Progesterone enhances L-dopa-stimulated dopamine release from the caudate nucleus of freely behaving ovariectomized-estrogen-primed rats.
In the present experiment we examined the effect of progesterone upon dopamine (DA) release induced by a direct infusion of unlabeled L-dihydroxyphenylalanine (L-DOPA) into the caudate nucleus of freely behaving rats. Ovariectomized rats were implanted with a push-pull cannula directed at the caudate nucleus and subjected to perfusion under 3 different hormonal conditions: (1) following 4 days of treatment with estradiol benzoate (EB), (2) following 4 days of treatment with estradiol benzoate plus progesterone at 4-6 h prior to perfusion (EB + P-4-6 h) and (3) following 4 days of treatment with estradiol benzoate plus progesterone at 28 h prior to perfusion (EB + P-28 h). During each perfusion session and under each of the 3 hormonal treatment conditions, L-DOPA was infused through the push side of the cannula. Three increasing doses of L-DOPA (10(-6), 10(-5) and 10(-4) M) were infused with a 45-75 min interval between infusions. Regardless of hormonal treatment condition, a clear dose-response increase in DA and 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-HIAA, output was observed in response to the increasing doses of L-DOPA infusion. For each of the 3 doses of L-DOPA, maximal DA output was observed for animals tested under the EB + P-4-6 h hormonal condition, with statistically significant differences in the areas under the L-DOPA-stimulated DA response curves obtained following the 10(-6) and 10(-5) M doses of L-DOPA infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface.
Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2-specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.


Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1-5 years.
The prodrug oseltamivir has been shown to be efficacious and safe for the treatment of influenza for patients 1 year of age or older; however, pharmacokinetic information was lacking for children below 5 years of age. This study was conducted to assess the metabolic and excretory capacity of oseltamivir and its active carboxylate metabolite in young children. Twelve healthy children aged 1-5 years received a single oral suspension dose of oseltamivir (45 mg for 3-5 years, 30 mg for 1-2 years). Plasma and urine concentrations of oseltamivir and the carboxylate were determined by means of liquid chromatography/tandem mass spectrometry. Mean peak plasma concentration and area under the plasma concentration-time curve values normalized to milligram per kilogram oseltamivir dose in the 1- to 2-year group are lower than those in the 3- to 5-year group. Mean body weight normalized oral clearance of oseltamivir and its carboxylate in younger subjects aged 1-2 years (259 ml/min/kg and 12.2 ml/min/kg) were, respectively, 52% and 30% higher than those in older subjects aged 3-5 years (170 ml/min/kg and 9.4 ml/min/kg). The results demonstrate that infants as young as 1 year old can metabolize and excrete oseltamivir efficiently. The data derived from this study provide the starting dose of oseltamivir for further investigation in an efficacy study among influenza-infected infants less than 1 year of age.


[Comparative study of smallpox vaccines from strains B-51, EM-63 and L-IVP in a controlled epidemiologic trial. I. Reactogenic characteristics of the smallpox vaccines].
A comparative study of smallpox vaccines prepared from the l-ivp zm-63 and b-51 strains was carried out under conditions of controlled epidemiological trial. Children subject to planned vaccination were scarified with commercial batches of the preparations under study (with the same infectious activity). As a result of investigations it was found that in the group of those scarified with the vaccine from zm-63 strain strong local and catarrhal reactions and some disturbances of general condition were more frequent than in those scarified with preparations from the l-ivp and b-51 strain. Along with this, the temperature elevation of various intensity showed no statistically significant difference in the groups a vaccinated with the vaccines compared. Integral analysis of signs characterising different manifestations of reactigenic properties of the vaccines compared led to the conclusion that preparations made of zm-6 strain had greater reactogenic properties.


Interactions substrat-flavine-hemoproteine et stabilite thermique du cytochrome b(2) (L-lactate deshydrogenase de la levure).
We studied the thermal inactivation of yeast cytochrome b(2), the native flavohaemoprotein (FHP(n)) and its derivatives, the haemoprotein (HP) obtained by dissociation of FMN from FHP(n) and the reconstituted flavohaemoprotein (FHP(r)) (haemoprotein + FMN). The initial velocity of inactivation is faster in the presence of FMN. The substrate (L-lactate) or the competitive inhibitor (oxolate) protects only the flavohaemoproteins (FHP(n) and FHP(r)) from thermal inactivation by decreasing this velocity. In each case, the "protection constant", K(p), is determined.Several interpretations can be proposed to explain the lack of protection of the haemoprotein by its substrate: 1) the structure of the substrate-binding site depends on the presence of the FMN; 2) the substrate binding site exists, but the affinity is too small to be detected; 3) a hypothetical scheme is proposed, suggesting that the protein can exist under different thermally sensitive forms following whether FMN or substrate is present.


Hierarchical structure and mechanical properties of snake (Naja atra) and turtle (Ocadia sinensis) eggshells.
After hundreds of million years of evolution, natural armors have evolved in various organisms, and has manifested in diverse forms such as eggshells, abalone shells, alligator osteoderms, turtle shells, and fish scales. Eggshells serve as multifunctional shields for successful embryogenesis, such as protection, moisture control and thermal regulation. Unlike calcareous avian eggshells which are brittle and hard, reptilians have leathery eggshells that are tough and flexible. Reptilian eggshells can withstand collision damages when laid in holes and dropped onto each other, and reduce abrasion caused by buried sand. In this study, we investigate structure and mechanical properties of eggshells of Taiwan cobra snake (Naja atra) and Chinese striped-neck turtle (Ocadia sinensis). From Acid Fuchsin Orange G (AFOG) staining and ATR-FTIR examination, we found that both eggshells are mainly composed of keratin. The mechanical properties of demineralized snake and turtle eggshells were evaluated by tensile and fracture tests and show distinctly difference. Turtle eggshells are relatively stiff and rigid, while snake eggshells behave as elastomers, which are highly extensible and reversible. The exceptional deformability (110-230% tensile strain) and toughness of snake eggshells are contributed by the wavy and random arrangement of keratin fibers as well as collagen layers. Multi-scale toughening mechanisms of snake eggshells were observed and elucidated, including crack deflection and twisting, fibers reorientation, sliding and bridging, inter-laminar shear effect, as well as the α-β phase transition of keratin. Inspirations from the structural and mechanical designs of reptilian eggshells may lead to the synthesis of tough, extensible, lightweight composites which could be further applied in the flexible devices, packaging and bio-medical fields. Amniotic eggshells serve as multifunctional shields for successful embryogenesis. The avian eggshells have been extensively studied while there are very few studies on reptilian eggshells and most of them focused on mineralization and embryotic development. For the first time, the hierarchical structure and mechanical properties of snake and turtle eggshells are comprehensively and comparatively studied. Both snake and turtle eggshells are multilayer, hierarchically-structured composites consisting mainly of keratin yet their mechanical behaviors are distinctly different. Turtle eggshells are stiff and rigid, while snake eggshells are highly extensible (>200%) and reversible due to multiple deformation stages, phase transition of keratin and various toughening mechanisms. We believe that this study will make positive scientific impact and interest the broad and multidisciplinary readership.


Evolution of testicular architecture in the Drosophilidae: a role for sperm length.
Evolutionary biologists have so far largely treated the testis as a black box with a certain size, a matching resource demand and a resulting sperm output. A better understanding of the way that the testis responds to selection may come from recent developments in theoretical biology aimed at understanding the factors that influence the evolution of tissue architecture (i.e. the logical organisation of a tissue). Here we perform a comparative analysis of aspects of testicular architecture of the fruit fly family Drosophilidae. Specifically, we collect published information on the number of first (or primary) spermatocytes in spermatogenesis, which allows to infer an important aspect of testicular architecture. We show that testicular architecture is much more variable (both within and between species) than is generally appreciated. Moreover, the number of first spermatocytes is strongly correlated to the sperm length, which is inversely related to the sperm production, and thus the workload of the testis. Our study clearly documents that tissue architecture can evolve, and that in the Drosophilidae it may do so in response to sexual selection. We conclude that the testis of the Drosophilidae is a promising model organ to test recent models of tissue architecture.


Intestinal histological findings in patients with spondyloarthritis: a study of the relationship with disease activity.
The role of intestinal microbioma and subclinical bowel inflammation in the etiology of sponsyloarthritis (SpA) has gained a lot of attention recently. Almost 65% of SpA patients will have asymptomatic bowel inflammation if assessed by ileocolonoscopy. The connection between intestinal inflammation and SpA originated the gut-joint axis hypothesis in which monocytes and T cells found in the joint would have origin in the gut.


Trace metal analysis by laser-enhanced ionization in flames.
We review atomic flame spectrometry of metals based on the selective laser-enhancement of the rate of atomic ionization. A discussion of basic principles, prior literature, and instrumentation is followed by an overview of analytical figures of merit for the technique, and a look at its present status and areas for future development.


Schizophrenia and velo-cardio-facial syndrome.
Velo-cardio-facial syndrome (VCFS), the most frequent known interstitial deletion identified in man, is associated with chromosomal microdeletions in the q11 band of chromosome 22. The VCFS phenotype is complex, with multiple congenital abnormalities affecting several tissues and organs, many of which are derived from neural crest cells. Although phenotypic variability occurs, individuals with VCFS have high rates of psychiatric disorder, especially schizophrenia. Additionally, an increased prevalence of chromosome 22q11 deletions has been reported in populations of people with schizophrenia. Furthermore, results of molecular genetic studies suggest that a schizophrenia susceptibility locus maps to chromosome 22q. These data indicate that aside from being the child of two parents with schizophrenia or the monozygotic co-twin of an affected individual, VCFS and deletion 22q11 represents the highest known risk factor for the development of schizophrenia. Since the entire sequence of chromosome 22 has now been identified, the study of VCFS offers a timely and uniquely powerful opportunity to identify susceptibility genes for schizophrenia in the general population. Furthermore, the strength of the association between schizophrenia and VCFS has important implications for the clinical management of these disorders.


[Pharmacological treatment of fibromyalgia syndrome].
An interdisciplinary guideline for the treatment of fibromyalgia syndrome (FMS) and chronic widespread pain (CWP) was developed in cooperation with ten German medical and psychological associations and two patients' self-help organizations. Using the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/ 2006) a systematic literature search was performed, which included all randomised controlled trials (RCT) evaluating multicomponent therapy in FMS and CWP. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. The strength of recommendation was graded according to the German program for disease management guidelines. Consensus was achieved using a multi-step nominal group procedure. The short-term use of amitriptyline is strongly recommended (grade A) and the short-term use of fluoxetine und duloxetine is recommended (grade B). The recommendations regarding pharmacological treatment of FMS are limited by the short duration of the RCT, the lack of follow-ups and absence of cost-effectiveness studies.


Individualized fluid management in extremely preterm neonates to ensure adequate diuresis without increasing complications.
Decrease the incidence of inadequate diuresis (ID, loss of <6% of birth weight) in extremely preterm neonates (EPT, <28 weeks of gestation at birth) during the first week of life by 50% in 1 year. Quality improvement project in a level IV neonatal intensive care unit. A fluid management protocol was implemented, including the use of a fluid guide sheet and closer monitoring of hydration parameters. Seventy-nine baseline EPT neonates were compared to 83 post intervention. The incidence of ID was tracked monthly, along with prespecified morbidities and complications. Statistical data analyses also compared the pre- and post-intervention periods. Fluid volumes in the first week were decreased (p < 0.001). ID decreased from 43 to 29% (p = 0.061). Tracked morbidities and complications were not statistically different. Intentional and individualized adjustment of fluids led to decreased ID without increased hypernatremia and dehydration, or a change in tracked morbidities.


Natural biomacromolecule based composite scaffolds from silk fibroin, gelatin and chitosan toward tissue engineering applications.
Natupolymer-based scaffolds can increase cell affinity to biomaterials and improve cell responses. Silk fibroin, chitosan and gelatin that mimic the properties of natural extra-cellular matrix (ECM) were chosen due to their biocompatibility, biodegradability and less immunogenic reactions. We prepared composite scaffolds with different blending ratios of silk fibroin-chitosan-gelatin by freeze-drying technique. Silk fibroin was extracted from the Bombyx mori silkworm. The scaffolds were characterized by scanning electron microscopy (SEM), surface wettability, swelling measurements, In Vitro enzymatic degradation measurements and tensile test. The composite scaffolds showed pore sizes from 125 μm to 175 μm, good interconnectivity between pores and suitable porosity which are desirable for cell growth. The addition of chitosan-gelatin to silk fibroin increased water uptake and degradation rate and reduced mechanical strength but silk fibroin affect reversely on the degradation and mechanical strength of composite scaffolds. Biocompatibility of scaffolds was demonstrated by MTT-assay and hematoxylin-eosin (H&E) staining which lead to the growth and adhesion of endothelial cells. In this study, the fabricated composite scaffolds have the potential for tissue engineering applications.


Indecainide for treatment of ventricular ectopic depolarizations: efficacy, pharmacokinetics, hemodynamic effects and safety.
Ten patients were treated with oral indecainide for frequent ventricular ectopic depolarizations during a short-term, dose-ranging, single blind inpatient trial followed by open label long-term therapy for 2 years. During dose ranging, patients received placebo followed by 50, 75 and 100 mg of indecainide three times daily. Eight of the 10 patients achieved greater than or equal to 80% reduction in ventricular ectopic depolarizations during inpatient therapy. Mean ventricular ectopic depolarizations decreased from 15,792/24 h to 2,357/24 h on optimal dosage (p less than 0.01). Nine patients had paired ventricular ectopic depolarizations; four of the nine had greater than or equal to 99% reduction of these beats. Among seven patients with nonsustained ventricular tachycardia, five had 100% elimination of these events with indecainide and all had greater than or equal to 90% reduction in these events. Indecainide prolonged the PR interval 44 +/- 27 ms (p less than 0.0001) and the QRS interval 11 +/- 9 ms (p less than 0.0001) from baseline without prolongation of the QTc or JTc interval. The mean trough plasma level of indecainide on optimal dosage was 409 +/- 173 ng/ml and the mean plasma elimination half-life was 10.3 +/- 2.3 h (range 7.1 to 14.2). No adverse hemodynamic effects of indecainide were detected. Side effects during short-term therapy were mild and did not require discontinuation of the drug. Efficacy was maintained for some patients during long-term therapy for 2 years, although five patients discontinued therapy because of loss of efficacy or side effects. Indecainide is a highly effective and well tolerated antiarrhythmic drug for suppression of frequent and repetitive ventricular ectopic depolarizations.


Simple indicators for projecting short-term dental market fluctuations.
There have been fluctuations over time in dental care expenditures in the United States. This project aims to develop simple indicators that are easily available to people and that can be useful to predict short-term market fluctuations. The authors analyzed data concerning 30 variables for the period of 1980 through 2012 for correlations with dental care expenditures during that period, looking for factors that historically moved in a highly correlated manner, either positively or negatively, with dental care expenditures. The authors lagged the factors to determine their potential predictive value for dental care expenditures. Personal consumption expenditures and gross domestic product emerged as valid leading indicators for predicting short-term dental market fluctuations. Two simple measures that are easily available to dentists and others can serve as indicators of short-term fluctuations in the dental marketplace. Their validity as indicators can, and should, be monitored regularly. These indicators can be of significant value for practitioners in being alerted to potential market changes and planning to accommodate these changes. Combined, these factors can tell what changes are coming and when they have arrived.


Effect of Dexmedetomidine on Perioperative Stress Response and Immune Function in Patients With Tumors.
This study aims to investigate the effect of dexmedetomidine on perioperative stress response and immune function in patients with tumors. Sixty patients who underwent selective radical gastrectomy for cancer were randomly divided into 3 groups: remifentanil group (group R), dexmedetomidine group (group D), and sufentanil group (group S). Remifentanil, dexmedetomidine, and sufentanil were used as general anesthetics. Endotracheal intubation and mechanical ventilation were performed after the spontaneous respiration disappeared. Then, the data were recorded, and blood samples were collected at all time points. The heart rate significantly increased (P < 0.05) at T1 in group S, and both heart rate and mean arterial pressure significantly increased (P < 0.05) in group R when compared to group D. The heart rate significantly increased (P < 0.05) at T2 in group S and group R. Furthermore, the heart rate significantly increased (P < 0.05) at T3 and T4 in group S and group R. Intra-group comparison: The heart rate at T1-T4 and mean arterial pressure at T1-T4 significantly increased (P < 0.05) in group S, and the heart rate at T1 and T4, and mean arterial pressure at T2-T4 significantly increased (P < 0.05) in group R when compared to T0. The serum IL-6, IFN-γ, and β-EP significantly increased (P < 0.05) at T0' in group S and group R when compared to group D. Blood glucose, and serum IL-10, IFN-γ, and β-EP significantly increased (P < 0.05), while IL-18 significantly decreased (P < 0.05) at T1' in group S and group R. Continuous infusion of dexmedetomidine in combination with the inhalation of sevoflurane is superior to sevoflurane + remifentanil or sufentanil in patients undergoing tumor surgery.


Semi-IPN hydrogels of collagen and gum arabic with antibacterial capacity and controlled release of drugs for potential application in wound healing.
The preparation of hydrogels based on biopolymers like collagen and gum arabic gives a chance to provide novel options that can be used in biomedical field. Through a polymeric semi-interpenetration technique, collagen-based polymeric matrices can be associated with gum arabic while controlling its physicochemical and biological properties. To create novel hydrogels with their potential use in the treatment of wounds, the semi-interpenetration process, altering the concentration (0-40% by wt) of gum arabic in a collagen matrix is explored. The ability of gum arabic to create intermolecular hydrogen bonds in the collagen matrix enables the development of semi-interpenetrating polymeric networks (semi-IPN)-based hydrogels with a faster gelation time and higher crosslinking. Amorphous granular surfaces with linked porosity are present in matrices with 30% (by wt) of gum arabic, enhancing the storage modulus and thermal degradation resistance. The hydrogels swell to very high extent in hydrolytic and proteolytic environments, good hemocompatibility, and suppression of growth of pathogens like E. coli, and all it is enhanced by gum arabic included them, in addition to enabling the controlled release of ketorolac. The chemical composition of theses semi-IPN matrices have no deleterious effects on monocytes or fibroblasts, promoting their proliferation, and lowering alpha tumor necrosis factor (α-TNF) secretion in human monocytes.


Enuresis and sleep fellowship education.
Enuresis is a common sleep-related concern in school aged children that gradually decreases into adulthood. We performed a survey of sleep providers in order to assess their comfort level in managing patients with enuresis. Survey participants were recruited via the Pedsleep listserv and sleep medicine program directors in the USA on basecamp application. The Pedsleep list includes a mixture of physicians, psychologists, and other sleep providers/researchers. Forty-two sleep providers completed the survey. Forty (95%) were board certified in sleep medicine, and 32 (76%) were board certified in pediatrics. Practice patterns for management of enuresis varied among respondents, with 69% who evaluate for possible contributions from other sleep disorders such as obstructive sleep apnea then refer for additional management. Nineteen (45%) respondents felt that they received inadequate or very inadequate training during their sleep fellowship for management of enuresis. While 83% of respondents worked in an academic medical center setting, none of their respective sleep clinics were the primary managing clinic at their own situation. Participants who endorsed their training as adequate/very adequate were significantly more likely to feel comfortable/very comfortable managing enuresis (90% vs 37.5%, p = 0.009). A large percentage of sleep providers are lacking essential training to manage enuresis patients. These results suggest the need for additional educational initiatives in this area.


Studies of the inhibitory non-adrenergic neuromuscular transmission in the smooth muscle of the normal human intestine and from a case of Hirschsprung's disease.
A modified sucrose-gap method was used to study both non-adrenergic inhibitory neuromuscular transmission and effects of adenosine 5'-triphosphate (ATP) on isolated smooth muscle preparations from the human intestine. It was found that non-adrenergic inhibition in the circular smooth muscle layer was of larger amplitude than in the longitudinal layer. Study of the ionic mechanisms underlying non-adrenergic inhibition indicated that an increase in K+ conductance was responsible for the generation of non-adrenergic inhibitory junction potentials (IJPs). The results suggest that the inhibitory actions of the endogenous neurotransmitter and exogenous ATP are due to increases in Ca2+-dependent K+ conductance. The K+-channel blockers tetraethylammonium and 4-aminopyridine had no effect on IJPs or ATP, while apamin slightly decreased both the amplitude of the IJP and the hyperpolarization of the circular smooth muscle caused by ATP. These results are consistent with the purinergic hypothesis of non-adrenergic inhibition. In addition to inhibitory purinoceptors, the existence of excitatory purinoceptors was identified in the longitudinal muscle, activation of which probably caused an increase in Na+-conductance. The excitatory purinoceptor-mediated contraction in the longitudinal muscle from the constricted region of large intestine from patients with Hirschsprung's disease was greater than that found in control specimens. It is possible that excitatory purinoceptors play a role in the pathophysiology of Hirschsprung's disease.


Exploring the methylation status of CFTR and PKIA genes as potential biomarkers for lung adenocarcinoma.
One of the most prevalent cancers in the world is lung cancer, with adenocarcinoma (LUAD) making up a significant portion of cases. According to the National Cancer Institute (NCI), there are new cases and fatality rates per 100,000 individuals as follows: New instances of lung and bronchial cancer occur annually at a rate of 50.0 per 100,000 persons. The yearly death rate for men and women is 35.0 per 100,000. DNA methylation is one of the earliest discovered and widely studied epigenetic regulatory mechanisms, and its abnormality is closely related to the occurrence and development of cancer. However, the prognostic value of DNA methylation and LUAD needs to be further explored to improve the survival prediction of LUAD patients. The transcriptome data and clinical data of LUAD were downloaded from TCGA and GEO databases, and the Illumina Human Methylation450 array (450k array) data were downloaded from the TCGA database. Firstly, the intersection of the expressed genes of the two databases is corrected, the differential analysis is performed, and the methylation data is evaluated by the MethylMix package to obtain differentially methylated genes. Independent prognostic genes were screened out using univariate and multivariate Cox regression analysis, and a methylation prognostic model was developed using univariate Cox analysis and validated with the GSE30219 dataset in the GEO database. Survival analysis between methylation high-risk and low-risk groups was performed and a methylation-based gene prognostic model was constructed. Finally, the prediction of potential drugs associated with the LUAD gene signature using Drug Sensitivity Genomics in Cancer (GDSC). In this study, a total of 555 samples from the TCGA database and 307 samples from GSE30219 were included, and a total of 24 differential methylation driver genes were identified. Univariate and multivariate Cox regression analyzes were used to screen out independent prognostic genes, involving 2 genes: CFTR, PKIA. Survival analysis was different between the methylation high-risk group and the low-risk group, the CFTR high methylation group and the low methylation group were poor, and the opposite was true for PKIA. Our study revealed that the methylation status of CFTR and PKIA can serve as potential prognostic biomarkers and therapeutic targets in lung cancer.


Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders.
The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.


[Verification of the proteolytic and lipolytic activities of the microbial flora isolated from raw, refrigerated, type B milk. II. Psychrotrophic microorganisms].
The aim of this work was to evaluate the microbiological quality of raw type B milk, kept under refrigeration at 3 degrees C, for a period of 15 days. The milk was enumerated and isolated a total of 180 microorganisms, of which 80 were psychrotrophics. The ability of these microorganisms to produce lipolysis and/or proteolysis in the milk was evaluated. Concerning the microbiological analysis, the samples analyzed presented high values for total counting. The results from the initial counting were 2.7 x 10(4) UFC/ml for psychrotrophic, with a predominance of Gram negative bacilli, which were highly lipolytic and had proteolytic activities associated.


Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules.
This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed-HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4(+) T cells stimulated by autologous monocytes induced by HBsAg.


Ischemic myocardial protection. Comparison of nonoxygenated crystalloid, oxygenated crystalloid, and oxygenated fluorocarbon cardioplegic solutions.
This study was designed to compare myocardial protection with a nonoxygenated crystalloid solution, an oxygenated crystalloid solution, and an oxygenated fluorocarbon cardioplegic solution. Postischemic ventricular performance was studied in three equal (N = 7) groups of dogs subjected to 120 minutes of global ischemia induced at an average myocardial temperature of 18.5 degrees +/- 1.4 degrees C (range 17.0 degrees to 21.0 degrees C). Left ventricular global and regional function was evaluated by sonomicrometry and micromanometers before ischemia and at 45 and 60 minutes after ischemia. Stroke volume index, left ventricular pressure-minor external diameter loop area, percent shortening, first derivative of left ventricular pressure, mean velocity of circumferential fiber shortening, and the slope of the end-systolic pressure were used to evaluate myocardial contractility. In vitro oxygen content of the three cardioplegic solutions was measured at a mean injection temperature of 8.3 degrees +/- 0.6 degrees C: 0.8 +/- 0.1 vol% (nonoxygenated crystalloid cardioplegia), 3.2 +/- 0.2 vol% (oxygenated crystalloid cardioplegia), and 6.2 +/- 0.2 vol% (oxygenated fluorocarbon cardioplegia). Recovery of global and regional function was significantly (p less than 0.05) better with both oxygenated solutions than with the nonoxygenated solution. Differences between the oxygenated crystalloid and fluorocarbon groups were not significant. We conclude: (1) Compared to nonoxygenated crystalloid cardioplegia, oxygenated crystalloid and oxygenated fluorocarbon cardioplegic solutions gave superior myocardial protection during 2 hours of ischemic arrest; (2) no difference was found in protective effects between an oxygenated crystalloid and an oxygenated fluorocarbon solution.


Osmotic swelling and residual stress in cardiovascular tissues.
Osmotic swelling (OS) and residual stress (RS) significantly affect the function of cardiovascular (CVS) tissues and organs. The physical mechanisms of OS and RS are reviewed and analyzed with focus on the theoretical background and related experimental evidence. It will be shown that swelling of CVS tissues stems from the presence of charged proteoglycan macro-molecules in these tissues, and that this swelling is a key determinant of RS. In view of OS and RS functional significance in mechanical function, modeling attempts which incorporate them in CVS stress analysis will be presented and discussed.


Accuracy and conformity of stereotactically guided interstitial brain tumour therapy using I-125 seeds.
To assess the accuracy of the stereotactic implantation procedure of catheters containing I-125 seeds in brain tumours and investigate the effect of catheter deviations on the dose distribution in patients. A randomised sample (n = 37) of all patients treated with I-125 seeds in our department between 6/1994 and 2/2002 was examined. Intraoperative X-ray images were used to measure deviations of implanted I-125 seed catheters from their planned positions and the influence on dose conformity, tumour surface dose and dose burden of surrounding healthy brain tissue was determined. The mean spatial target point deviation was 2.0 mm (maximum 4.1 mm, SD 0.9 mm) and in 54.1% of the cases, reduction of the planned dose was greater than 5%. Target point deviations less than 1.5 mm have only minor influence on surface dose and conformity. Results indicated that in 10.8% of the cases the realized dose distribution showed a 'slight deviation', according to the guideline criteria for external radiosurgery of the Radiation Therapy Oncology Group. In 89.2% of the patients the applied dose conformed to the target volume. Stereotactically guided interstitial irradiation with I-125 seeds can be used to treat brain tumours and metastases with high conformity comparable to radiosurgery. The observed deviations of the stereotactically implanted I-125 seed catheters from their planned target points were smaller when compared to frameless procedures. In order to maintain the required spatial accuracy of 1.5 mm in interstitial therapy using I-125 seeds, it appears necessary to optimise stereotactic instruments further.


Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment.
Chemotherapy-induced cognitive impairment (CICI) is one of the major adverse effects of antineoplastic drugs, which decrease the quality of life in cancer survivors. Extensive experimental and clinical research suggests that chemotherapeutic drugs generate an enormous amount of reactive oxygen species (ROS), contributing to oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal death, eventually leading to CICI. Despite the progress in exploring different pathological mechanisms of CICI, effective treatment to prevent CICI progression has not been developed yet. Nrf2 is the principal transcription factor that regulates cellular redox balance and inflammation-related gene expression. Emerging evidence suggests that upregulation of Nrf2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase neurogenesis. This review discusses the role of Nrf2 in CICI, how it responds to oxidative stress, inflammation, neurotoxicity, and potential Nrf2 activators that could be used to enhance Nrf2 activation in CICI.


18-FDG PET/ CT Scan in the Diagnosis and Follow-up of Chronic Q fever Aortic Valve Endocarditis.
Chronic Q fever endocarditis is a rare but important infection associated with risk of morbidity and mortality. Echocardiography rarely visualises the vegetative lesion. We describe the first Australian report of chronic Q fever aortic valve endocarditis confirmed with the use of 18 -FDG PET/ CT scan. Following valvular replacement, the patient had ongoing high serological titres despite active treatment and he was managed with yearly serial PET/ CT scan to confirm the absence of active infection. The utility of serial PET /CT scan imaging as a follow-up management strategy has not been described in the literature previously and should be investigated further.


The source of the respiratory drive to nasolabialis motoneurones in the rabbit; a HRP study.
Lower brainstem projections to the motoneurones of the nasolabialis muscles, which show rhythmic respiratory-phased activity were studied in the rabbit using the horseradish peroxidase (HRP) technique. The nasolabial motoneurone pool was first identified by the retrograde transport of HRP injected intramuscularly, and by antidromic stimulation and microelectrode recording techniques. The results from subsequent iontophoretic injection of HRP into the lateral division of the facial nucleus (the nasolabial pool) produced significant ipsilateral labelling in the nucleus ambiguus-retroambigualis (NA-NRA) complex. Labelled cells, predominantly ipsilateral, were also consistently observed in the parvocellular reticular nucleus. Smaller numbers of labelled cells were identified in the ventral, dorsal and gigantocellular nuclei of the reticular formation on both sides of the medulla. A large proportion of HRP-labelled cells of the NRA was located in the caudal medulla where the presence of propriobulbar and bulbospinal respiratory neurones has been well documented. These results suggest that some neurones of the NA-NRA complex may serve as upper respiratory motoneurones to the nasolabial musculature.


Hemin protects against oxygen-glucose deprivation-induced apoptosis activation via neuroglobin in SH-SY5Y cells.
This study aimed to investigate the mechanism underlying the neuroprotective effect of hemin in oxygen-glucose deprivation (OGD)-treated neurons. OGD-treated SH-SY5Y cells (human neuroblastoma cells) were used in the study. The cellular viability of SH-SY5Y cells was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell apoptosis rate was determined by flow cytometry analysis with Annexin V-fluorescein isothiocyanate and propidium iodide staining with or without hemin pretreatment. Cell viability and apoptotic activation were detected after hemin administration combined with neuroglobin (Nqb), thioredoxin-1, peroxiredoxin-2, or heme oxygenase-1 siRNA transient transfection. The release of cytochrome c from mitochondria and the interaction between Ngb and cytochrome c were examined with hemin pretreatment. Hemin had a neuroprotective effect in OGD-treated SH-SY5Y cells, which was mainly mediated by the upregulation of Ngb. Moreover, the release of cytochrome c from mitochondria was inhibited by hemin-induced Ngb expression through facilitating the interaction of Ngb with cytochrome c in mitochondria. The present findings provided new insights into the neuroprotective mechanisms of hemin. It was concluded that low-dose hemin pretreatment had a neuroprotective effect in OGD-treated SH-SY5Y cells, through inhibiting cell apoptosis. The neuroprotective effects of hemin following hypoxic-ischemic neuronal damage were mainly mediated by Ngb. One underlying mechanism was hemin-induced overexpression of mitochondrial Ngb, which inhibited endogenous apoptosis via the association with cytochrome c.


Evidence that the Tfg1/Tfg2 dimer interface of TFIIF lies near the active center of the RNA polymerase II initiation complex.
The ssu71 alleles of the TFG1 gene, which encodes the largest subunit of TFIIF, were isolated as suppressors of a TFIIB defect that affects the accuracy of transcription start site selection in the yeast Saccharomyces cerevisiae. Here we report that ssu71-1 also suppresses the cell growth and start site defects associated with an altered form of the Rpb1 subunit of RNA polymerase II (RNAP II). The ssu71-1 and ssu71-2 alleles were cloned and found to encode single amino acid replacements of glycine-363, either glycine to aspartic acid (G363D) or glycine to arginine (G363R). Two other charged replacements, G363E and G363K, were constructed by site-directed mutagenesis and suppress both TFIIB E62K and Rpb1 N445S, whereas neither G363A nor G363P exhibited any effect. G363 is phylogenetically conserved and its counterpart in human TFIIF (RAP74 G112) is located within the RAP74/RAP30 dimerization domain. We propose that the TFIIF dimerization domain is located in proximity to the B-finger of TFIIB near the active center of RNAP II where the TFIIB-TFIIF-RNAP II interface plays a key role in start site selection.


Cadmium-induced functional and ultrastructural alterations in roots of two transgenic cotton cultivars.
The toxic effect of cadmium (Cd) at increasing concentrations was studied with special attention being given to the root morphological and ultrastructural changes in two transgenic cotton cultivars viz. BR001 and GK30 and their wild relative viz. Coker 312. In comparison to their respective controls, low concentration (10 and 100microM) of Cd greatly stimulated seed germination, while it was inhibited by highest concentration of Cd (1000microM) in case of two transgenic cultivars. However, in Coker 312 the seed germination percentage progressively decreased over the control at all Cd levels. Various physiological and morphological parameters of the root and whole plant in both transgenic cotton cultivars and their relative wild cotton genotype respond differently towards the Cd toxicity. Bioavailability of Cd was concentration-dependent where seedling root captured more Cd as compared to shoot. BR001 accumulated more Cd followed by GK30, while Coker 312 was less Cd accumulator. The ultrastructural modifications in the root tip cells of both the transgenic cotton cultivars and their wild relative were also dose-dependent. With the increase in Cd levels, the fine structures of their root cells also invariably changed. Increase in plasmolysis of the plasma membrane, greater number of nucleoli and vacuoles and enlarged vacuoles could be observed in both transgenic cotton cultivars. In comparison to them, Coker 312 showed relatively well developed ultrastructures of the root tips except enlarged vacuoles and greater number of mitochondria. Moreover, the accumulation of Cd in the form of electron dense granules and crystals both in vacuoles and attached to cell walls were visible in both transgenic cotton cultivars and their wild relative. These results suggest that both transgenic cotton cultivars and their wild relative cotton genotype responded positively towards Cd stress at seedling stage, the internal Cd-detoxification might be through apoplastic and symplastic binding. Moreover, as a whole BR001 proved to be sensitive whereas; GK30 and Coker 312 were found as tolerant.


Modern analytics for synthetically derived complex drug substances: NMR, AFFF-MALS, and MS tests for glatiramer acetate.
Glatiramer acetate (GA) is a mixture of synthetic copolymers consisting of four amino acids (glutamic acid, lysine, alanine, and tyrosine) with a labeled molecular weight range of 5000 to 9000 Da. GA is marketed as Copaxone™ by Teva for the treatment of multiple sclerosis. Here, the agency has evaluated the structure and composition of GA and a commercially available comparator, Copolymer-1. Modern analytical technologies which can characterize these complex mixtures are desirable for analysis of their comparability and structural "sameness." In the studies herein, a molecular fingerprinting approach is taken using mass-accurate mass spectrometry (MS) analysis, nuclear magnetic resonance (NMR) (1D-(1)H-NMR, 1D-(13)C-NMR, and 2D NMR), and asymmetric field flow fractionation (AFFF) coupled with multi-angle light scattering (MALS) for an in-depth characterization of three lots of the marketplace drug and a formulated sample of the comparator. Statistical analyses were applied to the MS and AFFF-MALS data to assess these methods' ability to detect analytical differences in the mixtures. The combination of multiple orthogonal measurements by liquid chromatography coupled with MS (LC-MS), AFFF-MALS, and NMR on the same sample set was found to be fit for the intended purpose of distinguishing analytical differences between these complex mixtures of peptide chains.


Radiofrequency current application on immature porcine atrial myocardium: no evidence of areas of slow conduction after 12-month follow-up.
Radiofrequency current (RFC) application is a widely used procedure for treatment of supraventricular arrhythmias. The purpose of this study was to investigate late electrophysiologic sequelae of RFC lesions at immature atrial myocardium in pigs, as they have not yet been systematically investigated in vitro. RFC application (temperature guided) was performed in seven piglets (mean age 6 weeks) by a steerable 6-French electrode catheter positioned at the lateral aspect of the tricuspid valve annulus. After 12 months, hearts were removed, and lesions with surrounding tissue were isolated. The viable tissue at the border of the specimen was paced with a cycle length of 500 and 600 msec. One hundred fifty impalements were performed on each specimen using capillary microelectrodes to record action potential characteristics from the lesion's surface and the surrounding tissue. In all seven specimens, no transmembrane action potentials from the fibrotic surface of each of the lesions could be recorded. The surrounding viable tissue was sharply demarcated electrically. No areas of slow conduction were detected. Action potential characteristics as mean maximum diastolic transmembrane potential, mean action potential duration at 90% repolarization, and upstroke velocity of phase 0 of the action potential were all normal. No evidence of areas of slow conduction 12 months after RFC application at immature atrial myocardium suggests that this technique is safe regarding occurrence of late atrial tachyarrhythmias after the procedure.


Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa.
The development in Plasmodium falciparum of the resistance to chloroquine (CQ) constitutes a public health priority, due to its direct influence in childhood mortality. The molecular basis for CQ resistance (CQR) is still unclear but, recently, a new relevant gene, named pfcrt, with several point mutations was identified in P. falciparum. Two mutations, K76T and A220S, have been considered crucial for CQR in further studies, making the pfcrt a good candidate as determinant for CQR in P. falciparum. To contribute to this topic, we have undertaken a molecular screening on 164 P. falciparum isolates from Africa: 120 isolates were Italian imported malaria cases, 27 and 17 isolates were from a school-children survey from Congo and Tanzania, respectively. In vitro tests (pLDH and WHO-Mark III tests) for CQ sensitivity have been also carried out on 28 plasmodial isolates and results compared to those obtained by molecular analysis in the same isolates. The SVIET pfcrt haplotype has been identified in the samples from Congo, and this is the first time that this haplotype is detected in Africa. Our results give further evidence to the reliability of the 76T (and the linked 74I-75E) pfcrt point mutation as molecular marker for CQR.


Measurement of the uniaxial elasticity of oral mucosa in vivo after CO2-laser evaporation and surgical excision.
The stress-strain relation of oral mucosa of dogs was measured before and 6 weeks after surgical removal of mucosa. Both CO2-laser evaporation and excision were employed. Measurements were done with a miniature tensile tester, especially developed for this purpose. The load-strain ratio of the healed mucosa was proportional to the histologically determined thickness of the healed epithelium and scar tissue together. Laser evaporation caused a 75% increase, excision almost a threefold increase of the load-strain ratio compared with untreated tissue.


IgG autoantibodies against ACE2 in SARS-CoV-2 infected patients.
How frequently autoantibodies against angiotensin-converting enzyme 2 (ACE2) occur in patients infected by SARS-CoV-2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long-lasting effects of COVID-19 observed in some individuals, particularly if IgG-class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS-CoV-2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti-ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID-19, but some severe and asymptomatic cases were also observed. Patients with severe infection had twofold higher titers than mild and asymptomatic cases. Age, comorbidities, and influenza vaccination status were not related to antibody prevalence. The prevalence of IgG anti-SARS-CoV-2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor-binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS-CoV-2 infection, particularly concerning long COVID-19.


Genome scan for spelling deficits: effects of verbal IQ on models of transmission and trait gene localization.
Dyslexia is a complex learning disability with evidence for a genetic basis. Strategies that may be useful for dissecting its genetic basis include the study of component phenotypes, which may simplify the underlying genetic complexity, and use of an analytic approach that accounts for the multilocus nature of the trait to guide the investigation and increase power to detect individual loci. Here we present results of a genetic analysis of spelling disability as a component phenotype. Spelling disability is informative in analysis of extended pedigrees because it persists into adulthood. We show that a small number of hypothesized loci are sufficient to explain the inheritance of the trait in our sample, and that each of these loci maps to one of four genomic regions. Individual trait models and locations are a function of whether a verbal IQ adjustment is included, suggesting mediation through both IQ-related and unrelated pathways.


Advances of microfluidic technology in reproductive biology.
According to World Health Organization (WHO) reports about 70 million couples suffer from infertility all over the world. A lot of research groups are working on this issue and have made therapeutic approaches by integrating biology, medicine, genetics, chemistry, psychology, mechanic, and many other branches of science. However, these methods have their own pros and cons. Assisted Reproductive Technologies (ART) has appeared to solve infertility problems. In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), Intrauterine Insemination (IUI) are the most common and conventional technologies in this regard. There are at least two characteristics of microfluidics, mechanical and biochemical, which can be influential in the field of mammalian gamete and preimplantation embryo biology. These microfluidic characteristics can assist in basic biological studies on sperm, oocyte and preimplantation embryo structure, function and environment. Using microfluidics in sorting sperm, conducting different steps of oocyte selection and preparation, and transferring embryo by passing sub-microliter fluid through microchannels results in low cost and short time. The size and shape of microchannels and the volume of used fluid differs from non-human cells to human cells. The most progressions have been seen in animal models. Results suggest that microfluidic systems will lead to improved efficiencies in assisted reproduction.


N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis.
Fatty acid amide hydrolase (FAAH) degrades 2 major classes of bioactive fatty acid amides, the N-acylethanolamines (NAEs) and N-acyl taurines (NATs), in central and peripheral tissues. A functional polymorphism in the human FAAH gene is linked to obesity and mice lacking FAAH show altered metabolic states, but whether these phenotypes are caused by elevations in NAEs or NATs is unknown. To overcome the problem of concurrent elevation of NAEs and NATs caused by genetic or pharmacological disruption of FAAH in vivo, we developed an engineered mouse model harboring a single-amino acid substitution in FAAH (S268D) that selectively disrupts NAT, but not NAE, hydrolytic activity. The FAAH-S268D mice accordingly show substantial elevations in NATs without alterations in NAE content, a unique metabolic profile that correlates with heightened insulin sensitivity and GLP-1 secretion. We also show that N-oleoyl taurine (C18:1 NAT), the most abundant NAT in human plasma, decreases food intake, improves glucose tolerance, and stimulates GPR119-dependent GLP-1 and glucagon secretion in mice. Together, these data suggest that NATs act as a class of lipid messengers that improve postprandial glucose regulation and may have potential as investigational metabolites to modify metabolic disease.


Prevalence of traumatic events and peritraumatic predictors of posttraumatic stress symptoms in a nonclinical sample of college students.
This study investigated lifetime prevalence of traumatic events and posttraumatic stress disorder (PTSD) symptoms among 937 college students. Participants rated their lifetime experiences of traumatic events and, in response to their "most stressful" event, completed measures of objective stressor dimensions, PTSD, and peritraumatic reactions. Approximately 67% of respondents reported at least one traumatic event. An estimated 4% of the full sample (12% of traumatized individuals) met PTSD criteria within the past week. After controlling for vulnerability factors and objective characteristics, peritraumatic reactions remained strongly predictive of PTSD symptoms. Results are discussed with respect to immediate reactions to traumatic events as potential precursors of PTSD symptomatology.


Estimated daily average per capita water ingestion by child and adult age categories based on USDA's 1994-1996 and 1998 continuing survey of food intakes by individuals.
Water ingestion estimates are important for the assessment of risk to human populations of exposure to water-borne pollutants. This paper reports mean and percentile estimates of the distributions of daily average per capita water ingestion for a number of age range groups. The age ranges, based on guidance from the US EPA's Risk Assessment Forum, are narrow for younger ages when development is rapid and wider for older ages when the rate of development decreases. Estimates are based on data from the United States Department of Agriculture's (USDA's) 1994-1996 and 1998 Continuing Survey of Food Intake by Individuals (CSFII). Water ingestion estimates include water ingested directly as a beverage and water added to foods and beverages during preparation at home or in local establishments. Water occurring naturally in foods or added by manufacturers to commercial products (beverage or food) is not included. Estimates are reported in milliliters (ml/person/day) and milliliters per kilogram of body weight (ml/kg/day). As a by-product of constructing estimates in terms of body weight of respondents, distributions of self-reported body weights based on the CSFII were estimated and are also reported here.


Localization of hepatitis B surface antigen in the human parotid gland.
Localization of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the human parotid gland and liver was studied by an immunohistochemical method in four cases with seropositive HBsAg. Neither HBsAg nor HBcAg could be detected in the parenchymal cells of the parotid gland in any of the cases. However, one of four cases, which had the highest titer of serum HBsAg, showed HBsAg immunoreactivity in the vascular wall and luminal fluid of the parotid gland. In liver, HBsAg was detected in three and HBcAg in two of the four cases, respectively. HBsAg was localized in the cytoplasm of hepatocytes, while HBcAg was localized mainly in their nuclei. The detection of HBsAg in the parotid gland and liver was correlated with the serum titer of the antigen. The results indicate that the HB virus does not have an affinity for or a replicate in the parotid gland. Also, it is suggested that the HBsAg found in saliva is derived from HBsAg circulating through the oral mucosa by capillary leakage and not from secretion into the mouth by the salivary gland.


On ten species of jumping spiders from Xishuangbanna, China (Araneae, Salticidae).
Nine new species of jumping spiders from Xishuangbanna Tropical Botanical Garden are described: Euochinyaoi sp. nov. (♀♂), Laufeiabanna sp. nov. (♀♂), Marengotangi sp. nov. (♀♂), Myrmarachneliui sp. nov. (♀♂), Nandiciusproszynskii sp. nov. (♂), Phintelloidespengi sp. nov. (♀♂), Poecilorchesteszhengi sp. nov. (♀♂), Rhenewandae sp. nov. (♂) and Simaethacheni sp. nov. (♀♂). The female of Chinattusinflatus Wang & Li, 2020 is described for the first time.


Adenosine-to-Inosine Editing of Vasoactive MicroRNAs Alters Their Targetome and Function in Ischemia.
Adenosine-to-inosine (A-to-I) editing in the seed sequence of microRNAs can shift the microRNAs' targetomes and thus their function. Using public RNA-sequencing data, we identified 35 vasoactive microRNAs that are A-to-I edited. We quantified A-to-I editing of the primary (pri-)microRNAs in vascular fibroblasts and endothelial cells. Nine pri-microRNAs were indeed edited, and editing consistently increased under ischemia. We determined mature microRNA editing for the highest expressed microRNAs, i.e., miR-376a-3p, miR-376c-3p, miR-381-3p, and miR-411-5p. All four mature microRNAs were edited in their seed sequence. We show that both ADAR1 and ADAR2 (adenosine deaminase acting on RNA 1 and RNA 2) can edit pri-microRNAs in a microRNA-specific manner. MicroRNA editing also increased under ischemia in vivo in a murine hindlimb ischemia model and ex vivo in human veins. For each edited microRNA, we confirmed a shift in targetome. Expression of the edited microRNA targetomes, not the wild-type targetomes, was downregulated under ischemia in vivo. Furthermore, microRNA editing enhanced angiogenesis in vitro and ex vivo. In conclusion, we show that microRNA A-to-I editing is a widespread phenomenon, induced by ischemia. Each editing event results in a novel microRNA with a unique targetome, leading to increased angiogenesis.


AMP deaminase deficiency in skeletal muscle is unlikely to be of clinical relevance.
The homozygous c.34C>T mutation in the AMPD1 gene encoding the muscle-specific isoform of AMP deaminase (AMPD) accounts for the vast majority of inherited skeletal muscle AMPD deficiencies. It is controversial (i) whether AMPD deficiency is associated with exercise-induced complaints and (ii) whether an acquired form exists in which an underlying neuromuscular disorder additionally lowers the AMPD activity. c.34C>T mutation (homozygous- TT, heterozygous-CT,wildtype-CC) was screened in 107 healthy blood donors and 294 patients with skeletal muscle biopsy including 200 with exercise-induced complaints. Additional screening for c.468G > T and c.860A > T mutations was performed in all CT.AMPD was analysed histochemically and biochemically. The mutant allele frequency (MAF) was not different in blood donors, patients with muscle biopsy, and the subgroup with exercise-induced complaints (12.9-16.8 %). CT was found in 63 and TT in 13 patients. The c.468G>T mutation was not detected. The c.860A > T mutation was found in 2.8 % blood donors and 1.6% CT. AMPD activities showed a substantial overlap in CC and CT, but not with TT. AMPD activities in TT, CT, and CC did not differ in patients with a defined neuromuscular disorder and those with only exercise-induced complaints. In TT, CT, and CC there were no differences in the frequency of signs and symptoms, hyperCKemia, or myopathological biopsy pattern. MAF did not differ in normal and diseased populations. The frequency of exertion-induced complaints was not higher in TT than CC. There was no specific phenotype of TT and no evidence for an acquired form of AMPD deficiency.


The association of transforming growth factor-beta 1 with myometrial invasion of endometrial carcinomas through effects on matrix metalloproteinase.
The association of transforming growth factor-beta 1 (TGF-beta 1) with a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase (TIMP), as well as myometrial invasion of endometrial cancer was studied. The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity, and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta receptor Type I in tumor tissue from the same patients also was detected. Invasiveness, gelatinase activity, and the expression of TIMP-1 were higher in KLE cells than in Ishikawa cells, and they were increased by treatment with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1. The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage-Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were ubiquitous. Myometrial invasion of endometrial cancers involves an increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an autocrine or paracrine fashion.


Designing a Transparent CdIn2 S4 /In2 S3 Bulk-Heterojunction Photoanode Integrated with a Perovskite Solar Cell for Unbiased Water Splitting.
The integration of photoelectrochemical photoanodes and solar cells to build an unbiased solar-to-hydrogen (STH) conversion system provides a promising way to solve the energy crisis. The key point is to develop highly transparent photoanodes, while its bulk separation efficiency (ηsep. ) and surface injection efficiency are as high as possible. To resolve this contradiction, first a novel CdIn2 S4 /In2 S3 bulk heterojunctions in the interior of nanosheets is designed as a photoanode with high transparency and an ultrahigh ηsep. up to 90%. Furthermore, decorating the ultrathin amorphous SnO2 layer by atomic layer deposition, the surface oxygen-evolution kinetics of the photoanode are increased significantly. As a result, the onset potential of the photoanode shifts negatively to 0.02 V vs RHE, and the photocurrent density boosts to 2.98 mA cm-2 at 1.23 V vs RHE, which is ten times higher than that of pristine CdIn2 S4 . Such a high-performance photoanode enables the integrated metal sulfide photoanode-perovskite solar cell system to deliver a STH conversion efficiency of 3.3%.


Effects of increasing the PSA cutoff to perform additional biomarker tests before prostate biopsy.
Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer. We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies. 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly. The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered. ISRCTN84445406 .


Complications in plastic surgical anesthesia.
The possibilities for complications in plastic surgical procedures are widespread. Many of these have been discussed elsewhere in this symposium. An attempt has been made to discuss a few other complications for which immediate action would be necessary by the plastic surgeon in charge. Immediate application of correct principles of diagnosis and treatment can be lifesaving. A thorough understanding of all mechanisms of injury abnormality may not be possible or even required. However, sufficient knowledge should be present to allow prompt diagnosis and initial emergency treatment by the operating surgeon. This knowledge will enable the surgeon to assume his responsibility in the complete care of his patient before, during, and after surgery.


Sensor to Monitor Localized Stresses on Steel Surfaces Using the Magnetostrictive Delay Line Technique.
In this paper, a new type of force sensor is presented, able to monitor localized residual stresses on steel surfaces. The principle of operation of the proposed sensor is based on the monitoring of the force exerted between a permanent magnet and the under-test steel which is dependent on the surface permeability of the steel providing a non-hysteretic response. The sensor's response, calibration, and performance are described followed by a discussion concerning the applications for steel health monitoring.


Abnormalities of esophageal transit in patients with sporadic nontoxic goitre.
Esophageal transit (E.T.) was investigated in 122 consecutive euthyroid patients with scintigraphically proven goitre, and compared to 26 control subjects. E.T. was quantified using the 81mKr transit time, a highly sensitive technique capable of detecting even minor E.T. disorders. Abnormal E.T. was observed in 39% of goitrous patients, while it was normal in all controls. Occurrence of delayed E.T. was not correlated with either goitre firmness, the presence of symptoms of neck discomfort, difficulties in swallowing, or nodularity. E.T. delay was more frequent and more severe with larger goitres. In addition, E.T. delay was significantly correlated with asymmetry and "low lying" goitres. In summary, the present studies are the first demonstration of frequent E.T. anomalies in goitrous patients. The data suggest that E.T. impairment could be mediated by two mechanisms: a direct compression effect in patients with large, asymmetrical, partially retrosternal goitres; and an indirect functional esophageal anomaly in patients with small goitres.


Different structural vascular changes in angiotensin II-treated and cold-stressed rats.
The role of the renin-angiotensin and sympathetic nervous system in the pathogenesis of structural vascular changes in experimental hypertension was investigated by comparing the effect of angiotensin II (ANG II) administration and of sympathetic stimulation by cold stress on the structure and composition of mesenteric arteries of rats. Adult male Sprague-Dawley rats were administered subcutaneously 100 ng/kg per min ANG II or exposed to 5 degrees C cold overnight for 12 weeks. Sham-operated rats were controls. At the end of treatment, the mesenteric circulation of rats was perfusion-fixed for morphometric measurements by light microscopy and volume density measurements by point counting on electron micrographs. Tail systolic blood pressure of ANG II-treated rats increased by 37 mm Hg at week 2 and remained elevated for the rest of the experiment. The systolic BP of cold-stressed rats measured at room temperature did not change. These findings were confirmed by direct measurement of mean arterial pressure in free-moving rats. Compared to control rats, medial thickening of large and small arteries in ANG II-treated and cold-stressed rats was the main finding of this study. Thickening of the media in the two treated groups of rats appeared to be due to hypertrophy of vascular muscle, as indicated by the increased width of smooth muscle cells. Loose matrix (interstitial fluid compartment) was increased in media of large arteries of ANG II-treated rats, and collagen was increased in the outer media of arteries of cold-stressed rats. Measurements of compositional changes in addition to morphometric changes are needed to detect differences in the pathogenesis of structural vascular changes in the various forms of hypertension.


Tetralogy of Fallot: prenatal diagnosis and postnatal survival.
To correlate prenatal echocardiographic findings with infant outcome in a large screening population affected by tetralogy of Fallot. Inclusion criteria required confirmed postnatal cardiac diagnosis, at least one fetal ultrasound examination with satisfactory heart visualization, and infant delivery at our institution. Aortic and pulmonary artery diameters were measured from real-time ultrasound or videotaped scans and compared against published nomograms. The pulmonary artery to aorta ratio was also evaluated in a similar manner. Infant survival was assessed 1 year after delivery. Seventeen fetuses were confirmed to have a ventricular septal defect and an overriding aorta with varying degrees of right ventricular outflow obstruction after delivery. All karyotypes were normal. Ultrasound screening identified 12 of 17 abnormal hearts at a mean gestational age of 22.9 +/- 5.1 weeks; two of these fetuses were thought to have only ventricular septal defect before delivery. Five fetuses had enlarged aortic roots during the initial scan. Only two of the ten fetuses with a measurable pulmonary artery had initial sonographic evidence for valve stenosis. Six other pulmonary arteries became abnormally small with advancing pregnancy. The pulmonary artery to aorta ratio was decreased in six of the ten fetuses with a measurable pulmonary artery. Sixteen infants survived at least 1 year after birth and successfully completed either corrective or palliative cardiac surgery. Fetuses with tetralogy of Fallot may present with only a ventricular septal defect and aortic septal override by prenatal ultrasound examination. Pulmonary artery stenosis is not always present at initial ultrasound examination, but this finding can develop or worsen during pregnancy. Furthermore, a normal aortic diameter does not exclude tetralogy of Fallot. Infant survival appears to be favorable in the absence of other major structural or chromosomal anomalies.


Synthesis and oxidation of some azole-containing thioethers.
Pyrazole and benzotriazole-containing thioethers, namely 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-thiapentane, 1,8-bis(3,5-dimethylpyrazol-1-yl)-3,6-dithiaoctane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-thiapropane were prepared and fully characterized. Oxidation of the pyrazole-containing thioether by hydrogen peroxide proceeds selectively to provide a sulfoxide or sulfone, depending on the amount of oxidant used. Oxidation of the benzotriazole derivative by hydrogen peroxide is not selective, and sulfoxide and sulfone form concurrently. Selenium dioxide-catalyzed oxidation of benzotriazole thioether by H(2)O(2), however, proceeds selectively and yields sulfoxide only.


Video Capsule Endoscopy in a Pediatric Patient With Hematemesis While on Ventricular Assist Device Support.
We report the first case of video capsule endoscopy usage to diagnose gastrointestinal bleeding in a pediatric patient on a ventricular assist device. The outcomes of this case are consistent with the findings of reports in adult patients, showing no patient complications, no pacemaker or ventricular assist device interactions, and successful identification of a gastrointestinal source of bleeding. Use of video capsule endoscopy in this patient changed the management plan and eliminated the need for further invasive investigations highlighting the potential utility of this diagnostic method in this patient population.


Study of molar properties of GO after doping with transition metals for photodegradation of fluorescent dyes.
We synthesized graphene oxide (GO) doped with transition metal ions and characterized it using XPS, FT-IR, TGA/DTG, XRD, SEM, AFM, ICP-OES, UV/vis, and Raman spectroscopy. An intrinsic viscosity [η] of 0.002-0.012 g% @ 0.002 aq-GO was determined for viscosity average molecular weight (M v) of GO at 288.15, 298.15, and 308.15 K. Mark-Houwink (M-H) constants k (cm3 g-1) and a (cm3 mol g-2) were calculated for 5-15 mg/100 mL polyvinylpyrrolidone (PVP), using 29, 40, 55 kg mol-1 as markers for calculating M v by fitting the [η] to the Mark-Houwink-Sakurada equation (MHSE). We obtained 48 134.19 g mol-1 M v at 298.15 K, and the apparent molar (V ϕ m , cm3 mol-1), limiting molar volumes (V 0 GO)GO⃑0, enthalpy (ΔH m, J mol-1), entropy (ΔS m, J mol-1 K-1), viscosity (η m, mPa s mol-1), surface tension (γ m, mN m-1 mol-1), friccohesity (σ m, scm-1 mol-1), fractional volume (ϕ m, cm3 mol-1), isentropic compressibility (K sϕ,m, 10-4 cm s2 g-1 mol), infer GO molar consistency throughout the chemical processes. Molar properties (MPs) infer a GO monodispersion producing negative electrons (e-) and positive holes (h+) under sunlight. The transition metal ions (Fe2+, Mn2+, Ni2+, Cr3+, TMI) doped onto GO (TMI-GO), can photodegrade methylene blue (MB) in 60 min compared with 120 min using GO alone. The 4011 C atoms, 688 hexagonal sheets, 222 π-conjugations, and 4011 FE were calculated from the 48 134.19 g mol-1. The functional edges are the negative and positive holes generating centres of the GO 2D sheets.


An attempt to identify predictors of treatment outcome in two comprehensive weight loss programs.
The present study attempted to predict weight loss in, and completion of, low-calorie diet (LCD, n=167) and very low-calorie diet (VLCD, n=96) weight loss programs. Program completion and weight loss were examined in association with three groups of variables: demographic (e.g., age), medical/physical (e.g., body mass index [BMI]), and motivational/behavioral (e.g., exercise, ratings for motivation and commitment for the program). In the LCD group, age was positively associated with program completion, and commitment to the program was negatively associated with both program completion and weight loss. In the VLCD group, no variables predicted program completion, and only male gender predicted weight loss. Our results offer little to contradict previous findings that preexisting participant characteristics are of limited utility in predicting weight loss treatment outcome. In the LCD group, the negative associations of commitment with program completion and weight loss were surprising. If replicated, they might suggest the need to clarify patients' expectations about the level of commitment required for successful treatment.


Galectin-7 in cardiac allografts in mice: increased expression compared with isografts and localization in infiltrating lymphocytes and vascular endothelial cells.
We sought to identify elevated expression of galectin-7, a T-cell-binding protein, in renal allograft recipients undergoing acute rejection episodes. Allografts and isografts were examined immunohistologically and using quantitative Western blot analysis for galectin-7 protein. The expression of galectin-7 in T lymphocytes from draining lymph nodes in the recipient mice was examined using flow cytometry. We observed galectin-7 to gradually increase with time in the allografts to be significantly higher than that in isografts at days 3, 5, and 7 postoperative: 0.85 ± 0.03 versus 0.69 ± 0.05; 1.15 ± 0.11 versus 0.81 ± 0.02; and 2.02 ± 0.12 versus 0.81 ± 0.05 (P < .05). The majority of galectin-7 was located in the infiltrating lymphocytes and vascular endothelial cells. Furthermore, the percentage of CD4+galectin-7+ and CD8+galectin-7+ T cells from draining lymph nodes in the allograft group was higher than that in the isograft group: 28.0 ± 1.0% versus 1.2 ± 0.2%; and 12.4 ± 0.8% versus 0.4 ± 0.1% (P < .01). In conclusion, galectin-7 relates to acute allograft rejection and T-cell responses possibly as an accelerant.


Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores.
Fatty acids (FAs) are essential components of all lipid classes and pivotal substrates for energy production in all vertebrates. Additionally, they act directly or indirectly as signaling molecules and, when bonded to amino acid side chains of peptides, anchor proteins in biological membranes. In vertebrates, FAs are predominantly stored in the form of triacylglycerol (TG) within lipid droplets of white adipose tissue. Lipid droplet-associated TGs are also found in most nonadipose tissues, including liver, cardiac muscle, and skeletal muscle. The mobilization of FAs from all fat depots depends on the activity of TG hydrolases. Currently, three enzymes are known to hydrolyze TG, the well-studied hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL), discovered more than 40 years ago, as well as the relatively recently identified adipose triglyceride lipase (ATGL). The phenotype of HSL- and ATGL-deficient mice, as well as the disease pattern of patients with defective ATGL activity (due to mutation in ATGL or in the enzyme's activator, CGI-58), suggest that the consecutive action of ATGL, HSL, and MGL is responsible for the complete hydrolysis of a TG molecule. The complex regulation of these enzymes by numerous, partially uncharacterized effectors creates the "lipolysome," a complex metabolic network that contributes to the control of lipid and energy homeostasis. This review focuses on the structure, function, and regulation of lipolytic enzymes with a special emphasis on ATGL.


Fall-Risk-Increasing Drugs and Gait Performance in Community-Dwelling Older Adults: Exploratory Results from the Gait and Brain Study.
While several psychotropic and cardiovascular drugs have been identified as fall-risk-increasing drugs (FRIDs) in older adults, the intervening mechanisms linking FRIDs and falls are unclear. It is plausible that gait performance is an intermediate variable on the causal pathway between FRIDs and falls. The current evidence on the relationship between medication use and gait performance in older adults is scarce. We aimed to assess the association between FRIDs and gait performance in community-dwelling older adults. This was a cross-sectional analysis using data from the Gait and Brain Study, a study of community-dwelling older adults aged 65 years old and over (N = 345). The following drug classes were assessed: antidepressants, benzodiazepines, alpha-blockers, beta-blockers, vasodilators, diuretics, statins and aspirin. Medication use was ascertained through validated questionnaires and electronic medical records. Multiple linear regression models were used to assess the association between each of the drug classes and gait speed and gait variability. Gait variability was expressed as the coefficient of variation (CV = mean/standard deviation) of stride time. Models were adjusted for age, sex, education, body mass index (BMI), mini-mental status exam (MMSE) score, Geriatric Depression Scale (GDS) score, general activity level, use of other FRIDs and comorbidity propensity score. Diuretic use was associated with significantly reduced gait speed (B = -7.97 cm/s, 95% CI: -13.94, -2.00, P = 0.009). Statin use was associated with significantly increased stride time CV (B = 0.13, 95% CI: 0.02, 0.24, P = 0.026). Other drugs did not have a statistically significant relationship with gait speed or variability. The association between diuretic use and reduced gait speed is consistent with existing evidence on diuretic use and increased fall risk. The association between statins and increased stride time variability is notable given inconclusive evidence in previous studies. Our results provide initial estimates of the association between FRIDs and gait performance in older adults for future longitudinal studies.


Monolayer purification: a rapid method for isolating protein complexes for single-particle electron microscopy.
Visualizing macromolecular complexes by single-particle electron microscopy (EM) entails stringent biochemical purification, specimen preparation, low-dose imaging, and 3D image reconstruction. Here, we introduce the "monolayer purification" method, which employs nickel-nitrilotriacetic acid (Ni-NTA) functionalized lipids for simultaneously purifying His-tagged complexes directly from cell lysates while producing specimens suitable for single-particle EM. The method was established by using monolayers containing Ni-NTA lipid to specifically adsorb His-tagged transferrin-transferrin receptor (Tf-TfR) complexes from insect and mammalian cell extracts. The specificity and sensitivity of the method could be improved by adding imidazole to the extracts. The monolayer-purified Tf-TfR samples could be vitrified and used to calculate a 3D reconstruction of the complex. Monolayer purification was then used to rapidly isolate ribosomal complexes from bacteria by overexpressing a single His-tagged ribosomal subunit. The resulting monolayer samples allowed calculation of a cryo-EM 3D reconstruction of the Escherichia coli 50S ribosomal subunit.


Use of electrical impedance scanning in the differentiation of sonographically suspicious and highly suspicious lymph nodes of the head-neck region.
Sonographic differentiation between inflammatory and malignant lymph nodes is difficult, due in part to almost unchanged morphology of small lymph node metastases; however, as cancer cells exhibit altered dielectric properties, measurement of local electrical field distortions may be useful as adjunct to ultrasound in detection of malignancy. In this study, we evaluated the ability of electrical impedance scanning (EIS) to differentiate cervically located sonographically suspicious or highly suspicious lymph nodes. Seventy patients with 106 sonographically suspicious lymph nodes (mean size 20 x 13 x 13 mm, mean depth 8 mm) were examined using TransScan TS2000 (Siemens, Erlangen, Germany; manufactured by TransScan Research and Development Co., Israel). Included in the study were cervical ( n=64), inframandibular/periparotideal ( n=32) and nuchal/supraclavicular ( n=10) nodes. The EIS results were compared with histopathological ( n=100) and serological ( n=6) findings. Sixty-two of 64 malignant lymph nodes were correctly detected using EIS; 19 of 42 inflammatory/benign lymph nodes were correctly identified as benign (true positive 96.9%, true negative 45.2%; accuracy 71.3%, negative predictive value 90.5%, positive predictive value 59.6%). The high tumour detection rate achieved in this study suggests that EIS may be of value as an adjunctive technique in differentiation of lymph nodes of the head-neck region. Software changes to reduce the high number of false-positive markers are, however, necessary to improve the value in the evaluation during a regular clinical routine.


Design of a CRISPR-Cas system to increase resistance of Bacillus subtilis to bacteriophage SPP1.
Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (cas) genes form an adaptive prokaryotic immune system which provides acquired resistance against viruses and plasmids. Bacillus subtilis presently is the best-characterized laboratory model for Gram-positive bacteria and also widely used for industrial production of enzymes, vitamins and antibiotics. In this study, we show that type II-A CRISPR-Cas system from Streptococcus thermophilus can be transferred into B. subtilis and provides heterologous protection against phage infection. We engineered a heterologous host by cloning S. thermophilus Cas9 and a spacer targeting bacteriophage SPP1 into the chromosome of B. subtilis, which does not harbor its own CRISPR-Cas systems. We found that the heterologous CRISPR-Cas system is functionally active in B. subtilis and provides resistance against bacteriophage SPP1 infection. The high efficiency of the acquired immunity against phage could be useful in generation of biotechnologically important B. subtilis strains with engineered chromosomes.


Strategies for sentence perception.
Three experiments are reported in which rapid sequential visual presentation of sentences--RSVP--was used to determine some perceptual processes in sentence perception. It was found that adjectives, when they are actually or potentially modifiers of a noun, are far less likely to be reported than any other part of the sentence. On the other hand, adjectives which are attribute adjectives are as likely to be reported as any other part of the sentence. Conclusions are drawn concerning sentence perception in general.


Predictors of somatic symptom persistence in patients with chronic kidney disease (SOMA.CK): study protocol for a mixed-methods cohort study.
Seven of 10 patients with non-dialysis chronic kidney disease (CKD) experience burdensome persistent somatic symptoms (PSS). Despite the high prevalence and relevance for quality of life, disease progression and mortality, the pathogenesis of PSS in CKD remains poorly understood. The SOMA.CK study aims to investigate biopsychosocial predictors and their interactions for PSS in non-dialysis CKD and to develop a multivariate prognostic prediction model for PSS in CKD. The study is a mixed-methods cohort study with assessments at baseline, 6 and 12 months. It aims to include 330 patients with CKD stages G2-4 (eGFR=15-89 mL/min/1.73 m2). Primary outcome is the CKD-specific somatic symptom burden assessed with the CKD Symptom Burden Index. Secondary outcomes include quality of life, general somatic symptom burden and functioning. The interplay of biomedical (eg, biomarkers, epigenetics), treatment-related (eg, therapies and medication) and psychosocial variables (eg, negative affectivity, expectations) will be investigated to develop a prognostic prediction model for PSS. In an embedded mixed-methods approach, an experimental study in 100 patients using an affective picture paradigm will test the effect of negative affect induction on symptom perception. An embedded longitudinal qualitative study in 40-50 newly diagnosed patients will use thematic analysis to explore mechanisms of symptom development after receiving a CKD diagnosis. SOMA.CK is part of the interdisciplinary research unit 'Persistent SOMAtic Symptoms ACROSS Diseases'. The study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10195-BO-ff). Findings will be disseminated through peer-reviewed publications, scientific conferences, the involvement of our patient advisory board and the lay public. Focusing on subjective symptom burden instead of objective disease markers will fundamentally broaden the understanding of PSS in CKD and pave the path for the development of mechanism-based tailored interventions. ISRCTN16137374.


On diversity of human-nature relationships in environmental sciences and its implications for the management of ecological crisis.
Decision makers addressing the ecological crisis face the challenge of considering complex ecosystems in their socioeconomic decisions. Complementary to ecological sciences, other scientific frameworks, grouped under the umbrella term environmental sciences, offer decision makers the opportunity to pursue sustainable paths. Because the environmental sciences are drawn from different branches of science, environmental ethics must go beyond the legacy of ecology and the life sciences to describe the contribution of scientific knowledge to addressing the ecological crisis. In this regard, I analyze and compare three environmental sciences based on their seminal articles: Conservation Biology, Sustainability Science, and Sustainability Economics. My analysis shows that conservation biology and sustainability economics share strong similarities despite their different disciplinary backgrounds (life versus social sciences). Both seek to contrast a biocentric and an anthropocentric perspective. The goal of sustainability is therefore understood as a balance that must be found between these two perspectives. If the issue of balancing human and non-human interests is still relevant to sustainable science, it is more likely to take place in an ecocentric perspective based on alternative ontological and normative prescriptions. Based on this analysis, I distinguish between 'proscriptive value-based' scientific work that cannot be used for policy advice but is flexible to different value systems, and 'prescriptive value-based' scientific work that can be used for policy advice but is fixed within a given value system. Conflicting recommendations from environmental scientists therefore result from the coexistence of multiple 'prescriptive value-based' scientific approaches based on different conceptions of the relationship between humans and nature.


Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells.
Cancer cells thrive when challenged with proteotoxic stress by inducing components of the protein folding, proteasome, autophagy and unfolded protein response (UPR) pathways. Consequently, specific molecular chaperones have been validated as targets for anti-cancer therapies. For example, inhibition of Hsp70 family proteins (hereafter Hsp70) in rhabdomyosarcoma triggers UPR induction and apoptosis. To define how these cancer cells respond to compromised proteostasis, we compared rhabdomyosarcoma cells that were sensitive (RMS13) or resistant (RMS13-R) to the Hsp70 inhibitor MAL3-101. We discovered that endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated in RMS13-R cells, suggesting that resistant cells overcome Hsp70 ablation by increasing misfolded protein degradation. Indeed, RMS13-R cells degraded ERAD substrates more rapidly than RMS cells and induced the autophagy pathway. Surprisingly, inhibition of the proteasome or ERAD had no effect on RMS13-R cell survival, but silencing of select autophagy components or treatment with autophagy inhibitors restored MAL3-101 sensitivity and led to apoptosis. These data indicate a route through which cancer cells overcome a chaperone-based therapy, define how cells can adapt to Hsp70 inhibition, and demonstrate the value of combined chaperone and autophagy-based therapies.This article has an associated First Person interview with the first author of the paper.


Prostate-specific antigen (PSA) rate of decline post external beam radiotherapy predicts prostate cancer death.
To assess the association between PSA velocity (PSAV) in the first 24 months after external beam radiotherapy (EBRT) and prostate cancer-specific mortality (PCSM) and all cause mortality. All eligible patients in the South Australian (SA) Prostate Cancer Clinical Outcomes registry were followed. 848 Patients treated by definitive EBRT with more than one PSA recorded in the two year post-treatment were included. We calculated PSAV by linear regression. The mean number of PSA measurements in the 2year period was 4.4 (SD1.9). The median PSAVs across quartiles (Q1-Q4) were -4.17, -1.29, -0.38 and 0.20ng/ml/yr. In multivariable analysis, a U-shaped relationship was seen between PSAV and PCSM with Q1-Q4 hazard ratios (HR) being 3.82 (1.46-10.00), 3.07 (1.10-8.58), 1, 5.15 (1.99-13.30) respectively. HR for all cause mortality in a similar model were 1.79 (1.07-2.98), 1.55 (0.93-2.59), 1.00 and 1.74 (1.04-2.90) for Q1 to Q4 respectively. A rapid PSA decline in the first year was a strong predictor of PCSM. However, in the second year PSA increase was positively associated with PCSM. A rapid decline in PSA in the first year following EBRT is positively associated with PCSM. This may be a useful early indicator of the need for additional therapies.


Cyclic changes and actions of progesterone and allopregnanolone on cognition and hippocampal basal (stratum oriens) dendritic spines of female rats.
Ovarian steroids modulate the neuronal structure and function during the estrous cycle, contrasting peak effects during the proestrus cycle and low effects during the metestrus cycle. An ovariectomy (OVX) decreases gonadal hormones and tests the effects of substitutive therapies. We studied female rats with a normal estrous cycle and we also studied the effects of systemic progesterone (P4, 4.0 mg/kg) or its reduced metabolite allopregnanolone (ALLO, 4.0 mg/kg, both for 10 days) in females who had had an OVX 16.5 weeks prior to the study (long-term OVX) with the novel object recognition test (NORT) for associative memory. The dendritic shape and spine density in Golgi-impregnated basal dendrites (stratum oriens) of hippocampal pyramidal neurons was also studied. Proestrus females had a better performance than metestrus or OVX females in short-term memory (tested 1 h after the acquisition phase). Proestrus and metestrus females showed better results than OVX females for long-term memory (24 h after the initial phase). Both P4 and ALLO recovered the cognitive impairment induced by long-term OVX. Also, proestrus females had a higher density of dendritic spines than metestrus females, OVX reduced the density of spines when compared to intact females, whereas both P4 and ALLO treatments increased the dendritic spine density, number of dendritic branches along the dendritic length, and branching order compared to vehicle. These data add the dendrites of the stratum oriens as an additional site for naturally occurring changes in spine density during the estrous cycle and evidence the actions of progestins in both behavioral recovery and the structural dendritic rearrangement of hippocampal pyramidal neurons in long-term OVX female rats.