Analysis of surface properties of fixed and live cells using derivatized agarose beads.
A novel assay has been developed for the histochemical characterization of surface properties of cells based on their adhesion to agarose beads derivatized with more than 100 types of molecules, including sugars, lectins and other proteins, and amino acids. The assay simply involves mixing small quantities of washed cells and beads in droplets on glass microscope slides and determining to which beads various cell types adhere. Distilled water was found to be the best medium for this assay because added ions or molecules in other media inhibit adhesion in some cases. Many cells, however, cannot tolerate distilled water. Here we show that cells fixed with either of two fixatives (1% formaldehyde or Prefer fixative) displayed similar bead-binding properties as did live cells. Specificity of cell-bead binding was tested by including specific free molecules in the test suspensions in hapten-type inhibition experiments. If a hapten compound inhibited live-cell adhesion to a specific bead, it also inhibited fixed-cell adhesion to a specific bead. The results of these experiments suggest that fixed cells display authentic surface properties, opening the door for the use of this assay with many cell types that cannot tolerate distilled water.


MATERNAL DEPRESSIVE SYMPTOMS IN CHILDHOOD AND OPENNESS TO EXPERIENCE IN ADULTHOOD.
We examined the role of maternal depressive symptoms reported during childhood as a predictor of an important personality trait, Openness to Experience (O), in middle adulthood. Participants were 95 adults (38 previously malnourished, 57 control, mean age 42.1 years) who had been followed longitudinally since childhood by the Barbados Nutrition Study. Maternal depressive symptoms had been measured when the participants were 5-11 years of age by the General Adjustment and Morale Scale; O was measured in adulthood by the Revised NEO-Personality Inventory (NEO-PI-R). Multiple regression analyses, adjusted for childhood household standard of living, showed a significant main effect on O of maternal depressive symptoms (p < 0.01). Maternal depression also attenuated the significant effect of childhood malnutrition by 14%. Maternal depressive symptoms in childhood may therefore play a causal role in adult personality, in particular Openness to Experience, with implications for creativity.


New "green" approaches to the synthesis of pyrazole derivatives.
A novel approach to the synthesis of pyrazole derivatives from tosylhydrazones of alpha,beta-unsaturated carbonyl compounds possessing a beta-hydrogen is proposed, exploiting microwave (MW) activation coupled with solvent free reaction conditions. The cycloaddition was studied on three ketones (trans-4-phenyl-3-buten-2-one, beta-ionone and trans-chalcone). The corresponding 3,5-disubstituted-1H-pyrazoles were obtained in high yields and after short reaction times. In order to simplify and point out the green chemistry features of the method, a further improvement was achieved under the same catalytic conditions with a "one pot" synthesis of these heterocyclic compounds, starting directly from their carbonyl precursors via tosylhydrazones generated in situ. For an exhaustive study, the dielectric properties of the solid reaction mixtures were also measured, in order to obtain input data for the numerical simulation of their heating behaviour in the single mode MW cavity which was used for experimental work. In order to supply a valid methodology and tool for measuring the environmental impact, a comparative study between the synthetic route proposed and the classical synthetic route has been carried out.


Bacterial Genome Mining of Enzymatic Tools for Alkyne Biosynthesis.
The alkyne is an important functionality widely used in material science, pharmaceutical science, and chemical biology, but the importance of this functionality is contrasted by the very limited number of enzymes known to be involved in alkyne biosynthesis. We recently reported the first known carrier protein-dependent pathway for terminal alkyne formation, and in silico analysis suggested that this mechanism could be widespread in bacteria. In this paper, we screened additional homologous gene cassettes presumed to be involved in alkyne biosynthesis using both in vitro biochemical study and an E. coli-polyketide synthase (PKS) reporting system for in vivo analysis. We discovered and characterized a new terminal alkyne biosynthetic pathway comprised of TtuA, -B, and -C from Teredinibacter turnerae T7901. While the acyl-CoA ligase homologue (TtuA) demonstrated promiscuity in the activation and loading of medium-chain fatty acids onto the carrier protein (TtuC), the desaturase homologue (TtuB) showed stringent substrate specificity toward C10 fatty acyl moieties. In addition, TtuB was demonstrated to be a bifunctional desaturase/acetylenase that efficiently catalyzed two sequential O2-dependent dehydrogenation reactions. A novel terminal-alkyne bearing polyketide was further produced upon coexpression of ttuABC and a PKS gene in E. coli. The discovery and characterization of TtuA, -B, and -C provides us with a new bifunctional desaturase/acetylenase for mechanistic and structural study and expands the scarce enzyme inventory for the biosynthesis of the alkyne functionality, which has important applications in synthetic and chemical biology.


Chiral-Induced Ultrathin Covalent Organic Frameworks Nanosheets with Tunable Circularly Polarized Luminescence.
Development of covalent organic frameworks (COFs) with circularly polarized luminescence (CPL) is still challenging. Here we first reported ultrathin COFs nanosheets (NS) based CPL materials using a chiral induced-synthesis strategy. Chiral amines served as chiral inducers to give COF TpBpy with chirality and participated in the modification of TpBpy, inhibiting the fluorescence quenching caused by π-π stacking to form ultrathin luminescent chiral COFs (chirCOFs) NS. The obtained chirCOFs R-/S-TpBpy NS had strong chirality and intense red CPL property with a |glum| of ∼0.02. Afterward, the carboxyl containing green and blue fluorescent dye molecules were postmodified onto the chirCOFs NS (chirCOFs/Dyes) to achieve color-adjustable CPL. Due to the chirality and energy transfer between chirCOFs and dye groups, the obtained chirCOFs/Dyes showed strong chirality and increased and tunable photoluminescence, exhibiting excellent, tunable, and amplified CPL performance with a maximum |glum| of ∼0.1, which was ∼5 times stronger than that of as-prepared chirCOFs NS. Moreover, the corresponding chirCOFs NS were dispersed into a polydimethylsiloxane (PDMS) matrix to form wafer size, highly transparent, and flexible COFs/PDMS films for practical CPL application. This study opens a new strategy to prepare ultrathin chirCOFs NS with strong and tunable CPL by chiral induction and provides a new approach for the preparation of transparent, large size, and flexible COFs composite films in chiral optical applications.


Graphene spintronics: the role of ferromagnetic electrodes.
We report a first principles study of spin transport under finite bias through a graphene-ferromagnet (FM) interface, where FM = Co(111), Ni(111). The use of Co and Ni electrodes achieves spin efficiencies reaching 80% and 60%, respectively. This large spin filtering results from the materials specific interaction between graphene and the FM which destroys the linear dispersion relation of the graphene bands and leads to an opening of spin-dependent energy gaps of ≈0.4-0.5 eV at the K points. The minority spin band gap resides higher in energy than the majority spin band gap located near E(F), a feature that results in large minority spin dominated currents.


Understanding recovery Capital in relation to categorical 12-Step involvement and abstinence social support.
Although recovery capital represents various resources for persons recovering from substance use disorders, measures of this construct examine components that might not necessarily reflect the recovery goals of individuals who base their recovery through involvement in 12-step groups such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA). It is not clear whether 12-step involvement is related to recovery capital, particularly among individuals living in recovery homes who utilize social networks of recovering peers for their recovery. Thus, categorical involvement in a set of 12-step activities was examined in relation to recovery capital and abstinence social support. Differences in terms of general (recovery capital scores, retention rates) and abstinence-specific (abstinence social support) resources were examined in relation to recovery home residents who were (n = 395) and were not (n = 232) categorically involved in their 12-step recovery. Residents with categorical 12-step involvement reported significantly higher levels of recovery capital and abstinence social support, and there was no significant difference observed in retention rates between residents who were/were not categorically involved in 12-step groups. Findings suggest community resources such as recovery homes and categorical involvement in 12-step groups are important recovery capital components that help individuals who use a 12-step approach to their recovery. Recovery capital among those involved with 12-step fellowships such as AA and NA should be assessed by examining abstinence-specific components such as representative involvement in 12-step groups and social support that is abstinence-specific.


Pharmacologic trials in the treatment of cerebellar tremor.
We studied the effect of long-term administration of propranolol hydrochloride and isoniazid and the acute action of ethyl alcohol on cerebellar tremor in patients with multiple sclerosis and primary cerebellar degeneration in a placebo-controlled double-blind crossover test. None of the drugs decreased the severity of either static or kinetic cerebellar tremors.


Neuroendocrine tumors of the thyroid gland.
The neuroendocrine lesions of the thyroid are few in number and include C-cell lesions (C-cell hyperplasia and medullary carcinoma), mixed C-cell and follicular-derived tumors, paraganglioma, intrathyroidal parathyroid adenoma, and metastasis to the thyroid from neuroendocrine carcinoma arising elsewhere. However, some follicular-derived lesions of the thyroid can show trabecular and nesting growth patterns characteristic of neuroendocrine tumors. These lesions should also be included in the differential diagnosis of primary and secondary neuroendocrine tumors of the thyroid.


PCP: a dangerous drug.
PCP is again becoming a popular drug of abuse in the United States, particularly among the young. A variety of medical, psychiatric and pathologic effects make PCP both appealing and profoundly dangerous to naive and chronic drug users. Pharmacologic intervention is helpful in PCP-induced acute intoxication and psychosis. Effective long-term treatment is available in addiction programs.


Autonomous Data Collection Using a Self-Organizing Map.
The self-organizing map (SOM) is an unsupervised learning technique providing a transformation of a high-dimensional input space into a lower dimensional output space. In this paper, we utilize the SOM for the traveling salesman problem (TSP) to develop a solution to autonomous data collection. Autonomous data collection requires gathering data from predeployed sensors by moving within a limited communication radius. We propose a new growing SOM that adapts the number of neurons during learning, which also allows our approach to apply in cases where some sensors can be ignored due to a lower priority. Based on a comparison with available combinatorial heuristic algorithms for relevant variants of the TSP, the proposed approach demonstrates improved results, while also being less computationally demanding. Moreover, the proposed learning procedure can be extended to cases where particular sensors have varying communication radii, and it can also be extended to multivehicle planning.


Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons.
Vesicle sharing between synaptic boutons is an important component of the recycling process that synapses employ to maintain vesicle pools. However, the mechanisms supporting and regulating vesicle transport during the inter-synaptic exchange remain poorly understood. Using nanometer-resolution tracking of individual synaptic vesicles and advanced computational algorithms, we find that long-distance axonal transport of synaptic vesicles between hippocampal boutons is partially mediated by the actin network, with myosin V as the primary actin-dependent motor that drives this vesicle transport. Furthermore, we find that vesicle exit from the synapse to the axon and long-distance vesicle transport are both rapidly and dynamically regulated by activity. We corroborated these findings with two complementary modeling approaches of vesicle exit, which closely reproduced experimental observations. These findings uncover the roles of actin and myosin V in supporting the inter-synaptic vesicle exchange and reveal that this process is dynamically modulated in an activity-dependent manner.


A computational modelling study of oxygen vacancies at LaCoO3 perovskite surfaces.
Atomistic computational modelling of the surface structure of the catalytically-active perovskite LaCoO(3) has been undertaken in order to develop better models of the processes involved during catalytic oxidation processes. In particular, the energetics of creating oxygen ion vacancies at the surface have been investigated for the three low index faces (100), (110) and (111). Two mechanisms for vacancy creation have been considered involving dopant Sr(2+) cations at the La(3+) site and reduction of Co(3+) to Co(2+). For both mechanisms, there is a general tendency that the smaller the cation defect separation, the lower the energy of the cluster, as would be expected from simple electrostatic considerations. In addition, there are clear indications that oxygen vacancies are more easily created at the surface than in the bulk. The results also confirm that the presence of defects strongly influences crystal morphology and surface chemistry. The importance of individual crystal surfaces in catalysis is discussed in terms of the energetics for the creation of oxygen vacancies.


Effect of flow and surface area on angiotensin-converting enzyme activity in rabbit lungs.
Pulmonary angtiotensin-converting enzyme (ACE) is located on the luminal surface of pulmonary microvasculature. Multiple indicator-dilution techniques have been used to measure pulmonary ACE activity in vivo and in isolated lungs. These studies suggest that ACE activity is depressed in several forms of acute lung injury. Depression of ACE activity may reflect impaired substrate delivery to enzyme sites because of flow-related reduction of perfused surface area. To assess the role of altered microvascular flow and surface area in the measurement of ACE activity, we utilized similar techniques to estimate the apparent Km and Vmax of pulmonary ACE in isolated, Krebs-perfused rabbit lungs. Km is an estimate of the affinity of a synthetic ACE substrate, [3H]benzoyl-phenyl-alanyl-alanyl-proline ([3H]BPAP), for ACE and should not be influenced by the rate of substrate delivery to luminal enzyme sites. Conversely, Vmax is an index of the number of ACE sites and should be influenced by perfusion changes that alter the number of perfused sites (recruitment or derecruitment). When isolated lungs were subjected to physiological maneuvers designed to increase or decrease perfused surface area, apparent Vmax increased or decreased respectively. Apparent Km was not altered by these maneuvers. Km and Vmax were independent of changes in perfusion rate when surface area was held constant. Thus these parameters should be useful in evaluating perfusion changes in normal and injured lungs.


Alexithymia and Self-Esteem in Patients with Ankylosing Spondylitis.
Ankylosing spondylitis (AS), which has an unknown etiology, inflammatory disorder, characterized by inflammation of the spinal joints and adjacent structures. It has a negatif effect on all aspects of a patients's life: Physcally, psychologically and socially. The purpose of this study was to determine the effect of AS on self-esteem and alexithymia. In this study, 50 patients from the department of physical therapy and rehabilitation with the diaognosis of AS who were under traetment and follow-up and 50 healty volunteers who matched for age and gender were taken. Toronto Alexithymia Scale (TAS), Beck Depression Inventory (BDI), Rosenberg Self-Esteem Scale (RSES), Beck Anxiety Inventory (BAI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were performed to both patients and control group. Compared to the control group, the anxiety and depression scores were higher in the patient group and the alexithymic characteristics were significantly higher, self-esteem scores were significantly lower in the patient group (p<.05). Like all the other inflammatory chronic diseases, depression and anxiety are commonly seen in AS patients. Alexithymai and self-esteem of these patients should be considered carefully. More studies are needed on this regard.


Clofarabine and nelarabine: two new purine nucleoside analogs.
Both clofarabine and nelarabine recently received an accelerated approval by the US Food and Drug Administration for use in refractory or relapsed pediatric acute lymphoblastic leukemia and in refractory-relapsed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Both drugs have been studied for their metabolism and mechanisms of action in preclinical investigations and for their efficacy in clinical trials. This review will summarize these investigations and will suggest future plans with these nucleoside analogs. Clofarabine and nelarabine were designed based on preclinical and clinical findings with other nucleoside analogs or normal deoxynucleotides such as dGTP. Studies in cell lines have demonstrated that triphosphate is the active metabolite for both these purine nucleoside analogs. Pharmacokinetic and pharmacodynamic investigations during clinical trials have verified the importance of triphosphate levels in achieving clinical responses. Several phase I and II clinical explorations have suggested the utility of clofarabine in acute leukemias and nelarabine in T-cell diseases. Dose-limiting toxicities were nonhematologic: hepatotoxicity for clofarabine and neurotoxicity for nelarabine. Clofarabine is the first deoxyadenosine analog that shows promise in adult and pediatric acute leukemias without untoward toxicity. Nelarabine, as expected from its design, is a drug that may be directed to T-cell diseases.


Heat Shock Protein 20 Gene Superfamilies in Red Algae: Evolutionary and Functional Diversities.
Heat shock protein 20 (Hsp20) genes play important roles in plant growth, development, and response to environmental stress. However, the Hsp20 gene family has not yet been systematically investigated, and its function in red algae (Rhodophyta) remains poorly understood. Herein, we characterized Hsp20 gene families in red algae by studying gene structure, conserved motifs, phylogenetic relationships, chromosome location, gene duplication, cis-regulatory elements, and expression profiles. In this study, 97 Hsp20 genes were identified using bioinformatic methods and classified into 13 subfamilies based on phylogenetic relationships. Phylogenetic analysis revealed that Hsp20 genes might have a polyphyletic origin and a complex evolutionary pattern. Gene structure analysis revealed that most Hsp20 genes possessed no introns, and all Hsp20 genes contained a conserved α-crystalline domain in the C-terminal region. Conserved motif analysis revealed that Hsp20 genes belonging to the same subfamily shared similar motifs. Gene duplication analysis demonstrated that tandem and segmental duplication events occurred in these gene families. Additionally, these gene families in red algae might have experienced strong purifying selection pressure during evolution, and Hsp20 genes in Pyropia yezoensis, Pyropia haitanensis, and Porphyra umbilicalis were highly evolutionarily conserved. The cis-elements of phytohormone-, light-, stress-responsive, and development-related were identified in the red algal Hsp20 gene promoter sequences. Finally, using Py. yezoensis, as a representative of red algae, the Hsp20 gene expression profile was explored. Based on the RNA-seq data, Py. yezoensis Hsp20 (PyyHsp20) genes were found to be involved in Py. yezoensis responses against abiotic and biotic stresses and exhibited diverse expression patterns. Moreover, PyyHsp20 is involved in Py. yezoensis growth and development and revealed spatial and temporal expression patterns. These results provide comprehensive and valuable information on Hsp20 gene families in red algae and lay a foundation for their functional characterization. In addition, our study provides new insights into the evolution of Hsp20 gene families in red algae and will help understand the adaptability of red algae to diverse environments.


Analysis of cell cycle arrest and apoptosis induced by RCAS1.
A tumor-associated antigen RCAS1 (receptor binding cancer antigen expressed on SiSo cells) induces cell cycle arrest and apoptosis to a putative RCAS1 receptor (RCAS1-R) expressing cells such as T, B, and natural killer cells. Its expression is related with clinical poor prognosis of some malignant tumors. It is suggested that the expression of RCAS1 in tumor cells plays an important role in evasion from host immune system resulting tumor progression, invasion and metastasis. However, the mechanism of RCAS1 induced cell cycle arrest and apoptosis has not been clarified. In this study, we established a mouse L cell line transformed with tetracycline-induced rcas1 gene expression system and analyzed the RCAS1 functions. We showed that RCAS1 induced cytochrome c release and activation of caspase-3 for apoptosis. Moreover, we investigated cell cycle associated proteins and revealed that cyclin D3 decreased significantly and no change was seen in the expression levels of the other proteins. These results suggest that cyclin D3 is one of the key target molecules in the RCAS1-RCAS1-R signaling pathway.


Distinct actions of Flt3 ligand and stem cell factor on myeloid lineage selection and maturation of granulocytes versus macrophages.
Flt3/Flk2 ligand (FL) and stem cell factor (SCF; c-kit ligand) interact with different but related surface receptor tyrosine kinases expressed on early hematopoietic cells. Both FL and SCF stimulate the proliferation of stem cells and progenitors, but the mechanisms by which these cytokines exert their functions are currently unknown. Here we show that FL and SCF have different effects on myeloid differentiation and lineage selection of early hematopoietic cells using a defined subpopulation of mouse bone marrow (BM) expressing c-Kit but lacking mature lineage markers (c-Kit+Lin-). SCF, together with IL-6, induced the differentiation of a large fraction of these progenitor cells toward mature granulocytes and to a lesser extent toward monocytes. In contrast, FL combined with IL-6 favored differentiation into mature monocytes and macrophages, and very few if any granulocytes could be identified. When FL and SCF were analyzed for their ability to support growth of multilineage erythroid colonies (pre-CFCmulti) and myeloid-committed colony-forming progenitors of granulocytes and monocytes (CFC-G/M), a clear discrepancy was also found. Both FL and SCF had synergistic effects on the proliferation of immature cells with blast-like morphology, but the expansion of pre-CFCmulti and CFC-G/M was favored by SCF but not by FL. FL synergized with both SCF and IL-6 with respect to proliferative response and maintenance of undifferentiated cells; however, the numbers of CFC-G/M after 7 or 14 days in culture were significantly lower than those observed with SCF combined with IL-6. Interestingly, in contrast to SCF, no pre-CFCmulti was recovered from BM cells expanded in the presence of FL and IL-6.


Flexibility of idiopathic congenital clubfeet treated by posteromedial release without talocalcaneal joint release.
We retrospectively reviewed 57 patients with 84 idiopathic clubfeet and followed them up for at least 15 years. All feet were rated as good or excellent according to the International Clubfoot Study Group score. Stress radiographs showed that the arc of forefoot motion of conservatively treated feet was 81%, in operated feet of patients aged more than 1 year it was 74%, and in feet of patients aged less than 1 year during surgery it was 65%, compared with those in contralateral normal feet. Despite the severity of the deformity, feet treated by our posteromedial release without talocalcaneal joint release were flexible and functional.


Behavioral-neuroendocrine-immunologic interactions in myocardial infarction.
An enduring state of exhaustion as opposed to chronic hostility-a long-term risk factor-has been found to be a more proximal precursor of myocardial infarction. The strength of the association with exhaustion suggests that this behavioral factor reflects not only a breakdown in adaptation to chronic stressors but also the disease process itself. Recent research on the pathogenesis of myocardial infarction lends credence to a role for immunological factors. herein, we outline a two-stage theoretical model, postulating a feedback relationship between behavior, associated neuroendocrine changes, immunological responses, and the pathogenesis of this disease. We propose a long-term first stage consisting of chronic hostility, prolonged occupational over-exertion, and exposure to other life stressors, terminating eventually in a much shorter second stage of 'vital exhaustion'. Stressor-associated neuroendocrine changes result in immunosuppression leading to reactivation of latent, systemic infections (such as cytomegalovirus) and potentially to autoimmune reactions as well. The consequent release of pro-inflammatory cytokines exacerbates fatigue and induces a stimulus for cytokine production in brain. This cytokine production stimulates a chronically activated, over-compensated limbic-hypothalamic-pituitary-adrenal axis, resulting in a dampened response, continued exhaustion, and a potential 'reverberating circuit' between behavior, neuroendocrine change, cytokine release and coronary artery occlusion, culminating in myocardial infarction.


Experimental tumor therapy in mice using the cyclophosphamide-activating cytochrome P450 2B1 gene.
Most malignant tumors of the central nervous system do not respond well to chemotherapy. The anticancer drug cyclophosphamide (CPA) is largely ineffective against these neoplasms as its conversion to DNA-alkylating, cytotoxic metabolites is restricted primarily to the liver and these metabolites do not readily cross the blood-brain barrier. Here, we show that brain tumor cells can be sensitized to the cytotoxic effects of CPA, both in culture and in vivo, by introduction of the hepatic enzyme responsible for the activation of CPA, cytochrome P450 2B1. Stable transfection of rat C6 glioma cells with the P450 2B1 gene rendered the cultured tumor cells sensitive to CPA. Further, C6 cells bearing this gene were more sensitive than parental cells to the cytotoxic action of CPA when grown subcutaneously in the flanks of athymic mice. Murine fibroblasts producing a retrovirus vector encoding P450 2B1 and expressing this enzyme were then prepared and grafted into the brains of athymic mice seeded with rat C6 gliomas. Intrathecal administration of CPA prevented the development of meningeal neoplasia and led to partial regression of the parenchymal tumor mass. By contrast, C6 glioma-bearing mice receiving fibroblasts expressing the Escherichia coli lacZ gene and CPA exhibited extensive meningeal tumors and parenchymal solid brain tumors. The in situ activation of CPA by cytochrome P450 2B1 provides a novel approach not only for brain tumor gene therapy, but also for negative, drug-conditional selection of other defined cell populations.


Validation of automated contour analysis of intravascular ultrasound images after vascular intervention.
The purpose of this study was to determine the feasibility of automated contour analysis of intravascular ultrasound images obtained after vascular intervention. This was a descriptive study. Intravascular ultrasound images obtained from patients after balloon angioplasty (n = 10), stent (n = 10), or stent graft placement (n = 10) were analyzed. A comparison was made between lumen area measured with an automated and a manual system. The location showing the smallest lumen area derived from the automated system was compared with the smallest lumen area selected by visual estimation. Images containing a dissection as a result of balloon angioplasty could not be analyzed by the automated system. The coefficient of variation between the lumen area measurements obtained with the automated system and the manual tracing system of images with a stent (n = 76) or stent graft (n = 79) was 2.7% and 2.1%, respectively. Correlation between the two systems was high (r = 1.00, p < 0.01) both for images containing stents or stent grafts. Minimum lumen area measured with the automated analysis system was smaller than minimum lumen area selected by visual estimation (mean difference 0.8 mm2 (4.9%) for stents and 2.4 mm2 (10.9%) for stent grafts). The location of the smallest lumen area determined with both systems was the same (<1 cm) in 16 cases and differed more than 1 cm in 4 other cases. The automated analysis system shows good agreement with manual contour analysis of lumen area in images with a stent or stent graft and is a reliable tool for determination of the smallest lumen area. The system is not able to analyze an irregular-shaped lumen area caused by a dissection.


Engineering of the yeast ubiquitin ligase Rsp5: isolation of a new variant that induces constitutive inactivation of the general amino acid permease Gap1.
Rsp5 is an essential ubiquitin-protein ligase in Saccharomyces cerevisiae. We found previously that the Ala401Glu rsp5 mutant is hypersensitive to various stresses that induce protein misfolding, suggesting that Rsp5 is a key enzyme for yeast cell growth under stress conditions. To isolate new Rsp5 variants as suppressors of the A401E mutant, PCR random mutagenesis was used in the rsp5(A401E) gene, and the mutagenized plasmid library was introduced into rsp5(A401E) cells. As a phenotypic suppressor of rsp5(A401E) cells, we isolated a quadruple variant (Thr357Ala/Glu401Gly/Lys764Glu/Glu767Gly) on a minimal medium containing the toxic proline analogue azetidine-2-carboxylate (AZC). Site-directed mutagenesis experiments showed that the rsp5(T357A/K764E) cells were much more tolerant to AZC than the wild-type cells, due to the smaller amounts of intracellular AZC. However, the T357A/K764E variant Rsp5 did not reverse the hypersensitivity of rsp5(A401E) cells to other stresses such as high growth temperature, ethanol, and freezing treatment. Interestingly, immunoblot and localization analyses indicated that the general amino acid permease Gap1, which is involved in AZC uptake, was absent on the plasma membrane and degraded in the vacuole of rsp5(T357A/K764E) cells before the addition of ammonium ions. These results suggest that the T357A/K764E variant Rsp5 induces constitutive inactivation of Gap1.


[ISSR analysis of genetic diversity of Coptis deltoidea].
To study the genetic diversity of Coptis deltoidea. The genetic diversity of 90 individuals from 8 populations was analyzed by ISSR. Twelve primers were selected to produce highly reproducible ISSR bands. Among 128 amplified bands, 94 showed polymorphism, the percentage of polymorphic bands reached 73.44%. Nei's gene diversity index (H) was 0.1925, Shannon's information index (I) was 0.3028, Gst was 0.7212. The genetic distance coefficient and similarity were 0.0858-0.2314 and 0.8046-0.9425, respectively. C. deltoidea held a high genetic diversity and the majority of genetic variation occurs among populations. By cluster analysis, the geographical distribution is very obvious. The ISSR marker can be used for the analysis of genetic diversity and genetic variation of C. deltoidea.


An oxygenated metabolite of benzo[a]pyrene increases hepatic β-oxidation of fatty acids in chick embryos.
Polycyclic aromatic hydrocarbons (PAHs) are well-known carcinogens to humans and ecotoxicological effects have been shown in several studies. However, PAHs can also be oxidized into more water soluble-oxygenated metabolites (Oxy-PAHs). The first purpose of the present project was to (1) assess the effects of a mixture containing three parent PAHs: anthracene, benz[a]anthracene, and benzo[a]pyrene versus a mixture of their oxygenated metabolites, namely: anthracene-9,10-dione, benz[a]anthracene-7,12-dione, and 9,10-dihydrobenzo[a]pyrene-7-(8H)-one on the hepatic fatty acid β-oxidation in chicken embryos (Gallus gallus domesticus) exposed in ovo. The second and also main purpose of the project was to (2) assess the effects of the parent PAHs versus their oxy-PAHs analogues when injected individually, followed by (3) additional testing of the individual oxy-PAHs. The hepatic β-oxidation was measured using a tritium release assay with [9,10-(3)H]-palmitic acid (16:0) as substrate. The result from the first part (1) showed reduced hepatic β-oxidation after exposure in ovo to a mixture of three PAHs, however, increased after exposure to the mixture of three oxy-PAHs compared to control. The result from the second part (2) and also the follow-up experiment (3) showed that 9,10-dihydrobenzo[a]pyrene-7-(8H)-one was the causative oxy-PAH. The implication of this finding on the risk assessment of PAH metabolite exposure in avian wildlife remains to be determined. To the best of our knowledge, no similar studies have been reported.


Comparison of immediate and long-term outcome of percutaneous transvenous mitral commissurotomy in patients who have and have not undergone previous surgical commissurotomy.
This study compared the immediate and long-term outcome of percutaneous transvenous mitral commissurotomy (PTMC) in patients who had (restenosis group, n = 9) or had not (de novo group, n = 27) previously undergone surgical mitral commissurotomy. The baseline echocardiographic score, which is an index of deformity of the mitral valve apparatus, was significantly higher in the restenosis group than in the de novo group (11 +/- 3 vs 7 +/- 2, p < 0.01), although age, left atrial diameter, and the prevalence of atrial fibrillation were similar. PTMC was performed by the Inoue technique, and was abandoned in 1 patient from the restenosis group because of failed trans-septal puncture. Including this patient, 3 patients (33%) in the restenosis group had a thickened atrial septum compared with only 1 (4%) in the de novo group. One patient in the de novo group developed cardiac tamponade during this procedure. In both groups, the mitral valve area increased significantly, but the success rate of PTMC was lower in the restenosis group (4/9 patients, 44%) than in the de novo group (22/27 patients, 81%) (p < 0.05). Twenty-six patients who had successful PTMC were followed up over 51 +/- 14 months. After 4 years of follow-up. 3 out of 4 patients (75%) in the restenosis group and 3 out of 22 patients (14%) in the de novo group demonstrated echocardiographic restenosis (p < 0.01). Stepwise multivariate analysis revealed that the echocardiographic score was the only significant predictor of both the immediate and long-term outcome. In conclusion, the immediate and long-term outcome of PTMC were worse in patients who had undergone previous surgical mitral commissurotomy than in those who had not. This was mainly attributable to the difference in the severity of the valvular lesions. In addition, our data suggested that a thickened atrial septum, possibly related to surgery as well as chronic rheumatic disease, may affect the performance of PTMC.


Chronic morphine administration increases beta-adrenergic receptor kinase (beta ARK) levels in the rat locus coeruleus.
Based on the established role of beta-adrenergic receptor kinase (beta ARK) and beta-arrestin in the desensitization of several G protein-coupled receptors, we investigated the effect of chronic morphine administration on beta ARK and beta-arrestin levels in selected brain areas. Levels of beta ARK were measured by blot immunolabeling analysis using antibodies specific for two known forms of beta ARK, i.e., beta ARK1 and beta ARK2. It was found that chronic morphine treatment produced an approximately 35% increase in levels of beta ARK1 immunoreactivity in the locus coeruleus, but not in several other brain regions studied. In contrast, chronic morphine treatment failed to alter levels of beta ARK2 immunoreactivity in any of the brain regions studied. Levels of beta-arrestin immunoreactivity, measured using an antiserum that recognizes two major forms of this protein in brain, were also found to increase (by approximately 20%) in the locus coeruleus. It is proposed that chronic morphine regulation of beta ARK1 and beta-arrestin levels may contribute to opioid-receptor tolerance that is known to occur in this brain region.


Narrow- and Broad-Spectrum Antibiotic Use among U.S. Children.
To provide updated estimates of narrow- and broad-spectrum antibiotic use among U.S. children. Linked nationally representative data from the 2004-2010 Medical Expenditure Panel Survey Household Component and the 2000 Decennial Census. Relationships between individual-, family-, and community-level characteristics and the use of antibiotics overall and in the treatment of respiratory tract infections (RTIs) are examined using multinomial choice models. More than one quarter (27.3 percent) of children used at least one antibiotic each year with 12.8 percent using broad-spectrum and 18.5 percent using narrow-spectrum antibiotics. Among children with use, more than two-thirds (68.6 percent) used antibiotics to treat RTIs. Multivariate models revealed many differences across groups in antibiotic use, overall and in the treatment of RTIs. Differential use was associated with a broad range of factors related to need (e.g., age, health status), resources (e.g., insurance status, parental income, and education), race-ethnicity, and Census region. Despite encouraging reports regarding the declining use of antibiotics, large differences in use associated with resources, race-ethnicity, and Census regions suggest a need for further improvement in the judicious and appropriate prescribing of antibiotics for U.S. children.


Manikin families representing obese airline passengers in the US.
Aircraft passenger spaces designed without proper anthropometric analyses can create serious problems for obese passengers, including: possible denial of boarding, excessive body pressures and contact stresses, postural fixity and related health hazards, and increased risks of emergency evacuation failure. In order to help address the obese passenger's accommodation issues, this study developed male and female manikin families that represent obese US airline passengers. Anthropometric data of obese individuals obtained from the CAESAR anthropometric database were analyzed through PCA-based factor analyses. For each gender, a 99% enclosure cuboid was constructed, and a small set of manikins was defined on the basis of each enclosure cuboid. Digital human models (articulated human figures) representing the manikins were created using a human CAD software program. The manikin families were utilized to develop design recommendations for selected aircraft seat dimensions. The manikin families presented in this study would greatly facilitate anthropometrically accommodating large airline passengers.


Anatomy and formation mechanisms of early amyloid-β oligomers with lateral branching: graph network analysis on large-scale simulations.
Oligomeric amyloid-β aggregates (AβOs) effectively trigger Alzheimer's disease-related toxicity, generating great interest in understanding their structures and formation mechanisms. However, AβOs are heterogeneous and transient, making their structure and formation difficult to study. Here, we performed graph network analysis of tens of microsecond massive simulations of early amyloid-β (Aβ) aggregations at near-atomic resolution to characterize AβO structures with sizes up to 20-mers. We found that AβOs exhibit highly curvilinear, irregular shapes with occasional lateral branches, consistent with recent cryo-electron tomography experiments. We also found that Aβ40 oligomers were more likely to develop branches than Aβ42 oligomers, explaining an experimental observation that only Aβ40 was trapped in network-like aggregates and exhibited slower fibrillization kinetics. Moreover, AβO architecture dissection revealed that their curvilinear appearance is related to the local packing geometries of neighboring peptides and that Aβ40's greater branching ability originates from specific C-terminal interactions at branching interfaces. Finally, we demonstrate that whether Aβ oligomerization causes oligomers to elongate or to branch depends on the sizes and shapes of colliding aggregates. Collectively, this study provides bottom-up structural information for understanding early Aβ aggregation and AβO toxicity.


Obesity Paradox in Lung Diseases: What Explains It?
Obesity is a globally increasing health problem that impacts multiple organ systems and a potentially modifiable risk factor for many diseases. Obesity has a significant impact on lung function and is strongly linked to the pathophysiology that contributes to lung diseases. On the other hand, reports have emerged that obesity is associated with a better prognosis than for normal weight individuals in some lung diseases, including pneumonia, acute lung injury/acute respiratory distress syndrome, chronic obstructive pulmonary disease, and lung cancer. The lesser mortality and better prognosis in patients with obesity is known as obesity paradox. While obesity paradox is both recognized and disputed in epidemiological studies, recent research has suggested possible mechanisms. In this review, we attempted to explain and summarize these factors and mechanisms, including immune response, pulmonary fibrosis, lung function, microbiota, fat and muscle reserves, which are significantly altered by obesity and may contribute to the obesity paradox in lung diseases. We also discuss contrary literature that attributes the "obesity paradox" to confounding. The review will illustrate the possible role of obesity in the prognosis or course of lung diseases, leading to a better understanding of the obesity paradox and provide hints for further basic and clinical research in lung diseases.


Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.
Epstein-Barr virus (EBV) is a human herpesvirus associated with B-cell and epithelial cell malignancies. EBV lytically infects normal differentiated oral epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia (OHL) in immunosuppressed patients. However, the cellular mechanism(s) that enable EBV to establish exclusively lytic infection in normal differentiated oral epithelial cells are not currently understood. Here we show that a cellular transcription factor known to promote epithelial cell differentiation, KLF4, induces differentiation-dependent lytic EBV infection by binding to and activating the two EBV immediate-early gene (BZLF1 and BRLF1) promoters. We demonstrate that latently EBV-infected, telomerase-immortalized normal oral keratinocyte (NOKs) cells undergo lytic viral reactivation confined to the more differentiated cell layers in organotypic raft culture. Furthermore, we show that endogenous KLF4 expression is required for efficient lytic viral reactivation in response to phorbol ester and sodium butyrate treatment in several different EBV-infected epithelial cell lines, and that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, is highly synergistic for inducing lytic EBV infection. We confirm that both KLF4 and BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably expressed in B cells, where EBV normally enters latent infection, although KLF4 over-expression is sufficient to induce lytic EBV reactivation in Burkitt lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in mediating lytic EBV reactivation in epithelial cells.


Normalization of essential-fatty-acid-deficient keratinocytes requires palmitic acid.
Cultured adult human keratinocytes show accelerated growth rates in medium that is essential fatty acid deficient. The cells also show decreased amounts of the essential fatty acids 18:2, 20:3, and 20:4 and contain increased amounts of the monounsaturated fatty acids 16:1 and 18:1. These lower levels of polyunsaturated fatty acids were only partially restored by supplementing the medium with 18:2 and 20:4 fatty acid. The addition of the non-essential fatty acid 16:0 (5 microM), along with the essential fatty acids, resulted in the successful normalization of the major fatty acids in the deficient keratinocytes. Normalized cells showed a constant total fatty acid/mg of protein in the phospholipid fraction, as the total cell fatty acid content per cell increased with augmenting fatty acid supplementation. Supplementation of the medium with 16:0 and essential fatty acids decreased the growth and passage potential of the cells. Use of 18:1 in lieu of 18:2 fatty acid yielded essential-fatty-acid-deficient keratinocyte growth values. Likewise the least supplemented medium (5 microM 18:2 + 5 microM 16:0) also gave the accelerated cell growth rates. This study shows that manipulation of the essential fatty acid levels, if accompanied by 5 microM 16:0 in the growth medium, alters the growth properties of adult human primary keratinocytes.


Targeting the Bcl-2 Family in B Cell Lymphoma.
Although lymphoma is a very heterogeneous group of biologically complex malignancies, tumor cells across all B cell lymphoma subtypes share a set of underlying traits that promote the development and sustain malignant B cells. One of these traits, the ability to evade apoptosis, is essential for lymphoma development. Alterations in the Bcl-2 family of proteins, the key regulators of apoptosis, is a hallmark of B cell lymphoma. Significant efforts have been made over the last 30 years to advance knowledge of the biology, molecular mechanisms, and therapeutic potential of targeting Bcl-2 family members. In this review, we will highlight the complexities of the Bcl-2 family, including our recent discovery of overexpression of the anti-apoptotic Bcl-2 family member Bcl-w in lymphomas, and describe recent advances in the field that include the development of inhibitors of anti-apoptotic Bcl-2 family members for the treatment of B cell lymphomas and their performance in clinical trials.


Nucleoside triphosphate-dependent DNA-binding properties of mos protein.
We have previously shown that the mos gene product, p40mos, produced in Escherichia coli binds ATP and has ATPase activity. In the present study, we investigated the DNA-binding properties of p40mos and two mos deletion mutant proteins. Nitrocellulose blot protein-DNA binding assays showed that p40mos binds DNA in the presence of Mg2+-ATP and certain other nucleoside triphosphates. Ninety percent of the p40mos-bound DNA is dissociated if the complex is washed in the presence of 1 M NaCl or in the absence of ATP. p40mos-DNA binding is not observed in the presence of AMP or the nonhydrolyzable ATP analog adenosine 5'-[beta, gamma-methylene]-triphosphate; however, in the presence of ADP, p40mos binds DNA at 20% of the level that is observed with ATP. An N-terminal-deletion mutant protein, p19mos, has no DNA-binding activity, whereas a C-terminal-deletion mutant protein, p25mos, does. p25mos contains the ATP-binding domain, binds DNA in the presence of either ADP or ATP, and shows 5% and 45% binding (relative to that in the presence of ATP) in the presence of AMP and adenosine 5'-[beta, gamma-methylene]triphosphate, respectively. These results suggest that the N-terminal domain of p40mos is responsible for nucleoside triphosphate-mediated DNA binding. We also observed differential histone-DNA binding in the presence and absence of ATP.


Resveratrol Relieves Hyperoxia-Induced Brain Injury in Neonatal Rats by Activating Sirt1.
Neonatal rats with hyperoxia-induced brain injury were treated with resveratrol to investigate its protective effects through analyzing changes in reactive oxygen species (ROS), Sirt1, p53, and acetylated p53 levels. Neonatal rats were randomly divided into hyperoxia and resveratrol intervened groups. Rats in both groups were placed in a hyperoxia chamber for 7 days to induce hyperoxia-induced brain injury. The rats in the resveratrol intervened group were administered resveratrol 60 μg/g body weight daily, whereas those in the hyperoxia group were administered a dimethyl sulfoxide-based solvent. Brain tissues were collected, and hematoxylin and eosin (H&E) and TUNEL staining, ROS measurements, real time-polymerase chain reaction, and western blotting were performed. H&E and TUNEL staining revealed increased cell damage and apoptosis in brain tissue from hyperoxia-exposed animals compared with the findings in animals in the resveratrol intervened group. Real time-polymerase chain reaction and western blotting identified increases in Sirt1 expression and decreases in p53 expression in the resveratrol intervened group. In addition, acetylated p53 protein expression was lower in the intervened group than in the hyperoxia group. Resveratrol alleviated brain apoptosis induced by hyperoxia in neonatal rats by upregulating Sirt1-mediated pathways, suggesting its potentially beneficial role in the treatment of brain injury induced by hyperoxia.


Inclusion of the Number of Metastatic Lymph Nodes in the Staging System for Medullary Thyroid Cancer: Validating a Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System.
Background: The current American Joint Committee on Cancer (AJCC) staging system (8th edition) for medullary thyroid cancer (MTC) was originally extrapolated from the staging system for differentiated thyroid cancer. However, the current staging system does not accurately predict the prognosis of patients with MTC. Patients and Methods: The present study was based on data from the Surveillance, Epidemiology, and End Results (SEER) database and validated by multicenter data from the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Xuzhou City Central Hospital, and Suzhou Ninth People's Hospital. Hazard ratio with its 95% confidence interval [CI] was estimated by Cox proportional hazards regression analysis. The concordance index (C-index) was used to evaluate the discrimination accuracy of the current AJCC tumor-node-metastasis (TNM) staging system and the modified AJCC (mAJCC) TNM staging system. Results: A total of 1175 MTC patients were selected from the SEER database and 312 from the three hospitals in China. We redefined the N category according to the number of metastatic lymph nodes (LNs) as follows: N'0 category (0 metastatic LNs), N'1 category (1-9 metastatic LNs), and N'2 category (≥10 metastatic LNs). The four distinct tumor stages were reclassified in the mAJCC staging system as follows: stage I (T1-4N'0M0, T1N'1M0), stage II (T2-3N'1M0, T1N'2M0), stage III (T4N'1M0, T2-4N'2M0), and stage IV (TanyN'anyM1). The C-index of the current AJCC staging system and the mAJCC staging system was 0.72 [CI, 0.67-0.78] and 0.78 [CI, 0.73-0.84], respectively. Similar results were observed in the survival analysis of the multicenter data set. Conclusions: The mAJCC staging system could discriminate the prognosis of MTC patients more effectively than the current AJCC staging system, indicating that it is feasible and appropriate to modify the current AJCC staging system by introducing the number of metastatic LNs instead of the location of LNs. These findings might be adopted in the next edition of the AJCC staging system and be used to guide clinical practice.


Females with Down syndrome: lost opportunities in primary care.
Nurse practitioners (NPs) need to be aware of the health disparities that exist between adult females with and without Down syndrome (DS). It is essential that necessary primary and preventive healthcare services are available to women with DS to maintain adequate health and quality of life, and reduce the occurrence of misdiagnosed or underdiagnosed treatable diseases. Review of published literature, DS society reports, and U.S. government reports. A lack of agreed guidelines for the screening of adult females with DS contributes to unmet health needs in primary care for this population. Adequate promotion of health in all persons with disabilities, including the specific needs of women with DS, will help prevent the development of preventable secondary disabilities. Research shows that health promotion, screenings, and preventive care are overlooked or ignored in the female population with DS. Barriers to this care were consistent with misconceived attitudes and beliefs about adults with DS and a lack of training for primary care providers in caring for persons with disabilities. Although much research is needed, there are some resources for NPs who provide care for this vulnerable population. Screening for preventable conditions, such as obesity, sexually transmitted infections, and sexual exploitation, can improve the quality of life for adult women with DS.


Familial Mediterranean fever: perspective on female fertility and disease course in pregnancy from a multicenter nationwide network.
The aim of this study was to analyze the pregnancy process, especially the Familial Mediterranean fever (FMF) disease course and attack types during pregnancy, and to examine the relationship between disease-related factors and female infertility in FMF patients. The study, which was planned in a multicenter national network, included 643 female patients. 435 female patients who had regular sexual intercourse were questioned in terms of infertility. Pregnancy and delivery history, FMF disease severity and course during pregnancy were evaluated. The relationship between demographic and clinical findings, disease severity, genetic analysis results and infertility was investigated. 401 patients had at least 1 pregnancy and 34 patients were diagnosed with infertility. 154 patients had an attack during pregnancy. 61.6% of them reported that attacks during pregnancy were similar to those when they were not pregnant. The most common attack symptoms were fever, fatigue and abdominal pain-peritonitis (96%, 87%, and 83%, respectively) in the pregnancy period. The disease-onset age, disease activity score, gene mutation analyses, and regular colchicine use (> 90%) were similar between the fertile and infertile groups, while the frequency of previous appendectomy and alcohol consumption rates were higher in individuals with infertility. Our results indicated no significant change in the frequency and severity of attacks during pregnancy. The low rate of infertility (7.8%) in our patients was noted. It has been suggested that the risk of FMF-related infertility may not be as high as thought in patients who are followed up regularly and received colchicine.


Effect of bit wear on hammer drill handle vibration and productivity.
The use of large electric hammer drills exposes construction workers to high levels of hand vibration that may lead to hand-arm vibration syndrome and other musculoskeletal disorders. The aim of this laboratory study was to investigate the effect of bit wear on drill handle vibration and drilling productivity (e.g., drilling time per hole). A laboratory test bench system was used with an 8.3 kg electric hammer drill and 1.9 cm concrete bit (a typical drill and bit used in commercial construction). The system automatically advanced the active drill into aged concrete block under feed force control to a depth of 7.6 cm while handle vibration was measured according to ISO standards (ISO 5349 and 28927). Bits were worn to 4 levels by consecutive hole drilling to 4 cumulative drilling depths: 0, 1,900, 5,700, and 7,600 cm. Z-axis handle vibration increased significantly (p<0.05) from 4.8 to 5.1 m/s2 (ISO weighted) and from 42.7-47.6 m/s2 (unweighted) when comparing a new bit to a bit worn to 1,900 cm of cumulative drilling depth. Handle vibration did not increase further with bits worn more than 1900 cm of cumulative drilling depth. Neither x- nor y-axis handle vibration was effected by bit wear. The time to drill a hole increased by 58% for the bit with 5,700 cm of cumulative drilling depth compared to a new bit. Bit wear led to a small but significant increase in both ISO weighted and unweighted z-axis handle vibration. Perhaps more important, bit wear had a large effect on productivity. The effect on productivity will influence a worker's allowable daily drilling time if exposure to drill handle vibration is near the ACGIH Threshold Limit Value. [1] Construction contractors should implement a bit replacement program based on these findings.


Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma.
Untreated female (NZB X NZW)F1 hybrid mice (B/W F1) were found to develop lymphosarcoma spontaneously as they aged. Tumor incidence was evaluated in B/W F1 mice immunosuppressed with total lymphoid irradiation (TLI) and in TLI-conditioned B/W F1 mice reconstituted with 3 X 10(7) BALB/c bone marrow (BM) cells. BALB/C leads to B/W F1 chimerism (79 to 89% BALB/c-type cells) was confirmed by typing peripheral blood lymphocytes with specific alloantisera and complement by using a microcytotoxicity assay. Chimeras showed no clinical signs of graft-vs-host disease (GVHD). TLI-treated mice seemed to show a slightly accelerated onset of lymphosarcoma as compared with untreated controls, but the difference was not significant (p = 0.08). BALB/c leads to B/W F1 chimeras reconstituted at 1 to 3 mo of age (25 mice) developed no tumors for an observation period of 18 mo after transplantation. In contrast, tumors developed in 24/130 of age-matched controls, and in 13/57 of TLI-treated nonreconstituted age-matched B/W F1 mice. Tumor incidence in BALB/c leads to B/W F1 chimeras transplanted at an older age (9 to 11 mo) was similar to that observed in age-matched TLI-treated B/W F1 mice and age-matched untreated controls. The data suggests that the high naturally occurring incidence of lymphosarcoma could be reversed by reconstituting TLI-treated mice with BM cells (p = 0.027). Thus, allogeneic BM transplantation may exert potent graft-vs-tumor effects (GVT) when tumor susceptible hosts are reconstituted at an early age, whereas GVT is relatively ineffective at an advanced age, which probably correlates with an advanced stage of tumor development. Allogeneic BM transplantation should be additionally explored as a potential clinical tool for eradication of certain solid tumors in adjunct to high-dose radiochemotherapy, inasmuch as GVT seems to be independent of GVHD.


Changes in muscle strength in u19 soccer players during an annual training cycle.
The aim of the study was to investigate the seasonal variation in isokinetic strength of the knee flexors and extensors, and conventional (H/QCONV) and functional (H/QFUNC) hamstring to quadriceps strength ratios in highly trained adolescent soccer players. The players (n=11; age 17.8±0.3) were measured at the end of the competitive season (autumn), at the beginning and the end of pre-season (winter) and during the sixth week of a new competitive season. Isokinetic peak torque (concentric and eccentric) was measured at 60°·s-1 in a sitting position with the hip flexed at 100°. The testing range of motion was set from 10 - 90° of knee flexion. The players performed a set of five maximum repetitions for both the dominant and non-dominant leg. Statistically significant differences (p<0.001) between the four seasonal measurements were noted for peak torque of the dominant leg knee flexors in concentric muscle action only. A post hoc analysis revealed a statistically significant increase in peak torque from the 1st to the 4th measurement (p<0.001; d=0.692) and from the 2nd to the 4th (p<0.01; d=0.564). The differences in the changes of peak torque of the knee flexors and extensors depending on type of muscle action and tendencies found in the H/Q ratios throughout the annual training cycle indicate that strength assessment of the knee flexors and extensors and their balance throughout the annual training cycle could be beneficial for elite male adolescent soccer players both in terms of performance and risk of injury.


Regulation of cell shape in the Cloudman melanoma cell line.
We show that Cloudman melanoma cells undergo rapid arborization in response to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone, a potent analogue of alpha-melanocyte stimulating hormone (alpha-MSH). The arbors were established by extension of processes and resembled dendrites. We used this system to study the regulation of cell shape. alpha-MSH is known to induce increases in cAMP levels, and agents such as forskolin and isobutylmethylxanthine that led to increased cAMP also caused arborization. However, equally dramatic arbors were formed after incubation with the protein kinase C inhibitor H-7 [1-(5-isoquinolinesulfonyl)-alpha-methyl-piperazine]. Phorbol diesters that activate protein kinase C led to cell rounding and antagonized alpha-MSH. The actions of protein kinase C cannot be rationalized in terms of indirect effects on cAMP: neither H-7 nor phorbol diesters alone altered cAMP levels, nor did they affect the increase in cAMP induced by MSH. We show also that MSH produced longer-term effects that cannot be mimicked by cAMP. Specifically, even in the continued presence of alpha-MSH, arborization was followed by morphological reversal to the unstimulated flattened configuration within 2 hr. (This did not occur with other agents that increase cAMP or with H-7.) Most importantly, whereas MSH-induced arborization occurred in the presence of cycloheximide, actinomycin D, or in enucleated cells, the reversal of arborization did not. Thus, MSH induced a program of rapid shape change that was dependent on new protein synthesis and gene transcription.


Muc5ac Production Inhibited by Decreased lncRNA H19 via PI3K/Akt/NF-kB in Asthma.
LncRNAs play important roles in multiple diseases including asthma, while there are a few reports on the role of lncRNA H19 about asthma. This study aimed to investigate the roles and mechanisms of lncRNA H19 in asthma. We detected lncRNA H19 and Muc5ac mRNA by establishing a murine asthma model and an in vitro inflammation model. Regulatory roles of lncRNA H19 in asthma were explored by lncRNA H19 overexpression or knockdown in vitro. To study its mechanisms, we detect p-NF-κB and p-Akt expression, and treated 16-HBE cells with inhibitors of PI3K. To study regulatory effects of miR-675-3p on Muc5ac, miR-675-3p mimics and inhibitors were respectively transfected into 16-HBE cells. Firstly, we established a murine asthma model and an in vitro inflammation model. We found that lncRNA H19 expression was decreased, while Muc5ac mRNA was increased in lung tissues of murine asthma model and in the in vitro inflammation model. lncRNA H19 overexpression increased Muc5ac mRNA expression and lncRNA H19 knockdown decreased Muc5ac mRNA expression in 16-HBE cells. Moreover, lncRNA H19 overexpression further increased Muc5ac expression in TNFα-induced in vitro inflammation model. lncRNA H19 knockdown decreased p-Akt and p-NF-κB expression. Inhibitors of PI3K abolished Muc5ac induced by lncRNA H19 overexpression. Although miR-675-3p was increased by lncRNA H19 overexpression, it had no regulatory effects on Muc5ac expression. These results demonstrated that lncRNA H19 positively regulates Muc5ac expression through PI3K/Akt /NF-κB pathway in the in vitro inflammation model. Therefore, this study indicated that decreased lncRNA H19 in asthma might play a protective role relieving mucus overproduction, and lncRNA H19 might be a potential target for asthma treatment.


Performance of two commercial ELISAs for detecting IgA anti-human and anti-guinea pig tissue transglutaminase antibodies.
Sensitivity and specificity of anti-human tissue transglutaminase antibodies (anti-htTGA) seem to be superior to those of anti-tissue transglutaminase of guinea pig (anti-gptTGA) for screening patients with celiac disease (CD), but there are still controversies. The aim of this study was to evaluate the performance of two INOVA ELISA kits to detect IgA anti-htTGA and anti-gptTGA in patients with and without CD. The study groups were comprised of 49 anti-endomysial antibody (EMA)-positive untreated-CD, and 123 controls (EMA-negative treated CD, EMA-negative chronic diarrhea, autoimmune hepatitis, inflammatory bowel disease and healthy people). The agreement between the two ELISAs was statistically significant in all study groups and there was no significant difference between them (92.7% agreement; kappa = 0.70; kappa p = 0.001; McNemar p = 1). All patients with serum reactivity of more than 100 units had histologic diagnosis of CD. In seven of 10 patients with treated-CD who had control biopsies, villous atrophy was still present in four who tested positive by both kits. Two of three celiacs with histologic remission tested positive for both anti-tTGA. the anti-gptTGA and anti-htTGA determination were equally efficient in identifying patients with untreated-CD with high titers of EMA. Whatever the anti-tTGA ELISA used, the reactivity above 100 units was always related to active CD diagnosed by histologic alterations in intestinal biopsies. The anti-tTGA reactivity by both kits was not only similar in determining histologic activity in the follow-up of CD after a gluten free diet, but also in identifying positive sera from the control groups, regardless if CD has been confirmed by duodenal biopsies.


'They're all depressed, aren't they?' A qualitative study of social care workers and depression in older adults.
Statutory and voluntary social services provide care and support for vast numbers of vulnerable older adults, yet little is known about how social care practitioners respond to depression in this high risk population. This study elicited the perceptions and conceptualizations of this condition among social care staff, and views on how the response of social care and other agencies might be improved. Qualitative interviews were conducted with 20 social care practitioners working in generic services for older adults in south London. Depression was perceived to be remarkably common among clients, a phenomenon largely attributed to the adverse circumstances of old age, particularly social isolation. A key message from participants was that social causes indicate a need for social interventions. While primary care was criticised for not taking depression seriously in older people, mental health services were generally praised. Expansion of social, recreational and psychological interventions was advocated.


Laparoscopic vs. open adrenalectomy: perioperative data and survival analysis in 70 dogs with an adrenal tumor.
Adrenalectomy is the treatment of choice in case of functional adrenal tumors and malignant adrenal incidentalomas. Laparoscopic adrenalectomy (LA) in dogs has gained popularity in recent years, however, clinical studies on large patient populations are scarce. This retrospective study describes perioperative and recurrence data, survival, and prognostic factors in 70 dogs that underwent LA or open adrenalectomy (OA) in our hospital between 2008 and 2022. Diagnosis was based on history, clinical signs, endocrine function tests and advanced diagnostic imaging. Laparoscopic adrenalectomy was performed in 42 dogs (n = 27 naturally occurring hypercortisolism, n = 4 pheochromocytoma, n = 1 pheochromocytoma with concurrent hypercortisolism, n = 10 incidentaloma) and OA in 28 dogs (n = 22 hypercortisolism, n = 3 pheochromocytoma, n = 3 incidentaloma). Bilateral adrenalectomy was performed in 8/70 dogs. Surgical duration of LA and OA did not differ significantly in unilateral and bilateral procedures (P = 0.108 and P = 0.101, respectively). Systemic hypertension occurred in 7/41 and 1/28 dogs during LA and OA, respectively (P = 0.130). Hypotension occurred in 2/41 and 4/28 dogs during LA and OA, respectively (P = 0.214). A total of 40/42 dogs in the LA group and 27/28 in the OA group survived to discharge (P = 0.810). Mean hospital stay was significantly shorter (P = 0.006) after LA (1.5 days, range 1-3) than after OA (2.2 days, range 1-4). No significant differences were demonstrated between LA and OA groups in recurrence of adrenal-dependent endocrine disease (P = 0.332), disease-free period (P = 0.733) and survival time (P = 0.353). The disease-specific 1-, 2- and 3-year survival rates were 95, 89, and 89% after LA and 92, 88, and 81% after OA. Tumor size was significantly associated with the occurrence of a recurrence. In addition, tumor size had a negative effect on the disease-free period and survival time. This study shows a favorable outcome of both LA and OA in dogs. Based on low perioperative complication rate, short hospitalization time and long-term outcomes comparable to OA in selected cases, the less invasive laparoscopic approach is considered the preferred technique.


Backtransplantation for survival of the graft.
To assess survival of grafts after uncontrollable rejection, one performs backtransplantation from the recipient to the donor. This study investigated backtransplantation in an animal model. Hearts were transplanted heterotopically in rats. After a few days, the transplanted heart grafts were harvested from the recipients and backtransplanted to the donor strain heterotopically and a drug was administered. Cardiac grafts survived 6.2 days in the first recipients. After backtransplantation on day 5 or 6, all backtransplanted grafts survived well in the second recipients. After backtransplantation on day 7, when 4 of 5 grafts had no beat, 2 of 5 grafts recovered beating on day 3 after backtransplantation without any drug treatment. After backtransplantation on day 7, when 4 of 5 grafts had no beat, all (5 of 5 grafts) recovered beating well with the administration of FTY720 on day 3 after backtransplantation. CsA or FK506 had no effect on survival after backtransplantation. Pathological findings revealed mild cellular infiltration in the cases of FTY720 and severe necrosis in the cases of no drug, CsA, or FK506. After backtransplantation on day 8, no grafts (0 of 5 grafts in each drug) recovered beating with any drugs. These data document the possibility of backtransplantation.


Theoretical study of photonic band gaps in woodpile crystals.
We investigate numerically the existence of photonic band gaps in woodpile crystals. We present a numerical method specifically developed to solve Maxwell's equations in such photonic structures. It is based upon a rigorous mathematical formulation and leads to a considerable improvement of the convergence speed as compared to other existing numerical methods. We tested our method by comparing the calculated reflectivity with measurements on an actual sample, i.e., a silicon woodpile photonic crystal designed for 1.5 microm wavelength. Excellent agreement is obtained, provided the main structural imperfections of the sample are taken into account. We show that the existence of photonic band gaps in woodpile crystals requires an index contrast higher than 2.05 +/- 0.01. The effects of imperfections of such structures with an index contrast equal to 2.25 are also investigated. Thus, the relative band gap width falls from 3.5% to 2.2% with structurals imperfection similar to those of the sample.


Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium.
Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS. We recently found that CD36 overexpression enhanced HBV replication. In this study, we further explored the mechanism by which CD36 overexpression promotes HBV replication. Our data showed that CD36 overexpression increased HBV replication, and CD36 knockdown inhibited HBV replication. RNA sequencing found some of the differentially expressed genes were involved in calcium ion homeostasis. CD36 overexpression elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic calcium level. Calcium chelator BAPTA-AM could override the HBV replication increased by CD36 overexpression, and the calcium activator thapsigargin could improve the HBV replication reduced by CD36 knockdown. We further found that CD36 overexpression activated Src kinase, which plays an important role in the regulation of the store-operated Ca2+ channel. An inhibitor of Src kinase (SU6656) significantly reduced the CD36-induced HBV replication. We identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. CD36 may represent a potential therapeutic target for the treatment of CHB patients with MS.


Long-term spatiotemporal evolution and coordinated control of air pollutants in a typical mega-mountain city of Cheng-Yu region under the "dual carbon" goal.
Clarifying the spatiotemporal distribution and impact mechanism of pollution is the prerequisite for megacities to formulate relevant air pollution prevention and control measures and achieve carbon neutrality goals. Chongqing is one of the dual-core key megacities in Cheng-Yu region and as a typical mountain-city in China, environmental problems are complex and sensitive. This research aims to investigate the exceeding standard levels and spatio-temporal evolution of criteria pollutants between 2014 and 2020. The results indicated that PM10, PM2.5, CO and SO2 were decreased significantly by 45.91%, 52.86%, 38.89% and 66.67%, respectively. Conversely, the concentration of pollutant O3 present a fluctuating growth and found a "seesaw" phenomenon between it and PM. Furthermore, PM and O3 are highest in winter and summer, respectively. SO2, NO2, CO, and PM showed a "U-shaped", and O3 showed an inverted "U-shaped" seasonal variation. PM and O3 concentrations are still far behind the WHO, 2021AQGs standards. Significant spatial heterogeneity was observed in air pollution distribution. These results are of great significance for Chongqing to achieve "double control and double reduction" of PM2.5 and O3 pollution, and formulate a regional carbon peaking roadmap under climate coordination. Besides, it can provide an important platform for exploring air pollution in typical terrain around the world and provide references for related epidemiological research.Implications: Chongqing is one of the dual-core key megacities in Cheng-Yu region and as a typical mountain city, environmental problems are complex and sensitive. Under the background of the "14th Five-Year Plan", the construction of the "Cheng-Yu Dual-City Economic Circle" and the "Dual-Carbon" goal, this article comprehensively discussed the annual and seasonal excess levels and spatiotemporal evolution of pollutants under the multiple policy and the newest international standards (WHO,2021AQG) backgrounds from 2014 to 2020 in Chongqing. Furthermore, suggestions and measures related to the collaborative management of pollutants were discussed. Finally, limitations and recommendations were also put forward.Clarifying the spatiotemporal distribution and impact mechanism of pollution is the prerequisite for cities to formulate relevant air pollution control measures and achieve carbon neutrality goals. This study is of great significance for Chongqing to achieve "double control and double reduction" of PM2.5 and O3 pollution, study and formulate a regional carbon peaking roadmap under climate coordination and an action plan for sustained improvement of air quality.In addition, this research can advanced our understanding of air pollution in complex terrain. Furthermore, it also promote the construction of the China national strategic Cheng-Yu economic circle and build a beautiful west. Moreover, it provides scientific insights for local policymakers to guide smart urban planning, industrial layout, energy structure, and transportation planning to improve air quality throughout the Cheng-Yu region. Finally, this is also conducive to future scientific research in other regions of China, and even megacities with complex terrain in the world.


Proteomic Assessment of the Expression of Genes Related to Toluene Catabolism and Porin Synthesis in Pseudomonas stutzeri ST-9.
The organization and expression of Pseudomonas stutzeri ST-9 genes related to toluene catabolism and porin synthesis was investigated. Toluene-degrading genes were found to be localized in the chromosome close to a phage-type integrase. A regulatory gene and 21 genes related to an aromatics degradation pathway are organized as a putative operon. These proteins are upregulated in the presence of toluene. Fourteen outer membrane proteins were identified as porins in the ST-9 genome. The identified porins showed that the main detected porins are related to the OmpA and OprD superfamilies. The percentage of porins in the outer membrane protein fraction, as determined by mass spectrometry, was 73% and 54% when the cells were cultured with toluene and with glucose, respectively. Upregulation of OmpA and downregulation of OprD occurred in the presence of toluene. A porin fraction (90% OprD) from both cultures was isolated and examined as a toluene uptake system using the liposome-swelling assay. Liposomes were prepared with the porin fraction from a culture that was grown on toluene (T-proteoliposome) or glucose (G-proteoliposome). There was no significant difference in the permeability rate of the different solutes through the T-proteoliposome and the G-proteoliposome.


Women's protection public policies: evaluation of health care for victims of sexual violence.
Violence against women has increased over the years and is a serious violation of human rights. This study aimed to evaluate public policies, women's rights legislation and health care for victims of sexual violence. This is an exploratory and descriptive study, with interviews to professionals of the Care Center for Women Victims of Violence of Teresina-PI, and collection of medical records data of victims. We analyzed data in the light of legislation and guidelines recommended by the Ministry of Health, according to the established public policies. We noted an improvement of the Brazilian legislation and increasing intervention of government in order to control the violence. The evaluated service calls for the humanization of care, the principles of dignity, non-discrimination, confidentiality and privacy, avoiding exposure and distress of victims. Physical and gynecological examination are conducted, besides laboratory tests such as serological tests and collecting traces aiming at identifying the offender, as well as pharmaceutical care and multi-professional support. We can conclude that the current legislation and the guidelines and procedures recommended by public policies to protect women are effective in the referral service studied.


Evidence of Individual Superspin Relaxation in Diluted Fe3O4/Hexane Ferrofluids.
We used dc magnetization and ac susceptibility to investigate the magnetic relaxation of ferrofluids made of 8 nm average-diameter Fe3O4 nanoparticles dispersed in hexane. Samples of different concentrations (δ) spanning two orders of magnitude ranging from 0.66 to 0.005 mg (Fe3O4)/mL (hexane) were used to vary the interparticle interaction strength. Our data reveal a critical concentration, δc = 0.02 mg/mL, below which the ferrofluid behaves like an ideal nanoparticle ensemble where the superspins relax individually according to a Néel-Brown activation law τ(T) =τ0expEBkBT with a characteristic time τo ~10-9 s. That is further confirmed by the observed invariance of the relative peak temperature variation per frequency decade ∆=∆TT·∆log(f), which stays constant at ~0.185 when δ < δc. At higher concentrations, between 0.02 and 0.66 mg/mL, we found that Δ exhibits a monotonic increase with the inverse concentration, 1δ, and the collective superspin dynamics is described by a Vogel-Fulcher law, τ(T) =τ0expEBkBT-T0. Within this regime, the dipolar interaction strength parameter T0 increases from T0 = 0 K at δc = 0.02 mg/mL to T0 = 14.7 K at δ = 0.66 mg/mL.


Subacute Sclerosing Panencephalitis Presenting as Choreoathetosis and Basal Ganglia Hyperintensities.
Subacute sclerosing panencephalitis is a devastating neurodegenerative disorder characterized by cognitive and memory deterioration, personality changes, behavior abnormalities, and a steady motor decline. Extrapyramidal manifestations are commonly seen in the advanced stage of the disease. We discuss a 10-year-old boy with subacute sclerosing panencephalitis presenting with generalized choreoathetosis, myoclonus, and cognitive decline. He had not been immunized for measles. His elder sister had a viral exanthematous illness 4 years ago. Magnetic resonance imaging revealed bilateral, asymmetric putaminal hyperintensities. A diagnosis of subacute sclerosing panencephalitis was confirmed by periodic complexes in the electroencephalograph and elevated antimeasles antibody titers in the blood and cerebrospinal fluid (1:625). Our case highlights that atypical clinical and radiological features of subacute sclerosing panencephalitis should always be borne in mind in children from endemic areas. Generalized choreoathetosis and bilateral putaminal involvement in the index case add to the spectrum of atypical presentations of subacute sclerosing panencephalitis in children.


Ultrafast angular momentum orientation by linearly polarized laser fields.
We theoretically show and experimentally verify that a pair of linearly polarized intense femtosecond pulses can create molecular ensembles with oriented rotational angular momentum on an ultrafast (approximately ps) time scale, when the delay and the mutual polarization between them are appropriately arranged. An asymmetric distribution for +M and -M sublevels relies on quantum interference between rotational wave packets created in stimulated Raman excitation by the first and second pulses. The present approach provides spatiotemporally propagating ensembles, of which the classical perspective is molecules rotating in a clockwise or counterclockwise direction.


Remnant cholesterol associates with hypertension beyond low-density lipoprotein cholesterol among the general US adult population.
Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population. This study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups. A total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17). RC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.


Characteristic differences in the mini-mental state examination used in Asian countries.
The mini-mental state examination (MMSE) was adapted by individual countries according to their languages and cultures, though it has not been systematically compared. The objective of this study was to compare the linguistic and cultural variations of the MMSE used in various Asian countries. With this, we can analyze the strengths and weaknesses of the MMSE and consider using a common version in future international clinical studies in Asia. We collected the MMSEs used in 11 Asian nations. After translating those into English, we compared them to understand the differences in the questionnaires with regard to cultural aspects. Many items may be applicable or comparable with a little modification, for Asian countries. However, attention and calculation and repetition may be incomparable. There were some differences in the contents and the ways to administer. The lack of consideration of the cultural differences and their influences on the interpretation of the same cognitive test makes cross-cultural studies difficult. Some items of MMSE tasks need readjusting for, if any, multi-national studies. This study might serve as a first step in the development of a standardized cross-cultural cognitive instrument, especially in Asia.


Health-Related Quality of Life in Patients With Narcolepsy: A Review of the Literature.
Narcolepsy is a chronic disorder characterized by symptoms of excessive daytime sleepiness, irresistible sleep attacks that may be accompanied by cataplexy brought on by emotions, sleep paralysis, and hypnagogic hallucinations. This is a review of 32 empirical articles on health-related quality of life (HRQoL) published in peer-reviewed journals over the past 37 years. Deleterious implications on education, recreation, driving, sexual life, and personality are associated with the disease with a consequent negative psychosocial impact. Sleepiness has an important influence on HRQoL, more than the other symptoms of this disorder that have disrupting roles, too. Therefore, patients with narcolepsy need assistance not only for medication prescription but also in terms of psychological and social support. It is also of importance to assess patients with narcolepsy carefully in terms of depressive symptoms because they may have a major impact on HRQoL with important clinical implications.


Strategies to keep kidney transplant alive amid the SARS-CoV-2 pandemic.
This study aims to describe the result of the strategies adopted to maintain the transplant program amid the COVID-19 pandemic. Since March 2020, several measures have been adopted sequentially, including the compulsory use of personal protective equipment and the real-time polymerase chain reaction testing of collaborators, symptomatic patients, potential deceased donors, candidates for recipients, and in-hospital readmissions, regardless of symptoms. The living-donor transplantation was restricted to exceptional cases. Among 1013 health professionals, 201 cases of COVID-19 were confirmed between March and August 2020, with no severe cases reported. In this period, we observed a 19% institutional increase in the number of transplants from deceased donors compared with that observed in the same period in 2019. There was no donor-derived severe acute respiratory syndrome virus (SARS-CoV-2) infection. Four COVID-19-positive patients underwent transplantation; after 28 days, all were alive and with functioning allograft. Among the 11,875 already transplanted patients being followed up, there were 546 individuals with confirmed diagnosis, 372 who required hospitalization, and 167 on mechanical ventilation, resulting in a 27% mortality rate. These data confirm that the adoption of sequential and coordinated measures amid the pandemic was able to successfully maintain the transplant program and ensure the safety of health professionals and transplanted patients who were already in follow-up.


Reinfection with Ehrlichia chaffeensis in a liver transplant recipient.
Human monocytic ehrlichiosis is an emerging infection caused by Ehrlichia chaffeensis, but reinfection with this agent has not been described. We report a case of reinfection with E. chaffeensis after a 2-year interval in a 56-year-old liver transplant recipient with frequent tick attachments.


Fade of the responses of the isolated, blood-perfused dog atrium to cholinergic interventions.
In the isolated, blood-perfused, canine right atrium, intramural parasympathetic nerve stimulation and intra-arterial infusions of acetylcholine induced substantial negative chronotropic and inotropic responses. The responses to parasympathetic stimulation reached their maximum values quickly, and then usually faded back toward control levels over the next 1 or 2 min of stimulation. The fade of the responses at high stimulation frequencies (greater than or equal to 30 Hz) was significantly greater than that at lower frequencies. The inotropic responses to acetylcholine infusion (1 microgram/min) faded slightly but significantly, whereas the chronotropic responses did not fade at all. These results suggest that the fade of the cardiac responses to parasympathetic stimulation is mainly ascribable to a progressive reduction in the rate of acetylcholine release from the nerve endings, especially at higher stimulation frequencies. The fade of the inotropic responses was more pronounced and had a longer time course than that of the chronotropic responses. Furthermore, the fade of the inotropic responses diminished significantly as the response magnitude was augmented by an increase in stimulation voltage. Conversely, the fade of chronotropic responses was not significantly affected by this intervention. These differences in the inotropic and chronotropic responses to neural stimulation, and the occurrence of a slight fade of the inotropic response to acetylcholine infusion, suggest that in addition to the predominant prejunctional mechanism, a postjunctional phenomenon may also be partly responsible for the fade of the inotropic response to cholinergic interventions.


Cerebrospinal fluid otorhinorrhoea due to inner-ear malformations: clinical presentation and new perspectives in management.
In children cerebrospinal fluid (CSF) otorhinorrhoea can be due to congenital inner-ear malformations. Cochlear dysplasia associated with a defect in the stapes footplate is usually the cause of the CSF leak. Repair of the CSF leak in these cases is usually done by packing the vestibule with muscle or fascia. This traditional method of repair has a 30 to 60 per cent failure rate. CSF otorhinorrhoea due to congenital inner-ear anomalies in four patients was repaired using multiple-layer packing of the vestibule with glue, muscle and fascia, reinforced by a pedicle temporalis muscle graft. Intra-operatively, continous lumbar drainage was performed. Repair of the CSF leak was successful in four cases and no recurrence was noticed. Inner-ear magnetic resonance imaging (MRI) using three-dimensional fast-spin echo (3D FSE) T2-weighted imaging (T2WI) and 3D steady-state free precession (FIESTA) sequences was found to be a very helpful, noninvasive investigation to localize the site and route of the CSF leak. Children presenting with recurrent meningitis and CSF rhinorrhoea should be investigated for congenital inner-ear anomalies. In these cases CSF fistulae should be repaired using fibrin or cyanoacrylate glue and intra-operative continuous lumbar drainage; 3D FSE T2WI and 3D FIESTA MRI sequences of the inner ear are helpful.


Two-dimensional ultrafast fourier transform spectroscopy in the deep ultraviolet.
We demonstrate two-dimensional ultrafast fourier transform spectroscopy in the deep ultraviolet (approximately 260 nm) using an acousto-optic modulator based pulse shaper. The use of a pulse shaper in the ultraviolet allows for rapid scanning, high phase (time) stability (approximately 0.017 rad) and phase cycling. We present measurements on the DNA nucleobase Adenine.


Reassessment of the taxonomic status of Craseomys and three controversial species of Myodes and Alticola (Rodentia: Arvicolinae).
The genera Myodes (red-backed voles) and Alticola (mountain voles) appear to be sister taxa based on morphological similarities, but molecular analyses fail to resolve them as monophyletic genera owing to the uncertain taxonomic status of Craseomys and Phaulomys. As a result of incomplete sampling of related specimens, ongoing controversies on the taxonomic positions of several generic and specific taxa necessitate further clarifications. Herein, we combined molecular, morphometric, and geometric morphometric approaches to analyze 217 specimens of 10 taxa of Myodes and Alticola systematically. We sequenced three genes (Cytb, COI, GHR) de novo from specimens with fresh tissues, and published sequences for M. shanseius and A. stoliczkanus for the first time. Based on this new molecular dataset, we produced phylogenetic trees using Bayesian inference, maximum likelihood, and maximum parsimony approaches. Our molecular and morphological analyses both identified three primary clades within Myodes and Alticola. The Craseomys-Phaulomys clade consistently separated from Myodes sensu stricto (s. str.) and Alticola s. str.-Platycranius. Our results support the resurrection of the genus Craseomys and the treatment of Phaulomys as its junior synonym. As Craseomys shanseius clustered with C. rufocanus in three gene phylogenies and this assessment was congruent with morphological results, we assigned C. shanseius to a subspecies of C. rufocanus. Specimens from one sampling site in Pulan County of Tibet possess M3 patterns typical of A. stoliczkanus and A. stracheyi, despite clustering together in matrilineal genealogy. Thus, we tentatively assigned A. stracheyi as a junior synonym of A. stoliczkanus. Our analyses confirmed the validity of A. semicanus and unambiguously distinguished it from A. argentatus by the ratio of tail length to head-body length, color of tail and feet, M3 pattern, and distribution.


To the question of maximal permissible load with chemical substances in man.
The authors introduce an over-all evaluation of a maximum admissible drug load in man, as related to professional exposure, environmental atmosphere, water, soil, and foodstuffs. To minimize the occurrence of lesions, it is necessary to disclose and classify the environmental factors responsible for homeostasis of the human organism. Moreover, it is desirable to establish the limits of biologically adverse changes of the medium. A real adaptation is possible provided the above changes are sufficiently slow and enable development of optimum mechanisms of reactions within the biological homeostasis. The establishment of an effective system for optimalization of man's environment necessitates further advancement and improvement of methods and their more adequate selection. This adequacy should respond to the real conditions of evaluation of relationships of man and populations with dynamically changing environment. The understanding of general regularities and mechanisms of this complex action will be indispensable. The to-date experience implies that the criteria for determination of the maximum permissible load of environment and man with chemical compounds are quantitative relationships between intensity, frequency and duration of exposure to chemicals in the atmosphere, and the magnitude of undesirable changes in man and his environment. The classification of acceptable or permissible limits of concentration (or other index of exposure) of chemical substances in the atmosphere pursues the protection of the population from undesirable effects under variable conditions of exposure (chemical compounds in working places, atmosphere, alien foreign substances in food, water or soil). The number of potentially toxic substances to be evaluated both hygienically and toxicologically, amounts to about 25 000. Newly introduced chemical compounds annually make about 1000-5000, of which approximately 10% need a thorough examination. The limits can be divided into several groups: Maximum permissible concentrations of chemical compounds (MAC) in working and external atmosphere, water, and partially in soil and food. For these a denomination "derived working limits". Limits of chemical compounds based on their intake by the human organism are sometimes called "primary protection standard". These may correlate with the acceptable daily intake of foreign substances (additives and contaminating substances). The longest tradition enjoys the classification of food additives, which has been supervised since 1956 by the Joint Committee of FAO experts and WHO experts for pesticide residues (1).(ABSTRACT TRUNCATED AT 400 WORDS)