Seasonal Susceptibility of Sweet Cherry Pruning Wounds to Calosphaeria pulchella, Cytospora sorbicola, and Eutypa lata.
Fungal canker pathogens commonly infect trees at pruning wounds leading to branch dieback and loss of productivity in sweet cherry orchards. However, the seasonal susceptibility of sweet cherry pruning wounds to Calosphaeria pulchella, Cytospora sorbicola, and Eutypa lata is not well understood. This study compared the susceptibility of sweet cherry pruning wounds made during the dormant season (January) and the postharvest season (late May to June) to infection by main canker pathogens in California. Field trials were conducted in three cherry orchards and trees were pruned at the different periods over 2 years. Fresh pruning wounds were inoculated with spores of each pathogen, and pathogen recovery was assessed through microbiological isolations at 3 to 4 months after inoculations. Pruning wounds made in late May and June resulted in significantly higher infection by Cal. pulchella compared to pruning wounds made in January. Pruning wounds made during both seasons were generally equally susceptible to Cyt. sorbicola and E. lata infections. However, there was one orchard where dormant pruning wounds were more susceptible to infection by E. lata and there was one particularly cold winter where Cyt. sorbicola did not infect pruning wounds. Overall, our findings suggest that Cal. pulchella infections of cherry pruning wounds are more likely to occur during periods of warm temperatures such as late spring and early summer. However, infections by Cyt. sorbicola and E. lata can occur year-round if inoculum is present and if winter temperatures are not abnormally low for California. Finally, our results suggest that the emergence of Cal. pulchella as a major canker pathogen of sweet cherry in California may be the result of a shift from dormant to after-harvest pruning of sweet cherry trees.


Surgical Interventions for Congenital Ptosis: a Systematic Review and Meta-analysis of 14 Randomized Controlled Trials.
Several types of surgeries have been used in the treatment of congenital ptosis, but the optimal methods and materials for this treatment are unknown. The study aims to evaluate the comparative effectiveness and safety of various surgical methods and materials for treatment of congenital ptosis. We performed comprehensive searches of five databases, two clinical trial registries and one gray literature database from inception to January 2022 for related trials to include in this study. Meta-analysis was performed to evaluate the effect of surgical methods and materials on the primary outcomes: margin reflex distance 1 (MRD1), palpebral fissure height (PFH), and degree of lagophthalmos; and secondary outcomes: undercorrection, entropion, corneal epithelial defects, wound dehiscence, recurrence, infection, and cosmetic outcomes. A total of 14 trials evaluating 909 eyes of 657 patients were included in our study. Compared with the levator plication, the frontalis sling significantly increased the MRD1 (MD = - 1.21; 95% CI [- 1.69, - 0.73]), and the levator resection significantly increased the PFH (MD = 1.30; 95% CI [0.27, 2.33]). For the frontalis sling surgical patterns, the fox pentagon was significantly better than the double triangle at improving the degree of lagophthalmos (MD = 0.70; 95% CI [0.32, 1.08]), while the opened pattern provided statistically better cosmetic outcome than the closed frontalis sling. Analysis of surgical material showed that absorbable sutures significantly increased the MRD1 (MD = 1.16; 95% CI [0.60, 1.72]) compared to non-absorbable sutures when used in levator plication; frontalis sling surgeries performed with silicon rods significantly increased the PFH (MD = 0.88; 95% CI [0.29, 1.47]) compared to those performed with Gore-Tex strips, while autogenous fascia lata provided statistically better aesthetic outcome for lid height symmetry and contour. Different surgical methods and materials appear to affect different aspects of the congenital ptosis treatment outcome. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Membrane fluidity and lipid composition of rat small intestinal brush-border membranes during postnatal maturation.
Fluidity and lipid composition of rat small intestinal brush-border membranes (BBM) were studied during maturation in five age groups: newborns, sucklings (1-3 weeks), weaned (4-6 weeks), juveniles (8-10 weeks), and adults (12 weeks). Brush-border membrane fluidity was measured by steady-state fluorescence polarization. Fluorescent probes used were: 1,6-diphenyl-1,3,5-hexatriene, 1-(4-trimethylammonium)phenyl)-6-phenyl-1,3,5-hexatriene, and a set of n-(9-anthroyloxy) fatty acids. Fluorescence anisotropy measured with all fluorophores was increased in adult versus newborn rats (P less than 0.004). The weight ratio of saturated to cis-unsaturated fatty acids increased from birth to the suckling age (P less than 0.0004). The cholesterol to phospholipid molar ratio increased from birth to the weaned age (P less than 0.0001). Cholesterol to protein ratio and phospholipid to protein ratio decreased after the weaned age (P less than 0.004). The results not only describe maturational changes of brush-border membranes but also give a better understanding of the correlations between biophysical and biochemical data in biological membranes.


The "(a)moral brain": When things go wrong.
In the past decades, a growing interest of neuroscience on moral judgment and decision-making has shed new light on the neurobiological correlates of human morality. It is now understood that moral cognition relies on a complex integration of cognitive and affective information processes that implicate a widely distributed brain network. Moral cognition relies on the coordination of several domain-general processes, subserved by domain-general neural networks, rather than a specific moral cognition system subserved by a specific neural network. In this chapter, we will first briefly review what is currently known about the "moral brain," i.e., the network of brain regions consistently implicated in studies of moral cognition, which include decision-making, affective processing, mentalizing, and perspective-taking processing regions. We will then review the evidence of the impairments found in this network in individuals with psychopathy, a condition whose characteristics indicate profound disturbances in appropriate moral processing. We will present data from neuroimaging studies with forensic/clinical, general population, as well as child and adolescent samples, which seem to converge to support the notion that the moral dysfunction observed in individuals with psychopathy may stem from a disruption of affective components of moral processing rather than from an inability to compute moral judgments per se.


Disability methodology redesign: considerations for a new approach to disability determination.
Disability determination meets important societal needs, involving billions of dollars and millions of people every year. However, disability determination decisions often are incorrect, and the high proportion of decision appeals and reversals creates additional administrative expense and difficulty for the people that the disability determination system is intended to support. Projects funded by the United States Social Security Administration explored these issues and developed new conceptual models and tools to improve the accuracy and fairness of disability determination. This paper provides an introduction to the projects and the papers in this special issue of the Journal of Occupational Rehabilitation.


Fruit fate, frugivory, and fruit characteristics: a study of the hawthorn, Crataegus monogyna (Rosaceae).
The fate of fruits from a population of European hawthorn (Crataegus monogyna) in western Oregon, USA, was examined over a two-year period. Only one frugivore, the American robin (Turdus migratorius) foraged on the C. monogyna fruits, making this an unusually straightforward fruit-frugivore system. Dispersal efficiency was low, with an average 21% of seeds being dispersed (carried away from parent plants) each year; the most common fate of fruits was to simply fall. Robins dropped 20% of the fruits that they picked, and defecated/regurgitated 40% of the fruits (seeds) that they swallowed, beneath parent plants. One trait, gruit abundance, strongly affected the probability of bush visitation by robins, bushes with larger fruit displays being preferred. Both absolute dispersal success (number of seeds) and dispersal efficiency (proportion of seeds; success per propagule) were also found to be correlated most strongly with initial fruit abundance. Individual plant fecundity and fruit quality were found to vary little between years; as a result, dispersal efficiencies for individual plants were also annully consistent. Larger (older) plants produced more fruits and therefore had higher fitness. These results suggest that the optimal fruiting strategy for C. monogyna is therefore to get as big as possible as quickly as possible by delaying fruiting until later in life.


Molecular cloning, purification and functional implications of recombinant GST tagged hGMCSF cytokine.
We report the cloning, purification and cell proliferative activity of a novel recombinant GST tagged human granulocyte macrophage colony stimulating factor (GST-hGMCSF). The hGMCSF gene was PCR amplified from the cDNA of ACHN renal carcinoma cells and was cloned into the bacterial expression vector. The GST-hGMCSF was purified to homogeneity using glutathione agarose affinity chromatography and subsequently characterized by Western blot, circular dichroism (CD) and MALDI TOF-TOF analysis. Homology modelling studies revealed the possible binding domains of the recombinant cytokine with cognate receptor. The proliferation of THP-1, Raw 264.7, MCF-7 and U87MG cells upon GST-hGMCSF addition was found to be dose dependent. Hence, this functionally active recombinant cytokine has potential application in cancer therapy for stimulating facile growth recovery of normal cell population.


Designing nano ranged electrode modifier comprised of samarium niobate anchored carbon nanofibers for trace level detection of food colourant: Tartrazine.
Tartrazine (TRZ) is a predominantly used food color in food processing industries which is soluble in water to produce a orange colour. This food colorant is categorized under the mono-azo pyrazolone dye group known for the perilous azo group (-NN-) attached to the aromatic ring that threatens human health. In consideration of these aspects, a novel TRZ sensing platform with advanced electrode material is designed by incorporating nanotechnology with chemical engineering. This innovative sensor is prepared by electrode modification through a nano ranged electrode modifier of SmNbO4 decorated on the enmeshed carbon nanofibers. This is the first report on the investigation of SmNbO4/f-CNF as an electrode modifier to extricate the superlative electrochemical properties towards TRZ detection and protracted its practicality to food samples with a lower limit of detection (2 nmolL-1), broad linear range, good selectivity, and functional stability.


Genetic risk factors for venous thromboembolism among infertile men with Klinefelter syndrome.
Klinefelter syndrome (KS) is one of the commonest sex chromosome disorders. Affected males become infertile and highly susceptible to several health problems, including vascular thromboembolism (VTE). The risk of VTE may be exacerbated by an underlying genetically inherited thrombophilia. In this study, we aimed to investigate the genotype and allele frequencies of common gene polymorphisms related to hereditary thrombophilia in infertile males with KS compared to normal, fertile men. Eighty-five infertile males with KS and 75 healthy control males were included in this case-control study. Genetic testing was done using an extended thrombophilia gene panel by Multiplex PCR reverse hybridization method. There was an increased frequency of mutant alleles and heterozygous genotypes of FV Leiden, FV H 1299R, Pro G20210A, MTHFR C677T and PAI-1 4G/5G thrombophilic gene polymorphisms in KS patients compared to the control group. It was shown that 10.7% of KS patients had the A3 haplotype of the EPCR gene in comparison to 5.3% of control patients. The A3/A3 genotype was found only in KS patients (7.1%). Carriers of more than one mutant allele in KS patients exceeded the control (p < 0.001). A high prevalence of thrombophilic gene polymorphisms and the coexistence of different mutant alleles were evident in infertile KS males. These data highlight the importance of conducting further studies to understand the role of hereditary thrombophilia in predicting venous thrombosis in patients with Klinefelter syndrome.


Instrumental perforation of the esophagus in benign disease.
Over a period of seven years, a total of 1,831 endoscopic procedures were performed in patients with benign esophageal disease. These comprised flexible esophagoscopy (848), flexible esophagoscopy and dilation (924), pneumatic dilation (29), and rigid esophagoscopy (30). There were 14 episodes of perforation: 1 was cervical, 2 were abdominal, and 11 were perforations of the intrathoracic esophagus (7 occurred at or immediately above a stricture). The diagnosis was made immediately in 9 and within six hours in all but 1 patient. Treatment was emergency surgery in 12 patients, 2 of whom died. The major cause of death was respiratory failure. The overall incidence of perforation was 0.76%. The incidence of perforation was 0.35% (3/848) for flexible esophagoscopy alone, 0.38% (3/792) for dilation with Maloney mercury-weighted bougies, and 3.8% (5/132) for dilation with other bougies. Our experience indicates that instrumental perforation in benign esophageal disease carries a considerable mortality rate in spite of prompt recognition and surgical treatment. Successful dilation with mercury-weighted bougies can be achieved in 86% of benign strictures with an incidence of perforation similar to that for flexible esophagoscopy alone. Difficult strictures and the use of other bougies are associated with a tenfold higher incidence of perforation.


Efficacy and safety of N-acetylprocainamide in long-term treatment of ventricular arrhythmias.
Four patients with chronic ventricular arrhythmias, shown to respond over the short term to N-acetylprocainamide (NAPA), were treated for between 3 and 4 yr with NAPA, and 24-hr ambulatory ECGs were obtained monthly to monitor their responses. When the patients were ambulatory and receiving NAPA, the mean frequency of premature ventricular complexes averaged 70% (range 60% to 82%) below that recorded at 6-mo intervals when the patients were hospitalized and receiving placebo. Analysis of variance showed that NAPA exerted an antiarrhythmic effect in these patients and that tolerance to this effect did not develop with long-term therapy. Plasma NAPA concentrations required to achieve this level of response averaged 21 micrograms/ml (12 to 35 micrograms/ml) and were roughly twice as high as those which appeared to be maximally effective when the patients were hospitalized for their initial evaluation. NAPA therapy was associated with positive antibody titers in only one patient and seems less prone to cause drug-induced lupus erythematosus than procainamide, but NAPA shares the gastrointestinal and other side effects of procainamide.


New treatment strategy for severe heart failure: combination of ventricular assist device and regenerative therapy.
Heart transplantation and ventricular assist device for the patients with end-stage heart failure are limited by availability and durability due to limited donor or device-related complication. Thus, complementation or a new alternative is needed for the treatment of severe heart failure. Based on the results of basic experiments, we applied skeletal myoblast cell sheet transplantation in a clinical setting using cell-sheet methods with temperature-responsive dish for the treatment of heart failure patient from 2007. After confirming the safety of this treatment, we started a clinical trial of myoblast cell sheet transplantation as sole therapy. According to these results, in 2015, myoblast cell sheet transplantation with ischemic cardiomyopathy was approved by the Japanese government and now this treatment was covered by Japanese health insurance. Here we report our approach and future perspective of cardiac regenerative therapy using this new treatment method for severe heart failure including new strategy incorporating regenerative therapy in the conventional treatment of heart failure including VAD and heart transplantation.


Twenty Years of Addiction and Mental Illness in Alaska: Using the National Survey on Drug Use and Health to Understand Addiction in a Low Population and Rural State.
Understanding changes in substance use in a small population state is challenging. Many national datasets restrict data to reduce the probability of identifying persons. Alaska is a small population state (731,000 residents) with a large geographic region (25% the size of the lower 48), a diverse population, and highly variable seasons, with fewer than 10% of the state being road accessible. Given the uniqueness of Alaska, this project sought to understand what could be learned about addiction and its relationships with unemployment and median income in Alaska. National Survey on Drug Use and Health, State and Small Area Estimates (1999-2020) data were analyzed to measure prevalence changes. Outcome prevalence were independently correlated with median income and annual unemployment rate as the annual collection periods varied. Analyses were limited to simple bivariate analyses due to the data restrictions. Median income was found to have stronger correlational relationships and significant relationships with more negative outcomes compared to unemployment. While annual unemployment rates had statistically significant relationships with substance use outcomes, negative mental health outcomes appeared more related to unemployment than median income. Alcohol use in the past month, cigarette and tobacco use, and pain reliever misuse declined while binge drinking in the past month and illicit drug use increased. More people reported depression, serious mental illness, and suicidal ideation and planning over time peaking in the last year of data collection. While NSDUH data provide some idea of the changes in drug use over time, their effectiveness in Alaska is unknown. Many data sources claim they are nationally representative, but these statements cannot be objectively measured. We will use these outcomes and data as a baseline for future studies where we will explore state specific data sources.


E1B functions of type C adenoviruses play a role in the complementation of blocked adenovirus type 12 DNA replication and late gene transcription in hamster cells.
Adenovirus type 12 (Ad12) DNA cannot replicate in hamster cells and the late Ad12 genes cannot be expressed. It has been demonstrated previously that these defects can be at least partly overcome by coinfection of hamster cells with Ad12 and wild-type adenovirus type 2 (Ad2) or type 5 (Ad5) or by superinfection of Ad2- or Ad5-transformed cells with Ad12. These transformed cell lines carry in an integrated form and constitutively express the E1 region of Ad2 or Ad5. The compensation in Ad12 DNA replication and late gene transcription does not, however, lead to the assembly of intact Ad12 virions. In the present study, it has been demonstrated that the complementing functions in the Ad5 genome, which can effect Ad12 DNA replication and late transcription in hamster cells, reside predominantly but not exclusively in the E1B region. A supporting role in the E1A region is likely. These conclusions have been adduced from the results of double infection experiments using Ad12 and deletion mutants of Ad5. Inside the E1B region of Ad5 DNA, the complementing functions have not yet been precisely located. Although late Ad12 messenger RNAs are synthesized in Ad12 and Ad5-coinfected hamster cells, most of the late structural Ad12 proteins are not made or are made in minimal amounts, and consequently virions are not assembled. It is necessary to investigate whether hamster cells also exhibit a translational block vis à vis the expression of late Ad12-specific mRNAs. The data presented here also demonstrate that Ad12 functions can effectively complement E1A or to a lesser extent E1B deletions in the Ad5 genome in hamster cells. Upon coinfection with Ad12 and deletion mutants of Ad5 in either the E1A or the E1B region, Ad5 DNA and late proteins are synthesized, although Ad5 E1A or E1B functions cannot complement the deficient late Ad12 protein synthesis in hamster cells.


Immunochemical tests of acetylcholine receptor subunit models.
Acetylcholine receptors of fish electric organs and mammalian skeletal muscle comprise four structurally homologous glycoprotein subunits in the mole ratio alpha 2 beta gamma delta (refs 1-4). All four subunits have leader sequences and are exposed on both sides of the membrane. From amino acid sequencing, three groups have predicted that each subunit has four hydrophobic alpha-helical transmembranous domains. Because the N-terminus of each subunit is thought to remain on the extracellular surface after cleavage of the leader sequence, this model predicts that the N- and C- termini are both on the extracellular side. An alternative model proposed by two other groups predicts that there is, in addition, a fifth amphipathic transmembranous domain which would place the C-terminus on the cytoplasmic side. Here, using anti-subunit sera and monoclonal antibodies and their reaction with synthetic subunit peptides, we demonstrate that the C-terminus is in fact on the cytoplasmic surface. We also show that, contrary to other predictions, the most hydrophilic sequence on the extracellular domain of alpha-subunits is not the main immunogenic region.


Life-threatening parkinsonism induced by kava-kava.
We present a 45-year-old female with severe parkinsonism induced by kava-kava. The patient, who had a family history of essential tremor, developed severe and persistent parkinsonism after days of treatment with kava extract for anxiety. The symptoms improved with anticholinergics. Kava derivatives could produce severe parkinsonism in individuals with genetic susceptibility.


Radiologist assessment of breast density by BI-RADS categories versus fully automated volumetric assessment.
The objective of our study was to estimate mammographic breast density using a fully automated volumetric breast density measurement method in comparison with BI-RADS breast density categories determined by radiologists. A total of 791 full-field digital mammography examinations with standard views were evaluated by three blinded radiologists as BI-RADS density categories 1-4. For fully automated volumetric analysis, volumetric breast density was calculated with fully automated software. The volume of fibroglandular tissue, the volume of the breast, and the volumetric percentage density were provided. The weighted overall kappa was 0.48 (moderate agreement) for the three radiologists' estimates of BI-RADS density. Pairwise comparisons of the radiologists' measurements of BI-RADS density revealed moderate to substantial agreement, with kappa values ranging from 0.51 to 0.64. There was a significant difference in mean volumetric breast density among the BI-RADS density categories, and the mean volumetric breast density increased as the BI-RADS density category increased (p<0.001). A significant positive correlation was found between BI-RADS categories and fully automated volumetric breast density (ρ=0.765, p<0.001). Our study showed good correlation of the fully automated volumetric method with radiologist-assigned BI-RADS density categories. Mammographic density assessment with the fully automated volumetric method may be used to assign BI-RADS density categories.


Educating Residents and Students in the Clinic.
Training of students and residents in outpatient settings requires adequate exposure to a broad range of neurologic diseases. A competency-based method has been frequently used to provide a framework for the design and assessment of medical curriculums. However, it is the responsibility of the faculty within a medical school to design the curriculum and ensure its quality. In this article, we review learning objectives, assessment of core competencies, the current status of outpatient neurology education, and the flaws that may affect its quality. We also discuss potential strategies and approaches for the improvement of education and learning process in the outpatient setting, including early clinical exposure of students, cross-disciplinary courses, balancing case mix, near-peer teaching, active learning, electronic and online education, and virtual modules.


Susceptibility to hypoxia and breathing control changes after short-term cold exposures.
Hypoxia is the reduction of oxygen availability due to external or internal causes. There is large individual variability of response to hypoxia. The aim of this study was to define individual and typological features in susceptibility to hypoxia, its interrelation with hypoxic and hypercapnic ventilatory responses (HVR and HCVR, respectively) and their changes after cold acclimation. Twenty-four healthy men were tested. HVR and HCVR were measured by the rebreathing method during hypoxic and hypercapnic tests, respectively. These tests were carried out in thermoneutral conditions before and after cold exposures (nude, at 13°C, 2 h daily, for 10 days). Susceptibility to hypoxia (sSaO2) was determined as haemoglobin saturation slope during hypoxic test. It was found that HVR and HCVR significantly increased and susceptibility to hypoxia (sSaO2) tended to decrease after cold acclimation. According to sSaO2 results before cold exposures, the group was divided into 3: Group 1--with high susceptibility to hypoxia, Group 2--medium and Group 3--low susceptibility. Analysis of variances (MANOVA) shows the key role of susceptibility to hypoxia and cold exposures and their interrelation. Posterior analysis (Fisher LSD) showed significant difference in susceptibility to hypoxia between the groups prior to cold acclimation, while HVR and HCVR did not differ between the groups. After cold acclimation, susceptibility to hypoxia was not significantly different between the groups, while HCVR significantly increased in Groups 1 and 3, HVR significantly increased in Group 3 and HCVR, HVR did not change in Group 2. Short-term cold exposures caused an increase in functional reserves and improved oxygen supply of tissues in Group 1. Cold exposure hypoxia has caused energy loss in Group 3. Group 2 showed the most appropriate energy conservation reaction mode to cold exposures. No relation was found between the thermoregulation and the susceptibility to hypoxia.


[Signal-flow diagrams as aids to describe hypnotic trance states: an impulse for our statement].
A model is developed to show the formation of the hypnotic trance states. As experimental results are rare in this field the development of the model is mainly done by assuming possible and practicable connections. It is the beginning of cybernetic models for this domain and may encourage further work in this direction. The focal point is the separation of energy-flow from information-flow. Only the latter is needed with the arrangement of signal-flow diagrams. These diagrams show that the different trance states may be explained as different information-processing systems. We don't require the physiological background as we have transformed the problem into a pure psychology-problem - On this way we find two switch-over systems: One that opens the loop between the model of outer world and the inner decision system. By this way it gives to the other system the possibility to follow word-for-word the suggestions, given by the hypnotist.


Rwdd1, a thymus aging related molecule, is a new member of the intrinsically unstructured protein family.
We had previously identified a novel protein termed Rwdd1 whose expression in thymus is decreased in aged or oxidatively stressed mice. In the present study, we found that Rwdd1 expressed in both prokaryotic and eukaryotic cells showed a slower migration rate on SDS-PAGE gel. In addition, Rwdd1 was more sensitive to proteinase proteolysis. Furthermore, being a highly acidic protein which contains an RWD domain, Rwdd1 shared a high level of sequence similarity with Gir2, a member of the intrinsically unstructured protein (IUP). These findings suggest that Rwdd1 is a novel member of the IUP family.


Eletrochemical reduction of patulin and 5-hydroxymethylfurfural in both neutral and acid non-aqueous media. Their electroanalytical determination in apple juices.
The electro-reduction of patulin mycotoxin and 5-hydroxymethylfurfural at glassy carbon electrodes in acetonitrile +0.1 mol L(-1) tetrabutylammonium perchlorate, in both the absence and the presence of different aliquots of trifluoroacetic acid is reported. 5-hydroxymethylfurfural is the most common interference in the determination of patulin in products derived from apples. The electrochemical techniques were cyclic and square wave voltammetries, and controlled potential bulk electrolysis. The number of electrons exchanged in the patulin electro-reduction of n=1 could be inferred from controlled potential bulk electrolysis measurements. Ultraviolet-visible and infrared spectroscopies were used to identify patulin electro-reduction product/s. A value of (2.1±0.1)×10(-5) cm(2) s(-1) for the patulin diffusion coefficient was calculated from convoluted cyclic voltammograms. A method based on square wave voltammetry was developed for the quantitative determination of patulin in both fresh, and commercial apple juices in the presence of 5-hydroxymethylfurfural. Calibration curves obtained from solutions of the commercial reagent, and commercial apple juices were linear in the range from 3.0×10(-7) to 2.2×10(-5) mol L(-1). The lowest concentration measured experimentally for a signal to noise ratio of 3:1 was 3×10(-7) mol L(-1) (45 ppb) and a recovery percent of 84% was determined for commercial apple juices. This electroanalytical methodology appears as a good screening method for the determination of patulin in apple juices.


Hearing thresholds elevation and potential association with emotional problems among 1,914 children in Beijing, China.
School-aged children may experience hearing loss and emotional problems. Previous studies have shown a bidirectional relationship between hearing loss and emotional problems in the elderly population, and we aimed to analyze the association between hearing thresholds and emotional problems in school-aged children. Based on the Beijing Child Growth and Health Cohort (PROC) study, the hearing screenings were conducted in November 2019 using pure tone audiometry. A total of 1,877 parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's emotional and behavioral status. We used generalized linear regression analysis to assess the potential association of emotional problems with hearing thresholds, based on multiple imputed datasets with a sample size of 1,914. The overall pass rate of hearing screening was 91.5%. The abnormal rate of SDQ total difficulties was 55.8%. Emotional symptoms were positively associated with left ear average hearing thresholds (β = 0.24, 95%CI: 0.08-0.40), and right ear average hearing thresholds (β = 0.18, 95%CI: 0.04-0.32). Conduct problems, hyperactivity/inattention, peer problems, and prosocial behaviors had no association with the pass rate of the hearing screening. Regarding emotional symptoms, boys with many fears and who are easily scared coincided with increased right ear average hearing thresholds (β = 0.67, 95%CI: 0.01-1.33). Girls having many worries, frequently feeling unhappy and downhearted were positively associated with left and right ear average hearing thresholds, respectively (β = 0.96, 95%CI: 0.20-1.73; β = 0.72, 95%CI: 0.07-1.37). The co-occurrence of hearing problems and emotional problems of children aged 6-8 in Beijing attracts attention. It is important to address undiscovered hearing loss and emotional problems from the perspective of comorbidity driving factors.


Critical role for Daxx in regulating Mdm2.
The tumour suppressor p53 induces apoptosis or cell-cycle arrest in response to genotoxic and other stresses. In unstressed cells, the anti-proliferative effects of p53 are restrained by mouse double minute 2 (Mdm2), a ubiquitin ligase (E3) that promotes p53 ubiquitination and degradation. Mdm2 also mediates its own degradation through auto-ubiquitination. It is unclear how the cis- and trans-E3 activities of Mdm2, which have opposing effects on cell fate, are differentially regulated. Here, we show that death domain-associated protein (Daxx) is required for Mdm2 stability. Downregulation of Daxx decreases Mdm2 levels, whereas overexpression of Daxx strongly stabilizes Mdm2. Daxx simultaneously binds to Mdm2 and the deubiquitinase Hausp, and it mediates the stabilizing effect of Hausp on Mdm2. In addition, Daxx enhances the intrinsic E3 activity of Mdm2 towards p53. On DNA damage, Daxx dissociates from Mdm2, which correlates with Mdm2 self-degradation. These findings reveal that Daxx modulates the function of Mdm2 at multiple levels and suggest that the disruption of the Mdm2-Daxx interaction may be important for p53 activation in response to DNA damage.


Differences between national reference laboratories of the European community in their ability to serotype Salmonella species.
The capacity of national reference laboratories of the European Union member states to correctly serotype Salmonella strains was assessed in four collaborative studies on serotyping in the period 1995-1999. Participants were asked to identify 20 strains in studies I, II and III and 16 strains in study IV, using the typing method routinely performed in their laboratory. In the first study, the strains to be identified belonged to Salmonella enterica subsp. enterica, salamae or houtenae, while in the other studies only strains belonging to Salmonella enterica subsp. enterica were included. Significant differences between laboratories and between studies were found. Differences were related to the frequency of actual occurrence of the study strains in the area served by the laboratory and the number of antisera available in the laboratory.


Population Pharmacokinetic Analysis of Follicle-Stimulating Hormone During Ovarian Stimulation: Relation with Weight, Prolactin and Gene Polymorphism in THADA and ADIPOQ.
Personalisation strategies of ovarian stimulation for in vitro fertilisation (IVF)/ intracytoplasmic sperm injection (ICSI) treatments using exogenous follicle-stimulating hormone (FSH) have been extensively studied over the past 20 years. This research aimed to develop a FSH population pharmacokinetic (PPK) model taking into account the contribution of gene polymorphisms in Chinese reproductive-age women. Data from 173 patients undergoing GnRH agonist down-regulation long protocols of IVF/ICSI treatment were collected. PPK analysis was subsequently conducted using the nonlinear mixed-effect model (NONMEM) software. Several covariates, including 18 single nucleotide polymorphisms, demographic factors and biological characteristics, were evaluated. The final PPK model was extensively validated using bootstrapping and normalised prediction error distribution, as well as external validation on an independent group of 35 patients. FSH PPK was accurately described by a one-compartment model with first-order absorption. The typical population value of apparent clearance was estimated to be 0.81 L/h [relative standard errors (RSE) 5.3%] with an inter-individual variability (IIV) of 16.0%. The typical apparent distribution volume was 8.36 L (RSE 9.7%, 59.7% IIV), and the absorption rate constant was estimated to be 0.0444 h-1 (RSE 9.1%). Body weight, basal prolactin concentration and the gene ADIPOQ (rs1501299) showed a significant covariate effect on the FSH clearance rate and exposure concentration. Genotypes of THADA (rs12478601) significantly influenced the distribution volume. Simulation results indicated that patients with the TT genotype of THADA (rs12478601) required a longer time to reach steady state and had less fluctuation in FSH levels. Model evaluations showed that the final model accurately and precisely described the observed data and demonstrated effective prediction performance. PPK models of FSH have been developed, which could potentially be used for FSH dosage individualisation in the clinical setting. This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2100049142).


Endothelin and platelet function.
The effects of newly discovered vasoconstrictor peptide endothelin was studied on human, rabbit and canine platelet function. Endothelin (0.01 nM-1 microM) did not promote platelet aggregation. In human platelets, endothelin (0.1 microM) did not significantly affect aggregation responses to ADP, collagen, epinephrine, arachidonic acid, PGH2 or thrombin. Endothelin did not promote the mobilization of intracellular calcium in Fura2 loaded human platelets. In rabbit and canine platelets endothelin produced significant potentiation of platelet aggregation mediated by low concentrations of ADP. Aggregation responses to higher concentration of ADP (5 microM) were unaffected by endothelin. These data reveal that under certain circumstances endothelin may potentiate rabbit and canine platelet aggregation responses to ADP, however endothelin does not produce direct effects on human platelet function.


Interleukin 21 as a new possible player in pemphigus: Is it a suitable target?
Pemphigus is a rare autoimmune disease, which could be fatal without treatment. Recently, target therapy is increasingly being used in different autoimmune diseases. However, there are limited studies associated with target therapy in pemphigus. In this study, it was tried to identify the role of interleukin (IL) -21 in patients with pemphigus. Based on the available studies on the role of IL-21 associated with several cells, including T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells as well as regulatory B cells and regulatory T cells, the possible roles of this cytokine in pemphigus were discussed in detail. It was found that IL-21 is a crucial cytokine associated with pemphigus disease, which has not been discussed in this disease yet. It is able to promote T helper (Th) 2, Th17, T follicular helper (Tfh), CD8+ cytotoxic T lymphocytes (CTLs), NK and NKT cells. It also causes the production of immunoglobulin (Ig)G in addition to the decrease of Tregs. All the mentioned alterations seem to be involved in disease progression via different signaling pathways. Inhibition of these changes must cause improvement of disease severity. By inhibition of IL-21 or its receptor, it is expected that patients with severe pemphigus experience relative and gradual improvement. This inhibition could be induced by tofacitinib, which was approved by the US Food and Drug Administration as a treatment for rheumatoid arthritis patients, or anti-IL-21 monoclonal antibody, NNC114-0006. However, more studies are needed to confirm it as a promising therapy.


Synthesis of hybrid phosphorated indenoquinolines and biological evaluation as topoisomerase I inhibitors and antiproliferative agents.
This work describes the first synthesis of diethyl 6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolinylphosphonates 5, diethyl 7H-indeno[2,1-c]quinolinylphosphonates 6 and diethyl 7-oxo-7H-indeno[2,1-c]quinolinylphosphonates 7, which were prepared in good to high overall yields. The synthetic route involves a multicomponent reaction of 2-phosphonateaniline, aldehydes and indene as olefin and allows the selective generation of three stereogenic centres in a short, efficient and reliable manner. The selective dehydrogenation of 1,2,3,4-tetrahydroindenoquinolines leads to the formation of corresponding indenoquinolines, and subsequent oxidation of methylene group of the indenoquinolines allows the access to indenoquinolinones.


MicroRNA-mediated maturation of human pluripotent stem cell-derived cardiomyocytes: Towards a better model for cardiotoxicity?
Human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are a promising human cardiac model system for drug development and toxicity screening, along with cell therapy and mechanistic research. The scalable differentiation of human PSCs into CMs provides a renewable cell source that overcomes species differences present in rodent primary CMs. In addition, induced pluripotent stem cell (iPSC) technology allows for development of patient-specific CMs, representing a valuable tool that may lead to better prediction, prevention, and treatment of cardiovascular diseases in this new era of precision medicine. However, the utility of PSC-CMs as an in vitro model is currently limited by their immature phenotype when compared to adult CMs. Recent work has identified microRNAs (miRNAs) as critical regulators of heart development and function. These studies have shown that miRNAs are essential to key processes that span the life cycle of a cardiomyocyte, including proliferation, hypertrophy, beating rhythm, and apoptosis. Importantly, emerging evidence strongly suggests that modulation of select miRNAs can enhance the maturation of PSC-CMs. Here, we review key miRNAs associated with heart development and function, and discuss strategies to promote PSC-CM maturation, focusing on current knowledge surrounding miRNA-based approaches and the application of PSC-CMs with respect to drug screening and disease models. Ultimately, it is likely that combinations of both miRNA and non-miRNA maturation strategies may collectively provide the best path forward for producing mature cardiomyocytes in vitro.


Toxoplasmosis Infection in Newborn: A Systematic Review and Meta-analysis.
Toxoplasmosis is a disease caused by Toxoplasma gondii, and one-third of the world's population has T. gondii antibodies. Due to this issue, the aim of this study was to assess the mean prevalence and odds ratios of T. gondii infection and epidemiological features of neonatal infection worldwide. We performed a meta-analysis and systematic review of published studies reporting T. gondii infection using the PubMed, MEDLINE, Web of Science, EMBASE, and Scopus electronic databases through January 1999 to December 2020, regarding diagnostic tests, and prevalence data of infection among the newborn population. The pooled prevalence of T. gondii with a 95% confidence interval (CI) was calculated using the random-effects models. A total of thirty eligible articles were included. The estimated global prevalence rate was 44% (95% CI: 29%-0.58%); the highest prevalence rate was in America 47% (95% CI: 30%-64%), followed by Europe 41% (95% CI: 26%-57%) and Asia 33% (95% CI: 4%-61%). In this study, despite our careful analysis of possible modifiers, the heterogeneity was significant (P = 0.000). The publication bias was not significant based on the results of Egger's (P = 0.918) and Begg's tests (P = 0.230). Based on the results of this study, T. gondii infection can be a serious concern in newborns around the world. Therefore, further research is needed to provide better strategies to screen and diagnose T. gondii infection in neonates and determine the risk factors associated with the prevalence of infection in neonates worldwide.


Changes in mitral annular geometry and dynamics with ß-blockade in patients with degenerative mitral valve disease.
remodeling of the mitral annulus contributes to progression of mitral regurgitation (MR). In patients with moderate-to-severe MR, short-term treatment with β-blockers has been shown to increase left ventricular (LV) end-diastolic and end-systolic volume, and this could deleteriously increase mitral valve annular dimensions. The objective of this study was to quantify the effects of a short duration of β-blocker treatment on mitral annular dimensions and dynamics in patients with MR due to primary degenerative valve disease. twenty-five patients with moderate-to-severe degenerative MR and normal LV systolic function were studied in a double-blind crossover experiment using a β1-selective adrenergic blocker and placebo administered for 14±3 days. Cardiac MRI images were acquired after each treatment period to quantify mitral annular dimensions. At end diastole, there was no change in annular area (1659±331 versus 1632±299 mm(2); P<0.19), annular perimeter (154.3±16.4 versus 152±13.9 mm; P<0.13), septal-lateral (SL) dimension (38.0±5 versus 39.0±4.5 mm; P<0.15), or annular height (9.8±3.8 versus 9.5±2.5 mm; P<0.53). β-blockade resulted in significant end-diastole decreases in commissure-commissure dimension (48.9±4.6 versus 47.2±4.0 mm; P<0.01) and eccentricity (1.3±0.2 versus 1.2±0.1; P<0.01). At end systole (ES), β-blockade conferred a small, but significant decrease in annular perimeter (161.0±19.3 versus 156.8±16.9 mm; P<0.04) and eccentricity (1.2±0.1 versus 1.1±0.1; P<0.02), and the SL dimension significantly increased (41.5±5.7 versus 43.0±5.3 mm; P<0.03). Commissure-commissure dimension, annular area, and annular height at ES were not significantly different. despite significant increases in LV end-diastolic and end-systolic volume, short-term β-blocker treatment of patients with moderate-to-severe MR reduced or preserved all mitral annular dimensions except SL at ES.


Indinavir did not further increase mean triglyceride levels in HIV-infected patients treated with nucleoside reverse transcriptase inhibitors: an analysis of three randomized clinical trials.
Metabolic abnormalities including hyperlipidemia have developed in patients infected with the human immunodeficiency virus (HIV) after treatment with protease inhibitor drugs. It is unclear whether the deleterious effects on plasma triglyceride concentrations observed in patients receiving highly active antiretroviral therapy are a class effect of protease inhibitors. Hypertriglyceridemia may constitute a risk factor for cardiovascular disease. The purpose of this retrospective analysis of HIV-infected patients enrolled in three randomized, double-blind trials of indinavir therapy was to determine whether indinavir use was associated with a larger increase in triglyceride levels than treatment without a protease inhibitor. Using a mixed-effects model, we compared average changes in nonfasting plasma triglyceride levels among randomized treatment groups for each protocol separately. The median increase in triglyceride levels during the 1st year of antiretroviral monotherapy was less with indinavir than with either zidovudine or stavudine. The combination of indinavir and nucleoside-analogue reverse-transcriptase inhibitors (NRTI) resulted in smaller increments in triglyceride levels than NRTI monotherapy. Indinavir also augmented the reduction in triglyceride levels observed with combination therapy using zidovudine and lamivudine in persons with far advanced HIV-infection. However, up to 7% of patients receiving a NRTI and indinavir experienced elevations of nonfasting triglyceride levels in excess of 750 mg/dl. On average, the combination of indinavir and NRTI therapy was not associated with a greater elevation of non-fasting triglyceride levels in HIV-infected men with at least moderately advanced immunosuppression than treatment with NRTI drugs alone.


Simulating the spread of classical swine fever virus between a hypothetical wild-boar population and domestic pig herds in Denmark.
Denmark has no free-range wild-boar population. However, Danish wildlife organizations have suggested that wild boar should be reintroduced into the wild to broaden national biodiversity. Danish pig farmers fear that this would lead to a higher risk of introduction of classical swine fever virus (CSFV), which could have enormous consequences in terms of loss of pork exports. We conducted a risk assessment to address the additional risk of introducing and spreading CSFV due to the reintroduction of wild boar. In this paper, we present the part of the risk assessment that deals with the spread of CSFV between the hypothetical wild-boar population and the domestic population. Furthermore, the economic impact is assessed taking the perspective of the Danish national budget and the Danish pig industry. We used InterSpreadPlus to model the differential classical swine fever (CSF) risk due to wild boar. Nine scenarios were run to elucidate the effect of: (a) presence of wild boar (yes/no), (b) locations for the index case (domestic pig herd/wild-boar group), (c) type of control strategy for wild boar (hunting/vaccination) and (d) presence of free-range domestic pigs. The presence of free-range wild boar was simulated in two large forests using data from wildlife studies and Danish habitat data. For each scenario, we estimated (1) the control costs borne by the veterinary authorities, (2) the control-related costs to farmers and (3) the loss of exports associated with an epidemic. Our simulations predict that CSFV will be transmitted from the domestic pig population to wild boar if the infected domestic pig herd is located close to an area with wild boar (<5 km). If an outbreak begins in the wild-boar population, the epidemic will last longer and will occasionally lead to several epidemics because of periodic transfer of virus from groups of infected wild boar to domestic pig herds. The size and duration of the epidemic will be reduced if there are no free-range domestic pig herds in the area with CSF-infected wild boar. The economic calculations showed that the total national costs for Denmark (i.e. the direct costs to the national budget and the costs to the pig industry) related to an outbreak of CSF in Denmark will be highly driven by the reactions of the export markets and in particular of the non-EU markets. Unfortunately, there is a substantial amount of uncertainty surrounding this issue. If hunting is used as a control measure, the average expenses related to a CSF outbreak will be 40% higher if wild boar are present compared with not present. However, a vaccination strategy for wild boar will double the total costs compared with a hunting strategy.


In Defence of informed consent for health record research - why arguments from 'easy rescue', 'no harm' and 'consent bias' fail.
Health data holds great potential for improved treatments. Big data research and machine learning models have been shown to hold great promise for improved diagnostics and treatment planning. The potential is tied, however, to the availability of personal health data. In recent years, it has been argued that data from health records should be available for health research, and that individuals have a duty to make the data available for such research. A central point of debate is whether such secondary use of health data requires informed consent. In response to recent writings this paper argues that a requirement of informed consent for health record research must be upheld. It does so by exploring different contrasting notions of the duty of easy rescue and arguing that none of them entail a perfect duty to participate in health record research. In part because the costs of participation cannot be limited to 1) the threat of privacy breaches, but includes 2) the risk of reduced trust and 3) suboptimal treatment, 4) stigmatization and 5) medicalisation, 6) further stratification of solidarity and 7) increased inequality in access to treatment and medicine. And finally, it defends the requirement of informed consent by arguing that the mere possibility of consent bias provides a rather weak reason for making research participation mandatory, and that there are strong, independent reasons for making. Arguments from the duty of easy rescue in combination with claims about little risk of harm and potential consent bias fail to establish not only a perfect duty to participate in health record research, but also that participation in such research should be mandatory. On the contrary, an analysis of these arguments indicates that the duty to participate in research is most adequately construed as an imperfect duty, and reveals a number of strong reasons for insisting that participation in health records research is based on informed consent.


Feasibility of the direct coupling of solid-phase extraction-pipette tips with a programmed-temperature vaporiser for gas chromatographic analysis of drugs in plasma.
Solid-phase extraction-pipette tips (SPE-PTs) were used for micro solid-phase extraction of lidocaine and diazepam from plasma. Off-line extraction was followed by on-line desorption. On-line desorption was carried out by direct coupling of the SPE-PTs with the liner of the programmed-temperature vaporiser. This coupling only required shortening of the liner by maximally 16 mm, cutting the SPE-PT, and equipping the remaining part with two O-rings. Due to the heating of the injector the SPE-PTs were heated as well, which resulted in a significant amount of impurities. Pre-heating and pre-washing was performed prior to the extraction to reduce the impurity level. The internal coupling device was applied successfully for the analysis of plasma samples with gas chromatography (GC) and mass-selective detection. Detection limits of 0.75 ng/ml and 2.5 ng/ml were obtained for lidocaine and diazepam, respectively, using 200 microl plasma. Recoveries for both compounds were about 80%. Although it is possible, the internal coupling device was not developed to be used as such. The main goal of this coupling was to show the feasibility of the integration of SPE-PTs with GC and to realize an important step to new automated SPE-GC systems.


Propylene carbonate quantification by its derivative 3,5-diacetyl-1,4-dihydro-2,6-lutidine.
Propylene carbonate (PC) is a non-toxic solvent currently used in various pharmaceutical formulations. Consequently, a simple, cost-effective and most accurate analytical method for the quantification of this optical inert solvent is of major interest. Based on a consecutive three-step reaction 3,5-diacetyl-1,4-dihydro-2,6-lutidine was obtained from PC and used for quantification by either UV and fluorescent detection. Data were compared with results from LC-ESI-MS as a reference method. After using Mandel's test for linearity assessment of the calibration curves, linear fitting was used for LC-ESI-MS and spectrofluorimetry, while a polynomial 3rd order curve fitting was used for spectrophotometry. High intra- and inter-day precision as well as high accuracy were confirmed for all three analytical methods (spectrophotometry, spectrofluorimetry and LC-ESI-MS). The comparison of all three methods was assessed using correlation coefficients and Bland-Altman plots, both showing satisfying results with a high degree of agreement. The new method confirmed its applicability for PC quantification in two formulations, namely a PC-enriched cream and polyester microimplants. This new quantification method for PC is a reliable alternative to highly sophisticated chromatographic methods.


The nuclear elongation factor-1α gene: a promising marker for phylogenetic studies of Triatominae (Hemiptera: Reduviidae).
Molecular systematics is a remarkable approach for understanding the taxonomic traits and allows the exploration of the inter-population dynamics of several species in the Triatominae subfamily that are involved in Trypanosoma cruzi transmission. Compared to other relevant species that transmit vector-borne diseases, such as some species of the Diptera, there are relatively few nuclear genetic markers available for systematic studies in the Triatominae subfamily. Molecular systematic studies performed on Triatominae are based on mitochondrial gene fragments and, less frequently, on nuclear ribosomal genes or spacers. Due to the fact that these markers can occasionally present problems such as nuclear mitochondrial genes (NUMTs) or intra-genomic variation for high gene copy numbers, it is necessary to use additional nuclear markers to more reliably address the molecular evolution of Triatominae. In this study, we performed phylogenetic analysis using the nuclear elongation factor-1 alpha (EF-1α) gene in individuals from 12 species belonging to the Triatomini and Rhodniini tribes. Genetic diversities and phylogenetic topologies were compared with those obtained for the mitochondrial 16S rRNA and Cytochrome b (cyt b) genes, as well as for the D2 variable region of the ribosomal 28S rRNA gene. These results indicate that the EF-1α marker exhibits an intermediate level of diversity compared to mitochondrial and nuclear ribosomal genes, and that phylogenetic analysis based on EF-1α is highly informative for resolving deep phylogenetic relationships in Triatominae, such as tribe or genera.


Longitudinal Associations of Sleep Duration, Morning and Evening Cortisol, and BMI During Childhood.
This study aimed to examine associations between sleep duration, BMI, and cortisol levels across childhood. Participants included 361 children adopted domestically in the United States. Random-intercept cross-lagged panel models tested for between-person and bidirectional within-person associations of sleep duration, BMI, and morning and evening cortisol at age 4.5 to 9 years. Sleep duration and BMI were stable during childhood, inversely associated at the between-person level, and unrelated to morning or evening cortisol. BMI at age 6 years predicted longer sleep duration and lower evening cortisol at age 7 years, and lower morning cortisol at age 7 years predicted higher BMI at age 9 years within individuals. The association between sleep and BMI is more likely a stable between-person phenomenon rather than a unidirectional association that develops within individuals over time.


Isolated right ventricular infarction presenting with ST-segment elevation in precordial leads V1-V3.
We describe a rare case of a patient presenting with ST-segment elevation in precordial leads V1-V3 due to occlusion of the ventricular branch of the right coronary artery during primary percutaneous coronary angioplasty.


Real-world single-center experience with direct-acting antivirals for improvement of the liver fibrosis after chronic hepatitis C treatment.
Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3-73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant. The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.


Re-establishment of spermatogenesis by diethylstilbestrol after 2,5-hexanedione-induced irreversible testicular atrophy in rats.
To investigate the effects of diethylstilbestrol (DES) in reestablishing spermatogenesis and the mechanism by which estrogen works on spermatogenesis, rats were exposed to 1% 2,5-HD for 5 week. Then 0.1 mL of DES was given (s.c.) at a rate of 0.3 microg/kg, 30 microg/kg, 3 mg/kg every other day for 2 weeks respectively (DES group) while the other rats received ethyldeate only. Plasma testosterone (T) and LH were measured on the 8th week after the treatment. The rats were killed at the 18th week. The left testis was histopathologically examined. In all the rats in the DES groups, spermatogenesis was re-established and the rats in the 30 microg/kg group showed the best results. Serum T was suppressed markedly in rats of 30 microg/kg and 3 mg/kg groups while T was only mildly inhibited in 0.3 g/kg group, without significant difference found in serum LH. It is concluded that the nearly complete testicular atrophy could be reversed by DES treatment in rats. Estrogen plays an important part in spermatogenesis, and the role of estrogen in spermatogenesis is more than suppressing the hypothalamo-pituitary-testis axis.


Binder-free NiO/MnO2 coated carbon based anodes for simultaneous norfloxacin removal, wastewater treatment and power generation in dual-chamber microbial fuel cell.
Norfloxacin (NFX) is a commonly consumed synthetic antibiotic drug to cure many adverse infectious diseases of humans worldwide, but their presence in almost all aquatic environments has grown into severe global health concerns. In this study, the power performance of dual-chamber microbial fuel cells (MFCs) with two different types of base anodes (graphite felt and activated carbon cloth) were tested with a coating of NiO/MnO2 for removal of NFX in wastewater. As transition metal oxides have excellent electrochemical stability and a higher specific capacitance, their application in MFC for antibiotic removal and wastewater treatment would be an interesting study. Four different NFX concentrations were studied in two different base material with a coating of NiO/MnO2. Coating was done with 2 step hydro solvothermal method and modified anode surface was characterized by XRD and XPS analyses. Extracellular electron transfer between microorganisms and the modified anode improved significantly as a consequence of reduced internal resistance and a more biocompatible surface as measured by Electroscopy Impedance Spectroscopy (EIS) and polarization curves. NiO/MnO2 coated graphite felt performed 1.2 fold better than the control plain graphite felt. Similar results were found for activated carbon cloth (ACC). Modified ACC performed 1.3 fold better than the control plain ACC.


Effects of different cooking methods and of the inclusion of chestnut (Castanea sativa Miller) in the finishing diet of Celta pig breed on the physicochemical parameters and volatile profile of Longissimus thoracis et lumborum muscle.
The effect of different cooking methods and the influence of the use of chestnuts (Castanea sativa Miller) rather than commercial feed in the pig diet on physicochemical characteristics, oxidative stability and volatile profile of cooked Longissimus thoracis et lumborum Celta pig muscle was investigated. Four treatments were used for cooking meat from both diets: roasting, grilling, frying and microwaving. Analysis of cooked meat included the proximate composition (moisture, protein, fat, and ash contents), colour parameters (L*, a*, b*), cooking loss, shear force, lipid oxidation and volatile compounds. Overall, the cooking technique significantly affected the proximal composition, colour parameters, cooking loss, TBARS and volatile profile of Longissimus thoracis et lumborum, whereas the shear force was not affected by the heat treatment. Frying was the technique that led to a greater presence of fat. Additionally, microwaved and fried samples presented the highest cooking losses. Regarding to the lipid oxidation, grilling and microwaving showed more negative effects on the samples, while frying involved a lower presence of TBARS and hexanal contents. The major volatile compounds were aldehydes for all cooking methods except for the frying technique, which besides presented the lowest amount of total volatiles compounds. With respect to the finishing diet, in general the use of chestnuts did not affect the chemical composition, colour parameters, cooking loss and shear force of cooked Longissimus thoracis et lumborum. Nevertheless, a significant decrease in the TBARS value was found with the inclusion of this fruit in the finishing diet. At the same time, the use of chestnuts also affects the content of some volatile compounds such as heptanal and furan, 2-pentyl.


Impact of demographic changes on healthcare expenditures and funding in the EU.
While there are many international comparisons on the impact of demographic changes on future healthcare expenditures, there are few such comparisons with regard to the impact of demographic changes on future healthcare funding. The purpose of this article is to analyse the impact of demographic changes on healthcare expenditures and funding in 14 selected EU Member States. This article shows that in most countries, healthcare costs per worker are predicted to increase at a faster rate than per capita costs, because workers comprise a decreasing proportion of the total population. On the other hand, the impact of aging on healthcare payments per worker is about the same as healthcare costs per capita because citizens have to make out-of-pocket payments for healthcare. Roughly one-quarter of the predicted income growth of the work-force will be used for aging-related healthcare payments.


Low phosphorus intakes by beef suckler cows in late pregnancy and early lactation.
Two groups each of 10 suckler cows were given a basal diet of oat straw and pressed unmolassed sugar beet pulp for the last 19 weeks of pregnancy and the first 6 weeks of lactation. One group received 0.88 kg extracted soya bean meal (SBM) in pregnancy and 1.03 kg in lactation. The other was given 0.27 kg of a liquid supplement (LS) (containing inter alia urea and phosphoric acid) in pregnancy increasing to 0.33 kg in lactation. Both diets provided about the same amounts of digestible crude protein and about 10 g phosphorus (P) per day in pregnancy and 12 g P per day in lactation. Cows given SBM consumed marginally more straw but there were no differences in total diet digestibility. Cows given LS lost significantly more liveweight but their calves grew equally well. There were indications that cows given LS had slightly higher mean blood inorganic P and lower mean blood calcium (Ca) concentrations. Mean blood inorganic P concentrations were not below 1.4 mmol/l in pregnancy or 1.2 in lactation. There were no signs of reduction in voluntary straw intake or depraved appetite. When transferred to grass with a bull at the end of the experiment all cows were served within 24 days. It is concluded that these amounts of dietary P were adequate over the 25 weeks.


Not All Discharge Settings Are Created Equal: Thirty-Day Readmission Risk after Elective Colorectal Surgery.
Discharge to nonhome settings after colorectal resection may increase risk of hospital readmission. The purpose of this study was to determine the impact of various discharge dispositions on 30-day readmission after adjusting for confounding demographic and clinical factors. This was a retrospective cohort study. Data were obtained from the University HealthSystem Consortium (2011-2015). Adults who underwent elective colorectal resection were included. Thirty-day hospital readmission risk was measured. The mean age of the study population (n = 97,455) was 58 years; half were men and 78% were white. Seventy percent were discharged home routinely (home without service), 24% to home with organized health services, 5% to skilled nursing facility, 1% to rehabilitation facility, and <1% to long-term care hospital. Overall rate of readmission was 12%; 9% from home without service, 16% from home with organized home health services, 19% from skilled nursing facility, 34% from rehabilitation facility, and 22% from long-term care hospital (p < 0.001). Patients with an intensive care unit stay, more postoperative complications, and longer hospitalization stay were more likely to be discharged to home with organized home health services or to a facility (p < 0.001). Discharge to home with organized home health services, skilled nursing facility, or rehabilitation facility increased multivariable-adjusted readmission risk by 30% (OR = 1.3 (95% CI, 1.3-1.6)), 60% (OR = 1.6 (95% CI, 1.5-1.8)), or 200% (OR = 3.0 (95% CI, 2.5-3.6)). Discharge to long-term care hospital was not associated with higher adjusted readmission risk (OR = 1.2 (95% CI, 0.9-1.6)), despite this group having the highest comorbidity and postoperative complications. Among patients readmitted within 30 days, median time to readmission was significantly different among home without service (n = 7), home with organized home health services (n = 8), skilled nursing facility (n = 8), rehabilitation facility (n = 9), and long-term care hospital (n = 12; p < 0.001). This study was limited by its retrospective nature. Discharge to home with organized home health services, skilled nursing facility, or rehabilitation facility, but not long-term care hospital, is associated with increased adjusted risk of readmission compared with routine home discharge. Potential targets to decrease readmission include improving transition of care at discharge, improving quality of care after discharge, and improving facility resources. See Video Abstract at http://links.lww.com/DCR/B272. RIESGOS DE READMISIÓN A 30 DÍAS DESPUÉS DE CIRUGÍA COLORRECTAL ELECTIVA: El alta hospitalaria hacia el domicilio luego de una resección colorrectal puede aumentar el riesgo de readmisión.Determinar el impacto de varias configuraciones diferentes de alta en la readmisión a 30 días luego de ajustar factores demográficos y clínicos.Estudio de cohortes retrospectivo.Los datos se obtuvieron del Consorcio del Sistema de Salud Universitaria (2011-2015).Todos aquellos adultos que se sometieron a una resección colorrectal electiva.Los riesgos de readmisión hospitalaria a 30 días.La edad media de la población estudiada (n = 97,455) fué de 58 años; la mitad eran hombres y un 78% eran blancos. El 70% fueron dados de alta de manera rutinaria (a domicilio sin servicios complementarios), 24% alta a domicilio con servicios de salud organizados, 5% alta hacia un centro con cuidados de enfermería especializada, 1% alta hacia un centro de rehabilitación y <1% alta hacia un hospital con atención a largo plazo. La tasa global de readmisión fué del 12%; nueve por ciento desde domicilios sin servicios complementarios, 16% desde domicilios con servicios de salud organizados, 19% desde un centro de enfermería especializada, 34% desde el centro de rehabilitación y 22% desde un hospital con atención a largo plazo (p <0.001). Los pacientes con estadías en Unidad de Cuidados Intensivos, con más complicaciones postoperatorias y con una hospitalización prolongada tenían más probabilidades de ser dados de alta hacia un domicilio con servicios de salud organizados o hacia un centro de rehabilitación (p <0,001). El alta hospitalaria con servicios organizados de atención médica domiciliaria, centros de enfermería especializada o centros de rehabilitación aumentaron el riesgo de readmisión ajustada de múltiples variables en un 30% (OR 1.3, IC 95% 1.3-1.6), 60% (OR 1.6, IC 95% 1.5-1.8), o 200% (OR 3.0, IC 95% 2.5-3.6), respectivamente. El alta hospitalaria a largo plazo no fué asociada con un mayor riesgo de readmisión ajustada (OR 1.2, IC 95% 0.9-1.6), no obstante que este grupo fué el que tuvo las mayores comorbilidades y complicaciones postoperatorias. Entre los pacientes readmitidos dentro de los 30 días, la mediana del tiempo hasta el reingreso fue significativamente diferente entre el domicilio sin servicios complementarios (7), domicilio con servicios de salud organizados (8), el centro de cuidados de enfermería especializada (8), centros de rehabilitación (9) y hospitales con atención a largo plazo (12) (p <0,001).Naturaleza retrospectiva del presente estudio.El alta hospitalaria con servicios de salud domiciliarios organizados, hacia centros de enfermería especializada o hacia centros de rehabilitación se asocian con un mayor riesgo ajustado de readmisión en comparación con el alta domiciliaria de rutina y los hospitales con atención a largo plazo. Los objetivos potenciales para disminuir la readmisión incluyen mejorar la transición de la atención al momento del alta, mejorar la calidad de la atención después del alta y mejorar las diferentes facilidades para los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B272.


Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.
A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.


Disease-specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas.
Quality of life (QoL) is impaired in patients treated for pituitary adenomas. However, differences in age and gender distributions hamper a proper comparison of QoL. Therefore, we compared age- and gender-specific standard deviations (SD) scores (Z-scores) of QoL parameters in patients treated for pituitary adenomas. We determined Z-scores for health-related questionnaires [the Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI)-20, Nottingham Health Profile (NHP), and Short Form Health Survey (SF-36)] in patients during long-term follow-up (13 +/- 8 years) after treatment for pituitary adenomas. Z-scores were calculated by comparing the data for 403 patients with acromegaly (n = 118), Cushing's disease (CD; n = 58), prolactinoma (n = 128), and nonfunctioning macroadenoma (n = 99) with a control population (n = 440) for each subscale of the questionnaires and for total QoL score. All subscales of the questionnaires and the total QoL score were negatively affected in patients compared to controls. Comparing the Z-scores, patients treated for acromegaly reported more impairment in physical ability and functioning and more bodily pain compared to patients treated for nonfunctioning macroadenoma and those treated for prolactinoma. Patients with CD reported impairment in physical functioning compared to patients treated for nonfunctioning macroadenoma. Linear regression analysis, with correction for age and gender, confirmed these findings. Additionally, CD was associated with increased anxiety. Hypopituitarism negatively influenced multiple aspects of QoL. QoL is impaired in patients during long-term follow-up after treatment of pituitary adenomas. Patients with pituitary adenomas should be informed of these persistent adverse effects of their disease on QoL to prevent inappropriate expectations with respect to the long-term results of treatment.


Relation of Change of Body Mass Index to Long-Term Mortality After Cardiac Catheterization.
Body-mass index (BMI) is a risk marker and therapeutic target in cardiovascular prevention. The effect of changes in BMI on mortality in patients with cardiovascular diseases has not been completely delineated. We aimed to assess the association between percent change in BMI, as measured 3-years after cardiac catheterization, and long-term mortality. Patients who underwent cardiac catheterization (n = 11,220; mean age 63 ± 10 years) were categorized according to BMI groups (normal-weight, 18.50 to 24.99 kg/m2; overweight, 25.00 to 29.99 kg/m2; obesity, ≥30 kg/m2). Follow-up BMI was considered the level measured closest to the timepoint of 3 years post catheterization. Percent change in BMI was calculated and its association with long-term all-cause mortality was investigated. Change in BMI of ±5% was observed in 46% of the patients, a decrease >5% in 15.5%, and an increase of >5% of BMI in 38.5%. Compared with those with the lowest change in BMI (±5%), the adjusted hazard ratios for mortality were 1.45 (95% confidence interval [CI], 1.27 to 1.65), and 1.69 (1.46 to 1.95) in patients with 5% to 10% and >10% decrease in BMI, respectively, and 1.05 (0.94 to 1.17), 1.15 (1.03 to 1.28), and 1.40 (1.19 to 1.64) in patients with 5% to 10%, 10% to 20% and >20% increase in BMI, respectively. The pattern was similar in normal-weight, overweight, and obese subgroups at baseline. However, the magnitude of the association with decrease BMI was more pronounced in normal-weight patients (P-for-interaction 0.031). In conclusion, the association of percent changes in BMI after cardiac catheterization and all-cause mortality had a reversed J-shaped pattern, with both weight loss and weight gain being associated with increased risk. A decrease in BMI was related to higher mortality rates than was an increase in BMI for a comparable degree of percent change.


Turning gray selenium into a nanoaccelerator of tissue regeneration by PEG modification.
Selenium (Se) is an essential trace element involved in nearly all human physiological processes but suffers from a narrow margin between benefit and toxicity. The nanoform of selenium has been proven shown to be more bioavailable and less toxic, yet significant challenges remain regarding the efficient and feasible synthesis of biologically active nanoselenium. In addition, although nanoselenium has shown a variety of biological activities, more interesting nanoselenium features are expected. In this work, hydrosoluble nanoselenium termed Nano-Se in the zero oxidation state was synthesized between gray Se and PEG. A zebrafish screen was carried out in zebrafish larvae cocultured with Nano-Se. Excitingly, Nano-Se promoted the action of the FGFR, Wnt, and VEGF signaling pathways, which play crucial roles in tissue regeneration. As expected, Nano-Se not only achieved the regeneration of zebrafish tail fins and mouse skin but also promoted the repair of skin in diabetic mice while maintaining a profitable safe profile. In brief, the Nano-Se reported here provided an efficient and feasible method for bioactive nanoselenium synthesis and not only expanded the application of nanoselenium to regenerative medicine but also likely reinvigorated efforts for discovering more peculiarunique biofunctions of nanoselenium in a great variety of human diseases.


Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus.
The diagnosis and differential classification of systemic lupus erythematosus (SLE) is difficult, especially in patients with early-onset SLE who are susceptible to systemic multi-organ damage and serious complications and have difficulties in individualized treatment. At present, diagnosis is based mainly on clinical manifestations and the detection of serological antinuclear antibodies. The pathogenesis of SLE involves multiple factors, is clinically heterogeneous, and lacks specific biomarkers. Therefore, it is necessary to identify new biomarkers for the diagnosis and subtype classification of SLE. Non-coding RNAs (ncRNAs) are composed of microRNAs, long non-coding RNAs, small nucleolar RNAs, circular RNAs, and transfer RNAs. They play an important role in the occurrence and development of diseases and are used widely in the early diagnosis and prognosis of autoimmune diseases. In this review, we focus on the research progress in the diagnosis and prognostic assessment of SLE using humoral to tissue level ncRNAs.


Unexpected stereochemistry in the lithium salt catalyzed ring expansion of nonracemic oxaspiropentanes. formal syntheses of (-)-(4R,5R)-muricatacin and the pheromone (R)-japonilure.
[reaction: see text] The stereochemistry of the cyclobutanones 3, obtained by lithium salt catalyzed ring expansion of the optically pure oxaspiropentanes 2, depends not only on the lithium salt but also on the stereochemistry of 2. They constitute the starting material for the syntheses of the acetogenin (-)-(4R,5R)-muricatacin and the pheromone (R)-japonilure.


Clozapine for Treatment-Refractory Aggressive Behavior.
Emergency psychiatry has the main role of resolving suicidal behavior and aggression. These severe psychiatric symptoms can be found in many psychiatric disorders such as schizophrenia, bipolar disorder, major depression, personality disorders, cognitive disorders, intellectual disability and substance abuse. Although indications for the use of antipsychotics are limited to a specific group of diseases, they are frequently used as rescue medication in high-risk or nonresponsive cases. Clozapine, the gold standard for TRS (treatment resistant schizophrenia) is effective in controlling aggression. The aim of the research was to identify the use of clozapine for treatment-refractory aggressive behavior in psychiatric emergency. A retrospective study based on the paper files of patients admitted between 2010 and 2019 in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania. Were included all the patients admitted as a psychiatric emergency and treated with clozapine for aggressive behavior. The hospital is an academic institution with 150 beds for acute patients, serving an area of over 600,000 inhabitants. It is the main public institution where patients with psychiatric emergencies are hospitalized. Off 19,000 patients admitted during the study period, 504 patients (2,4%) with a diagnosis other than schizophrenia or schizoaffective disorder received clozapine for aggressiveness (89.5%). The first four diagnoses identified were bipolar disorder (n = 172), intellectual disability (n = 128), cognitive impairment (n = 112), and personality disorder (n = 92). Other disorders identified but with a smaller number of cases were major depressive disorder (n = 3), adjustment disorders (n = 2), delusional disorder (n = 2), obsessive compulsive disorder (n = 2) and postpartum psychosis (n = 1). Clozapine was used as 3rd or 4th choice. The dose was greater for manic patients (350.29 ± 98.01 mg/day) compared with all the other diagnoses. Clozapine was effective and safe in cases of patients with treatment-refractory aggressive behavior.


Resolution of left atrial appendage thrombi: No difference between phenprocoumon and non-vitamin K-dependent oral antagonists.
Atrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life-threatening condition. Thrombus resolution may prevent embolic events and allow rhythm-control strategies, which have been shown to reduce cardiovascular complications. There is no significant difference between phenprocoumon and non-Vitamin K-dependent oral anticoagulants (NOACs) in the resolution of LAA-thrombi in a real-world setting. Consecutive patients with LAA-thrombi from June 2013 to June 2017 were included in an observational single-center analysis. The primary endpoint was defined as the resolution of the thrombus. The observational period was 1 year. Resolutions rates in patients on phenprocoumon or NOACs were compared and the time to resolution was analyzed. We identified 114 patients with LAA-thrombi. There was no significant difference in the efficacy of resolution between phenprocoumon and NOACs (p = .499) at the time of first control which took place after a mean of 58 ± 42.2 (median 48) days. At first control most thrombi were dissolved (74.6%). The analysis after set-time intervals revealed a resolution rate of 2/3 of LAA-thrombi after 8-10 weeks in the phenprocoumon and NOAC groups. After 12 weeks a higher number of thrombi had resolved in the presence of NOAC (89.3%) whereas in the presence of phenprocoumon 68.3% had resolved (p = .046). In this large observational study NOACs were found to be potent drugs for the resolution of LAA-thrombi. In addition, the resolution of LAA-thrombi was found to be faster in the presence of NOAC as compared to phenprocoumon.


Ultrasound-guided percutaneous endovascular aneurysm repair success is predicted by access vessel diameter.
Ultrasound scan-guided access allows for direct visualization of the access artery during percutaneous endovascular aortic aneurysm repair. We hypothesized that the use of ultrasound scan guidance allowed us to safely increase the utilization of percutaneous endovascular aortic aneurysm repair to almost all patients and decrease access complications. A retrospective chart review of all elective endovascular aortic aneurysm repairs, both abdominal and descending thoracic, from 2005 to 2010 was performed. Patients were identified using International Classification of Disease, 9th Revision, Clinical Modification Codes and stratified based on access type: percutaneous vs cut-down. We examined the success rate of percutaneous access and the cause of failure. Sheath size was large (18-24 F) or small (12-16 F). Minimum access vessel diameter was also measured. Outcomes were wound complications (infections or clinically significant hematomas that delayed discharge or required transfusion), operative and incision time, length of stay, and discharge disposition. Predictors of percutaneous failure were identified. One hundred sixty-eight patients (296 arteries) had percutaneous access endovascular aneurysm repair (P-EVAR) whereas 131 patients (226 arteries) had femoral cutdown access EVAR. Ultrasound scan-guided access was introduced in 2007. P-EVAR increased from zero cases in 2005 to 92.3% of all elective cases in 2010. The success rate with percutaneous access was 96%. Failures requiring open surgical repair of the artery included seven for hemorrhage and six for flow-limiting stenosis or occlusion of the femoral artery. P-EVAR had fewer wound complications (0.7% vs 7.4%; P = .001), shorter operative time (153.3 vs 201.5 minutes; P < .001), and larger minimal access vessel diameter (6.7 mm vs 6.1 mm; P < .01). Patients with failed percutaneous access had smaller minimal access vessel diameters when compared to successful P-EVAR (4.9 mm vs 6.8 mm; P < .001). More failures occurred in small sheaths than large ones (7.4% vs 1.9%; P = .02). Access vessel diameter <5 mm is predictive of percutaneous failure (16.7% of vessels <5 mm failed vs 2.4% of vessels ≥ 5 mm failed; P < .001; odds ratio, 7.3; 95% confidence interval, 1.58-33.8; P = .01). Ultrasound scan-guided P-EVAR can be performed in the vast majority of patients with a high success rate, shorter operative times, and fewer wound complications. Access vessel diameters <5 mm are at greater risk for percutaneous failure and should be treated selectively.


Epithelial urinary bladder tumors from cows with enzootic hematuria: structural and cell cycle-related protein expression.
Thirty-nine epithelial bladder tumor samples from 37 animals affected with bovine enzootic hematuria (BEH) were selected for immunohistochemical studies. The expression of structural proteins such as uroplakin III (UPIII) and cytokeratin 7 (CK7) and the cell cycle-related proteins cyclin D1 and p53 were evaluated in urothelial papillomas and carcinomas. Loss of UPIII and CK7 expression was seen in both high-grade and high-stage urothelial carcinomas (P < .001 and P < .02). Cyclin D1 expression showed no statistically significant association with grade or stage. In contrast, p53 immunoreactivity was positive in high-grade and high-stage carcinomas (P < .05 and P < .01), confirming its association with the highest malignant behavior of the bladder tumors in BEH.


Evaluation of right ventricular functions and B-type natriuretic peptide levels by cardiopulmonary exercise test in patients with pulmonary regurgitation after repair of tetralogy of Fallot.
Impairment of right ventricular functions, especially due to chronic pulmonary regurgitation (PR), is a well-known entity in patients with tetralogy of Fallot (ToF) after repair. The aim of this study was to examine the relation between B-type natriuretic peptide (BNP) levels and right ventricular dysfunction by cardiopulmonary exercise test (ET) in patients after repair of ToF. Twenty-five patients with a mean age of 14.1 +/- 4.4 years at follow-up who underwent repair of ToF at a mean age of 4.9 +/- 5.1 years and 29 age- and sex-matched healthy children at a mean age of 13.1 +/- 2.8 years were enrolled in this study. Plasma BNP levels were measured at baseline and at maximal exercise. The volume of right ventricle (RV) and the degree of PR were assessed by two-dimensional echocardiography and color Doppler. Plasma BNP levels were significantly higher in patients with ToF than in controls (28.3 +/- 24.1 vs 7.4 +/- 2.3 pg/mL, p = 0.0001). Exercise was associated with increased plasma BNP levels in both groups. A greater increase in BNP was noted in patients with ToF than in controls (37.6 +/- 27.5 vs 11.3 +/- 4.5 pg/mL, p = 0.0001). Forced vital capacity (FVC%) (84.9 +/- 16.9 vs 98.4 +/- 18.2, p = 0.01) and forced expiratory volume during the 1st second (FEV1%) (91.5 +/- 19.3 vs 103.8 +/- 16.1, p = 0.02) were decreased, exercise duration (ED) (10.1 +/- 1.9 vs 11.4 +/- 1.7 min, p = 0.02), maximum heart rate (HRmax) (171.2 +/- 18.9 vs 186.4 +/- 13.9 /min, p = 0.004), and maximum oxygen uptake (VO(2)max) (1.56 +/- 0.53 vs 2.1 +/- 0.6 L/min, p = 0.007) were lower in patients with ToF. There were significant correlations between the degree of PR and ED (r =-0.3, p = 0.009), HRmax (r =-0.4, p = 0.001), and VO(2)max (r =-0.4, p = 0.001). The correlations were significant both before and after exercise, being more pronounced after exercise between BNP level and the degree of PR (r = 0.6, p = 0.0001). As a result, the severity of PR has a negative influence on right ventricular functions and there is significant relation between right ventricular functions and exercise capacity after repair of tetralogy of Fallot.


Postpartum hypertension and nonsteroidal analgesia.
Nonsteroidal analgesics are frequently used in obstetrics. We present two cases where nonsteroidal analgesics contributed to significant elevations in blood pressure in postpartum women. We review the literature and consider the pathophysiologic causes for such a phenomenon.


The brain-gut axis: A prime therapeutic target in traumatic brain injury.
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in trauma patients. The primary focus of treating TBI is to prevent additional injury to the damaged brain tissue, known as secondary brain injury. This treatment can include treating the body's inflammatory response. Despite promise in animal models, anti-inflammatory therapy has failed to improve outcomes in human patients, suggesting a more targeted and precise approach may be needed. There is a bidirectional axis between the intestine and the brain that contributes to this inflammation in acute and chronic injury. The mechanisms for this interaction are not completely understood, but there is evidence that neural, inflammatory, endocrine, and microbiome signals all participate in this process. Therapies that target the intestine as a source of inflammation have potential to lessen secondary brain injury and improve outcomes in TBI patients, but to develop these treatments we need to better understand the mechanisms behind this intestinal inflammatory response.


Social distancing and prosocial behaviors: The replenishing effect of intense visual stimulation.
COVID-19 has disrupted lives across the world. This research investigates the psychological and behavioral consequences of social distancing, which is being globally practiced to contain its spread. Using seven experiments, we document the moderating role of high-intensity visual stimulation on social distancing's effect on psychologically distressed individuals' prosocial intentions and behaviors. The results reveal that social distancing resulted in ego depletion; however, exposure to high-intensity visual stimuli replenished cognitive resources and increased prosocial intentions and behaviors among those experiencing psychological distress due to social distancing.


Acetazolamide as Add-on Diuretic Therapy in Exacerbations of Chronic Heart Failure: a Pilot Study.
Congestion is the main cause of morbidity in patients with heart failure. Treatment of fluid overload is often challenging in everyday clinical practice. The aim of this study was to determine the diuretic effect of acetazolamide in patients with exacerbations of chronic heart failure, in addition to their stable diuretic therapy. This was a single-center, unblinded study. Patients hospitalized with chronic heart failure exacerbations, with left ventricular ejection fraction (EF) < 50% and signs of volume overload, with a stable dose of diuretics anticipated by the attending physician over the next 4 days, were considered eligible for the study. On day 1, patients were randomized to receive acetazolamide orally, once daily (dose-adjusted to body weight) or no treatment (control group) as add-on diuretic therapy, on days 2 and 3. Diuresis, natriuresis, fluid balance, and symptoms were assessed daily, up to day 4. Twenty patients (mean ± standard deviation age 72 ± 11.6 years; 85% men; mean EF 33.8 ± 11.4%; mean N-terminal pro-B-type natriuretic peptide 8064 ± 5593 pg/mL; mean intravenous furosemide dose 105 ± 55 mg) were enrolled. Diuresis, natriuresis, fluid balance, and symptoms were stable on days 1-4 in the control group. An increase in diuresis and natriuresis, and a greater change in fluid balance after administration of acetazolamide, were observed in patients randomized to acetazolamide. On day 4, there was a significant difference in fluid balance between the acetazolamide and control groups (-666 ± 1194 mL vs. +332 ± 705 mL; p = 0.035), and dyspnea was lower in patients receiving acetazolamide (visual scale, p < 0.001; 5-point Likert scale, 1.444 vs. 2.222; p = 0.04) CONCLUSIONS: In this pilot study, the addition of acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced an additional diuretic effect and alleviation of dyspnea.


Empirical Shaft Resistance of Driven Piles Penetrating Weak Rock.
In this paper, an empirical relationship between the Unconfined Compressive Strength (UCS) of intact rock and the unit shaft resistance of piles penetrating rock is investigated. A growing number of civil engineering projects are utilizing steel piles driven into rock where a significant portion of the pile capacity is derived from the shaft resistance. Despite the growing number of projects utilizing the technology, little to no guidance is offered in the literature as to how the shaft resistance is to be calculated for such piles. A database has been created for driven piles that penetrate bedrock. The database consists of 42 pile load tests of which a majority are steel H-piles. The friction fatigue model is applied to seven of the pile load tests for which sufficient UCS data exists in order to develop an empirical relation. The focus of this paper is on case histories that include driven pipe piles with at least 2 m penetration into rock.


The control issue in biofeedback training.
Well-delineated models and procedural descriptions are noticeably missing from the clinical biofeedback literature dealing with the training of physiological self-control. As a consequence, optimal protocols for the assessment and training of self-control of physiological functions have not eventuated. The present article reviews evidence suggesting that researchers have (a) confused self-control training, assessment, and measurement of tonic response levels, (b) neglected to determine the degree of acquired physiological self-control, and (c) failed to report the relationship between level of acquired physiological control and clinical outcome. The article also proposes an assessment and training paradigm that may be useful in reducing these methodological problems in future biofeedback research.


[Quantitative and qualitative study of the fecal flora of cirrhotic patients].
In this study, the qualitative and quantitative fecal flora was determined in 30 cirrhotic patients. The flora of these patients was composed of some bacterial populations and does not differ appreciably from the normal.


Communication disorders and children with mental retardation.
Within both the pragmatics orientation and the revised definition of MR, the discussion of communication disorders for children with MR has begun to de-emphasize a developmental content-form protocol for assessment and intervention. Instead, the current model suggests the importance of communication stimulation and support in daily routines, the nature of which includes the perceptions and expectations of communication partners, and the characteristics of the social interaction that affect communication style.