Developmental expression and localization of the catalytic subunit of protein phosphatase 2A in rat lung.
Protein phosphatase type-2A (PP2A) is a highly conserved serine/threonine phosphatase known to play a key role in cell proliferation and differentiation in vitro, but the role of PP2A in mammalian embryogenesis remains unexplored. No particular information exists as to the tissue or cell specific expression of PP2A or the relevance of PP2A expression to mammalian development in vivo. To examine expression of PP2A during mammalian lung development, we studied fetal rats from day 14 of gestation (the lung bud is formed on day 12 of gestation) to parturition. Western analysis with a specific PP2A catalytic subunit antibody identified a single 36 kDa protein, with protein levels two-fold higher in the 17 and 19 day embryonic lung as compared to the adult. With in situ hybridization and immunohistochemistry, both mRNA and protein for PP2A were localized equally to the epithelial lining of the embryonic lung airway and the surrounding mesenchyme in the 14 day embryonic lung. With maturation of the lung, PP2A becomes highly expressed in respiratory epithelium. The highest level of expression was in the earliest developing airways with columnar epithelium (the pseudoglandular stage, 15-18 days of gestation). There was a decrease in expression with the transformation to cuboidal epithelium by day 20 of gestation. This was most noticeable in the developing bronchial epithelium of the 19 and 20 day gestation lungs where only an occasional cell continues to express PP2A. Mesenchymal hybridization was most obvious in early endothelial cells of forming vascular channels at 17-19 days of gestation. PP2A respiratory epithelial expression mimicked the centrifugal development of the respiratory tree where the highest expression was in the peripheral columnar epithelium (15-18 days gestation) with only an occasional central bronchiolar cell continuing to express PP2A at 19 and 20 days gestation. Endothelial hybridization decreased with muscularization of large pulmonary arteries with low levels of expression detected in bronchial or vascular smooth muscle. In the newborn lung PP2A expression was decreased, but detectable in alveolar epithelium and vascular endothelium. In summary; 1) PP2A mRNA and protein exhibit cell specific expression during rat lung development; 2) PP2A is highly expressed in the respiratory epithelium of the fetal rat lung and is temporally related to the maturation of the bronchial epithelium; 3) and the PP2A subunit is highly expressed in early vascular endothelium, but not smooth muscle of the rat lung.


Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia.
Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean+/-sd age 54.4+/-10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in approximately 80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.


Autoantibodies and levels of polychlorinated biphenyls in persons living near a hazardous waste treatment facility.
Increased autoantibody prevalence has been described in instances of high-dose exposure to polychlorinated biphenyls (PCBs). In 1996, an equipment malfunction at the Swan Hills Treatment Centre in Alberta, Canada, caused the release of gases containing PCBs into the ambient air. In view of the immune effects of PCBs and their potential as endocrine disruptors, we assessed autoantibody prevalence and looked for correlations with PCB levels. Fifty-seven persons living within a 100 km radius of the waste treatment facility were assessed. Autoantibodies were measured by indirect immunofluorescence, double immunodiffusion, and immunoblotting. The levels of 26 congeners of PCBs were measured by gas chromatography and mass spectrometry. Provincial health records for physician visits and hospitalizations were reviewed for diagnoses of autoimmune disease. The prevalence of autoantibodies was 11% in the study participants and 0% in healthy controls. There was no correlation of PCB levels with autoantibody results. There was no associated increase in autoimmune disease noted on physician visits or hospitalizations. PCB levels were comparable to background levels reported for other populations. A correlation of titers of autoantibodies in the sera of individuals at risk and the blood levels of PCBs was not found, and the prevalence of autoantibodies in the at-risk group was not statistically different (p > .05) from that of an unexposed control group. The study group had higher titers of autoantibodies and some strong reactivity with intracellular antigens, but the significance of this observation may be understood only after long-term clinical assessments and follow-up.


Does aerial baiting for controlling feral cats in a heterogeneous landscape confer benefits to a threatened native meso-predator?
Introduced mammalian predators can have devastating impacts on recipient ecosystems and disrupt native predator-prey relationships. Feral cats (Felis catus) have been implicated in the decline and extinction of many Australian native species and developing effective and affordable methods to control them is a national priority. While there has been considerable progress in the lethal control of feral cats, effective management at landscape scales has proved challenging. Justification of the allocation of resources to feral cat control programs requires demonstration of the conservation benefit baiting provides to native species susceptible to cat predation. Here, we examined the effectiveness of a landscape-scale Eradicat® baiting program to protect threatened northern quolls (Dasyurus hallucatus) from feral cat predation in a heterogeneous rocky landscape in the Pilbara region of Western Australia. We used camera traps and GPS collars fitted to feral cats to monitor changes in activity patterns of feral cats and northern quolls at a baited treatment site and unbaited reference site over four years. Feral cat populations appeared to be naturally sparse in our study area, and camera trap monitoring showed no significant effect of baiting on cat detections. However, mortality rates of collared feral cats ranged from 18-33% after baiting, indicating that the program was reducing cat numbers. Our study demonstrated that feral cat baiting had a positive effect on northern quoll populations, with evidence of range expansion at the treatment site. We suggest that the rugged rocky habitat preferred by northern quolls in the Pilbara buffered them to some extent from feral cat predation, and baiting was sufficient to demonstrate a positive effect in this relatively short-term project. A more strategic approach to feral cat management is likely to be required in the longer-term to maximise the efficacy of control programs and thereby improve the conservation outlook for susceptible threatened fauna.


Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications.
Dietary calcium plays a pivotal role in the regulation of energy metabolism; high calcium diets attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Intracellular Ca2+ has a key role in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca2+ resulting in stimulation of lipogenic gene expression and lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. Moreover, we have recently demonstrated that the increased calcitriol released in response to low calcium diets stimulates Ca2+ influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. These findings are further supported by clinical and epidemiological data demonstrating a profound reduction in the odds of being obese associated with increasing dietary calcium intake. Notably, dairy sources of calcium exert a significantly greater anti-obesity effect than supplemental sources in each of these studies, possibly due to the effects of other bioactive compounds, such as the angiotensin converting enzyme inhibitor found in milk, on adipocyte metabolism, indicating an important role for dairy products in the control of obesity.


Dietary and hormonal interrelationships in premenopausal women: evidence for a relationship between dietary nutrients and plasma prolactin levels.
To investigate possible differences in tissue exposures to reproductive hormones and to determine hormone-nutrient interrelationships, we studied 10 vegetarian and 10 nonvegetarian premenopausal Seventh-day Adventist women. Over 3 d in each of three consecutive menstrual cycles, we collected diet records, fasting midluteal phase blood, and 24-h urine samples. During each study period, we measured plasma and urinary estrogens, plasma free and protein bound-estradiol-17 beta, the binding capacity of sex-hormone-binding globulin (SHBG), androgens, progesterone, and prolactin levels. The omnivores consumed significantly more protein, total and saturated fatty acids, oleic and linoleic acids, and cholesterol than did the vegetarians. Hormonal status and binding capacity of SHBG were similar in both groups. However, for nonvegetarians, prolactin levels were positively correlated with dietary energy, protein, total and saturated fatty acids, and oleic acid. Further study delineating the effects of specific dietary nutrients on the basal level of prolactin secretion is warranted.


Nurses' work-related stress in China: a comparison between psychiatric and general hospitals.
Little is known about the level of work-related stress in nurses in China.This study compared the level of work-related stress between female nurses working in psychiatric and general hospitals in China. A descriptive comparative cross-sectional design was used.A consecutive sample of nurses from two psychiatric hospitals (N = 297) and a medical unit (N = 408) of a general hospital completed a written survey including socio-demographic data and a measure of work-related stress (Nurse Stress Inventory). Compared to the nurses working in the general hospital, those working in the psychiatric setting had a higher level of stress in the domains of working environment and resources (p < .001) and patient care (p < .001), but lower workload and time (p < .001).Multivariate analyses revealed that college or higher level of education(b = .1, p < .001), exposure to violence in the past 6 months (b = .2, p < .001),longer working experience, and working in psychiatric hospitals were associated with high work-related stress (b = .2, p < .001). Considering the harmful effects of work-related stress, specific stress management workshops and effective staff supportive initiatives for Chinese nurses are warranted.


Remodeling of the infection chamber before infection thread formation reveals a two-step mechanism for rhizobial entry into the host legume root hair.
In many legumes, root entry of symbiotic nitrogen-fixing rhizobia occurs via host-constructed tubular tip-growing structures known as infection threads (ITs). Here, we have used a confocal microscopy live-tissue imaging approach to investigate early stages of IT formation in Medicago truncatula root hairs (RHs) expressing fluorescent protein fusion reporters. This has revealed that ITs only initiate 10 to 20 h after the completion of RH curling, by which time major modifications have occurred within the so-called infection chamber, the site of bacterial entrapment. These include the accumulation of exocytosis (M. truncatula Vesicle-Associated Membrane Protein721e)- and cell wall (M. truncatula EARLY NODULIN11)-associated markers, concomitant with radial expansion of the chamber. Significantly, the infection-defective M. truncatula nodule inception-1 mutant is unable to create a functional infection chamber. This underlines the importance of the NIN-dependent phase of host cell wall remodeling that accompanies bacterial proliferation and precedes IT formation, and leads us to propose a two-step model for rhizobial infection initiation in legume RHs.


Expressed interest in health-related lifestyle change in three communities.
Little is known about the public's motivation to change lifestyles in a healthy direction. This study reports results from surveys conducted in three divergent New Zealand communities, two urban and one rural (total n = 467), and shows a striking degree of interest in changing lifestyles, and a uniformity of preferences. Two-thirds or more of all adults interviewed expressed interest in changing their lifestyles, and three lifestyle areas consistently emerged as being of top priority: fitness, losing weight and stress-management. When a Maori subsample is examined, an even higher degree of interest was found than that for Europeans. The implications of these findings for the planning of health promotion activities are discussed.


An atypical cytochrome b in the colorless alga Polytomella spp.: the high potential bH heme exhibits a double transition in the alpha-peak of its absorption spectrum.
Polytomella spp. is a colorless alga of the family Chlamydomonadaceae that lacks chloroplasts and cell wall. A highly active ubiquinol-cytochrome c oxidoreductase (bc1 complex), sensitive to antimycin and myxothiazol, has been purified and characterized from this alga (Gutiérrez-Cirlos et al., 1994, J. Biol. Chem. 269, 9147-9154). Both in mitochondrial membranes and in the isolated complex, the visible spectrum of cytochrome b from Polytomella spp. exhibits an atypical alpha-band with a maximum at 567 nm. This maximum is shifted 3-4 nm to the red when compared with b-type cytochromes from other organisms. Analysis of the b hemes of the bc1 complex by high performance liquid chromatography revealed no differences in the retention time and in the absorption spectra of the b-type hemes from Polytomella spp. and hemin, indicating that the prosthetic group in this alga is protoheme and thus ruling out the possibility that the red-shift could be due to different chemical substitutions in the porphyrin rings of the bL or bH hemes. The two b hemes were characterized by electrochemical redox titration; at pH 7.8-8.0, the midpoint potential for bL was-143 mV and for bH +25 mV. The spectra of the two b-type hemes were recorded in the presence of different reductants, at selected electrochemical potentials, and in the presence of antimycin A, to distinguish between the contribution of bL and bH to the visible spectrum. Both hemes bL and bH of the algal cytochrome b contribute to the observed bathochromic absorption maximum in the alpha-band of the spectrum. The data also show that the low potential bL heme from Polytomella spp. is spectroscopically similar to that of other organisms, with two transitions in the alpha-peak at 558.7 and 568.4 nm. The high-potential heme bH also exhibits a spectrum with two transitions at 557.2 and 568.9 nm, which surprisingly differs from the spectra of cytochrome bH of mammals, plants, yeasts, and bacteria, which all exhibit a single transition centered around 560 nm.


[Actual use of milk and its products and estimation of the degree of their contamination].
The actual use of milk and its products was studied in the population of the Fergana Valley and the daily intake of heavy metals, pesticides, nitrates, antibiotics, and other foreign substances was hygienically evaluated. Guidelines were developed to set up critical control points for the hazard analysis of production factors and the sale and storage of dairy products, which were approved by the Ministry of Health of the Republic of Uzbekistan.


[Normal and pathological aging of the brain].
The number of people of old age in western countries is growing, leading to an increased prevalence of degenerative brain diseases. These diseases are widely regarded as a limiting factor of quality of life in old age. The possibilities to maintain intellectual performance of the brain even in old age historically met with scepticism and diseases like Alzheimer's or Parkinson's disease were accepted as an inevitable consequence of aging. "The older, the sicker." However, during recent years new concepts were developed: The physiologic aging of the brain is distinct from diseases of the brain occurring during old age and pathogenesis of degenerative brain diseases is increasingly revealed. This results in novel, even neuroprotective, therapy strategies, implying that these diseases cannot only be seen as inevitable and incurable, but also as a target for prevention and symptomatic and causal therapy strategies.


Structural organization of (Na+ + K+)-ATPase in purified membranes.
The structural organization of crystalline, membrane-bound (Na+ + K+)-ATPase was studied by negative staining and thin sectioning. The enzyme molecules were induced to form crystalline arrays within fragments of membrane by incubation in defined ionic conditions. The enzyme remained fully active after crystallization. Negative staining and computer processing of images of the crystalline specimens identified two discrete crystalline arrays. The dimensions of the unit cell of one of the arrays were large enough to accommodate an alpha beta protomer; those of the other array, an (alpha beta)2 diprotomer . Thin sections of the crystalline fraction contained a unique membrane complex that was formed from two apposed plasma membranes. The paired membranes in this complex were separated by a center-to-center space of 15 nm containing evenly spaced septa that connected the membrane surfaces; the overall thickness of the entire structure was 22-25 nm. The agglutinin from Ricinus communis, a lectin that binds to the carbohydrate moiety of the beta-subunit of (Na+ + K+)-ATPase, decorated the free surfaces of the complex. Therefore, this complex of paired membranes is the result of interactions between the cytoplasmic domains of the enzyme. From measurements of the dimensions of these structures, we estimate the overall length of the enzyme to be approximately 11.5 nm along the axis perpendicular to the plane of the membrane, and the molecular protrudes more (approximately 5 nm) on the cytoplasmic surface than on the extracytoplasmic surface (approximately 2 nm).


21-Hydroxylase deficiency: Mutational spectrum and Genotype-Phenotype relations analyses by next-generation sequencing and multiplex ligation-dependent probe amplification.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is autosomal recessive disorder of cortisol biosynthesis. Genetic defects in CYP21A2 cause 21OHD. The aim of this study was to determine spectrum of mutations in CYP21A2 in a large cohort and analyze the genotype-phenotype correlation to assess predictive characteristics of genotype. We investigated a total of 113 patients with 21OHD. Next-generation sequencing and Multiplex ligation-dependent probe amplification of the CYP21A2 gene were performed in patients and their parents. The genotypes were categorized into Groups 0, A, B, and C according to the residual 21-hydroxylase activities. In this study, the group A was divided into two subgroups as A1 and A2. Three novel variants were found. The genotype-phenotype correlation of the mutation classification was 91.5%. Positive predictivity of subgroups A1 was higher than groups A and subgroups A2. Our study reports genotype-phenotype correlations in the largest 21OHD cohort in Turkey. This correlation sustained when we analyzed our data in combination with metadata from other published studies. This study confirms that CYP21A2 genotyping with next-generation sequencing and MLPA can accurately and reliably confirm the diagnosis of 21OHD. We propose a new classification by dividing group A into two new subgroups to better predict the phenotype. In light of this very high genotype-phenotype correlation, with their ever-increasing availability, declining cost, and turnaround time, we propose that molecular genetic studies can be more economical and practical alternative to the current initial diagnostic laboratory studies based on assays of intermediary steroid metabolites.


Screening of 71 P. multocida proteins for protective efficacy in a fowl cholera infection model and characterization of the protective antigen PlpE.
There is a strong need for a recombinant subunit vaccine against fowl cholera. We used a reverse vaccinology approach to identify putative secreted or cell surface associated P. multocida proteins that may represent potential vaccine candidate antigens. A high-throughput cloning and expression protocol was used to express and purify 71 recombinant proteins for vaccine trials. Of the 71 proteins tested, only one, PlpE in denatured insoluble form, protected chickens against fowl cholera challenge. PlpE also elicited comparable levels of protection in mice. PlpE was localized by immunofluorescence to the bacterial cell surface, consistent with its ability to elicit a protective immune response. To explore the role of PlpE during infection and immunity, a plpE mutant was generated. The plpE mutant strain retained full virulence for mice. These studies show that PlpE is a surface exposed protein and was the only protein of 71 tested that was able to elicit a protective immune response. However, PlpE is not an essential virulence factor. This is the first report of a denatured recombinant protein stimulating protection against fowl cholera.


Positron emission tomography in the diagnostic work-up of screening-detected lung nodules.
Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screening-detected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for ⩾2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules ⩾15 mm, better (sensitivity 98%) for solid nodules ⩾15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ⩾15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used.


Genetic Characterization of a Captive Colony of Pigtailed Macaques (Macaca nemestrina).
Effective colony management is critical to guarantee the availability of captive NHP as subjects for biomedical research. Pigtailed macaques (Macaca nemestrina) are an important model for the study of human and nonhuman primate diseases and behavior. Johns Hopkins University hosts one of the largest captive colonies of pigtailed macaques in the United States. In this study, we used 56 single-nucleotide polymorphisms (SNP) to characterize this population of pigtailed macaques, understand their population structure, and assess the effectiveness of their colony management. The results demonstrate that the colony has maintained a high level of genetic diversity, with no loss of heterozygosity since its origin, and low levels of inbreeding and genetic subdivision.


Inner Conflict of Personality in the Paradigm of Existential-Phenomenological Ontology.
This article analyzes the problem of internal personality conflicts from the the standpoint of existential-phenomenological ontology. The article presents a theoretical substantiation of phenomenological ontology as a nonclassical paradigm in the human sciences to solve existential conflicts in personality. It is noted that the main models of internal conflict do not give a satisfactory answer to the question of psychogenesis and psychological mechanisms for resolving existential conflicts. It is emphasized that it is perspective to analyze internal conflicts, relying upon phenomenological ontology and the existential approach. The main provisions of phenomenological ontology presented in the works of Husserl and Heidegger, as the founders of this scientific direction, are considered in a psychological context. A classification of existential experiences of a difficult life world is proposed, depending on the intra- and inter-orientation of mental processes. The concepts of the self-closing life world, ambivalent Other, ambivalent intentionality, spontaneous involvement are introduced, making it possible to substantiate a conceptual model for resolving existential personality conflicts. It is concluded that the resolution of existential conflicts is associated with the feeling of an intersubjective life-world, in which the ambivalent Other and spontaneous bodily involvement play a primary role.


Antileishmanial activity, uptake, and biodistribution of an amphotericin B and poly(α-Glutamic Acid) complex.
A noncovalent, water-soluble complex of amphotericin B (AMB) and poly(α-glutamic acid) (PGA), with AMB loadings ranging from 25 to 55% (wt/wt) using PGA with a molecular weight range of 50,000 to 70,000, was prepared as a potential new treatment for visceral leishmaniasis (VL). The AMB-PGA complex was shown to be as active as Fungizone (AMB deoxycholate) against intracellular Leishmania donovani amastigotes in differentiated THP-1 cells. The in vitro uptake of the AMB-PGA complex by differentiated THP-1 cells was similar to that of Fungizone and higher than that of AmBisome (liposomal AMB). The AMB-PGA complex also displayed a dose-response profile similar to that of AmBisome in vivo in BALB/c mice against L. donovani, with 50% effective doses (ED50s) of 0.24 ± 0.03 mg/kg of body weight for the AMB-PGA complex and 0.24 ± 0.06 mg/kg for AmBisome. A biodistribution study with mice indicated that the AMB-PGA complex cleared more rapidly from plasma than AmBisome, with a comparable low level of distribution to the kidneys.


Homograft immunity in pregnancy. The placental transfer of cytotoxic antibody in rabbits.
The mammalian fetus affixed to the uterine wall in some ways resembles a homograft, but maternal homograft immunity even when specifically directed against her fetuses fails to destroy them. The placental barrier appears to be critical in protecting the fetus against maternal immunologic attack. In order to evaluate the means by which it affords protection, we have measured in rabbits the transfer of cytotoxic antibody from mother to fetus. When the offspring were not the specific targets for maternal antibody, we found titers of cytotoxic antibody in the newborn animals at or near maternal levels in 16 of 18 cases (89 per cent), demonstrating the ability of this antibody to cross the rabbit placenta. When the offspring were appropriate targets for antibody, however, 11 of 18 newborn animals (61 per cent) had no demonstrable titer. We believe that in these latter cases, antibody had become fixed to antigenic sites and thereby had been removed from the fetal circulation. There was, however, no evidence of harm to any of the fetuses, either in survival (as demonstrated in a previous study) or in spleen or thymus weights or peripheral leukocyte and mononuclear cell counts. Cytotoxic antibody appears to reach the embryo early in gestation, since we found antibody in 8-day-old blastocyst fluid in each of 2 trials. We conclude that the fetus neither receives nor requires protection against cytotoxic antibody, and believe that fetal protection against maternal homograft immunity is afforded by a placental barrier to maternal mononuclear leukocytes.


Ginseng and heme oxygenase-1: The link between an old herb and a new protective system.
Ginseng is an ancient herb, belonging to Asian traditional medicine, that has been considered as a restorative to enhance vitality for centuries. It has been demonstrated that the antioxidant action of ginseng may be mediated through activation of different cellular signaling pathways involving the heme oxygenase (HO) system. Several compounds derived from ginseng have been studied for their potential role in brain, heart and liver protection, and the Nrf2 pathway seems to be the most affected by these natural molecules to exert this effect. Ginseng is also popularly used in cancer patients therapy for the demonstrated capability to defend tissues from chemotherapy-induced damage. Reported results suggest that the effect of ginseng is primarily associated with ROS scavenging, mainly exerted through the activation of Nrf2 pathway, and the consequent induction of HO-1 levels. This review aims to discuss the connection between the antioxidant properties of ginseng and the activation of the HO system, as well as to outline novel therapeutic applications of this medicinal plant to human health.


Identification of candidate amino acids involved in the formation of blue pigments in crushed garlic cloves (Allium sativum L.).
The color-forming ability of amino acids with thiosulfinate in crushed garlic was investigated. We developed reaction systems for generating pure blue pigments using extracted thiosulfinate from crushed garlic and onion and all 22 amino acids. Each amino acid was reacted with thiosulfinate solution and was then incubated at 60 degrees C for 3 h to generate pigments. Unknown blue pigments, responsible for discoloration in crushed garlic cloves (Allium sativum L.), were separated and tentatively characterized using high-performance liquid chromatography (HPLC) and a diode array detector ranging between 200 and 700 nm. Blue pigment solutions exhibited 2 maximal absorbance peaks at 440 nm and 580 nm, corresponding to yellow and blue, respectively, with different retention times. Our findings indicated that green discoloration is created by the combination of yellow and blue pigments. Eight naturally occurring blue pigments were separated from discolored garlic extracts using HPLC at 580 nm. This suggests that garlic discoloration is not caused by only 1 blue pigment, as reported earlier, but by as many as 8 pigments. Overall, free amino acids that formed blue pigment when reacted with thiosulfinate were glycine, arginine, lysine, serine, alanine, aspartic acid, asparagine, glutamic acid, and tyrosine. Arginine, asparagine, and glutamine had spectra that were more similar to naturally greened garlic extract.


Heat transfer in the thermo-electro-hydrodynamic convection under microgravity conditions.
This article deals with the thermal convection in a dielectric fluid confined in a finite-length plane capacitor with a temperature gradient under microgravity conditions. The dielectrophoretic force resulting from differential polarization of the fluid plays the role of buoyancy force associated with an electric effective gravity. It induces the convection when the Rayleigh number based on this electric gravity exceeds a critical value. Two-dimensional numerical simulation for a geometry with a large aspect ratio is used to determine the convective flow in the saturated state. The Nusselt number Nu is computed for a wide range of Prandtl number (0.01 ≤ Pr ≤ 10(3)) and its dependence on the distance from the critical condition is determined. A correlation between Nu and Pr in the vicinity of criticality is obtained and compared with that of the Rayleigh-Bénard convection. The behavior of the convection is analyzed in detail from an energetic viewpoint: electrostatic energy, power inputs by different components of the electric gravity and viscous and thermal dissipations are computed.


Are There Any Experimental Perfusion Data that Preferentially Support the Dispersion and Parallel-Tube Models over the Well-Stirred Model of Organ Elimination?
In reviewing previously published isolated perfused rat liver studies, we find no experimental data for high-clearance metabolized drugs that reasonably or unambiguously support preference for the dispersion and parallel-tube models versus the well-stirred model of organ elimination when only entering and exiting drug concentrations are available. It is likely that the investigators cited here may have been influenced by: 1) the unphysiologic aspects of the well-stirred model, which may have led them to undervalue the studies that directly test the various hepatic disposition models for high-clearance drugs (for which model differences are the greatest); 2) experimental assumptions made in the last century, which are no longer valid today, related to the predictability of in vivo outcomes from in vitro measures of drug elimination and the influence of albumin in hepatic drug uptake; and 3) a lack of critical review of previously reported experimental studies, resulting in inappropriate interpretation of the available experimental data. The number of papers investigating the theoretical aspects of the dispersion, parallel-tube, and well-stirred models of hepatic elimination greatly outnumber the papers that actually examine the experimental evidence available to substantiate these models. When all experimental studies that measure organ elimination using entering and exiting drug concentrations at steady state are critically reviewed, the simple but unphysiologic well-stirred model is the only model that can describe all trustworthy published available data. SIGNIFICANCE STATEMENT: Although the dispersion model of hepatic elimination more adequately reflects physiologic reality, there are no convincing experimental data that unambiguously favor this model. The well-stirred model can describe all well-designed perfusion studies with high-clearance drugs and nondrug substrates, but the field has not recognized this because of hesitation to accept a nonphysiologic model and flawed attempts to utilize in vitro-in vivo extrapolation approaches.


Effect of sample preparation techniques upon single cell chemical imaging: A practical comparison between synchrotron radiation based X-ray fluorescence (SR-XRF) and Nanoscopic Secondary Ion Mass Spectrometry (nano-SIMS).
Analytical capabilities of Nanoscopic Secondary Ion Mass Spectrometry (nano-SIMS) and Synchrotron Radiation based X-ray Fluorescence (SR nano-XRF) techniques were compared for nanochemical imaging of polymorphonuclear human neutrophils (PMNs). PMNs were high pressure frozen (HPF), cryo-substituted, embedded in Spurr's resin and cut in thin sections (500 nm and 2 μm for both techniques resp.) Nano-SIMS enabled nanoscale mapping of isotopes of C, N, O, P and S, while SR based nano-XRF enabled trace level imaging of metals like Ca, Mn, Fe, Ni, Cu and Zn at a resolution of approx. 50 nm. The obtained elemental distributions were compared with those of whole, cryofrozen PMNs measured at the newly developed ID16A nano-imaging beamline at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Similarities were observed for elements more tightly bound to the cell structure such as phosphorus and sulphur, while differences for mobile ions such as chlorine and potassium were more pronounced. Due to the observed elemental redistribution of mobile ions such as potassium and chlorine, elemental analysis of high pressure frozen (HPF), cryo-substituted and imbedded cells should be interpreted critically. Although decreasing analytical sensitivity occurs due to the presence of ice, analysis of cryofrozen cells - close to their native state - remains the golden standard. In general, we found nanoscale secondary ion mass spectrometry (nano-SIMS) and synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) to be two supplementary alternatives for nanochemical imaging of single cells at the nanoscale.


Extended liver resections for intrahepatic cholangiocarcinoma: friend or foe?
In patients with intrahepatic cholangiocarcinoma (ICC), extended liver resections (ELRs) increase the rate of resectability. The aims of the present study were to evaluate the morbidity and oncologic outcomes of ELR compared with other liver resections (LR) for ICC. All LR for ICC that were performed in our center between January 1997 and September 2013 and conducted with curative intent were included in this retrospective analysis. ELRs were defined by resections of ≥5 liver segments. The factors that influenced the occurrence of major complications (Clavien ≥ 3) and overall survival (OS) were tested with univariate and multivariate analyses. One hundred seven patients (82 men and 25 women) were resected, and 27 (25.3%) underwent ELRs. Compared with the LRs, the ELRs were performed in larger tumors (P = .003) and were significantly associated with more complex surgeries such as vascular (P < .001) or biliary reconstructions (P < .001). Multivariate analysis revealed that ELR was an independent risk factor for major complications (odds ratio [OR], 6.2; 95% CI, 2.11-19.62; P < .001). Compared with the other LRs, ELRs had no effects on OS or disease-free survival (P = .881 and P = .228, respectively). Perioperative blood transfusion (Hazard ratio (HR), 2.51; 95% CI, 1.49-4.23; P < .001), the presence of >1 nodule (HR, 3.17; 95% CI, 1.67-5.97; P < .001), and age ≥65 years (HR, 1.72; 95% CI, 1.03-2.86; P = .036) were independent prognostic factors for OS. This study suggests that ELRs performed for large ICCs do not affect negatively oncologic outcomes, despite the increased risk of major complications.


Sequential and one-pot post-polymerization modification reactions of thiolactone-containing polymer brushes.
Thiolactone chemistry has garnered significant attention as a powerful post-polymerization modification (PPM) route to mutlifunctional polymeric materials. Here, we apply this versatile chemistry to the fabrication of ultrathin, multifunctional polymer surfaces via aminolysis and thiol-mediated double modifications of thiolactone-containing polymer brushes. Polymer brush surfaces were synthesized via microwave-assisted surface-initiated polymerization of DL-homocysteine thiolactone acrylamide. Aminolysis and thiol-Michael double modifications of the thiolactone-functional brush were explored using both sequential and one-pot reactions with bromobenzyl amine and 1H,1H-perfluoro-N-decyl acrylate. X-ray photoelectron spectroscopy and argon gas cluster ion sputter depth profiling enabled quantitative comparison of the sequential and one-pot PPM routes with regard to conversion and spatial distribution of functional groups immobilized throughout thickness of the brush. While one-pot conditions proved to be more effective in immobilizing the amine and acrylate within the brush, the sequenital reaction enabled the fabrication of multifunctional, micropattterned brush surfaces using reactive microcontact printing.


[Clinical significance of Willebrand's factor in allergic dermatoses in children].
An original micromethod for assaying Willebrand's factor (WF) was used to measure the content of the protein in 45 children with different allergic dermatoses. WF measurement were at the height of the clinical manifestations and during remissions. It has been established that children with allergic dermatoses manifest a fairly appreciable increase fo WF in the plasma, which is likely to reflect objectively the systematic nature and gravity of vascular endothelium derangement. The increase of WF correlates with the gravity of the clinical manifestations of the disease. As the clinical symptoms were being removed, the level of WF was progressively decreasing. Its normalization attests to a genuine arrest of allergic vasculitis. Platelet activation detected in all the forms of allergic dermatoses in the basis for inclusion of antiaggregation agents into those patients' treatment.


Palliative care experience and training of Scottish general practitioner trainees.
(a) To establish the clinical experience of Scottish general practice trainees in palliative care. (b) To establish the extent of their training in the discipline. (c) To elicit their views on home care. Postal questionnaire survey. Forty-seven trainee general practitioners attending the Scottish National Trainees Conference in Aberdeen in February 1995. Experience of palliative care in hospital and in general practice and training received in each setting. Perception of need for further training. Views on home care.


The place of enucleation and enucleo-resection in the treatment of pancreatic metastasis of renal cell carcinoma.
Renal cell carcinoma has shown less response to systemic therapies including chemotherapy, radiotherapy and immunotherapy than other cancers. Metastasis of renal cell carcinoma to the pancreas occurs, even after long term radical nephrectomy, surgical resection remains the only potentially curative intervention. We performed surgery for pancreatic metastatic renal cell carcinoma and analyzed the results. We retrospectively analyzed 11 patients who had undergone pancreatic resection or metastasectomy at our hospital from January 1994 to January 2010. Patient's demographics, clinical variables, types of pancreatic resections (standard or atypical resection), primary histopathology, surgical outcomes, survival and disease free interval were examined. We compared the standard pancreatic resection to atypical resection (enucleation or enucleo-resection). Eleven patients underwent 14 pancreatic resections or metastasectomy (3 pancreaticoduodenectomy, 4 distal pancreatectomy, 1 completion of pancreatectomy, 4 enucleations and two enucleo-resections) for pancreatic renal cell carcinoma metastasis. The median age was 73 years, the median time period between nephrectomy and finding of pancreatic metastasis was 11.4 years. One patient showed synchronous pancreatic metastatic lesions on radiology. One patient died from a splenic artery pseudoaneurysm rupture 35 days after the surgery. Major complications occurred in 4 patients with standard resection (one hemoperitoneum, three pancreatic fistulas), and in one patient with atypical resection (duodenal fistula); six patients with standard resection presented postoperative diabetes mellitus. Median survival age was 6.5 years (range 1-9 years). Two patients died of metastatic disease 5 to 6 years, while 7 patients are alive and well 1 to 9 years after surgery. According to these results and regardless of the small number of cases, atypical resection of metastatic renal cell carcinoma has a high median survival rate even after pancreatic recurrence or distant metastasis. It seems reasonable to favor a good quality of life and less diabetes with a limited atypical resection.


[French ccAFU guidelines - Update 2018-2020: Management of kidney cancer].
To update the French guidelines on kidney cancer. A systematic review of the literature between 2015 and 2018 was performed. The most relevant articles regarding the diagnosis, the classification, surgical treatment, medical treatment and follow-up of kidney cancer were retrieved and included in the new guidelines. The guidelines were updated with corresponding levels of evidence. Thoraco-abdominal CT scan with injection is the best radiological exam for the diagnosis of kidney cancer. MRI and contrast ultrasound can be useful in some cases. Percutaneous biopsy is recommended when histological results will affect clinical decision. Renal tumours must be classified according to pTNM 2017 classification and ISUP grade. Metastatic kidney cancers must be classified according to IMDC criteria. Partial nephrectomy is the recommended treatment for T1a tumours and can be done through an open, laparoscopic or robotic access. T1b tumours can be treated by partial or total nephrectomy according to tumour complexity. Radical nephrectomy is the recommended treatment of advanced localized tumours. In metastatic patients: cytoreductive nephrectomy is recommended in case of good prognosis; medical treatment must be offered first in case of intermediate or bad prognosis. Surgical or local treatment of metastases should be considered in case of solitary lesion or oligo-metastases. First-line recommended drugs in metastatic patients include sunitinib, pazopanib, and the association nivolumab/ipilimumab. Cabozantinib can be offered in option in intermediate and bad prognostic patients. Cystic tumours must be classified according to Bosniak Classification. Surgical excision should be offered to patients with Bosniak III and IV lesions. It is recommended to follow patients clinically and with imaging according to tumour aggressiveness. These updated recommendations should assist French speaking urologists for their management of kidney cancers.


RIPASA versus Alvarado score in the assessment of acute appendicitis: A prospective study.
This study aimed to compare Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) and Alvarado scoring to accurately identify acute appendicitis. A cross-sectional prospective study was carried out in the department of surgery. Patients were enrolled and scored using RIPASA and Alvarado scoring systems. Appendectomy was done, and the specimen was sent for histopathology examination, which was used as the gold standard for diagnosis. Among 400 recruits, 11 patients were lost to follow-up, giving us a sample size of 389 patients. The cut-off value for RIPASA and Alvarado scores was 7.5 and 7.0, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in diagnosing acute appendicitis of both scores were analyzed using SPSS. Among 389 patients, 256 (66%) were males, and 277 (71%) were under the age of 40 years. RIPASA was more than 7.5 in 345 cases, while Alvarado was more than 7.0 in 261 patients. RIPASA score had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 95.8%, 87.9%, 98.9%, and 65.9%, respectively. In contrast, the ALVARADO score was 71.1% sensitive and 75.8% specific. RIPASA had a diagnostic accuracy of 95.12%, while Alvarado was only 71.46% accurate in diagnosing acute appendicitis. Compared to the Alvarado scoring system, RIPASA is a better tool in terms of accuracy, sensitivity, and specificity for diagnosing acute appendicitis.


Lupus antibodies to the HMGB1 chromosomal protein: epitope mapping and association with disease activity.
The high mobility group box 1 (HMGB1) protein is a non-histone chromosomal protein that acts as a potent proinflammatory cytokine when actively secreted from LPS- or TNF-activated macrophages, monocytes, and other cells. Anti-HMGB1/2 antibodies have been previously identified in sera from a high proportion of patients with autoimmune diseases. In this study, we examined anti-HMGB1 antibody titers in sera of patients with systemic rheumatic diseases and the correlations between the presence of anti-HMGB1 antibodies and disease activity in systemic lupus erythematosus (SLE) patients by enzyme-linked immunosorbent assay and western blotting. We detected increases in both the levels and the frequency of anti-HMGB1 antibodies in sera from SLE and polymyositis/dermatomyositis (PM/DM) patients, and observed that the presence of anti-HMGB1 antibodies positively correlates with SLE disease activity index. Through epitope mapping, we found that multiple HMGB1 epitopes were recognised in SLE sera, with the major epitope mapping to box A. Another epitope, the joiner region of HMGB1, was preferentially recognized by SLE sera, but not by PM/DM sera. Collectively, these observations suggest that the presence of anti-HMGB1 antibodies correlates with disease activity in SLE patients.


[A framework for evaluating primary health care in Latin America].
To determine the relevancy of applying the Canadian primary health care (PHC) assessment strategy to Latin America and to propose any modifications that might be needed for reaching a consensus in Latin America. The Delphi method was used to reach a consensus among 29 experts engaged in PHC development or evaluation in Latin America. Four virtual sessions and a face-to-face meeting were held to discuss the PHC evaluation logic model and the seven goals and six conditioning factors that make up the Canadian strategy, as well as any questions regarding the evaluation and indicators. The relevance of each concept was ranked according to the perspective of the Latin American countries. The experts considered the Canadian strategy's objectives and conditioning factors to be highly relevant to assessing PHC in Latin America, though they acknowledged that additional modification would increase relevance. The chief suggestions were to create a PHC vision and mission, to include additional objectives and conditioning factors, and to rework the original set. The objectives that concerned coordination and integrated comprehensive care did not achieve a high degree of consensus because of ambiguities in the original text and multiple interpretations of statements regarding certain aspects of the evaluation. Considerable progress was made on the road to building a PHC evaluation framework for the Region of the Americas. Indicators and information-gathering tools, which can be appropriately and practically applied in diverse contexts, need to be developed.


The current status of endoscopic thyroidectomy in Korea.
We investigate the current status of endoscopic thyroidectomy in Korea. A representative questionnaire was sent to 21 members of the Korean Association of Endocrine Surgeons who were thought to be performing endoscopic thyroidectomy. All the reply letters were collected and analyzed. The response rate was 95%. A total of 1616 cases of endoscopic thyroidectomy were performed from the year 1998 to the year 2005. The patients included 71 men and 1545 women, with a mean age of 36.17 years. The mean operation time was 124.18 minutes and overall length of hospital stay was 4.31 days. Thyroid lobectomy and nodular hyperplasia were the most common procedures and prominent pathologic findings. Axillary approach was the most popular operative approach method. Gas insufflation and skin-lifting gasless method were used in 800 cases and 816 cases, respectively. Postoperative complication rate was 14.2%. Skin paresthesia was the most common complication. Conversion rate to conventional thyroidectomy was 2.2%. Korean experiences show that endoscopic thyroidectomy is a technically safe and feasible procedure. It is considered to be an important surgical tool that can be further progressed and that also has an excellent potential in a management of thyroid neoplasm.


Kinetic studies on urea hydrolysis by immobilized urease in a batch squeezer and flow reactor.
The immobilization of urease on the reticulated polyurethane foam, and the kinetic phenomenon of urea hydrolysis by the resulting immobilized urease in both batch squeezer and circulated flow reactors were studied. Urease was immobilized with bovine serum albumin and glutaraldehyde on polyurethane foam support of 7 to 15 mum thickness. The residual apparent activity of urease after immobilization was about 50%. The good hydrodynamic property and flexibility of polyurethane foam were retained in solution after immobilization. A modified biofilm reactor model was used to describe the kinetic phenomenon of urea hydrolysis in both batch squeezer and circulated flow reactors. The characteristic parameters of the reactor model for both bioreactors were obtained by combining the Rosenbrock optimization method, the Rungs-Kutta method, and the Newton-Raphson method. The best-fit results were in good agreement with the experimental data. This study suggests another application of polyurethane foam in enzyme immobilization and immobilized enzyme reactors, which offers potential for practical applications in various bioreactors.


MUSCULAR HYPERTROPHY AS ATYPICAL INITIAL PRESENTATION OF HYPOTHYROIDISM.
Hypothyroidism is a common endocrine disease with characteristic symptoms and signs such as fatigue, weight gain, intolerance of cold, constipation, depression, mental slowdown and muscle cramps. Myopathic changes are observed in 30-80% of patients with hypothyroidism, but muscular hypertrophy with muscle stiffness has been reported in less than 10% of patients. Hoffmann's syndrome is a specific form of the hypothyroid-associated myopathy, rarely seen. Symptoms of this syndrome include proximal muscle weakness, hypertrophies in extremities, stiffness, muscle cramps, spontaneous muscle pain; and are associated with increased muscle enzymes. These findings can be seen at any time during hypothyroidism. Hofmann's syndrome has a very good prognosis. Its response to hormone replacement therapy is very good. Therefore, in patients with myopathy-like symptoms, considering in the differential diagnosis that the myopathy may be a reflection of hypothyroidism will facilitate the diagnosis and treatment. In this case, we aimed to present together Hashimoto thyroiditis and muscular hypertrophy, which is an atypical presentation of hypothyroidism and rarely seen in the literature, namely Hoffmann's syndrome.


Cleaner wrasse indirectly affect the cognitive performance of a damselfish through ectoparasite removal.
Cleaning organisms play a fundamental ecological role by removing ectoparasites and infected tissue from client surfaces. We used the well-studied cleaning mutualisms involving the cleaner wrasse, Labroides dimidiatus, to test how client cognition is affected by ectoparasites and whether these effects are mitigated by cleaners. Ambon damselfish (Pomacentrus amboinensis) collected from experimental reef patches without cleaner wrasse performed worse in a visual discrimination test than conspecifics from patches with cleaners. Endoparasite abundance also negatively influenced success in this test. Visual discrimination performance was also impaired in damselfish experimentally infected with gnathiid (Crustacea: Isopoda) ectoparasites. Neither cleaner absence nor gnathiid infection affected performance in spatial recognition or reversal learning tests. Injection with immune-stimulating lipopolysaccharide did not affect visual discrimination performance relative to saline-injected controls, suggesting that cognitive impairments are not due to an innate immune response. Our results highlight the complex, indirect role of cleaning organisms in promoting the health of their clients via ectoparasite removal and emphasize the negative impact of parasites on host's cognitive abilities.


SIVA: a hybrid knowledge-and-model-based advisory system for intensive care ventilators.
The Sheffield Intelligent Ventilator Advisor is a hybrid knowledge-and-model-based advisory system designed for intensive care ventilator management. It consists of a top-level fuzzy rule-based module to give the qualitative component of the advice, and a lower-level model-based module to give the quantitative component of the advice. It is structured to offer adaptive patient-specific decision support. It can be operated in either invasive or noninvasive modes depending on the availability of data from invasive clinical measurements. The user can choose between the full-advisory mode and the clinician-directed mode. The advice given by the top-level module has been validated against retrospective real patient data and compared with intensivists expertise and performance under simulation conditions. Closed-loop simulations were performed assuming various clinical scenarios including sudden changes in the patient parameters such as the shunt or deadspace with noise and disturbances. They have shown that the advice given was appropriate and the blood gases resulting from the closed-loop decision support were acceptable. The system was also shown to be tolerant to noise and disturbances. It is implemented in MATLAB/SIMULINK and LabVIEW.


Assessment of seroprevalence of Toxoplasma gondii in blood donors applied to the blood center of Gazi university hospital.
Toxoplasmosis is a life-threatening zoonotic infection in immunosuppressive individuals. Determining the prevalence and seropositivity rates of toxoplasmosis in asymptomatic blood donors is crucial in terms of the risk status of the transmission of this infection to the blood recipients. In this study, the presence and level of the specific Toxoplasma IgG and IgM antibodies in blood donors was investigated by electrochemiluminescence immunoassay (ECLIA). The statistical significance levels between Toxoplasma seropositivity and demographic characteristics of the donors such as age, educational status, raw meat consumption, drinking water supply were examined. Toxoplasma IgG seropositivity was found among the 225 (25.6%) of the donors present in the study group, while IgM seropositivity was detected in 20 donors (2.3%). The number of donors with only IgM (+) was 8 (0.9%). Both IgG and IgM seropositivities were found in 12 donors (1.4%). Our study provides information about Toxoplasma seropositivity based on the samples collected from the donors who were admitted to the blood center of a university hospital in Ankara, Turkey. This study demonstrates that Toxoplasma seropositivity is high in the rural areas and the regions where the education level is low.


Different types of combined training programs to improve postural balance in single and dual tasks in children with intellectual disability.
The study explored the effects of two combined training (Strength-Proprioceptive versus Cognitive-Balance) programs on postural balance during single-task and dual-task conditions in children with intellectual disability. The postural balance and the second cognitive-task performances were evaluated before and after 8-week of training in two groups: Strength-Proprioceptive Group (n = 12) and Cognitive-Balance Group (n = 10). Results showed that, in both groups and regardless of the training effect, the postural balance performance was significantly (p < 0.05) altered in the dual-task condition compared to the single-task one. After-training session, postural balance performance was improved significantly (p < 0.001) for all task conditions. After training session, the second cognitive-task performance was improved in the Strength-Proprioceptive Group (p < 0.001) and Cognitive-Balance Groupe (p < 0.05). In conclusion, the combined training programs, Strength-Proprioceptive and Cognitive-Balance, improved postural balance performance in single-task and dual-task conditions in children with intellectual disability.


The viral aetiology of influenza-like illnesses in Kampala and Entebbe, Uganda, 2008.
As the threat of zoonoses and the emergence of pandemic-prone respiratory viruses increases, there is a need to establish baseline information on the incidence of endemic pathogens in countries worldwide. To investigate the presence of viruses associated with influenza-like illnesses (ILI) in Uganda. A cross-sectional study was conducted in which nasopharyngeal swab specimens were collected from patients diagnosed with ILI in Kampala and Entebbe between 14 August 2008 - 15 December 2008. A multiplex polymerase chain reaction assay for detecting 12 respiratory viruses was used. A total of 369 patients (52.3% females) was enrolled; the median age was 6 years (range 1-70). One or more respiratory viruses were detected in 172 (46.6%) cases and their prevalence were influenza A virus (19.2%), adenovirus (8.7%), human rhinovirus A (7.9%), coronavirus OC43 (4.3%), parainfluenza virus 1 (2.7%), parainfluenza virus 3 (2.7%), influenza B virus (2.2%), respiratory syncytial virus B (2.2%), human metapneumovirus (1.4%), respiratory syncytial virus A (1.1%), parainfluenza virus 2 (0.5%) and coronavirus 229E (0.5%). There were 24 (14.0%) mixed infections. This study identified some of the respiratory viruses associated with ILI in Uganda. The circulation of some of the viruses was previously unknown in the study population. These results are useful in order to guide future surveillance and case management strategies involving respiratory illnesses in Uganda.


[Positive effects of psychoeducation on mental disorders in the Netherlands].
Mental Health First Aid (mhfa) is a psychoeducation program designed to recognize mental health problems in others, to approach and support them and to refer them to appropriate help.
 AIM: To discuss the possible contribution that mhfa can make to the early detection, intervention and destigmatization of mental health problems in the Netherlands.
 METHOD: Description of the characteristics, effectiveness and knowledge gaps of mhfa in the Dutch context based on literature and practice.
 RESULTS: Positive experiences abroad suggest that mhfa can also contribute to early detection, intervention and destigmatization of mental disorders in the Netherlands. Optimization of the program on the local context is important here.
 CONCLUSION: Dutch evaluation- and effect studies are needed to determine whether the positive effects from international research also apply in the Netherlands, whether adults and young people receive early and adequate help thanks to mhfa, and how the stigma surrounding mental disorders can be further reduced.


[Retropharyngeal abscess in children].
A retropharyngeal abscess is a collection of pus located behind the posterior pharyngeal wall. Main symptoms include torticoli, pyrexia and odynodysphagia. It can be secondary to upper airway infections, pharyngeal penetrating trauma or idiopathic. Complications are rare, but may be life-threatening due to airway obstruction or infection's spread to the surrounding structures. Surgery is conducted in case of abscess > 2 cm on CT scan images, complication or worsening of the symptoms. This article presents a clinical case with literature review.


Social competence in children with cochlear implants: is it possible to catch up with their peers?
The objective of this study is to compare social competence skills in children with CI and their normal hearing peers. Forty-six children with normal hearing and 46 children with CI between the ages of 42 and 72 months were included in the control group and study group, respectively. Preschool teachers rated children's social competence in the classroom using the Social Competence and Behavior Evaluation-Preschool Edition. Three subscales constitute the structure of the SCBE-30 scale: anger-aggression, social competence, and anxiety-withdrawal. The analyses showed that there were statistically significant differences between social competence scores of the study group and the control group. However, there was no statistically significant difference between anger-aggression scores and anxiety-withdrawal scores of the study group and the control group. There was a significant correlation found between anger-aggression score and the age of starting rehabilitation. Anger-aggression scores and anxiety-withdrawal scores were similar between children using cochlear implant and normal hearing peers, whereas children with CI show lower social competence abilities than normal hearing peers. Earlier beginning to the rehabilitation programs coincide with lower anger-aggression scores. To the best of our knowledge, this is the first study to reflect these findings more objectively, from the view of teachers.


Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study.
National Comprehensive Cancer Network (NCCN) guidelines for cutaneous melanoma (CM) recommend physicians consider increased surveillance for patients who typically have lower melanoma survival rates (stages IIB-IV as determined by the American Joint Committee on Cancer (AJCC), 8th edition). However, up to 15% of patients identified as having a low recurrence risk (stages I-IIA) experience disease recurrence, and some patients identified as having a high recurrence risk will not experience any recurrence. The 31-gene expression profile test (31-GEP) stratifies patient recurrence risk into low (Class 1) and high (Class 2) and has demonstrated risk-appropriate impact on disease management and clinical decisions. Five-year plans for lab work, frequency of clinical visits, and imaging pre- and post-31-GEP test results were assessed for a cohort of 509 stage I-III patients following an interim subset analysis of 247 patients. After receiving 31-GEP results, 50.6% of patients had a change in management plans in at least one of the following categories-clinical visits, lab work, or surveillance imaging. The changes aligned with the risk predicted by the 31-GEP for 76.1% of patients with a Class 1 result and 78.7% of patients with a Class 2 result. A Class 1 31-GEP result was associated with changes toward low-intensity management recommendations, while a Class 2 result was associated with changes toward high-intensity management recommendations. The 31-GEP can stratify patient recurrence risk in patients with CM, and clinicians understand and apply the prognostic ability of the 31-GEP test to alter patient management in risk-appropriate directions.


Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre.
Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC. DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline. Clinical actionability was defined within the molecular tumour board following European Society for Medical Oncology (ESMO) guidelines for oncogene-addicted NSCLC. Overall survival (OS) was estimated as per the presence of druggable GAs and treatment with targeted therapy. Most patients were males (69.5%) and former or current smokers (86.5%). Median age was 64 years. The most common histological type and tumour stage were lung adenocarcinoma (81%) and stage IV (64%), respectively. Sequencing was feasible in most patients (93.5%) and actionable GAs were found in 26.5% of patients. A high concordance was observed between single-gene testing and TSO500 NGS panel. Patients harbouring druggable GAs and receiving targeted therapy achieved longer OS compared to patients without druggable GAs. Conversely, patients with druggable GAs not receiving targeted therapy had a trend toward shorter OS compared with driver-negative patients. Hybrid capture sequencing using TSO500 panel is feasible to analyse clinical samples from patients with NSCLC and is an efficient tool for screening actionable GAs.


Thermal stability threshold for amyloid formation in light chain amyloidosis.
Light chain (AL) amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR) do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.


Preliminary research informing policy on remote alcohol monitoring in criminal justice: the Scottish experience.
To explore the views of Scottish offenders on the impact of alcohol on their experience of offending and their lives in general. Furthermore, to explore their views on the concept of remote alcohol monitoring (RAM) as a way to address alcohol misuse upon liberation from prison. A convenience sample of 12 serving offenders participated in one of three focus groups. Data were analysed using the principles of thematic analysis. Analysis of the data revealed the significant impact of alcohol on the lives of the participants. Key themes included the amount and frequency of alcohol consumption; the association of alcohol with harm; the association of alcohol with offending; the previous attempts to reduce alcohol consumption and possible reasons for failure; and the views of participants on the utility of RAM in relation to crime prevention. Participants had significant issues with alcohol misuse prior to incarceration that had impacted on their offending and resulted in both health and social harms. Participants were generally positive but pragmatic about RAM, recognising that technology alone may not be enough to change deeply ingrained and addictive behaviours.


Shepard's universal law supported by honeybees in spatial generalization.
An animal that is rewarded for a response in one situation (the S+) is likely to respond to similar but recognizably different stimuli, the ubiquitous phenomenon of stimulus generalization. On the basis of functional analyses of the probabilistic structure of the world, Shepard formulated a universal law of generalization, claiming that generalization gradients, as a function of the appropriately scaled distance of a stimulus from S+, should be exponential in shape. This law was tested in spatial generalization in honeybees. Based on theoretically derived scales, generalization along both the dimensions of the distance from a landmark and the direction to a landmark followed Shepard's law. Support in an invertebrate animal increases the scope of the law, and suggests that the ecological structure of the world may have driven the evolution of cognitive structures in diverse animals.


Hydration properties, soymilk and okara yield of soybean affected by agronomic factors.
The effects of row space and irrigation on 100-seed weight water uptake, leaching loss, soymilk, and okara yield of soybean were investigated. Row space affected leaching loss, whereas irrigation significantly altered 100-seed weight, water uptake, volume change, leaching loss, and the soymilk yield of soybeans. Irrigation on the third day resulted in desirable hydration properties. The soymilk yield significantly correlated (p < 0.01 or 0.05) to the hydration properties, e.g., 100-seed weight, water uptake, volume change, and leaching loss. A predictive regression model (R = 0.860) has been proposed for the soymilk yield.


State health insurance pools: current performance, future prospects.
State health insurance pools have been suggested to help cover the uninsured. Their attraction lies in the theoretical economies of pooling and the limited public role intended for their administration and funding. Almost all existing pools have targeted high health risks, otherwise uninsurable people who can still afford high premiums for conventional, major-medical-style coverage. Enrollments have been low, even relative to the small eligible population, and medical spending high. Little risk pooling or other savings seem to have occurred. Deficits have therefore mounted, necessitating increased assessments on all private health insurers in pool states and indirectly burdening state treasuries as well. Better pools would have to attract a broader mix of risks, actively manage medical spending, or both.


[Childhood cholestasis and bile transporters].
Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults.


Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography.
Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification due to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture, and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here, we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural l-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale.


Yersinia canariae sp. nov., isolated from a human yersiniosis case.
A Gram-negative rod from the Yersinia genus was isolated from a clinical case of yersiniosis in the United Kingdom. Long read sequencing data from an Oxford Nanopore Technologies (ONT) MinION in conjunction with Illumina HiSeq reads were used to generate a finished quality genome of this strain. Overall Genome Related Index (OGRI) of the strain was used to determine that it was a novel species within Yersinia, despite biochemical similarities to Yersinia enterocolitica. The 16S ribosomal RNA gene accessions are MN434982-MN434987 and the accession number for the complete and closed chromosome is CP043727. The type strain is SRR7544370T (=NCTC 14382T/=LMG 31573T).


Automated techniques in pKa determination: Low, medium and high-throughput screening methods.
Drug discovery programs that generate hundreds of new molecular entities need efficient methodologies for physicochemical profiling. Several high-throughput methods for pKa screening have been developed in the last 15 years to determine this key physicochemical parameter. Separation techniques such as HPLC-MS or capillary electrophoresis are particularly well-suited due to their high throughput and capacity to deal with impure or complex samples. In addition, potentiometric and (mostly) UV-metric-based methods (plate-based and automated systems), find their place as very precise methodologies for pKa determination despite of somewhat lower throughput. Finally, pKa prediction software packages are useful estimator tools but, to date, they cannot replace experimental measurements when accurate pKa values are required.


A population study of killer viruses reveals different evolutionary histories of two closely related Saccharomyces sensu stricto yeasts.
Microbes have evolved ways of interference competition to gain advantage over their ecological competitors. The use of secreted killer toxins by yeast cells through acquiring double-stranded RNA viruses is one such prominent example. Although the killer behaviour has been well studied in laboratory yeast strains, our knowledge regarding how killer viruses are spread and maintained in nature and how yeast cells co-evolve with viruses remains limited. We investigated these issues using a panel of 81 yeast populations belonging to three Saccharomyces sensu stricto species isolated from diverse ecological niches and geographic locations. We found that killer strains are rare among all three species. In contrast, killer toxin resistance is widespread in Saccharomyces paradoxus populations, but not in Saccharomyces cerevisiae or Saccharomyces eubayanus populations. Genetic analyses revealed that toxin resistance in S. paradoxus is often caused by dominant alleles that have independently evolved in different populations. Molecular typing identified one M28 and two types of M1 killer viruses in those killer strains. We further showed that killer viruses of the same type could lead to distinct killer phenotypes under different host backgrounds, suggesting co-evolution between the viruses and hosts in different populations. Taken together, our data suggest that killer viruses vary in their evolutionary histories even within closely related yeast species.


Sequential enhancer state remodelling defines human germline competence and specification.
Germline-soma segregation is a fundamental event during mammalian embryonic development. Here we establish the epigenetic principles of human primordial germ cell (hPGC) development using in vivo hPGCs and stem cell models recapitulating gastrulation. We show that morphogen-induced remodelling of mesendoderm enhancers transiently confers the competence for hPGC fate, but further activation favours mesoderm and endoderm fates. Consistently, reducing the expression of the mesendodermal transcription factor OTX2 promotes the PGC fate. In hPGCs, SOX17 and TFAP2C initiate activation of enhancers to establish a core germline programme, including the transcriptional repressor PRDM1 and pluripotency factors POU5F1 and NANOG. We demonstrate that SOX17 enhancers are the critical components in the regulatory circuitry of germline competence. Furthermore, activation of upstream cis-regulatory elements by an optimized CRISPR activation system is sufficient for hPGC specification. We reveal an enhancer-linked germline transcription factor network that provides the basis for the evolutionary divergence of mammalian germlines.


Sero-silence and sero-sharing: managing HIV in serodiscordant heterosexual relationships.
Research shows that couples with differing HIV status can face a number of social, sexual and relationship challenges. Communication is often emphasised as the key to couples' ability to cope with these challenges. Silence by implication becomes positioned as inherently negative, even dysfunctional. The privileging of communication as proper therapeutic adjustment to illness forecloses consideration of the complexities of managing HIV as a serodiscordant couple, let alone any enabling aspects of silence. Drawing on qualitative research interviews with HIV-serodiscordant couples in Australia, this article examines the usefulness of this polarisation between communication and silence and explores alternative ways of understanding silence that might offer useful tools for HIV health workers and researchers.


Distinguishing lymphatics from blood vessels in normal and diseased skin.
If it were true that lymphatics are essential for the removal of macromolecules and in this way the oncotic and hydrostatic pressures within the interstitium are determined; if it were true that lymphatics are the principal pathway for the exit of antigen and of macrophages and hence, important for cell mediated immunity, then on both accounts the lymphatics are of great significance. There must be some anxiety that none of this can be confirmed and that some tissues such as the brain and the eye do not need lymphatic vessels as such. We must also note that in many diseases the lymphatic system seems to be severely disrupted, and yet it is difficult to show that the tissues are severely compromised. One wonders to what extent blood vessels or any other system, such as the mononuclear phagocytic system, can take over the role of the lymphatic. To answer these questions one needs to be able to identify the lymph clearance system as distinct from the blood supply system. Although this is easy in health, it becomes very difficult in disease.


Treatment of Work Type II Congenital First Branchial Cleft Anomalies: A Summary of 35 Cases.
Objective: This study aims to summarize the data and treatment of 35 children with Work type II congenital first branchial cleft anomalies (CFBCAs) to provide significant insights into the correlation between these anomalies and the facial nerve. Methods: A total of 35 children diagnosed with Work type II CFBCAs who received treatment at the Department of Otolaryngology-Head and Neck Surgery at Shenzhen Children's Hospital from August 2017 to March 2023 were analyzed retrospectively. Pearson chi-square tests and Fisher's exact tests were used to examine the relationship between clinical characteristics and the location of the lesion, which included the superficial and deep surfaces as well as the area between the branches of the facial nerve. Results: All 35 children underwent open incision and complete resection of fistulae. During the surgery, the lesions were found to be in the superficial facial nerve in 12 (34.3%) cases, between branches in 5 (14.3%) cases, and in the deep facial nerve in 18 (51.4%) cases. In those patients, lesions in females, with a lower edge of the lesion located below the angle of the mandible and the presence of a tympanic membranous attachment, are more likely to be located deep to the facial nerve or between its branches. The difference is statistically significant (P = .007, .032, .015). Conclusion: The treatment principle of Work type II CFBCAs consists of achieving a quiescent stage of inflammation, followed by a complete resection of the lesion on the premise of preserving facial nerve function. Certain clinical features of this disease can predict the relationship between the lesion and the facial nerve. The lesions in females, with a lower edge of the lesion located below the angle of the mandible, non-cystic type of Olsen, and the presence of tympanic membranous attachment, tend to be located deep to the facial nerve or between its branches.


Novel in vitro assay for the detection of pharmacologic inducers of fetal hemoglobin.
Current techniques for identifying fetal hemoglobin (HbF) inducers are complex and time consuming. We developed a rapid and efficient method for detecting HbF inducers. Our system uses a recombinant DNA construct in which the coding sequences of 2 different luciferase reporter genes, firefly and renilla, are substituted for those of human gamma and beta globin genes, respectively. The activity of these genes can be distinguished by a simple, highly sensitive enzymatic assay in cell lysates. GM979 cells stably transfected with the construct are cultured in the presence of compounds, and their effects are determined by measuring the changes in activity of the 2 luciferase genes. Specific gamma globin gene inducers are recognized by their ability to increase gamma-firefly luciferase (gamma(F)) gene activity significantly more than beta-renilla luciferase (beta(R)) gene activity, identified by an increased ratio of gamma-firefly luciferase activity over total luciferase activity. These results suggest that the use of the 2 luciferase reporter genes provides a simple, highly sensitive, and reproducible system for the detection of compounds that increase gamma-globin gene expression. It can therefore be used for the screening of chemical agents that may have gamma-globin gene inducibility.


Dispersion engineering of a microsphere via multi-layer coating.
Controlling dispersion of a whispering gallery mode resonator is of critical importance for many nonlinear applications, such as frequency comb generation, parametric oscillators, Raman lasers, stimulated Brillouin lasers, and ultrafast optics. Here, we show by numerical and theoretical modeling that dispersion can be strongly engineered in a three-layer-coated microsphere of high, low, and high refractive indices (RIs). We investigate the impact of the coating thickness, the gap between the two high-RI layers, the surrounding medium, and the coating materials on the group-velocity dispersion and discover that the dispersion is controllable over a broad range in both normal and anomalous dispersion regimes. Our approach provides dispersion engineering flexibility in any axisymmetric resonator with a three-layer-coating structure.


DNA cleavage patterns as indicators of genotypic heterogeneity among strains of Acholeplasma and Mycoplasma species.
Electrophoretic patterns of digestion products of Acholeplasma and Mycoplasma DNA by restriction endonucleases were compared. The patterns of Acholeplasma axanthum strains isolated from a variety of hosts and habitats differed markedly from each other, indicating considerable genotypic heterogeneity among strains included in this species. Heterogeneity was less marked among the Acholeplasma oculi strains tested, and was minimal among strains of the avian pathogen Mycoplasma gallisepticum. Strains of Mycoplasma genitalium isolated from the urethra of patients with non-gonococcal urethritis and from the urethra of an experimentally infected chimpanzee yielded identical cleavage patterns, indicating a high degree of genetic homogeneity of these strains. The data support the notion that mycoplasma species of strict host and tissue specificity exhibit marked genetic homogeneity. The advantages and deficiencies of the use of DNA cleavage patterns for classification purposes are discussed.


Not in my backyard: a systematic review of clinicians' knowledge and beliefs about antibiotic resistance.
To systematically review clinicians' knowledge and beliefs about the importance and causes of antibiotic resistance, and strategies to reduce resistance. Four databases were searched (until July 2014), without restrictions on language, setting or study design. Fixed responses (from surveys) were grouped into categories. The proportion of participants who agreed with each category was expressed as median, percentage and IQR. Qualitative data were coded into emergent themes. Quantitative categories and qualitative themes were grouped into four overarching categories that emerged from the data. There were 57 included studies (38 quantitative, 14 qualitative, 5 mixed methods) of 11593 clinicians. Most clinicians (69%, IQR 63%-72%, n=5 studies) had heard of antibiotic resistance and 98% (IQR 93%-99%, n=5 studies) believed it was serious. The proportion who believed it was a problem for their practice (67%, IQR 65%-74%, n=13 studies) was smaller than the proportion who believed it was a problem globally (89%, IQR 85%-97%, n=5 studies) or nationally (92%, IQR 88%-95%, n=21 studies). Most believed excessive antibiotic use (97%, IQR 91%-98%, n=12 studies) and patient non-adherence (90%, IQR 82%-92%, n=7 studies) caused resistance. Most knew of strategies to reduce resistance (e.g. clinician education, 90%, IQR 85%-96%, n=7 studies). Qualitative findings support these data: they attributed responsibility for antibiotic resistance to patients, other countries and healthcare settings; resistance was considered a low priority and a distant consequence of antibiotic prescribing. Clinicians believe antibiotic resistance is a serious problem, but think it is caused by others. This needs to be accommodated in interventions to reduce antibiotic resistance.


Negative regulation of germination-arrest factor production in Pseudomonas fluorescens WH6 by a putative extracytoplasmic function sigma factor.
Pseudomonas fluorescens WH6 secretes a germination-arrest factor (GAF) that we have identified previously as 4-formylaminooxyvinylglycine. GAF irreversibly inhibits germination of the seeds of numerous grassy weeds and selectively inhibits growth of the bacterial plant pathogen Erwinia amylovora. WH6-3, a mutant that has lost the ability to produce GAF, contains a Tn5 insertion in prtR, a gene that has been described previously in some strains of P. fluorescens as encoding a transmembrane regulator. As in these other pseudomonads, in WH6, prtR occurs immediately downstream of prtI, which encodes a protein homologous to extracytoplasmic function (ECF) sigma factors. These two genes have been proposed to function as a dicistronic operon. In this study, we demonstrated that deletion of prtI in WT WH6 had no effect on GAF production. However, deletion of prtI in the WH6-3 mutant overcame the effects of the Tn5 insertion in prtR and restored GAF production in the resulting double mutant. Complementation of the double prtIR mutant with prtI suppressed GAF production. This overall pattern of prtIR regulation was also observed for the activity of an AprX protease. Furthermore, reverse transcription quantitative real-time PCR analysis demonstrated that alterations in GAF production were mirrored by changes in the transcription of two putative GAF biosynthetic genes. Thus, we concluded that PrtI exerted a negative regulatory effect on GAF production, although the mechanism has not yet been determined. In addition, evidence was obtained that the transcription of prtI and prtR in WH6 may be more complex than predicted by existing models.


Sunlight Inactivation of Enveloped Viruses in Clear Water.
Enveloped virus fate in the environment is not well understood; there are no quantitative data on sunlight inactivation of enveloped viruses in water. Herein, we measured the sunlight inactivation of two enveloped viruses (Phi6 and murine hepatitis virus, MHV) and a nonenveloped virus (MS2) over time in clear water with simulated sunlight exposure. We attenuated UV sunlight wavelengths using long-pass 50% cutoff filters at 280, 305, and 320 nm. With the lowest UV attenuation tested, all decay rate constants (corrected for UV light screening, k̂) were significantly different from dark controls; the MS2 k̂ was equal to 4.5 m2/MJ, compared to 16 m2/MJ for Phi6 and 52 m2/MJ for MHV. With the highest UV attenuation tested, only k̂ for MHV (6.1 m2/MJ) was different from the dark control. Results indicate that the two enveloped viruses decay faster than the nonenveloped virus studied, and k̂ are significantly impacted by UV attenuation. Differences in k̂ may be due to the presence of viral envelopes but may also be related to other differing intrinsic properties of the viruses, including genome length and composition. Reported k̂ values can inform strategies to reduce the risk from exposure to enveloped viruses in the environment.


[Psychosocial factors as risk for coronary heart disease--status with special reference to the KORA platform].
Psychosocial factors derived from concepts in health psychology and psychopathology are subject of extensive research to assess their power to predict a future coronary artery disease event in apparently healthy subjects. However, bio-behavioural factors have not been implemented in current guidelines of scoring schemes for calculating the risk of coronary events. The presented data were derived from the population-based MONICA Augsburg studies (S1-S3) conducted between 1984 and 1995. The psychosocial data set was available in approximately 13,000 subjects. The KORA follow-up study assessed the vital status for all participants (except for 56 persons) in 1998. Until then, 772 participants (531 men, 241 women) had died. The depressive symptomatology was derived from the von Zerrssen affective symptom check list combining 24 single symptom items with scores ranging from 0 to 3. Risks of total mortality and myocardial infarction were estimated from Cox proportional hazard ratio (HR) models adjusted for age and survey and multiple risk factors. Male participants with high scores in depression exhibited a significantly increased risk in total mortality (adjusted HR: 1.55; 95 % CI: 1.28 - 1.83, p < 0.0001) and for fatal and non-fatal coronary events (adjusted HR: 1.36; 95 % CI: 1.02 - 1.81, p < 0.035). Female participants reported higher values in depression scores; however, depression was not predictive for subsequent total mortality and fatal and non-fatal events in females. Depression in men yielded a significant interaction with obesity and increased levels of C-reactive protein (CRP). The inclusion of psychosocial factors, as demonstrated for depression, is likely to improve prediction of future adverse cardiovascular and total mortality. These factors may also play a crucial role in genotype-phenotype interaction.


Patient safety: why does the NHS always seem to get a bad press?
John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, considers different viewpoints on patient safety issues.


High platelet turnover and reactivity in renal transplant recipients patients.
Renal transplant recipients (RTRs) patients are at increased risk of cardiovascular morbidity and mortality. We aimed this study to assess reticulated platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA) treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the percentage of RP of the total optical platelet count (immature platelet fraction; IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA) induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 μM ADP (ADP2-PA and ADP10-PA) and 2 μg/ml collagen (Coll-PA). vWF levels were measured by using a miniVidas analyser. Group A and group B showed significant higher values of RP than controls. At a multiple linear regression analysis IPF and IPF# were significantly and positively related to collagen-PA. By analysing group B according to residual platelet reactivity (RPR), we observed a significant higher number of RP among patients with RPR by collagen. Moreover at a multiple logistic regression analysis, IPF# significantly affected the risk of having a RPR by collagen. With regard to vWF, RTRs patients showed higher levels than control subjects. We documented a higher platelet turn-over in both groups of RTRs patients and increased platelet reactivity in RTRs patients not on ASA therapy than controls.


Development and applications of the Veterans Health Administration's Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide.
Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record