Statistical agreement of left ventricle measurements using cardiac magnetic resonance and 2D echocardiography in ischemic heart failure.
The aim of this study was to compare cardiac magnetic resonance imaging (CMR) with 2-dimensional echocardiography (2D echo) in the assessment of left ventricle (LV) function parameters and mass in patients with ischemic heart disease and severely depressed LV function. Although 2D echo is commonly used to assess LV indices, CMR is the state-of-the-art technique. Agreement between these 2 methods in these patients has not been well established. LV indexed end systolic and diastolic volumes (EDVi and ESVi), indexed mass (LVMi) and ejection fraction (EF) were assessed in 67 patients (12 women), using 2D echo and CMR. According to statistical analysis (Bland-Altman), 2D echo underestimated LV EDV and ESV and overestimated EF and LVMi compared to CMR. The highest correlation between 2D echo and CMR was found for EDVi (R2=0.73, p<0.0001) and ESVi (R2=0.69, p<0.0001) and the lowest for EF (R2=0.21, p=0.001) and LVMi (R2=0.20, p=0.002). The maximal differences between 2D echo and CMR were found for highest mesurements of LV volumes and mass, and for lowest EF values. There is moderate to strong correlation between CMR and 2D echo in the assessment of LV function parameters and mass in patients with ischemic heart failure. Between-method agreement depends on the degree of LV dysfunction. The results of assessment of the severely damaged LV obtained by the use of 2D echo should be interpreted with caution.


Talk outside the box: Parents' decontextualized language during preschool years relates to child numeracy and literacy skills in middle childhood.
Children's literacy and numeracy skills are fundamental for early academic performance and later academic success, mental health, and employment prospects in adulthood. Given that parents play a key role in promoting child development, identifying early parenting behaviors that predict literacy and numeracy skills is a research imperative. Emerging evidence suggests that parental use of decontextualized language (DL)-talk that requires cognitive abstraction and transcends the here and now-predicts children's literacy skills. However, its relation to numeracy remains underexplored. Accordingly, the current study examined how DL during interaction with children in infancy (T1) and preschool years (T2) relates to child literacy and numeracy in middle childhood (T3). Participants were 26 Irish mother-father-child triads (16 female children). At T1 and T2, participants engaged in 5-min interactions that were coded for DL. At T3, child literacy and numeracy were assessed using the Wechsler Intelligence Scale for Children-Fourth Edition and teacher report of child scores on national standardized tests. Controlling for child age and contextualized utterances, child reading in middle childhood was negatively related to maternal and child DL in infancy but was positively related to DL during preschool years, suggesting that the benefits of DL may become apparent later in development. Mothers', fathers', and children's DL during preschool years was also positively linked with child numeracy in middle childhood. Thus, embedding DL in conversation with children may have positive domain-specific and cross-domain effects on children's literacy and numeracy performance. Findings provide incentive for future research to examine relations between DL and children's school performance across a wider range of developmental domains.


Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. This retrospective study enrolled 202 patients with TIO. Occurrence of HPT in patients with TIO. HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.


A composite screening tool for medication reviews of outpatients: general issues with specific examples.
Regular performance of medication reviews is prominent among methods that have been advocated to reduce the extent and seriousness of drug-related problems, such as adverse drug reactions, drug-disease interactions, drug-drug interactions, drug ineffectiveness and cost ineffectiveness. Several screening tools have been developed to guide practising healthcare professionals and researchers in reviewing the medication patterns of elderly patients; however, each of these tools has its own limitations. This review discusses a wide range of general prescription-, treatment- and patient-related issues that should be taken into account when reviewing medication patterns by implicit screening. These include generic and therapeutic substitution; potentially superfluous or inappropriate medications; potentially inappropriate dosages or duration of treatment; drug-disease and drug-drug interactions; under-treatment; making use of laboratory test results; patient adherence, experiences and habits; appropriate dosage forms and packaging. A broad selection of specific examples and references that can be used as a basis for explicit screening of medication patterns in outpatients is also offered.


Morphological and immunological studies on pustulosis palmaris et plantaris, especially on its focal infection theory.
The deposition of immunoglobulins and complement was examined in skin lesions of pustulosis palmaris et plantaris by applying a direct-immunofluorescence technique. Linear deposition of IgG and C3 was demonstrated in the horny layer in 5 cases out of 10. The antikeratinlayer antibody was measured using the sera of patients with PPP, and elevated levels were recorded in patients with a maximum ratio of 1:80. Light and electron-microscopical examinations revealed a structure similar to the epidermal keratin layer of the tonsillar epidermis and phagocytosis of the structure by macrophages. This is an interesting finding in view of the antigen of the epidermal keratin layer.


Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus-response in spinal muscular atrophy.
Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn (survival of motor neuron) deficiency that could contribute to axonopathy and presynaptic dysfunction in SMA. Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation. We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In addition, in axon terminals of Smn-deficient motoneurons, ribosomes failed to respond to the brain-derived neurotrophic factor stimulation, and did not undergo rapid association with the axonal ER in response to extracellular stimuli. These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.


Improved thermoelectric performance of Bi-deficient BiCuSeO material doped with Nb, Y, and P.
Thermoelectric materials convert waste heat into electric energy. Oxyselenide-based material, specifically, p-type BiCuSeO, is one of the most promising materials for these applications. There are numerous approaches to improve the heat-to-electricity conversion performance. Usually, these approaches are applied individually, starting from the pure intrinsic material. Higher performance could, however, be reached by combining a few strategies simultaneously. In the current work, yttrium, niobium, and phosphorous substitutions on the bismuth sites in already bismuth-deficient Bi1-xCuSeO systems were investigated via density functional theory. The bismuth-deficient system was used as the reference system for further introduction of substitutional defects. The substitution with phosphorous showed a decrease of up to 40 meV (11%) in the energy gap between conduction and valence bands at the highest substitution concentration. Doping with niobium led to the system changing from a p-type to an n-type conductor, which provides a possible route to obtain n-type BiCuSeO systems.


Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation.
Leptin is a nutritionally regulated adipocyte-derived cytokine. Previous studies in obese patients have demonstrated increased inflammatory markers and increased platelet aggregation in association with leptin. However, the effects of leptin administration on markers of inflammation and platelet aggregation in a human model of undernutrition have not previously been studied. The objective of the study was to investigate markers of inflammation, platelet activation, and platelet aggregation in a model of caloric deprivation and increased leptin sensitivity. This study was a randomized, placebo-controlled study conducted between November 2002 and November 2003. The study was conducted at an inpatient care setting at the General Clinical Research Center. Twenty healthy, young (18-35 yr old), normal-weight (body mass index, 20-26 kg/m2) women were recruited from local advertisements. No subjects withdrew due to adverse effects. The effects of physiological recombinant methionyl human leptin or identical placebo administration were investigated over a 4-d fast. The primary outcome measures for this study were C-reactive protein (CRP) and indices of platelet activity. Leptin administration prevented the fasting-induced decline in leptin (P < 0.05 vs. placebo at each time point). Leptin administration increased CRP (6.3 +/- 2.4 vs. 0.7 +/- 0.3 mg/liter; P = 0.04), circulating P-selectin (11.6 +/- 10.2 vs. -28.9 +/- 15.6 ng/ml; P = 0.04), and induction of platelet aggregation (5.8 +/- 2.6 vs. -2.7 +/- 2.9%, P = 0.04, percent maximum platelet aggregation) relative to placebo administration (change in leptin vs. change in placebo, respectively, for each variable). Leptin tended to increase serum amyloid A [0.1 +/- 0.2 vs. -0.3 +/- 0.1 log10 (ng/ml); P = 0.07], and the changes in serum amyloid A and CRP were highly correlated (r = 0.83; P < 0.0001). No changes in TNFalpha, IL-6, IL-10, plasminogen activator inhibitor-1, haptoglobin, intercellular adhesion molecule, or vascular cell adhesion molecule were seen between the groups. Our data provide evidence that physiological leptin administration stimulates inflammatory and platelet responses in humans during caloric deprivation.


Use of an insertable loop recorder in a myotonic dystrophy patient.
The case of a 66-year-old woman with myotonic dystrophy is presented. This patient underwent implantation of an insertable loop recorder as a participant in a clinical trial. At 1-month follow-up, interrogation of the insertable loop recorder revealed multiple episodes of wide complex tachycardia. She underwent electrophysiologic study, which revealed moderate His-Purkinje disease, focal atrial tachycardia, monomorphic ventricular tachycardia, and ventricular fibrillation. Successful radiofrequency ablation of the focal atrial tachycardia and implantation of a dual-chamber implantable cardioverter defibrillator was performed.


Effect of seven low-dose combined oral contraceptive preparations on carbohydrate metabolism.
The effect of seven low-dose oral contraceptive preparations on carbohydrate metabolism was investigated in groups of 10 healthy volunteers. All preparations contained a similar amount of ethinyl estradiol but differed in the content and type of progestogen. The following progestogens were used: levonorgestrel (monophasic and triphasic), norethisterone (monophasic), cyproterone acetate (monophasic), desogestrel (monophasic and biphasic) and gestodene (triphasic). An oral glucose tolerance test was performed before and after 6 months of treatment; glucose disappearance and insulin response curve were determined. Long-term glucose homeostasis was assessed by the estimation of the extent of glycosylation of plasma proteins and hemoglobin A1. The area under the curve for insulin and glucose did not change during treatment with any of the preparations. In addition the representative variables for long-term glucose control did not increase for any of the preparations during treatment. We conclude from these results that the low-dose pills investigated in this study do not have any adverse effects on glucose metabolism after treatment for 6 months.


From the pages of AllergyWatch®: November 2020.
For this month's edition of "From the Pages of AllergyWatch," I have chosen reviews of articles of interest to the clinical allergist. The first study found that wheezing infants with atopic sensitization at the time of the first wheezing episode was strongly associated with bronchial reactivity in childhood. The next review, of an article published in the Annals of Allergy, Asthma & Immunology, investigated the complexity of atopic sensitization to foods in children with atopic dermatitis (AD). The final study confirms the determination of the US Environmental Protection Agency to the likely causal link between exposures to particulate matter and ozone and respiratory illness.


Occupational health hazards of trichloroethylene among workers in relation to altered mRNA expression of cell cycle regulating genes (p53, p21, bax and bcl-2) and PPARA.
Trichloroethylene (TCE) is widely used as a metal degreaser in industrial processes. The present study reports on the effects of TCE exposure on workers employed in the lock industries. To ensure exposure of the workers to TCE, its toxic metabolites, trichloroacetic acid (TCA), dichloroacetic acid (DCA) and trichloroethanol (TCEOH) were detected in the plasma of the subjects through solid phase microextraction-gas chromatography-electron capture detection. TCA, DCA and TCEOH were detected in the range of 0.004-2.494 μg/mL, 0.01-3.612 μg/mL and 0.002-0.617 μg/mL, respectively. Quantitative reverse transcription polymerase chain reaction analysis revealed up-regulated expression of p53 (2.4-fold; p < 0.05), p21 (2-fold; p < 0.01), bax (2.9-fold; p < 0.01) mRNAs and down-regulated expression of bcl-2 (67%; p < 0.05) mRNAs, indicating DNA damaging potential of these metabolites. No effects were observed on the levels of p16 and c-myc mRNAs. Further, as TCA and DCA, the ligand of peroxisome proliferator activated receptor alpha (PPARA), are involved in the process of hepatocarcinogenesis in rodents, we examined expression of PPARA mRNA and let-7c miRNA in the workers. No statistically significant differences in expression of PPARA mRNA and let-7c miRNA in patients were observed as compared to values in controls. Dehydroepiandosterone sulfate (DHEAS) is a reported endogenous ligand of PPARA so its competitive role was also studied. We observed decreased levels of DHEAS hormone in the subjects. Hence, its involvement in mediation of the observed changes in the levels of various mRNAs analyzed in this study appears unlikely.


Effect of degranulation on superoxide dismutase activity in human neutrophils.
Resting neutrophils possess cytosolic cyanide-sensitive (CNs) superoxide dismutase (SOD) and cyanide-insensitive (CNi) SOD, located in an undefined organelle of the 27,000 g sedimentable fraction of its homogenate. Stimulated neutrophils generate large amounts of superoxide anion, part of which is released in the extracellular medium and contributes to changes that occur in inflammatory foci. Our purpose was to assess whether or not the neutrophil upon stimulation secreted either or both CNs and CNi SOD activity, because the process could protect against the release of superoxide anion. Human neutrophils stimulated in vitro with phorbol myristate acetate released 32.6% and 53% of their content in myeloperoxidase (an azurophilic granule marker) and vitamin B12 binding activity, respectively. The CNi SOD was not secreted at all, whereas 16% and 23% of CNs SOD were released by resting and stimulated neutrophils, respectively. In contrast, lactate dehydrogenase, a cytosolic marker, was released by both resting and stimulated cells (approximately equal to 9%). These results suggest that CNi SOD is not located in the granules but in another organelle that does not degranulate upon stimulation and consequently does not protect against superoxide anion formed by neutrophils in the extracellular medium. In contrast, CNs SOD is slightly but significantly released (P less than .02) and may be protective. Neutrophils from two patients with chronic granulomatous disease behaved similarly to control neutrophils but their content of both types of SOD was higher than that of the controls.


Comparison of two newly suggested power, refrigeration, and hydrogen production, for moving towards sustainability schemes using improved solar-powered evolutionary algorithm optimization.
In the third millennium, developing countries will confront significant environmental problems such as ozone depletion, global warming, the shortage of fossil resources, and greenhouse gas emissions. This research looked at a multigenerational system that can generate clean hydrogen, fresh water, electricity, heat, and cooling. The system's components include Rankine and Brayton cycles, an Organic Rankine Cycle (ORC), flash desalination, an Alkaline electrolyzer, and a solar heliostat. The proposed process has been compared for two different start-up modes with a combustion chamber and solar heliostat to compare renewable and fossil fuel sources. This research evaluated various characteristics, including turbine pressure, system efficiency, solar radiation, and isentropic efficiency. The energy and exergy efficiency of the proposed system were obtained at around 78.93% and 47.56%, respectively. Exergy study revealed that heat exchangers and alkaline electrolyzers had the greatest exergy destruction rates, at 78.93% and 47.56%, respectively. The suggested system produces 0.04663 kg/s of hydrogen. Results indicate that at the best operational conditions, the exergetic efficiency, power, and hydrogen generation of 56%, 6000 kW, and 1.28 kg/s is reached, respectively. Also, With a 15% improvement in the Brayton cycle's isentropic efficacy, the quantity of hydrogen produced increases from 0.040 kg/s to 0.0520 kg/s.


Monogenic Versus Polygenic Forms of Hypercholesterolemia and Cardiovascular Risk: Are There Any Differences?
Common DNA variants with small effects work together to create susceptibility to polygenic hypercholesterolemia. Some clinicians wonder whether patients with polygenic hypercholesterolemia have less severe clinical features compared to patients with monogenic familial hypercholesterolemia (FH) caused by rare deleterious variants. Studies performed in cohorts of patients with both monogenic and polygenic hypercholesterolemia have assessed lipid levels, non-invasive markers of atherosclerosis, and clinical end points, including major adverse cardiovascular events. The totality of data suggests a gradient across genotypes. Specifically, individuals with polygenic hypercholesterolemia have deleterious phenotypes that are intermediate in severity between those in patients with monogenic hypercholesterolemia and in control subjects. Although clinical variables in patients with polygenic hypercholesterolemia are less severe than in those with monogenic hypercholesterolemia, cardiovascular risk is still very high in these patients compared to controls. Patients with polygenic hypercholesterolemia must be treated assertively.


A Novel Gaussian Extrapolation Approach for 2-D Gel Electrophoresis Saturated Protein Spots.
Analysis of images obtained from two-dimensional gel electrophoresis (2-D GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software currently available have proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this chapter, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate proteins quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2-D GE images, comparing reconstructed spots with the corresponding non-saturated image. The results demonstrate that the algorithm enables correct spot quantification.


Longitudinal Renal Function in Liver Transplant Recipients With Acute-on-Chronic Liver Failure.
To analyze the impact of acute-on-chronic liver failure (ACLF) immediately before liver transplantation (LT) on short-term kidney function. In this retrospective study, we included 416 of 687 consecutive patients who had an estimated glomerular filtration rates (eGFRs) at 3-month post-LT. We compared the non-ACLF (N = 356), ACLF with eGFR ≥30 mL/min/1.73 m (A-HGFR, N = 32), and ACLF with eGFR <30 mL/min/1.73 m (A-LGFR, N = 28) groups at LT and for 2 kidney-related outcomes: (i) slope of eGFR by linear mixed model and (ii) time to development of composite kidney outcomes (eGFR < 15 mL/min/1.73 m or need for dialysis). The mean eGFRs at LT in non-ACLF, A-HGFR, and A-LGFR groups were significantly different as follows: 83.9 ± 29.5, 56.5 ± 31.2, and 21.6 ± 5.0 mL/min/1.73 m, respectively. The eGFR slope significantly increased in A-LGFR group (+7.26 mL/min/1.73 m/mo), whereas it remained stable in A-HGFR group (+1.05 mL/min/1.73 m/mo) and significantly declined in non-ACLF group (-7.61 mL/min/1.73 m/mo) by the first 3-month period. On the other hand, the eGFR slope in all groups stabilized after 3 months post-LT. A-LGFR group showed significantly increased risk of developing composite kidney outcomes in adjusted analysis (hazard ratio = 3.61, 95% confidence interval: 1.35-9.70) compared with the non-ACLF group. However, this significance disappeared after the further adjustment for eGFR at 3-month post-LT (hazard ratio = 1.91, 95% confidence interval: 0.70-5.23). The slopes of eGFR before 3-month post-LT were significantly different among non-ACLF, A-HGFR, and A-LGFR groups. The renal dysfunction in A-LGFR group stabilized after partial recovery by 3-month post-LT (eGFR reset point).


Cloning of the recB, recC, and recD genes from Proteus mirabilis in Escherichia coli: in vivo formation of active hybrid enzymes.
We cloned chromosomal DNA fragments from Proteus mirabilis which complement recBCD deletion mutants of Escherichia coli by restoring (i) recombination proficiency in conjugation, (ii) normal resistance to UV irradiation, and (iii) ATP-dependent exonuclease activity for duplex DNA. The data indicate that the order of the genes thyA, recC, recB, recD, and argA is similar in both P. mirabilis and E. coli. Hybrid enzymes formed in vivo were active in repair and recombination.


Microarchitectural changes in the aging skeleton.
The age-related reduction in bone mass is disproportionally related to skeletal weakening, suggesting that microarchitectural changes are also important determinants of bone quality. The study of cortical and trabecular microstructure, which for many years was mainly based on two-dimensional histologic and scanning electron microscopy imaging, gained a tremendous momentum in the last decade and a half, due to the introduction of microcomputed tomography (μCT). This technology provides highly accurate qualitative and quantitative analyses based on three-dimensional images at micrometer resolution, which combined with finite elemental analysis predicts the biomechanical implications of microstructural changes. Global μCT analyses of trabecular bone have repeatedly suggested that the main age-related change in this compartment is a decrease in trabecular number with unaltered, or even increased, trabecular thickness. However, we show here that this may result from a bias whereby thick trabeculae near the cortex and the early clearance of thin struts mask authentic trabecular thinning. The main cortical age-related change is increased porosity due to negatively balanced osteonal remodeling and expansion of Haversian canals, which occasionally merge with endosteal and periosteal resorption bays, thus leading to rapid cortical thinning and cortical weakening. The recent emergence of CT systems with submicrometer resolution provides novel information on the age-related decrease in osteocyte lacunar density and related micropetrosis, the result of lacunar hypermineralization. Last but not least, the use of the submicrometer CT systems confirmed the occurrence of microcracks in the skeletal mineralized matrix and vastly advanced their morphologic characterization and mode of initiation and propagation.


Neonatal neurobehavior in infants with autism spectrum disorder.
To investigate neurobehavioral maturation for neonates who are later diagnosed with autism spectrum disorder (ASD). In a prospective longitudinal design, neonatal neurobehavior was examined monthly in 1- to 3-month-old infants at elevated and low familial likelihood of ASD (n=60). At 2 years, infants were seen for a clinical best-estimate evaluation, resulting in 18 infants with ASD and 36 typically developing infants. Repeated-measures analysis of variance models were conducted to examine the effects of age, diagnostic group, and their interactions. Neurobehavioral maturation of infants diagnosed with ASD was largely comparable to typically developing infants from 1 to 3 months, with the exception of the development of attention. Object-focused attention was significantly attenuated for infants with ASD beginning at 2 to 3 months and was predictive of social-communication skills 2 years later. This is the first study to prospectively examine neonatal neurobehavior of infants at an elevated familial likelihood of ASD who later received a diagnosis. Despite relatively intact neurological and behavioral maturation in the neonatal period, attention to objects emerged as a key early indicator of ASD. This suggests a complex attentional vulnerability within the first 3 months of life that may be associated with cascading sequelae of social-communication challenges and the emergence of ASD.


Kinetics of inactivation and molecular asymmetry of NAD-specific glyceraldehyde-3-phosphate dehydrogenase of Pisum sativum.
Glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 220.127.116.11) has been purified to homogeneity from pea seeds. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis (with and without sodium dodecyl sulfate; subunit molecular weight 38 000). It is free from bound nucleotides. The kinetics of heat inactivation of the crude enzyme extract as well as the purified enzyme are biphasic, in that exactly half of the activity is destroyed more rapidly than the residual half. The data are consistent with the rate equation: (formula: (see text): where A0 and A are activities at times zero and t, respectively, and k1 and k2 are first-order rate constants for the fast and slow phases, respectively. Addition of NAD+ slows down thermal inactivation, without altering the overall kinetic pattern. The activity lost due to the fast component (k1) of the reaction is regained on colling ('annealing'), whereas the slow reaction (k2) is not reversed, suggesting the following scheme: formula (see text): This is confirmed by plotting the activity after 'annealing' against initial period of heating. A single first-order rate constant (k2) is observed. The enzyme possesses about one reactive SH group per subunit which can be titrated with 5,5'-dithio-bis-(2-nitrobenzoic acid). Blocking of these groups inactivates the enzyme. Inactivation with 20 micrometer N-ethylmaleimide and 30 micrometer iodoacetate (at pH 8.6 and 33 degrees C) follows simple first-order kinetics (rate constants 0.099 and 0.139 min-1, respectively), suggesting that all SH groups react equally readily with these reagents. Reaction of the enzyme with 0.6 micrometer p-chloromercuri benzoate, however, shows biphasic kinetics similar to thermal inactivation. The reaction of p-chloromercuri benzoate with partially heat-inactivated enzyme (residual activity 37.5%) follows simple first-order kinetics. The molecular asymmetry demonstrated by these results must arise from the unique quaternary structure of the enzyme molecule, which is apparently made up of chemically identical subunits (pseudo-isologous association).


Tumor Wide Horizontal Invasion Predicts Local Recurrence for Scrotal Extramammary Paget's Disease.
Extramammary Paget's disease (EMPD) is a rare malignancy, and little was known about its prognostic factors and optimal treatment. In the current study, we aimed to discuss clinical and pathological features of scrotal EMPD and determine the prognostic factors for cancer-specific survival and local recurrence. A total of 206 patients with scrotal EMPD lesions surgically treated at our institute were studied. All clinical and pathological data were reviewed. Immunohistochemical staining of TP53 and Ki67 was examined as well. At the last follow-up, 175 patients (84.95%) were alive. Twelve patients (5.83%) had died of the disease due to distant metastases. Fifteen patients (7.28%) developed local recurrences of scrotal EMPD. Ki67 expression was significantly elevated in patients with wide horizontal invasion (P = 0.003). In univariate analysis, high invasion level, presence of nodule, presence of lymphovascular invasion, adnexa invasion, lymph node metastasis and high p53 expression were significant factors for poor cancer-specific survival. In multivariate analysis, high p53 expression was significantly correlated with poor cancer-specific survival. Wide horizontal invasion was independently correlated with local recurrence-free survival of scrotal EMPD. In conclusion, wide horizontal invasion is an independent risk factor for local recurrence-free survival in the patients with scrotal EMPD.


Association between mental health and physical activity in patients with chronic heart failure.
Poor mental health (MH) is common in chronic heart failure (CHF) patients. No studies have reported a relation between MH status and objectively measured physical activity (PA) in CHF patients. The study aim was to determine self-reported MH-related differences associated with PA and target values of PA for improved MH in CHF outpatients. We divided 243 CHF outpatients (mean age 57.1 years) into two groups according to MH assessed by Short Form-36 score: high-MH (≥68 points) group (n = 148) and poor-MH (<68 points) group (n = 95). Average step count (steps) and energy expenditure on PA (EE) (kcal) per day for 1 week of PA were assessed by an accelerometer and compared between groups. PA resulting in high MH was determined by the receiver-operating characteristic (ROC) analysis. PA correlated positively with MH in all patients (steps: r = 0.46, p < 0.001; EE: r = 0.43, p < 0.001). After adjusting for patient characteristics, steps and EE were significantly lower in the poor-MH versus high-MH group (5020.1 ± 280.7 versus 7174.1 ± 221.5 steps, p < 0.001; 133.9 ± 10.8 versus 215.9 ± 8.4 kcal, p < 0.001). Cut-off values of 5590.8 steps and 141.1 kcal were determined as PA target values associated with improved MH. Poor MH status may reduce PA. Attaining PA target values may improve MH status of CHF outpatients.


Doctors as managers: moving towards general management? The case of unitary management reform in Norwegian hospitals.
The paper seeks to explore whether the development in department management in Norwegian hospitals after the unitary management reform in 2001 constitutes a development in the direction of general management. Interviews were conducted with ten managers from different levels in a large Norwegian university hospital in 2001-2002, as a unitary management model was implemented. There is an emerging change of practice among the physician managers according to this study. The manager function is more explicit and takes a more general responsibility for the department and the professions. However, the managerial function is substantiated by conditions related to the professional field of knowledge, which gives legitimacy within a medical logic. Contact with the clinic is stressed as important, but it is possible to adjust both amount and content of a clinical engagement to the demands of the new manager position. This has both a symbolic and a practical significance, as it involves both legitimacy and identity issues. The paper shows that the institutionalised medical understanding of management has a bearing on managerial reforms. Managerial changes need to relate to this if they are to have consequences for the managerial roles and structures on department level in hospitals. The paper suggests that the future development of this role will depend on the way the collectivist and individualist aspects of responsibility are handled, as well as on the further development of managerial knowledge of physicians.


Tc-99m human serum albumin: a suitable agent for plasma volume measurements in man.
In 16 patients we have carried out simultaneous plasma-volume measurements with human serum albumins tagged with Tc-99m (Tc-99m HSA) and I-131 (I-131 HSA). The correlation coefficient was 0.987. Tc-99m HSA, prepared from kits that predictably yield high labeling efficiency (and thereby negligible amounts of TCO4-), is clearly a superior agent for repeat plasma volume determinations, because of its shorter half-life and the reduced radiation dose to the subject.


Transmogrification of ocean into continent: implications for continental evolution.
When continents collide, the typical embayments and protrusions along their rifted margins make it likely that fragments of seafloor will be trapped within the growing orogenic belt. These trapped seafloor fragments become preferential depocenters for marine and terrestrial sedimentation. After ∼0.5 Gy, the high radioactivity of their thick terrigenous sediment pile converts former seafloor into a unique form of continental crust and underlying lithosphere. We call this process transmogrification. Initially strong and low-lying basins that act as mechanically stronger blocks in the collisional orogeny will eventually warm, weaken, and thermoisostatically rise and will eventually transform into preferred sites for future continental rifting. In modern Asia, transmogrifying basins have induced the characteristic paired-mountain belt geomorphology associated with the assembly of this supercontinent, for example, the Himalaya/Tibet + Tian Shan surrounding the Tarim Basin that has greatly strengthened the East Asian Monsoon. The time-dependent temperature, uplift, and strength changes associated with transmogrification are relevant for improving our understanding of continental evolution, basin modeling, paleoclimate studies, and natural resources prospection.


Correlation of clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification.
This study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma (LSCC) subtypes according to the 2015 WHO classification. We identified 824 operable LSCC patients undergoing a complete surgical resection at Shanghai Chest Hospital between April 2015 and January 2017. Immunohistochemistry was used to investigate the clinicopathologic features. Among them, the percentages of LSCC subtypes were 66.1% (545/824), 28.6% (236/824), and 5.2% (43/824) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more males, more smokers, and more pneumonectomy surgeries in KSCC patients (p = 0.008, p = 0.000, p = 0.043). There were more N2 lymph node involvement and pathological stage III in NKSCC patients (p = 0.01, p = 0.03). BSCC did not demonstrate specificity to anything, but expressed adenocarcinoma markers more frequently. No significant difference existed between pathological subtypes and other clinicopathologic features, such as age, location type, visceral pleural involvement and lymphovascular invasion. The frequencies of EGFR sensitive mutations and ALK rearrangements were not significantly different among three subtypes. Significant relationships exist between some clinicopathologic features and LSCC subtypes.


Case Study: The Recurrent Fusion RNA DUS4L-BCAP29 in Noncancer Human Tissues and Cells.
Traditional gene fusions are involved in the development of various neoplasias. DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-related fusion in prostate and gastric cancers. This chimeric RNA is believed to play a tumorigenic role. Here, we showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal tissues. It is also present in noncancerous epithelial and fibroblast cell lines. Quantitatively, the fusion transcript has a similar expression level in noncancerous gastric and prostate cell lines and tissues to its expression in cancerous cell lines and tissues. Previously, a loss-of-function approach was used to report a probable functionality for this fusion. However, this approach is not sufficient to prove such functionality. Alternatively, a gain-of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell growth and motility, even in noncancerous cell lines. Finally, we provide further evidence that the fusion transcript is a product of cis-splicing between adjacent genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L-BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript that exists in normal physiology and its progrowth effect is not unique to cancer situations.


Relationships between body image and mental health in white, cisgender college students.
Previous studies have suggested that drive for leanness (DL) may be less maladaptive than drive for thinness (DT) or drive for muscularity (DM). However, no studies have examined whether there might be gender differences in the relationships between these three drives and mental health variables. The purpose of this study was twofold. First, we wanted to examine DL in the context of mental health and to see if it is less maladaptive than DT and DM. Second, we wanted to examine gender differences in the relationships between body dissatisfaction (DT, DM, DL) and mental health in a sample of college students. A sample of 988 White, heterosexual, cisgender college students (76.8% female) completed an omnibus survey measuring body image (DL, DT, DM) and mental health (generalized anxiety, social physique anxiety, self-esteem) variables. Regression analyses evaluated associations between these drives and mental health variables. DT predicted all three mental health outcomes in both men and women. DM predicted generalized and social physique anxiety in women but only generalized anxiety in men. DL predicted social physique anxiety only in women. Because we found gender differences in body image and relationships between body image and mental health, future studies should take gender into account when exploring body image and related variables. V Cross-sectional descriptive study.


13C- and 15N-incorporation of doubly stable isotope labelled Lactobacillus johnsonii in humans.
In the present study, Lactobacillus johnsonii (La1) doubly labelled with 15N and 13C (dlLa1) was used to follow the metabolic fate of orally administered dlLa1 in humans. Experimental study. Research Laboratory, Children's Hospital, University of Rostock. A total of 10 healthy adults aged 23-36 y. The subjects received 87 mg/kg body weight viable dlLa1 and 10 g raffinose together with breakfast. Expired air samples were taken over 14 h, whereas urine and faeces were collected over 2 days. A blood sample was taken after 2 h. 13C- and 15N-enrichments were measured by isotope ratio mass spectrometry (SerCon, UK) and H2-concentrations were measured by electrochemical detection (Stimotron, Germany). The orocaecal transit time (OCTT) was reached after 3.7 h. The 13CO2-exhalation amounted to 8.6% of ingested dose. The urinary excretion of 13C and 15N was 1.3 and 12.4% of ingested dose, respectively, whereas the faecal excretion was 39.9 and 37.6% of ingested dose, respectively. After 2 h, 13C- and 15N-enrichment of fibrinogen amounted to 70 and 90 ppm excess, respectively. In comparison to OCTT of 3.7 h, both stable isotopes appear after 30 min in breath and urine, indicating that dlLa1 is rapidly digested in the small bowel before reaching the caecum. This is confirmed by 13C-and 15N-enrichments of blood plasma fractions. The ingestion of dlLa1 led to an excretion of 50% of ingested dose of both stable isotopes.


Extensive hilar bile duct resection using a transhepatic approach for patients with hepatic hilar bile duct diseases.
Extensive hilar bile duct resection beyond the second- or third-order intrahepatic biliary radicals is usually required for patients with hilar cholangiocarcinoma as well as those with benign inflammatory stricture. Most hilar cholangiocarcinoma is resected with combined major hepatectomy to obtain free surgical margins. The purpose of this study was to show the surgical procedure and the usefulness of extensive hilar bile duct resection using a transhepatic approach for patients with hilar bile duct diseases. Five patients with hepatic hilar bile duct disease and who were unfit for major hepatectomy for several reasons underwent extensive hilar bile duct resection by way of a transhepatic approach. Four of the patients had hilar bile duct cancer, including 1 with mucous-producing bile duct cancer of low-grade malignancy and 1 with a postsurgical benign bile duct stricture. After extensive hilar bile duct resection, bile duct stumps ranged in number from 3 to 7 mm (mean 4.4). Surgical margins at bile duct stump were free of cancer in all 4 cancer patients. The long-term outcomes were as follows: 3 patients are alive at the time of publication, and 2 patients have died. A transhepatic approach may be useful when performing extensive hilar bile duct resection bile duct stricture of biliary disease at the hepatic hilus, especially in high-risk patients who are unfit for major hepatectomy as well as in those having benign bile duct stricture and low-grade malignancy.


The clinical anatomy and pathology of the human atrioventricular valves: implications for repair or replacement.
A critical understanding of cardiac anatomy is essential for design engineers and clinicians with the intent of developing and/or employing improved or novel technologies or therapies for treating an impaired atrioventricular valve. Likewise, such knowledge is required for directing translational research, including initiating preclinical research, assessing the feasibility of clinical trials, and performing first-in-man procedures. There are two atrioventricular valves in the human heart, namely the tricuspid and mitral valves. Both are complex structures whose normal anatomies can vary greatly amongst individuals, and also become modified by disease processes. In this review, we discuss the anatomy, pathology, and issues related to surgical and transcatheter repair of the atrioventricular valves in a translational manner. This article is part of a JCTR special issue on Cardiac Anatomy.


Identification of novel polyglutamine-expanded aggregation species in spinal and bulbar muscular atrophy.
Polyglutamine-repeat disorders are part of a larger family of neurodegenerative diseases characterized by protein misfolding and aggregation. In spinal and bulbar muscular atrophy (SBMA), polyglutamine expansion within the androgen receptor (AR) causes progressive debilitating muscular atrophy and lower motor neuron loss in males. Although soluble polyglutamine-expanded aggregation species are considered toxic intermediates in the aggregation process, relatively little is known about the spectrum of structures that are formed. Here we identify novel polyglutamine-expanded AR aggregates that are SDS-soluble and bind the toxicity-predicting antibody 3B5H10. Soluble, 3B5H10-reactive aggregation species exist in low-density conformations and are larger by atomic force microscopy, suggesting that they may be less compact than later-stage, insoluble aggregates. We demonstrate disease-relevance in vivo and draw correlations with toxicity in vitro. This article is part of a Special Issue entitled SI: Neuroprotection.


First trimester diagnosis of dicephalic parapagus conjoined twins via transvaginal ultrasonography.
Conjoined twins are rare, and most cases are thoracopagus. Parapagus conjoined twins (one body with two heads) are extremely rare. We report a case of dicephalic parapagus twins that was diagnosed in the first trimester at 10 weeks via transvaginal ultrasonography.


The triple-flap nipple-reduction technique.
Pure nipple hypertrophy (macrothelia) is a known but rare condition. Nevertheless, minor disproportions between nipple diameter or height and the areola are quite common. During breast surgery, the surgeon often faces the patient's wish to perform nipple reduction. However the methods described are difficult or have drawbacks. This article proposes a simple technique for both height and diameter, or height only, nipple reduction. A technique consisting of the creation of 3 symmetrical triangular flaps in a "Y" fashion and excision of the core of the nipple was performed on 15 consecutive patients between 2001 and 2004. The esthetic results, scars, sensibility, erectility, and complications were evaluated. All patients presented good to excellent esthetic results, with inconspicuous scars. No major complications occurred in this series. Erectility function of the nipple was preserved in all 15 patients, which is a significant difference when compared with previously published techniques. Alterations in sensibility were temporary and were comparable with summarized alterations in representative published clinical series of both breast reduction and augmentation. The triple-flap nipple-reduction technique has the advantage of feasibility, applicable in both height and diameter nipple hypertrophy, with excellent esthetic results and the preservation of both sensibility and erectility.


Daily metabolism and hepatic balance studies of plasma cortisol and aldosterone in the preruminant calf.
Intestinal and hepatic catabolism of cortisol and aldosterone were studied in the calf using blood samples from the mesenteric artery and portal and hepatic veins collected over 24 h, the hepatic blood flow being continuously recorded during this period. The total hepatic blood flow remained broadly constant over the 24 h, although meals were followed by decreasing flow in the portal vein and by increasing flow in the hepatic artery. The intestinal tract catabolizes cortisol as intensively as the liver (both 13% of cortisol reaching the organ). The part played by the gut and the liver in the catabolism of aldosterone were also equivalent (both 30% of aldosterone reaching the organ). This 24-h study demonstrated that a constant ratio existed between secretion and catabolism of cortisol while the hepatic balance of aldosterone seemed to be modified during the night.


Three Primary Cancers in a Veteran With Agent Orange and Agent Blue Exposures.
A Vietnam War veteran's exposures likely contributed to his cancer diagnoses, but these associations are confounded by his substance use, particularly cigarette smoking.


Solvation models and computational prediction of orientations of peptides and proteins in membranes.
Membrane-associated peptides and proteins function in the highly heterogeneous environment of the lipid bilayer whose physico-chemical properties change non-monotonically along the bilayer normal. To simulate insertion of peptides and proteins into membranes and correctly reproduce the energetics of this process, an adequate solvation model and physically realistic representation of the lipid bilayer should be employed. We present a brief overview of the existing solvation models and their application for prediction of binding affinities and orientations of proteins in membranes. Particular emphasis is placed on the recently proposed PPM method, the corresponding web server, and the OPM database that were designed for positioning in membranes of integral and peripheral proteins with known three-dimensional structures.


Fabrication of ordered arrays of InP microstructures by wet chemical etching with Au masks.
Ordered arrays of InP microstructures have been fabricated on InP(001) substrates by wet chemical etching in aqueous HCl with patterned Au masks. The masks were produced by Au deposition through copper grids or a monolayer of polystyrene microspheres. Square InP mesas (20 x 20 microns) and pillars (approximately 100 nm in both diameter and height) were both produced and characterized by scanning electron microscopy and atomic force microscopy.


The natural course of bacillus Calmette-Guérin induced bladder lesions: A long-term follow-up study and systematic review.
Bacillus Calmette-Guérin (BCG) instillation is the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. Nevertheless, its toxicity often causes bladder complications. On follow-up cystoscopy, post-BCG bladder lesions can be pathologically benign, urothelial carcinoma recurrence, or other types of bladder malignancy. Only a small number of case reports have been published on post-BCG bladder lesions. Their clinical features, natural course, and management remain unknown. We retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center. During a long-term follow-up, we took biopsies on tumor-like lesions and described their changes. In addition, we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review. We described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years. Those lesions could last, grow, or disappear spontaneously, and remain pathological benign for years. In systematic review, we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information. Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type. Based on previous studies and our experience, benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone, even under narrow band imaging mode. Nonetheless, given most of them have a good prognosis, random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.


Imidacloprid susceptibility survey and selection risk assessment in field populations of Nilaparvata lugens (Homoptera: Delphacidae).
Imidacloprid has been used for many years to control planthopper Nilaparvata lugens (Stål) (Homoptera: Delphacidae) in China. To provide resistance assessment for the national insecticide resistance management program, we collected a total of 42 samples of the planthoppers from 27 locations covering eight provinces to monitor their dose responses and susceptibility changes to imidacloprid over an 11-yr period (1996-2006). Results showed that most field populations maintained susceptibility from 1996 to 2003 except for a population from Guilin, Guangxi, in 1997, which showed a low level of resistance to imidacloprid. However, surveys conducted in 2005 indicated that 16 populations from six provinces quickly developed resistance with resistance ratios ranging from 79 to 811. The data collected in 2006 revealed that the resistance levels in 12 populations collected from seven different provinces decreased slightly (RR = 107-316), except the Tongzhou population (Jiangsu Province), which developed 625-fold resistance. Dominant and intensive use of imidacloprid in a wide range of rice, Oryza savita L., growing areas might be a driving force for the resistance development. Migration of the insect also significantly boosted the resistance levels due to extensive and intensive use of imidacloprid in emigrating areas and continuous postmigration sprays of the chemical. In addition, laboratory resistance selection using imidacloprid showed that resistance ratio increased to 14-fold after 27 generations, suggesting that quick resistance development might be associated with more frequent applications of the insecticide in recent years.


CT diagnosis of unsuspected von Hippel-Lindau disease.
Von Hippel-Lindau disease is a hereditary disorder with complex, multi-organ involvement including retinal, central nervous system, and abdominal manifestations. We report a case of clinically unsuspected von Hippel-Lindau disease identified during computed tomography (CT) evaluation of a renal mass. The CT demonstration of a coexisting pancreatic tumor and renal cell carcinoma suggested the correct diagnosis of von Hippel-Lindau disease, which was subsequently confirmed. This case reemphasizes the value of preoperative assessment of renal tumors by CT. The finding of coexisting renal and pancreatic tumors should stimulate the search for further evidence of von Hippel-Lindau disease.


Expression of a ribosome inactivating protein (curcin 2) in Jatropha curcas is induced by stress.
The open reading frame (ORF) encoding curcin 2 was cloned from total genomic and cDNA of Jatropha curcas leaves, which were treated by drought, temperature stress and fungal infection, by polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR amplification. The ORF has 927 bp that encodes a precursor protein of 309 amino acid residues. There are high similarities with curcin and the conserved domain of ribosome inactivating proteins (RIPs). Antiserum to curcin recognized one band of 32 kDa on Western blot of the leaves treated by temperature stresses at 4 degree C and 50 degree C and by fungal infections of Pestalotia funerea, Curvularia lunata (Walk) Boed, Gibberelle zeae (Schw.) Petch. Two bands of 32 kDa and 65 kDa were recognized on Western blot of the leaves treated by 10--40 percent polyethylene glycol (PEG). In addition, the 32 kDa band is nearly the molecular weight of curcin 2. This finding suggests that the protein of 32 kDa should be related to curcin 2. The presence of this protein molecular marker under stresses may provide an experimental foundation to study the stress proteins in J. curcas.


[Preliminary application of combined auditory monitoring technique in resection of vestibular neurinoma].
Objective: To explore the value of electrically evoked auditory brainstem response (EABR) monitoring combined with brainstem auditory evoked potential (BAEP) and compound action potential (CAP) monitoring during vestibular schwannoma resection for the protection of the cochlear nerve. Methods: Clinical data from 12 patients with vestibular schwannomas who had useful hearing prior to surgery were analyzed at the PLA General Hospital from January to December 2021. Among them, there were 7 males and 5 females, ranging in age from 25 to 59 years. Before surgery, patients underwent audiology assessments (including pure tone audiometry, speech recognition rate, etc.), facial nerve function evaluation, and cranial MRI. They then underwent vestibular schwannoma resection via the retrosigmoid approach. EABR, BAEP, and CAP were simultaneously monitored during surgery, and patients' hearing preservation was observed and analyzed after surgery. Results: Prior to surgery, the average PTA threshold of the 12 patients ranged from11 to 49 dBHL, with a SDS of 80% to 100%. Six patients had grade A hearing, and six patients had grade B hearing. All 12 patients had House-Brackman grade I facial nerve function prior to surgery. The MRI indicated tumor diameters between 1.1 and 2.4 cm. Complete removal was achieved in 10/12 patients, while near-total removal was achieved in 2/12 patients. There were no serious complications at the one-month follow-up after surgery. At the three-month follow-up, all 12 patients had House-Brackman grade I or II facial nerve function. Under EABR with CAP and BAEP monitoring, successful preservation of the cochlear nerve was achieved in six of ten patients (2 with grade B hearing, 3 with grade C hearing, and 1 with grade D hearing). Successful preservation of the cochlear nerve was not achieved in another four patients (all with grade D hearing). In two patients, EABR monitoring was unsuccessful due to interference signals; however, Grade C or higher hearing was successfully preserved under BAEP and CAP monitoring. Conclusion: The application of EABR monitoring combined with BAEP and CAP monitoring during vestibular schwannoma resection can help improve postoperative preservation of the cochlear nerve and hearing.


(2S,4S)-amino-4-(2,2-diphenylethyl)pentanedioic acid selective group 2 metabotropic glutamate receptor antagonist.
(2S,4S)-2-Amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid 1m, is a novel metabotropic glutamate receptor (mGluR) antagonist with insignificant ionotropic affinity. It is selective antagonist of negatively-coupled cAMP-linked mGluRs with no effect on phosphoinositide coupled mGluRs. A series of 4-substituted glutamic acid analogues were prepared and it was found that compound 1k is tenfold more potent than 1m. Compound 1k has neither significant affinity for ionotropic glutamate receptors nor group 1 and 3 metabotropic receptors.


Problems in detecting misfit of latent class models in diagnostic research without a gold standard were shown.
The objective of this study was to evaluate the performance of goodness-of-fit testing to detect relevant violations of the assumptions underlying the criticized "standard" two-class latent class model. Often used to obtain sensitivity and specificity estimates for diagnostic tests in the absence of a gold reference standard, this model relies on assuming that diagnostic test errors are independent. When this assumption is violated, accuracy estimates may be biased: goodness-of-fit testing is often used to evaluate the assumption and prevent bias. We investigate the performance of goodness-of-fit testing by Monte Carlo simulation. The simulation scenarios are based on three empirical examples. Goodness-of-fit tests lack power to detect relevant misfit of the standard two-class latent class model at sample sizes that are typically found in empirical diagnostic studies. The goodness-of-fit tests that are based on asymptotic theory are not robust to the sparseness of data. A parametric bootstrap procedure improves the evaluation of goodness of fit in the case of sparse data. Our simulation study suggests that relevant violation of the local independence assumption underlying the standard two-class latent class model may remain undetected in empirical diagnostic studies, potentially leading to biased estimates of sensitivity and specificity.


Anaplastic glioma after high-dose proton-photon radiation treatment for low-grade skull base chondrosarcoma.
We report the case of a 63-year-old man who developed an anaplastic oligoastrocytoma of the brain stem and midbrain 13 years after postoperative high-dose proton-photon radiation therapy for a recurrent low-grade chondrosarcoma of the skull base. To our knowledge, this is the first reported case of an anaplastic glioma after proton-photon irradiation.


Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation.
Recent findings have indicated that nitric oxide (NO) may change the duration of immobility biphasically in the forced swimming test, which is a useful experimental model for screening antidepressant-like activity in rodents. In the present study, we have investigated the role of serotonin and of potassium (K(+)) channels in the dual effects of NO in the mouse forced swimming test (MFST). For this purpose, we tested the effects of l-arginine, an NO precursor, the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and of K(+)-channel blockers tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-DAP). In addition, we used sertraline as a serotonin reuptake inhibitor and cyproheptadine as a serotonin antagonist. l-Arginine increased the duration of immobility in the MFST in low doses (25 mg/kg ip) but decreased it in higher doses (500 and 1000 mg/kg ip). Low doses of l-NAME (50 and 75 microg icv) decreased while higher dose of this drug (150 microg icv) increased the immobility time. TEA (5 microg icv) and 3,4-DAP (0.05 microg icv) significantly reduced the time, whereas K(+) channel opener pinacidil increased the duration of immobility. l-Arginine (100 mg/kg ip) significantly antagonised the effects of l-NAME (50 microg), 3,4-DAP and TEA. Higher dose of l-arginine (500 mg/kg ip) significantly potentiated the effects of 3,4-DAP and TEA, but reduced the effect of pinacidil. Low doses of l-arginine antagonized, but higher doses of l-arginine potentiated the antidepressant-like effect of sertraline. Sertraline potentiated the effects of 3,4-DAP and TEA, but reversed the effect of pinacidil. Cyproheptadine reduced the anti-immobility effect of l-arginine and 3,4-DAP. At the highest effective doses, drugs did not impair the motor functions. These data support the hypothesis that NO effects may involve the release of serotonin and/or modulation of K(+) channels.


[Node status in 454 ductal breast cancers cases according to the association with in situ component].
Studies have shown that breast infiltrating ductal carcinoma develops from precursor lesions or pre-invasive. It is accepted that the risk of invasive ductal carcinoma increased slightly in hyperplasia, but especially in cases of atypical hyperplasia and intraductal carcinoma. To evaluate and compare the nodal status between ductal breast cancer with in situ component (group 1) or without it (group 2). Descriptive and retrospective study that included 454 ductal breast cancers. Data concerning clinical and pathological variables was collected. All data was compared between both groups. Among all cases, 176 (38.8%) showed positive lymph nodes, 136 patients (39.5%) from group 1 and 40 cases (36.4%) from group 2. Among group 1 cases, high-grade subgroup showed higher positive lymph node rate (82 cases, 55.4%) than the extensive in situ carcinomas subgroup (84 cases, 49.7%). Both of them had a significant higher rate than group 2 cases (p = 0.003 y p = 0.028, respectively). Moreover, the low-grade in situ carcinomas without cellular necrosi had positive lymph nodes just in 30 cases (24%), significantly lower (p = 0.034) than group 2. We did not find overall statistical differences between groups depending on in situ associated component. But when we analyzed in situ subgroups, we found differences with higher positive lymph node rate in high grade carcinomas and extensive in situ carcinomas subgroups, while lower affectation rates were observed in low grade carcinomas (without cellular necrosis), compared to the group of breast cancers without in situ component associated.


The radiographic acromiohumeral interval is affected by arm and radiographic beam position.
The objective was to determine whether arm and radiographic beam positional changes affect the acromiohumeral interval (AHI) in radiographs of healthy shoulders. Controlling for participant's height and position as well as radiographic beam height and angle, from 30 right shoulders of right-handed males without shoulder problems four antero-posterior (AP) radiographic views each were obtained in defined positions. Three independent, blinded physicians measured the AHI to the nearest millimeter in 120 randomized radiographs. Mean differences between measurements were calculated, along with a 95% confidence interval. Controlling for observer effect, there was a significant difference between AHI measurements on different views (p< 0.01). All pair-wise differences were statistically significant after adjusting for multiple comparisons (all p values<0.01). Even in healthy shoulders, small changes in arm position and radiographic beam orientation affect the AHI in radiographs.


Reliability of 3-D ultrasound measurements of cervical lymph node volume.
This study was undertaken to evaluate the reliability of three-dimensional (3-D) ultrasound in measuring cervical lymph node volume. Ultrasound examination of the neck was performed on 15 healthy subjects (eight men and seven women). For each subject, the volume of cervical lymph nodes was measured twice with 3-D ultrasound by two operators, to evaluate the reproducibility of measurements (interoperator variability). 3-D ultrasound measurements of cervical node volume were performed with and without using SonoCT and XRES imaging. Each 3-D data set was reviewed and remeasured by the operators to evaluate the repeatability of measurements (intra-operator variability). Results showed that the reproducibility and repeatability of 3-D ultrasound volumetric measurements of cervical nodes was improved when SonoCT and XRES imaging were used. There was a high repeatability of 3-D ultrasound measurements of cervical node volume (> 90%). A high reproducibility of measurements was found in the posterior triangle nodes (90.3% - 90.9%). When SonoCT and XRES imaging were used with the scanning, there was a high reproducibility for parotid node measurements (87.4%) and a satisfactory level of reproducibility for submental (61.8%), submandibular (69.3%) and upper cervical node (79%) measurements. 3-D ultrasound is a useful and reliable method in measuring cervical lymph node volume. However, further studies to improve the reproducibility of 3-D ultrasound measurements of submental, submandibular and upper cervical node volume are suggested.


The KDR gene maps to human chromosome 4q31.2----q32, a locus which is distinct from locations for other type III growth factor receptor tyrosine kinases.
KDR (kinase insert domain receptor), a new type III receptor tyrosine kinase gene, maps to human chromosome 4q31.2----q32 by fluorescence in situ hybridization. This differs from the chromosomal locations of other members of this gene family.


Arc-scanning very high-frequency digital ultrasound for 3D pachymetric mapping of the corneal epithelium and stroma in laser in situ keratomileusis.
To test and demonstrate measurement precision, imaging resolution, 3D thickness mapping, and clinical utility of a new prototype 3D very high-frequency (VHF) (50 MHz) digital ultrasound scanning system for corneal epithelium, flap, and residual stromal thickness after laser in situ keratomileusis (LASIK). VHF ultrasonic 3D data was acquired by arc-motion, meridional scanning within a 10-mm zone. Digital signal processing techniques provided high-resolution B-scan imaging, and I-scan traces for high-precision pachymetry in 4 eyes. Thickness maps of individual corneal layers were constructed. Reproducibility of epithelial, flap, and full corneal pachymetry was assessed for single-point and 3D thickness mapping by repeated measures. Thickness mapping of the epithelium, stroma, flap, and full cornea were determined before and after LASIK. Preoperative to postoperative difference maps for epithelium, flap, and stroma were produced to demonstrate anatomical changes in the thickness profile of each layer. Surface localization precision was 0.87 microm. Central reproducibility for single-point pachymetry of epithelium was 0.61 microm; flap, 1.14 microm; and full cornea, 0.74 microm. Reproducibility for central pachymetry on 3D thickness mapping was 0.5 microm for epithelium and 1.5-microm for full cornea. B-scans and 3D thickness maps after LASIK demonstrated resolution of epithelial, stromal component of the flap, and residual stromal layers. Large epithelial profile changes were demonstrated after LASIK. Topographic variability of flap thickness and residual stromal thickness were significant. VHF digital ultrasound arc-B scanning provides high-resolution imaging and high-precision three-dimensional thickness mapping of corneal layers, enabling accurate anatomical evaluation of the changes induced in the cornea by LASIK.


Safety precautions in the rehabilitation medicine prescription.
The rehabilitation medicine prescription is a communication tool between the referring physician and the rehabilitation team in both the inpatient and outpatient settings. This instrument is critical in both directing a course of treatment as well as minimizing risk to the patient during the treatment sessions. The goal of this article is to provide an overview of the rehabilitation prescription with an emphasis on safety.


[Myocarditis or subendocardial myocardial infarction: role of MRI illustrated by a case report].
A 50-year-old male patient treated with mesalazine for Crohn's disease was admitted in our unit for a chest pain, associated with nonspecific ST depression or ECG and troponin elevation. Coronarography showed minimal changes while SPECT imagery suggested a posterobasal subendocardial infarction, so that the diagnosis was unclear between ischemic disease and mesalazine-induced myocarditis. Eventually, MRI demonstrated clearly a subendocardial posterior infarction eliciting the diagnosis of mesalazine-induced myocarditis. This case report illustrates, in our opinion, that MRI is of invaluable interest in evaluating the characteristics of myocardium, and must be the cornerstone in the diagnosis of myocardial diseases.


Sub-Nanometer Thick Gold Nanosheets as Highly Efficient Catalysts.
2D metal nanomaterials offer exciting prospects in terms of their properties and functions. However, the ambient aqueous synthesis of atomically-thin, 2D metallic nanomaterials represents a significant challenge. Herein, freestanding and atomically-thin gold nanosheets with a thickness of only 0.47 nm (two atomic layers thick) are synthesized via a one-step aqueous approach at 20 °C, using methyl orange as a confining agent. Owing to the high surface-area-to-volume ratio, abundance of unsaturated atoms exposed on the surface and large interfacial areas arising from their ultrathin 2D nature, the as-prepared Au nanosheets demonstrate excellent catalysis performance in the model reaction of 4-nitrophenol reduction, and remarkable peroxidase-mimicking activity, which enables a highly sensitive colorimetric sensing of H2O2 with a detection limit of 0.11 × 10-6 m. This work represents the first fabrication of freestanding 2D gold with a sub-nanometer thickness, opens up an innovative pathway toward atomically-thin metal nanomaterials that can serve as model systems for inspiring fundamental advances in materials science, and holds potential across a wide region of applications.


Lifting wavelet transform for Vis-NIR spectral data optimization to predict wood density.
Visible and near infrared (Vis-NIR) spectroscopy is a mature analytical tool for qualitative and quantitative analysis in various sectors. However, in the face of "curse of dimensionality" due to thousands of wavelengths for a Vis-NIR spectrum of a sample, the complexity of computation and memory will be increased. Additionally, variable optimization technique can be used to improve prediction accuracy through removing some irrelevant information or noise. Wood density is a critical parameter of wood quality because it determines other important traits. Accurate estimation of wood density is becoming increasingly important for forest management and end uses of wood. In this study, the performance of two-dimensional (2D) correlation spectroscopy between wavelengths of various spectral transformations, i.e., reflectance spectra (R), reciprocal (1/R), and logarithm spectra (log (1/R)), were analyzed before optimizing spectral variable. The spectra of optimal transformation were decomposed using biorthogonal wavelet family from 3rd to 8th decomposition level based on lifting wavelet transform (LWT). The optimal wavelet coefficients of LWT were selected based on the performance of calibration set using partial least squares (PLS). Two frequent variable selection methods including uninformative variable elimination (UVE) and competitive adaptive reweighted sampling (CARS) were also compared. The results showed that the dimensionality of spectral matrix was reduced from 2048 to 16 and the best density prediction results of Siberian elm (Ulmus pumila L.) were obtained (Rp2R = 0.899, RMSEP = 0.016) based on LWT.


Transfusions in the Emergency department: More than a blood transfusion.
Increasing haemoglobin and haematocrit levels with blood transfusions has been the gold standard for treating severe anaemia; however, the indication for transfusing concentrated red blood cells is based merely on a few laboratory markers, such as haemoglobin and haematocrit levels, rather than based on the symptoms according to clinical practice guidelines, the implementation of legal regulations and the consensus achieved by the hospitals' transfusion committees. The aim of this multicentre study was to reassess the suitability of the indication for transfusing concentrated red blood cells and the volumes transfused in emergency departments. We established an observational, multicentre, cross-sectional design with 2 participating centres: the La Paz University Hospital and the Hospital of Salamanca. In total, we obtained data from 381 patients, 220 (57.74%) of whom were men with an average age of 71.4±14.0 years and 161 (42.26%) of whom were women with an average age of 75.3±15.3 years (P<.001). The most prevalent underlying diseases in the patients who underwent transfusions were heart disease, which included haemorrhaging due to antiplatelet or anticoagulant therapy (57.7%), haemato-oncologic (15.3%) diseases and neurological disease. Only 54.9% (209/381) of the prescriptions for transfusion were considered appropriate, with significant differences according to the indication.


Trifluoroethanol and its oxidative metabolites: comparison of in vivo and in vitro effects in rat testis.
Trifluoroethanol (TFE) and trifluoroacetaldehyde (TFALD) produced a reduction in testis weight 3 days after a single oral dose of 10 mg/kg. In contrast, administration of trifluoroacetic acid (TFAA) caused no observable testicular effects. Reduction in testis weight was accompanied by morphological changes, involving specific damage to pachytene and dividing spermatocytes, and round spermatids. In an in vitro Sertoli/germ cell co-culture system, only TFALD was found to produce dose-related effects at concentrations of 10(-3) and 10(-4) M. There was increased germ cell loss from the cultures, particularly loss of pachytene and dividing spermatocytes, accompanied by leakage of the pachytene spermatocyte marker enzyme, lactate dehydrogenase-X. TFE and TFAA did not produce these effects in the culture system at concentrations equimolar with TFALD. These results suggest that TFALD may play a critical role in the development of the testis lesion seen with TFE in vivo. The effects seen both in vivo and in vitro were remarkably similar to those previously reported for another substituted alcohol and its metabolites, ethylene glycol monomethyl ether. It is postulated that the two series of compounds may have a similar mode of action on rat testis.


Cutaneous plasmacytoma adjacent to Bowenoid actinic keratosis on the scalp: Is there a link?
Cutaneous extramedullary plasmacytoma without bone marrow involvement is very rare. We present a plasmacytoma on the scalp with an adjacent Bowenoid disease. An 86 year old man presented to our unit with an ulcerated lump on the vertex of the scalp. Excisional biopsy showed plasmacytoma with adjacent Bowenoid actinic keratosis. Blood tests did not show any systemic multiple myeloma. However, skeletal survey showed possible osteolytic lesions in some areas. Sixteen months afterwards, the patient remains well on follow up. As far as we know, this is the first reported case of a cutaneous plasma cell tumour next to an area of Bowenoid actinic keratosis. Relevant literature is investigated here for possible correlation. Within the limitations of this study, solitary primary cutaneous plasmacytoma can be treated surgically with a favourable outcome. A hypothesis of correlation between Bowenoid actinic keratosis and plasmacytoma is investigated here. Further research is needed to confirm this finding.


The effects of phenobarbital on lithium chloride induced taste aversion.
The dose related effects of phenobarbital on LiCl induced taste aversion were examined. Rats were adapted to a 23 hr 50 min water deprivation schedule. On the Treatment Day animals were offered a novel 0.125% saccharin solution during the 10 min drinking session and were then administered 3.0 mEq/kg LiCl. The saccharin solution was presented again on six subsequent Test Days. Sodium phenobarbital 20, 40, 60 and 80 mg/kg was administered 15 min prior to drinking on the first Test Day. Results indicated that all doses significantly attenuated taste aversion with the maximal effect occurring with the 60 mg/kg dose.


Gestational diabetes mellitus (GDM) screening in morbidly obese pregnant women.
To study the outcomes of two-stage GDM screening of morbidly obese women in our obstetric unit and to evaluate the diagnostic performance of 20-week oral glucose tolerance test (OGTT) values in predicting or excluding late onset GDM. A retrospective study in which 190 pregnant women with BMI ≥40 had two-stage screening: a 75g OGTT is performed at 20 weeks and repeated at 28 weeks if the 20-week OGTT was normal. Receiver operating characteristic (ROC) curves for 20-week OGTT values were constructed in order to obtain an optimal cut-off value of fasting and/or 2-h glucose at 20 weeks from which GDM could be predicted or excluded at 28 weeks. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were determined for each of the fasting and 2-h post-load glucose values at 20 weeks. Forty six (24%) women were diagnosed with GDM. Thirty-two (70%) were diagnosed at 20 weeks and 14 (30%) at 28 weeks. The 2-h cut-off value of ≥6mmol/l at the 20-week OGTT had a negative likelihood ratio of 0.12 to predict GDM at 28 weeks. The low negative likelihood ratio reduces the probability of detecting GDM at 28 weeks from 9% (pre-test probability) to 1% (post-test probability). Nearly 70% of the women were diagnosed with GDM at 20 weeks, which gives an early opportunity to treat maternal hyperglycaemia with consequent health benefits. A 2-h cut-off glucose value of 6mmol/l at 20 weeks OGTT has a low negative likelihood ratio which virtually excludes GDM at 28 weeks. Hence women with a 2h value of <6mmol/l at 20 weeks can avoid a repeat 28 week OGTT test.


Evaluation of the accuracy of the mechanical torque wrench by the number of uses and ratchet type.
To evaluate the accuracy of mechanical torque rachet types based on the number of uses. A total of 25 ratchets, including three frictional- and two spring-type torque ratchets from every mechanical torque ratchet group, were used in our study. A digital torque measurement device was used in assessing the efficiency of mechanical torque ratchets. All ratchets were tightened according to the torque values recommended by the companies. The ratchets were tightened 500 times in total. Given the changes in torque delivery by the number of uses, a statistically significant torque loss was observed in the Bego ratchets (P< 0.05), and a statistically significant increase was found in the torque values of the other ratchet groups (P< 0.05). The highest increase in torque values was obtained in the MEDENTIKA ratchet group. This study showed that there are changes in the torque values applied based on the number of rachet uses. Thus, clinicians are advised to regularly evaluate the accuracy of the rachets.


Age-related morphometric differences in responses of rat lungs to ozone.
The influence of age on morphologic changes in lungs of rats exposed to ozone was studied in female Sprague-Dawley rats, aged 60 and 444 days. Rats of both age groups were exposed continuously for 72 hr to either 0.35 or 0.80 ppm ozone, or to filtered air. Tissues were evaluated using light microscopic morphometry and scanning electron microscopy. The lungs from ozone-exposed 60-day-old rats had larger volume fractions of centriacinar lesions than lungs from exposed 444-day-old rats. Within each age group there was an observed dose response, with rats exposed to 0.80 ppm ozone having larger volume fractions of lesions than those exposed to 0.35 ppm. Only the 444-day-old rats lost body weight during the exposure period. They also had smaller fixed lung volumes than same-aged controls. All 60-day-old rats gained weight during the exposure period, although rats exposed to 0.80 ppm ozone gained less than filtered air controls. Lesions observed in both age groups of female rats were qualitatively similar to those previously described in young adult male rats. We conclude that there are age-related differences in the morphometric responses of rats to ozone exposure. Younger rats had larger proportions of centriacinar lesions and macrophages while older rats had greater body weight and lung volume changes.


Electrophilic prostaglandins: identification of protein targets and opportunities for drug discovery.
Electrophilic eicosanoids are endogenous mediators that play complex roles in signaling and adaptive responses. Basal generation of these species contributes to cell homeostasis, whereas their increased generation under situations of oxidative stress may contribute to cell adaptation or cytoprotection, and, if generated in amounts surpassing the cell detoxification mechanisms, may elicit cytotoxicity. Electrophilic prostaglandins with cyclopentenone structure (cyPG) have been shown to exert protective effects in numerous models of inflammation and tissue injury, as well as antitumoral effects. Protein covalent modification is a key mechanism of action of these species. We have used tagged electrophilic PG, mainly cyPG, as tools to characterize electrophilic lipid-protein interactomes. cyPG with different structure elicit the modification of subsets of proteins comprising both common and selective targets. Among the targets identified are proteins involved in inflammatory responses, the modification of which contributes to the anti-inflammatory effects of cyPG, signaling proteins, and proteins involved in chemoprevention, chemoresistance or tumorigenesis. Thus, some cyPG targets, including glutathione transferase and aldo-keto reductases, have broad implications both in redox signaling and as drug targets. We have observed that cyPG effects are highly dependent on cell type, context, and levels of both cyPG and endogenous antioxidants, in particular GSH. Moreover, the ability of cyPG to display biphasic or dual actions and the nature of the proteins modified depend on these factors. A detailed knowledge of cyPG targets and of the factors that modulate protein modification will contribute to the understanding of their mechanisms of action and define their potential as leads for drug discovery, but may also shed light on redox signaling mechanisms. MINECO SAF2012-36519, ISCIII RD12/0013/0008 (Spain), EU COST Action CM1001.


The effect of soil-borne pathogens depends on the abundance of host tree species.
The overarching issue for understanding biodiversity maintenance is how fitness advantages accrue to a species as it becomes rare, as this is the defining feature of stable coexistence mechanisms. Without these fitness advantages, average fitness differences between species will lead to exclusion. However, empirical evidence is lacking, especially for forests, due to the difficulty of manipulating density on a large-enough scale. Here we took advantage of naturally occurring contrasts in abundance between sites of a subtropical tree species, Ormosia glaberrima, to demonstrate how low-density fitness advantages accrue by the Janzen-Connell mechanism. The results showed that soil pathogens suppressed seedling recruitment of O. glaberrima when it is abundant but had little effect on the seedlings when it is at low density due to the lack of pathogens. The difference in seedling survival between abundant and low-density sites demonstrates strong dependence of pathogenic effect on the abundance of host species.


The novel gluconeogenesis inhibitor FR225654 that originates from Phoma sp. no. 00144. III. Structure determination.
A novel gluconeogenesis inhibitor, FR225654 was isolated from the culture broth of Phoma sp. No. 00144. Spectroscopic analysis concluded that FR225654 has a highly oxygenated trans-decalin ring and beta-keto-enol in its main part, and has a characteristic side chain possessing a conjugated carboxylic acid and tri-substituted olefin.


Between a rock and a hard place: Registered nurses' accounts of their work situation in cancer care in Swedish acute care hospitals.
Hospital organizational features related to registered nurses' (RNs') practice environment are often studied using quantitative measures. These are however unable to capture nuances of experiences of the practice environment from the perspective of individual RNs. The aim of this study is therefore to investigate individual RNs' experiences of their work situation in cancer care in Swedish acute care hospitals. This study is based on a qualitative framework analysis of data derived from an open-ended question by 200 RNs working in specialized or general cancer care hospital units, who responded to the Swedish RN4CAST survey on nurse work environment. Antonovsky's salutogenic concepts "meaningfulness", "comprehensibility", and "manageability" were applied post-analysis to support interpretation of results. RNs describe a tension between expectations to uphold safe, high quality care, and working in an environment where they are unable to influence conditions for care delivery. A lacking sense of agency, on individual and collective levels, points to organizational factors impeding RNs' use of their competence in clinical decision-making and in governing practice within their professional scope. RNs in this study appear to experience work situations which, while often described as meaningful, generally appear neither comprehensible nor manageable. The lack of an individual and collective sense of agency found here could potentially erode RNs' sense of meaningfulness and readiness to invest in their work.


DPP-4 (CD26) inhibitor alogliptin inhibits TLR4-mediated ERK activation and ERK-dependent MMP-1 expression by U937 histiocytes.
Dipeptidyl peptidase-4 (DPP-4)/CD26, a cell surface glycoprotein, is expressed by a variety of cells including T cells, B cells, NK cells, and macrophages. Although it has been shown that DPP-4/CD26 is involved in T cell activation, its role in biological functions in macrophages has not been well investigated. In this study, we used alogliptin, a specific inhibitor of DPP 4/CD26, to study the effect of DPP-4/CD26 on the activation of the extracellular signal-regulated kinase (ERK) that plays a critical role in the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) in U937 histiocytes. Results showed that 1nM of alogliptin inhibited ERK phosphorylation induced by lipopolysaccharide (LPS), a ligand for toll-like receptor (TLR)4, by 91%. Furthermore, results showed that alogliptin inhibited LPS-stimulated MMP-1 expression in a concentration-dependent manner and 1nM of alogliptin inhibited MMP-1 expression by 60%. To confirm the involvement of the ERK pathway in MMP-1 expression by U937 cells, we showed that PD98059, a specific inhibitor for the ERK pathway, blocked LPS-stimulated MMP-1 expression. In addition to MMP-1, our study showed that alogliptin also inhibited MMP-9, -12 and -15, but had no effect on TIMP-1 and -2 expression. Taken together, this study showed for the first time that the inhibition of DPP-4/CD26 by alogliptin suppressed TLR4-mediated ERK activation and ERK-dependent MMP expression by U937 cells, suggesting that DPP-4/CD26 may play an important role in macrophage-mediated inflammation response and tissue remodeling.


side-chain-oxidized oxysterols upregulate ACE2 and Mas receptor in rat primary neurons.
Disturbances in cholesterol metabolism have been associated with hypertension and Alzheimer's disease (AD). We recently reported increased angiotensin-converting enzyme (ACE) activity and angiotensinogen (AGT) levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and AD. ACE activity positively correlated with plasma and CSF 27-hydroxycholesterol (27-OH) levels, an oxysterol that passes to the brain from the blood. Additionally, we showed that 27-OH and 24(S)-hydroxycholesterol (24S-OH) enhance AGT synthesis and modulate renin and ACE activities in brain cells. To gain insight into how oxysterols affect the brain renin-angiotensin system (RAS), we analyzed the effects of 24S-OH and 27-OH on two other proteins in this system: ACE2 and Mas receptor (MasR). RT-PCR and Western blot analysis in rat primary neurons treated with either 24S-OH or 27-OH. The levels of ACE2 and MasR were increased by a physiological concentration (1 μM) of these oxysterols after 24 h. 24S-OH and 27-OH enhance the brain RAS by acting on different levels, from the precursor to several downstream enzymes. Our results support the idea that disturbances in cholesterol metabolism would contribute to alterations in the brain RAS, which further suggest mechanistic links between two well-known risk factors for AD: hypercholesterolemia and hypertension.


Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.
Most epithelial cancer types are polygenic in nature and are driven by coordinated dysregulation of multiple regulatory pathways, genes, and protein modifications. The process of coordinated regulation of cancer promoting pathways in response to extrinsic and intrinsic signals facilitates the dysregulation of several pathways with complementary functions, contributing to the hallmarks of cancer. Dysregulation and hyperactivation of cell surface human epidermal growth factor receptors (HERs) and cytoskeleton remodeling by p21-activated kinases (PAKs) are two prominent interconnected aspects of oncogenesis. We briefly discuss the discoveries and significant advances in the area of coordinated regulation of HERs and PAKs in the development and progression of breast and other epithelial cancers. We also discuss how initial studies involving heregulin signaling via HER3-HER2 axis and HER2-overexpressing breast cancer cells not only discovered a mechanistic role of PAK1 in breast cancer pathobiology but also acted as a bridge in generating a broader cancer research interest in other PAK family members and cancer types and catalyzed establishing the role of PAKs in human cancer, at-large. In addition, growth factor stimulation of the PAK pathway also helped to recognize new facets of PAKs, connecting the PAK pathway to oncogenesis, nuclear signaling, gene expression, mitotic progression, DNA damage response, among other phenotypic responses, and shaped the field of PAK cancer research. Finally, we recount some of the current limitations of HER- and PAK-directed therapeutics in counteracting acquired therapeutic resistance and discuss how cancer's as a polygenic disease may be best targeted with a polygenic approach.


Radiofrequency Ablation Versus Repeat Hepatectomy for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
An updated systematic review and meta-analysis was conducted to compare radiofrequency ablation (RFA) versus repeat hepatectomy (RH) for patients with recurrent hepatocellular carcinoma (rHCC) after a previous liver resection. PubMed, EMBASE, and Cochrane databases were searched from inception to October 2021 for randomized controlled trials and propensity-score matched studies. Individual participant survival data of disease-free survival (DFS) and overall survival (OS) were extracted and reconstructed followed by one-stage and two-stage meta-analysis. Secondary outcomes were major complications and length of hospital stay (LOHS). A total of seven studies (1317 patients) were analysed. In both one-stage and two-stage meta-analysis, there was no significant difference in OS between the RFA and RH cohorts (Hazard Ratio (HR) 1.15, 95% CI 0.98-1.36, P = 0.094 and HR 1.12, 95% CI 0.77-1.64, P = 0.474 respectively), while the RFA group had a higher hazard rate of disease recurrence compared to the RH group (HR 1.30, 95% CI 1.13-1.50, P < 0.001 and HR 1.31, 95% CI 1.09-1.57, P = 0.013, respectively). RFA was associated with fewer major complications and shorter LOHS versus RH (Odds Ratio 0.34, 95% CI 0.15-0.76, P = 0.009 and Weighted Mean Difference - 4.78, 95% CI - 6.30 to - 3.26, P < 0.001, respectively). RH may be associated with superior DFS for rHCC, at the expense of higher morbidity rate and longer LOHS. However, OS is comparable between both modalities. As such, these techniques may be utilized as complementary strategies depending on individual patient and disease factors. Large-scale, randomized, prospective studies are required to corroborate these findings.


Developmental delay in infants with congenital heart disease. Correlation with hypoxemia and congestive heart failure.
The mental and motor development of 173 infants with congenital heart disease was assessed by means of the Bayley Scales of Infant Development and clinical neurological examinations. The relationship between age, sex, congestive heart failure, hypoxemia, hospitalization, and test results was evaluated. The presence of congestive heart failure was found to be significantly associated with both mental and motor development delay. Hypoxemia and hospitalization were associated with delayed motor development. Developmental delay could be recognized as early as 2 months of age.


Synthesis of a C-glycoside analogue of beta-D-galactosyl hydroxylysine and incorporation in a glycopeptide from type II collagen.
A stereoselective synthesis of the C-glycoside analogue of beta-D-galactosyl-(5R,2S)-hydroxylysine (1) has been achieved starting from tetra-O-benzyl-D-galactopyranosyl lactone. The synthesis involved establishment of three stereogenic centers in an unambiguous manner. A facially selective Grignard reaction followed by a silane reduction was used for the anomeric position of the C-galactose residue. An Evans allylation established the configuration of the delta-aminomethylene group of the hydroxylysine moiety, whereas an asymmetric hydrogenation utilizing Burk's catalyst was used for the alpha-amino acid moiety itself. The synthesis was completed in 17 steps with an overall yield of 18%, resulting in the most complex and functionalized C-glycoside analogue of a naturally occurring glycosylated amino acid prepared to date. In addition, amino acid 1 was incorporated in a glycopeptide from type II collagen known to be crucial for the response of autoimmune T cells obtained in models of rheumatoid arthritis. A preliminary immunological study revealed that four out of five members in a panel of T cell hybridomas were able to recognize this C-linked glycopeptide when presented by A(q) class II MHC molecules.