GOAL: a simplified mental test for emergency medical admissions.
Several scoring systems are used in screening for cognitive impairment, but none are suited to the busy medical assessment environment. To construct, validate and assess the reliability of a simple scale (Gwent Orientation and Awareness Listing, GOAL) for this purpose, and to examine its application in consecutive emergency admissions in two general hospitals. Prospective cohort studies. The validity and reliability of GOAL was assessed in three studies of patients aged > or =65 years who had been pronounced medically fit for discharge. The evaluation studies were carried out over 4-week medical intake periods in each participating hospital. Correlation of GOAL with the standard 30-point Mini-Mental State Examination was 0.89, and the inter-observer reliability was 0.90. Based on Receiver Operating Characteristics Curves, patients scoring <8 on GOAL were deemed to be cognitively impaired. Assessment by GOAL took half the time required for the widely used Abbreviated Mental Test Score. Of 1037 consecutive patients admitted to two hospitals' acute medical intakes and remaining for >24 h, 952 were able and willing to be scored by GOAL, and of these 201 (21%) 'failed', with a score of <8. Loss of orientation and awareness is common among patients admitted via medical intakes. GOAL is a practical brief screen for identifying and following-up these patients.


Overexpression of PIK3R1 promotes hepatocellular carcinoma progression.
Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) could regulate cancer cell proliferation important for cancer cell proliferation; however, its role in Hepatocellular carcinoma (HCC) remains largely unknown. Here, we investigated the role of PIK3R1 in HCC and examined the underlying molecular mechanisms. The expression of PIK3R1 was evaluated by immunohistochemistry and qRT-PCR in a series of HCC tissues. The mRNA and protein expression of PIK3R1 was used by qRT-PCR and western blot assays in a series of human HCC cell lines, and then we choose MHCC97H and HCCLM3 cells as a model to investigate the effect of PIK3R1 on HCC progression. The effects of PIK3R1 knowdown on cell proliferation, migration, apoptosis of HCC were assessed by the MTT assay, clonogenic assays, wound healing assay and flow cytometry in vitro. Western blot assay was performed to assess the expression changes of PI3K/AKT/mTOR signaling pathway. Our results found that PIK3R1 was highly expressed in HCC tissues compared with adjacent normal tissues. Knockdown of PIK3R1 inhibited the proliferation, migration and promoted apoptosis of HCC cell lines. In addition, we proved that knockdown of PIK3R1 downregulated p-PI3K, p-AKT, and p-mTOR expressions in MHCC97H and HCCLM3 cells. In conclusion, PIK3R1 providing potential novel targets for the treatment of HCC.


Asymmetric catalysis of the [5 + 2] cycloaddition reaction of vinylcyclopropanes and pi-systems.
As part of our studies of metal-catalyzed [m + n (+...o)] cycloadditions, we have previously reported the rhodium-catalyzed [5 + 2] cycloaddition of vinylcyclopropanes (VCPs) and pi-systems. These studies have led to Rh(I) complexes that catalyze these reactions in minutes at room temperature or in water without organic solvents. We describe a comparative evaluation of several chiral catalysts for the [5 + 2] reaction, evaluation of a preferred catalyst, [((R)-BINAP)Rh]+SbF6-, with substrates differing in substitution and tether types-producing enantiomeric excesses >/=95% for several systems. A predictive model for the selectivity is also presented.


Chemical Composition and Insecticidal, Antiplasmodial, and Anti-Leishmanial Activity of Capparis spinosa Essential Oil and Its Main Constituents.
This investigation was designed to evaluate the insecticidal, antiplasmodial, anti-leishmanial, and cytotoxic effects of Capparis spinosa essential oil (CSEO) and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene. Insecticidal activity of CSEO and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene, was determined against Aedes aegypti 4th-instar larvae at 25 ± 2°C. Antiplasmodial and anti-leishmanial effects of CSEO and its main components were carried out against chloroquine-resistant Plasmodium falciparum K1 strain and Leishmania major amastigotes based on the Malstat method and the macrophage model, respectively. We also performed the cytotoxic activity of CZEO and its main components against J774A1 macrophage cells using the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In addition, the plasma membrane permeability and caspase-3-like activity CSEO and its main components were evaluated against L. major. CSEO and its main components showed considerable (p < 0.001) larvicidal activity against Ae. aegypti larva. The 50% lethal concentration values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 21.6, 30.9, 41.6, and 35.3 μg/mL, respectively. By antiplasmodial effects, the 50% inhibitory concentration (IC50) values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 7.4, 14.5, 19.6, and 21.3 μg/mL, respectively, while these values for their anti-leishmanial effects were 9.1, 20.7, 23.3, and 18.6 μg/mL, respectively. The 50% cytotoxic concentration values for CSEO, methyl isothiocyanate, hexadecanoic acid, and limonene were 93.7, 216.2, 199.4, and 221.3 μg/mL, respectively. Different concentrations of CSEO and its main components significantly (p < 0.05) increased the plasma membrane permeability and caspase-3-like activity against L. major promastigote level as dose-dependent response. Based on the obtained results, C. spinosa essential oil and its main components, methyl isothiocyanate, hexadecanoic acid, and limonene, displayed insecticidal, antiplasmodial, and anti-leishmanial activity against healthy 4th-instar larvae of A. aegypti, chloroquine-resistant P. falciparum K1 strain, and L. major amastigotes, respectively. However, further surveys are required to display the mechanisms of action mode of tested drugs and their efficacy in animal model and clinical settings.


Issues in transcatheter treatment of critical aortic stenosis in the newborn infant.
Critical aortic valve stenosis is not a frequently seen disease. In most cases, these patients are in critical condition. Transcatheter dilatation is one of the therapeutic options for treatment. This article addresses important issues in transcatheter dilatation in the newborn infant.


[Thermographic study of temperature gradient during ear surgery intervention].
During middle ear surgery manipulations like burring, cooling with water, suction or even screwing cause changes of temperature which should be known to the surgeon. An infrared thermovision device was introduced for registration. Thermography is an easy way for continuously recording thermic effects during surgery. If sufficient cooling is guaranteed, no temperatures high enough to cause tissue damage or functional defects could be observed. Adequate cooling provided, thermal injuries during ear surgery can be neglected. Thermography is an easy method for answering such questions, not only in ear surgery but also in other medical fields.


Cost-effectiveness of anterior implants versus fixed dental prostheses.
For the restoration of an anterior missing tooth, implant-supported single crowns (ISCs) or fixed dental prostheses (FDPs) are indicated, but it is not clear which type of restoration is more cost-effective. A self-selected trial was performed with 15 patients with ISCs and 11 with FDPs. Patient preferences were recorded with visual analog scales before treatment, 1 month following restoration, and then annually. Quality-adjusted tooth years (QATYs) were estimated by considering the type of reconstruction for replacing the missing tooth and its effect on the adjacent teeth. A stochastic cost-effectiveness model was developed using Monte Carlo simulation. The expected costs and QATYs were summarized in cost-effectiveness acceptability curves. ISC was the dominant strategy, with a QATY increase of 0.01 over 3 years and 0.04 over 10 years with a higher probability of being cost-effective. While both treatment options provided satisfactory long-term results from the patient's perspective, the lower initial costs, particularly laboratory fees, were responsible for the dominance of ISCs over FDPs.


The presence of pregnancy-associated plasma protein-A in human corpora lutea: cellular and subcellular distribution and dependence on reproductive state.
Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight glycoprotein primarily secreted by syncytiotrophoblasts of human placenta. It is not known, however, whether human CL of menstrual cycle or pregnancy also contain this protein. Therefore, light and electron microscope immunocytochemical studies were undertaken to investigate the presence, cellular and subcellular distribution, and dependence of luteal PAPP-A content on reproductive state. Human CL from early, mid, and late luteal phases and from term pregnancies immunostained specifically for PAPP-A. Immunostaining was found in large luteal cells (17-30 microns) but not in small luteal cells (7-16 microns) or in nonluteal cells in any of the reproductive states. Immunostaining was not found in negative control tissues, i.e. human liver or bovine CL of pregnancy. As expected however, term-pregnancy human placenta used for a positive control tissue immunostained intensely for PAPP-A. The luteal immunostaining was highest in early luteal phase, decreased progressively from early to mid and from mid to late luteal phases, and then disappeared in corpora albicantia. The relative intensity of immunostaining in early luteal phase human CL was similar to that in term-pregnancy human placenta and higher than in term-pregnancy human CL. The immunogold particles due to PAPP-A were primarily associated with secretory granules of large luteal cells. A small number of gold particles were also found in rough endoplasmic reticulum and cytoplasm. In conclusion, human CL contain immunoreactive PAPP-A. The luteal content varies with reproductive state, with the highest amount found in early luteal phase CL.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of dense, high-volume, artificial surfactant aerosol on a heated exhalation filter system.
To evaluate a supplemental heated filter system during mechanical ventilation with continuous nebulization of an artificial surfactant by a new, high-volume nebulizer. A new nebulizer system, containing artificial surfactant, provided half of a 20-L minute ventilation and the remainder of this minute ventilation was provided by a commonly used mechanical ventilator. Ventilation sources were joined in the inspiratory limb of the breathing circuit, which was connected to a test lung system. A supplemental filter system was placed upstream of the ventilator's heated filter in the expiratory limb of the circuit. Circuit pressures at the inlet of the supplemental filter (P1), between the filters (P2), and after the ventilator expiratory filter (P3) were monitored and recorded. Nebulizer canisters containing artificial surfactant were replaced every 4 hrs. The performance of four supplemental filters in continuous use was examined. Another four filters were each used over 4 hrs, steam autoclaved, and reused. The ventilator was set at a rate of 20 breaths/min, with a tidal volume of 0.5 L, a flow rate of 40 L/min, and positive end-expiratory pressure of 10 cm H2O. The nebulizer provided an equal volume and flow rate so that the delivered tidal volume was 1.0 L with a flow rate of 80 L/min. Ventilator failure and/or excessive airway pressure caused by increased filter resistance occurred at a mean of 7.3 +/- 1.3 (SD) hrs of continuous ventilation. Mean P1-peak increased from 67.5 +/- 8.2 to 94.0 +/- 10.7 cm H2O (p < .001) and P1-baseline increased from 9.3 +/- 1.0 to 53.5 +/- 17.1 cm H2O (p = .014). Filters that were autoclaved after 4 hrs of ventilation and reused lasted a total of 7.0 +/- 1.3 hrs. Mean P1-peak increased from 68.9 +/- 4.9 to 84.8 +/- 19.1 cm H2O and P1-baseline increased from 9.5 +/- 1.7 to 30.8 +/- 14.2 cm H2O (p < .05). The supplemental filter system was able to protect the ventilatory exhalation sensors for approximately 7 hrs at a minute ventilation of 20 L/min. Steam sterilization did not extend the supplemental filter life.


Surface micromorphology of dental composites [CE-TZP]-[Al2O3] with Ca(+2) modifier.
The objective of this study was to characterize the three-dimensional (3D) surface micromorphology of the ceramics produced from nanoparticles of alumina and tetragonal zirconia (t-ZrO2) with addition of Ca(+2) for sintering improvement. The 3D surface roughness of samples was studied by atomic force microscopy (AFM), fractal analysis of the 3D AFM-images, and statistical analysis of surface roughness parameters. Cube counting method, based on the linear interpolation type, applied for AFM data was used for fractal analysis. The morphology of non-modified ceramic sample was characterized by the rather big (1-2 μm) grains of α-Al2O3 phase with a habit close to hexagonal drowned in solid solution of t-ZrO2 with smooth surface. The pattern surfaces of modified composite content a little amount of elongated prismatic grains with composition close to the phase of СаСеAl3О7 as well as hexahedral α-Al2O3-grains. Fractal dimension, D, as well as height values distribution have been determined for the surfaces of the samples with and without modifying. It can be concluded that the smoothest surface is of the modified samples with Ca(+2) modifier but the most regular one is of the non-modified samples. A connection was observed between the surface morphology and the physical properties as assessed in previous works.


Neuroprotective effect of gypenosides against oxidative injury in the substantia nigra of a mouse model of Parkinson's disease.
Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD) and gypenosides (GP), which are saponins with various bioactivities, have shown antioxidative effects in vitro. The present study was designed to evaluate the effect of GP on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Acute administration of MPTP led to decreased glutathione content and reduced superoxide dismutase activity in the substantia nigra of the mice, which resulted in oxidative stress, loss of nigral dopaminergic neurons and motor dysfunction. Co-treatment with GP attenuated all the injuries induced by MPTP in a dose-dependent manner. The neuroprotective effect of GP may be attributed to increased antioxidation, as manifested by significantly increased glutathione content and enhanced superoxide dismutase activity in the substantia nigra. These results strongly indicate the possible therapeutic potential of GP as an antioxidant in PD.


Interleukin-6 (IL-6) and IGF-IGFBP system in children and adolescents with type 1 diabetes mellitus.
Some studies suggest that IL-6 is connected with glucose metabolism and insulin action, so like IGF-IGFBPs system it could play the role in diabetes etiopathogenesis. The aim of the study was therefore to test the hypothesis that in children and adolescents IL-6 is of importance for the etiopathogenesis of diabetes mellitus type 1 and that IL-6 is connected with carbohydrate metabolism and IGF-IGFBPs action. There were 49 patients with type 1 diabetes: 10 persons at onset diabetes and 39 with disease lasted at least 1 year and 33 age-matched healthy children included into the study. Serum IGF-I concentrations were measured by RIA; IGFBP-1 and IGFBP-2 by IRMA and IL-6 concentrations using quantitative ELISA immunoassays. HbA1c was measured by HPLC method. Multiple regression, ANOVA, and Student's t-test were used for statistical analysis. IL-6 and IGF-I, IGFBP-1 and IGFBP-2 levels did not differ statistically significant between diabetic patients and controls. IL-6 concentrations were statistically higher at onset diabetes than in diabetic patients with long-term disease. IL-6 did not correlate with IGF-I and its binding proteins - 1 and - 2 in examined groups. At onset of disease IL-6 correlated with insulin requirement. There were not found correlations between IL-6 and HbA1c in diabetic groups. IGF-I positively correlated with age and growth in both groups and with IGFBP-2 in diabetic patients. IGFBP-2 correlated negatively with BMI in all examined groups. IL-6 might play a significant role in type 1 diabetes mellitus etiopathogenesis. It seems that IL-6 does not regulate IGF-IGFBP system in diabetic children and adolescents or IL-6 maybe cooperate with IGF-I, but their significant dependence on insulin action influences their mutual relationships.


Rescue of His-42 --> Ala horseradish peroxidase by a Phe-41 --> His mutation. Engineering of a surrogate catalytic histidine.
Formation of the ferryl (FeIV=O) porphyrin radical cation known as Compound I in the reaction of horseradish peroxidase (HRP) with H2O2 is catalyzed by His-42, a residue that facilitates the binding of H2O2 to the iron and subsequent rupture of the dioxygen bond. An H42A mutation was shown earlier to decrease the rate of Compound I formation by a factor of approximately 10(6) and of guaiacol oxidation by a factor of approximately 10(4). In contrast, an F41A mutation has little effect on peroxidative catalysis (Newmyer, S. L., and Ortiz de Montellano, P. R. (1995) J. Biol. Chem. 270, 19430-19438). We report here construction, expression, and characterization of the F41H/H42A double mutant. The pH profile for guaiacol oxidation by this double mutant has a broad maximum at approximately pH 6.3. Addition of H2O2 produces a Compound I species (lambdamax = 406 nm) that is reduced by 1 eq of K4Fe(CN)6 to the ferric state (lambdamax = 407 nm) without the detectable formation of Compound II. A fraction of the heme chromophore is lost in the process. The rate of Compound I formation for the F41H/H42A double mutant is 3.0 x 10(4) M-1 s-1. This is to be compared with 0.9 x 10(7) M-1 s-1 for wild-type HRP and 19 M-1 s-1 for the H42A mutant. The kcat values for guaiacol oxidation by wild-type, H42A, and F41H/H42A HRP are 300, 0.015, and 1.8 s-1. The corresponding kcat values for ABTS oxidation are 4900, 0.41, and 100 s-1, respectively. These results show that a histidine at position 41 substitutes, albeit imperfectly, for His-42 in peroxidative turnover of the enzyme. The F41H/H42A double mutant has peroxidative properties intermediate between those of the native enzyme and the H42A mutant. The F41H/H42A double mutant, however, is a considerably better thioanisole sulfoxidation and styrene epoxidation catalyst than native or H42A HRP. The surrogate catalytic residue introduced by the F41H mutation thus partially compensates for the H42A substitution used to increase access to the ferryl oxygen.


Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release.
Intravenous injections of cocaine HCl are habit-forming because, among their many actions, they elevate extracellular dopamine levels in the terminal fields of the mesocorticolimbic dopamine system. This action, thought to be very important for cocaine's strong addiction liability, is believed to have very short latency and is assumed to reflect rapid brain entry and pharmacokinetics of the drug. However, while intravenous cocaine HCl has almost immediate effects on behavior and extracellular dopamine levels, recent evidence suggests that its central pharmacological effects are not evident until 10 or more seconds after IV injection. Thus the immediate effects of a given intravenous cocaine injection on extracellular dopamine concentration and behavior appear to occur before there is sufficient time for cocaine to act centrally as a dopamine uptake inhibitor. To explore the contribution of peripheral effects of cocaine to the early activation of the dopamine system, we used brain microdialysis to measure the effects of cocaine methiodide (MI)--a cocaine analogue that does not cross the blood brain barrier--on glutamate (excitatory) input to the dopamine cells. IP injections of cocaine MI were ineffective in cocaine-naïve animals but stimulated ventral tegmental glutamate release in rats previously trained to lever-press for cocaine HCl. This peripherally triggered glutamate input was sufficient to reinstate cocaine-seeking in previously trained animals that had undergone extinction of the habit. These findings offer an explanation for short-latency behavioral responses and immediate dopamine elevations seen following cocaine injections in cocaine-experienced but not cocaine-naïve animals.


Instrument design and protocol for the study of light controlled processes in aquatic organisms, and its application to examine the effect of infrared light on zebrafish.
The acquisition of reliable data strongly depends on experimental design. When studying the effects of light on processes such as behaviour and physiology it is crucial to maintain all environmental conditions constant apart from the one under study. Furthermore, the precise values of the environmental factors applied during the experiment should be known. Although seemingly obvious, these conditions are often not met when the effects of light are being studied. Here, we document and discuss the wavelengths and light intensities of natural and artificial light sources. We present standardised experimental protocols together with building plans of a custom made instrument designed to accurately control light and temperature for experiments using fresh water or marine species. Infrared light is commonly used for recording behaviour and in electrophysiological experiments although the properties of fish photoreceptors potentially allow detection into the far red. As an example of our experimental procedure we have applied our protocol and instrument to specifically test the impact of infrared light (840 nm) on the zebrafish circadian clock, which controls many aspects of behaviour, physiology and metabolism. We demonstrate that infrared light does not influence the zebrafish circadian clock. Our results help to provide a solid framework for the future study of light dependent processes in aquatic organisms.


Renin-angiotensin-aldosterone system in insulin resistance and metabolic syndrome.
Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation. Estrogen reduces appetite by its action on the brain in a way similar to leptin, an anorexigenic action that seems to be mediated via hypothalamic pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and synaptic plasticity in the arcuate nucleus similar to leptin. Estrogen stimulates lipoxin A4, a potent vasodilator and platelet anti-aggregator. Since both RAS and estrogen act on the hypothalamic neuropeptides and regulate food intake and obesity, it is likely that RAS modulates LXA4 synthesis. Thus, it is proposed that Angiotensin-II receptor blockers and angiotensin-converting enzymes and angiotensin-II antagonists may have the ability to augment LXA4 synthesis and thus bring about their beneficial actions.


[Trends of use of anxiolytics and hypnotics in Spain from 2000 to 2011].
For years, anxiolytics and hypnotics have been one of the most prescribed drug classes in most developed countries. The main aim of this study is to explore the pattern of use of anxiolytic and hypnotic drugs during the period 2000-2011, comparing their growth with that of five european countries. We performed an ecological and descriptive study of anxiolytics and hypnotics consumption in Spain. Consumption data were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the totality of the Spanish National Health System. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1000 inhabitants per day (DDD/1000 person/day) by each treatment subgroup, active substance and attending the plasma half-life of the medication. Approximate comparisons were also made with some European countries. The use of anxiolytics and hypnotics drugs was 56.7 DDD/1000 person/day in 2000 and 82.9 DDD/1000 person/day in 2011 (a +46.1% increase across the period). Lorazepam and alprazolam were the most used anxiolytics (20.5 and 15.6 DDD/1000 person/day in 2011, respectively), whereas lormetazepam was among the hypnotics (18.3 DDD/1000 person/day in 2011). In relative terms, hypnotics´ lormetazepam and zolpidem increased their use by 103.3% and 85.1%, respectively; while anxiolytics´ lorazepam and hydroxyzine increased 75.1% and 72.8%, respectively. In Spain (period 2003-2010), the total increase in the consumption of anxiolytics and hypnotics was +34.3%, with 24.0% for Portugal, 4.0% for Italy, but a reduction of -6.1% for France. A considerable increase in anxiolytics and hypnotics´ consumption has occurred in Spain during the last decade, being the growth higher than that reported in other European countries.


Synthesis of a recombinant DNA-derived HBV e antigen and its application in diagnosis.
The gene coding for HBV e antigen (HBeAg) and core antigen (HBeAg) are located in the C region of the HBV genome. In this paper 1.8 kb BamHI-EcoRI DNA fragment carrying HBc gene from adw2 HBV DNA was digested with Bal31 and HapII, a series of fragment with different length were produced and inserted into pUR222 and pUC18 vectors to construct various recombinant plasmids. Two new recombinants able to direct high level synthesis of HBeAg in E. coli were obtained. Recombinant HBeAg was then purified by DEAE chromatography and affinity chromatography. The preparation obtained were identified by electrophoresis and immunochemical analysis. Molecular weight of the recombinant HBeAg determined by SDS-PAGE was about 38 kd. It is considered to be a dimer of two fused antigen molecules in size of 19 kd. Bacterial extracts prepared from cells harboring one of the constructed plasmids have been used successfully as a diagnostic reagent for the detection of HBeAg and anti-HBe in human sera by ELISA.


Patterns of cytokeratins and lamins in rat liver and in rat liver cell lines as shown by immunoblotting using the monoclonal antibodies A 45-B/B3 and A 51-B/H4.
The cytokeratins and lamins of rat liver nuclei, nuclear lamina, and cytoskeleton preparations as well as of rat liver cell lines were studied by immunoblotting using the monoclonal broad-range cytokeratin antibodies A 45-B/B3 and A 51-B/H4. A 45-B/B3 is bound to 64-, 58-, 55-, 52.5-, 49-, 45-, 43-, 39-, and 35-kDa proteins, which are already known as rat liver cytokeratins, excepted the 64- and 35-kDa bands. This antibody can therefore be considered to be a pan-cytokeratin marker for the rat. A 51-B/H4 detected an epitope occurring in both lamins (70, 67, and 60-63 kDa) and cytokeratins (49, 45, 43, and 39 kDa). In a few experiments, this monoclonal antibody also indicated a 55-kDa protein. Furthermore, in some cell lines a 80-kDa protein was detected which possibly may correspond to a higher molecular member of the lamin family. In subcellular preparations, the full set of cytokeratins was found to be associated with the nuclei and the nuclear lamina fraction, suggesting a tight connection of the intermediate filaments with the nuclear lamina. Cell lines derived from fetal or neonatal rat liver exhibited cytokeratin patterns which resembled the phenotype of immature or atypically differentiated parenchymal liver cells.


The aggregation of pig articular chondrocyte and synthesis of extracellular matrix by a lactose-modified chitosan.
A reductive amination reaction (N-alkylation) obtained exploiting the aldheyde group of lactose and the amino group of the glucosamine residues of chitosan (d.a. 89%) afforded a highly soluble engineered polysaccharide (chitlac) for a potential application in the repair of the articular cartilage. Chitosan derivatives with 9% and 64% of side chain groups introduced have been prepared and characterized by means of potentiometric titration, (1)H-NMR and intrinsic viscosity. Both polymers, with respect to the unmodified chitosan, induce cell aggregation when in contact with a primary culture of pig chondrocytes, leading to the formation of nodules of considerable dimensions (up to 0.5-1 mm in diameter). The nodules obtained from chondrocytes treated with chitlac with the higher degree of substitution have been studied by means of optical and electron microscopy (SEM, TEM) and the production of glycosaminoglycans (GAGs) and collagen has been measured by means of colorimetric assays. The chondro-specificity of GAG and collagen was determined by RT-PCR. The results show that the lactose-modified chitosan is non-toxic and stimulates the production of aggrecan and type II collagen.


Use of the orthogonal design method to study the synergistic effects of asbestos fibres and 12-O-tetradecanoylphorbol-13-acetate (TPA) in the BALB/3T3 cell transformation system.
An orthogonal design method was used to study the transforming effects of chrysotile and crocidolite asbestos fibres in BALB/3T3 cells. Three experiments, designed by tables L9 (3(4)), L8 (2(7)) and L6 (3(1) x 2(2)) of the orthogonal method respectively, were performed separately. The results indicate exponential reductions in survival of treated cells concomitant with a linear increase in exposure concentrations from 0.1 to 10.0 micrograms/cm2, and that chrysotile was more toxic than crocidolite; the total transformation frequency was significantly increased with both chrysotile and TPA concentrations. There was synergism between chrysotile and TPA in sequential treatment, which suggests that chrysotile is an initiator and has a complete transforming effect at 10.0 micrograms/cm2. Crocidolite only has an initiating-like effect within the dose range of 0.1-10.0 micrograms/cm2, and no synergistic effect when associated with TPA.


Acute release of tissue factor pathway inhibitor after in vivo thrombin generation in baboons.
Tissue factor pathway inhibitor (TFPI), the major downregulator of the procoagulant activity of tissue factor (TF), is synthesised by endothelial cells (EC) and acutely released in vitro after thrombin stimulation. Expression of TF on EC and subsequent thrombin generation occurs in vivo during sepsis or malignancy, inducing disseminated intravascular coagulation (DIC). The present study investigates the changes in plasma TFPI in relation to markers of in vivo thrombin generation induced by injection of factor Xa (FXa)/phospholipids in baboons at dosages leading to partial (48%) or complete fibrinogen depletion. The plasma concentrations of thrombin-antithrombin III (TAT) and fibrinopeptide A (FpA), as markers of in vivo generation of thrombin, were strongly enhanced after injection of FXa/phospholipids. TFPI levels, whether measured as antigen or activity, increased significantly in both treatment groups within few minutes, and were dependent on the dose of FXa/phospholipids. Significant positive correlations between plasma levels of TFPI and of TAT or FpA were observed. Altogether, our results indicate that experimentally induced in vivo generation of thrombin causes the acute release of TFPI, high-lighting a possible novel function of thrombin in downregulation of the coagulation process, potentially relevant for the outcome of DIC.


Higher doses of (+)MK-801 (dizocilpine) induced mortality and procedural but not cognitive deficits in delayed testing in the active place avoidance with reversal on the Carousel.
Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute's breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists.


Changes in polypeptide-specific factor VIII antigen levels during whole blood clotting.
The time-course of factor VIII (FVIII) proteolysis during whole blood coagulation was monitored using polypeptide-specific enzyme-linked immunosorbent assays (ELISAs) developed with monoclonal antibodies to FVIII. Such assays of whole blood from normal subjects revealed that, within 30 min after coagulation had started, levels of the amino-terminal region of FVIII light chain and in the middle region of FVIII heavy chain had decreased to baseline in parallel with factor VIII procoagulant activity, but that levels of the 70 kDa thrombin digest decreased more slowly, with 75 U/dl of FVIII antigen (FVIII:Ag) remaining even after 2 h. Similar analysis of the blood of a patient with congenital hypoprothrombinemia indicated a lag phase of 20 min before proteolysis started. No significant change was observed until 1 h after calcium chloride was added to prothrombin-depleted plasma. On the other hand, in the presence of tissue thromboplastin, levels of FVIII:Ag in all ELISAs decreased rapidly. These results indicate a requirement for thrombin generation in the proteolysis of FVIII during the process of whole blood clotting.


Non-coding RNAs in diseases with a focus on osteoarthritis.
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.


Clinical and instrumental evaluation of pelvic floor disorders before and after bariatric surgery in obese women.
Obesity, well known as a risk factor for several diseases, can also lead to pelvic floor dysfunction (PFD). However, scant data are available regarding PFD in obese individuals. Our study was designed to assess the prevalence, severity, and the quality of life (QOL) effect of PFD in obese women before and after bariatric surgery at a university hospital in Italy. A total of 100 obese (body mass index [BMI] ≥30 kg/m(2)) women completed 6 validated specific and QOL questionnaires about PFD. The patients were evaluated by physical examination, endoanal ultrasonography, rectal balloon distension test, and dynamic magnetic resonance imaging. Of the 100 patients, 87 were reassessed 12 months after bariatric surgery. The prevalence of PFD was 81%, and 49% of patients reported that their symptoms adversely affected their QOL. Urinary incontinence (UI) was the most common disorder (61%) and was associated with the BMI (P = .04). Fecal incontinence and pelvic organ prolapse symptoms were reported by 24 and 56 patients, respectively. Urogenital prolapse and rectocele was documented in 15% and 74% of patients, respectively. After a mean BMI reduction of 10 kg/m(2), the prevalence of PFD decreased to 48% (P = .02), with a significant improvement in QOL. The prevalence of UI decreased to 9.2% (P = .0001) and was associated with the decrease in postoperative BMI (P = .04). The rate of resolution of the symptoms was 84%, 85%, and 74% for UI, fecal incontinence, and pelvic organ prolapse, respectively. In the present sample of obese women, PFD was common and adversely affected their QOL. A clear association was found between the BMI and UI. Weight loss resulted in improved UI, fecal incontinence, and symptoms of pelvic organ prolapse.


Determination of cystathionine beta-synthase activity in human plasma by LC-MS/MS: potential use in diagnosis of CBS deficiency.
Cystathionine β-synthase (CBS) deficiency is usually confirmed by assaying the enzyme activity in cultured skin fibroblasts. We investigated whether CBS is present in human plasma and whether determination of its activity in plasma could be used for diagnostic purposes. We developed an assay to measure CBS activity in 20 μL of plasma using a stable isotope substrate - 2,3,3-(2)H serine. The activity was determined by measurement of the product of enzyme reaction, 3,3-(2)H-cystathionine, using LC-MS/MS. The median enzyme activity in control plasma samples was 404 nmol/h/L (range 66-1,066; n = 57). In pyridoxine nonresponsive CBS deficient patients, the median plasma activity was 0 nmol/ho/L (range 0-9; n = 26), while in pyridoxine responsive patients the median activity was 16 nmol/hour/L (range 0-358; n = 28); this overlapped with the enzyme activity from control subject. The presence of CBS in human plasma was confirmed by an in silico search of the proteome database, and was further evidenced by the activation of CBS by S-adenosyl-L-methionine and pyridoxal 5'-phosphate, and by configuration of the detected reaction product, 3,3-(2)H-cystathionine, which was in agreement with the previously observed CBS reaction mechanism. We hypothesize that the CBS enzyme in plasma originates from liver cells, as the plasma CBS activities in patients with elevated liver aminotransferase activities were more than 30-fold increased. In this study, we have demonstrated that CBS is present in human plasma and that its catalytic activity is detectable by LC-MS/MS. CBS assay in human plasma brings new possibilities in the diagnosis of pyridoxine nonresponsive CBS deficiency.


Antifungal susceptibility and virulence factors of clinically isolated dermatophytes in Tehran, Iran.
Dermatophytes possess a wide array of virulence factors and various antifungal susceptibility patterns which influence their pathogenesis in humans and animals. The aim of this study was to evaluate antifungal susceptibility and keratinase and proteinase activity of 49 dermatophyte strains from the genera Microsporum, Trichophyton and Epidermophyton which were isolated from human cases of dermatophytosis. Forty-nine dermatophyte strains isolated from clinical samples were cultured on general and specific culture media. Keratinase and proteinase activity was screened on solid mineral media and confirmed in liquid cultures. Drug susceptibility toward azoles (fluconazole, ketoconazole and itraconazole), griseofulvin and terbinafine was evaluated using disk diffusion method on Mueller-Hinton agar and minimum inhibitory concentrations (MICs) were determined using microbroth dilution assay according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Our results indicated that clinically isolated dermatophytes from 7 major species produced keratinase and proteinase at different extents. The mean keratinase and proteinase activity was reported as 6.69 ± 0.31 (U/ml) and 2.10 ± 0.22 (U/ml) respectively. Disk diffusion and microbroth dilution (MIC) results of antifungal susceptibility testing showed that ketoconazole was the most effective drug against Epidermophyton floccosum and Trichophyton mentagrophytes, itraconazole against T. rubrum and E. floccosum, and griseofulvin and terbinafine against Trichophyton verrucosum. Our results showed that all dermatophyte isolates were resistant to fluconazole. Overall, ketoconazole and itraconazole were the most effective drugs for all dermatophyte species tested. Our results showed that antifungal susceptibility testing is an urgent need to select drugs of choice for treatment of different types of dermatophytosis and further indicated the importance of keratinase and proteinase in pathogenesis of dermatophyte species.


Estimating the dimensionality of the manifold underlying multi-electrode neural recordings.
It is generally accepted that the number of neurons in a given brain area far exceeds the number of neurons needed to carry any specific function controlled by that area. For example, motor areas of the human brain contain tens of millions of neurons that control the activation of tens or at most hundreds of muscles. This massive redundancy implies the covariation of many neurons, which constrains the population activity to a low-dimensional manifold within the space of all possible patterns of neural activity. To gain a conceptual understanding of the complexity of the neural activity within a manifold, it is useful to estimate its dimensionality, which quantifies the number of degrees of freedom required to describe the observed population activity without significant information loss. While there are many algorithms for dimensionality estimation, we do not know which are well suited for analyzing neural activity. The objective of this study was to evaluate the efficacy of several representative algorithms for estimating the dimensionality of linearly and nonlinearly embedded data. We generated synthetic neural recordings with known intrinsic dimensionality and used them to test the algorithms' accuracy and robustness. We emulated some of the important challenges associated with experimental data by adding noise, altering the nature of the embedding of the low-dimensional manifold within the high-dimensional recordings, varying the dimensionality of the manifold, and limiting the amount of available data. We demonstrated that linear algorithms overestimate the dimensionality of nonlinear, noise-free data. In cases of high noise, most algorithms overestimated the dimensionality. We thus developed a denoising algorithm based on deep learning, the "Joint Autoencoder", which significantly improved subsequent dimensionality estimation. Critically, we found that all algorithms failed when the intrinsic dimensionality was high (above 20) or when the amount of data used for estimation was low. Based on the challenges we observed, we formulated a pipeline for estimating the dimensionality of experimental neural data.


Heavy methanes as atmospheric tracers.
Methane-21 ((13)CD(4)) is potentially a useful nonradioactive tracer for testing atmospheric transport and diffusion models on a continental scale. In an experiment to demonstrate this long-range utility, the release of 84 grams of methane-21 was detected at distances of 1500 to about 2500 kilometers at concentrations of about 1 part in 2 x 10(16) parts (by volume) in the air by a technique in which methane was separated and the methane-21 content was measured with a mass spectrometer.


Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology.
The monoclonal antibodies ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) have shown remarkable antitumor activity in an increasing number of cancers. When combined, ipilimumab and nivolumab have demonstrated superior activity in patients with metastatic melanoma (CHECKMATE-067). Here we describe the preclinical development strategy that predicted these clinical results. Synergistic antitumor activity in mouse MC38 and CT26 colorectal tumor models was observed with concurrent, but not sequential CTLA-4 and PD-1 blockade. Significant antitumor activity was maintained using a fixed dose of anti-CTLA-4 antibody with decreasing doses of anti-PD-1 antibody in the MC38 model. Immunohistochemical and flow cytometric analyses confirmed that CD3+ T cells accumulated at the tumor margin and infiltrated the tumor mass in response to the combination therapy, resulting in favorable effector and regulatory T-cell ratios, increased pro-inflammatory cytokine secretion, and activation of tumor-specific T cells. Similarly, in vitro studies with combined ipilimumab and nivolumab showed enhanced cytokine secretion in superantigen stimulation of human peripheral blood lymphocytes and in mixed lymphocyte response assays. In a cynomolgus macaque toxicology study, dose-dependent immune-related gastrointestinal inflammation was observed with the combination therapy; this response had not been observed in previous single agent cynomolgus studies. Together, these in vitro assays and in vivo models comprise a preclinical strategy for the identification and development of highly effective antitumor combination immunotherapies.


Is cryopreservation of embryos a legitimate surrogate marker of embryo quality in studies of assisted reproductive technology conducted using national databases?
To investigate whether cryopreservation of supernumerary embryos is a good surrogate for embryo quality. Retrospective study of 6,859 assisted reproductive technology (ART) cycles from women aged <35 years with two fresh day 3 embryos transferred. National Society for Assisted Reproductive Technology Clinic Outcome Reporting System data from 2006-2008. Women undergoing ART. None. Embryo quality (good, fair, or poor), cell number, and live births were compared for cycles with and without cryopreservation, using χ(2) to evaluate statistical significance. The association of freezing with embryo quality was examined using multiple logistic regression after adjusting for confounders (patient age, oocyte yield, intracytoplasmic sperm injection [ICSI], assisted hatching, male factor infertility). Cycles with cryopreservation were more likely to have two embryos of good quality transferred (81.3% vs. 48.5%) and had more 8-cell embryos transferred (76.0% vs. 50.1%). Relative to cycles with two good embryos (good-good), the adjusted odds ratios (OR) for cryopreservation were: good-fair (OR = 0.301, 95% confidence interval [CI] = 0.257-0.354), fair-fair (OR = 0.308, 95% CI = 0.258-0.367), and any poor (OR = 0.058, 95% CI = 0.040-0.083). The live birth rate was 52.4% for cycles with freezing and 40.6% for cycles without. Embryo quality and cell number were both associated with embryo cryopreservation. However, although cryopreservation was a strong marker for good quality, not having cryopreservation did not reliably indicate poor quality, as almost half of those cycles had two good quality embryos.


Factors associated with mucoid transition of Pseudomonas aeruginosa in cystic fibrosis patients.
Although the mucoid form of Pseudomonas aeruginosa (Pa) is largely responsible for the progression of lung disease in cystic fibrosis (CF), the relationship between factors relating daily-care regimes to mucoidy acquisition are as yet poorly investigated. Fifty-two CF patients registered at the CF centre of Dijon, France, were retrospectively evaluated from the date of Pa colonization either to the first positive sputum culture for mucoid Pa (n = 26) or to the last culture in which the Pa remained non-mucoid (n = 26). All clinical, pathological and therapeutic events were recorded. The association between the parameters collected and mucoid transition of Pa was assessed in a Cox model with time-dependant covariables. The mean follow-up was 4.7 + or - 4.3 years. Three independent parameters were associated with the higher risk of mucoid transition of Pa: persistence of Pa in sputum (OR 7.89; p <0.01), use of inhaled bronchodilators (OR 3.40; p = 0.04), and the use of inhaled colimycin (OR 4.04; p = 0.02). Isolation of Staphylococcus aureus, Haemophilus influenzae or Streptococcus pneumoniae in sputum was associated with a lower risk (OR 0.24; p < 0.01). Mucoid transition of Pa was associated with variables that reflected the severity of both lung disease and Pa colonization. Although they do not lead to prophylactic measures, these results corroborate the need to avoid Pa persistence.


The main biomechanical risk factors for the prevalence of the left hip joint traumatic and degenerative changes.
The aim of this paper is to examine characteristic biomechanical features leading to the acetabular fracture and hip joint arthrosis, and to explain the prevalence of the left side traumatic and degenerative pelvic pathology that is usually seen in diverse groups of patients. A total of 253 patients were analyzed in a retrospective case-control study during a six-year period. The patients were divided into the case group of 103 patients suffering traumatic acetabular fractures and into the control group of 150 patients with hip joint arthrosis, where operative aloarthroplasty was not yet performed. The data of the affected hip joint range of motions in the case and control group of patients were statistically analyzed correlating the difference in frequency of the left and right hip joint pathology. The left acetabulum was affected more commonly in both groups of patients, while arthrosis of the left hip joint was more commonly recorded in the control group. More frequent pathology of the left hip joint, found in both groups of patients, was probably due to weaker neuromuscular function of the left pelvic side, which was also more exposed to injury due to the greater input of forces to the left hip joint during a traffic accident.


Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS.
The associated use of permissive hypercapnia (PHY) and high PEEP levels (PEEP(IDEAL)) has been recently indicated as part of a lung-protective-approach (LPA) in acute respiratory distress syndrome (ARDS). However, the net hemodynamic effect produced by this association is not known. We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients (mean age 34 +/- 13 yr) with ARDS, focusing on its immediate (after 1 h), early (first 36 h), and late (2nd-7th d) consequences. Twenty-five patients were submitted to LPA--with the combined use of permissive hypercapnia (PHY), VT < 6 ml/kg, distending pressures above PEEP < 20 cm H2O, and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve (P(FLEX))- and 23 control patients were submitted to conventional mechanical ventilation. LPA was initiated at once, resulting in an immediate increase in heart rate (p = 0.0002), cardiac output (p = 0.0002), oxygen delivery (DO2l, p = 0.0003), and mixed venous Po2 (p = 0.0006), with a maintained systemic oxygen consumption (p = 0.52). The mean pulmonary arterial pressure markedly increased (mean increment 8.8 mm Hg; p < 0.0001), but the pulmonary vascular resistance did not change (p = 0.32). Cardiac filling pressures increased (p < 0.001) and the systemic vascular resistance fell (p = 0.003). All these alterations were progressively attenuated in the course of the first 36 h, despite persisting hypercapnia. Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients (p < 0.0001). No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved. A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis, with no depressant effects ascribed to high PEEP levels. In contrast, high plateau pressures were associated with cardiovascular depression. Thus, as long as sufficiently low distending pressures are concomitantly applied, the sudden installation of PHY plus PEEP(IDEAL) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population.


Assisted suicide for prisoners? Stakeholder and prisoner perspectives.
For a wider project on aging in prison, the authors interviewed 35 older prisoners and 24 stakeholders (prison staff, prison healthcare professionals, and policy makers) about healthcare for prisoners. In all, 6 prisoners and 3 stakeholders spontaneously expressed their attitudes concerning assisted suicide. Some prisoners seek assisted suicide for medical reasons and others because they regard spending the rest of their lives in prison as undignified. However, stakeholders identified several ethical and practical challenges in providing assisted suicide to prisoners. This article presents these perspectives on assisted suicide in prison and provides an ethical analysis of the issues raised.


[Dorsal and lumbar metastases diagnosed by bone scintigraphy in a gastric adenocarcinoma patient].
A case of 67 year old man suffering from gastric cardia adenocarcinoma with disseminated bone metastases is reported. This case report describes multiple bone metastases from a gastric carcinoma diagnosed by bone scintigraphy without radiologic and computed tomography changes and confirmed by the patient's fulminating evolution. In this report the bone scintigraphy results in patients with osseous metastases secondary to gastric cancer and the role of diagnostic imaging methods in the assessment of metastatic bone lesions are reviewed.


Increased detection of circulating tumor cells in the blood of colorectal carcinoma patients using two reverse transcription-PCR assays and multiple blood samples.
The objectives of this study were to assess whether the use of two reverse transcription-PCR (RT-PCR) cDNA assays and multiple blood sampling increased circulating tumor cell detection in colorectal cancer patients. Systemic blood was sampled three times at 1-min intervals in 100 colorectal cancer patients (50 primary tumors only and 50 liver metastases), and in 70 control patients without known cancer. After removal of the erythrocytes, samples were subjected to separate RT-PCR reactions using specific primers for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). Statistical analysis was performed by the two-sample binomial test and the one-sided McNemar test. There were significant increases in circulating tumor cell positivity when CEA and CK20 assays were used together as compared with either CEA or CK20 assay used alone. There were also significant increases in circulating tumor cell positivity for either CEA or CK20 assay used alone when the results from two blood samples were compared with the results from one sample. Circulating colorectal cancer cell positivity rose from 48% (CEA) and 34% (CK20) with one assay of one sample to 74% when both assays of three samples were used to identify circulating tumor cells. Three non-cancer control patients (4.3%) were positive for either CEA (two patients) or CK20 (one patient). Tumor cells were identified more frequently in the circulation of colorectal cancer patients than had been suggested previously. RT-PCR-based studies of the clinical significance of circulating cancer cells in colorectal cancer should involve multiple blood samples with identification of multiple tumor-related cDNA products.


Association between benign prostatic hyperplasia and suicide in South Korea: A nationwide retrospective cohort study.
Benign prostatic hyperplasia is a commonly diagnosed disease in elderly men, but elderly men with benign prostatic hyperplasia are more likely to have a lower quality of life and depressive symptoms. This study aims to examine the association benign prostatic hyperplasia patients with suicide death relative to a control group comprising individuals without benign prostatic hyperplasia. We used the Korean National Health Insurance Service-National Sample Cohort from 2006 to 2015 comprising of 193,785 Korean adults ≥40 years old, and followed-up for suicide death during the 8.7 years period. Cox-proportional hazard model was used to estimate hazard ratios for suicide among patients with benign prostatic hyperplasia. From 2006 to 2010, a total of 32,215 people were newly diagnosed with benign prostatic hyperplasia. The suicide rate of people without benign prostatic hyperplasia was 61.6 per 100,000 person-years, whereas that of patients with benign prostatic hyperplasia was 97.3 per 100,000 person-years, 1.58 times higher than the control group (p<0.01). After adjusting for covariates, the hazard ratio for suicide among patients with benign prostatic hyperplasia was 1.47 (95% C.I. = 1.21 to 1.78; p<0.01) compared to people without benign prostatic hyperplasia. For men without mental disorders, the hazard ratio for suicide among patients with benign prostatic hyperplasia was 1.36 (95% CI = 1.05 to 1.76) compared to control group after adjusting for multiple covariates. Our study suggests that men with benign prostatic hyperplasia had a higher probability of suicide compared to men without benign prostatic hyperplasia in South Korea. This study suggests that physicians may be aware that men newly diagnosed with benign prostatic hyperplasia had high probability of suicide.


Employment of a metal microgrid as a front electrode in a sandwich-structured photodetector.
A highly UV-transparent metal microgrid was prepared and employed as the front electrode in a sandwich-structured ultraviolet (UV) photodetector using TiO(2) thin film as the semiconductor layer. The photo-generated charger carriers travel a shorter distance before reaching the electrodes in comparison with a photodetector using large-spaced interdigitated metal electrodes (where distance between fingers is several to tens of micrometers) on the surface of the semiconductor film. This photodetector responds to UV light irradiation, and the photocurrent intensity increases linearly with the irradiation intensity below 0.2 mW/cm(2).


An exploratory factor analysis of children's depression inventory scores in young children of substance abusers.
A factor analytic study of scores obtained on the Children's Depression Inventory from a sample of 202 young children (M = 7.5 yr., SD = 2.2) of alcoholics and substance abusers was completed. A principal components factor analysis with an oblique rotation yielded five separate factors related to Negative Self-concept, Acting-out. Somatic/Disturbed Symptoms, Mood, and Hopelessness. In previous factor analytic studies of the Children's Depression Inventory with normal and clinical populations the primary factor obtained was formed by mood-related items. In contrast, the primary factor of the present analysis was formed by items concerning perceptions of self-concept, not mood. These results corroborated previously reported data from the Child Behavior Checklist suggesting that the depressive symptoms displayed by children of substance abusers are related to self-concept and externalization.


[Condylomata acuminata--topical and systemic interferon therapy].
An open study was carried out to test the effect of systemic administration of interferon (IFN) gamma and local application of IFN beta as monotherapy and adjuvant treatment. The topical application of IFN beta gel had no effect as monotherapy and when it was given as adjuvant therapy the rate of recurrence was not significantly reduced. IFN gamma was given for monotherapy in two different doses (100 and 200 micrograms per s.c. injection). The response rate to the cyclic treatment was 45% in the group (20 patients) receiving a dosage of 100 micrograms, and 57% in the group (26 patients) receiving a dosage of 200 micrograms. Patients with a duration of the disease longer than 18 months and patients with immune deficiency did not respond to the monotherapy. A group of 15 patients with resistant genital warts received adjuvant treatment with IFN gamma over 7 days after surgical treatment. In patients with inconspicuous immune status it was possible to reduce the recurrence rate.


X-ray structures of Bacillus pallidus d-arabinose isomerase and its complex with l-fucitol.
d-Arabinose isomerase (d-AI), also known as l-fucose isomerase (l-FI), catalyzes the aldose-ketose isomerization of d-arabinose to d-ribulose, and l-fucose to l-fuculose. Bacillus pallidus (B. pallidus) d-AI can catalyze isomerization of d-altrose to d-psicose, as well as d-arabinose and l-fucose. Three X-ray structures of B. pallidus d-AI in complexes with 2-methyl-2,4-pentadiol, glycerol and an inhibitor, l-fucitol, were determined at resolutions of 1.77, 1.60 and 2.60 A, respectively. B. pallidus d-AI forms a homo-hexamer, and one subunit has three domains of almost equal size; two Rossmann fold domains and a mimic of the (beta/alpha) barrel fold domain. A catalytic metal ion (Mn(2+)) was found in the active site coordinated by Glu342, Asp366 and His532, and an additional metal ion was found at the channel for the passage of a substrate coordinated by Asp453. The X-ray structures basically supported the ene-diol mechanism for the aldose-ketose isomerization by B. pallidus d-AI, as well as Escherichia coli (E. coli) l-FI, in which Glu342 and Asp366 facing each other at the catalytic metal ion transfer a proton from C2 to C1 and O1 to O2, acting as acid/base catalysts, respectively. However, considering the ionized state of Asp366, the catalytic reaction also possibly occurs through the negatively charged ene-diolate intermediate stabilized by the catalytic metal ion. A structural comparison with E. colil-FI showed that B. pallidus d-AI possibly interconverts between "open" and "closed" forms, and that the additional metal ion found in B. pallidus d-AI may help to stabilize the channel region.


Callers' attitudes and experiences of UK breastfeeding helpline support.
Breastfeeding peer support, is considered to be a key intervention for increasing breastfeeding duration rates. Whilst a number of national organisations provide telephone based breastfeeding peer support, to date there have been no published evaluations into callers' experiences and attitudes of this support. In this study we report on the descriptive and qualitative insights provided by 908 callers as part of an evaluation of UK-based breastfeeding helpline(s). A structured telephone interview, incorporating Likert scale responses and open-ended questions was undertaken with 908 callers over May to August, 2011 to explore callers' experiences of the help and support received via the breastfeeding helpline(s). Overall satisfaction with the helpline was high, with the vast majority of callers' recalling positive experiences of the help and support received. Thematic analysis was undertaken on all qualitative and descriptive data recorded during the evaluation, contextualised within the main areas addressed within the interview schedule in terms of 'contact with the helplines'; 'experiences of the helpline service', 'perceived effectiveness of support provision' and 'impact on caller wellbeing'. Callers valued the opportunity for accessible, targeted, non-judgmental and convenient support. Whilst the telephone support did not necessarily influence women's breastfeeding decisions, the support they received left them feeling reassured, confident and more determined to continue breastfeeding. We recommend extending the helpline service to ensure support can be accessed when needed, and ongoing training and support for volunteers. Further advertising and promotion of the service within wider demographic groups is warranted.


[Positron-emission tomography: role of 18F-fluorodeoxyglucose (18FDG) imaging in oncology].
There is a renewed interest in positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) since the development of large field of view cameras and the capability of regional distribution of 18FDG. This method may help solve three types of problems in clinical oncology: tumor diagnosis and extension assessment, prediction of treatment response and follow-up (diagnosis of recurrences and complications). The aim of this paper is to review the literature in this field. This technique is mostly used for brain, lung, rectal and breast tumors as well as for sarcomas. It is possible to diagnose an anaplastic transformation of a low grade glioma since 18FDG uptake correlates with the histological grade. 18FDG plays another important role in the evaluation of the brain tumor response to treatment and of the secondary effects or sequelae of this treatment. This technique is also useful in breast carcinomas: diagnosis in the case of a dense breast, detection of lymph nodes or other metastases which could modify the strategy. One of the most established roles of 18FDG PET is the diagnosis of rectal tumor recurrences. Furthermore, future results will probably confirm its usefulness in lung carcinoma, for the diagnosis and for treatment evaluation. Lastly, it plays an important role in soft tissue sarcomas at all stages of diagnosis and treatment. The results of the literature still have to be completed. However, if the capability of predicting tumor response to treatment is confirmed, this method will play an important role in patient management and will modify treatment strategies.


Oxygen desaturation in a transgender man: initial concerns and recommendations regarding the practice of chest binding: a case report.
Over 1.4 million US adults identify as transgender when gender identity differs from the sex assigned at birth [1]. Although transgender patients face adverse health outcomes, they remain an understudied population [2]. A 2017 study surveyed 411 practicing clinicians and found that 80% had been involved in treating a transgender patient, but 80.6% had never received training on transgender care [3]. The purpose of this report is to describe prolonged desaturation in one case of a transgender patient who wore a chest binder intraoperatively owing to a lack of preoperative recognition. A 19-year-old transgender male of African-American descent with anxiety and class 3 obesity presented for an esophagogastroduodenoscopy to evaluate a 2-year history of upper abdominal pain unresponsive to proton pump inhibitor therapy, with a plan for monitored anesthesia care. His medications included sertraline, pantoprazole, zolpidem, ergocalciferol, leuprolide, and testosterone cypionate. Preoperatively, the patient was instructed to remove all clothing and to don a patient gown while in the bathroom. The attending anesthesiologist then conducted the interview and examination in the preoperative holding area. The patient was induced with 250 mg of propofol, and reassuring respirations were noted by capnography. Respirations and oxygen saturation remained stable upon insertion of the endoscope. Four minutes later, the patient's oxygen saturation rapidly decreased to 50% and end-tidal capnography was lost. The endoscope was removed, and the patient was given 200 mg of propofol and 20 mg succinylcholine. His oxygen saturation recovered to 80% and 100% after 2 and 5 minutes, respectively, of ventilation with 100% inspired oxygen. No further oxygen desaturation was noted throughout the procedure, and the patient was closely monitored for signs of respiratory difficulty during an uneventful postoperative course. After full emergence, it was revealed that the patient had been wearing a chest binder throughout the operative procedure. The patient was counseled on the necessity to communicate the presence of this accessory prior to all future procedures. In the clinical narrative, a healthy patient was observed to have prolonged oxygen desaturation after induction of anesthesia. Laryngospasm was suspected clinically owing to the sudden absence of end-tidal carbon dioxide. Prolonged oxygen desaturation despite appropriate interventions suggests the contribution of additional factors. We speculate that the presence of a chest binder intraoperatively predisposed the patient to more rapid oxygen desaturation less responsive to typical therapy. A chest binder would introduce mechanical restriction to the patient's breathing owing to its inherent design to compress. Although the patient was asked to remove all clothing, specific instructions were not provided regarding the removal of a chest binder. The presence of chest binding was also absent in the electronic health record, despite the documented presence of the patient's preferred gender, hormonal therapy regimen, and medical history. Ultimately, this case reflects the gap between practitioner knowledge and hospital guidelines and the practices of transgender patients. In reviewing existing literature and the potential for atelectasis with external compression, we would consider that patients refrain from chest binding for 12-24 hours before surgical procedures, resume no sooner than 24 hours after ambulation, and participate in diagnostic incentive spirometry pre- and postoperatively.


Dual Atomic Coherence in the Self-Assembly of Patchy Heterostructural Nanocrystals.
Advances in the synthesis and self-assembly of nanocrystals have enabled researchers to create a plethora of different nanoparticle superlattices. But while many superlattices with complex types of translational order have been realized, rotational order of nanoparticle building blocks within the lattice is more difficult to achieve. Self-assembled superstructures with atomically coherent nanocrystal lattices, which are desirable due to their exceptional electronic and optical properties, have been fabricated only for a few selected systems. Here, we combine experiments with molecular dynamics (MD) simulations to study the self-assembly of heterostructural nanocrystals (HNCs), consisting of a near-spherical quantum dot (QD) host decorated with a small number of epitaxially grown gold nanocrystal (Au NC) "patches". Self-assembly of these HNCs results in face-centered-cubic (fcc) superlattices with well-defined orientational relationships between the atomic lattices of both QD hosts and Au patches. MD simulations indicate that the observed dual atomic coherence is linked to the number, size, and relative positions of gold patches. This study provides a strategy for the design and fabrication of NC superlattices with large structural complexity and delicate orientational order.


Suppression by Hydrangeae Dulcis Folium of D-galactosamine-induced liver injury in vitro and in vivo.
Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SER. var. thunbergii MAKINO, suppressed D-galactosamine-induced liver injury by 85.2% when added to the diet at 1% and fed to rats for fifteen days. The hepatoprotective effect is more potent than that of a milk thistle extract and turmeric powder. Some fractionated extracts showed hepatoprotective activity in the D-galactosamine-induced in vitro liver injury model.


Stem cells propagate their DNA by random segregation in the flatworm Macrostomum lignano.
Adult stem cells are proposed to have acquired special features to prevent an accumulation of DNA-replication errors. Two such mechanisms, frequently suggested to serve this goal are cellular quiescence, and non-random segregation of DNA strands during stem cell division, a theory designated as the immortal strand hypothesis. To date, it has been difficult to test the in vivo relevance of both mechanisms in stem cell systems. It has been shown that in the flatworm Macrostomum lignano pluripotent stem cells (neoblasts) are present in adult animals. We sought to address by which means M. lignano neoblasts protect themselves against the accumulation of genomic errors, by studying the exact mode of DNA-segregation during their division. In this study, we demonstrated four lines of in vivo evidence in favor of cellular quiescence. Firstly, performing BrdU pulse-chase experiments, we localized 'Label-Retaining Cells' (LRCs). Secondly, EDU pulse-chase combined with Vasa labeling demonstrated the presence of neoblasts among the LRCs, while the majority of LRCs were differentiated cells. We showed that stem cells lose their label at a slow rate, indicating cellular quiescence. Thirdly, CldU/IdU- double labeling studies confirmed that label-retaining stem cells showed low proliferative activity. Finally, the use of the actin inhibitor, cytochalasin D, unequivocally demonstrated random segregation of DNA-strands in LRCs. Altogether, our data unambiguously demonstrated that the majority of neoblasts in M. lignano distribute their DNA randomly during cell division, and that label-retention is a direct result of cellular quiescence, rather than a sign of co-segregation of labeled strands.


Multi-functional graphene as an in vitro and in vivo imaging probe.
A strategy has been developed for the synthesis of multi-functional graphene (MFG) using green synthetic approach and explored its biomedical application as a promising fluorescent marker for in vitro and in vivo imaging. In-situ microwave-assisted reduction and magnetization process was adopted to convert the graphene oxide into magnetic graphene within 1 min, which was further covalently modified to build a polyacrylic acid (PAA) bridge for linking the fluorescein o-methacrylate (FMA) to yield MFG with water-dispersibility (∼2.5 g/l) and fluorescence property (emission maximum at 526 nm). The PAA bridges also functions to prevent graphene-induced fluorescence quenching of conjugated FMA. The extent of reduction, magnetization, and functionalization was confirmed with TEM, AFM, Raman, XPS, FT-IR, TGA, and SQUID measurements. In vitro cytotoxicity study of HeLa cells reveal that MFG could stand as a biocompatible imaging probe with an IC(50) value of ∼100 μg/ml; whereas in vivo zebrafish study does not induce any significant abnormalities nor affects the survival rate after microinjection of MFG. Confocal laser scanning microscopy images reveals that MFG locates only in the cytoplasm region and exhibits excellent co-localization and biodistribution from the head to tail in the zebrafish. Our results demonstrate the applicability of graphene based fluorescence marker for intracellular imaging and, more significantly, as well as whole-animal imaging. Hence, MFG could preferentially serve as a dual functional probe in biomedical diagnostics.


Interaction of Amyloidogenic Proteins with Membranes and Molecular Mechanism for the Development of Alzheimer's disease.
Molecular mechanism of diseases like Alzheimer's disease (AD) and Parkinson's diseases (PD) is associated with misfolding of specific proteins, such as amyloid beta (Aβ) proteins in the case of AD, followed by their self-assembly into toxic oligomers along with the formation of amyloid fibrils assembled as plaques in the brain. Interaction of Aβ with membrane can lead to membrane damage; this process is considered as the major factor associated with the AD development. Additionally, membrane can facilitate the aggregation process of Aβ proteins. This important property of membranes is discussed in this review. A specific emphasis is given to the recently discovered property of cellular membranes to catalyze the initial step of Aβ aggregation process by which self-assembly of Aβ can be observed at physiologically low concentrations of Aβ proteins. At such low concentrations, no spontaneous aggregation occurs in the bulk solution. This fact was a major weakness of the protein aggregation model for AD. The catalytic property of membrane surfaces towards Aβ aggregation depends on the membrane composition. This finding suggests a number of novel ideas on the development of treatments and preventions for AD, which is briefly discussed in the review.


Influence on cell-cell communication (dye-transfer) of the oncogenic beta-blocker DL-ZAMI 1305: possible relation to tumor promotion.
The effect of the oncogenic beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butyl-amino-propan-2-ol (DL-ZAMI 1305) on intercellular communication between cultured cells was studied. Intercellular communication of Chinese hamster V79 cells was measured by the dye-transfer method in which the spread of intracellularly microinjected fluorescent probe, Lucifer Yellow CH, through gap-junctions was used as an index of intercellular communication. When V79 cells are cultured with non-toxic doses (1-60 micrograms/ml) of DL-ZAMI 1305, a significant inhibition of dye-transfer is observed after 4 h. The inhibition is dose-related and greater than 90% inhibition is seen at the dose of 50 micrograms/ml. When DL-ZAMI 1305 is added at 0 and 24 h of experiment, its inhibitory effect is maintained for at least 48 h at high doses (50-60 micrograms/ml), whereas for lower doses of DL-ZAMI 1305, some recovery is seen after 24 h incubation. These results are suggestive of a possible tumor-promoting activity of DL-ZAMI 1305; in vivo studies on this carcinogen are in progress.


Restraint vs. hindlimb suspension on fluid and electrolyte balance in rats.
To determine the effect of hindlimb suspension on body fluid volume, salt and water balance, and relevant hormones, two series of experiments were performed in an experimental protocol including periods of isolation (7 days), horizontal attachment (7 days), and suspension (14 days). 1) During the first experiment, water and electrolyte balance, arginine vasopressin (AVP), and guanosine 3',5'- cyclic monophosphate (cGMP) were determined in urine, atrial natriuretic peptide in plasma and atria, and renin concentration and AVP in plasma in 30 rats. 2) During the second experiment, blood volume and extracellular fluid volume were measured by a dilution technique (Evans blue and sodium thiocyanate) in another 30 rats. We observed a pronounced and early effect of horizontal attachment on the renal variables. After 48 h, diuresis (49%), natriuresis (44%), kaliuresis (36%), osmotic load (39%), creatinine (28%), and AVP excretion (155%) were significantly increased in attached rats (P < 0.05). There was no short-term (24-h) effect of suspension on urine flow and Na+, K+, creatinine, and AVP excretion, but the urine cGMP decreased significantly (45%; P < 0.05). Significant decreases in natriuresis, kaliuresis, urine creatinine, and osmotic load occurred in the suspension group 7 days after suspension. After the 14-day tail suspension, plasma volume and extracellular fluid volume measured in suspended rats were not different from isolated rat values, whereas plasma volume increased by 15% (P < 0.05) in the attached rats. Plasma immunoreactive plasma atrial natriuretic levels of suspended rats were significantly reduced by 35% vs. isolated rats (P < 0.001) and by 18% vs. attached rats (P < 0.05). By using this experimental protocol, the physiological alterations revealed that suspension produced some acute and long-term effects, but the fixation to the suspension device, restraint, and confinement have their own influence on fluid distribution and renal function.


Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation.
Chromatin immunoprecipitation assays were employed to assess the kinetics of transcription factor assembly and histone modifications that occur during gamma interferon (IFN-gamma) induction of CIITA gene expression. CIITA is the master regulator of major histocompatibility complex class II transcription. Promoter IV (PIV), the major IFN-gamma responsive promoter for CIITA expression, requires both STAT1 and IFN regulatory factor 1 (IRF-1) for induction by IFN-gamma. STAT1 binding to PIV was detected first and was accompanied by a modest acetylation of histones H3 and H4 that were associated with the region. Despite these changes, which occurred within 30 min of IFN-gamma treatment, CIITA mRNA was not detected until IRF-1 protein was synthesized and bound to its site, a process that required >120 min. In contrast to these events, fetal trophoblast-like cell lines, which are refractory to CIITA induction by IFN-gamma, failed to assemble the above factors or modify their chromatin, suggesting that accessibility to the promoter is blocked. Bisulfite sequencing of PIV showed strong hypermethylation of PIV, providing a link between methylation, chromatin structure, and factor binding. Together, this analysis provides a kinetic view of the activation of the CIITA gene in response to IFN-gamma and shows that regulatory factor assembly, chromatin modification, and gene expression proceed in discrete steps.


Extracts of Waste from Poplar Wood Processing Alleviate Experimental Dextran Sulfate-Induced Colitis by Ameliorating Oxidative Stress, Inhibiting the Th1/Th17 Response and Inducing Apoptosis in Inflammatory Lymphocytes.
As a fast-growing tree, poplar is widely planted and typically used for wood processing in China. During poplar wood processing, a large amount of poplar sawdust (PS) and poplar leaves (PL) are produced and abandoned. To make full use of poplar resources and clarify the use of poplar as a feed additive, the active ingredients in PS and PL were extracted and isolated, and the anti-inflammatory effects of the extracts on mice with dextran sulfate sodium (DSS)-induced colitis were investigated. In vitro anti-inflammatory experiments showed that the ethyl acetate extract of PS and PL (PSE and PLE, respectively) could significantly inhibit the proliferation of concanavalin A (Con A)-activated lymphocytes. Salicortin, tremulacin and salireposide were identified in both PSE and PLE. Oral administration of PSE and PLE rescued DSS-induced colonic shortening, repaired tissue damage, and decreased the disease activity index (DAI). The antioxidant capacity, including the increased activities of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD and catalase (CAT) and decreased activity of myeloperoxidase (MPO), in the colons of mice with colitis was enhanced through the activation of ERK after treatment with PSE and PLE. The ratio of Th1 to Th17 cells, which can lead to inflammation in the spleen, was significantly decreased by the administration of PSE and PLE, while the phosphorylation of related transcription factors (p65, STAT1, and STAT3) was inhibited. Furthermore, PSE and PLE could induce apoptosis in Con A-activated lymphocytes, which may be associated with the increase in p-TBK1, as the molecular docking results also indicated that salireposide in PSE and PLE could interact with the TBK1 protein. Overall, our study provides a promising feed additive for improving intestinal inflammation in animals and a method for the full utilization of poplar resources.


Initial Treatment Choice Affects Cost-Effectiveness and Reintervention Rates for Dupuytren Contracture: A National Census Among Veterans Affairs Patients.
A multitude of treatments for Dupuytren contracture are available, including both invasive and minimally invasive options. This study compares the reintervention rates and costs associated with various treatment options for Dupuytren disease (DD) within the Veterans Affairs (VA) Health Administration. Using the Corporate Data Warehouse, a national census was performed including all patients treated for DD in years 2014 to 2020 within the VA health care system. Patients treated with collagenase clostridium histolyticum (CCH), percutaneous needle aponeurotomy (PNA), open fasciotomy, palmar fasciectomy, single finger fasciectomy, and multifinger fasciectomy were compared. The total cost of initial treatment was compared between modalities. The 5-year reintervention rates were compared using a Kaplan-Meier analysis. During the study period, 8530 patients were treated for DD (3501 fasciectomy, 3351 CCH, 880 PNA, 798 fasciotomy). The overall median treatment cost was found to be the least for PNA (P < .0001). The 5-year reintervention rates were significantly lower for single finger fasciectomy (6.5%), operative fasciotomy (8.2%), and palmar fasciectomy (9%) when compared with PNA (12.3%), multifinger fasciectomy (13.1%), and CCH (14.4%) (P < .001). However, reintervention rates were comparable between patients treated with PNA, multifinger fasciectomy, and CCH (P > .05). Within the VA population, PNA is the most affordable procedure per treatment episode and is associated with reintervention rates that are comparable to those of CCH. Multifinger fasciectomy, CCH, and PNA had comparable reintervention rates. The differences in reintervention rates may partially be explained by patients' willingness to consider additional treatment to correct any remaining or recurrent deformity.


Social network effects of nonlifesaving early-stage breast cancer detection on mammography rates.
We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography. We constructed an agent-based model of mammography decisions, in which 10 000 agents that represent women aged 40 to 100 years were linked together on a social network, which was parameterized with a survey of 716 women conducted through the RAND American Life Panel. Our model represents a population in equilibrium, with demographics reflecting the current US population based on the most recent available census data. The aggregate effect of women learning about 1 category of cancers-those that would be detected but would not be lethal in the absence of screening-was a 13.8 percentage point increase in annual screening rates. Anecdotes of detection of early-stage cancers relayed through social networks may substantially increase demand for a screening test even when the detection through screening was nonlifesaving.


Extracorporeal membrane oxygenation: radiographic appearance of the neonatal chest.
The chest radiographs of 26 newborns treated with extracorporeal membrane oxygenation (ECMO) for intractable respiratory failure were reviewed. The typical radiographic appearance of the lungs in these patients is that of diffuse pulmonary opacification with variable volume loss. Air bronchograms and patchy basilar atelectasis are also common findings. Generally, decreasing ECMO requirements were reflected in improving chest radiographs with radiographic improvement lagging behind clinical improvement. Of 167 chest radiographs available for evaluation, 105 (62.8%) reflected changes in ECMO flow rates. Radiographs in patients with individual diagnoses of hyaline membrane disease, meconium aspiration syndrome and sepsis showed the best correlation with clinical improvement (95 [69%] of 137 radiographs). Those obtained in patients with congenital diaphragmatic hernia and persistent pulmonary hypertension of the newborn alone showed the poorest correlation (10 [30%] of 30 of radiographs). Neither the absolute degree of radiographic abnormality nor degree of radiographic improvement correlated well with ECMO requirements. Initial radiographs were useful in confirming the position of bypass cannulae and respiratory tubes. Routine daily examinations did not reveal unexpected abnormalities. However, radiographs taken during periods of increased ECMO requirements due to patent ductus arteriosus or volume overload showed worsening lung opacification.


Assessment of quality of life in phase III trials of radiotherapy in localized or locally advanced head and neck cancer over the past 17 years.
We investigated the extent to which health-related quality of life (HRQOL) parameters have been used as endpoints in recent phase III trials on radiotherapy for head and neck cancer, as well as the frequency and correlates of significant HRQOL gains. Using the medical subject headings "head and neck neoplasms" and "radiotherapy", we searched PubMed for the main paper reporting phase III trials published between 1/1999 and 12/2015 in 16 leading journals. We found 88 trials that fulfilled the selection criteria (32,707 patients/191 trial arms). HRQOL was listed as an endpoint in 21.3% of trials. HRQOL comparisons between groups were reported in only 12 trials, with statistically significant differences between HRQOL parameters in only three studies, two of which favored the experimental arm. HRQOL has been infrequently investigated in phase III trials of radiotherapy in head and neck cancer, typically with no significant differences found between groups.


Femoral profunda artery aneurysm as an unusual first presentation of Behcet disease.
Behcet disease is a multisystem inflammatory disorder, rarely found in African Americans. Arterial involvement occurs in less than 8% of patients. Profunda femoral artery aneurysms (PFAAs) are extremely rare and often occur with synchronous aneurysms. We present a case of an African American man diagnosed with Behcet disease from his presentation with PFAA. He was also found to have a synchronous hypogastric artery aneurysm. The patient was immediately treated with corticosteroids and infliximab to control systemic and vascular inflammation, returning 1 month later for surgery. He had a repair of the left PFAA with a common femoral to profunda femoris artery bypass with reversed saphenous vein graft and aneurysmorrhaphy. When a patient presents with an aneurysm in an unusual location, it is important to evaluate for other aneurysms. A careful history and physical examination is also required to see if the aneurysm may be part of an underlying systemic syndrome.


Possibility of using the yes/no Angoff method as a substitute for the percent Angoff method for estimating the cutoff score of the Korean Medical Licensing Examination: a simulation study
The percent Angoff (PA) method has been recommended as a reliable method to set the cutoff score instead of a fixed cut point of 60% in the Korean Medical Licensing Examination (KMLE). The yes/no Angoff (YNA) method, which is easy for panelists to judge, can be considered as an alternative because the KMLE has many items to evaluate. This study aimed to compare the cutoff score and the reliability depending on whether the PA or the YNA standard-setting method was used in the KMLE. The materials were the open-access PA data of the KMLE. The PA data were converted to YNA data in 5 categories, in which the probabilities for a "yes" decision by panelists were 50%, 60%, 70%, 80%, and 90%. SPSS for descriptive analysis and G-string for generalizability theory were used to present the results. The PA method and the YNA method counting 60% as "yes," estimated similar cutoff scores. Those cutoff scores were deemed acceptable based on the results of the Hofstee method. The highest reliability coefficients estimated by the generalizability test were from the PA method and the YNA method, with probabilities of 70%, 80%, 60%, and 50% for deciding "yes," in descending order. The panelist's specialty was the main cause of the error variance. The error size was similar regardless of the standard-setting method. The above results showed that the PA method was more reliable than the YNA method in estimating the cutoff score of the KMLE. However, the YNA method with a 60% probability for deciding "yes" also can be used as a substitute for the PA method in estimating the cutoff score of the KMLE.


Arginine 469 is a pivotal residue for the Hsc70-GlcNAc-binding property.
The members of the 70kDa-heat shock proteins (HSP70) family play numerous fundamental functions in the cell such as promoting the assembly of multimeric complexes or helping the correct folding of nascent proteins to take place. In numerous previous studies we demonstrated that Hsp70 and its constitutive isoform Hsc70 are endowed of a GlcNAc-binding activity. The molecular modeling of the substrate binding domain of Hsc70 and in silico docking experiments using Ser/Thr-O-GlcNAc motifs allowed to define the potential carbohydrate-recognition region and to point out the crucial position of Arg469 as an amino-acid directly interacting with the sugar moiety. We cloned a flagged Hsc70 in a pCMV.SPORT6 vector and we showed that the mutation R469A decreased the GlcNAc-binding property of the chaperone of around 70%. This is the first work reporting the localization of the GlcNAc-binding domain of a member of the HSP70 family.


Incorporation of medical informatics and information technology as core components of undergraduate medical education - time for change!
It is generally accepted that Information Technology (IT) is a highly desirable and a very necessary ingredient of modern health care. Review of available literature reveals a paucity of medical informatics and information technology courses in undergraduate medical curricula and a lack of research to assess the effectiveness of medical informatics in undergraduate medical education. The need for such initiatives is discussed and a pilot project is described that evaluated the effectiveness of education in the use of Electronic Medical Record (EMR) applications. Educational activities, for example, could be medical students conducting virtual medical encounters or interacting with EMR applications. An EMR application, which was used in several related projects, has been adapted to the educational environment: standardized patient records can be created and cloned so that individual students can interact with a "standard" patient and alter the patient's data.


Involvement of the rat medial prefrontal cortex in novelty detection.
The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection.


[Diagnosis of prosthetic mitral valve regurgitation by Doppler color flow imaging using right parasternal approach: a comparative study with transesophageal method].
Doppler color flow imaging is a useful tool in evaluating mitral regurgitation (MR). However, it is frequently difficult to assess prosthetic valve MR by the conventional transthoracic approach using left parasternal or apical echo-windows, because of the interception of ultrasound by the prosthesis or artifacts produced by its motion. The purpose of this study is to determine the usefulness of the "right" parasternal approach (RPA) in the echo diagnosis of prosthetic MR. Six patients with pathological prosthetic MR determined by transesophageal approach (TEA) were studied. Transthoracic echo was performed using both the RPA and the conventional approach, and the presence or absence and the extent of MR signals by these transthoracic approaches were compared with those by TEA. Prosthetic MR was detected in five of six patients by the RPA and the extent of MR signals by the RPA was very similar to that by TEE in each of the five patients. MR could not be detected by the RPA only in one patient, whose MR was estimated to be very mild by TEE. By the conventional approach, MR could not be detected in three patients and the degree of MR was significantly underestimated in two of the remaining three patients. Thus, the transthoracic RPA is often as useful as TEA in diagnosing prosthetic MR, which is often undetectable or underestimated by the conventional approach. Because the RPA is less invasive than TEA, the RPA should be encouraged in patients with suspected prosthetic mitral valve dysfunction.


Contraceptive steroids influence the hemostatic activation state in healthy men.
Hormonal contraception for men requires administration of testosterone and gestagens. The effects of a long-acting testosterone ester and 2 different progestins on hemostatic activation parameters were studied in relation to cardiovascular risk. In phase 1, 7 healthy men aged 28-38 years received a single intramuscular injection of 200 mg norethisterone-enanthate (NET-EN) on Day 0. Plasma samples were obtained on Days 0, 14, 41, and 84. In phase 2, 3 groups of 14 healthy men aged 18-45 years received four injections (every 6 weeks) of 1000 mg testosterone undecanoate (TU), plus daily oral placebo or daily oral levonorgestrel (LNG, 250 microg); or four injections (every 6 weeks) of NET-EN. Treatment lasted 24 weeks. Plasma samples were obtained at weeks 0, 16, 24, and 52. All samples were assayed for levels of coagulation factors VIIc, VIIa, XIIc, and XIIa; prothrombin fragment F1+2 (F1+2); antithrombin; plasmin-alpha(2)-antiplasmin-complex (PAP); and fibrinogen. NET-EN alone led to a depletion of sexual hormones and a marked shift in hemostatic parameters with increasing levels of FXIIc, fibrinogen, antithrombin, and F1+2, whereas FVIIc and FVIIa levels decreased. PAP levels increased significantly. Opposite effects were seen in the TU/placebo group, with a significant down-regulation of fibrinolysis and the hemostatic turnover rate. Testosterone effects were attenuated by additional administration of gestagens. The effect of hormonal male contraception using long-acting testosterone esters with or without gestagens was significantly measurable within the hemostatic system. Down-regulation of the hemostatic system with testosterone alone may indicate an antithrombotic effect, whereas clinical consequences of an additional gestagen compound cannot be derived.