Magnetic resonance imaging of thyroid cancer.
Thyroid cancer is a unique malignancy arising from the endocrine system, and its nature is different from more common squamous cell carcinoma in the head and neck region. Multiple imaging modalities are used for imaging work up for thyroid cancer, including nuclear medicine imaging, ultrasound, computed tomography, and magnetic resonance imaging (MRI). Imaging findings of benign and malignant thyroid lesions overlap substantially, and differentiation may be difficult. The role of MRI is to evaluate the extent of disease and to assess the spread of nodal disease. In this chapter, we will discuss the role of MRI in thyroid cancer staging and key imaging appearance that affect staging of thyroid cancer.


Optimizing use of multistream influenza sentinel surveillance data.
We applied time-series methods to multivariate sentinel surveillance data recorded in Hong Kong during 1998-2007. Our study demonstrates that simultaneous monitoring of multiple streams of influenza surveillance data can improve the accuracy and timeliness of alerts compared with monitoring of aggregate data or of any single stream alone.


Origin of Drosophila mushroom body neuroblasts and generation of divergent embryonic lineages.
Key to understanding the mechanisms that underlie the specification of divergent cell types in the brain is knowledge about the neurectodermal origin and lineages of their stem cells. Here, we focus on the origin and embryonic development of the four neuroblasts (NBs) per hemisphere in Drosophila that give rise to the mushroom bodies (MBs), which are central brain structures essential for olfactory learning and memory. We show that these MBNBs originate from a single field of proneural gene expression within a specific mitotic domain of procephalic neuroectoderm, and that Notch signaling is not needed for their formation. Subsequently, each MBNB occupies a distinct position in the developing MB cortex and expresses a specific combination of transcription factors by which they are individually identifiable in the brain NB map. During embryonic development each MBNB generates an individual cell lineage comprising different numbers of neurons, including intrinsic γ-neurons and various types of non-intrinsic neurons that do not contribute to the MB neuropil. This contrasts with the postembryonic phase of MBNB development during which they have been shown to produce identical populations of intrinsic neurons. We show that different neuron types are produced in a lineage-specific temporal order and that neuron numbers are regulated by differential mitotic activity of the MBNBs. Finally, we demonstrate that γ-neuron axonal outgrowth and spatiotemporal innervation of the MB lobes follows a lineage-specific mode. The MBNBs are the first stem cells of the Drosophila CNS for which the origin and complete cell lineages have been determined.


The use of frozen-thawed lymphocytes for DRw typing.
Results of DRw typing using frozen-thawed plastic "adhered" cell preparations were comparable to those obtained using fresh sheep E-rosetted lymphocytes. Estimates of B-cell content of such preparations may be erroneously low if surface immunoglobulin fluorescence is the only method used.


Amino acid and protein scavenging of radicals generated by iron/hydroperoxide system: an electron spin resonance spin trapping study.
Reduction of free radicals generated by Fe(II)/cumene-hydroperoxide (CumOOH) by amino acids (Gly, Cys, Met, His, and Trp) and proteins (bovine serum albumin (BSA), beta-lactoglobulin, and lactoferrin) was followed by electron spin resonance spectroscopy using alpha-phenyl-N-tert-butylnitrone (PBN), 2-methyl-2-nitrosopropane (MNP), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin traps. The radical species detected were mostly carbon-centered radicals from CumOOH fragmentation (methyl/*H3 and ethyl/*H2CH3), although carbon-centered radicals originated from amino acids could be formed in the presence of Cys, Met, His, or Trp. All proteins and amino acids, except Cys, were effective at inhibiting generation of radicals from the Fe(II)/CumOOH system. Trp was the amino acid with the highest antiradical activity, followed by His > Gly approximately Met. Lactoferrin was the protein showing the most efficient inhibition of radical formation from the Fe(II)/CumOOH system, and BSA and beta-lactoglobulin were not significantly different in their antiradical activities. These results suggest that proteins with higher inhibitory activity on lipid oxidation promoted by transition metal catalytic decomposition of hydroperoxides should be those with elevated metal-chelating and radical-scavenging properties as well as low concentration and accessibility of reducing groups from amino acids capable of activating metals, such as sulfhydryl groups.


Anti-cardiac ryanodine receptor antibodies in thymoma-associated myasthenia gravis.
Sera from myasthenia gravis (MG) patients with thymoma were examined in Western blot for the presence of antibodies to proteins in the sarcoplasmic reticulum (SR) of cardiac muscle. Fourteen of 30 MG thymoma sera had IgG antibodies to a protein with the same electrophoretic mobility as cardiac muscle ryanodine receptor (RyR). Anti-cardiac RyR antibodies were not detected in any of the 45 sera from MG patients without thymoma. The same 14 MG thymoma sera, but none of the others, bound to RyR from skeletal muscle as well. Neutralization experiments showed that the anti-RyR antibodies in MG patient cross-reacted with cardiac and skeletal muscle RyR. Since skeletal and cardiac muscle RyRs are antigenically different, our findings may indicate that autoantibodies to RyR in MG originate by sensitization to a peptide shared by cardiac and skeletal muscle RyR, rather than to the complete native RyR.


A background to nuclear transfer and its applications in agriculture and human therapeutic medicine.
The development of a single celled fertilized zygote to an animal capable of reproduction involves not only cell division but the differentiation or specialization to numerous cell types forming each tissue and organ of the adult animal. The technique of nuclear transfer allows the reconstruction of an embryo by the transfer of genetic material from a single donor cell, to an unfertilized egg from which the genetic material has been removed. Successful development of live offspring from such embryos demonstrates that the differentiated state of the donor nucleus is not fixed and can be reprogrammed by the egg cytoplasm to control embryo and fetal development. Nuclear transfer has many applications in agriculture and human medicine. This article will review some of the factors associated with the success of embryo development following nuclear transfer and outline the potential uses of the technology.


The development of catecholaminergic innervation in chick spinal cord.
This combined biochemical and histofluorescent study of the embryonic chick was designed to investigate the temporal and spatial development of noradrenergic pathways in the spinal cord. The sequence of catecholaminergic innervation was analyzed by measuring the specific uptake of [3H]norepinephrine, the levels of endogenous norepinephrine, and the distribution of catecholamine histofluorescence. Uptake studies showed early axons present in all levels of spinal cord by 10 days incubation with subsequent increases of uptake activity appearing in a rostrocaudal fashion. Endogenous norepinephrine values were low until day 14, at which time transmitter levels began to increase, approaching hatched values on incubation day 17. Morphologic studies demonstrated catecholaminergic terminals first in the intermediate gray matter and later concentrated in the ventral and dorsal horns. These observations were interpreted to indicate that: (1) noradrenergic axons are an early descending supraspinal pathway; (2) arborization of this system occurs in a rostral-caudal sequence; and (3) monoaminergic uptake mechanisms develop prior to and independent of neurotransmitter synthesis and storage. The development of this noradrenergic system parallels alteration in spinal cord physiology and refinements in the motility of the embryo.


The use of a clinical case study in a clinical information system selection process.
The University of Pennsylvania Health System recently underwent an extensive selection process for a new clinical information system. In addition to a traditional system selection approach, a clinical case study was utilized during our selection process. This was done in an effort to better prepare the clinicians involved in the selection process, as well as to help identify key operational issues that the institution would need to resolve, related to the design and implementation of a new clinical system. We wil describe here the reasons this approach was chosen, how the case study was utilized, and provide an assessment of its usefulness.


Prevention of Mammary Tumor Development through Neuroimmunomodulation in the Spleen and Lymph Nodes of Old Female Sprague-Dawley Rats by L-Deprenyl.
Development of mammary tumors is an age-associated phenomenon that is likely due to deficits in the neuroendocrine-immune interactions. Previously, we demonstrated that L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, can enhance immune responses and restore noradrenergic (NA) innervation in the spleens of rats with carcinogen-induced and spontaneously developing mammary tumors. To investigate whether (1) treatment of early middle-aged female rats would prevent the spontaneous development of mammary tumors accompanied by restoration of immunity in the spleen and draining lymph nodes (DLN) and sympathetic NA innervation in the spleen and (2) deprenyl can influence the proliferation of estrogen receptor (ER)-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231 and Hs 578T) human breast cancer cells. Early middle-aged (8- to 9-month-old) female Sprague-Dawley rats were treated with 0, 1.0 or 2.5 mg of deprenyl/kg body weight (BW) daily i.p. for 12 months. Cells of ER-positive (ER+) and ER-negative (ER-) human breast cancer cell lines were incubated with media or 10(-3) to 10(-8) M deprenyl for 1, 2, 4 or 6 days to examine the proliferation of cells. Tumor incidence increased in saline-treated old female rats, while deprenyl treatment significantly reduced the incidence of mammary tumors in these rats. Saline-treated tumor-bearing rats exhibited reduced splenic NA innervation and norepinephrine (NE) content, splenic interleukin (IL)-2 and interferon (IFN)-γ levels and NK cell activity as well as DLN IL-2 and IFN-γ levels compared to young female rats without tumors. In contrast, treatment with 2.5 mg/kg of deprenyl enhanced IL-2 and IFN-γ production in both the spleen and DLN as well as splenic natural killer (NK) cell activity. Deprenyl treatment also increased concanavalin A (Con A)-induced proliferation of T lymphocytes in the DLN. Deprenyl-induced changes in immune responses were accompanied by enhanced NA innervation and NE content in the spleen. In vitro incubation of various concentrations of deprenyl with ER+ human breast cancer cell lines partly inhibited the proliferation of cells, while it had no effect on the ER- breast cancer cells. These results suggest that (1) development of mammary tumors is mediated through the loss of immunity and sympathetic NA nerve fibers accompanied by reduced NE levels in the spleen, (2) the prevention of mammary tumor development by deprenyl may involve the reversal of the tumor-associated decline in sympathetic NA activity and cell-mediated immune responses in the spleen and DLN and (3) the antitumor effects of deprenyl may be partially mediated through ER-dependent intracellular signaling pathways.


The identification of miR-375 as a potential biomarker in distal gastric adenocarcinoma.
MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level and play an important role in carcinogenesis. Herein, we characterized the global expression of miRNA in distal gastric adenocarcinomas and determined if circulating miRNAs could be used as biomarkers for distal gastric adenocarcinoma. We used a microarray screening system to detect dysregulated miRNAs in distal gastric adenocarcinoma tissues. The expression of a subset of five aberrantly expressed miRNAs (miR-375, -196b, -204, -18b, and -93) were further quantified in an independent set of clinical samples of distal gastric adenocarcinoma by real-time quantitative RT-PCR (rt-qRT-PCR). We also used rt-qRT-PCR to investigate the expression levels of putative miRNA biomarkers in serum and tumor cell lines. In our study, the expression of a subset of microRNAs was altered in distal gastric adenocarcinoma compared to normal tissue, miR-375 was significantly downregulated in distal gastric adenocarcinoma tissues, to a level that was significantly lower than cardia adenocarcinoma (p < 0.05). The circulating serum levels of miR-375 in patients who had distal gastric adenocarcinoma were also much lower than normal controls (p < 0.001). As a biomarker, miR-375 yielded a receiver operating characteristic area under the curve of 0.835. The specificity and sensitivity was 80% and 85%, respectively, in the discrimination of distal gastric adenocarcinoma from control, at a normalized cutoff of 0.218. The expression of miR-375 was downregulated both in distal gastric adenocarcinoma tissues and serum of patients with distal gastric adenocarcinoma. These data suggest miR-375 is a potential biomarker for distal gastric adenocarcinoma.


Disruption of dopaminergic transmission remodels tripartite synapse morphology and astrocytic calcium activity within substantia nigra pars reticulata.
The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia circuitry particularly sensitive to pathological dopamine depletion. Indeed, hyperactivity of SNr neurons is known to be responsible for some motor disorders characteristic of Parkinson's disease. The neuronal processing of basal ganglia dysfunction is well understood but, paradoxically, the role of astrocytes in the regulation of SNr activity has rarely been considered. We thus investigated the influence of the disruption of dopaminergic transmission on plastic changes at tripartite glutamatergic synapses in the rat SNr and on astrocyte calcium activity. In 6-hydroxydopamine-lesioned rats, we observed structural plastic changes of tripartite glutamatergic synapses and perisynaptic astrocytic processes. These findings suggest that subthalamonigral synapses undergo morphological changes that accompany the pathophysiological processes of Parkinson's disease. The pharmacological blockade of dopaminergic transmission (with sulpiride and SCH-23390) increased astrocyte calcium excitability, synchrony and gap junction coupling within the SNr, suggesting a functional adaptation of astrocytes to dopamine transmission disruption in this output nucleus. This hyperactivity is partly reversed by subthalamic nucleus high-frequency stimulation which has emerged as an efficient symptomatic treatment for Parkinson's disease. Therefore, our results demonstrate structural and functional reshaping of neuronal and glial elements highlighting a functional plasticity of neuroglial interactions when dopamine transmission is disrupted.


Early management of children with minor head injuries.
In the UK, about 260,000 children with head injuries attend emergency departments each year (National Institute for Health and Clinical Excellence (NICE) 2007, Scottish Intercollegiate Guidelines Network (SIGN) 2009). About 90 per cent of these injuries are minor and can be managed without admission to hospital (Swann and Teasdale 1999). Clinical guidelines for early management of head injury have recently been published by NICE in England and Wales, and by SIGN in Scotland, to standardise management across the UK. This article discusses the role of emergency nurses in implementing these guidelines.


Addition of ginkgo fruit to cattle feces and slurry suppresses methane production by altering the microbial community structure.
The effect of ginkgo fruit addition on methane production potential of cattle feces and slurry was assessed in relation to other fermentation products and the microbial community. Holstein cattle fresh feces and slurry were left at 30°C for 0, 30, 60, 90, and 180 days with/without ginkgo fruit to monitor the effect on fermentation potential. With the addition of ginkgo fruit, methane production potential of feces was reduced on Day 30 and thereafter, and that of slurry was consistently reduced over the experimental period. As a general trend, ginkgo fruit addition resulted in decreased acetate and increased propionate in feces and acetate accumulation in slurry. With ginkgo fruit addition, MiSeq analyses indicated decreases in methanogen (in particular Methanocorpusculum), Ruminococcaceae, and Clostridiaceae populations and increases in Bacteroidaceae and Porphyromonadaceae populations, which essentially agreed with quantitative real-time polymerase chain reaction (qPCR) assay results. These data indicate that direct addition of ginkgo fruit to cattle excreta is useful for reducing methane emissions by altering the microbial community structure. The application of ginkgo fruit to lower methane emissions from cattle excreta is, therefore, useful in cases in which the excreta is left without special management for a long period of time.


Impaired responsiveness to gamma interferon of macrophages infected with lymphocytic choriomeningitis virus clone 13: susceptibility to histoplasmosis.
Lymphocytic choriomeningitis virus clone 13 (LCMV clone 13), a variant isolated from the spleens of neonatally infected mice, causes persistent infections in mice infected as adults. Such persistently infected mice succumb to a normally sublethal dose of Histoplasma capsulatum, and their macrophages contain overwhelming numbers of yeast cells of the fungus. Both LCMV clone 13 and H. capsulatum yeast cells target and replicate in macrophages of the host. We sought to study the effects of LCMV clone 13 on the ability of macrophages to control growth of H. capsulatum in vitro. We show that the growth of H. capsulatum within macrophages was not directly affected by the presence of LCMV clone 13. However, macrophages containing LCMV clone 13 did not respond fully to gamma interferon (IFN-gamma) stimulation. Such unresponsiveness resulted in proliferation of the fungus within macrophages cultured in the presence of IFN-gamma. The addition of anti-IFN-alpha/beta antibodies to LCMV clone 13-infected macrophage cultures restored macrophage responsiveness to IFN-gamma. These results indicate that production of IFN-alpha/beta by LCMV clone 13-infected macrophages antagonizes their responsiveness to IFN-gamma. Such antagonism may be one of the mechanisms by means of which certain viruses cause immune suppression and susceptibility to opportunistic infections.


Redox specificity of 2-hydroxyacid-coupled NAD(+)/NADH dehydrogenases: a study exploiting "reactive" arginine as a reporter of protein electrostatics.
With "reactive" arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+)-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in "reactivity" of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on "reactive" arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of "reactive" arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD(+) (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme.


Transgenic expression of an altered angiotensin type I AT1 receptor resulting in marked modulation of vascular type I collagen.
The angiotensin II (AngII) type I receptor (AT1) was modified by replacing its third intracellular loop and C-terminal tail with the corresponding regions from the bradykinin B2 receptor. Transgenic mice were produced that overexpress this mutated receptor (AB3T). Considerably less collagen content in the intact aorta and in primary aortic smooth muscle cells (aSMCs) cultures was observed in the transgenic mice. On the other hand, elastin content remained unchanged as measured by Western blot, and insoluble amino acid quantitation. The contraction of isolated aortas also remained unaltered. The aSMCs derived from the transgenic mice showed a reduction in AngII responsive type I collagen production. In aSMCs from transgenic mice, the cascade of Akt to the mammalian target rapamycin (mTOR) to p70 S6 kinase (p70S6K) was not AngII activated, while in the aSMCs from wild-type (WT) mice the cascade was AngII activated. Angiotensin activation of Smad2 and Stat3 was also reduced in the AB3T aSMCs. However, no change in the effect of transforming growth factor β (TGFβ) on type I collagen production was observed. Also, the activation of ERK and JNK and G-protein linked signaling remained unaltered in response to AngII. Akt and PI3K activation inhibitors blocked AngII-stimulated type I collagen expression in WT aSMCs, whereas ERK inhibitor had no such effect. Our results point to an Akt/mTOR/p70S6K regulation of collagen production by AngII with participation of Smad2 and Stat3 cascades in this process.


Correlation of Subjective Hospital Compare Metrics With Objective Outcomes of Cranial Neurosurgical Procedures in New York State.
Public reporting is at the forefront of health care reform. To investigate whether patient satisfaction as expressed in a public reporting platform correlates with objective outcomes for cranial neurosurgery patients. We performed a cohort study involving patients undergoing cranial neurosurgery from 2009 to 2013 who were registered in the Statewide Planning and Research Cooperative System database. This cohort was merged with the corresponding data from the Centers for Medicare and Medicaid Services Hospital Compare website. The association of patient satisfaction metrics with outcomes was examined with the use of a propensity-adjusted regression model. Overall, 19 591 patients underwent cranial neurosurgery during the study. Using a propensity-adjusted multivariable regression analysis, we demonstrated that hospitals with a greater percentage of patient-assigned "high" scores had decreased mortality (OR, 0.60; 95% CI, 0.53-0.67), rate of discharge to rehabilitation (OR, 0.93; 95% CI, 0.88-0.98), length of stay (adjusted difference, -1.29; 95% CI, -1.46 to -1.13), and hospitalization charges (adjusted difference, -23%; 95% CI, -36% to -9%) after cranial neurosurgery. Similar associations were identified for hospitals with a higher percentage of patients, who would recommend these institutions to others. In a Centers for Medicare and Medicaid Services Hospital Compare-Statewide Planning and Research Cooperative System merged dataset, we observed an association of higher performance in patient satisfaction measures with decreased mortality, rate of discharge to rehabilitation, hospitalization charges, and length of stay.


Sustained efficacy and safety of pimecrolimus cream 1% when used long-term (up to 26 weeks) to treat children with atopic dermatitis.
Atopic dermatitis is a chronic, inflammatory condition affecting up to 20% of children. Here, we report the long-term extension study of previously published pivotal phase III studies with pimecrolimus cream 1%. Two identical, 26-week studies (6-week, double-blind, followed by 20-week, open-label phases) were conducted in children aged 2 to 17 years with atopic dermatitis. Pooled efficacy and safety analyses were performed. At day 43, 34.8% pimecrolimus-treated patients versus 18.4% in the vehicle group (p < 0.001) were clear/almost clear (Investigators' Global Assessment 0/1) of disease, with significant differences (p < 0.05) between treatment groups for all double-blind visits in all parameters. Pimecrolimus was significantly more effective (based on the Eczema Area and Severity Index) in treating the face and neck versus the rest of the body (p < 0.0001) and versus vehicle (p < 0.0001) in the double-blind phase. Disease control was sustained in the pimecrolimus group throughout the whole study. Patients treated with vehicle during the double-blind phase experienced rapid, marked improvement when switched to pimecrolimus in the open-label phase. The incidence of adverse events was low and comparable between treatment groups. In conclusion, pimecrolimus cream 1% is effective and well tolerated in the long-term control of children with mild to moderately severe atopic dermatitis.


Spectrum of Benign Bone Conditions on NaF-PET.
Fluoride imaging with 18F (NaF-PET), although not a new technique, is becoming increasingly utilized for evaluation of skeletal metastatic disease using PET/CT. As its use becomes more widespread, a variety of nonmalignant bone disorders will be encountered by the interpreting physician. It is important, therefore, to recognize these nonmalignant conditions to avoid errors in interpretation. Beyond this, there is increasing evidence in the literature that NaF-PET/CT imaging may provide valuable information for the primary diagnosis of these nonmalignant conditions, and furthermore may provide insight into the underlying biology leading to management decisions. In this article, we review a spectrum of benign bone conditions that can be visualized on NaF-PET.


Optimization and Prediction of Ultimate Tensile Strength in Metal Active Gas Welding.
We investigated the effect of welding parameters on ultimate tensile strength of structural steel, ST37-2, welded by Metal Active Gas welding. A fractional factorial design was used for determining the significance of six parameters: wire feed rate, welding voltage, welding speed, travel angle, tip-to-work distance, and shielded gas flow rate. A regression model to predict ultimate tensile strength was developed. Finally, we verified optimization of the process parameters experimentally. We achieved an optimum tensile strength (558 MPa) and wire feed rate, 19 m/min, had the greatest effect, followed by tip-to-work distance, 7 mm, welding speed, 200 mm/min, welding voltage, 30 V, and travel angle, 60°. Shield gas flow rate, 10 L/min, was slightly better but had little effect in the 10-20 L/min range. Tests showed that our regression model was able to predict the ultimate tensile strength within 4%.


Imaging of rotational wave-function in photodissociation of rovibrationally excited HCl molecules.
We demonstrate a visualization of quantum mechanical phenomena with the velocity map imaging (VMI) technique, combining vibrationally mediated photodissociation (VMP) of a simple diatomic HCl with the VMI of its H-photofragments. Free HCl molecules were excited by a pump infrared (IR) laser pulse to particular rotational J levels of the v = 2 vibrational state, and subsequently a probe ultraviolet laser photodissociated the molecule at a fixed wavelength of 243.07 nm where also the H-fragments were ionized. The molecule was aligned by the IR excitation with respect to the IR laser polarization, and this alignment was reflected in the angular distribution of the H-photofragments. In particular, the highest degree of molecular alignment was achieved for the J=1←0 transition, which exclusively led to the population of a single rotational state with M = 0. The obtained images were analyzed for further details of the VMP dynamics, and different J states were studied as well. Additionally, we investigated the dynamic evolution of the excited states by changing the pump-probe laser pulse delay; the corresponding images reflected dephasing due to a coupling between the molecular angular momentum and nuclear spin. Our measurements confirmed previous observation using the time-of-flight technique by Sofikitis et al. [J. Chem. Phys. 127, 144307 (2007)]. We observed a partial recovery of the originally excited state after 60 ns in agreement with the previous observation.


A nursing approach to easing pain.
Competency in pain assessment, analgesic administration, and evaluation of response to treatment is the responsibility of the nurse. The Agency for Health Care Policy and Research (AHCPR, 1994) suggests the mnemonic of "ABCDE". Ask about pain regularly and Assess pain systematically. Believe the patient in reports of pain and what relieves it. Choose pain control options appropriate for the patient, family and setting. Deliver interventions in a timely, logical and coordinated fashion. Empower patients and families. Enabling them to control their course to the greatest extent possible. The greatest gift we, as nurses, can give is to know and meet expected outcomes of pain management. The greatest gift we can give the patient/client/resident is to believe them and ease their pain. The greatest gift we can give family members is the ability to see their loved one free of pain. The memories of hours of pain and suffering will live with the patient, family and friends for the rest of their lives. Nurses can do so much to provide that comfort. What will you do?


Discovery of an Orally Bioavailable Inhibitor of Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation.
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg). This work lays out the discovery of an orally bioavailable analogue, NAcM-OPT (67). Compound 67 retains the favorable biochemical and cellular activity of compound 7 but is significantly more stable both in vitro and in vivo. Compound 67 is orally bioavailable, well tolerated in mice, and currently used to study the effects of acute pharmacologic inhibition of the DCN1-UBE2M interaction on the NEDD8/CUL pathway.


Quality of resistance training description in COPD trials: study protocol for a systematic review.
Limb muscle dysfunction is a common manifestation in patients with chronic obstructive pulmonary disease (COPD). Optimising of limb muscle function is therefore an important goal during pulmonary rehabilitation of patients with COPD. Resistance training (RT) is the best available intervention to achieve this goal. Previous systematic reviews on RT primarily focused on methodological quality. However, the intervention holds the essence of each experimental study. Replication of RT interventions requires clear, complete and accessible reporting of the essential components. The American College of Sports Medicine (ACSM) provides evidence-based guidelines for RT prescription and recommends RT models specific to desired outcomes, that is, improvements in strength, muscular hypertrophy, power or local muscle endurance. The aim of this review is to investigate if the application of the RT principles and key training variables is described sufficiently in current evidence on the effects of RT interventions in patients with COPD. Any research study (randomised, non-randomised controlled, controlled pre-post studies and observational studies) with an RT intervention in patients with COPD will be considered for this systematic review. Potentially relevant studies published in English from inception to 1 October 2017 will be identified from Embase, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Physiotherapy Evidence Database (PEDro). Studies exploring the effects of RT following a single session and RT interventions limited to other respiratory chronic diseases will not be included. Additionally, studies including non-COPD participants will be excluded, if the COPD data are not separated. Pairs of reviewers will independently extract data using data collecting sheets. Quality appraisal of RT description will be performed in timeframes according to the latest published ACSM position statement on exercise or RT. This protocol is a systematic review and therefore ethical approval is not required. The results of this review will be disseminated through peer-reviewed publication and presented at scientific conferences. CRD42017067403.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores allostimulatory function to accessory cells in patients with AIDS.
Impaired allostimulatory function of dendritic cells in patients with AIDS has been reported previously. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can restore the T-cell stimulatory function in transforming growth factor-beta 1 (TGF-beta 1)-inhibited murine accessory cells. We now report the effect of intravenous recombinant human GM-CSF (rhGM-CSF) on accessory cells of HIV-infected patients. The in vivo effect of GM-CSF on allostimulatory function of accessory cells was evaluated. Seventeen individuals with AIDS received a single infusion of rhGM-CSF (125 mg/m(2) over 120 minutes). Samples of peripheral blood lymphocytes (PBL) were taken at 1, 5, and 24 hours after infusion, and the allostimulatory capacity was measured. A single bolus infusion of rhGM-CSF resulted in significantly increased accessory cell function in 13/17 (88%) patients at one or more assayed time points after infusion. These results suggest that the administration of rhGM-CSF can potentially restore allostimulatory function to accessory cells in HIV-infected patients, and this presents a novel way of immune reconstitution. Clinical significance of this approach of immune reconstitution in AIDS patients warrants further investigations.


Diagnosis and Treatment of Arterial Occlusion after Knee Arthroplasty: The Sooner, the Better.
Knee arthroplasty, including total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA), is an effective procedure for patients with severe knee joint diseases. Arterial occlusion after knee arthroplasty is a rare but severe complication. However, there are few comprehensive reviews or analyses focusing on it. In this study, we presented a case of successful treatment of acute arterial occlusion of the popliteal artery after TKA by emergent balloon angioplasty, and conducted a review and analysis of published cases with this complication. After search and screening, 36 studies with 47 cases of arterial occlusion after knee arthroplasty in the past 35 years (1984-2018) were included. Among the 47 patients, there were 22 men and 25 women. The mean age was 68 years old. A total of 43 patients had primary TKA while 2 had revision surgery for TKA and 2 for UKA. For arterial occlusions, 66% presented symptoms in less than 1 day after knee surgery and 95% of the occlusion sites were around the popliteal artery. For treatment, 89% chose surgical treatment. Compared with conservative treatment, surgical treatment was more effective (P < 0.01). The patients who underwent surgical treatment less than 1 day after diagnosis had less sequelae (P < 0.05). For arterial occlusion after knee arthroplasty, we should pay attention to the perioperative risk factors and presentations, and diagnose and treat surgically at an early stage.


Recent developments in brief psychotherapy.
The clinical effectiveness and many of the therapeutic mechanisms of brief psychotherapy have been validated through research studies in recent years, as indicated in this review of developments in the psychodynamic and interpersonal brief therapies. However, the literature shows considerable variation in methods for establishing time limits and in exclusion criteria. In a major shift in therapeutic practice, interpersonal rather than intrapsychic concepts are used to identify the focus of therapy, and systematic techniques for defining the therapeutic focus have been developed. The therapeutic alliance and its relation to outcome also have received substantial attention. Trends in service delivery clearly indicate increasing emphasis on brief psychotherapy, which must be conceptualized as a specific modality, not just as long-term therapy compressed.


The investigation of ultrasound technology to measure breast muscle depth as a correlated trait to breast meat yield in turkey (Meleagris gallopavo).
Ultrasound measurements of muscle depth were analyzed to determine if these traits could be used to increase the rate of genetic gain in breast meat yield (BMY). Two measurements of breast depth, one taken horizontally across both breast lobes and one parallel to the keel, were captured using ultrasound. Heritabilities of muscle depth traits ranged from 0.35 to 0.70. These values were greater than heritabilities of conformation scores, which ranged from 0.25 to 0.47 within sex and line. The ultrasound traits also showed strong genetic correlations to BMY, ranging from 0.43 to 0.75, indicating that selection, using ultrasound depth as a correlated information source, could result in improved BMY. Including each ultrasound trait in a linear regression model predicting BMY increased the proportion of variation explained by the models by 0.08 to 0.17, relative to using conformation score as the only in vivo estimate. Based on results from a simulated turkey breeding program with selection pressure only on BMY, the ultrasound measures could increase the accuracy of a selection index for BMY by 0.02 to 0.16. As a result, ultrasound technology has the potential to improve the rate of genetic gain in BMY in a breeding program.


Intra-host Trypanosoma cruzi strain dynamics shape disease progression: the missing link in Chagas disease pathogenesis.
Chronic Chagasic cardiomyopathy develops years after infection in 20-40% of patients, but disease progression is poorly understood. Here, we assessed Trypanosoma cruzi parasite dynamics and pathogenesis over a 2.5-year period in naturally infected rhesus macaques. Individuals with better control of parasitemia were infected with a greater diversity of parasite strains compared to those with increasing parasitemia over time. Also, the in vivo parasite multiplication rate decreased with increasing parasite diversity, suggesting competition among strains or a stronger immune response in multiple infections. Significant differences in electrocardiographic (ECG) profiles were observed in Chagasic macaques compared to uninfected controls, suggesting early conduction defects, and changes in ECG patterns over time were observed only in macaques with increasing parasitemia and lower parasite diversity. Disease progression was also associated with plasma fibronectin degradation, which may serve as a biomarker. These data provide a novel framework for the understanding of Chagas disease pathogenesis, with parasite diversity shaping disease progression.IMPORTANCEChagas disease progression remains poorly understood, and patients at increased risk of developing severe cardiac disease cannot be distinguished from those who may remain asymptomatic. Monitoring of Trypanosoma cruzi strain dynamics and pathogenesis over 2-3 years in naturally infected macaques shows that increasing parasite diversity in hosts is detrimental to parasite multiplication and Chagasic cardiomyopathy disease progression. This provides a novel framework for the understanding of Chagas disease pathogenesis.


Identification of malaria parasites by fluorescence microscopy and acridine orange staining.
The need for a technique that is more sensitive than the use of Romanowsky-stained thick blood films for detecting malaria parasites at low concentration in the blood is well recognized. One of the more promising methods appeared to be fluorochrome staining with acridine orange. However, reports on the efficacy of the technique were contradictory and it was not clear to what extent blood films taken under survey conditions would contain fluorescing artefacts that might confuse diagnosis. An investigation indicated that, provided reasonable care was taken, blood films made under survey conditions contained few confusing artefacts. However, it was found that, while acridine orange staining might have a slight advantage when large malaria parasites were present, it was inferior to routine Romanowsky staining for the detection of young trophozoites, the inferiority becoming more pronounced as the parasite concentration decreased.


Laboratory diagnosis of human neurocysticercosis: double-blind comparison of enzyme-linked immunosorbent assay and electroimmunotransfer blot assay.
Neurocysticercosis is a common disease in underdeveloped countries. Its diagnosis is based on clinical, imaging (tomography or magnetic resonance), epidemiological, and laboratory data. Several methods based on the detection of antibodies against cysticerci in cerebrospinal fluid or serum have been tested. Among them, an enzyme-linked immunosorbent assay (ELISA) based on the use of a crude parasite antigen has been used by the laboratory network of cysticercosis in Mexico, which has given support to clinicians for up to 7 years. A Taenia solium-specific glycoprotein-based electroimmunotransfer blot (EITB) assay was reported to be highly sensitive and specific for this purpose. In order to compare both techniques, we studied 100 neurocysticercosis patients and 70 neurological noncysticercosis controls and searched for specific antibodies in paired samples of serum and cerebrospinal fluid using both techniques. We found that the EITB assay is more sensitive than the ELISA, especially when serum is being tested. Both techniques are more sensitive in cases with multiple living cysts than in cases with single cysts or calcified lesions. No global differences among cases with parasites located in different parts of the central nervous system were found. In the patients with cysts within the parenchyma, the sensitivity of the EITB assay was higher with serum than with cerebrospinal fluid. The immunodominant bands were found to be the same as those previously reported, i.e., GP-39 to -42, GP-24, and GP-13. Based on these results, we suggest the use of the EITB assay in routine diagnosis of cysticercosis for clinical cases.


How Well are Serious Illness Conversations Documented and What are Patient and Physician Perceptions of These Conversations?
Background: The Serious Illness Care Program (SICP), developed in 2011 by Ariadne Labs, restructures care so that knowing and then honoring patients' wishes becomes part of routine care. Objectives: 1) summarize patient perceptions of use of the Serious Illness Conversation Guide (SICG) components, 2) assess whether a serious illness conversation was documented in the electronic health record (EHR) and identify the SICG components that were included, 3) summarize clinician perceptions of use of the SICG components, and 4) assess the association of documented SICG components with the patient's perception of the SICG discussion. Methods: Clinicians at three family medicine offices were trained in serious illness conversations using the SICG. They documented their serious illness conversations in the medical record. Retrospective chart review for SICG components was conducted for patients. Patients and clinicians completed questionnaires about their experience with the SICG. Statistical analysis included the Pearson chi-square test for categorical variables and Cohen's kappa to determine agreement between clinician documentation and patient perception. Results: Eighty-nine patients consented and completed their baseline questionnaire. Mean age of the 89 patients was 72 years and 65 (73%) were female. Thirty (34%) medical records had one or more SICG components documented. Seventy-nine (89%) patients reported at least one individual component of the SICG being discussed. Clinicians reported they engaged in asking patients what is important to them at a mean of 5.9, with 7 being "all the time". There was slight agreement (kappa = .19) for patient perception and clinician documentation of discussing patient goals, but no agreement for any of the other SICG components. Conclusion: Even among trained clinicians, only one-third of patients had documentation of at least one SICG component. Only slight agreement was found between clinician documentation of SICG in the medical record and patient perception of SICG discussion.


Massive Organ Inflammation in Experimental and in Clinical Meningococcal Septic Shock.
Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock. Nine patients with lethal pneumococcal disease and 14 patients with sudden infant death syndrome served as controls. Frozen tissue were thawed, homogenized and prepared for quantification of bacterial DNA by real-time polymerase chain reaction, and key inflammatory mediators were measured by ELISA in the pig material and by multiplex in the human material. In addition, gene expression assayed by Affymetrix gene expression profiling was performed in the pig study. The porcine model revealed a major influx of N. meningitidis in lungs, liver, spleen, and kidneys accompanied with major production of cardinal inflammatory mediators including tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-8, far exceeding the amount detected in blood. Genes encoding for these mediators revealed a similar profile. By comparing the wild-type with a lipopolysaccharide (LPS) deficient meningococcal strain, we documented that LPS was the dominant group of molecules inducing organ inflammation and was required for IL-8 production. IL-10 production was predominantly stimulated by non-LPS molecules. The massive organ inflammation in the porcine model was present in the three patients dying of meningococcal shock and differed markedly from the patients with lethal pneumococcal infections and sudden infant death syndrome. In conclusion, in meningococcal sepsis, a massive local inflammatory response occurs in specific organs.


Emergence of biological organization through thermodynamic inversion.
Biological organization arises under thermodynamic inversion in prebiotic systems that provide the prevalence of free energy and information contribution over the entropy contribution. The inversion might occur under specific far-from-equilibrium conditions in prebiotic systems oscillating around the bifurcation point. At the inversion moment, (physical) information characteristic of non-biological systems acquires the new features: functionality, purposefulness, and control over the life processes, which transform it into biological information. Random sequences of amino acids and nucleotides, spontaneously synthesized in the prebiotic microsystem, in the primary living unit (probiont) re-assemble into functional sequences, involved into bioinformation circulation through nucleoprotein interaction, resulted in the genetic code emergence. According to the proposed concept, oscillating three-dimensional prebiotic microsystems transformed into probionts in the changeable hydrothermal medium of the early Earth. The inversion concept states that spontaneous (accidental, random) transformations in prebiotic systems cannot produce life; it is only non-spontaneous (perspective, purposeful) transformations, which are the result of thermodynamic inversion, that lead to the negentropy conversion of prebiotic systems into initial living units.


Excited-state dynamics of Wurster's salts.
The excited-state dynamics of a series of Wurster's salts (p-phenylenediamine radical cations) with different subtituents on the nitrogen atoms was investigated under a variety of experimental conditions using a combination of ultrafast spectroscopic techniques. At room temperature, the lifetime of the lowest excited state of all radical cations is on the order of 200 fs, independently of the solvent, that is, water, nitriles, alcohols, and room-temperature ionic liquid. On the other hand, all cations, except that with the bulky nitrogen substituents, become fluorescent below 120 K. The observed dynamics can be accounted for by the presence of a conical intersection between the D(1) and D(0) states. For the cations with a small nitrogen substituent, this conical intersection could be accessed through a twist of one amino group, as already suggested for Wurster's Blue. However, this coordinate cannot be invoked for the cation with bulky nitrogen subtituents, and more probably, pyramidalization of the nitrogen center and/or deformation of the phenyl ring play an important role. Consequently, the excited-state dynamics of these structurally very similar Wurster's salts involves different decay mechanisms.


Electronic Modulation Caused by Interfacial Ni-O-M (M=Ru, Ir, Pd) Bonding for Accelerating Hydrogen Evolution Kinetics.
Designing definite metal-support interfacial bond is an effective strategy for optimizing the intrinsic activity of noble metals, but rather challenging. Herein, a series of quantum-sized metal nanoparticles (NPs) anchored on nickel metal-organic framework nanohybrids (M@Ni-MOF, M=Ru, Ir, Pd) are rationally developed through a spontaneous redox strategy. The metal-oxygen bonds between the NPs and Ni-MOF guarantee structural stability and sufficient exposure of the surface active sites. More importantly, such precise interfacial feature can effectively modulate the electronic structure of hybrids through the charge transfer of the formed Ni-O-M bridge and then improves the reaction kinetics. As a result, the representative Ru@Ni-MOF exhibits excellent hydrogen evolution reaction (HER) activity at all pH values, even superior to commercial Pt/C and recent noble-metal catalysts. Theoretical calculations deepen the mechanism understanding of the superior HER performance of Ru@Ni-MOF through the optimized adsorption free energies of water and hydrogen due to the interfacial-bond-induced electron redistribution.


Anxiety sensitivity in smokers with indicators of cardiovascular disease.
There is growing recognition of the importance of understanding the nature of the associations between anxiety and cardiovascular disease (CVD), although limited research has examined mechanisms that may explain the anxiety-CVD link. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive-affective risk factor implicated in the development of anxiety psychopathology and various behavioral risk factors for CVD, although has not been examined among individuals with CVD. Adult daily smokers (n = 619; 50.9% female; Mage = 44.0, SD = 13.67) completed an online survey that included the Anxiety Sensitivity Index-3 (ASI-3) and the Patient Health Questionnaire (PHQ). The presence of CVD was assessed via the presence of ≥1 of the following: heart attack, heart murmur, positive stress test, heart valve abnormality, angina, and heart failure. Smokers with CVD indicators (n = 66, 10.7%) had significantly higher scores on the ASI-3 (M = 33.5, SD = 22.15), relative to smokers without CVD (M = 22.0, SD = 17.92; Cohen's d = .57). Those with CVD were significantly more likely to have moderate or high anxiety sensitivity (66.7%) relative to those without CVD (49.4%). Physical and social concerns about the meaning of somatic sensations were common among smokers with CVD.


Reduced transcription activity of rat liver chromatin after protein restriction and selective digestion of nuclei with micrococcus nuclease.
Restriction of protein intake in the diet has been shown to produce a change in transcription activity as determined in vitro. Conditions for a reduced transcription activity were investigated with selective digestion of nuclei with micrococcus nuclease (EC 184.108.40.206). Liver nuclei from young male rats fed a diet containing either 20 or 3% casein for 6 days were digested with 1.3 microgram of micrococcus nuclease protein/mg of nuclear DNA (specific enzyme activity 15,000 or 150 units/mg of protein). Part of the chromatin-bound RNA polymerase activity was transferred from the 2,000 x g to the 102,000 x g pellet. Independent of the type of endonuclease use, the specific activity of chromatin-bound and soluble RNA polymerase I plus III was similar in the two groups of rats. After protein restriction RNA polymerase II activity was significantly diminished in the 2,000 x g pellet, and was unchanged in the 102,000 x g pellet. Heparin-stimulated and soluble RNA polymerase II activities were significantly reduced. Number and length of RNA chains synthetized by chromatin-bound RNA polymerase I plus III remained unchanged by dietary treatment. After a low protein diet, RNA polymerase II in the absence and presence of heparin synthesized an unchanged number of RNA chains with reduced length. A selective digestion of chromatin with micrococcus nuclease is needed to show the reduction in RNA polymerase II activity after protein restriction.


Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in a Chinese adult: A case report.
Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock. A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis. CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes. Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir. He died after 12 hours of treatment. This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.


Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance.
COVID-19 is "public enemy number one" and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 -12), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10-6). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman's Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.


Sleep-based memory processing facilitates grammatical generalization: Evidence from targeted memory reactivation.
Generalization-the ability to abstract regularities from specific examples and apply them to novel instances-is an essential component of language acquisition. Generalization not only depends on exposure to input during wake, but may also improve offline during sleep. Here we examined whether targeted memory reactivation during sleep can influence grammatical generalization. Participants gradually acquired the grammatical rules of an artificial language through an interactive learning procedure. Then, phrases from the language (experimental group) or stimuli from an unrelated task (control group) were covertly presented during an afternoon nap. Compared to control participants, participants re-exposed to the language during sleep showed larger gains in grammatical generalization. Sleep cues produced a bias, not necessarily a pure gain, suggesting that the capacity for memory replay during sleep is limited. We conclude that grammatical generalization was biased by auditory cueing during sleep, and by extension, that sleep likely influences grammatical generalization in general.


[Oncogene expression in colonic cancers].
The expression of oncogenes plays a central role in the regulation of cell growth in normal and neoplastic tissue. Techniques developed recently (blot and in situ hybridization), enable the quantitative detection and topographical localization of oncogene expression at DNA and RNA level. In colonic adenomas and carcinomas and in non neoplastic mucosa of the large bowel, expression products of the oncogenes Ha-ras, Ki-ras, fos, and c-myc were detected. In most tumors a significant overexpression--as compared to the normal mucosa--of Ha-ras, Ki-ras, and fos mRNA was found. The overexpression of oncogenes, however, did not correlate with tumor progression, neither qualitatively nor quantitatively. According to recent studies (4, 7) it can be concluded, that the expression of the Ki-ras gene altered by a single point mutation, contributes significantly to the initiation and progression of epithelial neoplasias of the colon mucosa. It can be concluded, therefore, that the demonstration of oncogene expression products will play an important role in tumor diagnosis in the future.


Sequestration of heat damaged rat erythrocytes during experimental action of methyl palmitate on RES.
The effect of an i.v. injection of methyl palmitate emulsion (MP) on the clearance of heat damaged erythrocytes from the blood and their sequestration in organs of rats was followed. Twenty-four hours following application of MP in the dose of 1.5 g/kg of body weight the survival half time of erythrocytes (T1/2(51)Cr) significantly increased, whereas the amount of sequestrated red cells in the spleen decreased. The subsequent intervals of examination, however, showed no differences as compared to the controls.


Effect of a Financial Incentive for Colorectal Cancer Screening Adherence on the Appropriateness of Colonoscopy Orders.
Performance incentives for preventive care may encourage inappropriate testing, such as cancer screening for patients with short life expectancies. Defining screening colonoscopies for patients with a >50% 4-year mortality risk as inappropriate, the authors performed a pre-post analysis assessing the effect of introducing a cancer screening incentive on the proportion of screening colonoscopy orders that were inappropriate. Among 2078 orders placed by 23 attending physicians in 4 academic general internal medicine practices, only 0.6% (n = 6/1057) of screening colonoscopy orders in the preintervention period and 0.6% (n = 6/1021) of screening colonoscopy orders in the postintervention period were deemed "inappropriate." This study found no evidence that the incentive led to an increase in inappropriate screening colonoscopy orders.


[Brief introduction of acupuncture needling and teaching keypoint].
We summarized our accumulated clinical and teaching experiences and explored the regularity of acupuncture needling and teaching. It is of great importance in pressing hand during inserting needle. Stroking and pressing are two crucial parts which deserve more attention, and seldom useage of pressing hand should be abolished. Operating hand needs practice before inserting needle, while it should fully relaxed during inserting. Blending "touching", "stretch" "gathering" "erupting" and "advancing" in single moment, applying appropriate dynamic mode of inserting needle such as "join 3 forces as one" "3 points in a line" expertly and naturally. In addition, enough attention should be paid on "altering direction" and "shifting point". Inserting deftly and powerfully, no/slight sensation, deqi when inserting needle are the highest reflection as an acupuncturist.


CLINICAL FACTORS ASSOCIATED WITH SPONTANEOUS PASSAGE OF URETER STONES IN CONSERVATIVE MANAGEMENT: 6 mm IN MAXIMAL STONE SIZE MEASURED BY ULTRASONOGRAPHY CAN BE A PREDICTIVE BORDER.
(Purpose) To date there was no consensus regarding expectant size of stone and time to expulsion in the conservative treatment of ureter stones. The aim of this study was to find the clinical factors associated with stone passage by evaluating the outcome of ureter stones with expectant management in Japanese. (Materials and methods) A total of 679 ureter stone cases who visited our hospital with acute real colic and/or hematuria between 2009 and 2013, and who had decided to be treated by expectant management with or without medical expulsive therapy were enrolled in this study. All cases were examined size, location and presence of stone, and degree of hydronephrosis with ultrasonography. The examined data plus clinical data such as gender, age, side and body mass index were analyzed to find the factors related to spontaneous passage of ureter stones. Statistical analysis was performed to predict whether the factors were associated with the ureteral stone expulsion or not. (Results) Accumulated residual stone curve using Kaplan-Meier method showed time to 50%-expulsion as 15.7 days in cases with stone size no more than 6.0 mm and that as 21.8 days in those with greater than 6.0 mm, and time to 50%-expulsion as 28.8 days in cases with upper ureter stone whereas 15.6 days in those with middle or distal ureter stone. Analysis in groups with 1 mm-interval in stone size showed statistical significance only when compared 5-6 mm group with 6-7 mm group in size. Multivariate analysis showed stone size and location as statistically significant and independent factors to predict time to expulsion within 30 days. (Conclusion) Stone size and location was statistically reconfirmed to be associated with spontaneous passage in expectant management of ureter stones. This study statistically demonstrated the possibility that 6 mm in maximal stone size measured by ultrasonography can be a predictive border. 75% of ureter stones within 6 mm in maximal size measured by ultrasonography may expect to be expelled within 30 days.


The influence of spin effects on the gas phase reactions of carbanions with N and O atoms.
Molecular anions have been recently detected in the denser regions of the interstellar medium. However, the chemical reactions of molecular anions with atomic species that are abundant in the ISM remain largely unexplored. This work is an experimental and computational study of CH(2)CN(-), CH(3)CHCN(-), (CH(3))(2)CCN(-), and CH(2)CHO(-) reacting with N and O atoms. In all cases the reactions of anions with O atoms exhibit larger reaction rate constants compared to the corresponding reactions with N atoms. Our study indicates that spin-forbidden reactions are the probable pathways in the reactions with N atoms, whereas spin-allowed reactions are the dominant processes in the reactions with O atoms. The major factor influencing the reaction rate constants of anions with N and O atoms is whether a spin-allowed barrierless pathway exists. The rich chemistry observed in this work provides a greater understanding of the ion-atom reaction processes, as well as some new avenues for further spin chemistry research.


Detection of runs of homozygosity in conserved and commercial pig breeds in Poland.
Runs of homozygosity (ROH) are continuous segments of the genome that arose as a result of inbreeding, resulting in the inheritance of identical haplotypes from both parents who shared a common ancestor. In the present study, we performed a detailed characterization and comparison of ROH in four pig breeds, including intensively selected Polish Landrace as well as native unselected animals of Puławska and two Złotnicka breeds (White and Spotted). We used a medium-density PorcineSNP60 BeadChip assay (Illumina) and cgaTOH software to detect ROH covering a minimum of 30 adjacent SNPs and maintaining a size over 1 Mb. By analysing ROH distribution and frequency across the genome, we also identified genomic regions with high ROH frequency (so-called "ROH hotspots"). The obtained results showed that the analysed conserved breeds were characterized by a higher ROH span and higher ROH-based inbreeding coefficients (FROH ), which likely result from past population bottlenecks, increasing the overall inbreeding level within these populations. The analysis of ROH distribution across the genomes revealed the presence of both shared and breed-specific ROH hotspots. These hotspots, presumably representing genome regions under selection, overlapped with a variety of genes associated with processes connected with immune system functioning, reproduction, glucose homeostasis and metabolism. The genome regions with ROH hotspots overlapping in all analysed populations, located on SSC4 (51.9-55.9 Mb) and 13 (92.6-97.8 Mb), covered thirty-one different genes, including MMP16, SLC7A13, ATP6V0D2, CNGB3, WWiP1, RiMDN1 and CPNE3. These genes are primarily associated with biological regulation and metabolism, processes that could be responsible for the variety of the selected production and functional features.


Effect of combined application of carbonate salts and hot water treatment for the management of postharvest anthracnose (Colletotrichum gloeosporioides) of papaya.
Postharvest anthracnose (Colletotrichum gloeosporioides Penz.Sacc) is the most economically important biological constraint to papaya production and consumption, which causes substantial yield loss worldwide. The effect of combined application of carbonate salts and hot water treatments on the development of postharvest anthracnose and maintenances of postharvest quality of papaya fruit was studied in completely randomized design (CRD) under laboratory condition. The results revealed that combined application of hot water treatment and carbonate salts significantly (p < .05) reduced the incidence and severity of postharvest papaya anthracnose disease. The disease incidence reached 100% 21 days after inoculation in the control treatment; this level was significantly reduced to 26.70% by dipping the fruits in NH4CO3 at 50°C and NH4CO3 at 54°C. Similarly, treatments significantly (p < .05) reduced the disease severity in different degrees from the first day of disease appearance to the date of 100% unmarketability of control fruits. Furthermore, the combined application of carbonate salt and hot water treatments significantly improves fruit marketability by 93.33%. Moreover, the treatments showed significant (p < .05) effect on maintaining pH, TSS, TA, and reducing postharvest weight loss of papaya fruit. In conclusion, postharvest treatment of papaya fruit with NH4CO3 at 54°C, NH4CO3 at 52°C, and NaCO3 at 54°C can significantly reduce anthracnose development and improve marketability of the fruits without pronounced effect on their edible qualities.


Is women's household decision-making autonomy associated with their higher dietary diversity in Bangladesh? Evidence from nationally representative survey.
In Bangladesh, a low-quality repetitive diet characterized by starchy staple foods is typical, leading to disorders associated with micronutrient deficiencies, particularly among mothers and their children. The purpose of the study was to validate the link between women's decision-making autonomy and higher dietary diversity score. Participants were ever married women aged 15-49 years old with comprehensive dietary information (n = 17,842), selected from the Bangladesh Demographic and Health Survey, 2014. The dietary diversity score (DDS) was obtained from a 24-h recall of dietary intake from nine food groups, categorized into lower DDS (DDS ≤ 4) and higher DDS (DDS ≥ 5). Descriptive analysis, bivariate and multivariate logistic regression were conducted using STATA version 15. Almost all women consumed starchy foods, flesh (83.86%), and fruits (67.30%). Using logistic regression, the odds of achieving dietary diversity score were higher among women who participated in household purchases (OR 2.40; 95% CI: 1.52-3.83; p = 0.022). Women who had higher and secondary education were 2.72 (95% CI: 1.49-3.02; p = 0.025) and 1.31 (95% CI: 0.58-2.18; p = 0.029) times more likely to achieve higher DDS than women having no education, as well as women in the richest quintile (OR 6.49; 95% CI: 4.12-8.5; p = 0.037) compared to women in the lowest quintile. This study highlighted the association of several socioeconomic conditions of ever married women and their dietary diversity score in Bangladesh. Therefore, promoting the women's education status, improving the socioeconomic conditions, and prioritizing their decisions are recommended for the attainment of higher dietary diversity score.


The structure of the Escherichia coli phosphotransferase IIAmannitol reveals a novel fold with two conformations of the active site.
The bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) catalyses the cellular uptake and subsequent phosphorylation of carbohydrates. Moreover, the PTS plays a crucial role in the global regulation of various metabolic pathways. The PTS consists of two general proteins, enzyme I and the histidine-containing protein (HPr), and the carbohydrate-specific enzyme II (EII). EIIs are usually composed of two cytoplasmic domains, IIA and IIB, and a transmembrane domain, IIC. The IIA domains catalyse the transfer of a phosphoryl group from HPr to IIB, which phosphorylates the transported carbohydrate. Knowledge of the structures of the IIA proteins may provide insight into the mechanisms by which the PTS couples phosphorylation reactions with carbohydrate specificity. We have determined the crystal structure of the Escherichia coli mannitol-specific IIA domain, IIAmtl (M(r) 16.3 kDa), by multiple anomalous dispersion analysis of a selenomethionine variant of IIAmtl. The structure was refined at 1.8 A resolution to an R factor of 19.0% (Rfree 24.2%). The enzyme consists of a single five-stranded mixed beta sheet, flanked by helices on both sides. The phosphorylation site (His65) is located at the end of the third beta strand, in a shallow crevice lined with hydrophobic residues. The sidechains of two conserved active-site residues, Arg49 and His111, adopt two different conformations in the four independent IIAmtl molecules. Using a solution structure of phosphorylated HPr, and a combination of molecular modelling and NMR binding experiments, structural models of the HPr-IIAmtl complex were generated. The fold of IIAmtl is completely different from the structures of other IIA proteins determined so far. The two conformations of Arg49 and His111 might represent different states of the active site, required for the different phosphoryl transfer reactions in which IIAmtl is involved. A comparison of the HPr-IIAmtl model with models of HPr in complex with other IIA enzymes shows that the overall interaction mode between the two proteins is similar. Differences in the stabilisation of the invariant residue Arg17 of HPr by the different IIA proteins might be part of a subtle mechanism to control the hierarchy of carbohydrate utilisation by the bacterium.


Dynamic analysis and control of a rice-pest system under transcritical bifurcations.
A decision model is developed by adopting two control techniques, combining cultural methods and pesticides in a hybrid approach. To control the adverse effects in the long term and to be able to evaluate the extensive use of pesticides on the environment and nearby ecosystems, the novel decision model assumes the use of pesticides only in an emergency situation. We, therefore, formulate a rice-pest-control model by rigorously modelling a rice-pest system and including the decision model and control techniques. The model is then extended to become an optimal control system with an objective function that minimizes the annual losses of rice by controlling insect pest infestations and simultaneously reduce the adverse impacts of pesticides on the environment and nearby ecosystems. This rice-pest-control model is verified by analysis, obtains the necessary conditions for optimality, and confirms our main results numerically. The rice-pest system is verified by stability analysis at equilibrium points and shows transcritical bifurcations indicative of acceptable thresholds for insect pests to demonstrate the pest control strategy.


A novel procedure for the extraction of protein deposits from soft hydrophilic contact lenses for analysis.
A quick, simple, and efficient extraction technique was developed for the removal of protein from soft hydrophilic contact lenses. An extraction solvent consisting of a 50:50 mix of 0.2% trifluoroacetic acid and acetonitrile was used to remove protein from in vitro laboratory-deposited and human-worn contact lenses. The protein removed was analyzed using HPLC, bicinchoninic acid (BCA) analysis, and SDS-PAGE gel electreophoresis. Extraction efficiency for lysozyme from laboratory-deposited Group IV lenses was determined to be approximately 100%. Group IV human-worn contact lenses were extracted and analyzed for lysozyme by HPLC and total protein by bicinchoninic acid (BCA) analysis. Groups I, II, III, and IV contact lenses deposited with an artificial tear protein solution and human-worn lenses were extracted and analyzed by SDS-PAGE gel electreophoresis and micro-BCA. The ACN/TFA procedure offers a simple, quick, and efficient extraction technique for removal of protein from contact lenses for subsequent analysis.


Characterization of Theabrownins Prepared From Tea Polyphenols by Enzymatic and Chemical Oxidation and Their Inhibitory Effect on Colon Cancer Cells.
Theabrownins (TBs) are prepared from dark tea and contain a large number of complex heterogeneous components, such as carbohydrates, proteins, and flavonoids, which are difficult to remove. In addition, some toxic and harmful extraction solvents are used to purify TBs. These obstacles hinder the utilization and industrialization of TBs. In this study, tea polyphenols were used as substrates and polyphenol oxidase and sodium bicarbonate (NaHCO3) were used successively to prepare theabrownins (TBs-E). The UV-visible characteristic absorption peaks of the TBs-E were located at 203 and 270 nm and Fourier-transform IR analysis showed that they were polymerized phenolic substances containing the hydroxy and carboxyl groups. The TBs-E aqueous solution was negatively charged and the absolute values of the zeta potential increased with increasing pH. A storage experiment showed that TBs-E were more stable at pH 7.0 and in low-temperature environments around 25°C. HT-29 human colon cancer cells were used to evaluate the biological activity of TBs-E through 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT), H&E staining, propidium iodide immunofluorescent staining, flow cytometry, and real-time PCR assays. The TBs-E significantly inhibited cell growth and caused late apoptosis, particularly at the dose of 500 μg/ml. The TBs-E markedly reduced the expression of antioxidant enzyme genes and increased the generation of reactive oxygen species to break the redox balance, which may have led to cell damage and death. These results will promote research and industrialization of TBs.


Direct facile screening of recombinant DNA vector constructs.
Direct efficient facile screening of bacterial transformants with the goal of selecting, retrieving, and using recombinant DNA is exemplified by simple visual-based colorimetric inspections or fluorescent protein-based assays. We describe pRedScript, which introduces the constitutive expression of a very bright red fluorescent protein into transformants. On agar plates, red colonies are simply visualized in ambient white light in stark contrast to recombinant transformants that are white. In addition, the bright red fluorescence of the reporter protein can also be harnessed as a sensitive signal for screening bacterial promoters during the development of optimized fermentation conditions.


Intravital imaging of intestinal lacteals unveils lipid drainage through contractility.
Lacteals are lymphatic vessels located at the center of each intestinal villus and provide essential transport routes for lipids and other lipophilic molecules. However, it is unclear how absorbed molecules are transported through the lacteal. Here, we used reporter mice that express GFP under the control of the lymphatic-specific promoter Prox1 and a custom-built confocal microscope and performed intravital real-time visualization of the absorption and transport dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules in the intestinal villi in vivo. These analyses clearly revealed transepithelial absorption of these molecules via enterocytes, diffusive distribution over the lamina propria, and subsequent transport through lacteals. Moreover, we observed active contraction of lacteals, which seemed to be directly involved in dietary lipid drainage. Our analysis revealed that the smooth muscles that surround each lacteal are responsible for contractile dynamics and that lacteal contraction is ultimately controlled by the autonomic nervous system. These results indicate that the lacteal is a unique organ-specific lymphatic system and does not merely serve as a passive conduit but as an active pump that transports lipids. Collectively, using this efficient imaging method, we uncovered drainage of absorbed molecules in small intestinal villus lacteals and the involvement of lacteal contractibility.


Efficient photoelectrochemical overall water-splitting of MoS2/g-C3N4 n-n type heterojunction film.
The construction of heterojunctions has attracted considerable attention among the various strategies of water-splitting for hydrogen evolution due to their band structure advantages. In this research, we combined chemical vapor deposition and pulsed laser deposition to fabricate MoS2/g-C3N4 heterojunction films on indium-tin oxide glass substrates, and we studied the photoelectrochemical (PEC) performance. The x-ray diffraction, x-ray photoelectron spectroscopy (XPS), and scanning electron microscope characterizations suggested the successful preparation of MoS2/g-C3N4 heterojunction films. In particular, the shifts of the peak positions in the XPS spectra indicated the formation of a strong interaction between the g-C3N4 and MoS2 films. After depositing MoS2 on the g-C3N4 film, the visible-light absorption was enhanced and broadened, the electrical conductivity improved, and the intensity of the photoluminescence peak decreased. As a result, the greater generation, faster transport, and lower recombination rate of electrons and holes caused the heterojunction films to show higher PEC performance. More importantly, the obtained MoS2/g-C3N4 film was confirmed to be an n-n type heterojunction and to have a typical type-II band structure, which could indeed suppress the recombination and promote the separation, transfer, and transport of photogenerated electron-holes. Finally, the obtained MoS2/g-C3N4 film successfully achieved the overall water-splitting and the H2 evolution rate when the visible-light radiation reached 252 µmol/h.


A supplementary grading scale combining lesion-to-eloquence distance for predicting surgical outcomes of patients with brain arteriovenous malformations.
OBJECTIVE Case selection for the surgical treatment of brain arteriovenous malformations (BAVMs) remains challenging. This study aimed to construct a predictive grading system combining lesion-to-eloquence distance (LED) for selecting patients with BAVMs for surgery. METHODS Between September 2012 and September 2015, the authors retrospectively studied 201 consecutive patients with BAVMs. All patients had undergone preoperative functional MRI and diffusion tensor imaging (DTI), followed by resection. Both angioarchitectural factors and LED were analyzed with respect to the change between preoperative and final postoperative modified Rankin Scale (mRS) scores. LED refers to the distance between the lesion and the nearest eloquent area (eloquent cortex or eloquent fiber tracts) measured on preoperative fMRI and DTI. Based on logistic regression analysis, the authors constructed 3 new grading systems. The HDVL grading system includes the independent predictors of mRS change (hemorrhagic presentation, diffuseness, deep venous drainage, and LED). Full Score combines the variables in the Spetzler-Martin (S-M) grading system (nidus size, eloquence of adjacent brain, and venous drainage) and the HDVL. For the third grading system, the fS-M grading system, the authors added information regarding eloquent fiber tracts to the S-M grading system. The area under the receiver operating characteristic (ROC) curves was compared with those of the S-M grading system and the supplementary S-M grading system of Lawton et al. RESULTS LED was significantly correlated with a change in mRS score (p < 0.001). An LED of 4.95 mm was the cutoff point for the worsened mRS score. Hemorrhagic presentation, diffuseness, deep venous drainage, and LED were independent predictors of a change in mRS score. Predictive accuracy was highest for the HDVL grading system (area under the ROC curve 0.82), followed by the Full Score grading system (0.80), the fS-M grading system (0.79), the supplementary S-M grading system (0.76), and least for the S-M grading system (0.71). Predictive accuracy of the HDVL grading system was significantly better than that of the Spetzler-Martin grade (p = 0.040). CONCLUSIONS LED was a significant predictor for the preoperative risk evaluation for surgery. The HDVL system was a good predictor of neurological outcomes after BAVM surgery. Adding the consideration of the involvement of eloquent fiber tracts to preoperative evaluation can effectively improve its predictive accuracy.


Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease.
The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model. Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (alpha-naphthylisothiocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 mug/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 mug/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)-6 and tumor necrosis factor alpha expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days. Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor alpha expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups. Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury.


Cerebral ischemia and neurogenesis: a two-time comparison.
This study compares the effect of mild and severe cerebral ischemia on neuronal damage and neurogenesis. Sixteen Sprague-Dawley rats, anesthetized with 0.8 vol% halothane in O(2)/air, were subjected to forebrain ischemia by bilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure = 40 mmHg) for 8 (mild) or 13 (severe) min. Four non-ischemic animals were investigated as naïve controls. Bromodeoxyuridine (50 mg/kg), a marker of new cells, was administrated for seven consecutive postischemic days. After 28 days, animals were perfused with 4% paraformaldehyde and the brains were sliced. Histopathological damage of the hippocampus and the volume of the dentate gyrus were assessed by HE-staining. With immunohistochemistry BrdU-positve cells were detected in the dentate gyrus. The amount of new generated neurons was identified by double-immunofluorescence-staining of BrdU and neuronal marker (NeuN). In the CA-1 region of the hippocampus, mild ischemia induced damage up to 10% (HE-index 0.8 +/- 1.2) and severe ischemia up to 50% (HE-index 2.1 +/- 1.4). There was no histopathological damage in naïve control animals. The amount of new neurons was increased by 250% after mild insult and by 160% after severe insult compared to the naïve control animals. These data indicate that histopathological damage depends on the severity of the ischemic insult and that forebrain ischemia activates generation of new neurons. A mild ischemic challenge appears to be a more potent neurogenic stimulus than severe ischemia. The new neurons survive at least 28 days. This may relate to delayed histopathological and functional recovery after cerebral ischemia.


Human centromedian-parafascicular complex signals sensory cues for goal-oriented behavior selection.
Experimental research has shown that the centromedian-parafascicular complex (CM-Pf) of the intralaminar thalamus is activated in attentional orienting and processing of behaviorally relevant stimuli. These observations resulted in the hypothesis that the CM-Pf plays a pivotal role in goal-oriented behavior selection. We here set out to test this hypothesis with electrophysiological recordings from patients with electrodes implanted in CM-Pf for deep brain stimulation (DBS) treatment of chronic neuropathic pain. Six patients participated in (1) an auditory three-class oddball experiment, which required a button press to target tones, but not to standard and deviant tones and in (2) a multi-speaker experiment with a target word that required attention selection and a target image that required response selection. Subjects showed transient neural responses (8-15Hz) to the target tone and the target word. Two subjects additionally showed transient neural responses (15-25Hz) to the target image. All sensory target stimuli were related to an internal goal and required a behavior selection (attention selection, response selection). In group analyses, neural responses were greater to target tones than deviant and standard tones and to target words than other task-relevant words that did not require attention selection. The transient neural responses occurred after the target stimuli but prior to the overt behavioral response. Our results demonstrate that in human subjects the CM-Pf is involved in signaling sensory inputs related to goal-oriented selection of behavior.


The impact of hypothermia on serum potassium concentration: A systematic review.
Blood potassium is the main prognostic biomarker used for triage in hypothermic cardiac arrest. The aim of this review was to assess the impact of hypothermia on blood potassium levels and compare the underlying pathophysiological theories. The Medline electronic database was searched via PubMed for articles published from January 1970 to December 2016. The search strategy included studies related to hypothermia and potassium levels. The relevant literature on clinical studies and experimental studies was reviewed by the authors. Among the 50 studies included in the review, 39 (78%) reported a decrease in blood potassium levels upon hypothermia onset. Hypothermic hypokalaemia is linked to an intracellular shift rather than an actual net loss. The intracellular shift is caused by a variety of factors such as enhanced functioning of Na+K+ATPase, beta-adrenergic stimulation, pH and membrane stabilisation in deep hypothermia. In contrast, hypothermia can act as an aggravating factor in severe trauma with hyperkalaemia being an indicator of an irreversible state of cell death. An increase in the blood potassium level during hypothermia may result from a lack of enzyme functioning at cold temperatures and blocked active transport. Hypothermia causes an initial decrease of potassium levels; however, the final stage of hypothermic cardiac arrest can induce hyperkalaemia due to cell lysis and final depolarisation. Better understanding the physiopathology of potassium levels during accidental hypothermia could be critically important to better select patients who could benefit from aggressive resuscitation therapy such as extracorporeal cardiopulmonary resuscitation.


Perceptions of genetics research as harmful to society: differences among samples of African-Americans and European-Americans.
Genetics has the potential not only to find cures for diseases, but to possess the mechanisms to change the bio-social make-up of populations. A specific question that has arisen on this issue is how developments in genetic technology may intersect with existing race and ethnic relations. Evidence of the racialization of some genetic disorders has been demonstrated elsewhere. The purpose of this study is to compare and contrast African-American and European-American attitudes on the benefits of genetics research for society. Findings show that African-Americans were more likely to say genetics research is harmful for society. This relationship remained statistically significant after controls were introduced in a regression model. Demographic characteristics and self-rated knowledge of genetics had no effect on attitudes among African-Americans. A willingness to use genetic services correlated with favorable attitudes. Differences in social position may lead some groups to opposing interpretations and symbolic meanings of genetics. This may be true in the context of this study because the social meanings of genetics may be tainted by racialization, historical attempts at eugenics, and the potential abuse of genetics targeting groups partially defined by superficial genetic characteristics.


AMPAkines and morphine provide complementary analgesia.
Glutamate signaling in the central nervous system is known to play a key role in pain regulation. AMPAkines can enhance glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. previous studies have shown that AMPAkines are effective analgesic agents, and their site of action is likely in the brain. It is not known, however, if AMPAkines can provide complementary analgesia in combination with opioids, the most commonly used analgesics. Here, we show that the co-administration of an AMPAkine with morphine can provide additional analgesia, both in naïve rats and in rats that experience postoperative pain. Furthermore, we show that this AMPAkine can be administered directly into the prefrontal cortex to provide analgesia, and that prefrontal AMPAkine infusion, similar to systemic administration, can provide added pain relief to complement morphine analgesia.


Optogenetic Control of Nuclear Protein Import in Living Cells Using Light-Inducible Nuclear Localization Signals (LINuS).
Many biological processes are regulated by the timely import of specific proteins into the nucleus. The ability to spatiotemporally control the nuclear import of proteins of interest therefore allows study of their role in a given biological process as well as controlling this process in space and time. The light-inducible nuclear localization signal (LINuS) was developed based on a natural plant photoreceptor that reversibly triggers the import of proteins of interest into the nucleus with blue light. Each LINuS is a small, genetically encoded domain that is fused to the protein of interest at the N or C terminus. These protocols describe how to carry out initial microscopy-based screening to assess which LINuS variant works best with a protein of interest. © 2016 by John Wiley & Sons, Inc.


Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors.
Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.


[Diagnostic imaging of small liver tumors].
The recent introduction of the various imaging modalities including MRI has improved the diagnostic accuracy of metastatic liver tumor. Especially ultrasonography provides useful informations to demonstrate the relation of tumors to surrounding structures. However, at the same time it is still a fact that small lesions frequently escape detection and qualitative diagnosis is also rendered impossible in cases of small liver tumors. Repeated ultrasonographic examination combined with clinical informations is most important and qualitative diagnosis seems accomplishable by a combination of various imaging techniques including ultrasonically guided biopsy.


[Predictors of improved left ventricular systolic function after surgical revascularization in patients with ischemic cardiomyopathy].
Although it is known that the presence of myocardial viability predicts an increase in ejection fraction after revascularization in patients with ischemic cardiomyopathy, little is known about other predictive factors. The aim of this study was to identify variables that can predict an increase in ejection fraction after coronary revascularization surgery in patients with ischemic cardiomyopathy and a viable myocardium. The study included 30 patients (mean age 61.6 [11] years, one female) with ischemic cardiomyopathy (ejection fraction <or=40%) who fulfilled criteria for myocardial viability. All underwent ECG-gated single-photon emission computed tomography before and after surgery. An increase in ejection fraction >or=5% occurred after surgery in 17 of the 30 patients (56.6%). These patients were characterized by the presence of left main coronary artery disease (P< .004), a large number of grafts (P< .03), a high perfusion summed difference score (P< .012), a low end-diastolic volume (P< .013), and a low end-systolic volume (P< .01). An end-systolic volume <148 mL and a summed difference score >or=4 gave the best predictive model (P=.001, R2=0.73) for an increase in ejection fraction. In patients with ischemic cardiomyopathy and a viable myocardium, the main determinants of an increase in ejection fraction after revascularization surgery were low levels of left ventricular remodeling and myocardial ischemia.