Regional coronary endothelial dysfunction is related to the degree of local epicardial fat in people with HIV.
Coronary artery disease (CAD) is now an important cause of premature death in people with HIV but the causes of accelerated CAD are poorly understood. Epicardial adipose tissue (EAT) is metabolically-active and thought to contribute to CAD development. We tested the hypothesis that abnormal coronary endothelial function (CEF), an early marker and mediator of atherosclerosis, is related to the amount of local pericoronary EAT in HIV. We studied 36 participants with HIV and no CAD (HIV+ CAD-), 15 participants with HIV and known CAD (HIV+ CAD+), and 14 age-matched, healthy participants without HIV (HIV-CAD-). To measure CEF, coronary MRI was performed before and during isometric handgrip exercise (IHE), an endothelial-dependent stressor. EAT was measured with MRI at the same imaging plane as CEF. CEF was significantly depressed, as measured by IHE-induced % coronary cross sectional area (CSA) change, in HIV+ CAD- and HIV+ CAD+ as compared to HIV-CAD-participants (p<0.0001). EAT thickness was significantly greater in HIV+ CAD- and HIV+ CAD+ participants as compared to HIV-CAD-participants (p=0.001). There was a significant inverse relationship between CEF and local EAT thickness and area (R = -0.48 and R = -0.51 respectively, p<0.0001 for both) among participants with HIV even after adjustment for cardiovascular risk factors. In participants with multiple CEF measures, CEF was lower in segments with higher EAT, other factors being equivalent. There is a significant relationship between increased metabolically-active EAT and depressed local CEF in people with HIV, consistent with the hypothesis that increased epicardial fat contributes to accelerated CAD in persons with HIV.


Dopamine D2 receptors in the rat brain: autoradiographic visualization using a high-affinity selective agonist ligand.
The non-catechol, selective dopamine D2-agonist compound 3H-205-502 was used to localize dopamine D2 receptors by autoradiography after in vitro labeling of brain sections. The characteristics of the binding of this ligand to tissue sections were those expected from the labeling of dopamine D2 receptors. The binding of 3H-205-502 was inhibited selectively and stereospecifically by dopamine D2 agents but not by dopamine D1 compounds. The autoradiographic localization of 3H-205-502 binding sites showed high densities of dopamine D2 receptors in areas such as the glomerular layer of the olfactory bulb, the nucleus accumbens, caudate-putamen, olfactory tubercle, the lateral septum, and the islands of Calleja. Besides these dopamine-innervated areas the substantia nigra and the ventral tegmental area also showed important receptor densities. Other areas where dopamine D2 receptor binding was found were the stratum lacunosum-moleculare of the hippocampus, bands of labeling in the molecular layer of the 9th and 10th lobules of the cerebellum, and several components of the visual system. This distribution presents similarities and differences with previously reported distributions of dopamine D2 receptors visualized autoradiographically using 3H-labeled agonists and antagonists. In view of the high affinity, guanine nucleotide insensitivity, and dopamine D2 selectivity of this agonist ligand, it is suggested that dopamine D2 receptors exist in different states in different areas. 3H-205-502 appears to be a new and useful tool for the study of dopamine D2 receptors.


Orientation of the v-erb-B gene product in the plasma membrane.
The retroviral oncogene v-erb-B encodes a truncated version of the receptor for epidermal growth factor. To define the disposition of the v-erb-B protein within cells and across the plasma membrane, we raised antibodies against defined epitopes in the protein and used these in immunofluorescence to analyze cells transformed by v-erb-B. A small fraction of the v-erb-B protein was found on the plasma membrane in a clustered configuration. The bulk of the protein was located in the endoplasmic reticulum and Golgi apparatus. Epitopes near the amino terminus of the v-erb-B protein were displayed on the surface of the cell, whereas epitopes in the protein kinase domain were located exclusively within cells. We conclude that the v-erb-B protein spans the plasma membrane in a manner similar or identical to that of the epidermal growth factor receptor, even though the viral transforming protein does not possess the signal peptide that is thought to direct insertion of the receptor into the membrane.


Unplanned readmission after traumatic injury: A long-term nationwide analysis.
Long-term outcomes after trauma admissions remain understudied. We analyzed the characteristics of inpatient readmissions within 6 months of an index hospitalization for traumatic injury. Using the 2010 to 2015 Nationwide Readmissions Database, which captures data from up to 27 US states, we identified patients at least 15 years old admitted to a hospital through an emergency department for blunt trauma, penetrating trauma, or burns. Exclusion criteria included hospital transfers, patients who died during their index hospitalizations, and hospitals with fewer than 100 trauma patients annually. After calculating the incidences of all-cause, unplanned inpatient readmissions within 1 month, 3 months, and 6 months, we used multivariable logistic regression models to identify predictors of readmissions. Analyses adjusted for patient, clinical, and hospital factors. Among 2,763,890 trauma patients, the majority had blunt injuries (92.5%), followed by penetrating injuries (6.2%) and burns (1.5%). Overall, rates of inpatient readmissions were 11.1% within 1 month, 21.6% within 6 months, and 29.8% within 6 months, with limited variability by year. After adjustment, the following were associated with all-cause 6 months inpatient readmissions: male sex (adjusted odds ratio [aOR], 1.10; 95% confidence interval [95% CI], 1.09-1.10), comorbidities (aOR, 1.21; 95% CI, 1.21-1.22), low-income quartiles (first and second) (aOR, 1.08; 95% CI, 1.07-1.10 and aOR, 1.04; 95% CI, 1.03-1.06, respectively), Medicare (aOR, 1.65; 95% CI, 1.62-1.69), Medicaid (aOR, 1.51; 95% CI, 1.48-1.53), being treated at private, investor-owned hospitals (aOR, 1.15; 95% CI, 1.12-1.18), longer hospital length of stay (aOR, 1.01; 95% CI, 1.01-1.01) and patient disposition to short-term hospital (aOR, 1.55; 95% CI, 1.49-1.62), skilled nursing facility (aOR, 1.43; 95% CI, 1.42-1.45), home health care (aOR, 1.27; 95% CI, 1.25-1.28), or leaving against medical advice (aOR, 1.85; 95% CI, 1.78-1.92). Unplanned readmission after trauma is high and remains this way 6 months after discharge. Understanding the factors that increase the odds of readmissions within 1 month, 3 months, and 6 months offer a focus for quality improvement and have important implications for hospital benchmarking. Epidemiological study, level III.


Chemical Vapor Deposition-Fabricated Manganese-Doped and Potassium-Doped Hexagonal Tungsten Trioxide Nanowires with Enhanced Gas Sensing and Photocatalytic Properties.
Owing to its unique and variable lattice structure and stoichiometric ratio, tungsten oxide is suitable for material modification; for example, doping is expected to improve its catalytic properties. However, most of the doping experiments are conducted by hydrothermal or multi-step synthesis, which is not only time-consuming but also prone to solvent contamination, having little room for mass production. Here, without a catalyst, we report the formation of high-crystallinity manganese-doped and potassium-doped tungsten oxide nanowires through chemical vapor deposition (CVD) with interesting characterization, photocatalytic, and gas sensing properties. The structure and composition of the nanowires were characterized by transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS), respectively, while the morphology and chemical valence were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. Electrical measurements showed that the single nanowires doped with manganese and potassium had resistivities of 1.81 × 0-5 Ω·m and 1.93 × 10-5 Ω·m, respectively. The doping contributed to the phase transition from monoclinic to metastable hexagonal for the tungsten oxide nanowires, the structure of which is known for its hexagonal electron channels. The hexagonal structure provided efficient charge transfer and enhanced the catalytic efficiency of the tungsten oxide nanowires, resulting in a catalytic efficiency of 98.5% for the manganese-doped tungsten oxide nanowires and 97.73% for the potassium-doped tungsten oxide nanowires after four hours of degradation of methylene blue. Additionally, the gas sensing response for 20 ppm of ethanol showed a positive dependence of doping with the manganese-doped and potassium-doped responses being 14.4% and 29.7%, respectively, higher than the pure response at 250 °C. The manganese-doped and potassium-doped tungsten oxide nanowires are attractive candidates in gas sensing, photocatalytic, and energy storage applications, including water splitting, photochromism, and rechargeable batteries.


Identification of motifs that function in the splicing of non-canonical introns.
While the current model of pre-mRNA splicing is based on the recognition of four canonical intronic motifs (5' splice site, branchpoint sequence, polypyrimidine (PY) tract and 3' splice site), it is becoming increasingly clear that splicing is regulated by both canonical and non-canonical splicing signals located in the RNA sequence of introns and exons that act to recruit the spliceosome and associated splicing factors. The diversity of human intronic sequences suggests the existence of novel recognition pathways for non-canonical introns. This study addresses the recognition and splicing of human introns that lack a canonical PY tract. The PY tract is a uridine-rich region at the 3' end of introns that acts as a binding site for U2AF65, a key factor in splicing machinery recruitment. Human introns were classified computationally into low- and high-scoring PY tracts by scoring the likely U2AF65 binding site strength. Biochemical studies confirmed that low-scoring PY tracts are weak U2AF65 binding sites while high-scoring PY tracts are strong U2AF65 binding sites. A large population of human introns contains weak PY tracts. Computational analysis revealed many families of motifs, including C-rich and G-rich motifs, that are enriched upstream of weak PY tracts. In vivo splicing studies show that C-rich and G-rich motifs function as intronic splicing enhancers in a combinatorial manner to compensate for weak PY tracts. The enrichment of specific intronic splicing enhancers upstream of weak PY tracts suggests that a novel mechanism for intron recognition exists, which compensates for a weakened canonical pre-mRNA splicing motif.


BDNF Expression in Cortical GABAergic Interneurons.
Brain-derived neurotrophic factor (BDNF) is a major neuronal growth factor that is widely expressed in the central nervous system. It is synthesized as a glycosylated precursor protein, (pro)BDNF and post-translationally converted to the mature form, (m)BDNF. BDNF is known to be produced and secreted by cortical glutamatergic principal cells (PCs); however, it remains a question whether it can also be synthesized by other neuron types, in particular, GABAergic interneurons (INs). Therefore, we utilized immunocytochemical labeling and reverse transcription quantitative PCR (RT-qPCR) to investigate the cellular distribution of proBDNF and its RNA in glutamatergic and GABAergic neurons of the mouse cortex. Immunofluorescence labeling revealed that mBDNF, as well as proBDNF, localized to both the neuronal populations in the hippocampus. The precursor proBDNF protein showed a perinuclear distribution pattern, overlapping with the rough endoplasmic reticulum (ER), the site of protein synthesis. RT-qPCR of samples obtained using laser capture microdissection (LCM) or fluorescence-activated cell sorting (FACS) of hippocampal and cortical neurons further demonstrated the abundance of BDNF transcripts in both glutamatergic and GABAergic cells. Thus, our data provide compelling evidence that BDNF can be synthesized by both principal cells and INs of the cortex.


Case for diagnosis. Pachydermodactyly.
Pachydermodactyly is a rare and benign form of acquired digital fibromatosis characterized by the expansion of soft tissue around proximal phalanges and interphalangeal joints. The etiology remains unknown, although it is suggested that repetitive mechanic trauma like the interlacing or rubbing of the fingers can lead to skin thickening. We report a case of a young man with skin thickening around interphalangeal joints and compulsive finger manipulation habit. The histopathology disclosed hyperkeratosis, discrete papillomatosis, mild increase of fibroblasts and dermal mucinosis. The lesions regressed partially, after finger manipulation was stopped.


Influence of stem temperature changes on heat pulse sap flux density measurements.
While natural spatial temperature gradients between measurement needles have been thoroughly investigated for continuous heat-based sap flow methods, little attention has been given to how natural changes in stem temperature impact heat pulse-based methods through temporal rather than spatial effects. By modelling the theoretical equation for both an ideal instantaneous pulse and a step pulse and applying a finite element model which included actual needle dimensions and wound effects, the influence of a varying stem temperature on heat pulse-based methods was investigated. It was shown that the heat ratio (HR) method was influenced, while for the compensation heat pulse and Tmax methods changes in stem temperatures of up to 0.002 °C s(-1) did not lead to significantly different results. For the HR method, rising stem temperatures during measurements led to lower heat pulse velocity values, while decreasing stem temperatures led to both higher and lower heat pulse velocities, and to imaginary results for high flows. These errors of up to 40% can easily be prevented by including a temperature correction in the data analysis procedure, calculating the slope of the natural temperature change based on the measured temperatures before application of the heat pulse. Results of a greenhouse and outdoor experiment on Pinus pinea L. show the influence of this correction on low and average sap flux densities.


PKC-theta selectively controls the adhesion-stimulating molecule Rap1.
The antigen-specific interaction of a T cell with an antigen-presenting cell (APC) results in the formation of an immunologic synapse (IS) between the membranes of the 2 cells. beta(2) integrins on the T cell, namely, leukocyte function-associated antigen 1 (LFA-1) and its counter ligand, namely, immunoglobulin-like cell adhesion molecule 1 (ICAM-1) on the APC, critically stabilize this intercellular interaction. The small GTPase Rap1 controls T-cell adhesion through modulating the affinity and/or spatial organization of LFA-1; however, the upstream regulatory components triggered by the T-cell receptor (TCR) have not been resolved. In the present study, we identified a previously unknown function of a protein kinase C- theta (PKC-theta)/RapGEF2 complex in LFA-1 avidity regulation in T lymphocytes. After T-cell activation, the direct phosphorylation of RapGEF2 at Ser960 by PKC- theta regulates Rap1 activation as well as LFA-1 adhesiveness to ICAM-1. In OT-II TCR-transgenic CD4(+) T cells, clustering of LFA-1 after antigen activation was impaired in the absence of PKC- theta. These data define that, among other pathways acting on LFA-1 regulation, PKC- theta and its effector RapGEF2 are critical factors in TCR signaling to Rap1. Taken together, PKC- theta sets the threshold for T-cell activation by positively regulating both the cytokine responses and the adhesive capacities of T lymphocytes.


Myiasis in the neotropical amphibian Hypsiboas beckeri (Anura: Hylidae) by a new species of Lepidodexia (Diptera: Sarcophagidae).
The first case of myiasis in the anuran Hypsiboas beckeri Caramaschi and Cruz by Lepidodexia centenaria n. sp. (subgenus Notochaeta ) is reported, from the Serra da Pedra Branca, Minas Gerais, in southeastern Brazil. The new species differs from closely related species mainly by the straight apex of the phallus, the ventrally broader vesica, and the shape of the juxta and median and lateral styli. The new species appears to be host-specific to H. beckeri and endemic to high-altitude regions of the Brazilian Atlantic Forest, in contrast to the habitat- and host-generalist Lepidodexia (N.) bufonivora .


Extracellular charge adsorption influences intracellular electrochemical homeostasis in amphibian skeletal muscle.
The membrane potential measured by intracellular electrodes, E(m), is the sum of the transmembrane potential difference (E(1)) between inner and outer cell membrane surfaces and a smaller potential difference (E(2)) between a volume containing fixed charges on or near the outer membrane surface and the bulk extracellular space. This study investigates the influence of E(2) upon transmembrane ion fluxes, and hence cellular electrochemical homeostasis, using an integrative approach that combines computational and experimental methods. First, analytic equations were developed to calculate the influence of charges constrained within a three-dimensional glycocalyceal matrix enveloping the cell membrane outer surface upon local electrical potentials and ion concentrations. Electron microscopy confirmed predictions of these equations that extracellular charge adsorption influences glycocalyceal volume. Second, the novel analytic glycocalyx formulation was incorporated into the charge-difference cellular model of Fraser and Huang to simulate the influence of extracellular fixed charges upon intracellular ionic homeostasis. Experimental measurements of E(m) supported the resulting predictions that an increased magnitude of extracellular fixed charge increases net transmembrane ionic leak currents, resulting in either a compensatory increase in Na(+)/K(+)-ATPase activity, or, in cells with reduced Na(+)/K(+)-ATPase activity, a partial dissipation of transmembrane ionic gradients and depolarization of E(m).


Evolution of antimicrobial resistance of Salmonella enteritidis (1972-2005).
With the extensive use of antibiotics in livestock production, surveillance revealed an increase in Salmonella resistance to the commonly used antimicrobials in veterinary and public health. This serious threat to health care is further exacerbated by the limited epidemiological information about the common zoonotic agent, Salmonella enteritidis, required to determine antibiotic therapy. The aim was to characterise the antimicrobial resistance patterns of S. enteritidis isolates across different timelines (1972-2005) with accompanying genetic changes being investigated. Thirty-seven stored S. enteritidis isolates were collected from the Central Veterinary Laboratory, Harare, with antimicrobial susceptibility determined against eight antibiotics. Plasmids were isolated to analyse any genetic variation. An overall significant increase in resistance (p < 0.05) to nalidixic acid (0% - 10%), ampicillin (14.3% - 50%), tetracycline (14.3% - 30%) and erythromycin (71.4% - 100%) was observed across the timeline. However, the highest rates of susceptibility were maintained for gentamicin, sulphamethoxazole-trimethoprim, kanamycin and chloramphenicol. We report an increase in multidrug resistance (MDR) of 14.2% - 50% with an increase in resistotypes and plasmid profiles across the timeline. Eleven plasmid profiles were obtained in the 37 isolates studied with a minority of isolates (21.6%, 8/37) harbouring a 54 kb plasmid, commonly serovar-specific. A concerning increase in antimicrobial resistance to commonly administered drugs was observed across the timeline. The surge in MDR is of great concern and implies the need for consistent antimicrobial stewardship. No correlation was observed between the plasmid and antibiotic profiles.


Three-dimensional deformation of orthodontic brackets.
Braces are used by orthodontists to correct the misalignment of teeth in the mouth. Archwire rotation is a particular procedure used to correct tooth inclination. Wire rotation can result in deformation to the orthodontic brackets, and an orthodontic torque simulator has been designed to examine this wire-bracket interaction. An optical technique has been employed to measure the deformation due to size and geometric constraints of the orthodontic brackets. Images of orthodontic brackets are collected using a stereo microscope and two charge-coupled device cameras, and deformation of orthodontic brackets is measured using a three-dimensional digital image correlation technique. The three-dimensional deformation of orthodontic brackets will be evaluated. The repeatability of the three-dimensional digital image correlation measurement method was evaluated by performing 30 archwire rotation tests using the same bracket and archwire. Finally, five Damon 3MX and five In-Ovation R self-ligating brackets will be compared using this technique to demonstrate the effect of archwire rotation on bracket design.


Tuberculosis in a rural population of South India: a five-year epidemiological study.
Tuberculosis is a serious health problem in India, but because of inadequate facilities for diagnosis in many parts of the country clinical data are incomplete. However, data on prevalence are available from a few sample surveys conducted in the general population during the last two decades. The study reported here provides information on the incidence of infection and disease as well as on the source and fate of cases. The information was obtained by means of surveys, repeated at intervals during 1961-68 in a randomly selected rural population of South India. In each survey, a tuberculin test was given and X-ray and sputum examinations were made. There were virtually no tuberculosis control facilities in the study area, since this was not covered by the national tuberculosis programme at the time.The annual rate of tuberculous infection in previously uninfected children and in adults was found to be about 1%. The incidence of tuberculosis (confirmed by culture) was about 1 per thousand (excluding children below the age of 5 years). About 30% of newly detected cases came from the population uninfected at an earlier survey. The prevalence of disease was four times as high as the incidence. Among cases found in the initial survey one-half died within 5 years and one-fifth continued to excrete bacilli after 5 years. Both infection and disease tended to decline during the observation period, though in an uneven manner that does not permit extrapolation. There was no evidence of an increase in drug-resistance among newly diagnosed cases. The findings of the study could be used in developing epidemetric models to predict the tuberculosis problem and to assess tuberculosis control measures applied in the community.


Repetitive hypoxia rapidly depresses cardio-respiratory responses during active sleep but not quiet sleep in the newborn lamb.
1. Arousal from sleep is an important protective response to hypoxia that becomes rapidly depressed in active sleep (AS) when hypoxia is repeated. This study questioned whether there might also be selective depression of cardio-respiratory responses to hypoxia during AS. 2. Nine newborn lambs (7-22 days of age) were studied over three successive nights. The first and third nights were baseline studies (inspired oxygen fraction, Fi,O2 = 0.21). During the second night, during every epoch of sleep, lambs were exposed to 60 s episodes of isocapnic hypoxia (Fi,O2 = 0.10). 3. During quiet sleep (QS), the probability of arousal in hypoxia exceeded the probability of spontaneous arousal (P < 0.001) throughout repeated exposures to hypoxia. Similarly, there were persisting increases in ventilation (135 +/- 25 %), blood pressure (3 +/- 1 %) and heart rate (3 +/- 1 %). 4. By contrast, rapid depression of all responses occurred during repetitive hypoxia in AS. Thus, the probability of arousal in hypoxia exceeded the probability of spontaneous arousal during the first 10 hypoxia exposures (P < 0.001) but not thereafter. Similarly, during the first 10 exposures to hypoxia, the changes in ventilation (88 +/- 15 %) and blood pressure (5 +/- 1 %) were greater than subsequent responses (P < 0.05). 5. We conclude that, when repeated, hypoxia rapidly becomes ineffective in stimulating protective arousal, ventilatory and blood pressure responses in AS, but not in QS. Selective depression of responses during AS may render the newborn particularly vulnerable to hypoxia in this state.


Word-to-picture recognition is a function of motor components mappings at the stage of retrieval.
Embodied approaches of cognition argue that retrieval involves the re-enactment of both sensory and motor components of the desired remembering. In this study, we investigated the effect of motor action performed to produce the response in a recognition task when this action is compatible with the affordance of the objects that have to be recognised. In our experiment, participants were first asked to learn a list of words referring to graspable objects, and then told to make recognition judgements on pictures. The pictures represented objects where the graspable part was either pointing to the same or to the opposite side of the "Yes" response key. Results show a robust effect of compatibility between objects affordance and response hand. Moreover, this compatibility improves participants' ability of discrimination, suggesting that motor components are relevant cue for memory judgement at the stage of retrieval in a recognition task. More broadly, our data highlight that memory judgements are a function of motor components mappings at the stage of retrieval.


Allergy and Ménière's disease.
Ménière's disease (MD), which by definition is idiopathic, has been ascribed to various causes, including both inhalant and food allergies. Patients with MD report higher rates of allergy history and positive skin or in vitro tests compared to a control group of patients with other otologic diseases and to the general public. Recent immunologic studies have shown higher rates of circulating immune complexes, CD4, and other immunologic components in patients with MD compared to normal controls. Published treatment results have shown benefit from immunotherapy and/or dietary restriction for symptoms of MD in patients with both allergy and MD.


Identification of very small embryonic like (VSEL) stem cells in bone marrow.
Bone marrow (BM) develops in mammals by the end of the second/beginning of the third trimester of gestation and becomes a major hematopoietic organ in postnatal life. The alpha-chemokine stromal derived factor-1 (SDF-1) to CXCR4 (G ai-protein-coupled seven transmembrane-spanning chemokine receptor) axis plays a major role in BM colonization by stem cells. By the end of the second trimester of gestation, BM becomes colonized by hematopoietic stem cells (HSC), which are chemoattracted from the fetal liver in a CXCR4-SDF-1-dependent manner. Whereas CXCR4 is expressed on HSC, SDF-1 is secreted by BM stroma and osteoblasts that line BM cavities. Mounting evidence indicates that BM also contains rare CXCR4(+) pluripotent stem cells (PSC). Recently, our group has identified a population of CXCR4(+) very small embryonic like stem cells in murine BM and human cord blood. We hypothesize that these cells are deposited during development in BM as a mobile pool of circulating PSC that play a pivotal role in postnatal tissue turnover, both of non-hematopoietic and hematopoietic tissues.


Sharing of the home base: a social test in rats.
The open field provides abundant opportunities for a pair of rats to express social interactions. Rats demonstrate social proximity while exploring the open field and also during simultaneous occupancy of a home base (HB). The HB is defined as a place in the field for which rats show a long-term preference, both in terms of occupancy and as a starting and ending point of exploratory excursions. In the present study, the social proximity of pairs of rats treated with phencyclidine (PCP; 2 mg/kg) or saline (Sal), and rats treated with clozapine (CLZ; 1.3 mg/kg) alone or in combination with PCP (CLZ-PCP), was videotaped and analysed algorithmically. PCP was tested for its disruptive effects on social interactions, and CLZ was tested for its ability to reverse some forms of the disruptive effects of PCP. The results showed that PCP reduced the rate of pairs establishing a common HB and shortened social HB occupancy, but had no effect on episodes of social exploration in the field. These findings demonstrate that the antisocial effect of PCP cannot be generalized across the entire spectrum of behavioural states in the open field. CLZ further decreased rather than increased social HB occupancy. This effect was derived from the reduction in rate of pairs establishing a common HB.


Nucleotide sequence and genetic analysis of a 13.1-kilobase-pair Pseudomonas denitrificans DNA fragment containing five cob genes and identification of structural genes encoding Cob(I)alamin adenosyltransferase, cobyric acid synthase, and bifunctional cobinamide kinase-cobinamide phosphate guanylyltransferase.
A 13.1-kb DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contained five different cob genes named cobN to cobQ and cobW. Based on the similarity of NH2-terminal sequences and molecular weights of the purified Cob proteins, CobQ was identified as cobyric acid synthase, CobP was identified as a bifunctional enzyme exhibiting both cobinamide kinase and cobinamide phosphate guanylyltransferase activities, and CobO was identified as cob(I)alamin adenosyltransferase. CobN is proposed to play a role in cobalt insertion reactions. Four other open reading frames were identified on the 13.1-kb fragment, but their chromosomal inactivation did not lead to a cobalamin-minus phenotype.


Peroxidasin Deficiency Re-programs Macrophages Toward Pro-fibrolysis Function and Promotes Collagen Resolution in Liver.
During liver fibrosis, tissue repair mechanisms replace necrotic tissue with highly stabilized extracellular matrix proteins. Extracellular matrix stabilization influences the speed of tissue recovery. Here, we studied the expression and function of peroxidasin (PXDN), a peroxidase that uses hydrogen peroxide to cross-link collagen IV during liver fibrosis progression and regression. Mouse models of liver fibrosis and cirrhosis patients were analyzed for the expression of PXDN in liver and serum. Pxdn-/- and Pxdn+/+ mice were either treated with carbon tetrachloride for 6 weeks to generate toxin-induced fibrosis or fed with a choline-deficient L-amino acid-defined high-fat diet for 16 weeks to create nonalcoholic fatty liver disease fibrosis. Liver histology, quantitative real-time polymerase chain reaction, collagen content, flowcytometry and immunostaining of immune cells, RNA-sequencing, and liver function tests were analyzed. In vivo imaging of liver reactive oxygen species (ROS) was performed using a redox-active iron complex, Fe-PyC3A. In human and mouse cirrhotic tissue, PXDN is expressed by stellate cells and is secreted into fibrotic areas. In patients with nonalcoholic fatty liver disease, serum levels of PXDN increased significantly. In both mouse models of liver fibrosis, PXDN deficiency resulted in elevated monocyte and pro-fibrolysis macrophage recruitment into fibrotic bands and caused decreased accumulation of cross-linked collagens. In Pxdn-/- mice, collagen fibers were loosely organized, an atypical phenotype that is reversible upon macrophage depletion. Elevated ROS in Pxdn-/- livers was observed, which can result in activation of hypoxic signaling cascades and may affect signaling pathways involved in macrophage polarization such as TNF-a via NF-kB. Fibrosis resolution in Pxdn-/- mice was associated with significant decrease in collagen content and improved liver function. PXDN deficiency is associated with increased ROS levels and a hypoxic liver microenvironment that can regulate recruitment and programming of pro-resolution macrophages. Our data implicate the importance of the liver microenvironment in macrophage programming during liver fibrosis and suggest a novel pathway that is involved in the resolution of scar tissue.


Hybridization of antisense oligonucleotides with alpha-sarcin loop region of Escherichia coli 23S rRNA.
Binding of complementary oligonucleotides (ONs) with alpha-sarcin loop region (2638-2682) of Escherichia coli 23S rRNA was investigated. Four of the tested pentadecanucleotides efficiently bound to target sequences with association rate and equilibrium constants approximately 10(3) M(-1)s(-1) and 10(7) M(-1), respectively. ON S5 (CGAGAGGACCGGAGU) complementary to the sequence 2658-2672 displayed the highest affinity to the target. Activation energy for binding of ON S5 was measured to be 11 kcal/mol; this value corresponds to approximately 10% of the calculated enthalpy of the local RNA structure unfolding in the presence of this oligonucleotide. The activation energy value is evidence for the heteroduplex formation to occur via strand displacement pathway; the initiation of heteroduplex formation requires disruption of 1-2 base pairs in RNA hairpin.


Multimodality management of esophageal cancer.
Esophageal cancer is a highly lethal and aggressive disease and a major public health problem worldwide. The incidence of esophageal cancer in the western hemisphere has increased by 400 % in the past few decades (Posner et al. 2011). Surgery is the mainstay of definitive management of esophageal cancer; however, the results of surgery alone have been dismal, with survival rates of approximately 15 to 20 % at 5 years (Hingorani et al., Clin Oncol 23:696-705, 2011). The last three decades have seen growing interest in various adjuvant and neoadjuvant treatment strategies, with an aim to improve disease control and overall survival. However, due to conflicting and often contradictory results, there was controversy on the ideal treatment paradigm. Recent evidence suggests an improvement in overall survival with neoadjuvant therapy, both chemotherapy and chemoradiotherapy, over surgery. In this review we address various issues concerning multimodality management of locally advanced esophageal cancers: Does neoadjuvant therapy offer a definite benefit over surgery alone? If so, which neoadjuvant strategy? Does the survival benefit outweigh the increased treatment related toxicity/morbidity? Finally, is neoadjuvant treatment the standard of care for locally advanced resectable esophageal cancer?


Neuropsychological Clustering in Bipolar and Major Depressive Disorder.
Cognitive dysfunction is a key feature of major depressive (MDD) and bipolar (BD) disorders. However, rather than a single cognitive profile corresponding to each diagnostic categories, recent studies have identified significant intra- and cross-diagnostic variability in patterns of cognitive impairment. The goal of this study was to contribute to the literature on cognitive heterogeneity in mood disorders by identifying cognitive subprofiles in a population of patients with MDD, BD type I, BD type II, and healthy adults. Participants completed a neuropsychological battery; scores were converted into Z-scores using normative data and submitted to hierarchical cluster analysis. Three distinct neuropsychological clusters were identified: (1) a large cluster containing mostly control participants, as well as some patients with BD and MDD, who performed at above-average levels on all neuropsychological domains; (2) a cluster containing some patients from all diagnostic groups, as well as healthy controls, who performed worse than cluster 1 on most tasks, and showed impairments in motor inhibition and verbal fluency; (3) a cluster containing mostly patients with mood disorders with severe impairments in verbal inhibition and cognitive flexibility. These findings revealed multiple cognitive profiles within diagnostic categories, as well as significant cross-diagnostic overlap, highlighting the importance of developing more specific treatment approaches which consider patients' demographic and cognitive profiles in addition to their diagnosis. (JINS, 2017, 23, 584-593).


A combination method for electrocardiogram rejection from surface electromyogram.
The electrocardiogram signal which represents the electrical activity of the heart provides interference in the recording of the electromyogram signal, when the electromyogram signal is recorded from muscles close to the heart. Therefore, due to impurities, electromyogram signals recorded from this area cannot be used. In this paper, a new method was developed using a combination of artificial neural network and wavelet transform approaches, to eliminate the electrocardiogram artifact from electromyogram signals and improve results. For this purpose, contaminated signal is initially cleaned using the neural network. With this process, a large amount of noise can be removed. However, low-frequency noise components remain in the signal that can be removed using wavelet. Finally, the result of the proposed method is compared with other methods that were used in different papers to remove electrocardiogram from electromyogram. In this paper in order to compare methods, qualitative and quantitative criteria such as signal to noise ratio, relative error, power spectrum density and coherence have been investigated for evaluation and comparison. The results of signal to noise ratio and relative error are equal to 15.6015 and 0.0139, respectively.


Functional and Dysfunctional Neuroplasticity in Learning to Cope with Stress.
In this brief review, we present evidence of the primary role of learning-associated plasticity in the development of either adaptive or maladaptive coping strategies. Successful interactions with novel stressors foster plasticity within the neural circuits supporting acquisition, consolidation, retrieval, and extinction of instrumental learning leading to development of a rich repertoire of flexible and context-specific adaptive coping responses, whereas prolonged or repeated exposure to inescapable/uncontrollable stressors fosters dysfunctional plasticity within the learning circuits leading to perseverant and inflexible maladaptive coping strategies. Finally, the results collected using an animal model of genotype-specific coping styles indicate the engagement of different molecular networks and the opposite direction of stress effects (reduced vs. enhanced gene expression) in stressed animals, as well as different behavioral alterations, in line with differences in the symptoms profile associated with post-traumatic stress disorder.


Contrast enhancement of the liver. Evaluation by automated contiguous pixel search.
Eight dogs were infused with one of three different contrast agents: meglumine diatrizoate, iosulamide meglumine, or an ethiodized oil emulsion (EOE 13). Image intensity in the liver was evaluated globally and regionally by means of an automated pixel sampling method to determine differences in the rate of enhancement produced by the three agents. The results of the automated method were compared with those of the standard manual cursor method. The automated method showed that liver parenchyma was enhanced uniformly by all three contrast agents. The maximum degree of enhancement (Mean +/- SEM) for the three agents was diatrizoate, 12.0 +/- 3.5 Hounsfield units (HU); iosluamide, 21.3 +/- 3.5 HU; and EOE 13, 37.2 +/- 4.25 HU. With the manual cursor method, contrast enhancement was about 20% more than estimated by the automated method. The automated method is better for evaluating the magnitude and pattern of contrast agent enhancement of the entire liver, since the currently employed cursor technique requires multiple evaluations to evaluate the entire liver.


[School of the rational nutrition for children and adolescents with obesity].
The article presents the principles of the classes organizations in the school of the rational nutrition for children and adolescents with overweight and obesity, and also for their parents. The school consists of six interactive lessons, which explains the negative consequences of obesity, understand the basic principles of optimal diet. Each class has "minilections", that adapted for both children and parents and accompanied by interactive dialogues, which are attended by all family members of children who are overweight or obese. Presented own observational data for 20 families that attended school. A positive result was achieved in 15 families. The article analyzes the reasons that didn't lead to the expected result in 5 families.


[Determination of the size of the myocardial lesion by electrocardiographic and pathologico-anatomic methods].
Precordial mapping was performed in 16 patients with acute anteroseptal myocardial infarction admitted to the clinic within 10 hours after the onset of the disease. Changes in the QRS complex, ST segment, and Q and R waves as well as the total number of points with QS type complexes were appraised on the cartograms. The findings of precordial mapping were compared with the mass and area of the affected tissue determined on autopsy. It was established that the number of QS type complexes recorded on the cartogram is highly informative in appraising the mass of myocardial infarction. The extreme values of the area of the QS complex and R wave correlate well with the area of the affection. The revealed regularities made it possible to deduce a formula for determining the mass of damaged tissue in various degrees of necrosis.


Radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE PET activity.
Our aim was to determine the radiologic and clinicopathologic characteristics of thyroid nodules with focal 68Ga-DOTATATE activity. In this retrospective study of 1927 consecutive 68Ga-DOTATATE PET scans, 85 patients with incidental and nonincidental focal 68Ga-DOTATATE avid thyroid nodules were identified, of which 31 patients with 33 thyroid nodules underwent fine-needle aspiration (FNA) or surgery. These 33 nodules were reviewed for Krenning score and SUVmax of the thyroid nodule, contralateral thyroid lobe and left atrium. Cytology/histopathology included 58% (19/33) with benign findings, 18% (6/33) medullary thyroid carcinoma (MTC), 9% (3/33) atypia or follicular lesion of undetermined significance (AUS/FLUS), 9% (3/33) suspicious for follicular neoplasm and Hurthle cell adenoma (SFN/HCA) and 6% (2/33) nondiagnostic cytology. Median serum calcitonin was 1156 pg/mL (range, 460-1828) in MTC and was <5.0 pg/mL (<5.0-12.5) in patients with benign nodules. Nodules had Krenning score of 1, 2 and 3 in 46% (15/33), 27% (9/33) and 27% (9/33). The majority of MTC and AUS/FLUS nodules had a Krenning score of 3, and there was substantial intragroup variation in Krenning score among the benign nodules. The mean SUVmax for the entire cohort was 5.5 ± 2.9 (mean ± SD), and the range was 2.0-13.0. There was overlap in the nodule/contralateral thyroid SUVmax ratios between groups. The MTC and AUS/FLUS nodules tended to have a higher nodule/blood pool SUVmax ratio than the other pathologic groups. There was considerable variation in radiologic characteristics among benign thyroid nodules. The ratio of thyroid nodule SUVmax/blood pool SUVmax may be useful to differentiate pathologic groups, but larger studies are needed to investigate this further. Given the potential for malignancy in thyroid nodules with focal 68Ga-DOTATATE activity, further evaluation with serum calcitonin and FNA may be considered.Video Abstract: http://links.lww.com/NMC/A186.


A review of nutritional effects on fat composition of animal products with special emphasis on n-3 polyunsaturated fatty acids.
The fatty acid composition of animal products (eggs, milk and meat) is the reflect of both the tissue fatty acid biosynthesis and the fatty acid composition of ingested lipids. This relationship is stronger in monogastrics (pigs, poultry and rabbits) than in ruminants, where dietary fatty acids are hydrogenated in the rumen. There is an increasing recognition of the health benefits of polyunsaturated fatty acids (PUFA), because these fatty acids are essential for humans. In addition, the ratio n-6/n-3 fatty acids in the human diet is important. This ratio by far exceeds the recommended value of 5. Therefore, inclusion of fish meals, or n-3 PUFA rich oils, or linseed in animal diets is a valid means of meeting consumer demand for animal products that are nutritionally beneficial. The studies that are undertaken on animals mainly use diets supplemented with linseed, as a source of n-3 fatty acids. The use of linseed diets generally leads to an increased n-3 fatty acid content in animal products (egg, meat, milk) in ruminants and monogastrics. Recent studies have also demonstrated that neither the processing nor the cooking affects the PUFA content of pork meat or meat products. The ability of unsaturated fatty acids, especially those with more than two double bonds, to rapidly oxidise, is important in regulating the shelf life of animal products (rancidity and colour deterioration); however, a good way to avoid such problems is to use antioxidant products (such as vitamin E) in the diet. Some studies also show that it is not necessary to feed animals with linseed-supplemented diets for a long time to have the highest increase in PUFA content of the products. So, short-term diet manipulation can be a practical reality for industry. As the market for n-3 PUFA enriched products is today limited in most countries, other studies must be undertaken to develop this kind of production.


Correlates of Suicidal Ideation and Behaviors Among Former Military Personnel Not Enrolled in the Veterans Health Administration.
The current study sought to explore suicidal concomitants, both demographic and psychological, among former military personal. The sample included 645 veterans who are at increased risk for suicide but have not yet pursued Veterans Health Administration (VHA) services. Descriptive statistics revealed that these veterans are primarily young Caucasian males who served in the U.S. Army. In terms of psychological characteristics, the current sample reported clinically significant levels of depression, post-traumatic stress, and insomnia. Furthermore, respondents acknowledged use of various substances and high levels of perceived burdensomeness and thwarted belongingness. The demographic and psychological makeup of our sample was somewhat similar to that of VHA-connected veterans except that our sample was slightly more educated and reported less physical pain.


Chlorin p6 as a fluorescent probe for the investigation of surfactant-cyclodextrin interactions.
Cyclodextrins (CD) are often proposed as potential vehicles in targeted drug delivery. However, if the membrane structure is disrupted by CD, then it cannot be considered to be a good drug delivery vehicle. When an extrinsic fluorescence probe is used to monitor such interactions, there are no less than three possible equilibria that can operate simultaneously: surfactant-cyclodextrin, surfactant-fluorophore and cyclodextrin-fluorophore. The fluorescence intensity/lifetime might be affected by all these and so, the results depend strongly on the fluorophore used as well as the nature of the surfactant. This aspect highlights the importance of the suitability of the fluorescence probe to be used to study complicated systems and interaction. In the present work, chlorin p6, prepared from chlorophyll from spinach leaves, has been used as the fluorescence probe to investigate the interaction between alpha-CD and beta-CD with the neutral surfactants Triton X 100 (TX 100) and cetyl trimethyl ammonium bromide (CTAB). The fluorophore is found to be a sensitive one for the study of the interaction of alpha, beta and gamma-CD with the surfactants TX 100 and CTAB. It is found that contrary to earlier reports, a complex between alpha-CD and TX 100 is formed, even though the binding constant is not very high. This observation can be obtained with chlorin p6, which does not bind to the CDs, but not with a fluorophore, which binds to the CD as well and thus complicates the situation as the binding with CD is stronger than that between TX 100 and alpha-CD as compared to that between TNS and CD.


[The outlook for the use of diode laser radiation for trabeculoplasty in treating primary open-angle glaucoma].
Clinical efficacy of diode laser trabeculoplasty is assessed in 35 eyes of 30 patients with primary open-angle glaucoma during during the initial and well-developed stages of diseases. Changes in the anterior segment of the eye, intraocular pressure, ocular hydrodynamics, visual functions, and status of the optic nerve were assessed 6-12 months after the operation. Diode laser trabeculoplasty is characterized by areactive clinical course and leads to a significant decrease of intraocular pressure, stabilizes and improves visual functions, and ameliorates intraocular humor discharge. The treatment runs a smooth course without complications. The method is recommended for clinical practice and further studies.


Force and electromyography responses during isometric force release of different rates and step-down magnitudes.
This study investigated motor responses of force release during isometric elbow flexion by comparing effects of different ramp durations and step-down magnitudes. Twelve right-handed participants (age: 23.1 ± 1.1) performed trajectory tracking tasks. Participants were instructed to release their force from the reference magnitude (REF; 40% of maximal voluntary contraction force) to a step-down magnitude of 67% REF or 33% REF and maintain the released magnitude. Force release was guided by ramp durations of either 1 s or 5 s. Electromyography of the biceps brachii and triceps brachii was performed during the experimental task, and the co-contraction ratio was evaluated. Force output was recorded to evaluate the parameters of motor performance, such as force variability and overshoot ratio. Although a longer ramp duration of 5 s decreased the force variability and overshoot ratio than did shorter ramp duration of 1 s, higher perceived exertion and co-contraction ratio were followed. Force variability was greater when force was released to the step-down magnitude of 33% REF than that when the magnitude was 67% REF, however, the overshoot ratio showed opposite results. This study provided evidence proving that motor control strategies adopted for force release were affected by both duration and step-down magnitude. In particular, it implies that different control strategies are required according to the level of step-down magnitude with a relatively short ramp duration.


Airway and systemic inflammation in obese children with asthma.
Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8-17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.


Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors.
Preconditioning with brief ischemia before a sustained period of ischemia reduces infarct size in the perfused heart. A cultured chick ventricular myocyte model was developed to investigate the role of adenosine receptor subtypes in cardiac preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to prolonged hypoxia, protected myocytes against injury induced by the prolonged hypoxia. Activation of the adenosine A1 receptor with CCPA or the A3 receptor with C1-IB-MECA can replace preconditioning hypoxia and simulate preconditioning, with a maximal effect at 100 nM. While activation of the A2a receptor by 1 microM CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury. Blockade of A2a receptors with the selective antagonist CSC (1 microM) during preconditioning hypoxia enhanced the protective effect of preconditioning. Nifedipine, which blocked the A2a receptor-mediated calcium entry, abolished the A2a agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and BayK 8644, which stimulated calcium entry, also attenuated preconditioning. Nifedipine blocked the increase in calcium uptake by these agents as well as their attenuating effect on preconditioning. The present study provides the first evidence that the adenosine A3 receptor is present on ventricular myocytes and can mediate simulation of preconditioning. The data demonstrate, for the first time, that activation of the A2a receptor antagonizes the preconditioning effect of adenosine, with increased calcium entry during the preconditioning stimuli as a novel mechanism.


Patient-derived xenograft models in gynecologic malignancies.
In the era of targeted therapies, patients with gynecologic malignancies have not yet been major beneficiaries of this new class of agents. This may reflect the fact that the main tumor types-ovarian, uterine, and cervical--are a highly heterogeneous group of cancers with variable response to standard chemotherapies and the lack of models in which to study the diversity of these cancers. Cancer-derived cell lines fail to adequately recapitulate molecular hallmarks of specific cancer subsets and complex microenvironments, which may be critical for sensitivity to targeted therapies. Patient-derived xenografts (PDX) generated from fresh human tumor without prior in vitro culture, combined with whole genome expression, gene copy number, and sequencing analyses, could dramatically aid the development of novel therapies for gynecologic malignancies. Gynecologic tumors can be engrafted in immunodeficient mice with a high rate of success and within a reasonable time frame. The resulting PDX accurately recapitulates the patient's tumor with respect to histologic, molecular, and in vivo treatment response characteristics. Orthotopic PDX develop complications relevant to the clinic, such as ascites and bowel obstruction, providing opportunities to understand the biology of these clinical problems. Thus, PDX have great promise for improved understanding of gynecologic malignancies, serve as better models for designing novel therapies and clinical trials, and could underpin individualized, directed therapy for patients from whom such models have been established.


Dynamic analysis of load carriage biomechanics during level walking.
This paper describes an investigation into the biomechanical effects of load carriage dynamics on human locomotion performance. A whole body, inverse dynamics gait model has been developed which uses only kinematic input data to define the gait cycle. To provide input data, three-dimensional gait measurements have been conducted to capture whole body motion while carrying a backpack. A nonlinear suspension model is employed to describe the backpack dynamics. The model parameters for a particular backpack system can be identified using a dynamic load carriage test-rig. Biomechanical assessments have been conducted based on combined gait and pack simulations. It was found that the backpack suspension stiffness and damping have little effect on human locomotion energetics. However, decreasing suspension stiffness offers important biomechanical advantages. The peak values of vertical pack force, acting on the trunk, and lower limb joint loads are all moderated. This would reduce shoulder strap pressures and the risk of injury when heavy loads are carried.


Multifaceted Prospective Memory Intervention to Improve Medication Adherence.
To test whether a multifaceted prospective memory intervention improved adherence to antihypertensive medications and to assess whether executive function and working memory processes moderated the intervention effects. Two-group longitudinal randomized control trial. Community. Individuals aged 65 and older without signs of dementia or symptoms of severe depression who were self-managing prescribed medication. After 4 weeks of initial adherence monitoring using a medication event monitoring system, individuals with 90% or less adherence were randomly assigned to groups. The prospective memory intervention was designed to provide strategies that switch older adults from relying on executive function and working memory processes (that show effects of cognitive aging) to mostly automatic associative processes (that are relatively spared with normal aging) for remembering to take medications. Strategies included establishing a routine, establishing cues strongly associated with medication taking actions, performing the action immediately upon thinking about it, using a medication organizer, and imagining medication taking to enhance encoding and improve cuing. There was significant improvement in adherence in the intervention group (57% at baseline to 78% after the intervention), but most of these gains were lost after 5 months. The control condition started at 68% and was stable during the intervention, but dropped to 62%. Executive function and working memory moderated the intervention effect, with the intervention producing greater benefit for those with lower executive function and working memory. The intervention improved adherence, but the benefits were not sustained. Further research is needed to determine how to sustain the substantial initial benefits.


Therapeutic Approaches for Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.
Chronic Obstructive Pulmonary Disease (COPD) is a progressive pulmonary disorder underpinned by poorly reversible airflow resulting from chronic bronchitis or emphysema. The prevalence and mortality of COPD continue to increase. Pharmacotherapy for patients with COPD has included antibiotics, bronchodilators, and anti-inflammatory corticosteroids (but with little success). Oral diseases have long been established as clinical risk factors for developing respiratory diseases. The establishment of a very similar microbiome in the mouth and the lung confirms the oral-lung connection. The aspiration of pathogenic microbes from the oral cavity has been implicated in several respiratory diseases, including pneumonia and chronic obstructive pulmonary disease (COPD). This review focuses on current and future pharmacotherapeutic approaches for COPD exacerbation including antimicrobials, mucoregulators, the use of bronchodilators and anti-inflammatory drugs, modifying epigenetic marks, and modulating dysbiosis of the microbiome.


Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries.
Brain natriuretic peptide (BNP), a hormone secreted predominantly in ventricular myocytes, may influence coronary vascular tone. We studied the coronary vasodilatory response to BNP under physiological conditions and after preconstriction with endothelin-1 (ET-1) in anesthetized pigs. Average peak-flow velocity (APV) was measured using intracoronary Doppler, and cross-sectional area (CSA) was measured using intravascular ultrasound. Coronary blood flow (CBF) was calculated. Intracoronary BNP induced dose-dependent increases in CSA, APV, and CBF similar in magnitude to those induced by nitroglycerin (NTG). The magnitude of BNP-induced vasodilation was accentuated after preconstriction with ET-1. Pretreatment with either the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester or the cyclooxygenase inhibitor indomethacin attenuated the coronary vasodilator effect of BNP in resistance arteries without influencing epicardial vasodilation. Pretreatment with the ATP-sensitive potassium-channel blocker glibenclamide enhanced epicardial vasodilation in response to BNP. We conclude that BNP exerts coronary vasodilator effects, predominantly in epicardial conductance vessels. An accentuated vasodilatory response to BNP occurs in ET-1-preconstricted arteries. BNP-induced vasodilation in coronary resistance arteries may be partially mediated via nitric oxide and/or prostaglandin release.


The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to promote the accumulation of SUMO conjugates and the release of infectious virus.
Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) regulates a variety of cellular functions, and is hijacked by viruses to remodel the host cell during latent and productive infection. Here we have monitored the activity of the SUMO conjugation machinery in cells productively infected with Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the late phase of the productive virus cycle, and identified several viral proteins as bone fide SUMOylation substrates. Analysis of the mechanism involved in the accumulation of SUMOylated proteins revealed upregulation of several components of the SUMO-conjugation machinery and post-transcriptional downregulation of the SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1 resistant RNF4 was associated with reduced levels of early and late viral proteins and impaired virus release. These findings illustrate a novel strategy for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1 and the cellular RNF4 as regulators of the productive virus cycle.


Maternal copper supplementation protects the neonatal rat lung against the adverse effects of maternal nicotine exposure.
Maternal nicotine exposure interferes with the extracellular formation of the connective tissue framework of the neonatal lung, a process that is dependent on copper-dependent lysyl oxidase. It has been shown that, during the phase of lung development associated with alveolarization, maternal nicotine exposure resulted in a reduction in the copper content and thus conceivably in the activity of lysyl oxidase of the neonatal lung. Therefore the aims of this study were (a) to determine the effects of maternal nicotine exposure during gestation and lactation on neonatal lung development, and (b) to establish whether maternal copper supplementation during gestation and lactation prevented the effect of maternal nicotine exposure on neonatal lung development. Pregnant rats were randomly divided into four groups: the control group received saline; the second group received 1 mg nicotine (kg bodyweight)(-1) day(-1) subcutaneously; the third group received 1 mg copper (kg bodyweight)(-1) day(-1); and the fourth group received both nicotine and copper in the same quantities as the previous two groups. Lung tissue of 14- and 42-day-old rat pups were processed for light microscopy. Maternal nicotine exposure during gestation and lactation resulted in (a) decreased alveolar number, (b) reduced internal surface area and (c) increased alveolar volume. Copper supplementation during gestation and lactation prevented the adverse effects of maternal nicotine exposure during gestation and lactation on the development of the alveolar region of the rat lung.


University hospitals as drivers of career success: an empirical study of the duration of promotion and promotion success of hospital physicians.
German hospitals have a well-defined career structure for clinicians. In this hierarchical career system university hospital are stepping stones for career advancement. This longitudinal study investigates the impact of working in university hospitals on the career success of junior physicians and senior physicians. Consideration of the career trajectories of 324 hospital physicians. Discrete-time event history analysis is used to study the influence of working in university hospitals on the chance of promotion from junior physician to senior physician and senior physician to chief physician. A comparison of medians provides information about the impact of working in university hospitals on the duration of promotion to senior and chief physician positions. Working in university hospitals has a negative impact for advancement to a senior physician position in terms of promotion duration (p = 0.005) and also in terms of promotion success, where a short time span of just 1-2 years in university hospitals has a negative effect (OR = 0.38, p < 0.01), while working there for a medium or long term has no significant effect. However, working in universities has a positive effect on the duration of promotion to a chief physician position (p = 0.079), and working in university hospitals for 3-4 years increases the chance of promotion to a chief physician position (OR = 4.02, p < 0.05), while working there > =7 years decreases this chance (OR = 0.27, p < 0.05). In addition, physicians have a higher chance of promotion to a chief physician position through career mobility when they come to the position from a university hospital. Working at university hospitals has a career-enhancing effect for a senior physician with ambitions to become a chief physician. For junior physicians on the trajectory to a senior physician position, however, university hospitals are not drivers of career success.


A mathematical approach to best luminance maps.
An algorithm to calculate the best global mapping from color to grayscale is presented. We assert that the best mapping minimizes the difference between the multi-channel local tensor and the tensor of the resultant mono-chromatic image. To minimize the objective function, we represent the grayscale image as a weighted sum of the RGB channels, three channels and their second-order polynomial and three channels and their root polynomial. The optimization searches for the best weights to combine the linear, polynomial, and root polynomial functions. Our results show that the optimal weights can half the root mean square difference between the color gradients and those achieved by the conventional luminance transformation. Further improvement is achieved by adding the squared and root squared channels to the solution. The improvements are also visually evident.


Articular ganglia of the volar aspect of the wrist: arthroscopic resection compared with open excision. A prospective randomised study.
Our aim was to compare two methods of treatment of ganglia on the volar aspect of the wrist (the open excision done through a longitudinal volar skin incision and the arthroscopic resection through two or three dorsal ports), to see if arthroscopy could reduce the risks of operating in this area and the time to healing. Twenty radiocarpal and five midcarpal volar ganglia were operated on by open approach and an equivalent group was treated by arthroscopy. Fifteen radiocarpal and five midcarpal ganglia were treated with good results in the open group and 18 radiocarpal and one midcarpal ganglia in the arthroscopic group (no visible or palpable ganglion, a full range of active wrist movement, grip strength equal to preoperatively, no pain, and a cosmetically acceptable scar). In the open group there were four injuries to a branch of the radial artery, two cases of partial stiffness of the wrist associated with a painful scar, one case of neuropraxia, and one recurrence (all of which were among the 20 radiocarpal ganglia). In the arthroscopic group there was one case of neuropraxia, one injury to a branch of the radial artery, and three recurrences (three of the complications were among the five midcarpal ganglia). The mean functional recovery time was equal to 15 (6) days in the open group and 6 (2) days in the arthroscopic group. The mean time lost from work was equal to 23 (11) days in the open group and 10 (5) days in the arthroscopic group. Our results suggest that arthroscopic resection is a reasonable alternative to open excision in treating radiocarpal volar ganglia because it has less postoperative morbidity and a better cosmetic result. Midcarpal volar ganglia, however, should still be treated by open operation.


Novel quality control strategies for the determination of 25-hydroxyvitamin D by LC-MS/MS.
Mass spectrometry analysis has been applied in many important diagnostic fields of laboratory medicine. However, there is little literature to guide quality management systems for LC-MS/MS methods. In this study, LC-MS/MS 25-hydroxyvitamin D (25(OH)D) was used as an example to establish internal quality control strategies to ensure the accuracy of clinical vitamin D results. A total of 141 batches of samples were analyzed. Sample internal standard peak area variability, ion pair ratio, and physical examination population data were monitored as quality control strategies for 25(OH)D results. The analytical performance was evaluated by calculated Sigma metrics. Applying our quality control strategies, several abnormal data were monitored in the routine analysis. The daily peak area CV of 25(OH)D fluctuated within a certain range. By selecting P99 CV as the control target, two abnormal batches were found. The ratio of 25(OH)VD3 ion pairs was relatively stable. Among them, batch20230120 had a high CV value, which may be due to the bias caused by the limited number. According to the physical examination data, batch20220913 and batch20220919 exceeded the alarm limit. Sigma level of 25(OH)VD3 in the laboratory was 6.52, which achieved "excellent" performance. In conclusion, we established comprehensive quality control strategies for the determination of 25(OH)D by LC-MS/MS, which has high analytical performance and can provide more accurate reports for the clinic.


Mean platelet volume in patients with prehypertension and hypertension.
Patients with hypertension have evidence of platelet activation. Mean platelet volume (MPV), an indicator of platelet activation has been shown to be elevated in patients with hypertension. Prehypertension is also associated with an increase in cardiovascular morbidity and mortality. The aim of this study was to assess the MPV in patients with prehypertension and hypertension. This study included newly diagnosed and untreated 87 prehypertensive patients, 30 hypertensive patients and 35 normotensive control subjects matched for age, gender, and body mass index. All patients and controls gave informed consent. The MPV values of patients with prehypertension and hypertension were significantly higher than those of the control group (8.4 +/- 0.8 and 8.8 +/- 0.7 versus 7.9 +/- 0.5 fl; p < 0.05 and p < 0.001 respectively). It was also higher in hypertensives than in prehypertensives (8.8 +/- 0.7 versus 8.4 +/- 0.8 fl; p < 0.05). However, we found that the presence of the hypertension (beta = 0.28, P = 0.003) was only significant predictors of higher MPV in a multivariable model that adjusted for other variables. We have shown that, MPV, an indicator of platelet activation was significantly higher in patients with prehypertension and hypertension when compared with control subjects. We have also showed that MPV was also higher in patients with hypertension than in patients with prehypertension. However, presence of the hypertension was only significant predictor of higher MPV.


ABrox-A user-friendly Python module for approximate Bayesian computation with a focus on model comparison.
We give an overview of the basic principles of approximate Bayesian computation (ABC), a class of stochastic methods that enable flexible and likelihood-free model comparison and parameter estimation. Our new open-source software called ABrox is used to illustrate ABC for model comparison on two prominent statistical tests, the two-sample t-test and the Levene-Test. We further highlight the flexibility of ABC compared to classical Bayesian hypothesis testing by computing an approximate Bayes factor for two multinomial processing tree models. Last but not least, throughout the paper, we introduce ABrox using the accompanied graphical user interface.


Representation of visual scenes by local neuronal populations in layer 2/3 of mouse visual cortex.
How are visual scenes encoded in local neural networks of visual cortex? In rodents, visual cortex lacks a columnar organization so that processing of diverse features from a spot in visual space could be performed locally by populations of neighboring neurons. To examine how complex visual scenes are represented by local microcircuits in mouse visual cortex we measured visually evoked responses of layer 2/3 neuronal populations using 3D two-photon calcium imaging. Both natural and artificial movie scenes (10 seconds duration) evoked distributed and sparsely organized responses in local populations of 70-150 neurons within the sampled volumes. About 50% of neurons showed calcium transients during visual scene presentation, of which about half displayed reliable temporal activation patterns. The majority of the reliably responding neurons were activated primarily by one of the four visual scenes applied. Consequently, single-neurons performed poorly in decoding, which visual scene had been presented. In contrast, high levels of decoding performance (>80%) were reached when considering population responses, requiring about 80 randomly picked cells or 20 reliable responders. Furthermore, reliable responding neurons tended to have neighbors sharing the same stimulus preference. Because of this local redundancy, it was beneficial for efficient scene decoding to read out activity from spatially distributed rather than locally clustered neurons. Our results suggest a population code in layer 2/3 of visual cortex, where the visual environment is dynamically represented in the activation of distinct functional sub-networks.


Sedentary behaviour, physical activity, and renal function in older adults: isotemporal substitution modelling.
Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. In 174 older Japanese adults (age, 50-83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour (rs = - 0.229), LPA (rs = 0.265), and MVPA (rs = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR (β = 2.26, p = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR (β = 5.49, p < 0.05). These cross-sectional findings suggest that sedentary behaviour (detrimentally) and physical activity (beneficially) may affect renal function and that replacing sedentary behaviour with MVPA may benefit renal health in older adults.


Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.
Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or µg/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 µg/ml and vitamin E at 2500 µmol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E.


Delayed Photoluminescence and Modified Blinking Statistics in Alumina-Encapsulated Zero-Dimensional Inorganic Perovskite Nanocrystals.
We demonstrate enhancement of the photoluminescence (PL) properties of individual zero-dimensional (0D) Cs4PbBr6 perovskite nanocrystals (PNCs) upon encapsulation by alumina using an appropriately modified atomic layer deposition method. In addition to the increased PL intensity and improved long-term stability of encapsulated PNCs, our single-particle studies reveal substantial changes in the PL blinking statistics and the persistent appearance of the long-lived, "delayed" PL components. The blinking patterns exhibit a modification from the fast switching between fluorescent ON and OFF states found in bare PNCs to a behavior with longer ON states and more isolated OFF states in alumina-encapsulated PNCs. Controlled exposure of 0D nanocrystals to moisture suggests that the observed PL lifetime changes may be related to water-induced "reservoir" states that allow for longer-lived charge storage with subsequent back-feeding into the emissive states. Viable encapsulation of PNCs with metal oxides that can preserve and even enhance their PL properties can be utilized in the fabrication of extended structures on their basis for optoelectronic and photonic applications.


Human tubal fluid: production, nutrient composition and response to adrenergic agents.
Vascularly perfused Fallopian tubes have been used to study the formation and composition of human tubal fluid and the response to adrenergic agents. An artery serving the tube was cannulated and perfused with Medium 199 supplemented with bovine serum albumin (BSA) and antibiotics. A second cannula was attached to the fimbriated end for native tubal fluid collection. The preparation was viable for up to 2 h. Tubal fluid was only obtained in tubes removed in the proliferative and early secretory phases of the ovarian cycle. Isoproterenol (1 mM) added to the perfusate stimulated fluid production, whereas dibutyryl cyclic AMP (1 mM) reduced fluid formation by 66%. Glucose, pyruvate and lactate concentrations in tubal fluid, measured by microfluorescence assays, were 1.11, 0.14 and 5.4 mM respectively. The concentrations of 17 amino acids in tubal fluid were measured by high performance liquid chromatography following fluorescence derivatization. Arginine (0.19 mM) > alanine (0.11 mM) > glutamate (0.09 mM) were present in highest concentration in all phases of the cycle. All 17 amino acid concentrations in tubal fluid were below those in the vascular perfusate. These data provides the basis for a culture medium whose composition mimics the physiological environment to which early human embryos are exposed.


Mandibular and hyoid muscles of Galeomorph sharks (Chondrichthyes: Elasmobranchii), with remarks on their phylogenetic intrarelationships.
The superorder Galeomorph comprises the orders Heterodontiformes, Orectolobiformes, Lamniformes, and Carcharhiniformes. Recent morphological and molecular support that it is a monophyletic taxon. The phyletic relationship within the Galeomorphi are also well resolved. However, only few morphological characters of the mandibular and hyoid muscles have been employed, and a detailed description of these muscles and their variations may contribute new interpretations of homology and to the discussion of different hypothesis of intrarelationships. This paper provides a detailed description of mandibular and hyoid arch muscles in galeomorph sharks, within a comparative elasmobranch framework, with the objective to discuss putative homologies that may elucidate our understanding of galeomorph evolution. Twenty-eight galeomorph species were dissected, described, illustrated and compared with other elasmobranchs and with data from the literature. The Galeomorphi are supported as monophyletic by presenting the m. levator labii superioris attached directly to the neurocranium, different from the attachment through a tendon in basal squalomorphs. Heterodontiformes and Orectolobiformes share particular variations in the position and insertion of the m. levator labii superioris and the presence of a well-defined m. levator hyomandibulae. Lamniformes and Carcharhiniformes show similar patterns in the position and attachment of the m. levator labii superioris, subdivision of the m. adductor mandibulae, and the presence of an almost indivisible m. levator hyomandibulae and m. constrictor hyoideus dorsalis, similar to the condition, albeit independently, in basal squalomorphs. No specific mandibular or hyoid arch muscle character was found to support the clade composed of Orectolobiformes, Lamniformes, and Carcharhiniformes, as advocated by recent phylogenetic analyses.


[Acute and chronic injuries after electrical accidents].
Electrical accidents are potentially fatal incidents with effect on the cardiovascular, nerve and musculoskeletal systems and on the skin (burns). The electrical engineering industry points out that the follow-up of injured persons from site of accident to hospital is quite random. This paper gives a review of the current literature and proposes guidelines for the follow-up of victims of electrical accidents. A search of the literature was conducted on Medline, Embase, Biosis, Healthline, the Cochrane Library, the ISI citation databases, and on several other search engines. The revised guidelines were developed in consultation with 23 medical and industry institutions. Serious acute effects of electrical accidents include cardiac arrest, respiration failure, burns (also (internal burns) with necrosis of e.g. muscle tissue), injuries to the nerve system, and renal failure. Traumas caused by falls are also frequent. Possible chronic effects are mostly seen in the nerve system as encephalopathy and psychological sequelae or as spinal cord and peripheral nerve injury. Most importantly, long latent periods are possible for some chronic nerve injuries. This paper suggest guidelines for acute (on the spot) action and criteria for referral to hospital, observation in hospital and further follow-up.


Sitophilus granarius L. (Coleoptera) Toxicity and Biological Activities of the Essential Oils of Tanacetum macrophyllum (Waldst. & Kit.) Schultz Bip.
Insecticides of the natural origin are an important alternative to the synthetic insecticides that are being employed for the preserving stored products. The volatiles obtained from T. cinerariifolium (=Pyrethrum cinerariifolium) is being used for many types of insecticidal applications; however there is a very little information on the insecticidal activity of the essential oils of other Tanacetum species. The main purpose of the present study is to determine the chemical composition of T. macrophyllum (Waldst. & Kit.) Schultz Bip. essential oils and evaluate their insecticidal activity against S. granarius as well as its other beneficial biological activities. Highest contact toxicity was observed in the leaf oil of (88.93%) against S. granarius. The flower oil showed considerable fumigant toxicity against L. minor at 10 mg/mL application concentration (61.86 %) when compared with other samples at the same concentration. The highest DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging activity (47.7%) and phosphomolybdenum reducing activity was observed also for the flower oil of T. macrophyllum at 10 mg/mL concentration. The essential oils were analyzed by GC, GC/MS. The flower and leaf oils were characterized with γ-eudesmol 21.5%, (E)-sesquilavandulol 20.3%, copaborneol 8.5% and copaborneol 14.1%, 1,8-cineole 11%, bornyl acetate 9.6%, borneol 6.3% respectively. AHC analysis of the qualitative and quantitative data obtained from the essential oil composition of the T. macrophyllum essential oil from the present research and previous reports pointed out that two different chemotypes could be proposed with current findings which are p-methyl benzyl alcohol/ cadinene and eudesmane chemotypes.


MEASURES OF HIP MUSCLE STRENGTH AND RATE OF FORCE DEVELOPMENT USING A FIXATED HANDHELD DYNAMOMETER: INTRA-TESTER INTRA-DAY RELIABILITY OF A CLINICAL SET-UP.
Evaluation of hip muscle function is considered an important part of the examination and treatment of physically active subjects with hip and groin pain. However, methods to reliably measure explosive hip muscle strength are lacking. The purpose was to investigate the reliability of a clinically available set-up using a fixated handheld dynamometer to test isometric peak force and rate of force development of the hip abductors, adductors, flexors, and extensors. Seventeen subjects (males: 9, females: 8, mean aged 25.4 (+/- 4.2) y, with mean body mass of 73.9 (+/- 15.2) kg, and mean height 174.2 (+/- 12.4) cm) were included. One experienced tester performed all measures in a randomized order. Three trials of isometric peak force and early- (0-100 ms) and late-phase (0-200 ms) rate of force development for the hip abductors, adductors, flexors, and extensors were obtained using a fixated handheld dynamometer. The trial with the highest value for each measure was used for analysis. Test-retest sessions were separated by 30 minutes of rest. No systematic between-session bias were observed for any of the measures. The relative intra-tester reliability (ICC2,1) for peak force, 0-100 ms rate of force development, and 0-200 ms rate of force development ranged from 0.93-0.96, 0.82-0.93, and 0.85-0.92, respectively, corresponding to good reliability for all force measures. The present study shows that assessment of isometric hip muscle peak force, including early- (0-100 ms) and late-phase (0-200 ms) rate of force development using a fixated handheld dynamometer have good intra-tester reliability for testing of the hip adductors, abductors, flexors and extensors. Thus, in clinical research settings where an isokinetic dynamometer may not always be readily accessible, the present test procedure can be used as a feasible alternative to reliably provide objective of hip muscle function relevant for rehabilitation of patients with hip and groin pain. Level 3, Reliability study.


p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer.
To analyse and compare expression patterns of three potential biomarkers-p16(INK4A), CDC6, and MCM5-and evaluate their use as predictive biomarkers in squamous and glandular cervical preinvasive neoplasia. Immunocytochemical analysis of p16(INK4A), MCM5, and CDC6 expression was performed on 20 normal, 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, 10 squamous cell carcinoma, 19 cervical glandular intraepithelial neoplasia (cGIN), and 10 adenocarcinoma samples. Staining intensity was assessed using a 0-3 scoring system. p16(INK4A), MCM5, and CDC6 expression was also examined in ThinPrep slides exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) was detected using a modified SYBR green assay. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. All three markers showed a linear correlation between expression and grade of dysplasia. p16(INK4A) and MCM5 protein expression was upregulated in all grades of squamous and glandular dysplasia. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinoma. p16(INK4A) expression was closely associated with high risk HPV infection-all grades of squamous and glandular cervical lesions were immunohistochemically positive. MCM5 staining intensity was independent of high risk HPV infection, highlighting its potential as a biomarker in both HPV dependent and independent cervical dysplasia. CDC6 may be a biomarker of high grade and invasive lesions of the cervix, with limited use in low grade dysplasia. p16(INK4A) was the most reliable marker of cervical dysplasia. Combinations of dysplastic biomarkers may be useful in difficult diagnostic cases.


[Haemolytic anaemia as a complication to intravenous infusion of human immunoglobulin].
A 85-year-old female treated for chronic inflammatory demyelinating polyradiculoneuropathy had three episodes of anaemia one week following treatment with large doses (2g/kg body weight) of immunoglobulin (Ig). At the final episode, she presented with haemolytic anaemia with fatigue, jaundice and loss of appetite. During the next two months anaemia was recognized in two additional cases. Subsequently, a series of twelve conseuntively studied IVIg treated patients showed a significant decrease of haemoglobin of 0.80 mmol/l 8-15 days after infusion. Haemolytic anaemia is a severe side effect that seems to be more frequent than previously recognized. It may possibly be prevented by the use of lyophilized Ig-preparations with low isohaemagglutinin titers or by slower Ig infusion rates.


[Successful lysis therapy in acute unilateral renal vein thrombosis].
A nephrotic syndrome developed in a 50-year-old man who, because of rheumatoid arthritis for the last three years, had been receiving gold therapy (30-50 mg sodium aurothiomalate weekly for 10 months). Treatment for the nephrotic syndrome was initiated with 100 mg prednisone daily. Ten days later he complained of severe pain in his right flank and haematuria was noted. Serum creatinine concentration increased from 1.0 to 1.8 mg/dl, while creatinine clearance fell to 62 ml/min. Computed tomography demonstrated significant enlargement of the right kidney and a thrombus in the right renal vein which extended cranial into the inferior vena cava. High dosage infusion of urokinase (4.5-7.5 mill. IU daily for nine days) achieved complete lysis of the thrombus. The creatinine concentration fell to 1.1 mg/dl, while creatinine clearance rose to 104 ml/min. On the 5th day the right kidney had 25% of total function, several days later 40%.--This case illustrates that, as long as there are no contraindications, adequately high doses of urokinase can be appropriate treatment of acute renal vein thrombosis associated with the nephrotic syndrome.


Quantitative single-cell gene expression measurements of multiple genes in response to hypoxia treatment.
Cell-to-cell heterogeneity in gene transcription plays a central role in a variety of vital cell processes. To quantify gene expression heterogeneity patterns among cells and to determine their biological significance, methods to measure gene expression levels at the single-cell level are highly needed. We report an experimental technique based on the DNA-intercalating fluorescent dye SYBR green for quantitative expression level analysis of up to ten selected genes in single mammalian cells. The method features a two-step procedure consisting of a step to isolate RNA from a single mammalian cell, synthesize cDNA from it, and a qPCR step. We applied the method to cell populations exposed to hypoxia, quantifying expression levels of seven different genes spanning a wide dynamic range of expression in randomly picked single cells. In the experiment, 72 single Barrett's esophageal epithelial (CP-A) cells, 36 grown under normal physiological conditions (controls) and 36 exposed to hypoxia for 30 min, were randomly collected and used for measuring the expression levels of 28S rRNA, PRKAA1, GAPDH, Angptl4, MT3, PTGES, and VEGFA genes. The results demonstrate that the method is sensitive enough to measure alterations in gene expression at the single-cell level, clearly showing heterogeneity within a cell population. We present technical details of the method development and implementation, and experimental results obtained by use of the procedure. We expect the advantages of this technique will facilitate further developments and advances in the field of single-cell gene expression profiling on a nanotechnological scale, and eventually as a tool for future point-of-care medical applications.


Music in the NICU: The Role of Nurses in Neuroprotection.
Early exposure to age-appropriate, meaningful auditory stimuli, such as lullaby singing, has been shown to advance various medical and developmental goals in premature infants in the NICU while reducing medical costs. A primary goal of NICU music therapists is to control auditory stimuli in the unit to help premature infants reach the greatest possible sedation. In hospitals with limited or no NICU music therapy (NICU-MT) coverage, nurses and other NICU staff can play an important role in providing neuroprotection to these premature infants while also optimizing neurodevelopment via use of recorded music. Based on current literature, this article provides a set of evidence-based guidelines for the use of recorded music with premature infants.


Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway.
Lysophosphatidic acid is a small extracellular signaling molecule, which is elevated in pathological conditions such as ischemic stroke and traumatic brain injury (TBI). LPA regulates the survival of neurons in various diseases. However, the molecular mechanisms underlying LPA-induced neuronal death remain unclear. Here we report that LPA activates LPA1 and LPA2 receptors, and the downstream MAPK pathway to induce the apoptosis of PC12 cells through mitochondrial dysfunction. LPA elicits the activation of ERK1/2, p38, and JNK pathways, decreases the expression of Bcl2, promotes the translocation of Bax, and enhances the activation of caspase-3, resulting in mitochondrial dysfunction and cell apoptosis. This process can be blocked by LPA1 receptor antagonist and LPA2 receptor antagonist and MAPK pathway inhibitors. Our results indicate that LPA1 receptor, LPA2 receptor and MAPK pathway play a critical role in LPA-induced neuronal injury. LPA receptors and MAPK pathways may be novel therapeutic targets for ischemic stroke and TBI, where excessive LPA signaling exist.


[Results and mechanism of action of non-perforating deep sclerotomy in intraoperative monitoring of the hypotensive effect].
A total of 45 patients (45 eyes) were operated on by using the technique of non-perforating deep sclerotomy (NDST). A conclusion on the action mechanism, efficiency and indications for NDST was made on the basis of determining the retention degree and of the intraoperative monitoring of tonometry and tonography parameters. Perforations of various scopes were proven to have an impact on the surgical hypotensive effect; finally, intraoperative measures were suggested in case of NDST inefficiency.