Phenylalanine ammonia lyase functions as a switch directly controlling the accumulation of calycosin and calycosin-7-O-beta-D-glucoside in Astragalus membranaceus var. mongholicus plants.
Previously it had been shown that calycosin and calycosin-7-O-beta-D-glucoside (CGs) accumulate in whole plants, mainly in leaves, of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao (A. mongholicus) plants in response to low temperature. In this work, it was demonstrated that the influences of different conditions on CGs biosynthesis, by examining the changes in CGs content, as well as the expression of related genes, including phenylalanine ammonia lyase (PAL1), cinnamic acid 4-hydroxylase (C4H), chalcone synthase (CHS), chalcone reductase (CHR), chalcone isomerase (CHI), isoflavone synthase (IFS), and isoflavone 3'-hydroxylase (I3'H). The seven gene mRNAs accumulated in leaves of A. mongholicus upon exposure to low temperature in a light-dependent manner, though they exhibited different expression patterns. Transcriptions of CHS, CHR, CHI, IFS, and I3'H of the calycosin-7-O-beta-D-glucoside pathway were all up-regulated when plants were transferred from 16 degrees C to 2 degrees C or 25 degrees C or from 2 degrees C (kept for 24 h) to 25 degrees C. However, fluctuations in temperature influenced differently the transcriptions of PAL1 and C4H of the general phenylpropanoid pathway in leaves. Moreover, the amount of PAL1 expression changed sharply up and down, consistent with the variation of the content of CGs. PAL enzyme activity appears to be the limiting factor in determining the CGs levels. The inhibitor of PAL enzyme, L-alpha-aminooxy-beta-phenylpropionic acid, almost entirely shut down CGs accumulation at low temperature. All these results confirmed that PAL1, as a smart gene switch, directly controls the accumulation of CGs in A. mongholicus plants, in a light-dependent manner, during low temperature treatment.


Integrin β1 and the Repair after Nervous System Injury.
Integrin β1, as a member of the adhesion molecule family, is widely distributed in many kinds of cells and participates in multiple biological functions of the nervous system, including cytoskeleton reorganization, axon growth, and inflammatory injury. After nervous system injury, integrin β1 expressed by microglia is mainly involved in promoting inflammatory damage; integrin β1 expressed by astrocytes plays an important role in axon regeneration; integrin β1 expressed by endothelial cells mainly participates in vascular remodeling. We concluded that the function of integrin β1 depends on the location of the receptor cells. The mechanism of integrin β1, which is involved in the inflammatory response of immune regulatory cells and affects the axonal regeneration of neuronal cells, is the key to explore the repair after nervous system injury. The development of drugs targeting integrin β1 is expected to bring a breakthrough in the treatment of nervous system injury. This paper expounds the important role of integrin β1 in neurons of the nervous system and emphasizes the central role of integrin β1 in regulating non-neuronal cells after nervous system damage.


A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations.
In spite of effective antiretroviral therapy (ART), cognition is impaired in upwards of 35% of the HIV-infected population. We investigated a possible link between peripheral immune activation and brain metabolite concentrations. Thirty-five HIV-seropositive (HIV+) and eight HIV-seronegative adults were recruited to this cross-sectional study. All HIV-positive patients were on ART or a treatment interruption. Participants were evaluated for monocyte gene expression, cognitive status, and brain metabolite concentrations using 4-Tesla short echo-time proton magnetic resonance spectroscopy. Absolute concentrations of brain metabolites in the frontal white matter (FWM), anterior cingulate cortex (ACC), and basal ganglia were derived and related to monocyte gene expression and global deficit scores. Analysis of monocyte gene arrays revealed an interferon (IFN)-α-induced activation phenotype. Fourteen genes having the greatest fold increase in response to HIV were IFN genes. Monocyte activation as measured by gene expression profiles strongly correlated with lower N-acetylaspartate (NAA) in FWM. The IFN response gene Interferon-gamma inducible protein-10 (IP-10) was activated in monocytes from HIV individuals and strongly correlated with plasma protein levels. Plasma IP-10 correlated significantly and inversely with ACC NAA, which was lower in HIV-positive patients with mild compared to no cognitive impairment. Chronic peripheral immune activation driven by a type 1 IFN correlates with neuronal injury in FWM and ACC and cognitive dysfunction. Easily measured IFN-induced blood markers may be clinically significant in following early neural cell damage.


Immunochemical studies on blood groups. LI. A comparative study of the reaction of A 1 and A 2 blood group glycoproteins with human anti-A.
The immunochemical properties of purified A(1) and A(2) glycoproteins have been compared to ascertain whether their antigenic determinants differ. Quantitative precipitin and complement-fixation studies using several anti-A sera as well as purified gammaG anti-A antibodies clearly showed a specificity difference. This was also supported by absorption studies: A(2) substance specifically removed antibodies reacting with A(2) substance leaving anti-A(1) activity. A(1) substance was more effective than A(2) substance in dissolving an A(1) anti-A(1)-specific precipitate. Purified gammaM anti-A hemolyzed A(1) cells more readily than A(2) cells. Inhibition studies using mono- and difucosyl type 2 A-active oligosaccharides showed that type 2 difucosyl receptors are present in A(2) substance. The structural basis for the specificity difference between A(1) and A(2) would appear to be that A(2) substances lack type 1 A determinants; this would account for the observed higher H and Le(b) activity in A(2) substances.


[Scientific production in microbiology and affinity areas in Spain during 1990-2002].
To analyze the production and repercussions of the scientific activity of Spanish authors in the fields of microbiology, mycology, parasitology and virology. Documents published during the period of 1990 to 2000 compiled on the MEDLINE database >(WEBSPIRS 4.2) were retrieved using the following search terms ("Spain" OR "Espana") AND ("microb*" OR "virol*" OR "parasit*" OR "bacter*" OR "micol*" OR "mycol*" OR "retrovirus*) in the field, author's address. A total of 5259 documents were retrieved. Over the period studied, the number of documents published annually increased two-fold, from 256 documents in 1990 to 512 in 2002 (r = 0.92; p < 0.001), particularly those in foreign journals, from 175 to 447 documents (r = 0.95; p < 0.001). 50.9% of the documents came from universities, 35.8% from hospitals, 5.4% from the Consejo Superior de Investigaciones Científicas (CSIC) (5.4%), and 5.3% from the Instituto de Salud Carlos III. The CSIC centers (r 2 = 0.90), and universities (r 2 = 0.88) showed the highest rate of growth in the number of publications. The University of Barcelona (5.3%) had the largest number of publications among teaching institutions and Hospital Ramón y Cajal (2.9%) was the first among hospitals. The Autonomous Communities of Madrid (29.2%) and Catalonia (17.5%) showed the highest scientific production. The mean expected impact factor for all the published documents was 2.340. The expected impact factor grew from 1.977 in 1990 to 2.507 en 2002 (r 2 = 0.81). The published scientific production of Spanish researchers and the repercussion of these studies in the field of microbiology and related areas increased during the period of 1990 to 2002, particularly in the number of articles published in foreign journals. The Universities are the most productive institutions in this field.


Bacterial colonization and infection of electrophysiological cardiac devices detected with sonication and swab culture.
Electrophysiological cardiac devices are increasingly used. The frequency of subclinical infection is unknown. We investigated all explanted devices using sonication, a method for detection of microbial biofilms on foreign bodies. Consecutive patients in whom cardiac pacemakers and implantable cardioverter/defibrillators were removed at our institution between October 2007 and December 2008 were prospectively included. Devices (generator and/or leads) were aseptically removed and sonicated, and the resulting sonication fluid was cultured. In parallel, conventional swabs of the generator pouch were performed. A total of 121 removed devices (68 pacemakers, 53 implantable cardioverter/defibrillators) were included. The reasons for removal were insufficient battery charge (n=102), device upgrading (n=9), device dysfunction (n=4), or infection (n=6). In 115 episodes (95%) without clinical evidence of infection, 44 (38%) grew bacteria in sonication fluid, including Propionibacterium acnes (n=27), coagulase-negative staphylococci (n=11), Gram-positive anaerobe cocci (n=3), Gram-positive anaerobe rods (n=1), Gram-negative rods (n=1), and mixed bacteria (n=1). In 21 of 44 sonication-positive episodes, bacterial counts were significant (>or=10 colony-forming units/mL of sonication fluid). In 26 sterilized controls, sonication cultures remained negative in 25 cases (96%). In 112 cases without clinical infection, conventional swab cultures were performed: 30 cultures (27%) were positive, and 18 (60%) were concordant with sonication fluid cultures. Six devices and leads were removed because of infection, growing Staphylococcus aureus, Streptococcus mitis, and coagulase-negative staphylococci in 6 sonication fluid cultures and 4 conventional swab cultures. Bacteria can colonize cardiac electrophysiological devices without clinical signs of infection.


The novel thermostable cellulose-degrading enzyme DtCel5H from Dictyoglomus thermophilum: crystallization and X-ray crystallographic analysis.
Cellulose-based products constitute the great majority of municipal waste, and applications of cellulases in the conversion of waste biomass to biofuels will be a key technology in future biorefineries. Currently, multi-enzymatic pre-treatment of biomass is a crucial step in making carbohydrates more accessible for subsequent fermentation. Using bioinformatics analysis, endo-β-(1,4)-glucanase from Dictyoglomus thermophilum (DtCel5H) was identified as a new member of glycosyl hydrolase family 5. The gene encoding DtCel5H was cloned and the recombinant protein was overexpressed for crystallization and biophysical studies. Here, it is shown that this enzyme is active on cellulose substrates and is highly thermostable. Crystals suitable for crystallographic investigations were also obtained in different crystallization conditions. In particular, ordered crystals of DtCel5H were obtained using either ammonium sulfate or polyethylene glycol (PEG) as a precipitant agent. The crystals obtained in the presence of ammonium sulfate belonged to space group P32, with unit-cell parameters a = 73.1, b = 73.1, 73.1, c = 127.8 Å, and diffracted to 1.5 Å resolution, whereas the second crystal form belonged to the orthorhombic space group P212121, with unit-cell parameters a = 49.3, b = 67.9, c = 103.7 Å, and diffracted to 1.6 Å resolution. The crystal structure was solved in both space groups using molecular-replacement methods. Structure-activity and structure-stability studies of DtCel5H will provide insights for the design of high-performance enzymes.


Effect of sodium butyrate treatment of HeLa cells on the transcriptional activity of their isolated nuclei.
Sodium n-butyrate has been used as a tool to study the presumptive effects of the in vivo hyperacetylation of histones from HeLa cells on the transcriptional activity of their isolated nuclei. No gross differences were found in either initiation or RNA synthetic capacity among the nuclei from control or butyrate treated cells. The electrophoretic pattern of the RNA synthesized in nuclear suspensions was markedly affected by prior exposure of the cells to the fatty acid.


Receptor-Mediated Surface Charge Inversion Platform Based on Porous Silicon Nanoparticles for Efficient Cancer Cell Recognition and Combination Therapy.
Negatively charged surface-modified drug delivery systems are promising for in vivo applications as they have more tendency to accumulate in tumor tissues. However, the inefficient cell uptake of these systems restricts their final therapeutic performance. Here, we have fabricated a receptor-mediated surface charge inversion nanoparticle made of undecylenic acid modified, thermally hydrocarbonized porous silicon (UnTHCPSi) nanoparticles core and sequentially modified with polyethylenimine (PEI), methotrexate (MTX), and DNA aptamer AS1411 (herein termed as UnTHCPSi-PEI-MTX@AS1411) for enhancing the cell uptake of nucleolin-positive cells. The efficient interaction of AS1411 and the relevant receptor nucleolin caused the disintegration of the negative-charged AS1411 surface. The subsequent surface charge inversion and exposure of the active targeting ligand, MTX, enhanced the cell uptake of the nanoparticles. On the basis of this synergistic effect, the UnTHCPSi-PEI-MTX@AS1411 (hydrodynamic diameter is 242 nm) were efficiently internalized by nucleolin-positive MDA-MB-231 breast cancer cells, with an efficiency around 5.8 times higher than that of nucleolin-negative cells (NIH 3T3 fibroblasts). The receptor competition assay demonstrated that the major mechanism (more than one-half) of the internalized nanoparticles in MDA-MB-231 cells was due to the receptor-mediated surface charge inversion process. Finally, after loading of sorafenib, the nanosystem showed efficient performance for combination therapy with an inhibition ratio of 35.6%.


[Ventricular fibrillation following hyperventilation and apneic underwater swimming].
This is a case study of an 18 years old boy who lost consciousness during apneic underwater swimming. When cardiopulmonary resuscitation was initiated ventricular fibrillation was seen on cardiac monitoring. Bradycardia, atrial and ventricular premature beats are a known response to hyperventilation and apneic underwater diving. This case is the first documentation of ventricular fibritllation as a cause of sudden cardiac death during apneic underwater swimming.


Expectancy-Related Changes in Dopaminergic Error Signals Are Impaired by Cocaine Self-Administration.
Addiction is a disorder of behavioral control and learning. While this may reflect pre-existing propensities, drug use also clearly contributes by causing changes in outcome processing in prefrontal and striatal regions. This altered processing is associated with behavioral deficits, including changes in learning. These areas provide critical input to midbrain dopamine neurons regarding expected outcomes, suggesting that effects on learning may result from changes in dopaminergic error signaling. Here, we show that dopamine neurons recorded in rats that had self-administered cocaine failed to suppress firing on omission of an expected reward and exhibited lower amplitude and imprecisely timed increases in firing to an unexpected reward. Learning also appeared to have less of an effect on reward-evoked and cue-evoked firing in the cocaine-experienced rats. Overall, the changes are consistent with reduced fidelity of input regarding the expected outcomes, such as their size, timing, and overall value, because of cocaine use.


Central antinociceptive effects of meloxicam on rat spinal cord in vitro.
Non-steroidal anti-inflammatory drugs inhibit constitutive (COX-1) and induced cyclooxygenase (COX-2), blocking prostaglandin production. We have compared the effects on nociceptive reflexes of meloxicam, which is COX-2 selective, with indomethacin, which is non-selective, using an in vitro spinal cord preparation. Cords were taken from naive rats, and from rats with carrageenan-induced hyperalgesia of one hindpaw. Reflex thresholds were lower in carrageenan preparations. Superfusion with meloxicam (10-100 microM) dose-dependently inhibited baseline reflexes and wind-up in normal and carrageenan preparations, whereas indomethacin (100-300 microM) had no effect. Thus meloxicam inhibits spinal reflexes, whereas indomethacin does not, despite its high affinity for both COX isoforms. We conclude that meloxicam has spinal antinociceptive actions which cannot be explained by the current concept of COX inhibition.


Portal vein embolisation with application of haematopoietic stem cells in patients with primarily or non-resectable colorectal liver metastases.
Insufficient future liver remnant volume (FLRV) is the main cause of low resectability of liver metastases from colorectal cancer (CLMs). One option for enhancing FLVR growth is the use of portal vein embolisation (PVE) with the application of autologous haematopoietic stem cells (HSCs). PVE with the application of HSCs was used in 11 patients (group 1) with primarily non-resectable CLMs due to insufficient FLRV without signs of extrahepatic metastases. The control group (group 2) consisted of 14 patients in whom only PVE was performed. We evaluated the product quality, FLRV growth, CLM volume, median survival and progression-free survival (PFS). Product quality was achieved in all collections. In all group-I patients, sufficient FLRV growth occurred within three weeks. In the first and second weeks, FLRV increased optimally in most patients (p<0.006). In 13 out of the 14 group-2 patients, optimum FLVR growth was observed within three weeks following PVE (p<0.002). More rapid FLVR growth was observed in group 1 patients (p<0.01). CLM volume was significantly increased in both the group-2 (p<0.0005) and group-1 (p<0.008) patients at the time of liver resection. There was no significant difference in the growth of the CLM volume between the groups (p<0.18). The median survival was 7.3 and 6.8 months for group 1 and 2 patients, respectively, and the two-year PFS was 28% and 22% (p<0.18), respectively. PVE with HSC application is a promising method for effectively stimulating FLRV growth in patients with primarily non-resectable CLMs.


A novel bornane synthesis by an old idea.
Aiming at a synthesis of spiro[2.4]hepta-4,6-dienes with a carbon substituent at C-4, we investigated solvolysis reactions of the thiatricycle 2, obtained from spiro[2.4]hepta-4,6-diene (1) and thiophosgene by [4 + 2] cycloaddition. With methanol or ethanol a mixture of the esters 7 and 8 was formed. Desulfurization of the thionoesters 8 gave methyl and ethyl spiro[2.4]hepta-4,6-diene-4-carboxylate (10a,b). The corresponding alcohol (11) was prepared from 10b by LiAlH(4) reduction. Ethenetetracarbonitrile combined with the 4-substituted spiro[2.4]hepta-4,6-dienes to give the [4 + 2] cycloadducts 12a-c. Diels-Alder reaction between 11 and 2-chloroacrylonitrile afforded the spiro(bicyclo[2.2.1]hept-5-ene-7,1'-cyclopropane) derivative 14a that was transformed in three steps to rac-10-hydroxycamphor (17). This synthesis of a bornane derivative opens opportunity for variations and thus may find further applications.


Interprofessional Peer-Assisted Learning as a Model of Instruction in Doctor of Audiology Programs.
This study reports on interprofessional peer-assisted learning (PAL) as a model of instruction in the preparation of doctoral audiology students. Ten Doctor of Audiology (AuD) students provided training in audiologic screening for 53 graduate speech-language pathology students in 9 individual PAL sessions. Pre- and post-surveys assessed the peer teaching experience for AuD students in 5 areas of their confidence in audiologic screening: knowledge, skill, making a referral based on outcomes, teaching, and supervising. Pre- and post-learning outcomes in audiologic screening for the speech-language pathology student trainees determined the effectiveness of training by their AuD student peers. Survey outcomes revealed significant (p < .001) improvement in the overall confidence of AuD student peer instructors. Speech-language pathology students trained by their AuD peers exhibited significant (p = .003) improvements in their knowledge and skill and making outcome-based referrals in audiologic screening, supporting the effectiveness of the PAL paradigm. In addition to meeting required accreditation and professional certification competency standards, the PAL instructional model offers an innovative curricular approach in interprofessional education and in the teaching and supervisory preparation of students in doctoral audiology programs.


Coupled metamaterial optical resonators for infrared emissivity spectrum modulation.
We study the absorptivity of coupled metamaterial resonators in the mid-infrared range. We consider resonators supporting either a bright mode or a dark mode, introducing an additional degree of freedom for spectral modulation relative to bright modes alone. In a dark-bright coupled resonator system, we demonstrate tunable spectral splitting by changing the separation between resonators. We show via coupled mode theory that resonator separation can be mapped to coupling constant. We further introduce a dark-dark coupled resonator system, which gives rise to an emissive bright mode only in the presence of inter-resonator coupling. The dark-dark system yields a broadband emissivity that decays to zero exponentially with resonator separation, providing a design method for strong thermal emissivity control.


High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles.
To develop biocompatible, tumor-specific multifunctional iron-oxide nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy. Clinical-grade humanized monoclonal antibody (hu14.18K322A), designed to target GD2 antigen on neuroblastoma with reduced nonspecific immune interactions, was conjugated to hydroxyethyl starch-coated iron-oxide nanoparticles. Targeting capability in vitro and in vivo was assessed by immunofluorescence, electron microscopy, analytical spectrophotometry, histochemistry and magnetic resonance R2* relaxometry. The biocompatible nanoconstructs demonstrated high tumor specificity in vitro and in vivo, and low background uptake in a mouse flank xenograft model. Specific accumulation in tumors enabled particle visualization and quantification by magnetic resonance R2* mapping. Our findings support the further development toward clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and therapeutic scaffold for neuroblastoma and potentially other GD2-positive malignancies.


Multiphase protein microgels.
Peptides and proteins represent attractive building blocks for the development of new functional materials due to the biocompatibility and biodegradability of many naturally abundant proteins. In nature, sophisticated material functionality is commonly achieved through spatial control of protein localisation and structure on both the nano and micro scales. We approached this requirement in an artificial setting by exploiting the propensity of proteins to self-assemble into amyloid fibrils to achieve nano scale order, and utilised aqueous liquid/liquid phase separation to control the micron scale localization of the proteinaceous component under microconfinement. We show that in combination with droplet microfluidics, this strategy allows the synthesis of core-shell microgel particles composed of protein nanofibrils.


Chemistry and biological activity of steroidal glycosides from the Lilium genus.
Plants from the Lilium genus are a rich source of chemical diversity and have been the focus of natural products chemistry research for over twenty years. This manuscript provides a background on the chemistry and nomenclature of steroidal glycosides, as well as a chronological account of the progress between the years of 1989 up to 2014, with respect to their isolation and characterization from the genus. This review highlights the traditional use of lilies, as both food and medicine, and brings attention to the fact that the genus contains 110 accepted species of which the chemistry and biological activity of the steroidal glycosides from the majority have not been investigated to date. Thus, making the genus a relatively untapped resource that contains a potential treasure trove of chemical diversity waiting to be discovered.


Development of an eco-friendly material recycling process for spent lead glass using a mechanochemical process and Na2EDTA reagent.
To develop a novel nonheating method with lower energy consumption and higher efficiency for recovering both lead and SiO2 glass matrix from spent lead-glass powder, we attempted to treat the spent lead glass by the mechanochemical method using the metal chelate reagent, sodium ethylenediaminetetraacetate (Na2EDTA). As a result of the wet ball-milling treatment of spent lead-glass powder sealed in a polypropylene bottle with zirconia balls, Na2EDTA, and water at room temperature, we found that more than 99 mass % of lead contained in the spentlead-glass powder was extracted as a lead-EDTA species from the solid silica glass network matrix. This separation phenomenon was accelerated by the enlargement of the solid-liquid interface area due to ball-milling atomization and by the high stability constant of lead-EDTA. High extraction yield suggests that Pb-O-Pb bonds in lead glass are weakened or are broken down by the wet ball-milling treatment, i.e., the strong mechanical energy such as the potential and/ or friction energy provided by ball-milling may be high enough to elute lead ions from silica matrix. Moreover, we succeeded in recovering both lead ions as lead sulfate, which is the main compound of anglesite, and the EDTA as sodium-EDTA, which is reusable as the metal chelate reagent in wet chemical process using the ferric sulfate.


Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death.
In chronic liver disease, hepatic stellate cells (HSCs) are activated, highly proliferative and produce excessive amounts of extracellular matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen species (ROS) produced during chronic liver injury have been implicated in this activation process. Therefore, activated hepatic stellate cells need to harbor highly effective anti-oxidants to protect against the toxic effects of ROS. To investigate the protective mechanisms of activated HSCs against ROS-induced toxicity. Culture-activated rat HSCs were exposed to hydrogen peroxide. Necrosis and apoptosis were determined by Sytox Green or acridine orange staining, respectively. The hydrogen peroxide detoxifying enzymes catalase and glutathione-peroxidase (GPx) were inhibited using 3-amino-1,2,4-triazole and mercaptosuccinic acid, respectively. The anti-oxidant glutathione was depleted by L-buthionine-sulfoximine and repleted with the GSH-analogue GSH-monoethylester (GSH-MEE). Upon activation, HSCs increase their cellular glutathione content and GPx expression, while MnSOD (both at mRNA and protein level) and catalase (at the protein level, but not at the mRNA level) decreased. Hydrogen peroxide did not induce cell death in activated HSCs. Glutathione depletion increased the sensitivity of HSCs to hydrogen peroxide, resulting in 35% and 75% necrotic cells at 0.2 and 1mmol/L hydrogen peroxide, respectively. The sensitizing effect was abolished by GSH-MEE. Inhibition of catalase or GPx significantly increased hydrogen peroxide-induced apoptosis, which was not reversed by GSH-MEE. Activated HSCs have increased ROS-detoxifying capacity compared to quiescent HSCs. Glutathione levels increase during HSC activation and protect against ROS-induced necrosis, whereas hydrogen peroxide-detoxifying enzymes protect against apoptotic cell death.


Acute lymphoblastic leukemia: hand mirror variant.
The presence of numerous hand mirror cells in the bone marrow of patients with acute leukemia may be related to a good prognosis. To further evaluate this relationship, the bone marrows of 21 consecutive patients with a diagnosis of acute lymphoblastic leukemia were reviewed for the presence of greater than 40% hand mirror cells. Four of these 21 patients (19%) demonstrated this finding during the course of their illness. These patients were characterized by ease of remission and/or prolonged survival. Three (75%) patients are alive and well at the time of this writing. At the present time, of the 17 patients without hand mirror cells, seven (41%) are alive and ten (59%) are dead. Although not statistically significant, our findings suggest a positive relationship between the presence of greater than 40% hand mirror cells in the bone marrow ans a favorable prognosis. Future larger prospective studies are indicated to further understand the importance of this complex, apparently immunologically stimulated cell.


Psychiatric disorders and muscle tenderness in episodic and chronic migraine.
This review first reports on the data concerning the relationship between migraine and personality traits and psychiatric disorders. The relationship between migraine and tenderness of the pericranial and cervical muscles is then discussed. In one study, a psychologic assessment was performed in 56 women with migraine, and the Minnesota Multiphase Personality Inventory (MMPI) and State Trait Anxiety Inventory were administered at baseline (T0) and after 6-7 years (T2). Frequency, severity and duration of migraine were recorded at T0, after treatment (T1) and at T2, and their relationship to the prevalence of depression, MMPI and State Trait Anxiety Inventory data were examined. Pain parameters improved in all patients in T0-1, but were higher at T2 in patients with depression at T0. The patients whose migraine improved at T2 had significantly lower MMPI and State Trait Anxiety Inventory scores at T0 and T2. Moreover, the prevalence of depression of the patients whose migraine improved at T2 was 37.5% at T0 and decreased to 12.5% at T2. The authors subsequently studied the function of the frontal lobe in 23 female patients previously treated for chronic migraine and 23 controls by applying three neuropsychologic tests (gambling task, tower of hanoi-3 and object alternation test). The patient group performed significantly worse on the tower of hanoi-3 and the object alternation test. In order to assess the extent to which muscle tenderness may relate to psychiatric disorders in patients with migraine and tension-type headache, diagnosed according International Headache Society criteria [2004], a psychologic assessment was performed and palpation tenderness scores calculated for the pericranial and cervical muscles in 459 patients. In total, 125 patients had frequent episodic migraine, 97 had chronic migraine, 82 had frequent episodic tension-type headache and chronic tension-type headache was present in 83. In a further 72 patients, both episodic migraine and episodic tension-type headache were present. The main finding was a positive relationship between muscle tenderness and psychiatric disorders in patients with episodic migraine alone or associated with episodic tension-type headache.


An essential role for CD44 variant isoforms in epidermal Langerhans cell and blood dendritic cell function.
Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC) leave peripheral organs and home to lymph nodes via the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors to lymph nodes, we explored the expression of CD44 proteins on migrating LC and DC. We show that upon antigen contact, LC and DC upregulate pan CD44 epitopes and epitopes encoded by variant exons v4, v5, v6, and v9. Antibodies against CD44 epitopes inhibit the emigration of LC from the epidermis, prevent binding of activated LC and DC to the T cell zones of lymph nodes, and severely inhibit their capacity to induce a delayed type hypersensitivity reaction to a skin hapten in vivo. Our results demonstrate that CD44 splice variant expression is obligatory for the migration and function of LC and DC.


Estimation of attributable risk for case-control studies with multiple matching.
Kuritz and Landis considered case-control studies with multiple matching and proposed an asymptotic interval estimator of the attributable risk based on Wald's statistic. Using Monte Carlo simulation, Kuritz and Landis demonstrated that their interval estimator could perform well when the number of matched sets was large (>or=100). However, the number of matched sets may often be moderate or small in practice. In this paper, we evaluate the performance of Kuritz and Landis' interval estimator in small or moderate number of matched sets and compare it with four other interval estimators. We note that the coverage probability of Kuritz and Landis' interval estimator tends to be less than the desired confidence level when the probability of exposure among cases is large. In these cases, the interval estimator using the logarithmic transformation and the two interval estimators derived from the quadratic equations developed here can generally improve the coverage probability of Kuritz and Landis' interval estimator, especially for the case of a small number of matched sets. Furthermore, we find that an interval estimator derived from a quadratic equation is consistently more efficient than Kuritz and Landis' interval estimator. The interval estimator using the logit transformation, although which performs poorly when the underlying odds ratio (OR) is close to 1, can be useful when both the probability of exposure among cases and the underlying OR are moderate or large.


Correction of Lobule-type Microtia: Part 2: The Stage of Ear Elevation.
Here, we introduce our recent operative technique for ear elevation that results in (1) minimal morbidity for patients, (2) symmetric appearance, (3) clearer 3-dimensional structure with a deep concha, (4) good aesthetic appearance by hiding the grafted area behind the ear, and (5) maintenance of deep temporoauricular sulcus and angle. After a skin incision, the ear is elevated with temporoparietal fascia underlying the cartilage. On the conchal area, undermining is performed just below the skin so that the deep concavity can be maintained. Scalp and neck skin behind the ear is undermined subcutaneously and lifted up cranially to hide the entire area of grafted skin behind the ear. The postauricular surface is covered by full-thickness skin from the lower abdomen. A protective splint is applied for 3 months while sleeping. A total of 137 ears in 121 patients were corrected with our technique and followed up for at least 3 years. All of the scar tissue could be hidden behind the ear, an aesthetically excellent result. Our technique made it possible to acquire an excellent and symmetrical shape of the ear. The important points in our procedure are as follows: (1) subcutaneous posterior undermining to enlarge the conchal cavity, (2) careful arrangement of the temporoauricular angle and auriculo-earlobe angle, (3) reduction in the area of temporally grafted skin to hide all scars behind the ear, and (4) protection of the ear to maintain the shape using a postoperative splint.


Clinician attitudes, skills, motivations and experience following the implementation of clinical decision support tools in a large dental practice.
This study assesses dental clinicians' pre- and post-implementation attitudes, skills, and experiences with three clinical decision support (CDS) tools built into the electronic health record (EHR) of a multi-specialty group dental practice. Electronic surveys designed to examine factors for acceptance of EHR-based CDS tools including caries management by risk assessment (CAMBRA), periodontal disease management by risk assessment (PEMBRA) and a risk assessment-based Proactive Dental Care Plan (PDCP) were distributed to all Willamette Dental Group employees at 2 time points; 3 months pre-implementation (Fall 2013) and 15 months after implementation (winter 2015). The surveys collected demographics, measures of job experience and satisfaction, and attitudes toward each CDS tool. The baseline survey response rate among clinicians was 83.1% (n = 567) and follow-up survey response rate was 63.2% (n = 508). Among the 344 clinicians who responded to both before and after surveys, 27% were general and specialist dentists, 32% were dental hygienists, and 41% were dental assistants. Adherence to the CDS tools has been sustained at 98%+ since roll-out. Between baseline and follow-up, the change in mean attitude scores regarding CAMBRA reflect statistically significant improvement in formal training, knowing how to use the tools, belief in the science supporting the tools, and the usefulness of the tool to motivate patients. For PEMBRA, statistically significant improvement was found in formal training, knowing how to use the tools, belief in the science supporting the tools, with improvement also found in belief that the format and process worked well. Finally, for the PDCP, significant and positive changes were seen for every attitude and skill item scored. A strong and positive correlation with post-implementation attitudes was found with positive experiences in the work environment, whereas a negative correlation was found with workload and stress. Clinicians highly ranked a commitment to evidence-based care and sense that the tools were helping to improve patient care, health, and experience as motivations to use the tools. Peer pressure, fears about malpractice, and incentive pay were rated the lowest among the motivation factors. This study shows that CDS tools built into the EHR can be successfully implemented in a dental practice and widely accepted by the entire clinical team. Achieving a high level of adherence to use of CDS can be done through adequate training, alignment with the mission and purpose of the organization, and is compatible with an improved work environment and clinician satisfaction.


Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.
Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.


Pediatric choledochal cysts: diagnosis and current management.
Choledochal cysts are rare congenital disorders first described by Vater and Ezler in 1723. Their exact etiology remains incompletely understood; however, an anomalous pancreaticobiliary union (APBDU) and subsequent reflux of biliary contents into the biliary tree are thought to play a role. Accordingly, APBDU-associated choledochal cyst patients are significantly more likely to have evidence of hepatitis, cholangitis or pancreatitis and pathologically confirmed inflammation. In 1977, Todani and colleagues modified the original Alonso-Lej classification to include five types of CC. Type I and IV are the most common and most likely to be associated with malignancy. The majority of choledochal cysts are diagnosed in childhood. Clinical presentation varies and most often consists of nonspecific abdominal pain. Diagnosis is typically accomplished using multimodality imaging techniques including computed tomography, magnetic resonance imaging, ultrasound and MRCP. The use of diagnostic PTC and ERCP in CC has been largely replaced by MRCP. Appropriate management consists of prompt, complete cyst excision followed by restoration of biliary enteric continuity when necessary. Minimally invasive CC resection in the pediatric population has demonstrated acceptable outcomes. Prognosis is generally excellent; however, malignancy risk remains higher than the general population even after complete surgical excision.


Porphyrin-cobaloxime complexes for hydrogen production, a photo- and electrochemical study, coupled with quantum chemical calculations.
Two porphyrin-cobaloxime complexes; [{Co(dmgH)2Cl}{MPyTPP}] () and [{Co(dmgH)2Cl}{ZnMPyTPP}] () (dmgH = dimethylglyoxime, MPyTPP = 5-(4-pyridyl)-10,15,20-triphenylporphyrin) have been synthesised as model systems for the generation of hydrogen from water. Although initially envisaged as photocatalytic systems neither complex catalysed the reduction of water to hydrogen following irradiation. However, both complexes are molecular precursors for hydrogen evolution under electrochemical conditions. Turnover numbers for hydrogen production of 1.8 × 10(3) and 5.1 × 10(3) were obtained for and respectively following potentiostatic electrolysis at -1.2 V vs. Ag/AgCl while cobaloxime alone produced a turnover-number of 8.0 × 10(3). The photophysical properties of and were examined to provide an explanation for the lack of photochemical activity. These results, coupled with quantum chemical calculations, confirm that porphyrins fail to act as light-harvesting units for these systems and that the lowest energy excited states are in fact cobaloxime-based rather than porphyrin based.


Genetic variants including markers from the exome chip and metabolite traits of type 2 diabetes.
Diabetes-associated metabolites may aid the identification of new risk variants for type 2 diabetes. Using targeted metabolomics within a subsample of the German EPIC-Potsdam study (n = 2500), we tested previously published SNPs for their association with diabetes-associated metabolites and conducted an additional exploratory analysis using data from the exome chip including replication within 2,692 individuals from the German KORA F4 study. We identified a total of 16 loci associated with diabetes-related metabolite traits, including one novel association between rs499974 (MOGAT2) and a diacyl-phosphatidylcholine ratio (PC aa C40:5/PC aa C38:5). Gene-based tests on all exome chip variants revealed associations between GFRAL and PC aa C42:1/PC aa C42:0, BIN1 and SM (OH) C22:2/SM C18:0 and TFRC and SM (OH) C22:2/SM C16:1). Selecting variants for gene-based tests based on functional annotation identified one additional association between OR51Q1 and hexoses. Among single genetic variants consistently associated with diabetes-related metabolites, two (rs174550 (FADS1), rs3204953 (REV3L)) were significantly associated with type 2 diabetes in large-scale meta-analysis for type 2 diabetes. In conclusion, we identified a novel metabolite locus in single variant analyses and four genes within gene-based tests and confirmed two previously known mGWAS loci which might be relevant for the risk of type 2 diabetes.


Demographic and occupational correlates of workaholism.
Drawing on a convenience sample of 9,160 Dutch employees, the present study examined whether commonly held ideas about the associations between demographic, professional, and occupational characteristics and workaholism would be observed. For example, it is sometimes assumed that managers are more likely to display workaholic tendencies than others. Analysis of variance was used to relate workaholism scores (measured as the combination of working excessively and working compulsively) to participant age, sex, employment status (self-employed or not), profession, and occupational sector. Relatively high average scores on workaholism were obtained by workers in the agriculture, construction, communication, consultancy, and commerce/trade sectors, as well as managers and higher professionals. Low scores were found for those in the public administration and services industry sectors, and for nurses, social workers, and paramedics. The other characteristics were not or only weakly related to workaholism.


Synaptic cell adhesion molecule-2 and collapsin response mediator protein-2 are novel members of the matrix metalloproteinase-9 degradome.
The elucidation of entire sets of protease substrates ("proteodegradomes") is important for understanding proteolytic pathways, their networks, and their role in the regulation of cell function. Matrix metalloproteinase-9 (MMP-9) is an extracellularly operating protease that is expressed and released in the brain in response to enhanced neuronal activity. Under physiological conditions, MMP-9 is involved in neuronal plasticity, including long-term potentiation, learning, and memory. This function may be related to its activity at the synapse. Under pathological conditions (e.g., during excitotoxicity, stroke, and traumatic brain injury), when the concentration of glutamate is persistently increased, MMP-9 is detrimental to brain tissue. To assess the MMP-9 degradome, we used synaptoneurosomal fractions isolated from the hippocampus of wildtype and MMP-9 knockout mice. To induce MMP-9 activity, the synaptoneurosomal fractions were treated with 50 μM glutamate for 30 min at 37°C. To investigate MMP-9 targets, two-dimensional fluorescence difference gel electrophoresis was performed. This approach enabled the accurate analysis of differences in protein abundance between samples. The differential spots that contained potential MMP-9 substrates were excised from the gel, and proteins of interest were identified using mass spectrometry. Two novel MMP-9 targets were identified: synaptic cell adhesion molecule-2 and collapsin response mediator protein-2. The MMP-9-driven processing of the newly identified substrates was confirmed by western blot in primary hippocampal neurons after stimulation with either N-methyl-D-aspartate or glutamate or incubation with recombinant autoactivating MMP-9 and use of a specific inhibitor.


[Significance of immunocytochemical indices of body reactivity of workers engaged in the production of carbonic plastics on the base of formaldehyde-containing and epoxide resins].
Findings of the complex study carried out by means of hematologic, cytochemical and immunologic methods on 130 workers engaged for the 5-year period in carbonic plastic production on the basis of methanol-containing and epoxy resins are presented. Dependence of the trends and intensity of reactivity changes on the character of leading unfavourable occupational factors has been established. Immunotoxicity of carbonic plastic dust and prevalence of sensitization reaction under the impact of industrial chemical allergens (methanol, epichlorohydrine) are mainly demonstrated. The study has indicated immunocytochemical signs of forming skin allergic pathology under cytotoxic effect. Groups of workers have been registered for medical supervision on the basis of an individual analysis of functionally interdependent immunologic and cytochemical indices.


Honey as a topical treatment for wounds.
Honey is a viscous, supersaturated sugar solution derived from nectar gathered and modified by the honeybee, Apis mellifera. Honey has been used since ancient times as a remedy in wound care. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing. The objective was to determine whether honey increases the rate of healing in acute wounds (e.g. burns, lacerations) and chronic wounds (e.g. skin ulcers, infected surgical wounds). For this first update of the review we searched the Cochrane Wounds Group Specialised Register (searched 13 June 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2008 to May Week 5 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 12 June 2012); Ovid EMBASE (2008 to 2012 Week 23); and EBSCO CINAHL (2008 to 8 June 2012). Randomised and quasi-randomised trials that evaluated honey as a treatment for any sort of acute or chronic wound were sought. There was no restriction in terms of source, date of publication or language. Wound healing was the primary endpoint. Data from eligible trials were extracted and summarised by one review author, using a data extraction sheet, and independently verified by a second review author. We identified 25 trials (with a total of 2987 participants) that met the inclusion criteria, including six new trials that were added to this update. In acute wounds, three trials evaluated the effect of honey in acute lacerations, abrasions or minor surgical wounds and 12 trials evaluated the effect of honey in burns. In chronic wounds, two trials evaluated the effect of honey in venous leg ulcers, and single trials investigated its effect in infected post-operative wounds, pressure injuries, cutaneous Lieshmaniasis, diabetic foot ulcers and Fournier's gangrene. Three trials recruited people into mixed groups of chronic or acute wounds. Most trials were at high or unclear risk of bias. In acute wounds, specifically partial-thickness burns, honey might reduce time to healing compared with some conventional dressings (WMD -4.68 days, 95%CI -4.28 to -5.09 days), but, when compared with early excision and grafting, honey delays healing in partial- and full-thickness burns (WMD 13.6 days, 95% CI 10.02 to 17.18 days). In chronic wounds, honey does not significantly increase healing in venous leg ulcers when used as an adjuvant to compression (RR 1.15, 95% CI 0.96 to 1.38), and may delay healing in cutaneous Leishmaniasis when used as an adjuvant to meglumine antimoniate compared to meglumine antimoniate alone (RR 0.72, 95% CI 0.51 to 1.01). Honey dressings do not increase rates of healing significantly in venous leg ulcers when used as an adjuvant to compression. Honey may delay healing in partial- and full-thickness burns in comparison to early excision and grafting, and in cutaneous Leishmaniasis when used as an adjuvant with meglumine antimoniate. Honey might be superior to some conventional dressing materials, but there is considerable uncertainty about the replicability and applicability of this evidence. There is insufficient evidence to guide clinical practice in other types of wounds, and purchasers should refrain from providing honey dressings for routine use until sufficient evidence of effect is available.


Interface Promoted Reversible Mg Insertion in Nanostructured Tin-Antimony Alloys.
An interface promoted approach is developed for guiding the design of stable and high capacity materials for Mg batteries using SnSb alloys as model materials. Experimental and theoretical studies reveal that the SnSb alloy has exceptionally high reversible capacity (420 mA h g(-1)), excellent rate capability, and good cyclic stability for hosting Mg ions due to the stabilization/promotion effects of the interfaces between the multicomponent phases generated during repeated magnesiation-demagnesiation.


SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition.
The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell. We determined the crystal structure of a ternary complex between mouse SOCS3, JAK2 (kinase domain) and a fragment of the interleukin-6 receptor β-chain. The structure shows that SOCS3 binds JAK2 and receptor simultaneously, using two opposing surfaces. While the phosphotyrosine-binding groove on the SOCS3 SH2 domain is occupied by receptor, JAK2 binds in a phosphoindependent manner to a noncanonical surface. The kinase-inhibitory region of SOCS3 occludes the substrate-binding groove on JAK2, and biochemical studies show that it blocks substrate association. These studies reveal that SOCS3 targets specific JAK-cytokine receptor pairs and explains the mechanism and specificity of SOCS action.


Eyebrow Position and Shape Favored by Korean Women.
The shape and position of the eyebrows are among the most important facial features from an esthetic point of view. However, significant cultural differences exist with respect to the eyebrow shape and position that are considered ideal. The purpose of this study was to identify the position and shape of eyebrows preferred by Korean women and to apply these, including forehead lifts, to the clinics. The authors took full facial photographs in the Frankfort plane of Korean women aging from young childhood to their 50s. On the basis of these, 2 parameters were calculated: first, the height-to-width ratio (HWR), the ratio between the vertical distance from the brow apex to the palpebral fissure and the horizontal distance from the medial canthus to the lateral canthus; and second, the takeoff angle (TOA), the angle between the straight line connecting the 2 lateral canthi and the line from the brow apex through the center of the medial brow segment. The authors then had drawings of "Anastasia arch" eyebrows made; as high eyebrows are considered beautiful in Korea, and the eyebrows of women in their 20s were the highest, the drawings depicted the mean HWR and TOA values for this age group and their various degrees of deviation. These drawings were shown to 300 women aged 21 to 40 years from May 1 to June 30, 2014; they were instructed to choose the drawing they preferred among the 5 drawings differing in HWR and again among the 5 differing in TOA. Among the 99 Korean women in their 20s, the mean HWR and TOA was 1:1.01 ± 0.23 and 12° ± 5.2°, respectively. Regarding the survey, the most preferred HWR was 1:1.0, which was selected by 204 respondents (68%); the most preferred TOA was 10°, which was chosen by 122 respondents (40.7%). This study shows that HWR gradually decreases and TOA increases with age. Furthermore, Korean women's preferred eyebrows have an HWR of ∼1:1 and a TOA of ∼10°. These results could guide plastic surgeons performing periorbital rejuvenation surgeries, including brow lifts, not only for Koreans but also for North-East Asians.


Barriers to routine gynecological cancer screening for White and African-American obese women.
Obese women are reported to be at higher risk from gynecological cancers than nonobese women, yet these women are less likely to get cancer-screening tests. The specific factors that contribute to obese women not obtaining timely cancer screening have not been identified. To investigate the factors that contribute to lower rates of gynecological cancer screening as related to women's body size. A purposeful sample of 498 White and African-American women with body mass index (BMI) from 25 to 122 kg/m(2), including 60 women with BMI > 55 kg/m(2), was surveyed concerning access to gynecological cancer screening and potential barriers that could cause delay. Health care providers (N = 129) were surveyed concerning their education, practices, and attitudes about providing care and gynecological cancer-screening tests for obese women. Obese women reported that they delay cancer-screening tests and perceive that their weight is a barrier to obtaining appropriate health care. The percent of women reporting these statements increased significantly as the women's BMI increased. Women with BMI > 55 kg/m(2) had a significantly lower rate (68%) of Papanicolaou (Pap) tests compared to others (86%). The lower screening rate was not a result of lack of available health care since more than 90% of the women had health insurance. Women report that barriers related to their weight contribute to delay of health care. These barriers include disrespectful treatment, embarrassment at being weighed, negative attitudes of providers, unsolicited advice to lose weight, and medical equipment that was too small to be functional. The percentage of women who reported these barriers increased as the women's BMI increased. Women who delay were significantly less likely to have timely pelvic examinations, Pap tests, and mammograms than the comparison group, even though they reported that they were 'moderately' or 'very concerned' about cancer symptoms. The women who delay care were also more likely to have been on weight-loss programs five or more times. Many health care providers reported that they had little specific education concerning care of obese women, found that examining and providing care for large patients was more difficult than for other patients, and were not satisfied with the resources and referrals available to provide care for them. Since the goal of preventive cancer screening is to improve health outcomes for all women and since obese women are at greater risk, strategies must be designed to reduce the weight barriers to these tests and improve the quality of the health care experience. Providers should receive specific training related to care of large women.


A device for calibrating Rogowski coils in time domain.
In this article a device for calibrating Rogowski coils in time domain is designed, which can obtain the sensitivity and dynamic response of the Rogowski coil by means of measuring currents of long pulse durations and few nanoseconds rise time. Its key device is a current step wave generator, which can generate the output with rise time of <3 ns and with duration time of >300 ns.


Differential uptake of gold nanoparticles by 2 species of tadpole, the wood frog (Lithobates sylvaticus) and the bullfrog (Lithobates catesbeianus).
Engineered nanoparticles are aquatic contaminants of emerging concern that exert ecotoxicological effects on a wide variety of organisms. We exposed cetyltrimethylammonium bromide-capped spherical gold nanoparticles to wood frog and bullfrog tadpoles with conspecifics and in combination with the other species continuously for 21 d, then measured uptake and localization of gold. Wood frog tadpoles alone and in combination with bullfrog tadpoles took up significantly more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took up significantly more gold than controls. The rank order of weight-normalized gold uptake was wood frogs in combination > wood frogs alone > bullfrogs in combination > bullfrogs alone > controls. In all gold-exposed groups of tadpoles, gold was concentrated in the anterior region compared with the posterior region of the body. The concentration of gold nanoparticles in the anterior region of wood frogs both alone and in combination with bullfrogs was significantly higher than the corresponding posterior regions. We also measured depuration time of gold in wood frogs. After 21 d in a solution of gold nanoparticles, tadpoles lost >83% of internalized gold when placed in gold-free water for 5 d. After 10 d in gold-free water, tadpoles lost 94% of their gold. After 15 d, gold concentrations were below the level of detection. Our finding of differential uptake between closely related species living in similar habitats with overlapping geographical distributions argues against generalizing toxicological effects of nanoparticles for a large group of organisms based on measurements in only one species. Environ Toxicol Chem 2017;36:3351-3358. © 2017 SETAC.


Processing of human reduction mammoplasty and mastectomy tissues for cell culture.
Experimental examination of normal human mammary epithelial cell (HMEC) behavior, and how normal cells acquire abnormal properties, can be facilitated by in vitro culture systems that more accurately model in vivo biology. The use of human derived material for studying cellular differentiation, aging, senescence, and immortalization is particularly advantageous given the many significant molecular differences in these properties between human and commonly utilized rodent cells. Mammary cells present a convenient model system because large quantities of normal and abnormal tissues are available due to the frequency of reduction mammoplasty and mastectomy surgeries. The mammary gland consists of a complex admixture of many distinct cell types, e.g., epithelial, adipose, mesenchymal, endothelial. The epithelial cells are responsible for the differentiated mammary function of lactation, and are also the origin of the vast majority of human breast cancers. We have developed methods to process mammary gland surgical discard tissues into pure epithelial components as well as mesenchymal cells. The processed material can be stored frozen indefinitely, or initiated into primary culture. Surgical discard material is transported to the laboratory and manually dissected to enrich for epithelial containing tissue. Subsequent digestion of the dissected tissue using collagenase and hyaluronidase strips stromal material from the epithelia at the basement membrane. The resulting small pieces of the epithelial tree (organoids) can be separated from the digested stroma by sequential filtration on membranes of fixed pore size. Depending upon pore size, fractions can be obtained consisting of larger ductal/alveolar pieces, smaller alveolar clusters, or stromal cells. We have observed superior growth when cultures are initiated as organoids rather than as dissociated single cells. Placement of organoids in culture using low-stress inducing media supports long-term growth of normal HMEC with markers of multiple lineage types (myoepithelial, luminal, progenitor). Sufficient numbers of cells can be obtained from one individual's tissue to allow extensive experimental examination using standardized cell batches, as well as interrogation using high throughput modalities. Cultured HMEC have been employed in a wide variety of studies examining the normal processes governing growth, differentiation, aging, and senescence, and how these normal processes are altered during immortal and malignant transformation. The effects of growth in the presence of extracellular matrix material, other cell types, and/or 3D culture can be compared with growth on plastic. Cultured HMEC, starting with normal cells, provide an experimentally tractable system to examine factors that may propel or prevent human aging and carcinogenesis.


SARS-CoV-2-Specific T Cell Responses in Patients with COVID-19 and Unexposed Individuals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In the current review, we describe SARS-CoV-2-specific CD4+ and CD8+ T-cell responses in acute and convalescent COVID-19 patients. We also discuss the relationships between COVID-19 severity and SARS-CoV-2-specific T-cell responses and summarize recent reports regarding SARS-CoV-2-reactive T cells in SARS-CoV-2-unexposed individuals. These T cells may be cross-reactive cells primed by previous infection with human common-cold coronaviruses. Finally, we outline SARS-CoV-2-specific T-cell responses in the context of vaccination. A better understanding of SARS-CoV-2-specific T-cell responses is needed to develop effective vaccines and therapeutics.


[Application of modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy].
Objective: Traditional Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy can greatly decrease the anastomosis-related complications and reduce the incidence of reflux esophagitis, but its complexity limits the wide application. To decrease the complexity of Kamikawa anastomosis, the surgical team of Changzhi People's Hospital of Shanxi Changzhi Medical College improved this technique by using novel notion and reduced surgical procedures. This study aims to evaluate the efficacy and safety of modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy. Methods: A descriptive cohort study was carried out. Case enrollment criteria: (1) upper gastric carcinoma or esophagogastric junction carcinoma without distant metastasis was confirmed by preoperative gastroscopic biopsy and imaging examination; (2) tumor diameter was less than 4 cm; (3) preoperative clinical staging was cT1-3N1M0. Exclusion criteria: (1) patients received preoperative neoadjuvant chemotherapy; (2) patients had severe heart or lung disease, or poor nutritional status so that they could not tolerate surgery. Clinical data of 25 patients with upper gastric carcinoma or esophagogastric junction carcinoma who underwent modified Kamikawa anastomosis in digestive tract reconstruction in Heji Hospital (8 cases) and Changzhi People's Hospital (17 cases) from April 2019 to December 2020 were retrospectively collected. Of 25 patients, 21 were male and 4 were female, with mean age of 63.0 (49 to 78) years; 3 underwent open surgery and 22 underwent laparoscopic surgery. The modified Kamikawa anastomosis was as follows: (1) the novel notion of total mesangial resection of the esophagogastric junction was applied to facilitate the thorough removal of lymph nodes and facilitate hand-sewn anastomosis and embedding; (2) the diameter of the anastomotic stoma was selected according to the diameter of the esophageal stump, between 2.5 and 3.5 cm, to reduce the occurrence of anastomotic stenosis; (3) an ultrasonic scalpel was used to incise the esophageal stump, which could not only prevent bleeding of the esophageal stump, but also closely seal the esophageal mucosa, muscle layer and serosa to prevent esophageal mucosa retraction; (4) barbed suture was used to suture the remnant stomach fundus and esophagus to fix the stomach fundus in order to reduce the cumbersome and difficult intermittent sutures in a small space; (5) two barbed sutures were used to continuously suture the front and back walls of the anastomosis and complete the suture and fixation of the muscle flap. Relevant indicators of surgical safety, postoperative complications (using the Clavien-Dindo classification), esophageal reflux symptoms and the occurrence of esophagitis (using Los Angeles classification) were analyzed. The gastroesophageal reflux disease (GERD) score, gastroscopy, multi-position digestive tract radiography during postoperative follow-up were used to evaluate the residual gastric motility and anti-reflux efficacy. Results: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy was successfully performed in 25 patients. The surgical time was (5.8±1.8) hours, the intraoperative blood loss was (89.2±11.8) ml, and the average hospital stay was (13.8±2.9) days. Three cases (12.0%) developed postoperative anastomotic stenosis as Clavien-Dindo grade III and were healed after endoscopic dilation treatment. Postoperative upper gastrointestinal radiography showed 1 case (4.0%) with reflux symptoms as Clavien-Dindo grade I. Gastroscopy showed no signs of reflux esophagitis, and its Los Angeles classification was A grade. No anastomotic bleeding, local infection and death were found in all the patients. At postoperative 6-month of follow-up, GERD score showed no significant difference compared to pre-operation (2.7±0.6 vs. 2.4±1.0, t=-1.495, P=0.148). Conclusion: Modified Kamikawa anastomosis in digestive tract reconstruction after proximal gastrectomy is safe and feasible with good anti-reflux efficacy.


Comparative analysis of healthcare provision to individuals with cleft lip and/or palate at specialised academic centres in South Africa.
Cleft lip and/or palate (CLP) is the most common congenital anomaly of the craniofacial complex, with an estimated worldwide prevalence of 1/500 - 700 live births. Affected children require immediate medical treatment and prolonged management by a multidisciplinary team of health professionals. To describe and compare healthcare provision to individuals with CLP at specialised care centres in South Africa (SA). The study was conducted at all CLP care centres in 6 of SA's 9 provinces that provide specialised treatment and care to individuals with CLP. At each centre, the team leader was interviewed using a semi-structured questionnaire that focused on the point-of-care entry for CLP patients; type of services provided; whether treatment protocols were used, which treatment protocols were used and internal referral systems; and members of the healthcare team. Stata 13 (StataCorp., USA) was used to analyse the data. Eleven CLP team leaders participated in the study, of whom 5 were from Gauteng Province. The point-of-care for CLP patients in the majority of centres was plastic surgery (n=9/11; 81.8%). The majority of centres (n=10/11; 90.9%) followed similar treatment protocols and only 1 centre performed lip surgery at 12 - 18 months. Although all centres reported a multidisciplinary team approach for CLP care provision, there were gaps in the health professions categories, which influenced the type of treatment provided. Hence, surgical repair of the lip and palate (n=10/11; 90.9%) and speech therapy (n=7/11; 63.6%) dominated the type of treatment provided, and patients were referred to other provinces or to the private health sector for other types of treatment. The gaps in services at the CLP care centres in SA need to be addressed to ensure integrated, holistic care provision.


Comparison of the effects of Althesin, chloralose-urethane, urethane, and pentobarbital on mammalian physiologic responses.
Physiological responses to anesthetic doses of four chemically dissimilar agents, namely, Althesin, urethane, chloralose-urethane, and pentobarbital sodium were compared in rats. The tail-flick test revealed Althesin had greater antinociceptive potency than urethane, chloralose-urethane, and pentobarbital, but its duration of action was shorter than that of chloralose-urethane. Althesin produced minimal or no suppression of core body temperature and mean arterial pressure, and only moderate reduction of mean pulse pressure. The heart rate and respiratory rate of Althesin-treated rats were slower than those of chloralose-urethane and urethane-treated counterparts, respectively, but were not significantly decreased from normal controls. It is concluded that Althesin is a suitable anesthetic for short-term surgery and for studies of body temperature, heart rate, and mean arterial pressure. Because release of gonadotropin-releasing hormone into hypophysial portal blood can be observed under Althesin but is suppressed or blocked by chloralose-urethane, urethane, and pentobarbital, Althesin is the anesthetic of choice in studies concerned with the neural control of ovulatory hormone release.


Efficacy of peroperative liver function tests and ultrasound in detecting hepatic metastasis in carcinoma of the breast.
Two hundred and twenty patients with clinical stage I, II, or III carcinoma of the breast who presented for mastectomy were prospectively evaluated for hepatic metastases with abdominal sonography and routinely available liver enzymes (LE). Both abdominal ultrasound (US) and LE were assessed. There were two false-positive sonogram, both with normal enzymes, in patients with Stage I and II. There was one positive sonogram at presentation in a patient with Stage III, confirmed by needle biopsy, with a lactate dehydrogenase (LDH) elevation. The metastatic yield was low with ultrasound, but other findings were revealed. LE were not useful in the preoperative diagnosis of hepatic metastases, demonstrating a low specificity. Thirty-three patients demonstrated abnormalities of Le. Twenty-seven of 33 had elevation of a single enzyme, LDH being the most common. Three patients had an elevation of four enzymes preoperatively. Hepatic metastases were not diagnosed in these three patients preoperatively on ultrasound or biopsy. The patients were observed with physical examination (PE) and LE for a mean of 26 months. During the follow-up study, 0.9 per cent of the patients with Stage I, 3.4 per cent with Stage II and 12.5 per cent with Stage III had hepatic metastases develop. In patients with these metastases, involvement of the liver was suggested by elevated LE In 66 per cent, on PE in 42 per cent and by history in 28 per cent. LE were the first indication of liver involvement in two patients. We are in agreement with previous authors for abandonment of hepatic imaging in the preoperative assessment because of the low yield for metastases. Forty-eight thousand dollars would have have been spent on this cohort ot diagnose one instance of hepatic metastasis preoperatively. US may be efficacious in the subgroup of patients with grossly elevated LE or a PE suggestive of hepatic involvement. Those patients who demonstrate metastases by us should have histologic confirmation if treatment would thereby be altered.


Radiation pneumonia complicating adjuvant cytotoxic chemotherapy.
A patient with Hodgkin's disease developed acute radiation pneumonia four months after completion of mantle radiotherapy and during cyclical adjuvant chemotherapy. Respiratory function tests were useful in the diagnosis of the interstitial abnormality and in monitoring response to prednisone. Serial respiratory function tests in patients receiving bimodal therapy may facilitate early diagnosis of this potentially serious complication.


Correlation between severity of obstructive sleep apnea and prevalence of silent cerebrovascular lesions.
We investigated the prevalence of silent cerebrovascular lesions in patients with obstructive sleep apnea (OSA) and the correlation between OSA severity and prevalence of silent cerebrovascular lesions in Japanese patients. Study subjects were 192 polysomnography (PSG)-confirmed patients who visited the sleep disorders clinic in our university hospital. None had a history of cerebrovascular disease (CVD). We performed a cross-sectional study on OSA severity and the prevalence of silent cerebrovascular lesions detected by brain MRI analysis. The control (AHI < 5/h) group included 19 subjects with a mean AHI of 1.7 +/- 1.6/h, the mild OSAS (AHI 5 to < 15/h) group included 25 patients with a mean AHI of 9.5 +/- 3.7/h, the moderate OSAS (AHI 15 to < 30/h) group included 35 patients with a mean AHI of 22.0 +/- 7.0/h while the severe OSAS (AHI > or = 30/h) group included 113 patients with a mean AHI of 59.9 +/- 20.5/h. A larger percentage of patients with severe OSAS had a higher BMI and hyperglycemia than those with mild or moderate OSAS and control subjects (p < 0.05). Silent lacunar infarction was identified in 4 (21.1%) control subjects, 3 (12.0%) patients with mild OSA, 17 (48.6%) with moderate OSA and 61 (54.0%) with severe OSA. Among control subjects and the mild, moderate, and severe OSA groups, 4 (21.1%), 5 (20.0%), 19 (54.3%) and 61(54.0%), respectively, had periventricular hyperintensity (PVH); most PVH was mild to moderate. Results indicate that patients with moderate to severe (AHI > or = 15/h) OSA have a higher prevalence of silent cerebrovascular lesion than those with less severe OSA.


Tunable time response of the nonlinearity of nanocomposites by doping semiconductor quantum dots.
We report an approach to achieving a tunable time response of the nonlinearity of nano-Ag:polymer nanocomposites. The response time of the nonlinearity of the nanocomposite made of Ag nanoparticles dispersed in poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] matrix can be tuned by adjusting the doping concentration of CdTe(0.13)S(0.87) quantum dots. An ultrafast response time of 14.5 ps is achieved for a doping concentration of 27%. Moreover, the third-order nonlinear susceptibility, achieving the order of 10(-5) esu, is one order of magnitude larger than that of the undoped nanocomposite. An ultrafast and low-power photonic crystal all-optical switching is also realized based on the photonic bandgap shift.


Walking speed and step length asymmetry modify the energy cost of walking after stroke.
A higher energy cost of walking poststroke has been linked to reduced walking performance and reduced participation in the community. To determine the contribution of postintervention improvements in walking speed and spatiotemporal gait asymmetry to the reduction in the energy cost of walking after stroke. In all, 42 individuals with chronic hemiparesis (>6 months poststroke) were recruited to participate in 12 weeks of walking rehabilitation. The energy cost of walking, walking speed, and step length, swing time, and stance time asymmetries were calculated pretraining and posttraining. Sequential regression analyses tested the cross-sectional (ie, pretraining) and longitudinal (ie, posttraining changes) relationships between the energy cost of walking versus speed and each measure of asymmetry. Pretraining walking speed (β = -.506) and swing time asymmetry (β = .403) predicted pretraining energy costs: (adj)R(2) = 0.713; F(3, 37) = 34.05; P < .001. In contrast, change in walking speed (β = .340) and change in step length asymmetry (β = .934) predicted change in energy costs with a significant interaction between these independent predictors: (adj)R(2) = 0.699; F(4, 31) = 21.326; P < .001. Moderation by the direction or the magnitude of pretraining asymmetry was not found. For persons in the chronic phase of stroke recovery, faster and more symmetric walking after intervention appears to be more energetically advantageous than merely walking faster or more symmetrically. This finding has important functional implications, given the relationship between the energy cost of walking and community walking participation.


Bilateral shoulder fracture dislocations and radiculopathies secondary to electrical injury (a case report).
In this report a case of bilateral shoulder fracture dislocations and C5 radiculopathy developed after an electrical injury is presented. A 29 year-old male patient referred to our hospital with complaints of inability to raise his hands overhead starting 3 months ago after an electrical injury. The first physical examination revealed loss of strength (3/5) in deltoid muscles bilaterally, bilateral shoulder fracture dislocations and C5 radiculopathies. An open reduction and internal fixation (using K wire, cortical screw) procedure was applied for the right side in the Department of Orthopedics. Postoperatively active (A) and passive (P) ranges of motion (ROMs) were restricted extremely in the right and left shoulder respectively. Since applications of 15 sessions of electrical stimulation for deltoid muscle and physical treatment for both shoulders failed to achieve satisfactory ROMs, K wire extraction was instituted with resultant increase in the right shoulder A/P ROMs after 10 sessions of physical therapy postoperatively. At the last examination which was 18 months after the injury, ROMs of the right shoulder were increased, but not normal. It must be remembered that in electrical injury, fractures and dislocations might occur in affected sites without any evidence of trauma with associated neurologic complications, and that these cases must be promptly detected and managed without any delay.


[Progress and challenges in tissue engineering of intervertebral disc annulus fibrosus].
Degenerative disc disease (DDD) is a leading cause of low back pain, which severely affects the quality of life and incurs significant medical cost. Annulus fibrosus(AF) injuries can lead to substantial deterioration of intervertebral disc degeneration. However, the AF repair/regeneration remains a challenge due to the intrinsic cellular, biochemical and biomechanical heterogeneity of AF tissue. Tissue engineering would be a promising approach for AF regeneration. This article aims to provide a brief overview of the fundamental aspects of AF, the current achievements and future challenges of AF tissue engineering. A multidisciplinary approach is proposed for future studies to fully mimic the native AF tissue and its microenvironment, including choosing adequate cell source, preparing scaffolds with hierarchical microstructures, supplementing appropriate growth factors, and enforcing suitable mechanical stimulation. Hopefully, the engineered AF tissues would be effectively used to facilitate the treatment of DDD in the future.


Segmental origins of cardiac sympathetic nerve activity in rats.
The segmental origins of cardiac sympathetic nerve activity (CSNA) were investigated in 8 urethane-anesthetized, artificially ventilated rats. The left upper thoracic sympathetic chain was exposed retropleurally after removing the heads of the second to fourth ribs. The preganglionic inputs to the chain from segments T1-T3 and the trunk distal to T3 were marked for later sectioning. CSNA was recorded conventionally, amplified, rectified and smoothed. Its mean level was quantified before and after each preganglionic input was cut, usually in rostro-caudal sequence. The level after all inputs were cut (i.e. noise and residual ECG pickup) was subtracted from previous measurements. The signal decrement from cutting each preganglionic input was then calculated as a percentage. CSNA in all rats depended on preganglionic drive from two or more segments, which were not always contiguous. Over the population, most preganglionic drive came from T3 and below, while the least came from T1. But there was striking inter-individual variation, such that the strongest drive to CSNA in any one rat could come from T1, T2, T3, or below T3. These findings provide new functional data on the segmental origins of CSNA in rats.


Low-spatial-coherence high-radiance broadband fiber source for speckle free imaging.
We design and demonstrate a fiber-based amplified spontaneous emission (ASE) source with low spatial coherence, low temporal coherence, and high power per mode. ASE is produced by optically pumping a large gain core multimode fiber while minimizing optical feedback to avoid lasing. The fiber ASE source provides 270 mW of continuous wave emission, centered at λ=1055 nm, with a full width at half-maximum bandwidth of 74 nm. The emission is distributed among as many as ∼70 spatial modes, enabling efficient speckle suppression when combined with spectral compounding. Finally, we demonstrate speckle-free full-field imaging using the fiber ASE source. The fiber ASE source provides a unique combination of high power per mode with both low spatial and low temporal coherence, making it an ideal source for full-field imaging and ranging applications.


Retinoid acid supports granulocytic but not erythroid differentiation of myeloid progenitors in normal bone marrow cells.
In the new context of the use of retinoic acid (RA) therapy as an inducer of leukemic differentiation and a selective inhibitor of human myeloid leukemia cell growth, we undertook to explore the potential physiological role of retinoids on the proliferation and differentiation of normal bone marrow myeloid progenitors. The effects of continuous exposure of all-trans-RA, its naturally occurring isomer, 13-cis-RA, and its metabolite 4-oxo-all-trans-RA were studied on the growth of normal human bone marrow cells in soft agar, directly and after liquid culture. Retinoids enhanced the total number of granulocytic colony and macrocluster formation in the presence of exogenous colony-stimulating factor (n = 9). Dose-response curve were bell-shaped, with a maximal increment between concentration of 0.5 and 0.05 nM. In all cases, a concomitant decrease of macrophagic colonies was noted. The positive effect on granulocytic colony formation was observed with each of the retinoids tested (all-trans, 13-cis and 4-oxo-all-trans) (n = 5). On erythroid colony formation, all-trans-RA had the opposite effect. Constant suppression of CFU-E and BFU-E colony formation and coloring was observed in a dose-related fashion from 0.1 to 10 microM (n = 5). Thus, in granulocytic, as in erythroid colony formation, retinoids affected both proliferation and differentiation parameters. However, after short-term suspension culture in the presence of all-trans-RA, an increase of both CFU-GM and BFU-E colonies, was observed. These results suggest a specific effect of retinoids on late myeloid precursors and places retinoids as possible candidates for enhancement of normal granulocytic differentiation.


Idiopathic primary intraventricular hemorrhage and cerebral small vessel disease.
Although primary intraventricular hemorrhage is frequently due to trauma or vascular lesions, the etiology of idiopathic primary intraventricular hemorrhage (IP-IVH) is not defined. Herein, we test the hypothesis that cerebral small vessel diseases (cSVD) including hypertensive cSVD (HTN-cSVD) and cerebral amyloid angiopathy are associated with IP-IVH. Brain magnetic resonance imaging from consecutive patients (January 2011 to September 2019) with non-traumatic intracerebral hemorrhage from a single referral center were reviewed for the presence of HTN-cSVD (defined by strictly deep or mixed-location intracerebral hemorrhage/cerebral microbleeds) and cerebral amyloid angiopathy (applying modified Boston criteria). Forty-six (4%) out of 1276 patients were identified as having IP-IVH. Among these, the mean age was 74.4 ± 12.2 years and 18 (39%) were females. Forty (87%) had hypertension, and the mean initial blood pressure was 169.2 ± 40.4/88.8 ± 22.2 mmHg. Of the 35 (76%) patients who received a brain magnetic resonance imaging, two (6%) fulfilled the modified Boston criteria for possible cerebral amyloid angiopathy and 10 (29%) for probable cerebral amyloid angiopathy. Probable cerebral amyloid angiopathy was found at a similar frequency when comparing IP-IVH patients to the remaining patients with primary intraparenchymal hemorrhage (P-IPH) (27%, p = 0.85). Furthermore, imaging evidence for HTN-cSVD was found in 8 (24%) patients with IP-IVH compared to 209 (28%, p = 0.52) patients with P-IPH. Among IP-IVH patients, cerebral amyloid angiopathy was found in approximately one-third of patients, whereas HTN-cSVD was detected in 23%-both similar rates to P-IPH patients. Our results suggest that both cSVD subtypes may be associated with IP-IVH.


Adenovirus type 12-specific RNA sequences during productive infection of KB cells.
The complementary strands of adenovirus type 12 DNA were separated, and virus-specific RNA was analyzed by saturation hybridization in solution. Late during infection whole cell RNA hybridized to 75% of the light (1) strand and 15% of the heavy (H) strand, whereas cytoplasmic RNA hybridized to 65% of the 1 strand and 15% of the h strand. Late nuclear RNA hybridized to about 90% of the 1 strand and at least 36% of the h strand. Double-stranded RNA was isolated from infected cells late after infection, which annealed to greater than 30% of each of the two complementary DNA strands. Early whole cell RNA hybridized to 45 to 50% of the 1 strand and 15% of the h strand, whereas early cytoplasmic RNA hybridized to about 15% of each of the complementary strands. All early cytoplasmic sequences were present in the cytoplasm at late times.


Non-vascular action of calcium blockers in migraine: pupillopharmacological study.
A pupillopharmacological study has been carried out to evaluate the influence of two calcium blockers (CBs), flunarizine and nimodipine, on iris neurotransmission in migraine patients. Pretreatment with an oral dose of flunarizine or nimodipine markedly decreased the mydriasis induced by instillation of tyramine, a noradrenaline releaser. On the contrary, both drugs did not change the mydriasis by conjunctival phenylephrine, a postsynaptic adrenoceptor stimulant. In addition, nimodipine abolished the miosis caused by echothiophate iodide eye drops, a putative releaser of substance P from trigeminal sensory nerve endings. These findings suggest the idea that CBs treatment in migraine syndromes acts at presynaptic level by attenuating calcium-dependent release of monoaminergic and peptidergic neurotransmitters.


Regional cancer pain syndromes.
Cancer pain often presents in a body region. This review summarizes articles from 1999-2004 relevant to cancer pain syndromes in the head and neck, chest, back, abdomen, pelvis, and limbs. Although the evidence is limited, progress is being made in further development of the evidence base to support and guide current practice.


Cytomegalovirus Identification in Blood and Urine of Newborns by Nested Polymerase Chain Reaction.
To study the frequency of congenital cytomegalovirus (CMV) infection in newborns admitted to the Division of Neonatology, using nested polymerase chain reaction (PCR) and DNA to detect differences in blood and urine specimens. The study was carried out for eight months. Newborns (n = 520) hospitalized in five hospitals in Campo Grande, Mato Grosso do Sul, Brazil, were checked for CMV by analysing blood and urine samples. Cytomegalovirus was PCR positive in 13 urine and 10 blood samples. Of the 13 positive urine patients, three (23%) had no clinical signs suggestive of CMV, and another three (23%) patients admitted to the neonatal intensive care unit (NICU) had no definite findings of bacterial infection, with negative blood culture and some clinical signs consistent with CMV as cholestasis, hepatomegaly and eosinophilia. Three patients were on mechanical ventilation and showed improvement after prescription of ganciclovir. One CMV positive child progressed to death. Cytomegalovirus detection in urine was slightly more efficient than in blood, and showed better sensitivity than in serological analysis (p < 0.01) therefore, boiled urine may be a better and easier specimen tool for CMV diagnosis in neonatal infection. The findings of the present research suggest that patients admitted to the NICU, especially premature infants, whose laboratory results are not compatible with bacterial infection, and exhibiting signs suggestive of CMV infection should have PCR done on urine for confirmation.


FBW7 inhibits nucleus pulposus cells proliferation by downregulation of cyclin E in the intervertebral disc degeneration.
The article "FBW7 inhibits nucleus pulposus cells proliferation by downregulation of cyclin E in the intervertebral disc degeneration, by J.-W. Xu, J. Wang, K. Yang, S. Guo, C.-S. Feng, H.-Y. Chen, H.-P. Li, published in Eur Rev Med Pharmacol Sci 2020; 24(2):508-516. DOI: 10.26355/eurrev_202001_20026. PMID: 32016952" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.


The bronchial tree and lobular division of the dog lung.
The right lung of the dog consists of the cranial, middle, caudal and accessory lobes. The left lung consists of the bilobed middle and caudal lobes. These lobes are separated by interlobular fissures on either side. The dog lung has four bronchiole systems, dorsal, lateral, ventral and medial, on either side. The right cranial lobe is formed by the first bronchiole of the dorsal bronchiole system. The right middle lobe is formed by the first bronchiole of the lateral bronchiole system, and the right accessory lobe is formed by the first bronchiole of the ventral bronchiole system. The remaining bronchioles of the dorsal, lateral and ventral bronchiole systems and all the bronchioles of the medial bronchiole system constitute the right caudal lobe. In the left lung, the left middle lobe is formed by the first bronchiole of the lateral bronchiole system. The remaining bronchioles of the lateral bronchiole system and all the bronchioles of the dorsal, ventral and medial bronchiole systems constitute the left caudal lobe. These findings are compared with those in other domestic animals and man.


Screening for hearing loss in childhood: issues, evidence and current approaches in the UK.
Until recently, screening for childhood hearing loss in the UK was based on two universal (i.e. whole population) screens: the infant distraction test screen at age eight months and the school entry hearing screen at age four to five years. Evidence reviewed in the 1990s indicated that the infant distraction test screen was seriously underperforming, but that (based on technology that had become available in the 1980s and 1990s) universal newborn hearing screening could be efficacious. At the same time, evidence was emerging on the importance and value of very early identification and intervention for permanent congenital childhood hearing loss. This led to the decision to implement a national newborn hearing screening programme (NHSP) in England and to phase out the distraction test at eight months. The initial implementation of the programme will be completed in 2005, and we summarize the evidence on the effectiveness of the first phase of the programme here. A number of important issues concerning childhood hearing loss and its management remain unresolved: the burden of late-onset and temporary childhood hearing losses, the most effective approaches to intervention and management, the case for screening for mild and/or unilateral hearing loss, and the role of the School entry screen. Some of the current research efforts to address these are outlined.


Immunohistochemistry.
The use of the ABC technique, in which an avidin-biotin interaction is used for immunohistochemical studies, is a simple and straightforward procedure. All required reagents are commercially available. The main advantages of this technique are its sensitivity, specificity, and flexibility. It is crucial for the success of this staining procedure that the antibodies, the type of tissues, and the fixatives that are used be selected properly. The method can easily be adapted for electron microscopy, flow cytometry, in situ hybridization, Western blotting, and ELISA.


Reduced Hip Adduction Is Associated With Improved Function After Movement-Pattern Training in Young People With Chronic Hip Joint Pain.
Study Design Ancillary analysis, time-controlled randomized clinical trial. Background Movement-pattern training (MPT) has been shown to improve function among patients with chronic hip joint pain (CHJP). Objective To determine the association among treatment outcomes and mechanical factors associated with CHJP. Methods Twenty-eight patients with CHJP, 18 to 40 years of age, participated in MPT, either immediately after assessment or after a wait-list period. Movement-pattern training included task-specific training to reduce hip adduction motion during functional tasks and hip muscle strengthening. Hip-specific function was assessed using the Modified Harris Hip Score (MHHS) and Hip disability and Osteoarthritis Outcome Score (HOOS). Three-dimensional kinematic data were used to quantify hip adduction motion, dynamometry to quantify abductor strength, and magnetic resonance imaging to measure femoral head sphericity using the alpha angle. Paired t tests assessed change from pretreatment to posttreatment. Spearman correlations assessed associations. Results There was significant improvement in MHHS and HOOS scores (P≤.02), adduction motion (P = .045), and abductor strength (P = .01) from pretreatment to posttreatment. Reduction in hip adduction motion (r = -0.67, P<.01) and lower body mass index (r = -0.38, P = .049) correlated with MHHS improvement. Alpha angle and abductor strength change were not correlated with change in MHHS or HOOS scores. Conclusion After MPT, patients reported improvements in pain and function that were associated with their ability to reduce hip adduction motion during functional tasks. Level of Evidence Therapy, level 2b. J Orthop Sports Phys Ther 2018;48(4):316-324. doi:10.2519/jospt.2018.7810.


Sonic hedgehog signaling: A conserved mechanism for the expansion of outer radial glia and intermediate progenitor cells and for the growth and folding of the neocortex.
The expansion of outer radial glia (oRGs, also called basal RGs) and intermediate progenitor cells (IPCs) has played a key role in the evolutionary expansion and folding of the neocortex, resulting in superior sensorimotor and cognitive abilities. In particular, oRGs, which are critical for both the increased production and lateral dispersion of neurons, are rare in lisencephalic species but vastly expanded in gyrencephalic species. However, the mechanisms that expand oRGs and IPCs are not well understood. We recently identified Sonic hedgehog (Shh) signaling as the first known signaling pathway necessary and sufficient to expand both oRGs and IPCs. Elevated Shh signaling in the embryonic neocortex leads to neocortical expansion and folding with normal cytoarchitecture in otherwise smooth mouse neocortex, whereas the loss of Shh signaling decreases oRGs, IPCs, and neocortical size. We also showed that SHH signaling activity in fetal neocortex is stronger in humans than in mice and that blocking SHH signaling decreases oRGs in human cerebral organoids. Shh signaling may be a conserved mechanism that promotes oRG and IPC expansion, driving neocortical growth and folding in humans and other species. Understanding the mechanisms underlying species-specific differences in Shh signaling activity and how Shh signaling expands oRGs and IPCs will provide insights into the mechanisms of neocortical development and evolution.


Entropy loading for capacity maximization of RGB-based visible light communications.
In this work, we propose and experimentally demonstrate an entropy loading technique based on probabilistic constellation shaping for a visible light communication (VLC) system. The aggregated achievable bit rate of a multi-carrier signal is maximized, considering a given pre-estimated signal-to-noise ratio. A study of the ideal number of subcarriers and signal bandwidth was performed using multiplexed red, green and blue lasers diodes with a bandwidth of 1 GHz. With a 20 degree optical diffuser, the communication system is able to cover a wide area at a free-space distance of 0.90 m, while achieving a record aggregate bit rate of 31.2 Gbit/s for single-polarization RGB-VLC systems.