Better than CD: Eugénie Cotton (1881-1967).
Aimé Cotton is known for his invention of circular dichroism spectroscopy. In 1913, he married Eugénie Feytis, a scientist who studied physics with Marie Curie. Following the Second World War, Eugénie Cotton was determined to advance the rights and standing of women, sure in the belief that doing so was necessary not only because it was just but also because a world with women in the forefront would be more secure and less susceptible to the catastrophe worldwide military conflict. She was a cofounder of the Women's International Democratic Federation and served as its first president. In 1951, she was awarded the Stalin Peace Prize, and in 1961, the gold medal from the World Peace Council. The extraordinary life of Eugénie Cotton is reconstructed in a new biography by Loukia Efthymiou, Eugénie Cotton (1881-1967) (Éditions Universitaires Européennes, 2019) that is reviewed here. Among the contributions of Eugénie Cotton of particular interest to the Chirality readership is the biography she wrote of her husband, Aimé Cotton, l'optique et magneto-optique (Éditions Seghers, 1967), the most complete source of information on the founder of the science of circular dichroism. This biography is also discussed here, thereby building two reviews of books, one new and one old, one about Eugénie Cotton and one by her, into a single essay.


Chemicals to enhance microalgal growth and accumulation of high-value bioproducts.
Photosynthetic microalgae have attracted significant attention as they can serve as important sources for cosmetic, food and pharmaceutical products, industrial materials and even biofuel biodiesels. However, current productivity of microalga-based processes is still very low, which has restricted their scale-up application. In addition to various efforts in strain improvement and cultivation optimization, it was proposed that the productivity of microalga-based processes can also be increased using various chemicals to trigger or enhance cell growth and accumulation of bioproducts. Herein, we summarized recent progresses in applying chemical triggers or enhancers to improve cell growth and accumulation of bioproducts in algal cultures. Based on their enhancing mechanisms, these chemicals can be classified into four categories:chemicals regulating biosynthetic pathways, chemicals inducing oxidative stress responses, phytohormones and analogs regulating multiple aspects of microalgal metabolism, and chemicals directly as metabolic precursors. Taken together, the early researches demonstrated that the use of chemical stimulants could be a very effective and economical way to improve cell growth and accumulation of high-value bioproducts in large-scale cultivation of microalgae.


The effect of bilirubin photoisomers on unbound-bilirubin concentrations estimated by the peroxidase method.
Unbound bilirubin is oxidized to nearly colourless substances in the presence of H2O2 or ethyl hydroperoxide and horseradish peroxidase. To predict the risk of kernicterus (degenerated yellow pigmentation of nerve cells), this principle has been widely utilized for estimating the concentration of unbound bilirubin in hyperbilirubinaemic serum. However, the serum contains polar geometric photoisomers of bilirubin. Therefore, to clarify the effect of bilirubin photoisomer concentrations on unbound-bilirubin concentration, the concentration of bilirubin and its photoisomer and of unbound bilirubin in samples obtained from experiments in vivo and in vitro were simultaneously and individually estimated by h.p.l.c. and the peroxidase method. During photoirradiation, both in vivo and in vitro, the serum polar (ZE)-bilirubin IX alpha concentration increased remarkably, but unbound-bilirubin values were not affected at all. However, during experiments in vitro, unbound bilirubin concentrations increased only when concentrations of the rather polar (EZ)- and (EE)-cyclobilirubin IX alpha increased considerably in a human serum albumin-bilirubin solution irradiated with blue light. Thus it is concluded that unbound-bilirubin concentrations, and consequently the initial rate of the peroxidase reaction, is not accelerated by the increase in either (ZE)-bilirubin or (EZ)-cyclobilirubin concentration within the clinically observed range.


Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally.
Pertussis is a highly contagious, acute respiratory disease in humans caused by the Gram-negative pathogen Bordetella pertussis. Pertussis has resurged in the face of intensive vaccination and this has coincided with the emergence of strains carrying a particular allele for the pertussis toxin promoter, ptxP3, which is associated with higher levels of pertussis toxin (Ptx) production. Within 10 to 20 years, ptxP3 strains have nearly completely replaced the previously dominant ptxP1 strains resulting in a worldwide selective sweep. In order to identify B. pertussis genes associated with the selective sweep, we compared the expression of genes in ptxP1 and ptxP3 strains that are under control of the Bordetella master virulence regulatory locus (bvgASR). The BvgAS proteins comprise a two component sensory transduction system which is regulated by temperature, nicotinic acid and sulfate. By increasing the sulfate concentration, it is possible to change the phase of B. pertussis from virulent to avirulent. Until recently, the only distinctive phenotype of ptxP3 strains was a higher Ptx production. Here we identify additional phenotypic differences between ptxP1 and ptxP3 strains which may have contributed to its global spread by comparing global transcriptional responses under sulfate-modulating conditions. We show that ptxP3 strains are less sensitive to sulfate-mediated gene suppression, resulting in an increased production of the vaccine antigens pertactin (Prn) and Ptx and a number of other virulence genes, including a type III secretion toxin, Vag8, a protein involved in complement resistance, and lpxE involved in lipid A modification. Furthermore, enhanced expression of the vaccine antigens Ptx and Prn by ptxP3 strains was confirmed at the protein level. Identification of genes differentially expressed between ptxP1 and ptxP3 strains may elucidate how B. pertussis has adapted to vaccination and allow the improvement of pertussis vaccines by identifying novel vaccine candidates.


[The patient under antidepressive and antipsychotic therapy].
The family physician is responsible for the primary medical care of a mentally ill person. Because these patients are frequently treated with antidepressants or antipsychotic drugs, the family physician should be well-informed of the indication, dosage and side effects of these substances. Among antidepressants, selective serotonin reuptake inhibitors (SSRI) and newer substances usually have a more favorable side effect profile than tricyclic antidepressants (TCA). Atypical antipsychotic drugs show a lower risk for extrapyramidal motor disorders in contrast to conventional antipsychotic drugs. Undesired effects such as weight gain can, however, occur in all substance groups. The treatment of somatic comorbidities in these mentally ill patients and, likewise, the prophylaxis to prevent recurrence of depressive and schizophrenic diseases are also the responsibility of the family physician.


Pharmacologic management of chronic pain.
Chronic pain is a multifactorial condition with both physical and psychological symptoms, and it affects around 20% of the population in the developed world. In spite of outstanding advances in pain management over the past decades, chronic pain remains a significant problem. This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha(2)-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment.


[Vitamin and minerals supplements--required for good health?].
Both laymen and the learned are discussing the need for vitamin and minerals supplements and their eventual preventive and therapeutic potential. Documentation is needed, but this word is most of the time used without clarifying the criteria it is based on. In this article we use vitamin E in order to illustrate that there is generally a long way to go from initial hypothesis to eventual practical advice and recommendations. Promising cell and animal studies combined with epidemiological observation studies are not sufficient as evidence; randomised intervention studies are required before conclusions can be drawn. Because high intakes of vitamins and minerals can have negative health effects, we also present the work carried out to decide upper safe intake levels in the Nordic countries, the EU and the USA. Women of fertile age should under certain circumstance take iron and folate supplements, and everyone in Scandinavia should take a supplement with vitamin D. It is sensible and harmless to take a multivitamin and mineral pill for people in risk groups, e.g. people eating very little or have an unbalanced diet (children, old people, patients). Except for these groups it is poorly documented that vitamins and minerals in large doses have a preventive or therapeutic potential. The largest health potential lies in a healthy diet.


Flow cytometry expression of p53 and PCNA in oral/oropharynx carcinomas and their lymph node metastases.
The aim of this work was to characterize p53 and PCNA expression in primary tumours and lymph node metastases of oral/oropharynx carcinomas by flow cytometry and to evaluate the possibility of a relationship between these parameters in primary tumours and locoregional metastasis, clinical-histopathological parameters and survival time. A group of 28 patients was retrospectively selected: 13 with metastasis and 15 without metastasis. The following clinical and histopathological parameters were considered: degree of keratinization, Broders' grading of histological differentiation, invasive cell grading, thickness and tumour size. The nuclei of appropriately prepared cells were stained using anti-p53 and anti-PCNA FITC conjugated monoclonal antibodies. Analyses were performed by a Coulter Epics Elite flow cytometer. The following results were obtained: a close relationship between p53 and PCNA in primary tumours but no correlation between them and clinical-histopathological parameters; no correlation between p53 and PCNA expression in primary tumours and in lymph node metastasis; no correlation between p53 and PCNA values in primary tumours and survival. In conclusion, the difference in expression of these biological parameters in primary tumours and in lymph node metastases supports the theory that tumour cells in lymph nodes can display an independent behaviour. Since these biological parameters fail to correlate either with clinical-histopathological parameters or survival, their prognostic role is questionable.


Antithrombin III treatment improves parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection.
Antithrombin III (AT-III) is an antithrombotic agent with known anti-inflammatory properties that is also known to attenuate acute inflammation, prevent ischemia-reperfusion injury, and disseminated intravascular coagulation (DIC) associated with sepsis and endotoxemia. Here, we examined the ability of AT-III to modify parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection (AR). After left single lung transplantations (BN-->Lew), recipient animals were treated i.v. with 50 U/kg of human AT-III (low dose group), 500 U/kg of human AT-III (high dose group), or normal saline (control group) on days 2 and 4 posttransplant. All animals were sacrificed on day 6, and several pathological categories of acute inflammation related to AR were scored (0-4). The effect of AT-III on concanavalin A (Con A)-stimulated rat spleen cell proliferation was also examined. The stage of AR, and the degrees of edema, hemorrhage, and necrosis were significantly reduced in the high dose group compared with the control group. AT-III significantly inhibited rat spleen cell proliferation in response to Con A, in a dose-dependent manner. Maximal inhibition was seen at 15 U/ml in culture. Identical inhibition of Con-A-stimulated cultures occurred in both serum free and serum-containing media, indicating that AT-III inhibition of Con-A-stimulated rat spleen cell proliferation is independent of its actions on thrombin. 1) AT-III treatment significantly improves parameters of acute inflammation seen in a highly histoincompatible model of rat lung AR. 2) AT-III inhibits in vitro T cell proliferation to the potent mitogen Con A, suggesting that protease inhibition may inhibit T cell activation in vitro. 3). The beneficial effects of AT-III on parameters of lung AR relate to the anti-coagulant, anti-inflammatory, and possibly immunoregulatory actions of AT-III.


Yeast transcription elongation factor Spt5 associates with RNA polymerase I and RNA polymerase II directly.
Spt5 is a transcription factor conserved in all three domains of life. Spt5 homologues from bacteria and archaea bind the largest subunit of their respective RNA polymerases. Here we demonstrate that Spt5 directly associates with RNA polymerase (Pol) I and RNA Pol II in yeast through its central region containing conserved NusG N-terminal homology and KOW domains. Deletion analysis of SPT5 supports our biochemical data, demonstrating the importance of the KOW domains in Spt5 function. Far Western blot analysis implicates A190 of Pol I as well as Rpb1 of Pol II in binding Spt5. Three additional subunits of Pol I may also participate in this interaction. One of these subunits, A49, has known roles in transcription elongation by Pol I. Interestingly, spt5 truncation mutations suppress the cold-sensitive phenotype of rpa49Δ strain, which lacks the A49 subunit in the Pol I complex. Finally, we observed that Spt5 directly binds to an essential Pol I transcription initiation factor, Rrn3, and to the ribosomal RNA. Based on these data, we propose a model in which Spt5 is recruited to the rDNA early in transcription and propose that it plays an important role in ribosomal RNA synthesis through direct binding to the Pol I complex.


Optimal medical therapy vs revascularization in chronic coronary syndromes: Does ISCHEMIA move the needle toward or away from revascularization??
The optimal management of chronic coronary syndrome (CCS) patients has been a source of debate for several decades. Herein, we describe the evidence base comprising several landmark clinical trials including the most recent ISCHEMIA Trial, which, in aggregate, does not demonstrate a conclusive, incremental benefit of revascularization combined with optimal medical therapy (OMT) versus OMT alone in reducing prognostically-important clinical outcomes during long-term follow-up. For CCS patients with symptoms or quality of life not deemed refractory or unacceptable on medical therapy, a conservative approach to the judicious and selective use of revascularization plus OMT remains a justifiable evidence-based management strategy.


External validation of EPIC's Risk of Unplanned Readmission model, the LACE+ index and SQLape as predictors of unplanned hospital readmissions: A monocentric, retrospective, diagnostic cohort study in Switzerland.
Readmissions after an acute care hospitalization are relatively common, costly to the health care system, and are associated with significant burden for patients. As one way to reduce costs and simultaneously improve quality of care, hospital readmissions receive increasing interest from policy makers. It is only relatively recently that strategies were developed with the specific aim of reducing unplanned readmissions using prediction models to identify patients at risk. EPIC's Risk of Unplanned Readmission model promises superior performance. However, it has only been validated for the US setting. Therefore, the main objective of this study is to externally validate the EPIC's Risk of Unplanned Readmission model and to compare it to the internationally, widely used LACE+ index, and the SQLAPE® tool, a Swiss national quality of care indicator. A monocentric, retrospective, diagnostic cohort study was conducted. The study included inpatients, who were discharged between the 1st of January 2018 and the 31st of December 2019 from the Lucerne Cantonal Hospital, a tertiary-care provider in Central Switzerland. The study endpoint was an unplanned 30-day readmission. Models were replicated using the original intercept and beta coefficients as reported. Otherwise, score generator provided by the developers were used. For external validation, discrimination of the scores under investigation were assessed by calculating the area under the receiver operating characteristics curves (AUC). Calibration was assessed with the Hosmer-Lemeshow X2 goodness-of-fit test This report adheres to the TRIPOD statement for reporting of prediction models. At least 23,116 records were included. For discrimination, the EPIC´s prediction model, the LACE+ index and the SQLape® had AUCs of 0.692 (95% CI 0.676-0.708), 0.703 (95% CI 0.687-0.719) and 0.705 (95% CI 0.690-0.720). The Hosmer-Lemeshow X2 tests had values of p<0.001. In summary, the EPIC´s model showed less favorable performance than its comparators. It may be assumed with caution that the EPIC´s model complexity has hampered its wide generalizability-model updating is warranted.


Genome wide SNP identification in chickpea for use in development of a high density genetic map and improvement of chickpea reference genome assembly.
In the whole genome sequencing, genetic map provides an essential framework for accurate and efficient genome assembly and validation. The main objectives of this study were to develop a high-density genetic map using RAD-Seq (Restriction-site Associated DNA Sequencing) genotyping-by-sequencing (RAD-Seq GBS) and Illumina GoldenGate assays, and to examine the alignment of the current map with the kabuli chickpea genome assembly. Genic single nucleotide polymorphisms (SNPs) totaling 51,632 SNPs were identified by 454 transcriptome sequencing of Cicer arietinum and Cicer reticulatum genotypes. Subsequently, an Illumina GoldenGate assay for 1,536 SNPs was developed. A total of 1,519 SNPs were successfully assayed across 92 recombinant inbred lines (RILs), of which 761 SNPs were polymorphic between the two parents. In addition, the next generation sequencing (NGS)-based GBS was applied to the same population generating 29,464 high quality SNPs. These SNPs were clustered into 626 recombination bins based on common segregation patterns. Data from the two approaches were used for the construction of a genetic map using a population derived from an intraspecific cross. The map consisted of 1,336 SNPs including 604 RAD recombination bins and 732 SNPs from Illumina GoldenGate assay. The map covered 653 cM of the chickpea genome with an average distance between adjacent markers of 0.5 cM. To date, this is the most extensive genetic map of chickpea using an intraspecific population. The alignment of the map with the CDC Frontier genome assembly revealed an overall conserved marker order; however, a few local inconsistencies within the Cicer arietinum pseudochromosome 1 (Ca1), Ca5 and Ca8 were detected. The map enabled the alignment of 215 unplaced scaffolds from the CDC Frontier draft genome assembly. The alignment also revealed varying degrees of recombination rates and hotspots across the chickpea genome. A high-density genetic map using RAD-Seq GBS and Illumina GoldenGate assay was developed and aligned with the existing kabuli chickpea draft genome sequence. The analysis revealed an overall conserved marker order, although some localized inversions between draft genome assembly and the genetic map were detected. The current analysis provides an insight of the recombination rates and hotspots across the chickpea genome.


Prevalence and severity of osteochondrosis of the free thoracic vertebra in three modern broiler strains and the Athens Canadian Random Bred control broiler.
Osteochondrosis (OCD) results from a disturbance of endochondral ossification in articular cartilage and is an important cause of lameness in several animal species, including chickens. OCD lesions in the free thoracic vertebra (FTV) of chickens are essential to the pathogenesis of pathogenic Enterococcus cecorum. The goal of this study was to determine the prevalence of OCD in the FTV among three modern broiler chicken crosses (strains A/A, A/B, and C/C) and Athens Canadian Random Bred (ACRB) chickens, which served as the control group. The effect of sex, age, strain, body weight, and incubation temperature profile on OCD severity for each group was determined. At 2, 4, 6, and 8 weeks of age, the FTV of 10 male and 10 female birds from each strain exposed to either optimal or low-early, high-late incubation temperature profiles were collected and scored histologically for OCD lesion severity. OCD spectrum lesions were detected in >70% of all strain/sex combinations, including the ACRB controls. No association was observed between mean OCD score and broiler strain, incubation temperature profile, sex, age, or body weight. These findings indicate that OCD of the FTV is common in broiler chickens with similar prevalence observed in broilers with modern genetics and the ACRB broilers which represent 1950s broiler genetics. As the parameters examined did not have a statistical correlation with OCD, additional work is needed to understand factors that contribute to development of OCD in chickens.


Protection against Dictyocaulus viviparus in second year cattle after first year treatment with doramectin or an ivermectin bolus.
Forty-five calves were assigned randomly to three groups of 15 at turnout (day 0) in the spring of their first grazing season on to separate paddocks on a pasture known to carry infective larvae of Dictyocaulus viviparus. Group 1 calves were left as untreated controls, group 2 were injected with doramectin at 200 micrograms/kg at turnout and again on day 56, and group 3 were treated with an intraruminal bolus containing ivermectin. From day 42 onwards group 1 calves developed parasitic bronchitis which required repeated treatment with levamisole. The two endectocide regimes controlled lungworm infection, although some calves in group 2 developed some coughing during the week before the second dose of doramectin. After the end of the grazing season and again in May of the following year, five cattle from each group were infected experimentally with lungworm larvae and slaughtered 28 days later for lungworm counts and measurements of length to be made. At both times group 1 calves were found to be largely resistant to reinfection; group 2 were slightly more susceptible although the differences from group 1 were not statistically significant. Group 3 calves were more susceptible with no significant difference in worm counts from naive infection controls.


Ultrasonography and magnetic resonance imaging of elbow ligaments: a comparative study.
To determine the value of ultrasonography in elbow ligament assessment compared to magnetic resonance imaging. A prospective single-center study involving 30 volunteers with no elbow joint changes. Two experienced ultrasound specialists evaluated both elbows of each volunteer, resulting in 60 evaluations per physician and totaling up 120 evaluations. Magnetic resonance images were obtained using a 3-Tesla machine and evaluated by two experienced radiologists, totaling up 120 exams. Each examiner assigned subjective, zero-to-5 scores to ligaments imaged, where zero corresponded to non-identified ligament and 5 to visualization of the entire ligament. The level of significance was set at 5%. Bland-Altman dispersions and plots were prepared for each pair of measurements obtained. All ligaments were amenable to sonographic identification; scores of 4 or 5 were assigned by examiners based on ligament visibility. Ligaments could also be identified using magnetic resonance imaging and were assigned scores of 5 by examiners. All ligaments were described as intact and healthy by all four examiners. Comparative analysis of elbow ligament sonographic and magnetic resonance imaging findings did not differ significantly. Ultrasonography and magnetic resonance imaging can be considered equivalent modalities for elbow ligament assessment in the hands of experienced examiners.


Herpes simplex virus hepatitis in macrophage-depleted mice: the role of massive, apoptotic cell death in pathogenesis.
Infection with herpes simplex virus or hepatitis viruses can lead to fulminant hepatitis, but there is controversy about the underlying conditions needed for such disease. To investigate how the impairment of host defences might be involved, macrophages were depleted by administration of silica to mice before intravenous injection with herpes simplex virus type 1 (HSV-1). Such mice died rapidly and their livers were yellowish and shrunken (acute yellow atrophy), and occasionally grossly haemorrhagic. Small foci of apoptotic cells developed in the liver lobules; these rapidly became confluent and zonal over time. The overall lesion pattern was similar to massive hepatic necrosis, and there was extensive HSV replication in the liver lesions. In the liver, DNA fragmentation characteristic of apoptosis followed the time course of HSV-1 propagation. These findings suggest that one of the underlying conditions for fulminant viral hepatitis may be inadequate macrophage response, and that the massive hepatic damage, often defined as cell necrosis, may actually be apoptosis of liver cells subsequent to virus infection.


Prediction of anthracycline cardiotoxicity after chemotherapy by biomarkers kinetic analysis.
Anthracyclines are active drugs against breast cancer, but can exert cardiotoxic effects. We analyzed the association between the kinetics of various biomarkers during chemotherapy, and the risk of subsequent cardiac toxicity. 50 patients (49 women) with early breast cancer surgically treated and eligible to anthracycline-based adjuvant chemotherapy were analyzed. The left ventricular ejection fraction (LVEF) together with the plasma concentration of several blood markers was measured at the beginning of anthracycline chemotherapy (t (0)), 5 months (t (1)), 16 months (t (2)), 28 months (t (3)), and 40 months later (t (4)). A single measured LVEF value less than 50% or a clinically overt congestive heart failure (CHF) was considered cardiotoxic effects. We tested whether the kinetics of LVEF and blood biomarkers measured during chemotherapy was predictive of subsequent cardiotoxicity and overall cardiac fitness. The left ventricular ejection fraction measured at the end of treatment as well as the rate of change of hemoglobin concentration during anthracycline-based chemotherapy predicted cardiotoxicity in a 3-year follow-up period. When LVEF at the end of chemotherapy was lower than 53% or hemoglobin blood concentration declined more than 0.33 g/dL/month during chemotherapy, the odds ratio of subsequent cardiotoxicity was 37.3 and 18, respectively. The specificity of these two tests was 93.3% and 80%, whereas the sensitivity was 90.9 and 81.2%, respectively. Testing the rate of change of hemoglobin concentration during anthracycline-based chemotherapy, as well as the left ventricular ejection fraction at the end of treatment, seems a powerful method to assess the effects of anthracyclines on cardiac fitness and identify patients at high risk of CHF. Further validation of these tests on a large cohort of patients and cost-benefit analysis should be encouraged.


Cross-cultural adaptation of the Spence children's anxiety scale in Malaysia.
Anxiety among children has increased in recent years. Culturally adapted questionnaires developed to measure the level of anxiety are the best screening instruments for the general population. This study describes the scientific translation and adaptation of the Spence Children's Anxiety Scale (SCAS) into the Malay language. The process of scientific translation of this selfreport instrument followed the guidelines of the Task Force for Translation and Cultural Adaptation of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). The Malay version and its adaptation for a new cultural context are described. The Malay version achieved the aims of the original version and its conceptual and operational equivalence. It may be used as the first Malay instrument to measure anxiety among children in research and in clinical and community settings.


The catalytic activity of horse spleen apoferritin. Preliminary kinetic studies and the effect of chemical modification.
1. Horse spleen apoferritin catalyses the oxidation of Fe(2+) to Fe(3+) with molecular O(2) as electron acceptor under conditions where a number of other proteins have no such effect. The product is similar to ferritin by a number of criteria. 2. The progress curve is hyperbolic and the increase in initial velocity is linear with increasing apoferritin concentration. With respect to Fe(2+) the reaction follows Michaelis-Menten kinetics. The pH-dependence of the reaction was determined between pH4.3 and 6.0. 3. Modification of both tryptophan residues/apoferritin subunit with 2-nitrophenylsulphenyl chloride does not affect either k(cat.) or K(m) for the oxidation. Neither does the guanidination of seven out of nine lysine residues/subunit, the modification of nine out of ten arginine residues/subunit with cyclohexanedione, or the nitration of one out of five tyrosine residues/subunit with tetranitromethane. 4. The carboxymethylation of two out of three cysteine residues/subunit and of one out of six histidine residues/subunit can be achieved with iodoacetic acid. This carboxymethylated apoferritin is completely inactive in Fe(2+) oxidation. 5. Apoferritin does not take up Fe(3+). It appears from these results that Fe(2+) is the form in which iron is taken up by ferritin in a reaction where the protein acts as an enzyme which traps the product in the interior of the protein shell.


Muscle growth in teleost fish is regulated by factors utilizing the activin II B receptor.
The activin type IIB receptor (Acvr2b) is the cell surface receptor for multiple transforming growth factor β (TGF-β) superfamily ligands, several of which regulate muscle growth in mammals. To investigate the role of the Acvr2b signaling pathway in the growth and development of skeletal muscle in teleost fish, transgenic rainbow trout (RBT; Oncorhynchus mykiss) expressing a truncated form of the acvr2b-2a (acvr2b(▵)) in muscle tissue were produced. High levels of acvr2b(▵) expression were detected in the majority of P1 transgenic fish. Transgenic P1 trout developed enhanced, localized musculature in both the epaxial and hypaxial regions (dubbed 'six pack'). The F1 transgenic offspring did not exhibit localized muscle growth, but rather developed a uniform body morphology with greater girth, condition factor and increased muscle fiber hypertrophy. There was a high degree of variation in the mass of both P1 and F1 transgenic fish, with several fish of each generation exhibiting enhanced growth compared with other transgenic and control siblings. The 'six pack' phenotype observed in P1 transgenic RBT overexpressing acvr2b(▵) and the presence of F1 individuals with altered muscle morphology provides compelling evidence for the importance of TGF-β signaling molecules in regulating muscle growth in teleost fish.


Self-concept and body image of Turkish high school male athletes and nonathletes.
This study was conducted to determine the differences in self-concept and body image satisfaction and the relation between self-concept and body image among 174 Turkish high school male athletes and 174 nonathletes. The subjects were randomly selected from public high schools which represent middle socioeconomic status in Ankara. The Harter Self-Perception Profile for Adolescents and Berscheid, Walster, and Bohrnstedt's Body Image Questionnaire were administered to all participants. Significant differences were found in social acceptance, athletic competence, and physical appearance subscales of self-concept (p < .05), as well as in mean body image satisfaction among both groups (p < .05). There were also significant correlations between subscales of self-concept and body image for athletes and nonathletes.


Supercooled liquids under shear: theory and simulation.
We analyze the behavior of supercooled fluids under shear both theoretically and numerically. Theoretically, we generalize the mode-coupling theory of supercooled fluids to systems under stationary shear flow. Our starting point is the set of generalized fluctuating hydrodynamic equations with a convection term. A nonlinear integrodifferential equation for the intermediate scattering function is constructed. This theory is applied to a two-dimensional colloidal suspension. The shear rate dependence of the intermediate scattering function and the shear viscosity is analyzed. We have also performed extensive numerical simulations of a two-dimensional binary liquid with soft-core interactions near, but above, the glass transition temperature. Both theoretical and numerical results show the following. (i) A drastic reduction of the structural relaxation time and the shear viscosity due to shear. Both the structural relaxation time and the viscosity decrease as gamma(-nu) with an exponent nu< or =1, where gamma; is the shear rate. (ii) Almost isotropic dynamics regardless of the strength of the anisotropic shear flow.


Evolving in the darkness: Phylogenomics of Sinocyclocheilus cavefishes highlights recent diversification and cryptic diversity.
Troglomorphism-any morphological adaptation enabling life to the constant darkness of caves, such as loss of pigment, reduced eyesight or blindness, over-developed tactile and olfactory organs-has long intrigued biologists. However, inferring the proximate and ultimate mechanisms driving the evolution of troglomorphism (stygomorphism) in freshwater fish requires a sound understanding of the evolutionary relationships between surface and stygomorphic lineages. We use Restriction Site Associated DNA Sequencing (RADseq) to better understand the evolution of the Sinocyclocheilus fishes of China. With a remarkable array of derived stygomorphic traits, they comprise the largest cavefish diversification in the world, emerging as a multi-species model system to study evolutionary novelty. We sequenced a total of 120 individuals throughout the Sinocyclocheilus distribution. The data comprised a total of 646,497 bp per individual, including 4378 loci and 67,983 SNPs shared across a minimum of 114 individuals at a given locus. Phylogenetic analyses using either the concatenated RAD loci (RAxML) or the SNPs under a coalescent model (SVDquartets, SNAPP) showed a high degree of congruence with similar topologies and high node support (>95 for most nodes in the phylogeny). The major clades recovered conform to a pattern previously established using Sanger-based mt-DNA sequences, with a few notable exceptions. We now recognize six major clades in this group, elevating the blind cavefish S. tianlinensis and the micro-eyed S. microphthalmus as two new distinct clades due to their deep divergence from other clades. PCA plots of the SNP data also support the recognition of six major clusters of species congruent with the identified clades in ordination space. A Bayes factor delimitation (BFD) analysis showed support for 21 species, recognizing 19 previously described species and two putative new cryptic ones. Two species whose identities were previously disputed, S. furcodorsalis and S. tianeensis, are supported here as distinct species. In addition, our multi-species calibrated tree in SNAPP suggests that the genus Sinocyclocheilus originated around 10.16 Mya, with most speciation events occurring in the last 2 Mya, likely favored by the uplift of the Qinghai-Tibetan Plateau and cave occupation induced by climate-driven aridification during this period. These results provide a firm basis for future comparative studies on the evolution of Sinocyclocheilus and its adaptations to cave life.


Association of polymorphisms of the oestrogen receptor alpha gene with the age of menarche.
The age of menarche may be subject to hereditary influences, but the specific genetic determinants are largely unknown. We evaluated whether the XbaI and PvuII polymorphisms of the estrogen receptor alpha gene are associated with the age of menarche. We performed genotyping for XbaI and PvuII in a cohort of 145 adolescent females from a closed community in North-Western Greece. There was strong linkage disequilibrium between the two polymorphisms. Menarche occurred later in girls with the XX genotype than in girls with the Xx or xx genotype (mean +/- SD: 13.36 +/- 1.24 versus 12.80 +/- 1.14 and 12.75 +/- 1.35 years respectively; P = 0.017). Menarche also tended to occur later in PP homozygotes than in Pp and pp subjects, but the difference was not significant (mean +/- SD: 13.09 +/- 1.29 versus 12.80 +/- 1.19 and 12.85 +/- 1.33 years respectively). The strongest effect was seen when the PX haplotype was considered [mean +/- SD: 13.43 +/- 1.18 years for homozygotes versus 12.76 +/- 1.25 years in heterozygotes and in subjects without the PX allele, P = 0.006]. We document that the XbaI polymorphism, and possibly PvuII, may be genetic determinants of the age of menarche.


Informative Patterns of Health-Care Utilization Prior to the Diagnosis of Pancreatic Ductal Adenocarcinoma.
Early-detection tests for pancreatic ductal adenocarcinoma (PDAC) are needed. Since a hypothetical screening test would be applied during antecedent clinical encounters, we sought to define the variability in health-care utilization leading up to PDAC diagnosis. This was a retrospective cohort study that included patients diagnosed with PDAC in the Indianapolis, Indiana, area between 1999 and 2013 with at least 1 health-care encounter during the antecedent 36-month period (n = 1,023). Patients were classified by unique patterns of health-care utilization using a group-based trajectory model. The prevalences of PDAC signals, such as diabetes mellitus (DM) and chronic pancreatitis, were compared. Four distinct trajectories were identified, the most common (42.0%) being having few clinical encounters more than 6 months prior to PDAC diagnosis (late acceleration). In all cases, a minority of persons had DM (30.6%, with 9.5% <1.5 years before PDAC) or any pancreatic disorder (39.9%); these were least common in the late-acceleration group (DM, 14.7%; any pancreatic disorder, 32.1% (P < 0.001)). The most common pattern of antecedent care was having few clinical encounters until shortly before PDAC diagnosis. Since the majority of patients diagnosed with PDAC do not have an antecedent PDAC signal, early-detection strategies limited to these groups may not apply to the majority of cases.


Characterization of Extensive Microstructural Variations Associated with Punctate White Matter Lesions in Preterm Neonates.
Punctate white matter lesions are common in preterm neonates. Neurodevelopmental outcomes of the neonates are related to the degree of extension. This study aimed to characterize the extent of microstructural variations for different punctate white matter lesion grades. Preterm neonates with punctate white matter lesions were divided into 3 grades (from mild to severe: grades I-III). DTI-derived fractional anisotropy, axial diffusivity, and radial diffusivity between patients with punctate white matter lesions and controls were compared with Tract-Based Spatial Statistics and tract-quantification methods. Thirty-three preterm neonates with punctate white matter lesions and 33 matched controls were enrolled. There were 15, 9, and 9 patients, respectively, in grades I, II, and III. Punctate white matter lesions were mainly located in white matter adjacent to the lateral ventricles, especially regions lateral to the trigone, posterior horns, and centrum semiovale and/or corona radiata. Extensive microstructural changes were observed in neonates with grade III punctate white matter lesions, while no significant changes in DTI metrics were found for grades I and II. A pattern of increased axial diffusivity, increased radial diffusivity, and reduced/unchanged fractional anisotropy was found in regions adjacent to punctate white matter lesion sites seen on T1WI and T2WI. Unchanged axial diffusivity, increased radial diffusivity, and reduced/unchanged fractional anisotropy were observed in regions distant from punctate white matter lesion sites. White matter microstructural variations were different across punctate white matter lesion grades. Extensive change patterns varied according to the distance to the lesion sites in neonates with severe punctate white matter lesions. These findings may help in determining the outcomes of punctate white matter lesions and selecting treatment strategies.


Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders.


Role of 5-HT receptor antagonists in mediating intracavernous pressure response induced by fluvoxamine in conscious rats.
It has been reported that selective serotonin reuptake inhibitor (SSRI) may cause sexual dysfunction. To determine the relationship between serotonin and sexual function, we investigated the role of serotonergic receptors on changes in intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious and free-moving rats. ICP and BP were measured in male Sprague-Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Pressures were recorded 2 hours after catheterization. In other rats, this procedure was performed 2 weeks after spinal cord transection (spinal cord injury [SCI]) between the eighth and ninth thoracic vertebrae. To investigate the role of serotonergic receptors, fluvoxamine (an SSRI), WAY100635 (a 5-HT(1A)-receptor antagonist), and SB242084 (a 5-HT(2C)-receptor antagonist) were administered by intravenous (i.v.) or intracerebroventricular (i.c.v.) routes. BP and parameters of ICP were measured in conscious and free-moving rats. Administration of fluvoxamine (1- to 30-micromol/kg i.v. and 1- to 30-nmol i.c.v.) induced a transient increase in the ICP. The ICP parameters responded in a dose-dependent manner, especially the time to first response (TFR), which was significantly shortened. BP also increased in response to fluvoxamine. In contrast, ICP in SCI rats did not change after fluvoxamine administration. WAY100635 (10 or 30-nmol i.c.v.) induced an increase in the ICP. In combination with fluvoxamine, it significantly shortened the TFR in comparison with WAY100635 or fluvoxamine alone. However, SB242084 (10 or 30-nmol i.c.v.) actually had an inhibitory effect on fluvoxamine-induced ICP responses. These findings demonstrated that ICP is regulated at the supraspinal level when endogenous serotonin is increased by fluvoxamine. Furthermore, ICP is facilitated by 5-HT(2C)-receptors and inhibited by 5-HT(1A)-receptors in the rat brain.


The cortical actin determines different susceptibility of naïve and memory CD4+ T cells to HIV-1 cell-to-cell transmission and infection.
Memory CD4+ T cells are preferentially infected by HIV-1 compared to naïve cells. HIV-1 fusion and entry is a dynamic process in which the cytoskeleton plays an important role by allowing virion internalization and uncoating. Here, we evaluate the role of the cortical actin in cell-to-cell transfer of virus antigens and infection of target CD4+ T cells. Using different actin remodeling compounds we demonstrate that efficiency of HIV-internalization was proportional to the actin polymerization of the target cell. Naïve (CD45RA+) and memory (CD45RA-) CD4+ T cells could be phenotypically differentiated by the degree of cortical actin density and their capacity to capture virus. Thus, the higher cortical actin density of memory CD4+ T cells was associated to increased efficiency of HIV-antigen internalization and the establishment of a productive infection. Conversely, the lower cortical actin density in naïve CD4+ T cells restricted viral antigen transfer and consequently HIV-1 infection. In conclusion, the cortical actin density differentially affects the susceptibility to HIV-1 infection in naïve and memory CD4+ T cells by modulating the efficiency of HIV antigen internalization.


Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-h glucose and insulin excursions.
Consumption of sugar-sweetened beverages has been shown to be associated with dyslipidemia, insulin resistance, fatty liver, diabetes, and cardiovascular disease. It has been proposed that adverse metabolic effects of chronic consumption of sugar-sweetened beverages are a consequence of increased circulating glucose and insulin excursions, ie, dietary glycemic index (GI). We determined whether the greater adverse effects of fructose than of glucose consumption were associated with glucose and insulin exposures. The subjects were studied in a metabolic facility and consumed energy-balanced diets containing 55% of energy as complex carbohydrate for 2 wk (GI = 64). The subjects then consumed 25% of energy requirements as fructose- or glucose-sweetened beverages along with their usual ad libitum diets for 8 wk at home and then as part of energy-balanced diets for 2 wk at the metabolic facility (fructose GI = 38, glucose GI = 83). The 24-h glucose and insulin profiles and fasting plasma glycated albumin and fructosamine concentrations were measured 0, 2, 8, and 10 wk after beverage consumption. Consumption of fructose-sweetened beverages lowered glucose and insulin postmeal peaks and the 23-h area under the curve compared with the baseline diet and with the consumption of glucose-sweetened beverages (all P < 0.001, effect of sugar). Plasma glycated albumin concentrations were lower 10 wk after fructose than after glucose consumption (P < 0.01, effect of sugar), whereas fructosamine concentrations did not differ between groups. The results suggest that the specific effects of fructose, but not of glucose and insulin excursions, contribute to the adverse effects of consuming sugar-sweetened beverages on lipids and insulin sensitivity. This study is registered at clinicaltrials.gov as NCT01165853.


Epigenetic deregulation of the LMP1/LMP2 locus of Epstein-Barr virus by mutation of a single CTCF-cohesin binding site.
The chromatin regulatory factors CTCF and cohesin have been implicated in the coordinated control of multiple gene loci in Epstein-Barr virus (EBV) latency. We have found that CTCF and cohesin are highly enriched at the convergent and partially overlapping transcripts for the LMP1 and LMP2A genes, but it is not yet known how CTCF and cohesin may coordinately regulate these transcripts. We now show that genetic disruption of this CTCF binding site (EBVΔCTCF166) leads to a deregulation of LMP1, LMP2A, and LMP2B transcription in EBV-immortalized B lymphocytes. EBVΔCTCF166 virus-immortalized primary B lymphocytes showed a decrease in LMP1 and LMP2A mRNA and a corresponding increase in LMP2B mRNA. The reduction of LMP1 and LMP2A correlated with a loss of euchromatic histone modification H3K9ac and a corresponding increase in heterochromatic histone modification H3K9me3 at the LMP2A promoter region in EBVΔCTCF166. Chromosome conformation capture (3C) revealed that DNA loop formation with the origin of plasmid replication (OriP) enhancer was eliminated in EBVΔCTCF166. We also observed that the EBV episome copy number was elevated in EBVΔCTCF166 and that this was not due to increased lytic cycle activity. These findings suggest that a single CTCF binding site controls LMP2A and LMP1 promoter selection, chromatin boundary function, DNA loop formation, and episome copy number control during EBV latency.


Intestinal anaphylaxis induces Fos immunoreactivity in myenteric plexus of rat small intestine.
Fos immunohistochemistry was used to identify myenteric neurons activated as a consequence of intestinal anaphylaxis in Hooded-Lister rats sensitized to egg albumin (EA 10 micrograms ip). After incubation in test solutions, or after in vivo challenge, jejunal tissues were processed for immunohistochemistry with an anti-Fos antibody (1:500, TF161). The neuronal identity of the Fos-labeled nuclei was confirmed by double labeling with neuron-specific enclose (1:1,000). In in vitro studies, exposure of control tissue to 50 mM K(+)-Krebs-EA (2 x 10(-5) M) solutions significantly increased Fos immunoreactivity in the myenteric plexus, whereas a basal level of Fos was seen in control tissue incubated in Krebs solution, sham-sensitized tissue exposed to bovine serum albumin (BSA, 2 x 10(-5) M), or EA and sensitized tissue exposed to BSA. Pretreatment of sensitized tissue with doxantrazole (10(-4) M) markedly reduced Fos immunoreactivity observed after EA exposure. In in vivo studies, there was negligible Fos immunoreactivity in the myenteric plexus of control, sham-sensitized, or sensitized rats challenged with saline. A low level of Fos was seen in neurons of sham-sensitized rats challenged with BSA or EA and in sensitized rats challenged with BSA. Significantly greater levels of Fos were observed in the myenteric plexus of sensitized animals challenged with EA, even after pretreatment with capsaicin (125 mg/kg). These results suggest a role for myenteric neurons in intestinal anaphylaxis. In sensitized rats, activation of myenteric neurons is dependent on antigen-induced mast cell activation and occurs independently of capsaicin-sensitive afferent nerves.


Slow changes in currents through sodium channels in frog muscle membrane.
We used a patch clamp to measure Na currents across 10-15 micron diameter circular patches of frog and rat skeletal muscle membrane. We tested for electrophoretic mobility of Na channels, by applying steady lateral fields (of the order of 10 mV micron-1) across the wall of the patch pipette. Application of steady negative potentials to the inside of the pipette resulted in a fall in the number of functional Na channels in the patch. This fall took several minutes to complete and was reversible. It was assayed by applying suitable depolarizations at approximately 11 sec intervals. When a steady lateral field was applied in the absence of changes in membrane potential of the patch, the loss of Na current was virtually abolished. Thus it was not due to electrophoretic movement of channels, but instead to depolarization of the sarcolemma. Evidently, a very slow inactivation of Na conductance operates in skeletal muscle. In frog muscle, the rate constants for loss and recovery of Na current were about 0.1 min-1 (17 degrees C) at resting potential. Rate constants were higher at more positive and at more negative membrane potentials. Current amplitude was reduced to 0.5 at about -76 mV. Roughly similar results were found in rat omohyoid muscle. A further inactivation mechanism, whose rate was intermediate between conventional fast inactivation and the very slow process described here, was present also in both rat and frog muscle. In frog muscle, lateral fields do not alter the potential dependence of fast inactivation. Either the surface charge due to membrane lipids does not influence inactivation or the lipids immediately surrounding the Na channel are restricted in their mobility.


An evaluation of porcine epidemic diarrhea virus survival in individual feed ingredients in the presence or absence of a liquid antimicrobial.
Contaminated complete feed and porcine plasma are risk factors for PEDV introduction to farms and a liquid antimicrobial has been proven useful for reducing risk. This study provides information on the survivability of PEDV across common swine feed ingredients in the presence or absence of the liquid antimicrobial. Eighteen ingredients commonly included in commercial swine diets were selected, including 3 grain sources (corn, soybean meal (SBM), dried distillers grains with solubles (DDGS)), 5 porcine by-products (spray-dried plasma, purified plasma, intestinal mucosa, meat and bone meal and red blood cells (RBCs)), 3 vitamin/trace mineral (VTM) mixes (sow, nursery, finishing), 2 fat sources (choice white grease and soy oil), 3 synthetic amino acids (lysine HCL, D/L methionine, threonine), as well as limestone and dry choline chloride. Complete feed and stock PEDV served as controls. Thirty grams of each ingredient were inoculated with 2 mL PEDV. A matched set of samples were treated with the formaldehyde-based liquid antimicrobial SalCURB® (LA). All samples (n = 320) were stored outdoors under winter time ambient conditions for 30 days. Samples were submitted on 1, 7, 14 and 30 days post-inoculation (DPI) and tested by PCR and virus isolation (VI). All VI-negative samples were tested by swine bioassay. Viable PEDV was detected by VI or swine bioassay at 1, 7, 14 and 30 DPI from SBM, DDGS, meat & bone meal, RBCs, lysine HCL, D/L methionine, choice white grease, choline chloride, complete feed and stock virus control and at 7 DPI in limestone and at 14 DPI in threonine. Supplementary testing of complete feed and SBM indicated viable virus out to 45 and 180 DPI, respectively. All other samples were negative by VI and bioassay. In contrast, treatment with LA inactivated PEDV across all ingredients on 1 DPI and induced RNA reduction over time. Under the conditions of this study, PEDV viability in feed was influenced by ingredient with extended survival in SBM. Furthermore, LA treatment rendered virus inactive, independent of ingredient type.


Multiple electrosprays generated from a single polycarbonate microstructured fibre.
Electrospray ionization (ESI) has been invaluable to the mass spectrometric detection of biomolecules, due largely to the sensitivity afforded by the ionization technique. Lower flow rates, e.g. in the nanoelectrospray regime, result in smaller initial electrosprayed droplets, leading to higher ionization efficiency and greater signal. One approach to improving sensitivity without lowering flow rate is to generate multiple electrosprays (MESs) from the same sample, essentially splitting one larger flow into smaller flows in the nanoESI regime. Presented here is a series of novel MES emitters in the form of polycarbonate fibres. Based on microstructured fibre (MSF) technology whereby a set of homogeneous parallel channels are formed in a heat-drawn fibre intended to conduct light, a custom design was fabricated in which 3, 6, 9 and 12 holes were arranged in a radial pattern to prevent inhomogeneities in the electric field. The MSFs have dimensions that are compatible with current standards in nanoESI equipment, and the tip is more compatible with standard MS orifices than other larger multielectrospray emitters. By measuring the spray current provided by the various emitters under the same solvent/voltage/total flow rate conditions, a plot was obtained clearly demonstrating the expected dependence on the square root of the number of holes, i.e. the number of independent electrosprays. With this firm proof of principle using this design/format, further effort is justified in developing similar emitters in alternative materials that better prevent surface wetting and allow greater hole density, ultimately leading to greater signal enhancement.


Brain oscillations forever--neurophysiology in future research of child psychiatric problems.
For decades neurophysiology has successfully contributed to research and clinical care in child psychiatry. Recently, methodological progress has led to a revival of interest in brain oscillations (i.e., a band of periodic neuronal frequencies with a wave-duration from milliseconds to several seconds which may code and decode information). These oscillations will nurture future information processing research during normal and pathological brain development, allowing us to investigate basic neuronal connectivity as well as interactions of brain systems and their modulation (e.g., by temporal neuronal synchronisation) as close correlates of behaviour and intermediate phenotypes from genes to behavioural variations. Especially, a systematic neurodynamic look at transitional processes from rest to stimulus-triggered goal-directed performance will aid behavioural understanding and guidance of children. Preliminary data suggest two separate oscillatory mechanisms in this respect. One is ongoing from pre- to post-stimulus processing and related to quantitative modification of behaviour, while another is merely related to qualitative effects of behaviour and reflects 'on-top' post-stimulus processing by temporal neuronal synchronisation of the oscillatory network in question. Suggested neurodynamic models may be tested in multilevel clinical experiments as well as in the framework of computational neuropsychiatry.


Tick-Borne Flaviviruses, with a Focus on Powassan Virus.
The tick-borne pathogen Powassan virus is a rare cause of encephalitis in North America and the Russian Far East. The number of documented cases described since the discovery of Powassan virus in 1958 may be <150, although detection of cases has increased over the past decade. In the United States, the incidence of Powassan virus infections expanded from the estimated 1 case per year prior to 2005 to 10 cases per year during the subsequent decade. The increased detection rate may be associated with several factors, including enhanced surveillance, the availability of improved laboratory diagnostic methods, the expansion of the vector population, and, perhaps, altered human activities that lead to more exposure. Nonetheless, it remains unclear whether Powassan virus is indeed an emerging threat or if enzootic cycles in nature remain more-or-less stable with periodic fluctuations of host and vector population sizes. Despite the low disease incidence, the approximately 10% to 15% case fatality rate of neuroinvasive Powassan virus infection and the temporary or prolonged sequelae in >50% of survivors make Powassan virus a medical concern requiring the attention of public health authorities and clinicians. The medical importance of Powassan virus justifies more research on developing specific and effective treatments and prevention and control measures.


Heterogeneity of calcium compartmentation: electron probe analysis of renal tubules.
The objective of this study has been to determine the intracellular localization of calcium in cryofixed, cryosectioned suspensions of kidney proximal tubules using quantitative electron probe X-ray microanalysis. Two populations of cells have been identified: 1) "Viable" cells, representing the majority of cells probed, are defined by their relatively normal K/Na concentration ratio of approximately 4:1. Their measured Ca content is 4.1 +/- 1.4 (SEM) mmol/kg dry wt in the cytoplasm and 3.1 +/- 1.1 mmol/kg dry wt in the mitochondria, or an average cell calcium content of approximately 3.8 mmol/kg dry wt. 2) "Nonviable" cells, defined by the presence of dense inclusions in their mitochondria and a K/Na concentration ratio of approximately 1. The Ca content is 15 +/- 2 mmol/kg dry wt in the cytoplasm and 685 +/- 139 mmol/kg dry wt in the mitochondria of such cells. Assuming 25 to 30% of the cell volume is mitochondrial, the overall calcium content of such nonviable cells is approximately 210 mmol/kg dry wt. The presence of these inclusions in 4 to 5% of the cells would account for the average total Ca content measured in perchloric acid extracts of isolated proximal tubule suspensions (approximately equal to 18 nmol/mg protein or 12.6 mmol/kg dry wt). Whole kidney tissues display a large variability in total Ca content (4.5 to 18 nmol/mg protein, or 3.4 to 13.5 mmol/kg dry wt), which could be accounted for by inclusions in 0 to 4% of the cells. The electron probe X-ray microanalysis (EPXMA) data conclusively demonstrate that the in situ mitochondrial Ca content of viable cells from the kidney proximal tubule is low and support the idea that mitochondrial Ca may regulate dehydrogenase activity but probably does not normally control cytosolic free Ca.


A fibrin-based arterial media equivalent.
We report here, with respect to collagen production and the mechanical properties of a fibrin-based media equivalent (ME), on our efforts to optimize the culture conditions of neonatal SMCs entrapped in tubular fibrin gels. We examined several factors, including the concentration of fibrinolysis inhibitor, the cell source and initial number, the addition of TGF-beta and insulin to the culture medium, and the time in culture. We found that varying the concentration of epsilon-aminocaproic acid (ACA), an inhibitor of fibrinolysis, did not affect the collagen production, but that lower concentrations resulted in a compromised physical integrity of the ME. While use of neonatal SMCs yielded superior results over adult SMCs, a higher initial cell number did not improve results. The addition of 1 ng/mL of TGF-beta to the medium increased the collagen content fourfold and the ultimate tensile strength (UTS) and modulus approximately tenfold after 3 weeks, while the addition of both TGF-beta and insulin improved collagen content sixfold and UTS and modulus almost 20-fold. Additional TGF-beta (5 ng/mL) did not improve any of the properties measured, but additional time in culture did. Samples incubated for 6 weeks with TGF-beta and insulin contained about seven times the amount of collagen and had a three-times higher UTS and modulus than did samples incubated for only 3 weeks. When compared to collagen MEs, the fibrin MEs compacted to a greater extent and were both stronger and stiffer when cultured under the same conditions, having after 6 weeks a tensile modulus and ultimate tensile strength similar to those of rat abdominal aorta.


[Nutrition, cystic fibrosis and the digestive tract].
The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.


AGAP1-associated endolysosomal trafficking abnormalities link gene-environment interactions in neurodevelopmental disorders.
AGAP1 is an Arf1 GTPase-activating protein that regulates endolysosomal trafficking. Damaging variants have been linked to cerebral palsy and autism. We report three new cases in which individuals had microdeletion variants in AGAP1. The affected individuals had intellectual disability (3/3), autism (3/3), dystonia with axial hypotonia (1/3), abnormalities of brain maturation (1/3), growth impairment (2/3) and facial dysmorphism (2/3). We investigated mechanisms potentially underlying AGAP1 variant-mediated neurodevelopmental impairments using the Drosophila ortholog CenG1a. We discovered reduced axon terminal size, increased neuronal endosome abundance and elevated autophagy compared to those in controls. Given potential incomplete penetrance, we assessed gene-environment interactions. We found basal elevation in the phosphorylation of the integrated stress-response protein eIF2α (or eIF2A) and inability to further increase eIF2α phosphorylation with subsequent cytotoxic stressors. CenG1a-mutant flies had increased lethality from exposure to environmental insults. We propose a model wherein disruption of AGAP1 function impairs endolysosomal trafficking, chronically activating the integrated stress response and leaving AGAP1-deficient cells susceptible to a variety of second-hit cytotoxic stressors. This model may have broader applicability beyond AGAP1 in instances where both genetic and environmental insults co-occur in individuals with neurodevelopmental disorders.


Segmentation of left ventricle in late gadolinium enhanced MRI through 2D-4D registration for infarct localization in 3D patient-specific left ventricular model.
To evaluate a 2D-4D registration-cum-segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient-specific 3D LV models. A 3-step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion-corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland-Altman analysis. LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation. The framework showed high accuracy and robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of information between LGE- and cine-MRI scans, crucial in personalized model studies for treatment planning.


Methods for measuring plant vulnerability to cavitation: a critical review.
Xylem cavitation resistance has profound implications for plant physiology and ecology. This process is characterized by a 'vulnerability curve' (VC) showing the variation of the percentage of cavitation as a function of xylem pressure potential. The shape of this VC varies from 'sigmoidal' to 'exponential'. This review provides a panorama of the techniques that have been used to generate such a curve. The techniques differ by (i) the way cavitation is induced (e.g. bench dehydration, centrifugation, or air injection), and (ii) the way cavitation is measured (e.g. percentage loss of conductivity (PLC) or acoustic emission), and a nomenclature is proposed based on these two methods. A survey of the literature of more than 1200 VCs was used to draw statistics on the usage of these methods and on their reliability and validity. Four methods accounted for more than 96% of all curves produced so far: bench dehydration-PLC, centrifugation-PLC, pressure sleeve-PLC, and Cavitron. How the shape of VCs varies across techniques and species xylem anatomy was also analysed. Strikingly, it was found that the vast majority of curves obtained with the reference bench dehydration-PLC method are 'sigmoidal'. 'Exponential' curves were more typical of the three other methods and were remarkably frequent for species having large xylem conduits (ring-porous), leading to a substantial overestimation of the vulnerability of cavitation for this functional group. We suspect that 'exponential' curves may reflect an open-vessel artefact and call for more precautions with the usage of the pressure sleeve and centrifugation techniques.


Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts.
Diabetes is associated with increased incidence of myocardial dysfunction, which is partly characterized by interstitial and perivascular fibrosis. Cardiac fibroblasts have been identified as an important participant in the development of cardiac fibrosis. Exposure of cultured cardiac fibroblasts to high glucose resulted in increased collagen synthesis. Tanshinone IIA can alleviate the ventricular fibrosis that develops in a number of different experimental conditions. However, whether tanshinone IIA can prevent high glucose-induced collagen synthesis in cardiac fibroblasts remains unknown. The aim of this study was to evaluate the effects of tanshinone IIA on high glucose-induced collagen synthesis in cardiac fibroblasts. Rat cardiac fibroblasts were cultured in high glucose (25 mM) media in the absence or presence of tanshinone IIA and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production and related signaling molecules were assessed by 3H-proline incorporation, quantitative polymerase chain reaction, enzyme linked immunosorbent assay, and Western blotting. The results indicate cardiac fibroblasts exposed to high glucose condition show increased cell proliferation and collagen synthesis and these effects were abolished by tanshinone IIA treatment. Furthermore, the inhibitory effect of tanshinone IIA on high glucose induced cell proliferation and collagen synthesis may be associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of TGF-β1 production and Smad2/3 phosphorylation. In summary, our results highlights the critical role tanshinone IIA plays as an antioxidant in attenuating high glucose-mediated collagen synthesis through inhibiting TGF-β1/Smad signaling in cardiac fibroblasts which provide a mechanistic basis for the clinical application of tanshinone IIA in the treating diabetic-related cardiac fibrosis.


Gene expression changes in the course of normal brain aging are sexually dimorphic.
Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea.


A new N-nitroso compound, N-2-methylpropyl-N-1-methylacetonyl-nitrosamine, in moldy millet and wheat flour.
A new N-nitroso compound, N-2-methylpropyl-N-1-methylacetonyl-nitrosamine (MAMPNA), was found in millet and wheat flour inoculated with Fusarium moniliforme Sheldon, a common species of fungi occurring in foods in Linxian County, after 8-day incubation and an addition of a small amount of NaNO2. The compound has been identified by GC-MS and confirmed by synthesized MAMPNA. The present paper reports the isolation and detection of MAMPNA in moldy foods, and discusses the role of the fungus in processes of nitrosamine formation and possible biosynthetic approach of the new compound.


Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.
Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.


"No evident disease activity": The use of combined assessments in the management of patients with multiple sclerosis.
Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the "new normal" state of disease control for patients with MS.


BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma.
Brain-derived neurotrophic factor (BDNF) stimulation of its high-affinity receptor TrkB results in activation of pro-survival cell-signalling pathways that can afford neuroprotection to the retina. Reduction in retrograde axonal transport of neurotrophic factors such as BDNF from the brain to the neuronal cell bodies in the retina has been suggested as a critical factor underlying progressive and selective degeneration of ganglion cell layer and optic nerve in glaucoma. We investigated the role of BDNF in preserving inner retinal homeostasis in normal and glaucoma states using BDNF(+/-) mice and compared it with wild type controls. This study demonstrated that BDNF(+/-) animals were more susceptible to functional, morphological and molecular degenerative changes in the inner retina caused by age as well as upon exposure to experimental glaucoma caused by increased intraocular pressure. Glaucoma induced a down regulation of BDNF/TrkB signalling and an increase in levels of neurotoxic amyloid β 1-42 in the optic nerve head which were exacerbated in BDNF(+/-) mice. Similar results were obtained upon analysing the human optic nerve head tissues. Our data highlighted the role of BDNF in maintaining the inner retinal integrity under normal conditions and the detrimental effects of its insufficiency on the retina and optic nerve in glaucoma.


Tele-ophthalmology for age-related macular degeneration during the COVID-19 pandemic and beyond.
COVID-19 has disrupted how ophthalmic practice is conducted worldwide. One patient population that may suffer from poor outcomes during the pandemic are those with age-related macular degeneration (AMD). Many practices are performing some form of tele-ophthalmology services for their patients, and guidance is needed on how to maintain continuity of care amongst patients with AMD using tele-ophthalmology. A literature search was conducted, ending 1 August 2020, to identify AMD outcomes and telecare management strategies that could be used during the COVID-19 pandemic. 237 total articles were retrieved, 56 of which were included for analysis. Four American Academy of Ophthalmology and Center for Disease Control web resources were also included. Risk-stratification models have been developed that let providers readily screen existing patients for their future risk of neovascular AMD (nAMD). When used with at-home monitoring devices to detect nAMD, providers may be able to determine who should be contacted via tele-ophthalmology for screening. Telemedicine triage can be used for new complaints of vision loss to determine who should be referred to a retinal specialist for management of suspected nAMD. To increase access and provider flexibility, smartphone fundus photography images sent to a centralized tele-ophthalmology service can aid in the detection of nAMD. Considerations should also be made for COVID-19 transmission, and tele-ophthalmology can be used to screen patients for the presence of COVID-19 prior to in-person office visits. Tele-ophthalmology has additional utility in connecting with nursing home, rural, and socioeconomically disadvantaged patients in the post-pandemic period.


Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor.
Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective pituitary targeted pharmacotherapy for Cushing disease. Here, we generated germline transgenic zebrafish with overexpression of pituitary tumor transforming gene (PTTG/securin) targeted to the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features pathognomonic of corticotroph adenomas, including corticotroph expansion and partial glucocorticoid resistance. Adult Tg:Pomc-Pttg fish develop neoplastic coticotrophs and pituitary cyclin E up-regulation, as well as metabolic disturbances mimicking hypercortisolism caused by Cushing disease. Early development of corticotroph pathologies in Tg:Pomc-Pttg embryos facilitated drug testing in vivo. We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos. We further validated that orally administered R-roscovitine suppresses ACTH and corticosterone levels, and also restrained tumor growth in a mouse model of ACTH-secreting pituitary adenomas. Molecular analyses in vitro and in vivo showed that R-roscovitine suppresses ACTH expression, induces corticotroph tumor cell senescence and cell cycle exit by up-regulating p27, p21 and p57, and downregulates cyclin E expression. The results suggest that use of selective CDK inhibitors could effectively target corticotroph tumor growth and hormone secretion.


Coordinated Actions of Glyoxalase and Antioxidant Defense Systems in Conferring Abiotic Stress Tolerance in Plants.
Being sessile organisms, plants are frequently exposed to various environmental stresses that cause several physiological disorders and even death. Oxidative stress is one of the common consequences of abiotic stress in plants, which is caused by excess generation of reactive oxygen species (ROS). Sometimes ROS production exceeds the capacity of antioxidant defense systems, which leads to oxidative stress. In line with ROS, plants also produce a high amount of methylglyoxal (MG), which is an α-oxoaldehyde compound, highly reactive, cytotoxic, and produced via different enzymatic and non-enzymatic reactions. This MG can impair cells or cell components and can even destroy DNA or cause mutation. Under stress conditions, MG concentration in plants can be increased 2- to 6-fold compared with normal conditions depending on the plant species. However, plants have a system developed to detoxify this MG consisting of two major enzymes: glyoxalase I (Gly I) and glyoxalase II (Gly II), and hence known as the glyoxalase system. Recently, a novel glyoxalase enzyme, named glyoxalase III (Gly III), has been detected in plants, providing a shorter pathway for MG detoxification, which is also a signpost in the research of abiotic stress tolerance. Glutathione (GSH) acts as a co-factor for this system. Therefore, this system not only detoxifies MG but also plays a role in maintaining GSH homeostasis and subsequent ROS detoxification. Upregulation of both Gly I and Gly II as well as their overexpression in plant species showed enhanced tolerance to various abiotic stresses including salinity, drought, metal toxicity, and extreme temperature. In the past few decades, a considerable amount of reports have indicated that both antioxidant defense and glyoxalase systems have strong interactions in conferring abiotic stress tolerance in plants through the detoxification of ROS and MG. In this review, we will focus on the mechanisms of these interactions and the coordinated action of these systems towards stress tolerance.


Marketing Experimental Stem Cell Therapies in the UK: Biomedical Lifestyle Products and the Promise of Regenerative Medicine in the Digital Era.
Stem cell research has attracted much public and biomedical anticipation centred on the possibility of using stem cells to treat various diseases and conditions, but the number of evidence-based therapies is currently limited. Numerous commercial direct-to-consumer (DTC) businesses are nonetheless marketing experimental stem cell therapies online for myriad medical conditions and aesthetic ailments, which has attracted critique due to safety and efficacy concerns. Existing research has largely focused on the problem of unproven therapies and regulatory pathways for addressing it. The proliferation of these experimental products must also be examined, however, in the broader socio-technological context of consumer culture and changing practices of knowledge-making in the digital era. DTC stem cell therapies have emerged as a new biomedical 'lifestyle' product that blurs the boundaries between 'science,' 'medicine,' and 'consumer culture.' In using, conceptualising and marketing stem cells, commercial businesses build on and commercially co-opt alternative epistemic and ontological frames that challenge scientific medicine. They advance promissory narratives about their potential that tap on cultural aspirations around the future of medicine and health. This is key, not only for understanding how and why these therapies have proliferated but also in conceptualising what the 'problem' around them actually is.


Zeigarnik's sleepless nights: How unfinished tasks at the end of the week impair employee sleep on the weekend through rumination.
It is almost common sense that work stress leads to sleep impairment, but the question of how work-related stressors impair employee sleep remains open. This study focuses on the role of rumination as the underlying mechanism for sleep impairment. Specifically, the authors contribute to recent research differentiating affective rumination from problem-solving pondering and examine the impact of both forms of rumination on the stressor-sleep relationship. Following theories of rumination and the Zeigarnik effect, they focus on unfinished tasks as a key onset for rumination. Unfinished tasks have received much research attention in the memory context but have been neglected as a stressor that can impact recovery. Drawing on theory, differential indirect links between unfinished tasks and sleep through affective rumination versus problem-solving pondering are examined. Further, the number of unfinished tasks extending over a 3-month period may impair employee sleep more than unfinished tasks within the acute phase. In this study, intraindividual links in a diary study supplemented by depicting between-person effects of unfinished tasks over a period of 3 months are examined. The authors matched 357 Friday and Monday observations over a 12-week interval for 59 employees. The results of the multilevel analysis suggest that the within-person relationship between unfinished tasks and sleep is mediated by affective rumination. Although problem-solving pondering was negatively related to sleep impairment, the indirect effect was not significant. Finally, beyond the acute effect, the authors found higher levels of unfinished tasks over 3 months are related to increased sleep impairment on the weekend. (PsycINFO Database Record


Function of the Anterior Intermeniscal Ligament.
The function and importance of the anterior intermeniscal ligament (AIML) of the knee are not fully known. The purpose of this study was to evaluate the biomechanical and sensorimotor function of the AIML. Computational analysis was used to assess AIML and tibiomeniscofemoral biomechanics under combined translational and rotational loading applied during dynamic knee flexion-extension. Histologic and immunohistochemical examination was used to identify and characterize neural elements in the tissue. The computational models were created from anatomy and passive motion of two female subjects and histologic examinations were conducted on AIMLs retrieved from 10 fresh-frozen cadaveric knees. It was found that AIML strain increased with compressive knee loading and that external rotation of the tibia unloads the AIML, suppressing the relationship between AIML strain and compressive knee loads. Extensive neural elements were located throughout the AIML tissue and these elements were distributed across the three AIML anatomical types. The AIMLs have a beneficial influence on knee biomechanics with decreased meniscal load sharing with AIML loss. The AIML plays a significant biomechanical and neurologic role in the sensorimotor functions of the knee. The major role for the AIML may primarily involve its neurologic function.


Risk communication: a tool for behavior change.
This chapter presents some of the theories and models underpinning effective communication practice. It also emphasizes the central role of communication in achieving effective program implementation. Whether the communication is aimed at changing the attitudes and behavior of professionals, various segments of the public, or other target audiences, the basic approach is the same. The following checklist provides a guide to program planners (Arkin 1991): Commit adequate time, effort, and resources to communication planning and pretesting. Begin by singling out specific issues and specific target audiences. Then design messages based on the target audiences' values, needs, and interests. Conduct (or review existing) market research on the target audience to understand what will motivate them. Pretest messages and materials with the target audience to assure understanding and relevance to their needs and interests. Make sure that messages and materials appear where the target audience will pay attention to them (for sensitive issues, community and interpersonal channels that allow interactive discussion are very important). Produce public service announcements that are of high quality, community specific, marketed to stations, and targeted to audiences likely to see them when public service air time is available (such as fringe viewing times). Combine public service announcements with news and other uses of the mass media (e.g., building on related news) to increase exposure to issues. Use a combination of the mass media and community channels that will reach the target audience. Work collaboratively with other organizations, including drug treatment facilities, law enforcement and social service agencies, and other community organizations that have complementary strengths. Begin to coordinate efforts as early as possible in program planning. Use a multipronged communication strategy to focus on what an individual should do, how the individual can start to change, and factors that help reinforce individual change, such as peer approval and community support. Track progress and identify when, and what kind of, changes are needed in communications. Combine communications with other strategies needed to support change (e.g., access to treatment or positive alternatives to drug use). Set reasonable, short-term communication objectives to reach the long-term goal. Then, commit to communications as one program component over the long term. It is important to remember that one-shot campaigns are unlikely to have a lasting effect and that progress is incremental.


Sleep quality and athletic performance according to chronotype.
When studying the quality of sleep in relation to athletic performance, the athlete's chronotype and habitual time consider important factors. We aim to investigate the sleep quality and athletes' performance according to chronotype in elite athletes. Three hundred forty elite athletes (males = 261, females = 79) were recruited for the present study. All participants were screening for chronotype by the Korean versions of the Morningness - Eveningness Questionnaire (MEQ-K). The Pittsburgh Sleep Quality Index (PSQI) and Wingate Anaerobic Test (WAnT) were measurement after screening. PSQI global score, PSQI sleep quality, PSQI sleep onset latency, PSQI sleep disturbance, and PSQI daytime dysfunction were significant differences among the groups. WAnT mean power (W), mean power (W/kg), peak power (W), and peak power (W/kg) were significant differences among the groups. A negative correlation coefficient was found between PSQI score and WAnT mean power (W) (r = - 0.256, p < 0.01), mean power (W/kg) (r = - 0.270, p < 0.01), peak power (W) (r = - 0.220, p < 0.01), and peak power (W/kg) (r = - 0.248, p < 0.01). This study indicates that related poor sleep quality and late-type chronotype may reduce the athletes' performance in elite athletes. In addition, the sleep quality is much higher in the early-type chronotype than in the late-type chronotype. Moreover, it also the athletic performance was better in the early-type chronotype than in the late-type chronotype.


Effects of phentermine on responding maintained by progressive-ratio schedules of cocaine and food delivery in rhesus monkeys.
Previous reports indicate that intravenous pretreatment with phentermine can decrease cocaine-maintained responding without affecting food-reinforced responding under fixed-ratio schedules. The present experiments were designed to explore the generality of this effect using progressive-ratio schedules of reinforcement and different routes of phentermine administration. Unit doses of cocaine and food-pellet magnitudes were identified that maintained similar breaking points, and the effects of acute exposure to phentermine were assessed. In Experiment 1, a 'conventional' (one-trial) progressive-ratio schedule was used, in which response requirements increased after each reinforcer delivery; in Experiment 2, a 'modified' (five-trial) progressive-ratio schedule was used, in which response requirements increased after every five reinforcer deliveries. In one group of monkeys, responding was maintained by food; in another, cocaine infusions maintained responding. Phentermine (0.1-5.6mg/kg, intramuscularly (i.m.)) dose-dependently decreased breakpoints on both progressive-ratio schedules. There were no differences in phentermine's effects on cocaine- and food-maintained behavior. In Experiment 3, intravenous administration of phentermine had largely similar effects. Taken together with results from previous reports, these data suggest that the effects of phentermine pretreatment are influenced by the behavioral procedure used to maintain responding and/or by the efficacy of the food and cocaine reinforcers.


[Relative numerousness judgements in crows and pigeons in the urgent comparison of stimuli earlier linked to different amounts of reinforcement].
The ability of pigeons (Colomba livia, L.) and crows (Corvus corone cornix, L.) was studied to realize urgent numerousness judgement of reinforcement consisting of discrete elements (wheat grains and meal worm larvae, respectively). In the process of preliminary training the birds mastered the information about the conformity of the feeder colour with the definite number (1-9 for pigeons and 5-12 for crows) of reinforcement units at isolated presentation of feeders. In test at presentation of pairs formed from these feeders, pigeons and crows chose the stimulus connected with a greater quantity of reinforcement. In the range of 1-8 units the precision of choice in pigeons depended on absolute and relative differences between comparing values. In crows in the range of 6-12 this dependence was not revealed. The ability to solve the given test is considered as one of manifestations of elementary reasoning.