial inflammation (p = 0.522) or neointimal/medial inflammation (p = 0.384) between coated and uncoated stents as well as between the different stent groups regarding endothelial cell loss, surface fibrin/platelet deposition, medial smooth muscle cell loss, or adventitial fibrosis were found. Acute self-limiting thrombus formed on 6/16 implants (37.5%), and all of the thrombi were noted on devices implanted in the common or external carotid artery irrespective of the surface coating. Two of 12 p64 HPC-coated stents (16.7%) and 1/4 uncoated p64 stents (25%) showed severe or complete stenosis at delayed angiography. In these preliminary in vivo experiments, HPC-coated p64 FDSs appeared to be biocompatible, without acute inflammation.


Calcification and associated physiological parameters during a stress event in the scleractinian coral Stylophora pistillata.
High calcification rates observed in reef coral organisms are due to the symbiotic relationship established between scleractinian corals and their photosynthetic dinoflagellates, commonly called zooxanthellae. Zooxanthellae are known to enhance calcification in the light, a process referred as "light-enhanced calcification". The disruption of the relationship between corals and their zooxanthellae leads to bleaching. Bleaching is one of the major causes of the present decline of coral reefs related to climate change and anthropogenic activities. In our aquaria, corals experienced a chemical pollution leading to bleaching and ending with the death of corals. During the time course of this bleaching event, we measured multiple parameters and could evidence four major consecutive steps: 1) at month 1 (January 2005), the stress affected primarily the photosystem II machinery of zooxanthellae resulting in an immediate decrease of photosystem II efficiency, 2) at month 2, the stress affected the photosynthetic production of O2 by zooxanthellae and the rate of light calcification, 3) at month 3, there was a decrease in both light and dark calcification rates, the appearance of the first oxidative damage in the zooxanthellae, the disruption of symbiosis, 4) and finally the death of corals at month 6.


Circulating insulin-like growth factor-1 and risk of lung diseases: A Mendelian randomization analysis.
Insulin-like growth factor-1 (IGF-1) display a vital role in in the pathogenesis of lung diseases, however, the relationship between circulating IGF-1 and lung disease remains unclear. Single nucleotide polymorphisms (SNPs) associated with the serum levels of IGF-1 and the outcomes data of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer and idiopathic pulmonary fibrosis (IPF) were screened from the public genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was then performed to assess the independent impact of IGF-1 exposure on these lung diseases. Totally, 416 SNPs related to circulating IGF-1 levels among 358,072 participants in UK Biobank. According to a primary casual effects model with MR analyses by the inverse variance weighted (IVW) method, the circulating IGF-1 was demonstrated a significantly related with the risk of asthma (OR, 0.992; 95% CI, 0.985-0.999, P=0.0324), while circulating IGF-1 showed no significant correlation with CODP (OR, 1.000; 95% CI, 0.999-1.001, P=0.758), lung cancer (OR, 0.979, 95% CI, 0.849-1.129, P=0.773), as well as IPIGFF (OR, 1.100, 95% CI, 0.794-1.525, P=0.568). The present study demonstrated that circulating IGF-1 may be causally related to lower risk of asthma.


Spin-orbit qubits of rare-earth-metal ions in axially symmetric crystal fields.
Contrary to the well-known spin qubits, rare-earth-metal qubits are characterized by a strong influence of crystal field due to large spin-orbit coupling. At low temperature and in the presence of resonance microwaves, it is the magnetic moment of the crystal-field ground state which nutates (for several micros) and the Rabi frequency Omega(R) is anisotropic. Here, we present a study of the variations of Omega(R)(H(0)) with the magnitude and direction of the static magnetic field H(0) for the odd 167Er isotope in a single crystal CaWO(4):Er(3+). The hyperfine interactions split the Omega(R)(H(0)) curve into eight different curves which are fitted numerically and described analytically. These "spin-orbit qubits" should allow detailed studies of decoherence mechanisms which become relevant at high temperature and open new ways for qubit addressing using properly oriented magnetic fields.


Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish.
Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines including tumor necrosis factor-α and interleukin-1β in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of NF-κB p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.


Novel Immune Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia.
Adverse genetic risk acute myeloid leukemia (AML) includes a wide range of clinical-pathological entities with extremely poor outcomes; thus, novel therapeutic approaches are needed. Promising results achieved by engineered chimeric antigen receptor (CAR) T cells in other blood neoplasms have paved the way for the development of immune cell-based therapies for adverse genetic risk AML. Among these, adoptive cell immunotherapies with single/multiple CAR-T cells, CAR-natural killer (NK) cells, cytokine-induced killer cells (CIK), and NK cells are subjects of ongoing clinical trials. On the other hand, allogeneic hematopoietic stem cell transplantation (allo-HSCT) still represents the only curative option for adverse genetic risk AML patients. Unfortunately, high relapse rates (above 50%) and associated dismal outcomes (reported survival ~10-20%) even question the role of current allo-HSCT protocols and emphasize the urgency of adopting novel effective transplant strategies. We have recently demonstrated that haploidentical allo-HSCT combined with regulatory and conventional T cells adoptive immunotherapy (Treg-Tcon haplo-HSCT) is able to overcome disease-intrinsic chemoresistance, prevent leukemia-relapse, and improve survival of adverse genetic risk AML patients. In this Perspective, we briefly review the recent advancements with immune cell-based strategies against adverse genetic risk AML and discuss how such approaches could favorably impact on patients' outcomes.


Efficient Laser-Induced Construction of Oxygen-Vacancy Abundant Nano-ZnCo2 O4 /Porous Reduced Graphene Oxide Hybrids toward Exceptional Capacitive Lithium Storage.
Recently, binary ZnCo2 O4 has drawn enormous attention for lithium-ion batteries (LIBs) as attractive anode owing to its large theoretical capacity and good environmental benignity. However, the modest electrical conductivity and serious volumetric effect/particle agglomeration over cycling hinder its extensive applications. To address the concerns, herein, a rapid laser-irradiation methodology is firstly devised toward efficient synthesis of oxygen-vacancy abundant nano-ZnCo2 O4 /porous reduced graphene oxide (rGO) hybrids as anodes for LIBs. The synergistic contributions from nano-dimensional ZnCo2 O4 with rich oxygen vacancies and flexible rGO guarantee abundant active sites, fast electron/ion transport, and robust structural stability, and inhibit the agglomeration of nanoscale ZnCo2 O4 , favoring for superb electrochemical lithium-storage performance. More encouragingly, the optimal L-ZCO@rGO-30 anode exhibits a large reversible capacity of ≈1053 mAh g-1 at 0.05 A g-1 , excellent cycling stability (≈746 mAh g-1 at 1.0 A g-1 after 250 cycles), and preeminent rate capability (≈686 mAh g-1 at 3.2 A g-1 ). Further kinetic analysis corroborates that the capacitive-controlled process dominates the involved electrochemical reactions of hybrid anodes. More significantly, this rational design holds the promise of being extended for smart fabrication of other oxygen-vacancy abundant metal oxide/porous rGO hybrids toward advanced LIBs and beyond.


Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL.
Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a poor prognosis and high recurrence rate. In the present study, we identified CD133, one of the markers of cancer stem cells, as a novel molecular target of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In four human HCC cell lines established from primary HCC tumors, we found that CD133-high human liver cancer stem-like cells (CD133hi) derived from the SNU-475 cell line were highly susceptible to TRAIL compared to other HCC cell lines with a small population of CD133. CD133hi SNU-475 cells showed upregulation of TRAIL receptor DR5 and stemness-related genes such as c-Myc and ABC transporters compared to their CD133-low (CD133lo) cells. Hypersensitivity of CD133hi cells to TRAIL was associated with c-Myc-mediated upregulation of DR5 and downregulation of c-FLIPL in the cells. Knockdown of CD133 expression in CD133hi cells resulted in the downregulation of c-Myc, and depletion of c-Myc caused a decrease in the cell surface expression of DR5 and an increase in the expression of c-FLIPL and, consequently, attenuated TRAIL-induced cytotoxicity and apoptosis of CD133hi cells. These results suggest that TRAIL may provide a new strategy for CD133hi CSCs of HCC-targeted therapies and, potentially, for therapies of other CD133-expressing types of cancer.


Cytotoxic effect of MTA and CEM cement in human gingival fibroblast cells. Scanning electronic microscope evaluation.
In this ex-vivo study, we assessed the adhesion of human gingival fibroblast (HGF) to mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cement using a scanning electronic microscope (SEM). Test biomaterials were prepared and inserted in polyethylene wells (n = 18). Glass coverslips were used for control groups. HGFs were seeded in the glass coverslips, MTA and CEM. For the positive-control group, distilled water was added to the medium; the samples were observed with SEM at one, three and seven-day intervals. Normal cell morphology was observed in the negative controls. In the positive controls, round cells with rougher surfaces were seen; these cells showed few attachments to the glass coverslip. HGFs spread and adhered similarly on MTA and CEM by forming a monolayer of flat cells; there were no statistical differences between these two experimental groups. HGF cells displayed a favorable biologic response in contact with MTA and CEM. This demonstrates non-cytotoxicity of CEM as a novel endodontic biomaterial.


[Liver anatomy: CT and MRI].
Computed tomography and magnetic resonance imaging are widely used tools to appreciate liver anatomy. Vascular and segmental anatomy are adequately appreciated with CT, while biliary anatomy is mainly seen with MR imaging. Basic principles of techniques and anatomical landmarks will be detailed.


[Surgical treatment of lower extremity peripheral nerve injuries].
Peripheral nerve injuries of the lower extremities are not frequent. The most common are traction injury of the peroneal nerve at the knee level or iatrogenic trauma of the pelvic nerves during abdominal surgery. Civil sharp injuries are rare.Indications for surgical revision follow the general rules of nerve surgery. Sharp injury should be treated as soon as possible, ideally within 72 hours. Closed lesions are indicated for surgery if a complete denervation remains unchanged three months after the injury. Best results can be achieved within six months from the injury. Irritations caused by bone fragments or scarring or by iatrogenic injury (clamps, cement, screws, etc.) may be revised later. However, the most important is early clinical examination in a specialized neurosurgical department.


Change in Biased Thinking in a Treatment Based on the Motive-Oriented Therapeutic Relationship for Borderline Personality Disorder.
Biased thinking is a common feature of patients presenting with borderline personality disorder (BPD). For the treatment of BPD, it was shown that the individualizing of the treatment, by using the motive-oriented therapeutic relationship (MOTR), had a beneficial short-term effect on process and outcome. So far, it remains unclear what the role of early change in biased thinking is in these treatments. The present study aims to assess whether there is a link between the MOTR, change in biased thinking, and outcome. The sample (N = 60) is based on a randomized controlled trial with two conditions: (a) 30 patients in a 10-session version of psychiatric management, and (b) 30 patients in a 10-session version of psychiatric management augmented with the MOTR. For each patient, three sessions (intake, middle, late) were selected, transcribed, and rated using the Cognitive Errors Rating Scale (CERS). An overall decrease of negative cognitive errors during 10 sessions of treatment was observed, independently of the treatment condition. No specific effect related to change in biased thinking may be attributed to the individualizing of the treatment. These results are discussed with regard to mechanisms of change in treatments for BPD, in particular with regard to the central role that biased thinking, as well as the MOTR, might play early in treatment.


Hierarchical Semantic Risk Minimization for Large-Scale Classification.
Hierarchical structures of labels usually exist in large-scale classification tasks, where labels can be organized into a tree-shaped structure. The nodes near the root stand for coarser labels, while the nodes close to leaves mean the finer labels. We label unseen samples from the root node to a leaf node, and obtain multigranularity predictions in the hierarchical classification. Sometimes, we cannot obtain a leaf decision due to uncertainty or incomplete information. In this case, we should stop at an internal node, rather than going ahead rashly. However, most existing hierarchical classification models aim at maximizing the percentage of correct predictions, and do not take the risk of misclassifications into account. Such risk is critically important in some real-world applications, and can be measured by the distance between the ground truth and the predicted classes in the class hierarchy. In this work, we utilize the semantic hierarchy to define the classification risk and design an optimization technique to reduce such risk. By defining the conservative risk and the precipitant risk as two competing risk factors, we construct the balanced conservative/precipitant semantic (BCPS) risk matrix across all nodes in the semantic hierarchy with user-defined weights to adjust the tradeoff between two kinds of risks. We then model the classification process on the semantic hierarchy as a sequential decision-making task. We design an algorithm to derive the risk-minimized predictions. There are two modules in this model: 1) multitask hierarchical learning and 2) deep reinforce multigranularity learning. The first one learns classification confidence scores of multiple levels. These scores are then fed into deep reinforced multigranularity learning for obtaining a global risk-minimized prediction with flexible granularity. Experimental results show that the proposed model outperforms state-of-the-art methods on seven large-scale classification datasets with the semantic tree.


Mid-infrared chalcogenide glass Raman fiber laser.
We report the first demonstration of a Raman fiber laser (RFL) emitting in the mid-infrared, above 3 μm. The operation of a single-mode As2S3 chalcogenide glass based RFL at 3.34 μm is demonstrated by using a low-loss Fabry-Pérot cavity formed by a pair of fiber Bragg gratings. A specially designed quasi-cw erbium-doped fluoride fiber laser emitting at 3.005 μm is used to pump the RFL. A laser output peak power of 0.6 W is obtained with a lasing efficiency of 39% with respect to the launched pump power.


Highly active and selective oxygen reduction to H2O2 on boron-doped carbon for high production rates.
Oxygen reduction reaction towards hydrogen peroxide (H2O2) provides a green alternative route for H2O2 production, but it lacks efficient catalysts to achieve high selectivity and activity simultaneously under industrial-relevant production rates. Here we report a boron-doped carbon (B-C) catalyst which can overcome this activity-selectivity dilemma. Compared to the state-of-the-art oxidized carbon catalyst, B-C catalyst presents enhanced activity (saving more than 210 mV overpotential) under industrial-relevant currents (up to 300 mA cm-2) while maintaining high H2O2 selectivity (85-90%). Density-functional theory calculations reveal that the boron dopant site is responsible for high H2O2 activity and selectivity due to low thermodynamic and kinetic barriers. Employed in our porous solid electrolyte reactor, the B-C catalyst demonstrates a direct and continuous generation of pure H2O2 solutions with high selectivity (up to 95%) and high H2O2 partial currents (up to ~400 mA cm-2), illustrating the catalyst's great potential for practical applications in the future.


Treatment of malignant colonic obstructions with metal stents and laser.
The aim of this study was to evaluate the efficacy and safety of combined endoscopic therapy with self-expanding metallic endoprostheses and laser application in the management of malignant colonic obstruction. Between March 1998 and September 2000, obstruction of the distal colon was diagnosed in a total of 11 patients (6 M, 5 F, age range: 67-87 years, mean: 73). The site of obstruction was located in the rectosigmoid colon (n = 6), in the sigmoid colon (n = 4) and in the descending colon (n = 1). The etiology of stenosis was colorectal adenocarcinoma (n = 8), ovarian cancer (n = 2) and infiltrating bladder carcinoma (n = 1). In all patients the tumor was considered non-resectable. Six patients had confirmed metastases, one refused colostomy and 4 were unable to undergo surgery. After radiological visualization of the proximal extent of the stricture, the stenosis was dilated with Savary-like (10 patients) and pneumatic balloon dilators (1 patient-descending colon). Stents were placed successfully in 10 patients. Prostheses migration distal to lesion, into the sigmoid colon, was observed in one patient (bladder cancer). A mild autoresolved bleeding was observed in 8 patients. Five patients remained free of clinical colonic obstruction until their death, which occurred 6-16 weeks (mean: 10) after stent placement. A moderate non-occlusive ingrowth of tumor into the stent lumen was documented in the other 5 cases. These patients were treated with introspective application of Diomed laser in a total of 16 sessions (4120-12,476 Joules each session, mean: 6258, power 10-14 W, interval between 2 sessions 6 weeks) and died of progressive disease without clinical signs and endoscopic findings of reobstruction 22-56 weeks (mean: 32) after stent placement. Metallic stent placement is an adequate palliative and cost-effective option, effective and save, in advanced colonic obstruction due to non-resectable tumors. It circumvents the need for colostomy and allows the patient a better quality of life. Delayed stent occlusion with tumor ingrowth requires a regular follow-up and can be treated with introspective laser ablation.


PI3-kinase is essential for ADP-stimulated integrin alpha(IIb)beta3-mediated platelet calcium oscillation, implications for P2Y receptor pathways in integrin alpha(IIb)beta3-initiated signaling cross-talks.
Phosphatidylinositol 3-kinase (PI3K) pathway is important for platelet activation. Recent studies showed that PI3K and oscillative calcium could cross talk to each other and positively regulate integrin alpha (IIb)beta3-mediated outside-in signaling. However, the mechanism of this feedback regulation remains to be further characterized. Here we found that treatments of both PI3K inhibitor wortmannin and P2Y1 inhibitor A3P5P could inhibit granular secretion in platelets. Additionally, when RGD-substrate adherent platelets were treated with the ADP scavenger apyrase to deplete the granular-released ADP, their attachments in engaging with substrates became looser and the frequency of calcium oscillation decreased. Since it is known that ADP stimulates the PI3K and calcium signal primarily through P2Y12 and P2Y1 receptors respectively, our data indicated that integrin alpha(IIb)beta3 downstream PI3K and calcium activation might be not completely coupled to integrin associated signaling complex, but in part through feedback stimulation by granular released ADP. Our data indicates the important roles of PI3K and granular released ADP in coordinating the feedback regulations in integrin alpha(IIb)beta3-mediated platelet activation.


Anatomy of an energy-coupling mechanism--the interlocking catalytic cycles of the ATP sulfurylase-GTPase system.
ATP sulfurylase, from Escherichia coli K-12, conformationally couples the rates and chemical potentials of the two reactions that it catalyzes, GTP hydrolysis and activated sulfate synthesis. The enzyme is rare among such coupling systems in that it links the potentials of small-molecule chemistries to one another, rather than to vectorial motion. The pre-steady-state stages of the catalytic cycle of ATP sulfurylase were studied using tools capable of distinguishing between enzyme-bound and solution-phase product for each of the four products of the enzyme. The study reveals that the two chemistries are linked at multiple points in the reaction coordinate. Linking begins with an isomerization prior to chemistry that initiates an ordered cleavage of the beta,gamma and alpha,beta bonds of GTP and ATP, respectively; the rates of these three sequential events increase successively, causing them to appear simultaneous. Linking is again seen in the late stages of the catalytic cycle: product release is ordered with P(i) departing prior to either GDP or PP(i). Release rate constants are determined for each product and used to construct a quantitative model of the mechanism that accurately predicts the behavior of this complex system.


Phenolic acids are absorbed from the rat stomach with different absorption rates.
The intestinal absorption characteristics of phenolic acids (PAs) have been elucidated in terms of their affinity for the monocarboxylic acid transporter (MCT). Recently, the involvement of the stomach has been implicated in the absorption of polyphenols. The present work demonstrates that the gastric absorption efficiency of each PA is apparently different between various PAs. Various PAs with different affinities for MCT were administered (2.25 mumol) to rat stomach, and then the plasma concentration of the PA was measured. The plasma concentration of ferulic acid (FA) peaked 5 min after administration in the stomach. At 5 min after administration, the plasma concentration of each PA increased in the order: gallic acid = chlorogenic acid < caffeic acid < p-coumaric acid = FA. This order matches their respective affinity for MCT in Caco-2 cells, which we have demonstrated in previous studies. These results indicated that MCT might be involved in the gastric absorption of PAs, similar to the intestinal absorption.


Comparison of ultrasonography and radiography with arthroscopy for diagnosis of dorsoproximal osteochondral fragmentation of the proximal phalanx in 56 Thoroughbred racehorses.
Osteochondral fragmentation of the proximal phalanx (DPP1 fragment) is a common finding in the racehorse. Whilst radiographic assessment has been reported to lack diagnostic sensitivity, ultrasonographic examination has been documented to be extremely sensitive for identification of bone fragments in the metacarpophalangeal joint. To determine the sensitivity and specificity of ultrasonography as an imaging modality for diagnosis of DPP1 fragmentation and to compare it with radiography in the Thoroughbred racehorse. Retrospective cohort study. Medical records (radiographs and ultrasonographic examinations) of 56 Thoroughbred racehorses in training (average age 26.4 months [SD ±5.9]) with a history of forelimb fetlock joint effusion and arthroscopically confirmed DPP1 fragmentation were evaluated. Inter-observer agreement was calculated between three blinded reviewers for both ultrasonographic and radiographic findings. Median values were used for statistical analyses. Ultrasonographic and radiographic identification of DPP1 fragmentation was considered correct if in agreement with arthroscopic findings. The McNemar test was used to compare correct proportions between radiography and ultrasonography. Analyses were performed to evaluate correct identification of presence of fragment(s), location of fragment(s) and presence and location of fragment(s) within the joints, with values P < .05 considered significant. Eighty-one fetlock joints from 56 Thoroughbreds were evaluated. In total, 99 individual DPP1 fragments were confirmed arthroscopically. Ultrasonography was shown to have high levels of sensitivity (94%, 95% CI 89%-99%) and specificity (97%, 95% CI 92%-100%) for identification of DPP1 fragments, with transverse ultrasonographic images being more sensitive than sagittal ultrasonography (P = .001). Ultrasonography was also shown in this population to have significantly greater sensitivity than radiography (47%, 95% CI 37%-56%) (P < .001). Ultrasonography is an extremely sensitive and specific imaging modality for evaluation of DPP1 fragmentation, with transverse ultrasonographic imaging being the most sensitive technique. Radiographic evaluation was less sensitive than ultrasonography in this study.


Developmental regulation of protein phosphatase types 1 and 2A in post-hatch chicken brain.
The activity and subcellular distribution of protein phosphatases 1 and 2A were measured in chicken forebrain and cerebellum during post-hatch development. At all post-hatch ages, a large proportion of PP1 and PP2A was membrane bound and these enzymes were less active than their cytosolic counterparts. The protein concentration of PP1 in the membranes increased 40% between 2 and 14 days and a further 60% between 14 days and adult, whereas the PP1 enzyme activity in the membranes progressively decreased. In contrast to PP1, the protein concentration of PP2A remained constant in all fractions during post-hatch development, and the enzyme activity of PP2A did not change except for a decrease in the membrane-bound activity between 2 and 14 days. These results show that the subcellular distribution and activity of PP1 is selectively regulated during post-hatch development and that membrane association and inactivation of PP1 are independent events.


Monoclonal antibody therapy of inflammatory bowel disease.
Animal models of inflammatory bowel disease have provided insight in the regulation of mucosal inflammation. This has resulted in novel therapeutic approaches that specifically target a single inflammatory mediator. Monoclonal antibody therapy has been used in steroid refractory Crohn's disease patients. Anti-TNF antibody administration induced complete remissions and few side effects were observed. Although these findings need to be confirmed in controlled and long term treatment studies they may guide the development of specific and effective therapies for these diseases.


Electromagnetic image guidance in gynecology: prospective study of a new laparoscopic imaging and targeting technique for the treatment of symptomatic uterine fibroids.
Uterine fibroids occur singly or as multiple benign tumors originating in the myometrium. Because they vary in size and location, the approach and technique for their identification and surgical management vary. Reference images, such as ultrasound images, magnetic resonance images, and sonohystograms, do not provide real-time intraoperative findings. Electromagnetic image guidance, as incorporated in the Acessa Guidance System, has been cleared by the FDA to facilitate targeting and ablation of uterine fibroids during laparoscopic surgery. This is the first feasibility study to verify the features and usefulness of the guidance system in targeting symptomatic uterine fibroids-particularly hard-to-reach intramural fibroids and those abutting the endometrium. One gynecologic surgeon, who had extensive prior experience in laparoscopic ultrasound-guided identification of fibroids, treated five women with symptomatic uterine fibroids using the Acessa Guidance System. The surgeon evaluated the system and its features in terms of responses to prescribed statements; the responses were analyzed prospectively. The surgeon strongly agreed (96 %) or agreed (4 %) with statements describing the helpfulness of the transducer and handpiece's dynamic animation in targeting each fibroid, reaching the fibroid quickly, visualizing the positions of the transducer and handpiece within the pelvic cavity, and providing the surgeon with confidence when targeting the fibroid even during "out-of-plane" positioning of the handpiece. The surgeon's positive user experience was evident in the guidance system's facilitation of accurate handpiece tip placement during targeting and ablation of uterine fibroids. Continued study of electromagnetic image guidance in the laparoscopic identification and treatment of fibroids is warranted. ClinicalTrials.gov Identifier: NCT01842789.


Hydration properties of natural and synthetic DNA sequences with methylated adenine or cytosine bases in the R.DpnI target and BDNF promoter studied by molecular dynamics simulations.
Adenine and cytosine methylation are two important epigenetic modifications of DNA sequences at the levels of the genome and transcriptome. To characterize the differential roles of methylating adenine or cytosine with respect to their hydration properties, we performed conventional MD simulations and free energy perturbation calculations for two particular DNA sequences, namely the brain-derived neurotrophic factor (BDNF) promoter and the R.DpnI-bound DNA that are known to undergo methylation of C5-methyl cytosine and N6-methyl adenine, respectively. We found that a single methylated cytosine has a clearly favorable hydration free energy over cytosine since the attached methyl group has a slightly polar character. In contrast, capping the strongly polar N6 of adenine with a methyl group gives a slightly unfavorable contribution to its free energy of solvation. Performing the same demethylation in the context of a DNA double-strand gave quite similar results for the more solvent-accessible cytosine but much more unfavorable results for the rather buried adenine. Interestingly, the same demethylation reactions are far more unfavorable when performed in the context of the opposite (BDNF or R.DpnI target) sequence. This suggests a natural preference for methylation in a specific sequence context. In addition, free energy calculations for demethylating adenine or cytosine in the context of B-DNA vs. Z-DNA suggest that the conformational B-Z transition of DNA transition is rather a property of cytosine methylated sequences but is not preferable for the adenine-methylated sequences investigated here.


Halogen-Substituted Spin-Crossover Fe(III) Compounds with Photoresponsive Properties.
Halogen-substituted Fe(III) compounds, [Fe(HphsalpmX)2]PTFB (HphsalpmX = 5-X-(R,S)-((phenyl(2-pyridyl)methylimino)methyl)phenol, PTFB = phenyltrifluoroborate; X = F for 1, Cl for 2, Br for 3) and [Fe(HphsalpmX)2]PTFB·MeOH (X = I for 4·MeOH), were synthesized. Compounds 1, 4·MeOH, and its desolvated form 4 exhibited an invariant high-spin state in the whole temperature range, while 2 and 3 underwent gradual, nonhysteretic, and incomplete spin crossover (SCO) with transition temperatures (TC) of 153 and 220 K, respectively. Interestingly, the SCO-active compounds 2 and 3 showed light-induced excited spin-state trapping (LIESST) effects at 10 K, and light-induced reversible ON/OFF switching behaviors were realized by alternately using 880 and 1064 nm light, while the thermally inert compound 4·MeOH unexpectedly showed a reverse-LIESST effect. These results may help to design and synthesize new photoresponsive SCO Fe(III) compounds for the development of switchable materials.


Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial.
Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study. ISRCTN Registry identifier: ISRCTN89812075 . Registered on 30 August 2016.


Seasonal distribution of Henoch-Schönlein purpura.
A review of 76 Southampton children with Henoch-Schönlein purpura has confirmed that there is no evidence of a streptococcal aetiology in the majority of cases of this disease. Among these patients the frequency of preceding respiratory infection of all kinds was only 7 percent greater than that in controls. Data on month of admission in four areas of England and Scotland show that the incidence of the disease is lowest in the June-August period. Contrary to previous findings there is no marked peak of incidence in any single month.


E2F-dependent induction of p14ARF during cell cycle re-entry in human T cells.
The ARF protein, encoded by alternate exon usage within the CDKN2A locus, provides a link between the retinoblastoma (pRb) and p53 tumor suppressor pathways. Agents that disable pRb or otherwise impinge on the E2F family of transcription factors induce expression of ARF, resulting in stabilization of p53 and activation of p53-regulated genes. However, in some cell types ARF is not induced upon cell cycle re-entry, as expected of a conventional E2F target gene, leading to the suggestion that the ARF promoter only responds to supra-physiological or aberrant levels of E2F. These properties have recently been attributed to a variant E2F binding site but attempts to map specific response elements within the ARF promoter have generally yielded confusing answers. Here we show that in IL2-dependent T-lymphocytes, ARF expression is induced as cells progress from G(0) into S phase, in parallel with other bona fide E2F target genes. This is accompanied by increased association of E2F1 with the endogenous ARF promoter. Our findings suggest that the ability of ARF to register normal proliferative cues depends on the levels of E2F generated in different settings and argue against the idea that it reacts exclusively to oncogenic signals.


Pharmacy and Physician Assistant Dual Degree: An Analysis of Its Value and Implications on the Profession.
The pharmacy and physician assistant dual degree is one of the newest programs offered and has been predicted to have a high likelihood of growth in the future. With only an additional year of education, the PharmD-PA dual degree holder will have prescriptive authority upon graduation to expand their clinical roles. Additionally, by combining both medical and pharmacotherapeutics education, these mid-level practitioners could potentially improve healthcare shortages and allow for improvements in patient care. While there are established PharmD-PA dual degree programs, there is low enrollment coupled by rigorous curriculums and financial burdens that students must endure. Despite its limitations, this novel dual degree program offers pharmacy students another method to provide clinical care apart from the post-graduate opportunities. Schools of Pharmacy should look into the development of PharmD-PA dual degree programs as a unique marketing opportunity for admissions and as a non-traditional method of career advancement.


RNase activity of polynucleotide phosphorylase is critical at low temperature in Escherichia coli and is complemented by RNase II.
In Escherichia coli, the cold shock response is exerted upon a temperature change from 37 degrees C to 15 degrees C and is characterized by induction of several cold shock proteins, including polynucleotide phosphorylase (PNPase), during acclimation phase. In E. coli, PNPase is essential for growth at low temperatures; however, its exact role in this essential function has not been fully elucidated. PNPase is a 3'-to-5' exoribonuclease and promotes the processive degradation of RNA. Our screening of an E. coli genomic library for an in vivo counterpart of PNPase that can compensate for its absence at low temperature revealed only one protein, another 3'-to-5' exonuclease, RNase II. Here we show that the RNase PH domains 1 and 2 of PNPase are important for its cold shock function, suggesting that the RNase activity of PNPase is critical for its essential function at low temperature. We also show that its polymerization activity is dispensable in its cold shock function. Interestingly, the third 3'-to-5' processing exoribonuclease, RNase R of E. coli, which is cold inducible, cannot complement the cold shock function of PNPase. We further show that this difference is due to the different targets of these enzymes and stabilization of some of the PNPase-sensitive mRNAs, like fis, in the Delta pnp cells has consequences, such as accumulation of ribosomal subunits in the Delta pnp cells, which may play a role in the cold sensitivity of this strain.


Treatment of hyperthyroidism: effects on hepatic lipase, lipoprotein lipase, LCAT and plasma lipoproteins.
The activities of hepatic lipase and of lipoprotein lipase, the elimination rate of exogenous triglyceride and the cholesterol esterification rate were determined and related to plasma lipoprotein concentrations in 16 patients before and after treatment for hyperthyroidism. The activity of hepatic lipase was significantly higher (65%) before than after treatment, while the activity of lipoprotein lipase and the elimination rate of exogenous triglyceride remained unchanged. The endogenous cholesterol esterifying ability decreased after treatment, whereas no change occurred in the fractional cholesterol esterification rate measured with normal plasma as substrate. The concentrations of LDL-cholesterol and HDL-cholesterol increased significantly after treatment. The decrease in hepatic lipase activities was correlated to the decrease in S-T3 concentrations (r = 0.77, P less than 0.001) and to the increase in HDL-cholesterol concentrations (r = 0.51, P less than 0.05). The activities of lipoprotein lipase were positively correlated to the concentrations of HDL-cholesterol both before (r = 0.54, P less than 0.05) and after (r = 0.59, P less than 0.05) treatment. These results support the view that hepatic lipase and lipoprotein lipase are both important determinants of plasma HDL concentrations and suggest that an increased hepatic lipase activity contributes to the lower HDL levels in hyperthyroid patients.


BLOOD FLOW IN THE CIRCLE OF WILLIS: MODELING AND CALIBRATION.
A numerical model based on one-dimensional balance laws and ad hoc zero-dimensional boundary conditions is tested against experimental data. The study concentrates on the circle of Willis, a vital subnetwork of the cerebral vasculature. The main goal is to obtain efficient and reliable numerical tools with predictive capabilities. The flow is assumed to obey the Navier-Stokes equations, while the mechanical reactions of the arterial walls follow a viscoelastic model. Like many previous studies, a dimension reduction is performed through averaging. Unlike most previous work, the resulting model is both calibrated and validated against in vivo data, more precisely transcranial Doppler data of cerebral blood velocity. The network considered has three inflow vessels and six outflow vessels. Inflow conditions come from the data, while outflow conditions are modeled. Parameters in the outflow conditions are calibrated using a subset of the data through ensemble Kalman filtering techniques. The rest of the data is used for validation. The results demonstrate the viability of the proposed approach.


Factors Affecting Healthcare Provider Referral to Heart Function Clinics: A Mixed-Methods Study.
Heart failure (HF) care providers are gatekeepers for patients to appropriately access lifesaving HF clinics. The aim of this study was to investigate referring providers' perceptions regarding referral to HF clinics, including the impact of provider specialty and the coronavirus disease pandemic. An exploratory, sequential design was used in this mixed-methods study. For the qualitative stage, semistructured interviews were performed with a purposive sample of HF providers eligible to refer (ie, nurse practitioners, cardiologists, internists, primary care and emergency medicine physicians) in Ontario. Interviews were conducted via Microsoft Teams. Transcripts were analyzed concurrently by 2 researchers independently using NVivo, using a deductive-thematic approach. Then, a cross-sectional survey of similar providers across Canada was undertaken via REDCap (Research Electronic Data Capture), using an adapted version of the Provider Attitudes toward Cardiac Rehabilitation and Referral scale. Saturation was achieved upon interviewing 7 providers. Four themes arose: knowledge about clinics and their characteristics, providers' clinical expertise, communication and relationship with their patients, and clinic referral process and care continuity. Seventy-three providers completed the survey. The major negative factors affecting referral were skepticism regarding clinic benefit (4.1 ± 0.9/5), a bad patient experience and believing they are better equipped to manage the patient (both 3.9). Cardiologists more strongly endorsed clarity of referral criteria, referral as normative and within-practice referral supports as supporting appropriate referral versus other professionals ( P s < .02), among other differences. One-third (n = 13) reported the pandemic impacted their referral practices (eg, limits to in-person care, patient concerns). Although there are some legitimate barriers to appropriate clinic referral, greater provider education and support could facilitate optimal patient access.


Chronic daily administration of selegiline and EGb 761 increases brain's resistance to ischemia in mice.
Brief cerebral ischemia is reported to cause selective neuronal necrosis, apoptotic cell death, silent infarcts and, when recurrent, cognitive decline. Acute administration of selegiline and EGb 761 have been shown to have anti-apoptotic and neuroprotective effects in experimental ischemia. Their daily use is currently advised to slow down cognitive decline in patients with vascular dementia. Hence, unlike previous studies, we studied the neuroprotective action of chronic daily administration of these drugs in Swiss mice subjected to 30-min middle cerebral artery occlusion and 72 h of reperfusion since this model was reported to induce a slowly evolving infarct with profuse apoptotic cell death. Infarct area was evaluated by H&E staining on coronal brain sections and, apoptotic cells were identified by histological criteria, terminal transferase-mediated d-UTP nick-end labeling (TUNEL) and by immunohistochemical detection of caspase-cleaved actin fragments (fractin). Fifty-one mice received daily intraperitoneal injections of 10 mg/kg selegiline (n=18) or 50 mg/kg EGb 761 (n=17) or equal volume of saline (n=16) for 10-14 days before but not on the day of insult. The infarct volume, number of TUNEL- and fractin-positive cells were significantly reduced in treatment groups by 30, 42 and 51% (selegiline) and, 27, 27 and 29% (EGb 761), respectively. These data suggest that prophylactic use of selegiline and EGb 761 could increase the brain's resistance to mild ischemic injury.


Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats.
The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended. Meanwhile, in ASD group, the average escape latency and the frequency of crossing plates were decreased, the apoptotic index (AI) detected by TUNEL assay was increased, and the expression of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) analyzed was decreased with great difference compared with normal group (P<0.01). However, rapamycin treatment in ASD rats mitigated the ASD-like social behavior, such as the frequencies of straight and grooming. Furthermore, rapamycin shortened the average escape latency, but increased the frequency of crossing plates of ASD rats. In hippocampus, rapamycin decreased the AI, but increased the levels of BDNF and Bcl-2 (P<0.01) of ASD rats. These findings revealed that rapamycin significantly mitigated the social behavior by enhancing the expression of BDNF and Bcl-2 to suppress the hippocampus apoptosis in VPA-induced ASD rats.


Challenges to healthy eating for people with diabetes in a low-income, minority neighborhood.
This study used qualitative interviews with black and Latino participants with diabetes to further understanding about types of foods eaten, food preparation, sources of foods and meals, communication with providers, and effects of race and ethnicity on eating in this population. Researchers recruited black and Latino adults from East Harlem, New York, to participate in four English and Spanish focus groups. Discussions were transcribed, coded, and analyzed to uncover prevalent themes, which were interpreted with the Common Sense Model of Self-Regulation. Thirty-seven adults with diabetes participated in four focus groups. The following four major themes emerged from the analyses: 1) The food environment limited participants' access to healthy foods; 2) understanding of diabetes and communication with clinicians about healthy eating was limited and abstract; 3) the short-term, negative consequences of healthy eating outweighed the benefits; and 4) stress, in large part from poverty and discrimination, was seen as a causal factor for both poor eating and diabetes. Participants' responses indicated that using healthy eating to control diabetes does not provide immediate, tangible results. Thus, these participants followed their own common sense to guide their diabetes management and improve their health. Clinicians may be better able to help patients eat healthfully if they consider these factors during medical visits.


[Traumatic life events and problem solving skills in psychiatric outpatients: relationships with suicidal behavior].
To investigate the prevalence and the relationship of traumatic life events and problem solving skills to suicidal behavior in a group of psychiatric outpatients. The study was conducted with 121 (57 % women) psychiatric outpatients. Patients who accepted participation filled in a questionnaire that contained questions about socio-demographics, clinical features, suicidal behavior, traumatic life-events, and a problem-solving inventory. Data were analyzed by means of t-tests, chi-square tests, one-way analysis of variance and multiple logistic regression analyses. Of the patients, 43.2 % (47.8 % women) reported having thought and 28.7 % (29.7 % women) reported having attempted suicide. 75.4 % of the sample experienced at least one traumatic life-event. On average, a person experienced approximately 2 (SD = 1.7) traumatic events. Two logistic regression analyses showed that inefficient problem solving was an independent predictor of both suicidal thoughts and attempts. Number of traumatic events appeared to be an independent predictor of suicidal attempts after the problem solving skills. In accordance with diathesis-stress model, both suicidal thoughts and attempts were found to be most frequent among persons with inefficient problem solving skills and who were also exposed to a large amount of traumatic life events. Suicidal behavior and traumatic life events are common among psychiatric patients. Findings indicate that inefficient problem solving may be an independent predictor of both suicidal ideation and attempts. Suicidal behavior, traumatic life-events and problem solving skills should be addressed during psychiatric assessment. Study findings imply that problem solving therapy may be an important approach that can be used for the treatment of psychiatric patients exhibiting suicidal behavior.


Soil-transmitted helminth infection in school age children in Sierra Leone after a decade of preventive chemotherapy interventions.
Baseline mapping of soil-transmitted helminth (STH) infections among school age children (SAC) in 2008-2009 found high or moderate prevalence in 13 of the 14 districts in Sierra Leone. Following these surveys, mass drug administration (MDA) of mebendazole/albendazole was conducted biannually at national level targeting pre-school children (PSC) aged 12-59 months and intermittently at sub-national level targeting SAC. In addition, MDA with ivermectin and albendazole for eliminating lymphatic filariasis (LF) has been conducted nationwide since 2010 targeting individuals over 5 years of age. Each MDA achieved high coverage, except in 2014 when all but one round of MDA for PSC was cancelled due to the Ebola emergency. The objective of the current study was to determine the prevalence and intensity of STH infections among SAC after a decade of these deworming campaigns. Seventy-three schools in 14 districts were purposefully selected, including 39 schools from the baseline surveys, with approximately two sites from each of low, moderate and high prevalence categories at baseline per district. Fresh stool samples were collected from 3632 children aged 9-14 years (male 51%, female 49%) and examined using the Kato Katz technique. The prevalence of STH infections in Sierra Leone decreased in 2016 compared to 2008: Ascaris lumbricoides 4.4% (95% confidence interval [CI]: 3.7-5.1%) versus 6.6% (95% CI: 0-25%), Trichuris trichiura 0.7% (95% CI: 0.5-1.1%) versus 1.8% (95% CI: 0-30.2%), hookworm 14.9% (95% CI: 13.8-16.1) versus 38.5% (95% CI: 5.4-95.1%), and any STH 18.3% (95% CI:17.0-19.5%) versus 48.3% (CI: 5.4-96.3%), respectively. In 2016, no district had high hookworm prevalence and four districts had moderate prevalence, compared with eight and four districts respectively in 2008. In 2016, the arithmetic mean hookworm egg count in all children examined was light: 45.5 eggs per gram (EPG) of faeces, (95% CI:\ 35.96-55.07 EPG); three (0.08%) children had heavy infections and nine (0.25%) children had moderate infections. Sierra Leone has made considerable progress toward controlling STH as a public health problem among SAC. As LF MDA phases out (between 2017 and 2021), transition of deworming to other platforms and water and sanitation strategies need to be strengthened to maintain STH control and ultimately interrupt transmission.


Growth of wurtzite CdTe nanowires on fluorine-doped tin oxide glass substrates and room-temperature bandgap parameter determination.
The growth of CdTe nanowires, catalyzed by Sn, was achieved on fluorine-doped tin oxide glass by physical vapor transport. CdTe nanowires grew along the 〈0001〉 direction, with a very rare and phase-pure wurtzite structure, at 290 °C. CdTe nanowires grew under Te-limited conditions by forming SnTe nanostructures in the catalysts and the wurtzite structure was energetically favored. By polarization-dependent and power-dependent micro-photoluminescence measurements of individual nanowires, heavy and light hole-related transitions could be differentiated, and the fundamental bandgap of wurtzite CdTe at room temperature was determined to be 1.562 eV, which was 52 meV higher than that of zinc-blende CdTe. From the analysis of doublet photoluminescence spectra, the valence band splitting energy between heavy hole and light hole bands was estimated to be 43 meV.


Accuracy of enteral pumps: in vitro performance.
There are few data on the accuracy of pumps used to deliver enteral formulas. Enteral pump manufacturers claim that accuracy is within 10% of the selected flow rate. We evaluated 15 pumps: Flexiflo Companion (n = 5), Travenol 2100 (n = 5), and Kangaroo 324 (n = 5). Three types of formula at room temperature were infused at 10, 100, and 300 mL/h. The formulas used were Jevity, Ensure Plus, and Suplena with added Promod. The Flexiflo Companion and Kangaroo 324 pumps delivered 90% to 110% of the expected volume using the ready-to-feed formulas. The Travenol 2100 pumps averaged less than 90% of the selected flow rates for the three formulas infused. All three pumps delivered less than 90% of the expected volume using a formula with an added powder, but the Travenol 2100 delivered the highest volume of this same formula. There was no significant difference in the delivery of Jevity with the Flexiflo Companion (104% +/- 5% SD) and the Kangaroo 324 pumps (99% +/- 4% SD), but the flow rate was significantly lower with the Travenol 2100 pumps (80% +/- 6% SD). There was no significant difference in the flow rate of Ensure Plus with the Kangaroo 324 (95% +/- 7% SD) and the Travenol 2100 pumps (89% +/- 4% SD). The flow rate of Ensure Plus with the Flexiflo Companion pumps was significantly higher (107% +/- 4% SD).(ABSTRACT TRUNCATED AT 250 WORDS)


A goodness of fit test for sparse 2p contingency tables.
When a model is fitted to data in a 2p contingency table many cells are likely to have very small expected frequencies. This sparseness invalidates the usual approximation to the distribution of the chi-squared or log-likelihood tests of goodness of fit. We present a solution to this problem by proposing a test based on a comparison of the observed and expected frequencies of the second-order margins of the table. A chi2 approximation to the sampling distribution is provided using asymptotic moments. This can be straightforwardly calculated from the expected cell frequencies. The new test is applied to several previously published examples relating to the fitting of latent variable models, but its application is quite general.


[High frequency discharges as a non-specific EMG activity in adult acid maltase deficiency (author's transl)].
The clinical diagnosis of a 34-year-old man was muscular dystrophy of the ascending limb-girdle type. There were no detectable signs of myotonia. Histological and biochemical investigations confirmed an acid maltase deficiency (AMD). Electromyography demonstrated a myopathic pattern, fibrillation potentials, normal nerve conduction velocity, and so-called pseudomyotonic or bizarre high frequency discharges. In the literature this EMG activity has been described as characteristic for AMD. But it seems to be a nonspecific EMG sign, which occurs in myogenic and neurogenic lesions such as myositis, metabolic and dystrophic myopathy, nuclear damage, radiculopathy, and neuropathy. It is therefore of little diagnostic value.


Shape-control and electrocatalytic activity-enhancement of Pt-based bimetallic nanocrystals.
Due to the increasing worldwide energy demand and environ-mental concerns, the need for alternative energy sources is growing stronger, and platinum catalysts in fuel cells may help make the technologies a reality. However, the pursuit of highly active Pt-based electrocatalysts continues to be a challenge. Scientists developing electrocatalysts continue to focus on characterizing and directing the construction of nanocrystals and advancing their electrochemical applications. Although chemists have worked on Pt-based bimetallic (Pt-M) preparations in the past, more recent research shows that both shape-controlled Pt-M nanocrystals and the assembly of these nanocrystals into supercrystals are promising new directions. A solution-based synthesis approach is an effective technique for preparing crystallographic facet-directed nanocatalysts. This is aided by careful selection of the metal precursor, capping ligand, reducing agent, and solvent. Incorporating a secondary metal M into the Pt lattice and manipulating the crystal facets on the surface cooperatively alter the electrocatalytic behavior of these Pt-M bimetallic nanocrystals. Specifically, chemists have extensively studied the {111}- and {100}-terminated crystal facets because they show unique atomic arrangement on surfaces, exhibit different catalytic performance, and possess specific resistance to toxic adsorbed carbon monoxide (COads). For catalysts to have maximum efficiency, they need to have resistance to COads and other poisonous carbon-containing intermediates when the catalysts operate under harsh conditions. A necessary design to any synthesis is to clearly understand and utilize the role of each component in order to successfully induce shape-controlled growth. Since chemists began to understand Pt nanocrystal shape-dependent electrocatalytic activity, the main obstacles blocking proton exchange membrane fuel cells are anode poisoning, sluggish kinetics at the cathode, and low activity. In this Account, we discuss the basic concepts in preparation of Pt-M bimetallic nanocrystals, focusing on several immaculate examples of manipulation at the nanoscale. We briefly introduce the prospects for applying Pt-M nanocrystals as electrocatalysts based on the electronic and geometric standpoints. In addition, we discuss several key parameters in the solution-based synthesis approach commonly used to facilitate Pt-M nanocrystals, such as reaction temperature and time, the combination of organic amines and acids, gaseous adsorbates, anionic species, and solvent. Each example features various nanoscale morphologies, such as spheres, cubes, octahedrons, and tetrahedrons. Additionally, we outline and review the superior electrocatalytic performances of the recently developed high-index Pt-M nanostructures. Next, we give examples of the electrocatalytic capabilities from these shape-defined Pt-M architectures by highlighting significant accomplishments in specific systems. Then, using several typical cases, we summarize electrochemical evaluations on the Pt-based shape-/composition-dependent nanocatalysts toward reactions on both the anode and the cathode. Lastly, we provide an outlook of current challenges and promising directions for shape-controlled Pt-M bimetallic electrocatalysts.


[Depression in independently living elderly, a study with the Zung-12].
The psychometric properties of the Zung-12, a short rating scale for the measurement of depression, were studied in a random sample (N = 79) taken from an elderly population living in their own homes in a medium sized town. Both internal and test-retest reliability of the Zung-12 are satisfactory. According to factor analyses the rating scale has a unidimensional structure. High correlations with the Befindlichkeitsskala and the SSWO support the convergent validity. No relation is found between depression score and age, amount of help received and household composition. Women and subjects with lower education appeared to have higher depression scores than respectively men and subjects with higher education. Administration of the Zung-12 in the morning produces higher depression scores than in the afternoon. 10% of the subjects score above the cutting point on one of the occasions, 4% on both occasions. Reliable change scores were calculated to indicate the statistical significance of differences between two administrations.


Phenotypic effects of allotetraploidization of wild Arachis and their implications for peanut domestication.
Several species of Arachis have been cultivated for their edible seeds, historically and to the present day. The diploid species that have a history of cultivation show relatively small signatures of domestication. In contrast, the tetraploid species A. hypogaea evolved into highly domesticated forms and became a major world crop, the cultivated peanut. It seems likely that allotetraploidization (hybridity and/or tetraploidization) in some way enhanced attractiveness for cultivation. Here we investigate this using six different hybridization and tetraploidization events, from distinct Arachis diploid species, including one event derived from the same wild species that originated peanut. Twenty-six anatomical, morphological, and physiological traits were examined in the induced allotetraploid plants and compared with their wild diploid parents. Nineteen traits were transgressive (showed strong response to hybridization and chromosome duplication): allotetraploids had larger leaves, stomata and epidermal cells than did their diploid parents. In addition, allotetraploids produced more photosynthetic pigments. These traits have the same trend across the different hybrid combinations, suggesting that the changes are more likely due to ploidy rather than hybridity. In contrast, seed dimensions and seed mass did not significantly change in response to hybridization or tetraploidization. We suggest that the original allotetraploid that gave rise to cultivated peanut may have been attractive because of an increase in plant size, different transpiration characteristics, higher photosynthetic capacity, or other characteristics, but contrary to accepted knowledge, increased seed size was unlikely to have been important in the initial domestication.


Influences of the accommodative stimulus and aging on the accommodative microfluctuations.
The effects of the accommodative stimulus and age on the accommodative microfluctuations were investigated in human subjects. Accommodative responses were measured by using an infrared (IR) optometer, and accommodative microfluctuations were quantified by power spectrum analysis. Two frequency bands were determined: low frequency components (< 0.5 Hz, LFC) and high frequency components (1.3 to 2.2 Hz, HFC). Among younger subjects, the changes in the HFC in response to the accommodative stimuli differed between subjects. The activity of the HFC reached a peak in the center of the accommodation range, whereas the activity of the LFC was its maximum in the presence of darkness or blur in the over-accommodation range. Smaller changes in the magnitude of the HFC were observed in older subjects. Although the LFC may be controlled neurologically, the HFC seems to arise from mechanical and elastic properties of the lens, and may be modulated by other physiological rhythmic variations.


Pharmacists' Stellar experience can create Five-Star Success.
The evolving health care system has put an increasing emphasis on balancing quality, outcomes, and costs. As part of this evolution, the Centers for Medicare & Medicaid Services (CMS) is using a Five-Star Quality Rating System to evaluate the quality of care provided by Medicare Advantage and Part D prescription drug plans. At the same time, drug plans are using a Five-Star system to rate pharmacies, which contribute to the CMS ratings of nursing facilities. More than ever, pharmacists can play a significant role in helping facilities, plans, and even pharmacies achieve the highest possible ratings and maintain those standards over time.


Evolving sensitivity.
Engineering gene circuits with novel functions holds promise for broad applications in biology, engineering, and medicine. Directed evolution complements rational design as an important strategy for optimizing gene circuits and circuit elements.


Cyanidin suppresses autophagic activity regulating chondrocyte hypertrophic differentiation.
Cartilage is a kind of special connective tissue which does not contain neither blood vessels nor lymphatics and nerves. Therefore, the damage in cartilage is difficult to be repaired spontaneously. Constructing tissue engineered cartilage provides a new technique for cartilage repairing. Mesenchymal stem cells (MSCs) possess a unique capability of self-renew and can differentiate into pre-chondrocytes which are frequently applied as seed cells in tissue engineering. However, in regenerated cartilage the chondrocytes derived from MSCs can hardly maintain homeostasis and preferentially present hypertrophic like phenotype. We investigated the effects of cyanidin, a natural organic compound, on chondrogenic and subsequent hypertrophic differentiation of MSCs in order to seek approaches to inhibit chondrocyte hypertrophy. We evaluated the effects of cyanidin on expression of chondrogenic and hypertrophic marker genes through RT-PCR, Western blot, alcian blue staining, and immunocytochemistry. The results showed that both chondrogenic related genes Sox9, Col2a1, and hypertrophic marker genes Runx2, Col10a1 were inhibited by cyanidin. In addition, we found that cyanidin promoted Nrf2 and p62 expression and suppressed LC3B expression during chondrogenic stage of MSCs. Meanwhile phosphorylation of IκBα and autophagosome related protein LC3B were inactivated by cyanidin during chondrocyte hypertrophic stage. Furthermore, rapamycin, an autophagy activator, abrogated the inhibitory effect of cyanidin on chondrogenic, and hypertrophic differentiation of MSCs. In conclusion, one potential mechanism of cyanidin, by which the chondrogenic and hypertrophic differentiation of MSCs were inhibited, was due to decreased autophagy activity. Our results indicated that cyanidin was a potential therapeutic agent for keeping mature chondrocyte functions.


Live three-dimensional echocardiography: imaging principles and clinical application.
Live three-dimensional echocardiography (L3DE) is an important breakthrough in the field of medical ultrasound. It will provide a great potential tool for clinical diagnosis and treatment. In this article, the authors first review the bottlenecks in 3D cardiac imaging and the technical principles of L3DE that have been used to overcome some of these problems. We then discuss the scanning methods, clinical usefulness, and the future of L3DE, drawing on our experiences in examining 124 human patients and in conducting animal verification studies with a live 3D ultrasound system.


Giving room to subjectivity in understanding and assessing problem gambling: A patient-centered approach focused on quality of life.
Problem gambling is characterized by high stigma and self-stigma, making relevant measurement of the burden of the disorder complex. The aim of our qualitative study was to describe health-related quality of life (HRQOL) impacted by problem gambling from the patients' perspective. We conducted 6 focus groups with 25 current or lifetime at-risk problem gamblers to identify key domains of quality of life impacted by problem gambling. A content analysis from the focus groups data was conducted using Alceste© software, using descendant hierarchical classification analysis, to obtain stable classes and the significant presences of reduced forms. The class of interest, detailing the core of impacted quality of life, was described using a cluster analysis. Thematic content analysis identified three stable classes. Class 1 contained the interviewers' speech. Class 3 was composed of the vocabulary related to gambling practice, games and gambling venues (casino, horse betting, etc.). Class 2 described the core of impact of gambling on quality of life and corresponded to 43% of the analyzed elementary context units. This analysis revealed seven key domains of impact of problem gambling: loneliness, financial pressure, relationships deterioration, feeling of incomprehension, preoccupation with gambling, negative emotions, and avoidance of helping relationships. We identified, beyond objective damage, the subjective distress felt by problem gamblers over the course of the disorder and in the helping process, marked in particular by stigma and self-stigma. Four impacted HRQOL areas were new and gambling-specific: loneliness, feeling of incomprehension, avoidance of helping relationships, and preoccupation with gambling. These results support the relevance of developing, in a next step, a specific HRQOL scale in the context of gambling.


[Occult rectal prolapse: functional results after rectopexy].
In the present work the Authors have studied 19 patients with occult rectal prolapse evaluating symptoms and functional results after posterior abdominal rectopexy. Symptoms of internal rectal procidentia appear as a definite syndrome. In our patients pain upon defecation, this being often localized to the perineal and sacral region, was observed in 14 on 19 cases, while fecal incontinence was present in 5 cases (29%) and rectal bleeding in 8 (44%). These compliances are relieved by the anatomical correction of the rectal intussusception, but the preexisting functional disorders in the mechanism of defecation appear to be unaffected by rectopexy. (Sensation of obstruction 11 cases (58%) preop. e 9 cases (53%) postop.).


Functional classification, genomic organization, putatively cis-acting regulatory elements, and relationship to quantitative trait loci, of sorghum genes with rhizome-enriched expression.
Rhizomes are organs of fundamental importance to plant competitiveness and invasiveness. We have identified genes expressed at substantially higher levels in rhizomes than other plant parts, and explored their functional categorization, genomic organization, regulatory motifs, and association with quantitative trait loci (QTLs) conferring rhizomatousness. The finding that genes with rhizome-enriched expression are distributed across a wide range of functional categories suggests some degree of specialization of individual members of many gene families in rhizomatous plants. A disproportionate share of genes with rhizome-enriched expression was implicated in secondary and hormone metabolism, and abiotic stimuli and development. A high frequency of unknown-function genes reflects our still limited knowledge of this plant organ. A putative oligosaccharyl transferase showed the highest degree of rhizome-specific expression, with several transcriptional or regulatory protein complex factors also showing high (but lesser) degrees of specificity. Inferred by the upstream sequences of their putative rice (Oryza sativa) homologs, sorghum (Sorghum bicolor) genes that were relatively highly expressed in rhizome tip tissues were enriched for cis-element motifs, including the pyrimidine box, TATCCA box, and CAREs box, implicating the gibberellins in regulation of many rhizome-specific genes. From cDNA clones showing rhizome-enriched expression, expressed sequence tags forming 455 contigs were plotted on the rice genome and aligned to QTL likelihood intervals for ratooning and rhizomatous traits in rice and sorghum. Highly expressed rhizome genes were somewhat enriched in QTL likelihood intervals for rhizomatousness or ratooning, with specific candidates including some of the most rhizome-specific genes. Some rhizomatousness and ratooning QTLs were shown to be potentially related to one another as a result of ancient duplication, suggesting long-term functional conservation of the underlying genes. Insight into genes and pathways that influence rhizome growth set the stage for genetic and/or exogenous manipulation of rhizomatousness, and for further dissection of the molecular evolution of rhizomatousness.


miR-29a promotes hepatitis B virus replication and expression by targeting SMARCE1 in hepatoma carcinoma.
To investigate the functional role and underlying molecular mechanism of miR-29a in hepatitis B virus (HBV) expression and replication. The levels of miR-29a and SMARCE1 in HBV-infected HepG2.2.15 cells were measured by quantitative real-time PCR and western blot analysis. HBV DNA replication was measured by quantitative PCR and Southern blot analysis. The relative levels of hepatitis B surface antigen and hepatitis B e antigen were detected by enzyme-linked immunosorbent assay. The Cell Counting Kit-8 (CCK-8) was used to detect the viability of HepG2.2.15 cells. The relationship between miR-29a and SMARCE1 were identified by target prediction and luciferase reporter analysis. miR-29a promoted HBV replication and expression, while SMARCE1 repressed HBV replication and expression. Cell viability detection indicated that miR-29a transfection had no adverse effect on the host cells. Moreover, SMARCE1 was identified and validated to be a functional target of miR-29a. Furthermore, restored expression of SMARCE1 could relieve the increased HBV replication and expression caused by miR-29a overexpression. miR-29a promotes HBV replication and expression through regulating SMARCE1. As a potential regulator of HBV replication and expression, miR-29a could be a promising therapeutic target for patients with HBV infection.


[Inderdisciplinary care of patients with short-bowel-syndrome in Germany: A comparative Cost-of-Illness analysis of in- and outpatient care].
Short-bowel-syndrome (SBS) is an often chronic disease with high morbidity. The aim of this study was to evaluate the complexity of SBS treatment and the economic burden on a treating hospital. Anonymized data of eleven consecutive SBS patients from the University Hospital of Bonn were included. Parameters of medical resources were considered for year of diagnosis (YOD) and a follow-up (FU) period of three years. Subsequently, costs were evaluated according to the corresponding catalogues. Median inpatient days were 96 days in YOD and decreased to three days in the third year of FU. Median cost of inpatient treatment decreased from approximately 84 500 € auf 3200 €. While major visceral surgery was usually required in the YOD, catheter-associated interventions dominated during further FU. Actual reimbursement according to the G-DRG covered approximately 50 % of inpatient treatment cost, for outpatient care only est. 16.5 % of costs were covered. Annual costs for medication, parenteral nutrition and GLP-2-analogon treatment added up to 6752 €, 48 485 € and 138 442 €, respectively. The interdisciplinary medical care of SBS-patients is resource-intensive and expensive. The required treatment shifts from the in- to the outpatient sector. Both settings are at present not adequately reimbursed. Hence, this imbalance may endanger adequate care for SBS-patients in the future in times of economic rationale. In concordance with other rare disease management programs, additional measures are needed to provide and improve interdisciplinary treatment of SBS.


Complete defect in vWF-cleaving protease activity associated with increased shear-induced platelet aggregation in thrombotic microangiopathy.
Von Willebrand factor (vWF) cleaving metalloprotease activity represents an important factor in understanding the pathophysiology of thrombotic microangiopathies (TMA). Thrombotic events, leading to dramatic complications, occur preferentially in the microvasculature. Our aim was to determine the ability of TMA plasma with a complete deficiency of protease activity to promote shear-induced platelet aggregation (SIPA) at high shear rates using a coaxial cylinder shearing device. We have demonstrated the ability of four out of seven TMA plasma to aggregate normal washed platelets at 4,000 s(-1). In these four TMA plasma, significant SIPA was obtained, whereas control plasma did not induce more SIPA than buffer. The % of unusually large (UL) multimers in TMA plasma varied from 1 to 18%. Surprisingly, the extent of SIPA in TMA plasma appeared independent of the percentage of UL multimers. Interestingly, anti-GPIb antibody 6D1 could block completely this pathological aggregation, opening new therapeutic possibilities. In contrast, none of eight other TMA patients' plasma with a normal protease activity, exhibited any increase of SIPA compared with control plasma. These results strongly suggest that the deficiency of vWF-cleaving protease appears to be necessary, but not sufficient for elevated SIPA. In contrast, the % of UL is not associated with increased SIPA.