Associations of self-reported periodontal disease with metabolic syndrome and number of self-reported chronic conditions.
Increasing evidence supports associations between periodontal disease and various chronic conditions. Possible explanations include chronic inflammatory processes, shared pathogens, and shared risk factors, such as smoking and psychosocial stress. The objective of this study was to assess associations of periodontal disease with metabolic syndrome and number of chronic diseases. As part of the Washington Adult Health Survey, a household-based cross-sectional study conducted during 2006-2007 among adults aged 25 years or older in Washington State, we collected questionnaire data, blood samples, and anthropometric measures. We used these data to assess associations of periodontal disease with metabolic syndrome and the number of self-reported chronic diseases, controlling for age, sex, annual household income, smoking, and psychosocial stress. We used both complete case and multiple imputation Poisson regression analyses. In the adjusted complete case analysis, 1.4 times as many chronic conditions were found among people with severe compared with no periodontal disease, and people with severe periodontal disease were 1.5 times more likely to have metabolic syndrome than people with no periodontal disease. Arthritis and liver disease were individually associated with severe periodontal disease. Results of the multiple imputation analyses were similar. These results suggest that people with severe periodontal disease are likely to have more chronic diseases and are more likely to have metabolic syndrome compared with people without periodontal disease. Research about the effectiveness of periodontal treatment to help prevent or control chronic diseases is needed.


Expression Profiles of Genes Related to Development and Progression of Endometriosis and Their Association with Paraben and Benzophenone Exposure.
Increasing evidence has been published over recent years on the implication of endocrine-disrupting chemicals (EDCs), including parabens and benzophenones in the pathogenesis and pathophysiology of endometriosis. However, to the best of our knowledge, no study has been published on the ways in which exposure to EDCs might affect cell-signaling pathways related to endometriosis. We aimed to describe the endometriotic tissue expression profile of a panel of 23 genes related to crucial cell-signaling pathways for the development and progression of endometriosis (cell adhesion, invasion/migration, inflammation, angiogenesis, and cell proliferation/hormone stimulation) and explore its relationship with the exposure of patients to parabens (PBs) and benzophenones (BPs). This cross-sectional study included a subsample of 33 women with endometriosis from the EndEA study, measuring their endometriotic tissue expressions of 23 genes, while urinary concentrations of methyl-, ethyl-, propyl-, butyl-paraben, benzophenone-1, benzophenone-3, and 4-hydroxybenzophenone were determined in 22 women. Spearman's correlations test and linear and logistic regression analyses were performed. The expression of 52.2% of studied genes was observed in >75% of endometriotic tissue samples and the expression of 17.4% (n = 4) of them in 50-75%. Exposure to certain PB and BP congeners was positively associated with the expression of key genes for the development and proliferation of endometriosis. Genes related to the development and progression of endometriosis were expressed in most endometriotic tissue samples studied, suggesting that exposure of women to PBs and BPs may be associated with the altered expression profile of genes related to cellular pathways involved in the development of endometriosis.


Haemodynamic effects of negative pressure wound therapy when using a rigid barrier to prevent heart rupture.
Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up and damaged by the sharp sternum bone edges. The aim of this study was to investigate the haemodynamic effects of placing a rigid barrier over the heart to protect it from rupture during NPWT. Eight pigs underwent median sternotomy followed by NPWT at --70 and --120 mmHg, using foam, with or without a rigid plastic disc between the heart and the sternal edges. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded. Cardiac output was not affected by NPWT, regardless of whether a rigid barrier was used. Heart frequency decreased during NPWT without a disc, and showed a tendency towards a decrease when using a rigid disc. The blood pressure decreased during NPWT without a disc, and showed only a tendency towards a decrease when a disc was inserted between the heart and the sternum. In conclusion, the results of this haemodynamic study show that a rigid disc can safely be placed over the heart during NPWT, to prevent heart rupture. The haemodynamic effects of NPWT in sternotomy wounds are slightly reduced by the presence of the rigid disc.


Assessing knowledge, attitude, and practices of health-care providers toward pharmacovigilance and adverse drug reaction reporting at a comprehensive cancer center in Jordan.
Cancer patients are more likely to experience adverse drug reactions (ADRs) than other patients, because of both the complexity of the treatment regimens and the severity of disease. The objectives of this study were to determine the knowledge, attitude, and practice of health-care providers toward pharmacovigilance and ADR reporting, barriers to ADR reporting, and the association between the demographics of health-care providers and their knowledge and attitude toward reporting. A cross-sectional survey was conducted at the King Hussein Cancer Center. A self-administered questionnaire was distributed to dispensary pharmacists, clinical pharmacists, physicians, and nurses. Descriptive analysis was used, with testing for associations between variables. Of the 373 questionnaires, 306 were returned (response rate, 82%). Pharmacists and nurses were more knowledgeable than physicians; however, all participants had a highly positive attitude toward pharmacovigilance and ADR reporting, with a mean score of 3.87 out of 5. The main knowledge gaps were filling in an ADR reporting form, assessing the severity of ADRs, and differentiating between ADRs and adverse events. The main barriers to ADR reporting (37.5% of responses) were considered to be lack of training and of understanding reporting rules. No associations were found with age, gender, years of experience, attitude, or knowledge. Understanding of pharmacovigilance and ADR reporting could further be improved among health-care providers at our center.


Preponderance of clonality triggers loss of sex in Bulbophyllum bicolor, an obligately outcrossing epiphytic orchid.
Vegetative propagation (clonal growth) conveys several evolutionary advantages that positively affect life history fitness and is a widespread phenomenon among angiosperms that also reproduce sexually. However, a bias towards clonality can interfere with sexual reproduction and lead to sexual extinction, although a dearth of effective genetic tools and mathematical models for clonal plants has hampered assessment of these impacts. Using the endangered tropical epiphytic or lithophytic orchid Bulbophyllum bicolor as a model, we integrated an examination of breeding system with 12 microsatellite loci and models valid for clonal species to test for the "loss of sex" and infer likely consequences for long-term reproductive dynamics. Bagging experiments and field observations revealed B. bicolor to be self-incompatible and pollinator-dependent, with an absence of fruit-set over 4 years. Challenging the assumptions that clonal populations can be as genotypically diverse as sexually reproducing ones and that clonality does not greatly influence genetic structure, just 22 multilocus genotypes were confirmed among all 15 extant natural populations, 12 of the populations were found to be monoclonal, and all three multiclonal ones exhibited a distinct phalanx clonal architecture. Our results suggest that all B. bicolor populations depend overwhelmingly on clonal growth for persistence, with a concomitant loss of sex due to an absence of pollinators and a lack of mating opportunities at virtually all sites, both of which are further entrenched by habitat fragmentation. Such cryptic life history impacts, potentially contributing to extinction debt, could be widespread among similarly fragmented, outcrossing tropical epiphytes, demanding urgent conservation attention.


3D imaging of proximal caries in posterior teeth using optical coherence tomography.
Optical coherence tomography (OCT) can create cross-sectional images of tooth without X-ray exposure. This study aimed to investigate the diagnostic accuracy of 3D imaging of OCT for proximal caries in posterior teeth. Thirty-six human molar teeth with 51 proximal surfaces visibly 6 intact, 16 slightly demineralized, and 29 distinct carious changes were mounted to take digital radiographs and 3D OCT images. The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the diagnosis of enamel caries and dentin caries were calculated to quantify the diagnostic ability of 3D OCT in comparison with digital radiography. Diagnostic accuracy was evaluated by the agreement with histology using weighted Kappa. OCT showed significantly higher sensitivity, AUC and Kappa values than radiography. OCT can be a safer option for the diagnosis of proximal caries in posterior teeth that can be applied to the patients without X-ray exposure.


Environmental efficiency analysis of China's vegetable production.
To analyze and estimate the environmental efficiency of China's vegetable production. The stochastic translog frontier model was used to estimate the technical efficiency of vegetable production. Based on the estimated frontier and technical inefficiency levels, we used the method developed by Reinhard, et al. to estimate the environmental efficiency. Pesticide and chemical fertilizer inputs were treated as environmentally detrimental inputs. From estimated results, the mean environmental efficiency for pesticide input was 69.7%, indicating a great potential for reducing pesticide use in China's vegetable production. In addition, substitution and output elasticities for vegetable farms were estimated to provide farmers with helpful information on how to reallocate input resources and improve efficiency. There exists a great potential for reducing pesticide use in China's vegetable production.


Uncovering specific changes in network wiring underlying the primate cerebrotype.
Regular scaling of brain networks during evolution has been proposed to be the major process leading to enlarged brains. Alternative views, however, suggest that deviations from regular scaling were crucial to the evolution of the primate brain and the emergence of different cerebrotypes. Here, we examined the scaling within the major link between the cerebellum and the cerebral cortex by studying the deep cerebellar nuclei (DCN). We compared the major axonal and dendritic wiring in the DCN of rodents and monkeys in search of regular scaling. We were able to confirm regular scaling within the density of neurons, the general dendritic length per neuron and the Purkinje cell axon length. However, we also observed specific modification of the scaling rules within the primates' largest and phylogenetically newest DCN, the dentate nucleus (LN/dentate). Our analysis shows a deviation from regular scaling in the predicted dendritic length per neuron in the LN/dentate. This reduction in the dendritic length is also associated with a smaller dendritic region-of-influence of these neurons. We also detected specific changes in the dendritic diameter distribution, supporting the theory that there is a shift in the neuronal population of the LN/dentate towards neurons that exhibit spatially restricted, clustered branching trees. The smaller dendritic fields would enable a larger number of network modules to be accommodated in the primate LN/dentate and would provide an explanation for the unique folded structure of the primate LN/dentate. Our results show that, in some brain regions, connectivity maximization (i.e., an increase of dendritic fields) is not the sole optimum and that increases in the number of network modules may be important for the emergence of a divergent primate cerebrotype.


Functional Food and Cardiovascular Disease Prevention and Treatment: A Review.
Cardiovascular disease (CVD) is now the leading cause of death globally and is a growing health concern. Lifestyle factors, including nutrition, play an important role in the etiology and treatment of CVD. Functional foods based on their basic nutritional functions can decrease the risk of many chronic diseases and have some physiological benefits. They contain physiologically active components either from plant or animal sources, marketed with the claim of their ability to reduce heart disease risk, focusing primarily on established risk factors, which are hyperlipidemia, diabetes, metabolic syndrome, obesity/overweight, elevated lipoprotein A level, small dense low-density lipoprotein cholesterol (LDL-C), and elevated inflammatory marker levels. Functional foods are suspected to exert their cardioprotective effects mainly through blood lipid profile level and improve hypertension control, endothelial function, platelet aggregation, and antioxidant actions. Clinical and epidemiological observations indicate that vegetable and fruit fiber, nuts and seeds, sea foods, coffee, tea, and dark chocolate have cardioprotective potential in humans, as well whole-grain products containing intact grain kernels rich in fiber and trace nutrients. They are nutritionally more important because they contain phytoprotective substances that might work synergistically to reduce cardiovascular risk. This review will focus on the reciprocal interaction between functional foods and the potential link to cardiovascular health and the possible mechanisms of action.


Redox Status and Muscle Pathology in Rheumatoid Arthritis: Insights from Various Rat Hindlimb Muscles.
Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle-a muscle with mixed fiber type-but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P < 0.01), while the vastus lateralis muscle mass was increased by 35% (P < 0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P < 0.001), but vastus lateralis (22% smaller, P < 0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.


Scaphoid nonunion: diagnosis and treatment.
After studying this article, the participant should be able to: 1. Understand the anatomy and pathophysiology of scaphoid fractures. 2. Understand the risk factors for scaphoid nonunion. 3. Identify treatment options for scaphoid nonunion and their respective advantages and disadvantages. 4. Identify salvage procedures for scaphoid nonunion advanced collapse of the wrist. Scaphoid nonunion is a common but difficult problem for hand surgeons. The diagnosis of scaphoid nonunion is often delayed, and therefore, treatment must be tailored to the type of fracture, the duration of nonunion, and the presence or absence of resulting arthritis. This article reviews the diagnosis and work-up of scaphoid nonunion, classification schemes for scaphoid nonunion, and various treatment options, including internal fixation, nonvascularized and vascularized bone grafting, and salvage procedures.


Swine abortion caused by Candida parapsilosis.
In July 2020, a sow in a breeding herd in the Chiba Prefecture, Japan, suffered abortion. A necropsy revealed pale pulmonary foci scattered in the two fetuses. Histologically, multifocal pulmonary necrosis was detected with numerous yeasts. The yeast was positively stained using the periodic acid-Schiff reaction and Grocott's silver stain. Molecular identification indicated that the yeast was Candida parapsilosis. In conclusion, our results suggested that C. parapsilosis caused multifocal necrotizing pneumonia in the two fetuses. This study is the first report of a swine abortion with C. parapsilosis infection.


The epidemiology of college alcohol and gambling policies.
BACKGROUND: This article reports the first national assessment of patterns of drinking and gambling-related rulemaking on college campuses (e.g., punitive versus recovery oriented). Analyses relating school policies to known school rates of drinking or gambling identified potentially influential policies. These results can inform and encourage the development of guidelines, or "best practices," upon which schools can base future policy. METHODS: The college policy information was collected from handbooks, Web sites and supplemental materials of 119 scientifically selected colleges included in the fourth (2001) Harvard School of Public Health College Alcohol Study (CAS). A coding instrument of 40 items measured the scope and focus of school alcohol and gambling policies. This instrument included items to measure the presence of specific policies and establish whether the policies were punitive or rehabilitative. A total of 11 coders followed a process of information extraction, coding and arbitration used successfully in other published studies to codify policy information. RESULTS: Although all schools had a student alcohol use policy, only 26 schools (22%) had a gambling policy. Punitive and restrictive alcohol policies were most prevalent; recovery-oriented policies were present at fewer than 30% of schools. Certain alcohol and gambling policies had significant relationships with student binge drinking rates. CONCLUSIONS: The relative lack of college recovery-oriented policies suggests that schools might be overlooking the value of rehabilitative measures in reducing addictive behaviors among students. Since there are few college gambling-related policies, schools might be missing an opportunity to inform students about the dangers of excessive gambling.


[New aspects in the problem of retinal and optic nerve diseases].
Main trends in research and practical activities of Department of Retinal and Optic Nerve Diseases of Moscow Helmholtz Institute of Ocular Diseases are reviewed: vascular, inflammatory, and dystrophic diseases of the retina, choroid, and optic nerve, results of recent studies of the pathogenesis, diagnosis, and treatment of diabetic retinopathies, vascular abnormalities, uveitis, diseases of the optic nerve, and hereditary diseases of the retina are presented. Problems in surgical treatment of diseases of the retina and vascular tract and complications thereof are discussed.


The Chlamydomonas PF6 locus encodes a large alanine/proline-rich polypeptide that is required for assembly of a central pair projection and regulates flagellar motility.
Efficient motility of the eukaryotic flagellum requires precise temporal and spatial control of its constituent dynein motors. The central pair and its associated structures have been implicated as important members of a signal transduction cascade that ultimately regulates dynein arm activity. To identify central pair components involved in this process, we characterized a Chlamydomonas motility mutant (pf6-2) obtained by insertional mutagenesis. pf6-2 flagella twitch ineffectively and lack the 1a projection on the C1 microtubule of the central pair. Transformation with constructs containing a full-length, wild-type copy of the PF6 gene rescues the functional, structural, and biochemical defects associated with the pf6 mutation. Sequence analysis indicates that the PF6 gene encodes a large polypeptide that contains numerous alanine-rich, proline-rich, and basic domains and has limited homology to an expressed sequence tag derived from a human testis cDNA library. Biochemical analysis of an epitope-tagged PF6 construct demonstrates that the PF6 polypeptide is an axonemal component that cosediments at 12.6S with several other polypeptides. The PF6 protein appears to be an essential component required for assembly of some of these polypeptides into the C1-1a projection.


Mechanism of oligonucleotide release from cationic liposomes.
We propose a mechanism for oligonucleotide (ODN) release from cationic lipid complexes in cells that accounts for various observations on cationic lipid-nucleic acid-cell interactions. Fluorescent confocal microscopy of cells treated with rhodamine-labeled cationic liposome/ fluorescein-labeled ODN (F-ODN) complexes show the F-ODN separates from the lipid after internalization and enters the nucleus leaving the fluorescent lipid in cytoplasmic structures. ODN displacement from the complex was studied by fluorescent resonance energy transfer. Anionic liposome compositions (e.g., phosphatidylserine) that mimic the cytoplasmic facing monolayer of the cell membrane released ODN from the complex at about a 1:1 (-/+) charge ratio. Release was independent of ionic strength and pH. Physical separation of the F-ODN from monovalent and multivalent cationic lipids was confirmed by gel electrophoresis. Fluid but not solid phase anionic liposomes are required, whereas the physical state of the cationic lipids does not effect the release. Water soluble molecules with a high negative linear charge density, dextran sulfate, or heparin also release ODN. However, ATP, spermidine, spermine, tRNA, DNA, polyglutamic acid, polylysine, bovine serum albumin, or histone did not release ODN, even at 100-fold charge excess (-/+). Based upon these results, we propose that the complex, after internalization by endocytosis, induces flip-flop of anionic lipids from the cytoplasmic facing monolayer. Anionic lipids laterally diffuse into the complex and form a charged neutralized ion-pair with the cationic lipids. This leads to displacement of the ODN from the cationic lipid and its release into the cytoplasm.


Fourier methods for the perturbed harmonic oscillator in linear and nonlinear Schrödinger equations.
We consider the numerical integration of the Gross-Pitaevskii equation with a potential trap given by a time-dependent harmonic potential or a small perturbation thereof. Splitting methods are frequently used with Fourier techniques since the system can be split into the kinetic and remaining part, and each part can be solved efficiently using fast Fourier transforms. Splitting the system into the quantum harmonic-oscillator problem and the remaining part allows us to get higher accuracies in many cases, but it requires us to change between Hermite basis functions and the coordinate space, and this is not efficient for time-dependent frequencies or strong nonlinearities. We show how to build methods that combine the advantages of using Fourier methods while solving the time-dependent harmonic oscillator exactly (or with a high accuracy by using a Magnus integrator and an appropriate decomposition).


Polyunsaturated fatty acids and risk of preterm delivery.
Preterm delivery (PD) is characterized both by increased neonatal morbidity and mortality and by important late pathologic sequelae. From a clinical stand-point, PD may results from a medical condition where the continuation of pregnancy could bring about a marked risk for the foetus and/or for the mother, or from an adverse event where the pregnancy is going to end spontaneously before 37 weeks of gestation. In the past few years some epidemiological studies have shown that diet may interfere with complex multifactorial processes contributing to the preterm triggering of labour. The attention has been focused on polyunsaturated fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and linoleic acid, precursor Omega-6 series. Their importance in modulating Prostaglandin concentrations at different levels is already known. Moreover, it has been reported that in clinical situation, such as PD, the endogenous levels of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational and clinical studies suggest that dietary intake of Omega-3 fatty acids is capable of significantly prolonging the duration of gestation in the range of 4-7 days; such prolongation would possibly occur through the inhibition of prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3 appears to be marginal, and recommended assumption could be reached only by a ten-fold increase in blue fish ingestion. The recommended intake of EPA + DHA should be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in light of controlled clinical studies and of the actual categories of risk for preterm delivery, the dietary supplementation of Omega-3, in addition to other pharmacological measures (17alpha-hydroxyprogesterone caproate), could be implemented for the secondary and/or tertiary prophylaxis of preterm delivery.


Effects of human growth hormone on the porto-arterial concentration differences of glucose and amino acids in the newborn piglet.
It is known that growth hormone (GH) increases the mitotic index of duodenal crypt cells. In early life, such an effect could be of particular importance for the functional development of the intestine in terms of absorptive capacity. In this study, osmotic mini pumps were introduced into the abdominal cavity of newborn piglets. The pumps permitted a continuous infusion of either recombinant human growth hormone (rhGH) at a rate of 0.1 IU GH x kg(-1) x 24 h(-1) or of vehicle. After 7 days of treatment, a bolus of amino acids and glucose was infused into the duodenum. Following this bolus, there was a prompt rise in the plasma concentration of both amino acids and glucose, especially in blood withdrawn from the portal vein. Thus, when the differences in concentrations of both amino acids and glucose between portal and arterial blood plasma were calculated, these differences reached maximum values between 30 and 60 minutes after the bolus. In animals treated with GH, maximum values occurred at a lower level than in control animals. These reductions were in the order of 60% (P > 0.01) if calculated over the first hour of absorption. From this study, it might be concluded that GH does not improve the absorptive capacity of the small intestine in newborn piglets. Instead, GH seems to reduce the absorption dynamics of glucose and amino acids. The reason for this is obscure, but could imply a specific effect of GH on enterocyte function.


Cannibalism and protective behavior of eggs in Arctic charr (Salvelinus alpinus).
From video recordings of spawning events, we quantified protective and cannibalistic behavior of Arctic charr occurring immediately after spawning. The number of fish cannibalizing on stray eggs was examined regarding (a) whether more than one male shed milt during the spawning event, that is, whether sperm competition occurred, (b) whether the sperm competition included few or many males, that is, the intensity of sperm competition, and (c) the density of fish at the spawning site. Response behavior toward egg cannibalism was also examined among females and dominant males in order to determine any parental investment toward protecting the eggs after spawning. Cannibalistic behavior was seen in almost 50% of the spawnings, and the multiple spawning events showed the highest numbers of fish cannibalizing on eggs. Both the number of males releasing milt and the number of fish approaching the spawning site were positively correlated with egg cannibalism. Sperm competition was, however, not a prerequisite for egg cannibalism. Although we also observed partial filial cannibalism, protective behavior of eggs was seen both among dominant males and females, suggesting that charr actually conduct parental care.


Human embryonic stem cell-derived hematopoietic cells maintain core epigenetic machinery of the polycomb group/Trithorax Group complexes distinctly from functional adult hematopoietic stem cells.
Hematopoietic cells derived from human embryonic stem cells (hESCs) have a number of potential utilities, including the modeling of hematological disorders in vitro, whereas the use for cell replacement therapies has proved to be a loftier goal. This is due to the failure of differentiated hematopoietic cells, derived from human pluripotent stem cells (hPSCs), to functionally recapitulate the in vivo properties of bona fide adult hematopoietic stem/progenitor cells (HSPCs). To better understand the limitations of differentiation programming at the molecular level, we have utilized differential gene expression analysis of highly purified cells that are enriched for hematopoietic repopulating activity across embryonic, fetal, and adult human samples, including in vivo explants of human HSPCs 8-weeks post-transplantation. We reveal that hESC-derived hematopoietic progenitor cells (eHPCs) fail to express critical transcription factors which are known to govern self-renewal and myeloid/lymphoid development and instead retain the expression of Polycomb Group (PcG) and Trithorax Group (TrxG) factors which are more prevalent in embryonic cell types that include EZH1 and ASH1L, respectively. These molecular profiles indicate that the differential expression of the core epigenetic machinery comprising PcGs/TrxGs in eHPCs may serve as previously unexplored molecular targets that direct hematopoietic differentiation of PSCs toward functional HSPCs in humans.


Attachment-Based Family Therapy for Adolescent Substance Use: A Move to the Level of Systems.
This paper provides an account of the theoretical basis of a family-based intervention called Behaviour Exchange and Systems Therapy (BEST). The model described here has also been applied to adolescents with substance abuse and other mental health problems such as depression and anxiety disorders in both children and adolescents. Evaluative studies of the model have been published including randomised clinical trials as well as qualitative analyses. The current paper discusses a theory of the family system as a discourse and represents an integration of aspects of attachment, psychoanalytic, and systems theories. Key concepts elaborated are the attachment-family system, the family as a single discourse, the use of segregation as a defense in relation to trauma and loss and its manifestation in a family narrative, and the role of the family secure base in affect regulation. The paper also briefly describes specific treatment techniques that are derived from the theoretical model. Our approach has wide application as a discourse focused treatment for children and adolescents using a family systems approach. Future work requires the comparison of this model to similar attachment-based models of intervention for children and families, further development and validation of measures able to be used for whole families in a clinical setting, and further empirical demonstration of treatment efficacy in a variety of clinical settings.


My hip journey: A qualitative study of patients' experiences of an eHealth program for patient preparation and recovery from hip replacement surgery.
To explore patient experiences, perceived benefits and suggestions of an eHealth program for pre- and post-operative education for total hip arthroplasty. eHealth programs for surgical patients can facilitate the delivery of information, provide individualised rehabilitation plans and enable communication with health professionals to promote overall patient recovery. A qualitative descriptive study was conducted following the COREQ guidelines. A convenience sample of nine patients who had total hip arthroplasty and used the My Hip Journey eHealth program were recruited and participated in individual semi-structured telephone interviews. Interviews were audio recorded, transcribed verbatim and analysed using inductive thematic analysis. The participant group were aged between 53 and 70 years. The results are described in three overarching themes and sub-themes: (1) Supported surgical journey-how the My Hip Journey eHealth program supported them in their preparation and recovery from their surgery, and how the program provided information and encouraged engagement; (2) Motivated recovery-how patients found the program motivational, facilitated their self-management and enabled communication with the healthcare team if they had any concern; and (3) Functionality-how the program related to ease of use, its interactivity with the patient and suggestions for future use. The patients reported that using the eHealth program for pre- and post-operative education was helpful to their overall surgical experience and recovery. It was found to engage patients in their care, enabled self-management, encouraged communication with health professionals and motivated them with their recovery. These findings identify the potential for eHealth programs to support patients in the preparation and post-operative stages, and in their post-discharge self-care for other surgical and orthopaedic journeys. Patient experiences of eHealth education can inform nurses of the benefits of eHealth and the development of future eHealth education programs.


Perception of odor-induced tastes following insular cortex lesion.
Lesions of the insula can affect olfaction and gustation. Here, we examined the effect of insula lesions on taste and taste-like experiences generated via smelling (i.e., odor-induced tastes) in patients with focal insula lesions and intact olfaction. From a set of 16 patients with lesions to the insula, we found 7 (6 with right-sided lesions) who performed normally on various olfactory measures. These were compared to 42 normal control subjects on tests of gustatory and odor-induced taste perception as well as control measures. The patients were impaired relative to controls on most gustatory measures. They were also impaired on tests of odor-induced taste perception, primarily for stimuli presented on the left side. Examining cases individually revealed evidence of a dissociation: two patients exhibited no impairment in odor-induced taste perception in spite of gustatory deficits. Together, these findings suggest that the insula mediates taste recognition, hedonics, and intensity judgments as well as odor-induced taste perception. However, the areas responsible for aspects of taste perception and those responsible for odor-induced taste do not fully overlap each other and they are also independent of olfactory areas.


Hemato-oncology Tourism in Israel: A Retrospective Review.
Despite the significant increase in medical tourism worldwide, data on medical tourist (MT) clinical characteristics and treatment outcomes are lacking. Many MTs who choose Israel to receive medical services are individuals diagnosed with hematologic malignancies. The purpose of this study was to describe hemato-oncology MTs and to compare their disease characteristics and treatment outcomes to a control group of local (Israeli) hemato-oncology patients. In this retrospective review, we analyzed hospital records of all hemato-oncology tourists and Israeli patients diagnosed and/or treated at the Institute of Hematology, Assuta Medical Center, between 2014 and 2016. MT and local patient demographics, clinical characteristics, and treatment outcomes were compared. MT data were also analyzed according to their commitment to treatment in Israel. Data on 110 MTs (median age, 51.0 years; 53.6% women) and 122 local patients (median age, 65.0 years; 41.8% women) diagnosed with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and multiple myeloma were analyzed. The most common hematologic malignancy in both MTs and local patients was NHL (54.5% and 73.0%, respectively). Among MTs, 32.7% were fully committed to treatment in Israel, 32.7% were partially committed, and 34.6% were not committed. In 25.9% of MTs, a review of their biopsy resulted in a more definitive or different diagnosis. The percentage of patients who achieved complete response to treatment was similar among MTs and local patients. MTs often require a pathologic review of their initial diagnosis and are more likely to present with advanced stages of disease. Treatment of MTs according to the appropriate clinical parameters is expected to yield similar outcomes to those of local patients.


Consumption of black beans and navy beans (Phaseolus vulgaris) reduced azoxymethane-induced colon cancer in rats.
Beans (Phaseolus vulgaris) are an important food staple in many traditional diets. There is limited evidence to suggest an inverse relationship between bean consumption and colon cancer. The objective of this study was to determine whether consumption of black beans and/or navy beans would reduce colon carcinogenesis in rats. Rats were fed a modified AIN-93G diet (control) or diets containing 75% black beans or 75% navy beans for 4 wk, and then colon cancer was initiated by administration of two injections of azoxymethane 1 wk apart. At 31 wk after the second injection, the incidence of colon adenocarcinomas was significantly lower (P < 0.05) in rats fed the black bean (9%) and navy bean (14%) diets than in rats fed the control diet (36%). Total tumor multiplicity was also significantly lower in rats fed the black bean (1.1) and navy bean (1.0) diets than in rats fed the control diet (2.2). The 44-75% reduction in colon carcinogenesis in rats fed beans was attributed to 1) more controlled appetites, leading to significantly less body fat, and 2) much greater concentrations of butyrate in the distal colon. It was concluded that eating black beans and navy beans significantly lowered colon cancer incidence and multiplicity.


2-Dimensional beamsteering using dispersive deflectors and wavelength tuning.
We introduce a 2D beamscanner which is controlled by wavelength tuning. Two passive dispersive devices are aligned orthogonally to deflect the optical beam in two dimensions. We provide a proof of principle demonstration by combining an arrayed waveguide grating with a free space optical grating and using various input sources to characterize the beamscanner. This achieved a discrete 10.3 degrees by 11 degrees output field of view with attainable angles existing on an 8 by 6 grid of directions. The entire range was reached by scanning over a 40 nm wavelength range. We also analyze an improved system combining a virtually imaged phased array with a diffraction grating. This device is much more compact and produces a continuous output scan in one direction while being discrete in the other.


Dependence of the lethal effect of pore-forming haemolysins of Gram-positive bacteria on cytolytic activity.
Among bacterial haemolysins, cholesterol-dependent cytolysins (CDCs) produced by various Gram-positive bacteria are known to exhibit a lethal activity in mice. In this study, recombinant CDCs of streptolysin O, pneumolysin, ivanolysin O, listeriolysin O and several listeriolysin O mutants were constructed and the relationship between cytolytic activity and the lethal activity of each recombinant protein in mice was examined. Specific activity for cytolysis was determined by a quantitative haemolytic assay. Each protein was injected intravenously into mice and the lethal activity was evaluated by measuring the time until death of the mice. The four full-length CDC proteins exhibited lethal activity and their activities were highly proportional to their cytolytic activities. Inhibition of haemolytic activity resulted in the loss of lethal activity and non-haemolytic mutants of listeriolysin O did not exhibit any lethal activity. These data clearly indicate that the lethal effect of CDC proteins is dependent on the cytolytic activity.


Yeast recombination enhancer is stimulated by transcription activation.
Saccharomyces cerevisiae mating type switching is a gene conversion event that exhibits donor preference. MATa cells choose HMLalpha for recombination, and MATalpha cells choose HMRa. Donor preference is controlled by the recombination enhancer (RE), located between HMLalpha and MATa on the left arm of chromosome III. A number of a-cell specific noncoding RNAs are transcribed from the RE locus. Mcm1 and Fkh1 regulate RE activity in a cells. Here we show that Mcm1 binding is required for both the transcription of the noncoding RNAs and Fkh1 binding. This requirement can be bypassed by inserting another promoter into the RE. Moreover, the insertion of this promoter increases donor preference and opens the chromatin structure around the conserved domains of RE. Additionally, we determined that the level of Fkh1 binding positively correlates with the level of donor preference. We conclude that the role of Mcm1 in RE is to open chromatin around the conserved domains and activate transcription; this facilitates Fkh1 binding and the level of this binding determines the level of donor preference.


Supra-his alternate-beat Wenckebach dysrhythmia.
Alternate-beat Wenckebach, an uncommon dysrhythmia, usually is attributed to block within the His bundle or bundle branches (or in both). A patient with features of the "sick sinus" syndrome demonstrated A-V nodal (supra-His) alternate-beat Wenckebach during atrial pacing and His bundle electrocardiography. Electrophysiologic mechanisms are proposed.


Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome.
Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%. To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness. Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003. The primary outcome measure was 28-day mortality after symptom onset. Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (> or =7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery. Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.


Equivalence of mycobactins from Mycobacterium senegalense, Mycobacterium farcinogenes and Mycobacterium fortuitum.
Mycobactins were isolated from five strains designated Mycobacterium farcinogenes and a similar number designated Mycobacterium senegalense following growth under conditions of iron-limitation. These lipid-soluble iron-chelating compounds were characterized by a combination of thin-layer and high-performance liquid chromatography. The mycobactins from both the slow-growing M. farcinogenes and the rapidly-growing M. senegalense strains proved impossible to differentiate both from each other and from those produced by strains of Mycobacterium fortuitum, indicating a close relationship between all three species. However, Nocardia farcinica, previously implicated with the bovine farcy strains, produced a different mycobactin which was easily distinguished by thin-layer chromatography alone.


Dielectric Confinement and Excitonic Effects in Two-Dimensional Nanoplatelets.
Quasi-two-dimensional (2D) semiconductor nanoplatelets manifest strong quantum confinement with exceptional optical characteristics of narrow photoluminescence peaks with energies tunable by thickness with monolayer precision. We employed scanning tunneling spectroscopy (STS) in conjunction with optical measurements to probe the thickness-dependent band gap and density of excited states in a series of CdSe nanoplatelets. The tunneling spectra, measured in the double-barrier tunnel junction configuration, reveal the effect of quantum confinement on the band gap taking place mainly through a blue-shift of the conduction band edge, along with a signature of 2D electronic structure intermixed with finite lateral-size and/or defects effects. The STS fundamental band gaps are larger than the optical gaps as expected from the contributions of exciton binding in the absorption, as confirmed by theoretical calculations. The calculations also point to strong valence band mixing between the light- and split-off hole levels. Strikingly, the energy difference between the heavy-hole and light-hole levels in the tunneling spectra are significantly larger than the corresponding values extracted from the absorption spectra. Possible explanations for this, including an interplay of nanoplatelet charging, dielectric confinement, and difference in exciton binding energy for light and heavy holes, are analyzed and discussed.


Helminthiasis, the hypereosinophilic syndrome and endomyocardial fibrosis: some observations and an hypothesis.
It has been shown that chronic African endomyocardial fibrosis (E.m.f.) is most likely the burnt-out phase of parasite-induced hypereosinophilia. It has also been shown that African E.m.f. and Loffler's heart disease are pathologically identical. The mechanism by which these parasites and/or eosinophilia are associated with endomyocardial damage remains, however, unknown. The parasites which have been associated with induction of eosinophilia in E.m.f. include filariasis; trichinosis; ascariasis and hookworm and schistosomiasis. These parasites are known to produce neurologic, cardiac, pneumonic, hepatic and dermal damage during the migration of their larvae; at which time eosinophilia is usually most severe. The tissue damage induced by larval migration of these parasites appears comparable to findings seen in the hypereosinophilic syndrome. The evidence from our observations and this review suggests that the cardiac damage induced by larval migration, like the neurologic, pneumonic and dermal damage, is allergic in nature. Endomyocardial fibrosis has previously been shown to be an allergic heart disease. It appears reasonable to regard African endomyocardial fibrosis as representing the most intense, non-specific cardiac allergic reaction to helminthic larvae.


Hypothalamus as a mediator of chronic migraine: Evidence from high-resolution fMRI.
To identify pathophysiologic mechanisms of migraine chronification using a recently standardized protocol for high-resolution brainstem imaging of trigeminal nociceptive stimulation. Eighteen episodic migraineurs (EMs), 17 chronic migraineurs (CMs), and 19 healthy controls (HCs) underwent painful ammonia stimulation of the left nostril in a 3T MRI scanner. Functional images were acquired with a brainstem-optimized protocol for high-resolution echo-planar imaging. We detected a significantly stronger activation of the anterior right hypothalamus in CMs compared to HCs. To exclude the headache as a prime mediator of the hypothalamic activations, we compared all migraineurs with headaches (EMs and CMs) with all migraineurs without headaches (EMs and CMs) and HCs in a second analysis and found a more posterior region of the hypothalamus to be more activated bilaterally during headaches. Our data corroborate the fact that the hypothalamus plays a crucial role in the pathophysiology of migraine chronification and acute pain stage of migraineurs. While the more posterior part of the hypothalamus seems to be important for the acute pain stage, the more anterior part seems to play an important role in attack generation and migraine chronification.


Microfluidic Device for Coulometric Detection of Organophosphate Pesticides.
A microdevice for coulometric detection of organophosphate pesticides (OPs) was fabricated based on the measurement of the inhibition of an enzyme, acetylcholinesterase (AChE), by OPs. Thiocholine (TCh) produced in the enzymatic reaction of AChE with acetylthiocholine (ATCh) as a substrate was oxidized on a microelectrode array formed in a main flow channel. Volumes of plugs of necessary solutions were measured using a structure consisting of a row of rhombuses formed in an auxiliary flow channel. The plugs were merged and solution components were mixed at a T-junction formed with the main and auxiliary flow channels. A linear relationship was confirmed between the generated charge and the logarithm of the OP (malathion) concentration in a concentration range between 10(-6) and 10(-3) M with a correlation coefficient of 0.951. The lower limit of detection was 412 nM.


An integrative pipeline for circular RNA quantitative trait locus discovery with application in human T cells.
Molecular quantitative trait locus (QTL) mapping has proven to be a powerful approach for prioritizing genetic regulatory variants and causal genes identified by genome-wide association studies. Recently, this success has been extended to circular RNA (circRNA), a potential group of RNAs that can serve as markers for the diagnosis, prognosis, or therapeutic targets of various human diseases. However, a well-developed computational pipeline for circRNA QTL (circQTL) discovery is still lacking. We introduce an integrative method for circQTL mapping and implement it as an automated pipeline based on Nextflow, named cscQTL. The proposed method has two main advantages. Firstly, cscQTL improves the specificity by systematically combining outputs of multiple circRNA calling algorithms to obtain highly confident circRNA annotations. Secondly, cscQTL improves the sensitivity by accurately quantifying circRNA expression with the help of pseudo references. Compared to the single method approach, cscQTL effectively identifies circQTLs with an increase of 20%-100% circQTLs detected and recovered all circQTLs that are highly supported by the single method approach. We apply cscQTL to a dataset of human T cells and discover genetic variants that control the expression of 55 circRNAs. By colocalization tests, we further identify circBACH2 and circYY1AP1 as potential candidates for immune disease regulation. cscQTL is freely available at: https://github.com/datngu/cscQTL and https://doi.org/10.5281/zenodo.7851982.


Catechol O-methyltransferase. 8. Structure-activity relationships for inhibtion by 8-hydroxyquinolines.
A series of 5- and 7-substituted 8-hydroxyquinolines was evaluated as inhibitors of catechol O-methyltransferase (COMT, E.C. 18.104.22.168). The electronic character of the substituents in the 5 position appeared to have only a small effect if any on the inhibitory activity of these compounds. A significant factor which contributes to the inhibitory activity of these compounds appears to be the nature of the 7-substituent. The structure-activity relationship for this series of inhibitors is discussed relative to the nature of the enzymatic binding site.


[Medical revocation processes in the state of São Paulo under the bioethics perspective].
This study aimed to analyze, from the perspective of Bioethics, the characteristics of the ethical professional processes of physicians sentenced to have their license revoked in the State of São Paulo. Retrospective descriptive study of 41 Ethical Professional Processes of the Regional Board of Medicine of the State of São Paulo which resulted in the revocation of the medical license of 45 physicians, between January, 1988 and December, 2004. All processes were judged by the Federal Board of Medicine. The following variables were collected: origin of accusation, place of occurrence of the facts and time between acknowledgement of the facts and final decision taken by the Federal Board of Medicine, penalty of the Federal Board of Medicine and decision by the Federal Justice. The higher frequency of claims (33.3%) were made through an ex-officio action by the Board, 75.5% of the facts occurred in private institutions and the time between acknowledgement of the facts and the final decision taken by the Federal Board of Medicine was of 8 years and 4 months. Revocation of the medical license was refereed by the Federal Board of Medicine for 25 physicians (55.5%). Of these, 11 physicians appealed and 5 obtained from the Federal Justice annulment of the decisions by the Federal Board of Medicine. Under the perspective of Bioethics, revocation of the medical license is necessary for the protection of patients. The patients' vulnerability was the ethical reference of the Board. Teaching and education of Bioethics must necessarily be an important part of medical graduation and post-graduation, however Bioethics must be disseminated (and put into practice) in all segments of society for the purpose of preserving human dignity.


Ethnic differences in the VKORC1 gene polymorphism and an association with warfarin dosage requirements in cardiovascular surgery patients.
Vitamin K epoxide reductase (VKORC1) is the drug target for inhibition by coumarin-based anticoagulant drugs such as warfarin. Warfarin therapy has been reported as a leading cause of drug-related hospitalization and there is therefore an urgent need to develop tests for better warfarin prescription. We report here the distribution of the intron 1 -136 T>C (1173 T>C intron) polymorphism of VKORC1, previously reported to be associated with warfarin maintenance dose in Caucasians and Japanese, in several ethnic populations from Japan and Israel, and describe its significance for warfarin dosage in Japanese cardiovascular surgery patients. Subjects consisted of 132 Japanese individuals and 341 Israeli individuals from four Jewish ethnic groups (86 Ashkenazi Jews, 95 Yemenite Jews, 73 Moroccan Jews and 87 Libyan Jews). In addition, 31 Japanese patients receiving warfarin therapy after cardiovascular surgery, maintained with a target International Normalized Ratio, were studied. The genotyping for the 1173 T>C intron polymorphism of VKORC1 was determined using rapid real-time PCR. The allele frequency of the combined VKORC1 1173 CT and CC genotypes varied among the four Israeli ethnic groups and was, on average, much higher in the Israeli (0.728) than in the Japanese population (0.152). For the Japanese cardiovascular surgery patients, the maintenance dose of warfarin was significantly larger in the combined VKORC1 1173 TC and CC genotype group than in the 1173 TT genotype group (3.6 +/- 0.5 mg vs 2.8 +/- 0.7 mg, respectively; p = 0.02). The frequencies of the intron 1 VKORC1 1173 T>C SNP show significant differences between ethnic groups and are associated with warfarin dose requirements for achieving a recommended International Normalized Ratio range in Japanese cardiovascular surgery patients. This study supports the example of warfarin as an appropriate model for applying personalized medicine for anticoagulant drugs, and highlights the importance of ethnicity in pharmacogenetics.


Intermittent theta burst stimulation combined with cognitive training improves cognitive dysfunction and physical dysfunction in patients with post-stroke cognitive impairment.
Post-stroke cognitive impairment (PSCI) is a common complication of stroke. Intermittent theta burst stimulation (iTBS) can inducing motor learning. We observed the effects of combination of iTBS with cognitive training on physical/cognitive dysfunctions in PSCI patients. PSCI patients treated with basic treatment & cognitive training (Control group)/iTBS & cognitive training (iTBS group) were enrolled, with Mini-mental State Examination (MMSE)/Montreal Cognitive Assessment (MoCA)/Frontal Assessment Battery (FAB)/barthel index (BI)/Upper Limb Fugl-Meyer Assessment (U-FMA)/Action Research Arm Test (ARAT) scores compared. Gait spatiotemporal parameters/dynamic parameters were analyzed by 3D gait analysis. Correlations between MMSE/MoCA scores and gait parameters in PSCI patients after iTBS & cognitive training were analyzed by Spearman analysis. Increased MMSE/MoCA/FAB/BI/U-FMA/ARAT scores, step speed, step frequency, stride length, step width, step length on the affected side, percentage of swing phase on the affected side, hip joint flexion angle on the affected side, knee joint flexion angle on the affected side, and ankle plantar flexion angle on the affected side and reduced gait period on the affected side and percentage of stance phase on the affected side were found in patients of both groups after treatment, with the effects in the iTBS group more profound. iTBS & cognitive training obviously improved the cognitive function scores/upper limb function scores/gait parameters in PSCI patients versus cognitive training treatment. After combination therapy, the MMSE/MoCA scores of PSCI patients were significantly correlated with gait parameters. This provided more data support for iTBS & cognitive training application in the rehabilitation treatment of PSCI patients.


Increasing habilitative services for persons with profound handicaps: an application of structural analysis to staff management.
We evaluated a structural analysis methodology for enhancing the utility of a staff management program. In Experiment 1, a structural analysis of direct-care staff behavior in a mental retardation facility revealed differences in work patterns over time. Specific times were identified when few basic care duties were necessary and staff engaged in nonwork activity. In Experiment 2, a management program was implemented to increase staff members' training activities during periods identified through the structural analysis. The program was accompanied by increases in training activities and decreases in nonwork behavior. The improvements were maintained during a 43-week period while the most labor-intensive component of the program was withdrawn. Staff acceptability measures indicated a positive response to the management intervention, although responses varied across components within the multifaceted program. The increased training was accompanied by beneficial changes among clients with profound handicaps. Results are discussed regarding practical considerations for improving staff performance and for adopting innovations resulting from applied research.


Correlates of transitions in stage of change for quitting among adolescent smokers.
Longitudinal studies have been conducted to evaluate correlates of stage of change movement among adult smokers but no studies were found to be conducted among adolescent smokers. This study used longitudinal data to examine adolescents' abstinence self-efficacy over 10-week and six-month periods and determined whether stage transitions were associated with concomitant changes or baseline values in perceived abstinence self-efficacy, nicotine dependence and motivation to quit. From baseline to 10-weeks results showed a change in motivation to quit and baseline stage were significantly associated with stage progression and regression. Additionally, intervention school status was significantly associated with stage progression. On the other hand, baseline score for nicotine dependence predicted stage regression not progression. Adolescents' becoming more or less 'ready' to quit smoking are influenced by their nicotine dependence and motivation to quit.


GV 20's Role in In Vitro Fertilization and Frozen Embryo Transfer.
Background: Unexplained infertility is failure to conceive after 1 year in couples with normal semen samples and no abnormalities. Acupuncture to certain points along a meridian can affect the hypothalamic-pituitary-axis (HPA) by affecting the sensory nerve fibers, blood vasculature, and autonomic nervous system. GV 20, a point at the vertex of the head, is commonly utilized in acupuncture for infertility. Engagement of the HPA axis via GV 20 stimulation should always be considered when treating a woman, with a history of ovarian dysfunction and subsequent infertility, undergoing in vitro fertilization (IVF). This point, due to its systemic effects, should be considered prior to undergoing frozen embryo transfer (FET). Case: A patient was diagnosed with unexplained infertility when she underwent IVF and FET procedures. GV 20 stimulation helped this patient by improving her mood and ameliorating her psychiatric symptoms via suspected engagement of the HPA axis. Results: As of this writing, the patient has had a relatively uneventful, successful pregnancy and is currently at 28 weeks' gestation. The couple are happily expecting a baby boy. Conclusions: Practitioners should use GV 20 to address psychologic concerns, especially in patients seeking assistive reproductive technologies. The general sense of well-being induced by GV 20 stimulation involves engaging the HPA axis. More research on GV 20's effect on regulation of hormonal imbalances, mood, anxiety, and depression via the HPA axis is warranted as is research on how GV 20 stimulation affects prolactin levels when treating hyperprolactinemia, and subsequently, dopamine utilization.


Quantitation of melatonin and n-acetylserotonin in human plasma by nanoflow LC-MS/MS and electrospray LC-MS/MS.
Melatonin (MEL) and its chemical precursor N-acetylserotonin (NAS) are believed to be potential biomarkers for sleep-related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity, specificity and dynamic range needed to monitor MEL and its precursors and metabolites in small blood samples, such as those obtained from pediatric patients. In support of our ongoing study to determine the safety, tolerability and PK dosing strategies for MEL in treating insomnia in children with autism spectrum disorder, two highly sensitive LC-MS/MS assays were developed for the quantitation of MEL and precursor NAS at pg/mL levels in small volumes of human plasma. A validated electrospray ionization (ESI) method was used to quantitate high levels of MEL in PK studies, and a validated nanospray (nESI) method was developed for quantitation of MEL and NAS at endogenous levels. In both assays, plasma samples were processed by centrifugal membrane dialysis after addition of stable isotopic internal standards, and the components were separated by either conventional LC using a Waters SymmetryShield RP18 column (2.1 × 100 mm, 3.5 µm) or on a polyimide-coated, fused-silica capillary self-packed with 17 cm AquaC18 (3 µm, 125 Å). Quantitation was done using the SRM transitions m/z 233 → 174 and m/z 219 → 160 for MEL and NAS, respectively. The analytical response ratio versus concentration curves were linear for MEL (nanoflow LC: 11.7-1165 pg/mL, LC: 1165-116,500 pg/mL) and for NAS (nanoflow LC: 11.0-1095 pg/mL).


Laser light triggered smart release of silibinin from a PEGylated-PLGA gold nanocomposite.
In this work a new remotely-triggered drug delivery system based on PEG-PLGA_Au nanocomposite is proposed. Due to the optical properties of gold nanoparticles (Au NPs), the nanovector allows on-demand control of the dose, the timing and the duration of the drug release, upon irradiation with red laser light. The Au NPs are synthesized by laser ablation and subsequently embedded into the PEG-PLGA copolymer via a modified emulsion-diffusion method, devised in such a way that both Au NPs and silibinin (SLB), a flavonolignan with promising anti-neoplastic effects, can be co-loaded into the polymeric system in a single step procedure. A combination of analytical techniques including nuclear magnetic resonance (NMR), static and dynamic light scattering (SLS, DLS), gel permeation chromatography (GPC), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), infrared (FTIR) spectroscopy and scanning/transmission electron microscopies (SEM/STEM/TEM), have been used to study the structural and morphological properties of the nanocomposite. The loading efficiency and the drug content, evaluated by UV-vis absorption optical spectroscopy, are 89% and 8.8%, respectively. Upon laser irradiation the system releases the encapsulated drug with a higher efficiency (∼10%) than that without irradiation. This behaviour indicates that our nanoplatform is responsive to light and it could be considered a promising new type of light-activated drug delivery carrier applicable to the biomedical field.


High performance multilayer MoS2 transistors with scandium contacts.
While there has been growing interest in two-dimensional (2-D) crystals other than graphene, evaluating their potential usefulness for electronic applications is still in its infancy due to the lack of a complete picture of their performance potential. The focus of this article is on contacts. We demonstrate that through a proper understanding and design of source/drain contacts and the right choice of number of MoS(2) layers the excellent intrinsic properties of this 2-D material can be harvested. Using scandium contacts on 10-nm-thick exfoliated MoS(2) flakes that are covered by a 15 nm Al(2)O(3) film, high effective mobilities of 700 cm(2)/(V s) are achieved at room temperature. This breakthrough is largely attributed to the fact that we succeeded in eliminating contact resistance effects that limited the device performance in the past unrecognized. In fact, the apparent linear dependence of current on drain voltage had mislead researchers to believe that a truly Ohmic contact had already been achieved, a misconception that we also elucidate in the present article.


Electroencephalographic Correlates in Synthetic and Real Emotional Face Stimulation.
This work reports on physiological electroencephalographic (EEG) correlates in cognitive and emotional processes within the discrimination between synthetic and real faces visual stimuli. Human perception of manipulated data has been addressed in the literature from several perspectives. Researchers have investigated how the use of deep fakes alters people's ability in face-processing tasks, such as face recognition. Although recent studies showed that humans, on average, are still able to correctly recognize synthetic faces, this study investigates whether those findings still hold considering the latest advancements in AI-based, synthetic image creation. Specifically, 18-channels EEG signals from 21 healthy subjects were analyzed during a visual experiment where synthetic and actual emotional stimuli were administered. According to recent literature, participants were able to discriminate the real faces from the synthetic ones, by correctly classifying about 77% of all images. Preliminary encouraging results showed statistical significant differences in brain activation in both stimuli (synthetic and real) classification and emotional response.


The "Second Place" Problem: Assistive Technology in Sports and (Re) Constructing Normal.
Objections to the use of assistive technologies (such as prostheses) in elite sports are generally raised when the technology in question is perceived to afford the user a potentially "unfair advantage," when it is perceived as a threat to the purity of the sport, and/or when it is perceived as a precursor to a slippery slope toward undesirable changes in the sport. These objections rely on being able to quantify standards of "normal" within a sport so that changes attributed to the use of assistive technology can be judged as causing a significant deviation from some baseline standard. This holds athletes using assistive technologies accountable to standards that restrict their opportunities to achieve greatness, while athletes who do not use assistive technologies are able to push beyond the boundaries of these standards without moral scrutiny. This paper explores how constructions of fairness and "normality" impact athletes who use assistive technology to compete in a sporting venue traditionally populated with "able-bodied" competitors. It argues that the dynamic and obfuscated construction of "normal" standards in elite sports should move away from using body performance as the measuring stick of "normal," toward alternate forms of constructing norms such as defining, quantifying, and regulating the mechanical actions that constitute the critical components of a sport. Though framed within the context of elite sports, this paper can be interpreted more broadly to consider problems with defining "normal" bodies in a society in which technologies are constantly changing our abilities and expectations of what normal means.


Access to health care and mental health-Evidence from the ACA preexisting conditions provision.
This study evaluates the impact of the Affordable Care Act (ACA) preexisting conditions provision on mental health. The 2014 policy ensured individuals with preexisting health conditions the right to obtain insurance coverage. Using longitudinal data from the Panel Study of Income Dynamics between 2007 and 2017 and estimating difference-in-differences models, our study provides evidence that the policy reduced severe mental distress by 1.44 percentage points (baseline mean: 8.09%) among individuals with preexisting physical health conditions. Exploiting pre-ACA, state-level variation in policies providing insurance coverage options to people with preexisting conditions, we find that this improvement in mental well-being is highly associated with the presence of high-risk pools before 2014, which provided individuals with prior health conditions access to coverage. Specifically, we show that our main results are driven by individuals with preexisting health conditions living in the 16 states that did not have high-risk pools. Furthermore, gender-specific analysis shows that the reduction in mental distress is primarily observable among women. When examining potential mechanisms, our analysis provides evidence that increases in insurance coverage, reductions in healthcare expenditures, and improvements in physical health can explain the positive effects of the provision on mental well-being.


Phase II clinical study on the GEMOX regimen as second- line therapy for advanced ovarian cancer.
To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000 mg/m(2) with a fixed-dose rate of 10 mg/m(2)/min, on days 1 and 8 and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000 mg/m(2) within 30 min on days 1 and and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients.


[Operative treatment of terrible triad of the elbow].
To retrospectively reviewed the operative therapy of the terrible triad of the elbow. From October 2003 to September 2007, 10 cases of terrible triad were treated, with an elbow dislocation and an associated fracture of both the radial head and the coronoid process. There were 3 males and 7 females with the age of 18-66 years. The injury was caused by traffic accidents in 4 cases, falling from a height in 4 cases, and tumbling in 2 cases. The coronoid process fractures of the patients were 5 cases of type I, 3 cases of type II and 2 cases of type III according to Regan-Morrey classification. The radial head fractures of the patients were 1 case of type I, 6 cases of type II and 1 case of type III according to Mason classification, and their radial heads of the other 2 patients were resected before they were in hospital. The general approach was to repair the damaged structures sequentially from deep to superficial, from coronoid to anterior capsule to radial head to lateral ligament complex to common extensor origin. And selected cases were repaired of the medial collateral ligaments and assisted mobile hinged external fixation to keep the forearm fixed in functional rotation position. The function of the elbows were evaluated with the criteria of the HSS2 score system. The other wounds healed by first intention except 1 case which had infection 7 days after operation and whose soft tissue defect in posterior elbow were repaired with the pedicle thoracoumbilical flap. The patients were followed up 6 to 51 mouths (mean 24.9 mouths). The fracture healing time was 6 to 20 weeks (mean 9.6 weeks). Six mouths postoperatively, the mean flexion-extension arc of the elbow was 106.5 degrees (85-130 degrees), and the mean pronation-supination arc of the forearm was 138 degrees (100-160 degrees) respectively. According to the criteria of the HSS2 score, the results were excellent in 4 cases, good in 4 cases, and fair in 2 cases. No complications such as stiffness and ulnohumeral arthrosis occurred. The radial nerve injury was found in 1 patient 1 day after operation who was treated with neurolysis, and the nerve function was recovered after 4-6 months. And heterotopic ossification occurred in 6 patients 6 months after operation and radiographic subluxation developed in 1 patient 36 months after operation, and conservative treatment were given. The terrible triad of the elbow can lead to serious elbow instability and should be treated with operation to restore the anatomic structures, to repair the articular capsule and the collateral ligament, using the adjuvant hinged external fixation and early exercise to avoid immobilization and recover the articular function.


Use of H-2 mutations to quantitate alloreactivity: Alloreactivity is strongest against H-2 antigens which are closet to self.
Lymph-node cells from H-2 allogeneic, intra-H-2 recombinant and H-2 mutant congenic strains were sensitized in limiting dilution cultures to quantitate the cytotoxic T-lymphocyte precursor frequencies (CTL.Pf) against antigens encoded by different regions of the H-2 complex. When four H-2Kb mutants of C57BL/6 (B6) were tested, we observed anti-B6 CTL.Pf that were as high or higher than those of recombinant strains which differ from B6 at the K end of the H-2 complex. Relative to strains completely H-2 allogeneic to B6, the CTL.Pf in H-2bm3 and H-2bm5 averaged 40--50 percent, and H-2bm8 averaged 140 percent. Recombinant strains B10.A (4R) and B10.D2 (R103), which differ from B6 at the K end of the H-2 complex, averaged 60 percent of the completely H-2 allogeneic value. Since the mutant and wild-type gene products have no serological and minimal structural differences relative to other alleles at H-2K, these results indicate that the CTL.Pf does not increase with increasing H-2 antigenic disparity between andy two strains. Rather, the data suggests that the T-cell receptor repertoire recognizes those H-2 molecules or determinants closest to self.


Induction of secific immunological tolerance to histocompatible renal and skin allografts after donor strain spleen implantation.
Spleens from Lewis X BN F1 hybrid rats were directly anastamosed to the circulation of parental strain Lewis rats by a microvascular technique; no immunosuppressive drugs were given. Donor spleens enlarged massively during the first month after implantation, then grew gradually smaller over succeeding months without compromising their blood supply. Renal allografts were placed into bilaterally nephrectomised recipients that had already borne a splenic allograft for three months. The grafts functioned perfectly and showed no signs of rejection five months later. Donor LBN skin allografts transplanted to these animals showed markedly prolonged survival while third-party BUF rat skin allografts were rejected in first-set fashion. High titres of anti-LBN haemagglutinating antibody could be detected in the circulation of spleen-grafted animals during the first month; the titres fell to zero by the fourth month. Cellular reactivity of recipient cells against LBN antigens measured by the popliteal node GVH assay fell to minimal levels by the third month. These data indicate that the immune response to allografted tissues may be specifically and markedly suppressed in adult animals by continued presence of a donor-strain spleen.


Regulation of toxA by PtxR in Pseudomonas aeruginosa PA103.
Exotoxin A (ETA) production in Pseudomonas aeruginosa requires the regulatory locus regAB. Pseudomonas aeruginosa PA103 produces significantly higher levels of ETA than the prototypic strain PAO1 does, partly because of differences in the regAB locus. Other factors that contribute to this variation are not known. We previously described the P. aeruginosa gene ptxR that positively regulates production of ETA through regAB. ETA production was enhanced but still iron regulated in the PAO1 strain PAO1-XR that carries two copies of ptxR on its chromosome. Here we determine whether ptxR regulation of ETA is different in PA103. In contrast to PAO1-XR, ETA activity produced by PA103-2R, a PA103 strain carrying two copies of ptxR, is enhanced tenfold and partially deregulated in the presence of iron. Real-time PCR transcriptional analysis showed that the copy number of toxA mRNA in PA103-2R is significantly higher than in PA103 in both the presence and absence of iron, yet no similar increase in either regAB or ptxR mRNA copy number was detected. The integrated plasmid together with adjoining DNA was retrieved from the PA103-2R chromosome to determine whether integration-induced DNA changes played a role in this phenotype. Introduction of the retrieved plasmid in PA103 produced a phenotype similar to that of PA103-2R. Sequence analysis of the plasmid revealed the loss of 322 bp within the region 3' of ptxR. A plasmid construct carrying a 4-bp insertion in this same region produced in PA103 a phenotype similar to that of PA103-2R. Our results suggest that the effect of ptxR on toxA expression is different in PA103 than in PAO1 and that this variation in PA103-2R does not occur solely through regAB. Changes within the region 3' of ptxR are critical for the production of the unique PA103-2R phenotype, which occurs in trans and requires intact ptxR, but is not caused by ptxR overexpression.


Hostile attribution bias and angry rumination: A longitudinal study of undergraduate students.
Angry rumination and hostile attribution bias are important cognitive factors of aggression. Although prior theoretical models of aggression suggest that aggressive cognitive factors may influence each other, there are no studies examining the longitudinal relationship between angry rumination and hostile attribution bias. The present study used cross-lagged structural equation modeling to explore the longitudinal mutual relationship between hostile attribution bias and angry rumination; 941 undergraduate students (38.5% male) completed questionnaires assessing the variables at two time points. The results indicate that hostile attribution bias showed a small but statistically significant effect on angry rumination 6 months later, and angry rumination showed a quite small but marginally significant effect on hostile attribution bias across time. The present study supports the idea that hostile attribution bias influences angry rumination, and argue that the relationship between angry rumination and hostile attribution bias may be mutual. Additionally, the results suggest that there may be a causal relation of different aggression-related cognitive factors.


dCAPS, a simple technique for the genetic analysis of single nucleotide polymorphisms: experimental applications in Arabidopsis thaliana genetics.
PCR-based detection of single nucleotide polymorphisms is a powerful tool for the plant geneticist. Cleaved amplified polymorphic sequence analysis is the most widely used approach for the detection of single nucleotide polymorphisms. However, this technique is limited to mutations which create or disrupt a restriction enzyme recognition site. This paper presents a modification of this technique where mismatches in a PCR primer are used to create a polymorphism based on the target mutation. This technique is useful for following known mutations in segregating populations and genetic mapping of isolated DNAs used for positional based cloning of new genes. In addition, a computer program has been developed that facilitates the design of these PCR primers.


Homogeneity and distinctiveness of Polish paternal lineages revealed by Y chromosome microsatellite haplotype analysis.
Different regional populations from Poland were studied in order to assess the genetic heterogeneity within Poland, investigate the genetic relationships with other European populations and provide a population-specific reference database for anthropological and forensic studies. Nine Y-chromosomal microsatellites were analysed in a total of 919 unrelated males from six regions of Poland and in 1,273 male individuals from nine other European populations. AMOVA revealed that all of the molecular variation in the Polish dataset is due to variation within populations, and no variation was detected among populations of different regions of Poland. However, in the non-Polish European dataset 9.3% ( P<0.0001) of the total variation was due to differences among populations. Consequently, differences in R(ST)-values between all possible pairs of Polish populations were not statistically significant, whereas significant differences were observed in nearly all comparisons of Polish and non-Polish European populations. Phylogenetic analyses demonstrated tight clustering of Polish populations separated from non-Polish groups. Population clustering based on Y-STR haplotypes generally correlates well with the geography and history of the region. Thus, our data are consistent with the assumption of homogeneity of present-day paternal lineages within Poland and their distinctiveness from other parts of Europe, at least in respect to their Y-STR haplotypes. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00439-002-0728-0.


[Sleeve Resection for Right Upper Lobe Non-small Cell Lung Cancer After Systemic Chemotherapy and Immune Checkpoint Inhibitor Administration].
A man in his 50s was diagnosed with right upper lobe non-small-cell lung cancer (cT3N1M0, stage ⅢA) on bronchoscopy. The tumor was located at the right hilum and was bordered extensively on the pulmonary artery. We observed significant tumor shrinkage (ycT1bN1M0, stage ⅡB), following three cycles of systemic chemotherapy combined with an immune checkpoint inhibitor and performed right upper sleeve lobectomy + ND2a-2 via thoracotomy for radical resection. Postoperative histopathological examination showed no residual tumor cells, and the patient was deemed to have a histopathologic complete response. Currently, the patient is being followed up without adjuvant chemotherapy. Several recent studies have reported the usefulness of systemic chemotherapy combined with immune checkpoint inhibitor administration as preoperative induction chemotherapy. However, the role of adjuvant immunotherapy in patients with a histopathologic complete response remains unclear, and careful treatment decision-making is important.


Syneture stainless STEEL suture. A collective review of its performance in surgical wound closure.
Syneture (division of U.S. Surgical, division of Tyco Healthcare, Norwalk, Connecticut, USA) STEEL sutures are monofilament stainless steel sutures composed of 316L stainless steel conforming to ASTM Standard F138 grade 2 (" Stainless steel bar and wire for surgical implant"). STEEL sutures meet all requirements established by the United States Pharmacopeia (USP) for nonabsorbable surgical sutures. Steel sutures are for use in abdominal wound closure, intestinal anastomosis, hernia repair, sternal closure, and skin closure. They are attached to the following types of surgical needles: Roto-Grip Needles and SCC Needle. The sutures and needles are packaged in a Mylar/Tyvek outer envelope. The purposes of this clinical review are two fold. First, we will report the performance of the Syneture STEEL suture product in the largest studies of suture performance ever reported in the literature. In addition, we will provide comprehensive information from the surgical literature that highlights the unique benefits of stainless steel sutures for the following wound closure techniques: sternal fixation, abdominal wound repair, inguinal hernia repair, and skin wound closure. Consorta Inc. (Rolling Meadows, Illinois), a leading healthcare resource management group purchasing organization, and Syneture, jointly with a clinician task force, designed a reproducible surgical evaluation program for needles and sutures in a large cooperative of healthcare systems. Because of the subjective nature of the more commonly used suture selection techniques, a nonexperimental observational study approach was designed to replace perception of performance characteristics with actual clinical experience. In a report involving 19 Consorta shareholder hospitals, they discussed the preliminary part (Phase I) of a large nonexperimental observational study of the clinical performance of surgical needles and sutures. Performance characteristics of the sutures and needles produced by Syneture that were evaluated in 3407 surgical procedures included packaging/ease of opening, needle strength and sharpness, tissue drag, knot security, tensile strength, clinically acceptable determinations, and clinically unacceptable determinations. In this preliminary study, the surgeons concluded that the needles and sutures were clinically acceptable in 98.1% of the evaluations. Armed with this favorable experience, we wanted to expand this observational study to an entirely new group of shareholder hospitals that had a larger number of participating hospitals (Phase I, 19 hospitals; Phase II, 42 hospitals). This more than doubling of hospital observational base dramatically increased the number of patients and performance evaluations. In the Phase II expanded program involving 42 hospitals, the number of patients (8939) and the number of evaluations (25,545) were more than twofold the preliminary study. In the phase I multicentric evaluation of Syneture surgical sutures, the performance of 9266 sutures was evaluated. Of these performance evaluations, 130 evaluations focused on Syneture STEEL sutures. The surgeons were especially pleased by the performance of this suture product, with 129 Syneture STEEL products being judged as clinically acceptable in their performance. Only one Syneture STEEL suture was judged to be unacceptable in its performance, resulting in a 99.2% acceptability rating. In the expanded phase II evaluation of Syneture suture products, the performance evaluation involved 25,545 surgical suture evaluations. The performance of Syneture STEEL sutures was judged in 215 cases. Of these product performance evaluations, 207 were judged to be clinically acceptable in their performance (96.3%). It is important to emphasize that the phase I and phase II observational studies evaluated the performance of other sutures besides monofilament steel sutures. These comprehensive suture and needle performance evaluations included the following additional sutures: Plain Gut, Mild Chromic Gut, Chromic Gut, DEXON II, DEXON S, MAXON, BIOSYN, SOFSILK, SURGILON, BRALON, MONOSOF, DERMALON, SURGIDAC, POLY-SORB, TI.CRON, SURGIPRO, SURGIPRO II, NOVAFIL, VASCUFIL, and FLEXON. Finally, we provide a collective review of the literature that shows the reliable performance of monofilament stainless steel sutures in the following wound closure techniques: sternal fixation, abdominal wound closure, inguinal hernia repair, and skin wound closure.


Hemispheric specialization and the neurology of emotion.
The regulation of such biologic drives as sex and aggression is a critical evolutionary function required of the nervous system. There is evidence that, in humans, the right hemisphere is dominant for many "emotional" functions. In the cortical regions involved in emotion, there are two important, complementary, sensorilimbic connective pathways: a dorsal system critical for surveillance, attention, and arousal and a ventral system specialized for stimulus identification, learning, and emotional response. Hemispheric specialization may introduce lateral asymmetries in these sensorilimbic connections, which could account for contrasting dominance in both emotional functions and some cognitive domains.


Discovery of YSR734: A Covalent HDAC Inhibitor with Cellular Activity in Acute Myeloid Leukemia and Duchenne Muscular Dystrophy.
Histone deacetylases (HDACs) have emerged as powerful epigenetic modifiers of histone/non-histone proteins via catalyzing the deacetylation of ε-N-acetyl lysines. The dysregulated activity of these Zn2+-dependent hydrolases has been broadly implicated in disease, notably cancer. Clinically, the recurring dose-limiting toxicities of first-generation HDACi sparked a paradigm shift toward safer isoform-specific molecules. With pervasive roles in aggressive diseases, there remains a need for novel approaches to target these enzymes. Herein, we report the discovery of YSR734, a first-in-class covalent HDACi, with a 2-aminobenzanilide Zn2+ chelate and a pentafluorobenzenesulfonamide electrophile. This class I selective proof of concept modified HDAC2Cys274 (catalytic domain), with nM potency against HDAC1-3, sub-μM activity in MV4-11 cells, and limited cytotoxicity in MRC-9 fibroblasts. In C2C12 myoblasts, YSR734 activated muscle-specific biomarkers myogenin/Cav3, causing potent differentiation into myotubes (applications in Duchenne Muscular Dystrophy). Current efforts are focused on improving in vivo ADME toward a preclinical covalent HDACi.


Chimeric influenza-virus-like particles containing the porcine reproductive and respiratory syndrome virus GP5 protein and the influenza virus HA and M1 proteins.
Both porcine reproductive and respiratory syndrome and swine influenza are acute, highly contagious swine diseases. These diseases pose severe threats for the swine industry and cause heavy economic losses worldwide. In this study, we have developed a chimeric virus-like particle (VLP) vaccine candidate for porcine reproductive and respiratory syndrome virus (PRRSV) and H3N2 influenza virus and investigated its immunogenicity in mice. The HA and M1 proteins from the H3N2 influenza virus and the PRRSV GP5 protein fused to the cytoplasmic and transmembrane domains of the NA protein were both incorporated into the chimeric VLPs. Analysis of the immune responses showed that the chimeric VLPs elicited serum antibodies specific for both PRRSV GP5 and the H3N2 HA protein, and they stimulated cellular immune responses compared to the responses to equivalent amounts of inactivated viruses. Taken together, the results suggested that the chimeric VLP vaccine represents a potential strategy for the development of a safe and effective vaccine to control PRRSV and H3N2 influenza virus.


[CME-Sonography 102: Acute Epigastric Pain].
CME-Sonography 102: Acute Epigastric Pain Abstract. Acute upper abdominal pain is a common issue in emergency medicine. Next to the anamnesis and laboratory findings, sonography plays a leading role in differentiation. In addition to the direct representation of the respective pathologies (gallstones, duct dilatations, tumors), the clinical-sonographic examination, the so-called palpation under ultrasound view, is also important. In this article we aim to show the way of diagnosing acute epigastric pain.


SKF-83959 is not a highly-biased functionally selective D1 dopamine receptor ligand with activity at phospholipase C.
SKF-83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine] is reported to be a functionally selective dopamine D1 receptor ligand with high bias for D1-mediated phospholipase C (PLC) versus D1-coupled adenylate cyclase signaling. This signaling bias is proposed to explain behavioral activity in both rat and primate Parkinson's disease models, and a D1-D2 heterodimer has been proposed as the underlying mechanism. We have conducted an in-depth pharmacological characterization of this compound in dopamine D1 and D2 receptors in both rat brain and heterologous systems expressing human D1 or D2 receptors. Contrary to common assumptions, SKF-83959 is similar to the classical, well-characterized partial agonist SKF38393 in all systems. It is a partial agonist (not an antagonist) at adenylate cyclase in vitro and ex vivo, and is a partial agonist in D1-mediated β-arrestin recruitment. Contrary to earlier reports, it does not have D1-mediated effects on PLC signaling in heterologous systems. Because drug metabolites can also contribute, its 3-N-demethylated analog also was synthesized and tested. As expected from the known structure-activity relationships of the benzazepines, this compound also had high affinity for the D1 receptor and somewhat higher intrinsic activity than the parent ligand, and also might contribute to in vivo effects of SKF-83959. Together, these data demonstrate that SKF-83959 is not a highly-biased functionally selective D1 ligand, and that its reported behavioral data can be explained solely by its partial D1 agonism in canonical signaling pathway(s). Mechanisms that have been proposed based on the purported signaling novelty of SKF-83959 at PLC should be reconsidered.


Genome-Wide Identification of Metal Tolerance Protein Genes in Populus trichocarpa and Their Roles in Response to Various Heavy Metal Stresses.
Metal tolerance proteins (MTPs) are plant divalent cation transporters that play important roles in plant metal tolerance and homeostasis. Poplar is an ideal candidate for the phytoremediation of heavy metals because of its numerous beneficial attributes. However, the definitive phylogeny and heavy metal transport mechanisms of the MTP family in poplar remain unknown. Here, 22 MTP genes in P. trichocarpa were identified and classified into three major clusters and seven groups according to phylogenetic relationships. An evolutionary analysis suggested that PtrMTP genes had undergone gene expansion through tandem or segmental duplication events. Moreover, all PtrMTPs were predicted to localize in the vacuole and/or cell membrane, and contained typical structural features of the MTP family, cation efflux domain. The temporal and spatial expression pattern analysis results indicated the involvement of PtrMTP genes in poplar developmental control. Under heavy metal stress, most of PtrMTP genes were induced by at least two metal ions in roots, stems or leaves. In addition, PtrMTP8.1, PtrMTP9 and PtrMTP10.4 displayed the ability of Mn transport in yeast cells, and PtrMTP6 could transport Co, Fe and Mn. These findings will provide an important foundation to elucidate the biological functions of PtrMTP genes, and especially their role in regulating heavy metal tolerance in poplar.


Phase separation of myelin sheath in Triton X-114 solution: predominant localization of the 21.5-kDa isoform of myelin basic protein in the lipid raft-associated domain.
Myelin basic protein (MBP) isoforms in the myelin sheath are known to have distinct intracellular expression patterns, which are profoundly related to functional specificity. Determining the differential localization of MBP isoforms is therefore important for understanding their pathophysiological roles. In this study, we have developed a new method for phase separation of myelin. The non-ionic detergent Triton X-114 is used to solubilize myelin sheath which then undergoes phase separation to yield four fractions. The lipid raft-associated proteins and lipids in each fraction were analysed by immunoblotting and lipid analysis, respectively. The present method gives two lipid raft-enriched fractions, one of them was found to contain only lipid raft-associated galactocerebroside and cholesterol as the major lipids. The 21.5-kDa MBP isoforms (21.5 MBP), both unphosphorylated and phosphorylated, were exclusively contained in this fraction. Phosphorylated 21.5 MBP (21.5 pMBP) has been shown to specifically disappear from demyelinated loci. The present analytical method clearly indicated that disappearance of 21.5 pMBP corresponded to demyelination and its reappearance corresponded to prevention of demyelination. Demyelination was also associated with aging and was prevented by the myelin-protecting herbal medicine, Chinpi, a type of dried citrus peel.