Functional status outcomes in mothers with and without postpartum depression.
Our objective was to compare functional status between women with and without postpartum depression (PPD). A two-group cross-sectional design compared functional status between 23 women with and 23 women without PPD. Participants were 6 to 26 weeks postpartum and from obstetric practices in the northeastern United States. Structured clinical interviews were used to establish diagnoses of PPD. Participants were matched on type of delivery, weeks postpartum, and parity. Participants compared current functioning to prepregnancy functioning using the Inventory of Functional Status After Childbirth. The Postpartum Depression Screening Scale was used to measure PPD severity. Hierarchical multiple and logistic regression models were used to analyze data. We found that after controlling for infant gender, number of nighttime infant awakenings, and income, PPD predicted lower personal (P < .001), household (P < .05), and social functioning (P < .001), but no difference in infant care. Women with PPD were 12 times less likely to achieve prepregnancy functional levels. We conclude that interventions are needed to address household, social, and personal functioning in women with PPD. Clinicians may find functional assessment is a useful adjunct and a less threatening way to screen and monitor treatment for PPD.


Interactions Between Child Personality and Parenting in Relation to Child Well-Being: Support for Diathesis-Stress and Differential Susceptibility Patterns.
It is well-recognized that the individual characteristics of children moderate the effects of developmental conditions on the well-being of a child. The majority of interactions follow a diathesis-stress pattern; there is also evidence for differential susceptibility and vantage sensitivity models. The present study aimed to examine interactions between parenting and child personality in relation to the well-being of a Russian child and to evaluate the models for moderated relationships. Participants were primary caregivers of 370 children aged 2-7 years. Moderation effects were examined using hierarchical multiple regression and bivariate linear models. In order to differentiate between the models of environmental sensitivity, the analysis of regions of significance was used. Consistent with a diathesis-stress framework, the results revealed that among children low in conscientiousness and high in activity, punitive parenting was a risk factor for externalizing problems; among introverted and fearful children, punitive parenting was a risk factor for internalizing problems. Positive parenting/involvement was a protective factor for internalizing behavior, only for children low in openness. The findings also demonstrate the following evidence for the differential susceptibility model: children low in Beta higher-order personality trait (also known as plasticity or personal growth) showed more total problems when faced with low positive parenting, but fewer problems when experiencing high-quality parenting.


Apolipoprotein E genotype does not predict decline in intelligence in healthy older adults.
There is evidence of a genetic influence on the decline in cognitive performance of older adults, although the mechanisms responsible are unknown. A group of 767 subjects of the Manchester University Age and Cognitive Performance longitudinal study volunteer group, followed up from 1985 to the present, were genotyped for apolipoprotein E (APOE). The data from this were related to cross-sectional and longitudinal trends in the Heim intelligence test score (AH4-1) using previously reported random-effects models (Neuropsychologia 39 (2001) 532). There were no significant differences in mean scores for presence compared with absence of the APOE4 or APOE2 genotypes (P=0.48 and P=0.51, respectively). This research does not demonstrate a link between intelligence and APOE genotype in older adults.


Disparate Mutations Confer Therapeutic Gain of Hsp104 Function.
Hsp104, a protein disaggregase from yeast, can be engineered and potentiated to counter TDP-43, FUS, or α-synuclein misfolding and toxicity implicated in neurodegenerative disease. Here, we reveal that extraordinarily disparate mutations potentiate Hsp104. Remarkably, diverse single missense mutations at 20 different positions interspersed throughout the middle domain (MD) and small domain of nucleotide-binding domain 1 (NBD1) confer a therapeutic gain of Hsp104 function. Moreover, potentiation emerges from deletion of MD helix 3 or 4 or via synergistic missense mutations in the MD distal loop and helix 4. We define the most critical aspect of Hsp104 potentiation as enhanced disaggregase activity in the absence of Hsp70 and Hsp40. We suggest that potentiation likely stems from a loss of a fragilely constrained autoinhibited state that enables precise spatiotemporal regulation of disaggregase activity.


Nucleotide in monomeric actin regulates the reactivity of the thiol groups.
A new thiol reagent, 2,4-dinitrophenyl glutathionyl disulfide, allowed the characterization of four thiol groups in monomeric actin by stoichiometric reaction. The number of thiol groups exposed to the reagent was found to depend on the nucleotide bound. In the absence of ATP, G-actin exposed four thiol groups ( G4s ). On the addition of ATP (1 equiv), three of them were shielded. The resulting actin with one thiol group exposed ( G1s ) is the form of monomeric actin normally produced by depolymerization of F-actin in buffers containing ATP. G1s is stable over hours, while G4s , i.e., monomeric actin in ATP-free solution, is not. This must be concluded from the fact that the shielding effect of thiol groups induced by addition of ATP was lost within ca. 30 min probably due to denaturation of G4s to G4s *. Therefore, denaturation of monomeric actin must be understood in terms of loss of thiol shielding, rather than by oxidation of the thiol groups. Addition of equimolar amounts of Ca2+ significantly retarded the denaturation process. ADP (50 equiv) shielded only ca. two of the four thiol groups but, similar to ATP, protected actin from denaturation. Three ATP analogues (10 equiv) were tested but had no shielding effect. In the presence of these analogues actin ( G4s ) rapidly denatured (to G4s *) as in the absence of added nucleotides. It was shown that the thiol-shielding activity and the protective capacity of a nucleotide are interrelated with its binding capability to monomeric actin. G1s was found to be polymerizable as was G approximately 2s on the addition of ATP. No polymerization could be detected for G4s or G4s *.(ABSTRACT TRUNCATED AT 250 WORDS)


TRAIL-Expressing Monocyte/Macrophages Are Critical for Reducing Inflammation and Atherosclerosis.
Circulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) levels are reduced in patients with cardiovascular disease, and TRAIL gene deletion in mice exacerbates atherosclerosis and inflammation. How TRAIL protects against atherosclerosis and why levels are reduced in disease is unknown. Here, multiple strategies were used to identify the protective source of TRAIL and its mechanism(s) of action. Samples from patients with coronary artery disease and bone-marrow transplantation experiments in mice lacking TRAIL revealed monocytes/macrophages as the main protective source. Accordingly, deletion of TRAIL caused a more inflammatory macrophage with reduced migration, displaying impaired reverse cholesterol efflux and efferocytosis. Furthermore, interleukin (IL)-18, commonly increased in plasma of patients with cardiovascular disease, negatively regulated TRAIL transcription and gene expression, revealing an IL-18-TRAIL axis. These findings demonstrate that TRAIL is protective of atherosclerosis by modulating monocyte/macrophage phenotype and function. Manipulating TRAIL levels in these cells highlights a different therapeutic avenue in the treatment of cardiovascular disease.


Discrimination between the enantiomers of carvone and of terpinen-4-ol odorants in normal rats and those with lesions of the olfactory bulbs.
We assessed (1) whether the enantiomers of terpinen-4-ol, odorants that activate nearly identical areas of the olfactory bulb, are more difficult to discriminate than those of carvone, odorants that activate different areas of the olfactory bulb, and (2) whether olfactory bulb lesions that disrupt the pattern of bulbar activation produced by these enantiomers degraded the ability of rats to discriminate between them. In psychophysical tests, normal rats discriminated between the enantiomers of terpinen-4-ol and of carvone equally well. Surgical lesions that removed the majority of bulbar glomeruli activated by these odorants (as demonstrated in previous olfactory bulb studies using intrinsic optical imaging and 2-deoxyglucose) resulted in increased detection thresholds but few or no deficits in discriminating between suprathreshold concentrations of the enantiomers. These results fail to confirm predictions based on 2-deoxyglucose maps of bulbar activity that enantiomers of terpinen-4-ol should be more difficult to discriminate than those of carvone and that the ability to discriminate between enantiomers of an odorant are based on differences in patterns of bulbar activation revealed in such maps.


Preclinical evaluation of multi antigenic HCV DNA vaccine for the prevention of Hepatitis C virus infection.
Direct-acting antiviral treatment for hepatitis C virus (HCV) infection is costly and does not protect from re-infection. For human and chimpanzees, recovery from acute HCV infection correlates with host CD4+ and CD8+ T cell responses. DNA plasmids targeting the HCV non-structural antigens NS3, NS4, and NS5, were previously reported to induce robust and sustained T cell responses in mice and primates. These plasmids were combined with a plasmid encoding cytokine IL-28B, together named as VGX-6150. The dose-dependent T cell response and safety of VGX-6150 administered intramuscularly and followed by electroporation was assessed in mice. Immune responses plateaued at 20 μg/dose with IL-28B demonstrating significant immunoadjuvant activity. Mice administered VGX-6150 at 40, 400, and 800 μg given either as a single injection or as 14 injections given bi-weekly over 26 weeks showed no vaccine related changes in any clinical parameter compared to placebo recipients. There was no evidence of VGX-6150 accumulation at the injection site or in any organ 1 month following the 14th vaccination. Based on these studies, the approximate lethal dose (ALD) exceeds 800 μg/dose and the NOAEL was 800 μg/dose in mouse. In conclusion, VGX-6150 appears safe and a promising preventive vaccine candidate for HCV infection.


Optimizing antiviral agents for hepatitis B management in malignant lymphomas.
The global scale of hepatitis B infection is well known but its impact is still being understood. Missed hepatitis B infection impacts lymphoma therapy especially increased risk of hepatitis B virus (HBV) reactivation and poor treatment outcomes. The presence of undiagnosed chronic hepatitis also undermines chronic HBV screening methods that are based on a positive HBsAg alone. The goal of this review is to evaluate the literature for optimizing antiviral therapy for lymphoma patients with HBV infection or at risk of HBV reactivation. Relevant articles for this review were identified by searching PubMed, Embase, Ovid Medline, and Scopus using the following terms, alone and in combination: "chronic hepatitis B", "occult hepatitis B", "special groups", "malignant lymphoma", "non-Hodgkin's lymphoma", "Hodgkin's lymphoma", "immunocompromised host", "immunosuppressive agents", "antiviral", "HBV reactivation". The period of the search was restricted to a 15-year period to limit the search to optimizing antiviral agents for HBV infection in malignant lymphomas [2001-2016]. Several clinical practice guidelines recommend nucleos(t)ide analogues-entecavir, tenofovir and lamivudine among others. These agents are best initiated along with or prior to immunosuppressive therapy. Additional methods recommended for optimizing antiviral therapy include laboratory modalities such as HBV genotyping, timed measurements of HBsAg and HBV DNA levels to measure and predict antiviral treatment response. In conclusion, optimizing antiviral agents for these patients require consideration of geographic prevalence of HBV, cost of antiviral therapy or testing, screening modality, hepatitis experts, type of immunosuppressive therapy and planned duration of therapy.


Impact of frailty on mortality after transcatheter aortic valve implantation.
We sought to investigate the relation between frailty indices and 12-month mortality after transcatheter aortic valve implantation (TAVI). We included 101 consecutive patients with severe aortic stenosis who have undergone TAVI. Frailty indices according to Valve Academic Research Consortium-2 recommendations (5-m walk test [5MWT] and hand grip strength) as well as other available scales of frailty (Katz index, Elderly Mobility Scale [EMS], Canadian Study of Health and Aging [CSHA] scale, Identification of Seniors at Risk [ISAR] scale) were assessed at baseline. The primary endpoint was 12-month all-cause mortality. Twelve-month all-cause mortality was 17.8%. According to 5MWT, 17.8% were frail; hand grip test: 6.9%; Katz index: 17.8%; EMS: 7.9%; CSHA scale: 16.9%; and ISAR scale: 52.5%. Associations between frailty indices and 12-month all-cause mortality after TAVI were significant in Cox regression analysis (frail vs not frail, presented as hazard ratio[95%CI] adjusted for logistic EuroSCORE): for 5MWT, 72.38 (15.95-328.44); for EMS, 23.39 (6.89-79.34); for CSHA scale, 53.97 (14.67-198.53); for Katz index, 21.69 (6.89-68.25); for hand grip strength, 51.54 (12.98-204.74); and for ISAR scale, 15.94 (2.10-120.74). Similarly, such relationship was confirmed when 5MWT, EMS, and CSHA were used as continuous variables (hazard ratio [95%CI] adjusted for logistic EuroSCORE: for 5MWT per 1-second increase, 2.55 [1.94-3.37]; for EMS per 1-point decrease, 2.90 (1.99-4.21); and for CSHA per 1-point increase, 3.13 [2.17-4.53]). Our study confirmed a strong predictive ability of most of the proposed frailty indices for 12-month mortality after TAVI. For patients scheduled for TAVI, the use of frailty indices, which are easy and quick to assess on clinical basis but with strong performance, for example, 5MWT, EMS, or hand grip test, may be advocated.


Confinement effect on the low temperature specific heat for ultrathin silicon nanowires: a first principles study.
This work studied the phonon confinement effects at the low temperature specific heat of Si nanowires from first principles using density functional perturbation theory. The nanowires were modeled in the [0 0 1] direction for three different diameters, with the largest cross section being approximately 10 Å. The results indicate the specific heat can be described at low temperatures using a third-grade polynomial of the form c v = λT + βT 2 + γT3, where the coefficients of quadratic and cubic terms are almost nonexistent for small diameters. These terms begin to have relevance at larger diameters. Further analysis shows λ > β > γ, which shows the phonon confinement (λ) and surface atoms (β) become more important than the volumetric contribution (γ) for ultrathin nanowires at low temperatures.


A clinical trial comparing the effect of peer education and orientation program on the anxiety levels of pre-CABG surgery patients.
Background and Objectives: One of the main treatment methods of coronary artery disease is coronary artery bypass graft (CABG) surgery. The anxiety level in patients undergoing this surgery is relatively very high. Thus, reducing anxiety in these patients is an important step toward wellness. This study aimed to compare the effects of peer education (PE) and orientation program (OP) on the anxiety levels of patients before CABG surgery. Material and Methods:This randomized controlled trial was conducted in 2014 at the Mazandaran Heart Center on three groups of 50 persons each: PE, OP, and control (Cl). The anxiety levels of patients in each group were measured one day and one hour before the surgery. All groups received routine education. In addition, the PE group received PE and the OP group received OP. Two questionnaires were used to collect the demographics and the clinical data; and Spielberg state anxiety questionnaire was used to measure the anxiety level. Data from descriptive statistics, chi-square, ANOVA, ANCOVA, Bonferroni, and Fisher exact test were analyzed in SPSS v20 software. Findings: The mean anxiety score before surgery was not significantly different in the three groups (P=0.955). However, after the intervention at 1 h before surgery, the mean anxiety level in the PE and OP group was lower than in the Cl group (P=0.000). However, the mean anxiety score between PE and OP groups showed no significant difference (P=0.051). Conclusion: Both PE and OP group reduced the anxiety naturally developed in a patient before surgery. Although the influence of the PE group was greater in reducing anxiety, the use of this technique in clinical practices required further studies.


Interferon-induced disease in mice and rats.
Treatment of newborn mice with potent mouse interferon preparations resulted in an acute "early" syndrome characterized by inhibition of growth, delay in maturation of several organs, diffuse liver cell necrosis and death. When interferon treatment was discontinued at 1 week of life, mice appeared to recover, but subsequently developed a progressive glomerulonephritis ("late syndrome"). Treatment of newborn rats with potent rat interferon preparations also resulted in inhibition of growth, delay in maturation, and the subsequent development of glomerulonephritis. After infection at birth with lymphocyte choriomeningitis (LCM) virus, most strains of mice developed a similar acute early syndrome and surviving mice subsequently developed glomerulonephritis. We postulated that the endogenous interferon induced by LCM virus early in life was partially responsible for these syndromes. Administration of a potent anti-mouse interferon serum to LCM virus-infected mice neutralized the circulating endogenous interferon and inhibited the development of both the early and late syndromes. Our results suggest that large amounts of exogenous or endogenous interferon at a crucial stage of rapid growth or development of mice and rats can induce lesions in several different organs. Some lesions (i.e. the kidney) only become apparent weeks or even months after exposure to interferon.


[GGT activity in the blood serum of newborn foals after the absorption of a non-species specific colostrum preparation].
Eight vital, new-born foals were additionally administered a non-species-specific colostrum-substitute via stomach-tube within the first 18 hours of their life. The substitute had been made of cattle-colostrum. These foals as well as a control-group of eight foals constantly had free access to maternal colostrum. Object of measurement was GGT-activity in the blood-serum. The increase of GGT-activity within the first 24 hours after birth was very low in the control-group (up to 25 U/l), and very high in the tested animals (418 +/- 182 U/l). Obviously there is a direct connection between this rise and the absorption of colostral GGT which, compared to the mare is raised to a higher power in the cow.


Vertebrobasilar occlusion complicating nonpenetrating craniocervical trauma in a child.
We report a juvenile patient who developed vertebrobasilar occlusion following nonpenetrating head and neck trauma, with complete recovery. The patient presented with transient signs of brain-stem dysfunction that were secondary to embolization and/or extension of a thrombus. He was treated with anticoagulants. We have found no other reports of such treatment in juvenile vertebrobasilar occlusion that complicated nonpenetrating head and neck trauma.


Immunogenomic approaches to understand the function of immune disease variants.
Mapping hundreds of genetic variants through genome wide association studies provided an opportunity to gain insights into the pathobiology of immune-mediated diseases. However, as most of the disease variants fall outside the gene coding sequences the functional interpretation of the exact role of the associated variants remains to be determined. The integration of disease-associated variants with large scale genomic maps of cell-type-specific gene regulation at both chromatin and transcript levels deliver examples of functionally prioritized causal variants and genes. In particular, the enrichment of disease variants with histone marks can point towards the cell types most relevant to disease development. Furthermore, chromatin contact maps that link enhancers to promoter regions in a direct way allow the identification of genes that can be regulated by the disease variants. Candidate genes implicated with such approaches can be further examined through the correlation of gene expression with genotypes. Additionally, in the context of immune-mediated diseases it is important to combine genomics with immunology approaches. Genotype correlations with the immune system as a whole, as well as with cellular responses to different stimuli, provide a valuable platform for understanding the functional impact of disease-associated variants. The intersection of immunogenomic resources with disease-associated variants paints a detailed picture of disease causal mechanisms. Here, we provide an overview of recent studies that combine these approaches to identify disease vulnerable pathways.


Determination of trace metals by anodic stripping voltammetry using a bismuth-modified carbon nanotube electrode.
A bismuth-modified carbon nanotube electrode (Bi-CNT electrode) was employed for the determination of trace lead, cadmium and zinc. Bismuth film was prepared by in situ plating of bismuth onto the screen-printed CNT electrode. Operational parameters such as preconcentration potential, bismuth concentration, preconcentration time and rotation speed during preconcentration were optimized for the purpose of determining trace metals in 0.1M acetate buffer solution (pH 4.5). The simultaneous determination of lead, cadmium and zinc was performed by square wave anodic stripping voltammetry. The Bi-CNT electrode presented well-defined, reproducible and sharp stripping signals. The peak current response increased linearly with the metal concentration in a range of 2-100 microg/L. The limit of detection was 1.3 microg/L for lead, 0.7 microg/L for cadmium and 12 microg/L for zinc (S/N=3). The Bi-CNT electrode was successfully applicable to analysis of trace metals in real environments.


Sex differences in response to amphetamine in adult Long-Evans rats performing a delay-discounting task.
The use of animal models to investigate experimental questions about impulsive behavior can provide valuable insight into problems that affect human health. The delay-discounting paradigm involves subjects choosing between smaller reinforcers delivered immediately and larger reinforcers that are delivered after a delay. This is an important experimental paradigm for examining impulsive choice in both laboratory species and humans. However, a shortcoming of previously published delay-discounting studies in animals is that typically only males were studied, reducing the applicability of these studies to human populations. In the present study, both female and male adult Long-Evans rats were trained to perform a delay-discounting task, with delays of 0, 5, 10, 20 and 40 s before delivery of the larger reinforcer. Because dopaminergic signaling is important in mediating this task, the effects of d-amphetamine and the dopamine receptor antagonist, cis-flupenthixol, on task performance were then examined. The main experimental measure was percent larger-reinforcer choice, which was defined as the percentage of experimental trials at each delay in which the delayed, larger reinforcer was chosen. There was no sex difference in percent larger-reinforcer choice during baseline performance of the task. However, d-amphetamine administration disrupted choice in females, as evidenced by <80% larger-reinforcer choice in half of the females, but none of the males, at 0.5 mg/kg. D-Amphetamine also differentially altered the latency to choose between immediate versus delayed reinforcers in females compared to males. In contrast, cis-flupenthixol did not have a sex-related effect on percent larger-reinforcer choice. These findings parallel the sex differences in response to amphetamine seen in human delay-discounting studies and underscore the importance of evaluating sex-based differences in baseline performance and in response to pharmacologic agents when utilizing animal models.


Organocatalytic Asymmetric Mannich/Aza-Michael Cascade Reaction of δ-Formyl-α,β-unsaturated Ketones with Cyclic N-Sulfimines: Enantioselective Synthesis of Benzosulfamidate-Fused Pyrrolidines.
A catalytic highly enantioselective Mannich/aza-Michael cascade reaction of δ-formyl-α,β-unsaturated ketones with cyclic N-sulfimines, promoted by diphenylprolinol TMS ether as an organocatalyst, has been developed for the synthesis of chiral benzosulfamidate-fused pyrrolidines, which generated in good yields and with high diastero- and enantioselectivities. Further chemical transformations have been performed with chiral benzosulfamidate-fused pyrrolidines.


Staphylococcus sciuri causes disease and pathological changes in hybrid sturgeon acipenser baerii × acipenser schrencki.
Hybrid sturgeon is the main species of sturgeon cultured in China, with the advantages of a fast growth rate, early sexual maturity, fertile offspring, and more stable genetic traits. In May 2021, a large number of deaths characterized by superficial hemorrhage and liver damage occurred in a sturgeon farm in Yichang, Hubei Province, which posed a significant risk to hybrid sturgeon captive breeding. We isolated a pathogenic bacterium named D-59 from the diseased sturgeon with apparent symptoms. The pathogen was identified as Staphylococcus sciuri using 16S rRNA gene phylogenetic analysis combined with biochemical identification. Regression experiments showed that D-59 exhibited clinical signs similar to those of diseased sturgeon in the farm after intraperitoneal injection into hybrid sturgeon. High-throughput sequencing of gut microbes in D-59-infected sturgeon showed that the number of gut microbial species decreased in infected sturgeon, the number of some intestinal commensal bacteria decreased, and the balance of the intestinal microorganisms was disrupted. Histopathological sections indicated many inflammatory cells, congestion, and even necrosis in the tissue of diseased sturgeon. Analysis of blood indexes revealed an increase in the proportion of mononuclear cells and a decrease in the proportion of lymphocytes in the peripheral blood of diseased sturgeon. Significantly elevated serum levels of aspartate aminotransferase and alanine aminotransferase, whereas alkaline phosphatase, total protein, albumin, and globulin were decreased in diseased sturgeon. Antimicrobial susceptibility tests demonstrated that D-59 is susceptible to florfenicol, enrofloxacin, and neomycin sulfate. This study aimed to highlight the dangers of Staphylococcus sciuri infection during hybrid sturgeon culture and to provide recommendations for diagnosis and treatment.


Multi-Directional Sprint Training Improves Change-Of-Direction Speed and Reactive Agility in Young Highly Trained Soccer Players.
The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180° COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players. Key pointsDuring soccer, the players perform repeated sprints involving multi-directional COD movements, while most of these turns and twists are not pre-planned but executed in response to an external stimulus, such as ball movement, several interacting opponents and changing game situations.Both groups improved performance in the IAT. With the RSmulti on the Speedcourt however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility.The Speedcourt could serve as a valuable method to design and individualize specific conditioning drills for young highly-trained soccer players.


Chromosome Microarray.
Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed.


Where do we go from here? - Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals.
Clinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers' Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce. We conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes. The survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles. Career development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials.


Restrictions on undocumented immigrants' access to health services: the public health implications of welfare reform.
The Personal Responsibility and Work Opportunity Reconciliation Act of 1996 greatly restricts the provision of many federal, state, and local public services to undocumented immigrants. These restrictions have prompted intense debates about the provision of free and discounted primary and preventive health care-services and have placed significant burdens on institutions that serve large undocumented immigrant populations. Intended to serve as a tool for reducing illegal immigration and protecting public resources, federal restrictions on undocumented immigrants' access to publicly financed health services unduly burden health care providers and threaten the public's health. These deleterious effects warrant the public health community's support of strategies designed to sustain provision of health services irrespective of immigration status.


Construct validity of scores/measures from a developmental assessment in mathematics using classical and many-facet Rasch measurement.
Data from a developmental assessment comprised of 9 short answer mathematics tasks were validated using classical and three-faceted Rasch measurement methods. Field test data from a mixed age elementary school sample (N=280) were analyzed. Descriptive statistics on scores from the overall scale and two subdomains indicated improved performance with age. The data showed better fit with a two-factor model corresponding with the subdomain structure (Bentler's CFI=.94), than a one factor model (CFI=.87). The inter-factor correlation was.76. Convergent validity coefficients of scores with scaled scores of the Stanford AchievementTest mathematics battery ranged from.28 to.47; internal consistency reliability of the total and subdomain scores ranged from.87 to.89, respectively; and median inter-rater reliability was.75. On average, persons, tasks and raters showed acceptable fit with the three-facet Rasch model. Rasch logit difficulties of tasks suggested an ordered scale structure, although tasks tended to have high difficulty levels. The original and calibrated task ordering was consistent at the extreme ends of the scale. Gaps identified on the Rasch item map suggested a need for additional task construction. Conceptual and procedural differences in each technique are considered in deciding future improvements to the scale.


Through the eyes of a new dad: experiences of first-time fathers of late-preterm infants.
Fathers of late-preterm (34-36 weeks' gestation) infants may experience challenges in parenting. Late-preterm infants are more irritable and less responsive in interactions. The unexpected early birth of an infant may negatively affect fathers' cognitive and emotional experiences. The Father-Infant Interaction Program (FIIP) is a video-modeled play intervention that aims to increase fathers' sensitivity and responsiveness to infant cues. Using data from a larger randomized controlled trial (RCT) to evaluate FIIP, the purpose of the present study was to explore the experiences of first-time fathers of late-preterm infants and their perceptions of the intervention. We conducted semistructured qualitative interviews with 85 fathers of 8-month-old infants during the outcome home visit for the RCT and thematically analyzed data. Three main themes about fathers' experiences emerged: Fathers believed they had the "best job in the world," yet saw fathering as the "biggest job ever." Fathers viewed fatherhood as an opportunity for personal growth and reflected on how their lives had changed since the arrival of their infant. Fathers in the intervention and comparison groups liked the convenience of the home visits and validation of their role as a father. Fathers in the intervention group liked the tailored feedback about play.


Increased fecal bile acid excretion and changes in the circulating bile acid pool are involved in the hypocholesterolemic and gallstone-preventive actions of psyllium in hamsters.
The lipid-lowering effect of psyllium (PSY) is well established. Enhanced fecal bile acid excretion and a stimulation of hepatic bile acid synthesis are discussed as primary mechanisms of this action. To further examine the effect of bile acid excretion and specifically of compositional alterations in the bile acid pool on the cholesterol-lowering and gallstone-preventing action of PSY, male golden Syrian hamsters were fed lithogenic diets containing 5 g/100 g fat, 0.4 g/100 g cholesterol and 0 (control), 4 or 6% PSY or 1% cholestyramine (CHY). PSY significantly lowered plasma total cholesterol and triacylglycerol at a magnitude comparable to that induced by CHY. Although hepatic cholesteryl ester accumulation was completely inhibited by CHY, PSY did not prevent the hepatic storage of esterified cholesterol. PSY and CHY caused distinct alterations in the bile acid profile. PSY caused a selective reduction of taurine-conjugated bile acids, especially of taurochenodeoxycholate. As a result, the glycine:taurine conjugation and the cholate:chenodeoxycholate ratios were significantly higher in PSY-fed hamsters. PSY and CHY normalized the lithogenic index and prevented cholesterol gallstone formation compared with controls. Daily fecal bile acid excretion was approximately 400% greater in hamsters fed 6% PSY, whereas CHY caused an 11-fold increase. Daily neutral sterol excretion did not differ in PSY-fed hamsters but was >100% greater in those fed CHY than in controls. These data emphasize the potent lipid-lowering effect of PSY. Increased fecal bile acid excretion and alterations of the circulating bile acid pool by removal of dihydroxy bile acids (e.g., taurochenodeoxycholate) appear to be main modulators of the hypocholesterolemic action of PSY by leading to an up-regulation of hepatic bile acid synthesis.


Genetic architectures of cerebral ventricles and their overlap with neuropsychiatric traits.
The cerebral ventricles are recognized as windows into brain development and disease, yet their genetic architectures, underlying neural mechanisms and utility in maintaining brain health remain elusive. Here we aggregated genetic and neuroimaging data from 61,974 participants (age range, 9 to 98 years) in five cohorts to elucidate the genetic basis of ventricular morphology and examined their overlap with neuropsychiatric traits. Genome-wide association analysis in a discovery sample of 31,880 individuals identified 62 unique loci and 785 candidate genes associated with ventricular morphology. We replicated over 80% of loci in a well-matched cohort of lateral ventricular volume. Gene set analysis revealed enrichment of ventricular-trait-associated genes in biological processes and disease pathogenesis during both early brain development and degeneration. We explored the age-dependent genetic associations in cohorts of different age groups to investigate the possible roles of ventricular-trait-associated loci in neurodevelopmental and neurodegenerative processes. We describe the genetic overlap between ventricular and neuropsychiatric traits through comprehensive integrative approaches under correlative and causal assumptions. We propose the volume of the inferior lateral ventricles as a heritable endophenotype to predict the risk of Alzheimer's disease, which might be a consequence of prodromal Alzheimer's disease. Our study provides an advance in understanding the genetics of the cerebral ventricles and demonstrates the potential utility of ventricular measurements in tracking brain disorders and maintaining brain health across the lifespan.


Determination of pesticides in water by cone-shaped membrane protected liquid phase microextraction prior to micro-liquid chromatography.
A new sample pre-treatment technique termed cone-shaped membrane liquid phase microextraction (CSM-LPME) was developed and combined with micro-liquid chromatography (micro-LC) for the determination of selected pesticides in water samples. Four pesticides (hexaconazole, procymidone, quinalphos and vinclozolin) were considered as target analytes. Several important extraction parameters such as types of extraction solvent, agitation rate, pH value, total exposure time and effect of salt and humic acids were optimized. Enrichment factors of > 50 folds were easily achieved within 20 min of extraction. The analytical data demonstrated relative standard deviations for the reproducibility of the optimized CSM-LPME method ranging from 6.3 to 7.5%. The correlation coefficients of the calibration curves were at least 0.9995 across a concentration range of 2-100 microg/L. The detection limits for all the analytes were found to be in the range of 1.1-1.9 microg/L.


The cycle effect quantified: reduced tumour uptake in subsequent cycles of [177Lu]Lu-HA-DOTATATE during peptide receptor radionuclide therapy.
Clear evidence regarding the effect of reduced tumour accumulation in later peptide receptor radionuclide therapy (PRRT) cycles is lacking. Therefore, we aimed to quantify potential cycle effects for patients treated with [177Lu]Lu-HA-DOTATATE using a population pharmacokinetic (PK) modelling approach. A population PK model was developed using imaging data from 48 patients who received multiple cycles of [177Lu]Lu-HA-DOTATATE. The five-compartment model included a central, kidney, spleen, tumour and lumped rest compartment. Tumour volume and continued use of long-acting somatostatin analogues (SSAs) were tested as covariates in the model. In addition, the presence of a cycle effect was evaluated by relating the uptake rate in a specific cycle as a fraction of the (tumour or organ) uptake rate in the first cycle. The final PK model adequately captured observed radioactivity accumulation in kidney, spleen and tumour. A higher tumour volume was identified to increase the tumour uptake rate, where a twofold increase in tumour volume resulted in a 2.3-fold higher uptake rate. Also, continued use of long-acting SSAs significantly reduced the spleen uptake rate (68.4% uptake compared to SSA withdrawal (10.5% RSE)). Lastly, a cycle effect was significantly identified, where tumour uptake rate decreased to 86.9% (5.3% RSE) in the second cycle and even further to 79.7% (5.6% RSE) and 77.6% (6.2% RSE) in the third and fourth cycle, respectively, compared to cycle one. Using a population PK modelling approach, the cycle effect of reduced tumour uptake in subsequent PRRT cycles was quantified. Our findings implied that downregulation of target receptors is probably not the major cause of the cycle effect, due to a plateau in the decrease of tumour uptake in the fourth cycle.


5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA neurotransmission.
1. Intracellular recordings from neurons within dorsal raphe nucleus in slices from rat brain were used to study an inhibitory postsynaptic potential (IPSP) evoked by electrical stimulation. 2. The IPSP was observed in approximately 70% of neurons, had a latency to onset of 40-65 ms, reached a peak in 350-400 ms, had a total duration of 1-2 s, and reversed polarity at the potassium equilibrium potential. 3. This IPSP was blocked by spiperone (1 microM) and prolonged by fluoxetine (300 nM-30 microM) suggesting that it was mediated by 5-hydroxytryptamine (5-HT). 4. Superfusion with gamma-aminobutyric acid (GABA) and excitatory amino acid receptor antagonists were used to block "fast" synaptic potentials that preceded the IPSP such that it could be studied in isolation. Blockade of the GABA-mediated synaptic potentials increased the amplitude of the IPSP by 1.3-fold. The amplitude of the IPSP was reduced by 30% after blockade of the excitatory amino acid-mediated synaptic potential. 5. The results indicate that the IPSP recorded in dorsal raphe neurons was caused by 5-HT released at least in part from indirect (synaptically induced) excitation of 5-HT-containing cells within the slice.


Why contagious yawning does not (yet) equate to empathy.
Various studies and researchers have proposed a link between contagious yawning and empathy, yet the conceptual basis for the proposed connection is not clear and deserves critical evaluation. Therefore, we systematically examined the available empirical evidence addressing this association; i.e., a critical review of studies on inter-individual differences in contagion and self-reported values of empathy, differences in contagion based on familiarity or sex, and differences in contagion among individuals with psychological disorders, as well as developmental research, and brain imaging and neurophysiological studies. In doing so, we reveal a pattern of inconsistent and inconclusive evidence regarding the connection between contagious yawning and empathy. Furthermore, we identify study limitations and confounding variables, such as visual attention and social inhibition. Future research examining links between contagious yawning and empathy requires more rigorous investigation involving objective measurements to explicitly test for this connection.


Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution.
Lineage-specific gene loss, to a large extent, accounts for the differences in gene repertoires between genomes, particularly among eukaryotes. We derived a parsimonious scenario of gene losses for eukaryotic orthologous groups (KOGs) from seven complete eukaryotic genomes. The scenario involves substantial gene loss in fungi, nematodes, and insects. Based on this evolutionary scenario and estimates of the divergence times between major eukaryotic phyla, we introduce a numerical measure, the propensity for gene loss (PGL). We explore the connection among the propensity of a gene to be lost in evolution (PGL value), protein sequence divergence, the effect of gene knockout on fitness, the number of protein-protein interactions, and expression level for the genes in KOGs. Significant correlations between PGL and each of these variables were detected. Genes that have a lower propensity to be lost in eukaryotic evolution accumulate fewer substitutions in their protein sequences and tend to be essential for the organism viability, tend to be highly expressed, and have many interaction partners. The dependence between PGL and gene dispensability and interactivity is much stronger than that for sequence evolution rate. Thus, propensity of a gene to be lost during evolution seems to be a direct reflection of its biological importance.


Effects of Mo Particles Addition on the Microstructure and Properties of 316 L Stainless Steels Fabricated by Laser Powder Bed Fusion.
Application of the 316 L stainless steel (SS) is limited by its relatively low wear resistance, insufficient strength, and poor corrosion resistance in special environments. To this end, effects of Mo particles addition on the microstructure, mechanical properties, and corrosion resistance of the laser powder bed fusion (LPBF) 316 L SS are investigated in this study. The results show that the addition of Mo particles from 0 wt.% to 10 wt.% can modify the crystal orientation and improve the strength, wear resistance, and corrosion resistance of LPBF 316 L SSs. Particularly, the LPBF 316 L SS forms a biphasic structure with a similar ratio of α-Fe to γ-Fe with 5 wt.% Mo addition. As a result, the corresponding samples possess both the excellent toughness of austenitic SSs and the high strength and corrosion resistance of ferrite SSs, which reaches a high tensile strength of about 830 MPa, together with a low friction coefficient of 0.421 μ. Since the Mo particles addition is beneficial to increase the content of Cr2O3 on the samples surface from 13.48% to 22.68%, the corrosion current density of 316 L SS decreases by two orders of magnitude from 569 nA to 6 nA, while the mechanical properties remain favorable. This study is expected to serve as a reference for the preparation of LPBF SSs with excellent integrated performance.


Biosynthesis of phospholipids in Clostridium butyricum: kinetics of synthesis of plasmalogens and the glycerol acetal of ethanolamine plasmalogen.
The biosynthesis of the plasmalogen forms of phosphatidylethanolamine (plasmenylethanolamine) and phosphatidylglycerol (plasmenylglycerol) and of the glycerol acetal of plasmenylethanolamine has been studied in cultures of Clostridium butyricum IFO 3852. When growing cells were pulsed with [32P]orthophosphate, there was a lag of 5 to 7 min between the rapid incorporation of label into the acylphosphatides and the rapid incorporation of label into the corresponding plasmalogens. The labeling of the glycerol acetal of plasmenylethanolamine was even slower. In pulse-chase experiments with 32Pi, the kinetics of labeling indicated precursor-product relationships between phosphatidylethanolamine and plasmenylethanolamine and between the latter and its glycerol acetal. A precursor-product relationship was also seen between phosphatidylglycerol and cardiolipin, but the kinetics of labeling of the alkenyl-containing forms of these lipids were not consistent with direct precursor-product relationships with the acyl lipids. In the presence of hydroxylamine and 32Pi, both phosphatidylserine and plasmenylserine accumulated 32P in a ratio of ca. 15:1. Upon release of the inhibition of phosphatidylserine decarboxylase, label appeared in the following sequence: phosphatidylethanolamine, plasmenylethanolamine, and the glycerol acetal of plasmenylethanolamine. Acyl phosphatidylglycerol was identified as a major phospholipid (17% of lipid phosphorus) in C. butyricum grown in low-phosphate (1.13 mM) medium with 50 mM Tris buffer. Of the acyl phosphatidylglycerol, 13% was acid labile. There appear to be two plasmalogen forms of acyl phosphatidylglycerol. One of these has a single alkenyl ether group, and the other has alkenyl ether groups on both glycerols.


[The use of the medical rehabilitation technology for the correction of microcirculatory disorders in the patients presenting with gonarthrosis].
The objective of the present study was to estimate the efficacy of pulsed laser radiation from a matrix radiator for the treatment of patients suffering osteoarthrosis of the knee joint. A total of 25 patients aged from 50 to 75 years with I-II stage gonarthrosis (GA) were enrolled (20 without synovitis and 5 with mild synovitis). Nineteen patients presented with oligoosteoarthrosis and six with polyosteoarthrosis. The state of capillary blood flow was assessed from the results of laser Doppler flowmetry (LDF) using a LAKK-01 laser analyzer of surface capillary blood flow (NPP "LAZMA", Russia). Prior to the treatment, all the patients with gonarthrosis had microcirculatory disturbances; based on their character, the patients were allocated to two groups in accordance with the classification proposed by V.I. Makolkin. Group 1 was comprised of the patients (92%) with the hyperemic type of microcirculation while group 2 included patients (8%) with its normnnocirculatory type. A single course of pulsed laser therapy resulted in the appearance of the signs of normalization of capillary blood flow. LDF revealed a physiological response of microvessels to pulsed laser radiation that manifested itself in the first place as the improvement of active mechanisms of regulation of microcirculation.


The Efficacy of Calcium Hydroxide Powder mixed with 0.2% Chlorhexidine Digluconate or mixed with Normal Saline as Intracanal Medicament in the Treatment of Apical Periodontitis.
To compare the efficacy of calcium hydroxide powder mixed with 0.2% chlorhexidine digluconate or mixed with normal saline as intracanal medicament in the treatment of apical periodontitis. Subjects were 55 in number aged 17 to 60 years. Two-visit conventional root canal treatment was performed on 70 teeth. The teeth were divided by randomization (balloting) into two groups: control group and experimental group, each with 35 teeth treated with calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate as intracanal medicament respectively. All treated teeth were evaluated clinically and radiographically for signs and symptom of periapical infection at specified periods postoperatively. Overall efficacy of medicament was rated based on quality guidelines for endodontic treatment by the European Society of Endodontology 2006. A postoperative favorable outcome of 97.1% in the control group and 94.3% in the experimental group was observed at 6-month review. This difference was not statistically significant (p > 0.05). The use of normal saline or 0.2% chlorhexidine digluconate to mix calcium hydroxide used as intracanal medicament during endodontic treatment resulted in high postoperative favorable outcomes. Efficacy of 0.2% chlorhexidine digluconate as a vehicle for mixing calcium hydroxide as an intracanal medicament in the treatment of apical periodontitis is comparable to the efficacy of calcium hydroxide mixed with normal saline.


The Effect of Lumbar Spinal Surgery History on Intradiscal O2-O3 Treatment Results in Patients with Lumbar Disk Herniation.
The aim of the present study was to investigate the effect of previous spinal surgery on intradiscal ozone-oxygen (O2-O3) treatment in low back pain associated with lumbar disc herniation (LDH). Patients who underwent intradiscal O2-O3 therapy for LDH-induced low back pain were screened retrospectively from hospital records. To ensure homogenization of participants, patients who had received O2-O3 therapy to L4-L5 and L5-S1 intervertebral discs, those with pre-injection and post-injection month 1 data, and those who completed the first year of treatment were included in the study. Patients who completed the first year of treatment but with missing data were contacted and followed up by phone. Patients who underwent surgery at the same level as the injection level were classified as Group 1 (n=30), and those without surgery were classified as Group 2 (n=43). Pain and disability were measured by Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. There was no statistically significant difference between the pre-injection VAS and ODI scores of the groups (p=0.719 and p=0.108). Group 1 had significantly higher VAS and ODI scores on month 1 and year 1 than Group 2, and statistically significant decreases were seen in VAS and ODI scores in both groups at follow-up (p<0.001 for all). There was no statistically significant difference between month 1 and year 1 VAS evaluations of the groups with respect to ≥50% improvement in pain reduction (p=0.213 and p=0.347). In the present study, the effect of the history of spinal surgery on intradiscal O2-O3 treatment results was investigated. Intradiscal injection was found to be effective for both groups, but more successful results were obtained in patients without surgical history.


Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy.
Oxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte phenotype in vitro. Mice that have undergone partial nephrectomy serve as an experimental model of uremic cardiomyopathy. This study examined the effects on adipocytes of administering a peptide that reduces oxidative stress to the mouse model. A lentivirus vector introduced the peptide NaKtide with an adiponectin promoter into the mouse model of experimental uremic cardiomyopathy, intraperitoneally. Then adipocyte-specific expression of the peptide was assessed for mice fed a standard diet compared with mice fed a western diet enriched in fat and fructose. Partial nephrectomy induced cardiomyopathy and anemia in the mice, introducing oxidant stress and an altered molecular phenotype of adipocytes that increased production of systemic inflammatory cytokines instead of accumulating lipids, within 4 weeks. Consumption of a western diet significantly worsened the adipocyte oxidant stress, but expression of NaKtide in adipocytes completely prevented the worsening. The peptide-carrying lentivirus achieved comparable expression in skeletal muscle, but did not ameliorate the disease phenotype. Adipocyte-specific expression of NaKtide, introduced with a lentiviral vector, significantly ameliorated adipocyte dysfunction and uremic cardiomyopathy in partially nephrectomized mice. These data suggest that the redox state of adipocytes controls the development of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, the oxidative state of adipocytes may be a therapeutic target in chronic renal failure.


High sensitivity multiplex short tandem repeat loci analyses with massively parallel sequencing.
STR typing in forensic genetics has been performed traditionally using capillary electrophoresis (CE). However, CE-based method has some limitations: a small number of STR loci can be used; stutter products, dye artifacts and low level alleles. Massively parallel sequencing (MPS) has been considered a viable technology in recent years allowing high-throughput coverage at a relatively affordable price. Some of the CE-based limitations may be overcome with the application of MPS. In this study, a prototype multiplex STR System (Promega) was amplified and prepared using the TruSeq DNA LT Sample Preparation Kit (Illumina) in 24 samples. Results showed that the MinElute PCR Purification Kit (Qiagen) was a better size selection method compared with recommended diluted bead mixtures. The library input sensitivity study showed that a wide range of amplicon product (6-200ng) could be used for library preparation without apparent differences in the STR profile. PCR sensitivity study indicated that 62pg may be minimum input amount for generating complete profiles. Reliability study results on 24 different individuals showed that high depth of coverage (DoC) and balanced heterozygote allele coverage ratios (ACRs) could be obtained with 250pg of input DNA, and 62pg could generate complete or nearly complete profiles. These studies indicate that this STR multiplex system and the Illumina MiSeq can generate reliable STR profiles at a sensitivity level that competes with current widely used CE-based method.


Health-related quality of life in HIV-infected patients: the role of substance use.
HIV infection and substance use disorders are chronic diseases with complex contributions to health-related quality of life (HRQOL). We conducted a cross-sectional survey of 951 HIV-infected adults receiving care at 14 HIV Research Network sites in 2003 to estimate associations between HRQOL and specific substance use among HIV-infected patients. HRQOL was assessed by multi-item measures of physical and role functioning, general health, pain, energy, positive affect, anxiety, and depression. Mental and physical summary scales were developed by factor analysis. We used linear regression to estimate adjusted associations between HRQOL and current illicit use of marijuana, analgesics, heroin, amphetamines, cocaine, sedatives, inhalants, hazardous/binge alcohol, and drug use severity. Current illicit drug use was reported by 37% of subjects. Mental HRQOL was reduced for current users [adjusted beta coefficient -9.66, 95% confidence interval [(CI]) -13.4, -5.94] but not former users compared with never users. Amphetamines and sedatives were associated with large decreases in mental (amphetamines: beta = -22.8 [95% CI -33.5, -12.0], sedatives: beta = -18.6 [95% CI -26.2, -11.0]), and physical HRQOL (amphetamines: beta = -11.5 [95% CI -22.6, -0.43], sedatives: beta = -13.2 [95% CI -21.0, -5.36]). All illicit drugs were associated with decreased mental HRQOL: marijuana (beta = -7.72 [95% CI -12.0, -3.48]), non-prescription analgesics (beta = -13.4 [95% CI -20.8, -6.07]), cocaine (beta = -10.5 [95% CI -16.4, -4.67]), and inhalants (beta = -14.0 [95% CI -24.1, -3.83]). Facilitating sobriety for patients with attention to specific illicit drugs represents an important avenue for elevating HRQOL in patients living with HIV.


Psychosocial influences on central and peripheral vision and reaction time during demanding tasks.
We examined perceptual deficits hypothesized in a model of stress and injury relationships. An ophthalmologic perimeter was used to measure peripheral and central vision during baseline and demanding task situations for 201 intercollegiate athletes from 10 sports. We conducted analyses of covariance with the stress measures as dependent variables and their appropriate baseline measures as covariates. Performance under demanding tasks deteriorated significantly on all the perceptual variables. Individuals with high negative life events scores experienced greater peripheral narrowing and slower central vision reaction time during stress than did those with life events scores that were low. Men with low social support had more failures to detect cues, and men with high negative life events, low social support, and low coping skills had the lowest perceptual sensitivity. Women with high negative life events and low coping skills had more failures to detect cues. We discuss the findings in terms of how stress responsivity may influence injury risk through changes in perception and attention.


Enhanced UV-induced skin carcinogenesis in transgenic mice overexpressing proprotein convertases.
The proprotein convertases (PCs) furin and PACE4 process numerous substrates involved in tumor growth, invasion, and metastasis. We have previously shown that PCs increase the susceptibility to chemical skin carcinogenesis. Because of the human relevancy of UV radiation in the etiopathogenesis of human skin cancer, we investigated whether or not transgenic mice overexpressing either furin alone or both furin and PACE4 show increased susceptibility to UV carcinogenesis. After backcrossing our previously described furin and PACE4 transgenic lines, targeted to the epidermis, into a SKH-1 background, we exposed both single and double transgenic mice to UV radiation for 34 weeks. The results showed an increase in squamous cell carcinoma (SCC) multiplicity of approximately 70% in the single furin transgenic mouse line SF47 (P < .002) and a 30% increase in the other single transgenic line SF49 when compared to wild-type (WT) SKH-1 mice. Interestingly, there was also an increase in the percentage of high histologic grade SCCs in the transgenic lines compared to the WT mice, i.e., WT = 9%, SF47 = 15%, and SF49 = 26% (P < .02). Targeting both furin and PACE4 to the epidermis in double transgenic mice did not have an additive effect on tumor incidence/multiplicity but did enhance the tumor histopathologic grade, i.e., a significant increase in higher grade SCCs was seen in the bigenic mouse line SPF47 (P < .02). Thus, we observed an increased susceptibility to UV in single furin transgenic mice that was not substantially enhanced in the double furin/PACE4 transgenic mice.


MBR-SIFT: A mirror reflected invariant feature descriptor using a binary representation for image matching.
The traditional scale invariant feature transform (SIFT) method can extract distinctive features for image matching. However, it is extremely time-consuming in SIFT matching because of the use of the Euclidean distance measure. Recently, many binary SIFT (BSIFT) methods have been developed to improve matching efficiency; however, none of them is invariant to mirror reflection. To address these problems, in this paper, we present a horizontal or vertical mirror reflection invariant binary descriptor named MBR-SIFT, in addition to a novel image matching approach. First, 16 cells in the local region around the SIFT keypoint are reorganized, and then the 128-dimensional vector of the SIFT descriptor is transformed into a reconstructed vector according to eight directions. Finally, the MBR-SIFT descriptor is obtained after binarization and reverse coding. To improve the matching speed and accuracy, a fast matching algorithm that includes a coarse-to-fine two-step matching strategy in addition to two similarity measures for the MBR-SIFT descriptor are proposed. Experimental results on the UKBench dataset show that the proposed method not only solves the problem of mirror reflection, but also ensures desirable matching accuracy and speed.


Respiratory toxicology of mineral oils in laboratory animals.
Early subchronic and chronic inhalation toxicology studies on various petroleum mineral oils and formulated lubricants supported the ACGIH TLV of 5 mg/m(3) for mineral oil mist. Additional subchronic studies with aerosolized mineral base oils and lubricants during the last 15 years demonstrated that exposures to aerosols of mineral base oils (often >100 mg/m(3)) resulted mainly in concentration-related accumulation in the lung of alveolar macrophages laden with oil droplets. Inflammatory cells were observed with higher aerosol concentrations, consistent with the clinical literature from highly exposed workers. These pulmonary changes appeared to be a nonspecific response to the presence of deposited aerosol. Studies on sensory irritation during exposures of lab animals to mineral oils indicate possible effects only with very high aerosol concentrations. Coupled with changes in refining to remove carcinogenic polynuclear aromatic hydrocarbons from mineral oils several decades ago, this information indicates that current aerosols of mineral oils have a profile of low toxicity from acute to long-term exposures. Available information suggests that additives in some formulated products and/or maintenance of mineral-based metalworking fluids may play a much more significant role in potential health effects.


Challenges and solutions for therapeutic TCR-based agents.
Recent development of methods to discover and engineer therapeutic T-cell receptors (TCRs) or antibody mimics of TCRs, and to understand their immunology and pharmacology, lag two decades behind therapeutic antibodies. Yet we have every expectation that TCR-based agents will be similarly important contributors to the treatment of a variety of medical conditions, especially cancers. TCR engineered cells, soluble TCRs and their derivatives, TCR-mimic antibodies, and TCR-based CAR T cells promise the possibility of highly specific drugs that can expand the scope of immunologic agents to recognize intracellular targets, including mutated proteins and undruggable transcription factors, not accessible by traditional antibodies. Hurdles exist regarding discovery, specificity, pharmacokinetics, and best modality of use that will need to be overcome before the full potential of TCR-based agents is achieved. HLA restriction may limit each agent to patient subpopulations and off-target reactivities remain important barriers to widespread development and use of these new agents. In this review we discuss the unique opportunities for these new classes of drugs, describe their unique antigenic targets, compare them to traditional antibody therapeutics and CAR T cells, and review the various obstacles that must be overcome before full application of these drugs can be realized.


A uniform mechanism correlating dangling-end stabilization and stacking geometry.
The geometry of the dangling base in 105 published structures (from X-ray/NMR) containing single-stranded overhangs has been analyzed and correlated to the thermodynamic stabilization found (UV) for the corresponding dangling base/closing basepair combination in short oligonucleotides. The study considers most combinations of closing basepairs, sequence and dangling base residue type, attached in both the 3'- and 5'-ends of both DNA and RNA. Linear regression analysis showed a straightforward correlation (R = 0.873) between the degree of screening for the hydrogen bonds of the closing basepair provided by the dangling base and the resulting thermodynamic stabilization in both DNA and RNA series with dangling ends either at the 3'- or at the 5'-terminus. Regression analysis of only the datasets from RNA gives an improved correlation, R = 0.934, showing that dangling ends on RNA are more ordered than the dangling ends on DNA, R = 0.376. This study highlights the gain in the free energy of stabilization owing to the favorable stacking between the dangling nucleobase and the neighboring basepair and the resulting strengthening of the hydrogen bond of the closing basepair. By acting as a hydrophobic cap on the terminal of the DNA or RNA duplex, the dangling-end residue restricts the bulk water access to the terminal basepair, thereby providing it with a microenvironment devoid of water, which consequently enhances its thermodynamic stability, making it energetically comparable to the corresponding internal basepair. Thus, one single structural model consisting of the interplay of the above electrostatic interactions can be used to explain the molecular basis of the observed thermodynamic effects for dangling-end attachment to the 3'- and 5'-ends of both DNA and RNA duplexes, which is a key step toward accurate dangling-end effect prediction.


The late positive component of the evoked waveform II: Relationship to picture recognition processes.
Averaged evoked potentials were collected from Cz, C3', C4', and Pz while subjects made cognitive decisions about pairs of pictures using perceptual and semantic features. Decisions were made at three different levels within the picture recognition process. These levels correspond to feature detection and synthesis, and semantic memory activation at the basic category and superordinate category levels. The late positive component of the evoked waveform systematically varied as a function of the nature of the cognitive decision being made. The late positive component of the waveform was highly correlated with the response times associated with each experimental condition. It would appear that the late positive component of the waveform provides an internal index of the neural processes which accompany cognitive decisions. As such, the late positive component of the evoked waveform serves as a source of converging evidence, along with response latency measures, that the picture recognition process can be successfully tapped at several different levels within the information processing system. This work should be applicable for studying disruptions to the pattern recognition process which accompany stroke, head trauma, and neurological problems associated with learning disorders. It should also be sensitive to any disorder which influences central processing time more than early perceptual and peripheral processes.


Mechanisms of acid decomposition of dithiocarbamates. 3. Aryldithiocarbamates and the torsional effect.
The acid decomposition of some p-substituted aryldithiocarbamates (arylDTCs) was observed in 20% aqueous ethanol at 25 degrees C, mu = 1.0 (KCl, for pH > 0). The pH-rate profiles showed a dumbell shape with a plateau where the observed first-order rate constant k(obs) was equal to k(o), the rate constant of the decomposition of the dithiocarbamic acid species. The acid dissociation constants of the dithiocarbamic acids (pK(a)) and their conjugate acids (pK(+)) were calculated from the pH-rate profiles. Comparatively, k(o) was more than 10(4)-fold faster than alkyldithiocarbamates (alkDTCs) with similar pK(N) (the acid dissociation constant of the parent amine). It was observed that the values of pK(a) and pK(+)were 5 and 8 units of pK, respectively, higher than the expected values from the pK(N) of alkylDTCs. The higher values were attributed to the inhibition of the delocalization of the nitrogen electron pair into the benzene ring because of the strong electron withdrawal effect of the thiocarbonyl group. Comparison of the activation parameters showed that the rate acceleration was due to a decrease in the enthalpy of activation. Proton inventory indicated the existence of a multiproton transition state, and it was consistent with an S to N proton transfer through a water molecule. There are two hydrogens contributing to a secondary SIE, and there are also two protons that are being transferred at the transition state to form a zwitterion followed by fast C-N bond cleavage. The mechanism could also be a concerted asynchronic process where the N-protonation is more advanced than the C-N bond breakdown. The kinetic barrier is similar to the torsional barrier of thioamides, suggesting that the driving force to reach the transition state is the needed torsion of the C-N bond that inhibits the resonance with the thiocarbonyl group and the aromatic moiety, increasing the basicity of the nitrogen and making the proton transfer thermodynamically favorable.


Glucose Starvation Stimulates the Promoting Strength of a Novel Evolved Suc2 Promoter.
Promoters are essential for designing Saccharomyces cerevisiae cell factories. Identifying novel promoters tuned to produce specific metabolites under increasingly diverse industrial stresses is required to improve the economic feasibility of whole fermentation processes. In this study, a positively evolved Suc2 promoter (SUC 2p) with promoter activity stronger than that of the wild-type Suc2 promoter (SUC 2wtp) was obtained. Quantitative real-time PCR, fluorescence analysis, Western blotting, and a β-galactosidase activity assay revealed that SUC 2p is a medium-strength promoter compared with eight reported promoters at a medium glucose concentration (2% (w/v)). Different glucose concentrations modulated the strength of SUC 2p. Low glucose concentrations (0.05 and 0.5% (w/v)) enhanced the promoter strength of SUC 2p dramatically, with promoter activity higher than that of reported strong promoters. Glucose starvation resulted in the formation of a new Msn2/4 binding site on SUC 2p. Our work should facilitate the development of promoters with novel fine-tuning properties and the construction of S. cerevisiae cell factories suitable for the industrial production of essential chemicals under glucose-deprived conditions.


Onboarding advanced practice nurses: development of an orientation program in a cardiac center.
The advanced practice nurse (APN) is critical to continuity of patient care, particularly in an innovative and research-intensive environment. The intensity of the environment, steep learning curve, and lack of a structured orientation can lead to difficulties in role assimilation and feelings of disconnectedness. This led the authors to undertake an improvement project to develop an onboarding program for APNs and develop strategies to orient them to their role. The authors describe the program and discuss how it was perceived by the APNs. Program evaluation and suggestions for future nursing research are identified.


Ensemble Methods with Voting Protocols Exhibit Superior Performance for Predicting Cancer Clinical Endpoints and Providing More Complete Coverage of Disease-Related Genes.
In genetic data modeling, the use of a limited number of samples for modeling and predicting, especially well below the attribute number, is difficult due to the enormous number of genes detected by a sequencing platform. In addition, many studies commonly use machine learning methods to evaluate genetic datasets to identify potential disease-related genes and drug targets, but to the best of our knowledge, the information associated with the selected gene set was not thoroughly elucidated in previous studies. To identify a relatively stable scheme for modeling limited samples in the gene datasets and reveal the information that they contain, the present study first evaluated the performance of a series of modeling approaches for predicting clinical endpoints of cancer and later integrated the results using various voting protocols. As a result, we proposed a relatively stable scheme that used a set of methods with an ensemble algorithm. Our findings indicated that the ensemble methodologies are more reliable for predicting cancer prognoses than single machine learning algorithms as well as for gene function evaluating. The ensemble methodologies provide a more complete coverage of relevant genes, which can facilitate the exploration of cancer mechanisms and the identification of potential drug targets.


[Establishment of a rapid method for detection of influenza A/B virus' antigens].
This study aims to develop a rapid and convenient test card for simultaneous detection of influenza A and influenza B viruses using quantum dot-based immunochromatographic assay. The test card consists of a test strip and a plastic casing. The test strip is composed of absorbent paper, a buffer pad, nitrocellulose membrane (NC membrane), sample pad, quantum dot-labeled antibody pad, and polyvinyl chloride (PVC) board. The NC membrane is coated with mouse monoclonal antibodies against influenza A and influenza B viruses for the T lines (test lines), and reference proteins A and B for the C line (control line). The quantum dot-labeled antibody pad contains mouse monoclonal antibody-quantum dot conjugates against influenza A and influenza B viruses. The results showed that the detection limit of the test card for both viruses ranged from 1.51 ×102 to 2.71×103 TCID50/ml, indicating its sensitivity for accurate detection of influenza A and influenza B viruses without being affected by various variants. The test card exhibited specific reactions with different subtypes of influenza A and influenza B virus culture fluids and showed no cross-reactivity with adenovirus, novel coronavirus, Mycoplasma pneumoniae, respiratory syncytial virus, Staphylococcus aureus, and other pathogens. Overall, the sensitivity and specificity of the test card for simultaneous detection of influenza A and influenza B viruses meet the requirements for clinical use. It offers the advantages of simplicity, rapidity, and no requirement for special equipment, enabling quick auxiliary diagnosis to prevent disease transmission.


PATTERN OF CONSANGUINITY AND INBREEDING COEFFICIENT IN SARGODHA DISTRICT, PUNJAB, PAKISTAN.
Consanguinity is widespread in Pakistan. The majority of studies on consanguinity in Pakistan have been carried out in urban metropolitan areas, and data on rural populations are scarce. The present cross-sectional study was conducted in Sargodha district, upper Punjab, Pakistan where the majority of the population reside in rural areas. A random sample of 1800 married females belonging to six tehsils of Sargodha district was obtained and differentials in consanguinity rates and inbreeding coefficient (F) were investigated. The consanguinity rate was calculated to be 56.72% and the inbreeding coefficient was 0.0348. First cousin unions had the highest representation (49.11% of all marriages), and marriages up to distantly related/Biradari constituted 67.94% of all marriages. Among the six tehsils, consanguinity rates ranged from 50.38% in Bhalwal to 62.88% in Sillanwali. A high rate of consanguinity was observed in subjects speaking the Punjabi language, those with self-arranged/arranged-love marriages and those engaged in professional jobs. With respect to the occupation of husbands the highest consanguinity rate was found among landowners (77.59%; F=0.0539) and businessmen (62.62%; F=0.0377). However, consanguinity did not appear to be associated with rural/urban origin or literacy level. The data showed a wide variation in consanguinity rate and inbreeding coefficient across socio-demographic strata in the Sargodha district population. A comparison of Sargodha with other populations of Punjab also showed regional heterogeneity in the pattern of consanguinity, warranting further studies.


Uncoupling protein 3 mediates H₂O₂ preconditioning-afforded cardioprotection through the inhibition of MPTP opening.
Uncoupling protein 3 (UCP3), located in the mitochondrial inner membrane, is cardioprotective, but its mechanisms of preserving mitochondrial function during ischaemia/reperfusion (I/R) are not fully understood. This study investigated whether UCP3 mediates/mimics the cardioprotection of H₂O₂ preconditioning (H₂O₂PC) against I/R injury and the downstream pathway that mediates H₂O₂PC- and UCP3-afforded cardioprotection. H₂O₂PC at 20 µM for 5 min significantly improved post-ischaemic functional recovery and reduced lactate dehydrogenase (LDH) release and infarct size with concurrently up-regulated UCP3 expressions in perfused rat hearts subjected to global no-flow I/R. These protections were blocked by UCP3 knockdown with short hairpin RNA but mimicked by UCP3 overexpression. Consistently, H₂O₂PC-attenuated I/R-induced cytosolic and mitochondrial Ca(2+) overload, Ca(2+) transient suppression, mitochondrial reactive oxygen species burst, and loss of mitochondrial inner membrane potential were reversed by UCP3 knockdown but mimicked by UCP3 overexpression. Moreover, co-immunoprecipitation assay revealed an interaction of UCP3 with the mitochondrial permeability transition pore (mPTP) component, adenine nucleotide translocator (ANT), while the cardioprotection induced by H₂O₂PC- and UCP3 overexpression in mitochondria, cardiac function, and cell survival was abolished by atractyloside, a mPTP opener binding to ANT, and partially inhibited by a PI3K/Akt inhibitor wortmannin. Furthermore, H₂O₂PC up-regulated the phosphorylation of Akt, and glycogen synthase kinase 3β was blocked by UCP3 knockdown but mimicked by UCP3 overexpression. UCP3 mediates the cardioprotection of H₂O₂PC against I/R injury by preserving the mitochondrial function through inhibiting mPTP opening via the interaction with ANT and the PI3K/Akt pathway. Our findings reveal novel mechanisms of UCP3 in the cardioprotection.


Recent developments on the extraction and application of ursolic acid. A review.
Ursolic acid (UA) is a pentacyclic triterpenoid widely found in herbs, leaves, flowers and fruits; update information on the major natural sources or agro-industrial wastes is presented. Traditional (maceration, Soxhlet and heat reflux) and modern (microwave-, ultrasound-, accelerated solvent- and supercritical fluid) extraction and purification technologies of UA, as well as some patented process, are summarized. The great interest in this bioactive compound is related to the beneficial effects in human health due to antioxidant, antimicrobial, anti-inflammatory, hepatoprotective, immunomodulatory, anti-tumor, chemopreventive, cardioprotective, antihyperlipidemic and hypoglycemic activities, and others. UA may augment the resistance of the skin barrier to irritants, prevent dry skin and could be suitable to develop antiaging products. The development of nanocrystals and nanoparticle-based drugs could reduce the side effects of high doses of UA in organisms, and increase its limited solubility and poor bioavailability of UA which limit the potential of this bioactive and the further applications. Commercial patented applications in relation to cosmetical and pharmaceutical uses of UA and its derivatives are surveyed.


Unarmoured dinoflagellates with a small hyposome: Torodinium and Lebouridinium gen. nov. for Katodinium glaucum (Gymnodiniales, Dinophyceae).
We investigated the morphology and evolutionary relationships of Torodinium spp. and Katodinium glaucum, unarmoured dinoflagellates characterized by a small hyposome. An emended generic description of Torodinium was proposed based on light and scanning electron microscopy. Torodinium exhibited a unique combination of morphological features including a minute hyposome, a long episome with longitudinal ribs and a canal of unknown function on the dextro-lateral side. Unlike any known dinoflagellate both cingulum and sulcus extended in the episome. The apex surface showed ribs that converged in a bill-like projection. The shape of the apical groove was a circular spiral that extended around the apex running in 2.5 turns in an anticlockwise direction. The type species T. teredo was usually longer than T. robustum. The longitudinal outline of T. teredo was linear, with almost parallel margins, a circular transversal section, a relatively large hyposome and a conspicuous bill-like projection. The longitudinal outline of T. robustum was oblong, widened in the middle, with an ellipsoidal transversal section, a small hyposome and a less prominent bill-like projection. Several morphological features of Katodinium glaucum (=Gyrodinium glaucum) resembled Gyrodinium, such as the cingular displacement, longitudinal ribs, trichocysts, rod-shaped and refractile bodies and a capsule that surrounded the spherical nucleus. Distinctive features of K. glaucum were the horseshoeshaped apical groove under a tongue-shaped notch pointed towards the dorsal side, and a bifurcated proximal end of the cingulum. Phylogenetic analysis revealed that Torodinium spp. and K. glaucum formed two independent lineages with no close relationships with other known dinoflagellates. The morphology of K. glaucum was distant from the type species of Katodinium. We propose the new genus and combination Lebouridinium glaucum gen. nov., comb. nov. for the species Katodinium glaucum.


SHARE, from vision to road map: technical steps.
We present the 'HealthGrid' initiative and briefly review work carried out in various European healthgrid projects. We report on joint work with numerous European collaborators. Since the European Commission's Information Society Technologies programme funded the first gridbased health and medical projects, the HealthGrid movement has flourished in Europe. Many projects have now been completed and 'HealthGrid' consulted a number of experts to compile and publish a 'White Paper' which establishes the foundations, potential scope and prospects of an approach to health informatics based on a grid infrastructure. With a second generation of projects now funded, the EC has commissioned the SHARE Project, a study to define a research roadmap for a 'healthgrid for Europe' as the preferred infrastructure for medical and health care projects in the European Research Area. The project explores the ways in which the healthgrid approach supports modern trends both in research in biomedicine and in healthcare, such as evidence-based practice and information integration.


Temperament: concepts, issues and problems.
There are marked individual differences in children's temperamental styles-- differences thought to be constitutionally determined in part. The importance of temperamental features is evident in their links with various forms of psychopathology and in their effects on the manner in which other people respond to the child. For these and other reasons it has rightly come to be accepted that greater attention needs to be paid to temperamental issues in consideration of the processes of development, children's responses to stress situations, and the genesis of emotional, behavioural and learning disorders. However, major conceptual, methodological and theoretical problems remain. Problems of measurement are considered in terms of the relativity of measures, whether or not to take social context into account, the functional equivalence of measures at different ages, the circumstances to use in assessing temperament, the choice of measuring instrument and the categorization of temperamental features. The issues involved in the meaning of temperamental differences are discussed with respect to consistency, developmental change, genetic influences, brain damage and mental retardation, sex differences and the mechanisms by which temperamental variables exert their effects.


Validation of Dried Blood Spots for Capturing Hepatitis C Virus Diversity for Genomic Surveillance.
Dried blood spots (DBS) have emerged as a promising alternative to traditional venous blood for HCV testing. However, their capacity to accurately reflect the genetic diversity of HCV remains poorly understood. We employed deep sequencing and advanced phylogenetic analyses on paired plasma and DBS samples to evaluate the suitability of DBS for genomic surveillance. Results demonstrated that DBS captured equivalent viral diversity compared to plasma with no phylogenetic discordance observed. The ability of DBS to accurately reflect the profile of viral genetic diversity suggests it may be a promising avenue for future surveillance efforts to curb HCV outbreaks.


Anaphylaxis management in primary care.
The United Kingdom Resuscitation Council Project Team has issued revised guidelines on the emergency treatment of anaphylactic reactions in the community setting in response to community nurses' concerns. A consensus has now been reached.


[Prevalence of Hypertriglyceridemia: New Data Across the Russian Population. The PROMETHEUS Study].
The main purpose of the study was to estimate prevalence of subjects with hypertriglyceridemia (HTG) in Russia. Secondary objectives were to explore HTG prevalence by levels, age and sex, and to assess correlation between glycated hemoglobin (HbA1C) and triglyceride (TG) level. Additionally, we analyzed geographical differences in HTG prevalence in regions of Russia. This was a cross-sectional, retrospective, observational study using database of results of lipid profile determination in 357,072 subjects from 254 Russian cities during the 3-year period from 2011 to 2013. Altogether, 29.2% (95% confidence interval [CI] 29.1-29.4%) of Russian individuals had HTG (serum TG more or equal 1.7 mmol/L). The percentage of patients with very high (TG more or equal 5.6 mmol/L) and severe HTG (TG more or equal 10.0mmol/L) was low (0.01% and 0.011%, respectively). At the same time, the portion of subjects with mixed hyperlipidemia (total cholesterol [TC] more or equal 5.2mmol/L, low-density lipoprotein cholesterol [LDL-C] more or equal 3.4 mmol/L, TG more or equal 1.7 mmol/L) was 19% of the study population. Men had 1.25 (95% CI, 1.24-1.26) times higher risk of HTG than women. Prevalence of HTG increased with age: in women TG level was maximal in the age group 60-69 years (34%), whereas in men TG level was maximal in the age group 40-49 years (43%). Prevalence of HTG increased from 2011 to 2013 from 28 to 30% (p<0.0001). Risk of HTG was 1.69 times greater when high HbA1C more or equal 6.5% was present, and vice versa, risk of HbA1C more or equal 6.5% was 2.04 times higher in individuals with HTG. Distribution of HTG and dyslipidemia by regions of Russia had large variability being higher in the south and lower in the northern regions of European part of Russia. Almost a third of Russian population has HTG. Men have higher risk of HTG than women. Prevalence of HTG increases with age and reaches its peak in age groups 60-69 years in (women) and 40-49 years (men). There is a linear association between high HbA- and high level of TG. Prevalence of HTG and dyslipidemia is heterogeneous in Russian regions.


Resisting RECIST-Uniformity Versus Clinical Validity.
The Response Evaluation Criteria in Solid Tumors (RECIST) International Working Group developed criteria for tumor response and progression to standardize radiological assessment in patients receiving chemotherapy in phase 2 trials. However, it is unclear whether the defined percentage change in tumor size and volume reflects true clinical benefit for the patient. The RECIST criteria were designed to improve objectivity in trials, but not to replace clinical decision making. The aim of this study was to understand clinicians' opinions about RECIST in current oncology practice. Using Web-based questionnaires, we investigated attitudes to the use of RECIST at a large comprehensive cancer center and in an international group of gynecologic cancer specialists through the Gynecologic Cancer InterGroup. The results reported here relate to the survey focusing on gynecologic cancer. Sixty medical professionals from 13 countries responded to the survey. The majority of respondents worked at a tertiary or specialist cancer center (51; 86%). Overall, 66% of respondents felt RECIST increased trial objectivity and was a good measure of response. The majority of respondents (81%) reported that they infrequently challenged RECIST evaluation. Overall, 60% felt more than 10% of patients came off trial for clinical rather than radiological progression. In the context of a new small lesion, only 35% felt that should always be considered disease progression. The importance of both clinician and radiologist input was highlighted with nontarget progression. Nontarget progression and target progression were recognized as equally important for clinical decision making (72%). RECIST is a key criterion for endpoint assessment in clinical trials with its value recognized by clinicians. However, this survey also highlights the practical limitations of RECIST. Disconnect can be seen between the radiological result and the clinical picture-learning from these patients is critical. Continued efforts to improve metrics assessing patient benefit in trials remains a priority.


The use of theatre time for paediatric dentistry under general anaesthesia.
The aim of this paper was to determine the use of theatre time for all procedures performed under general anaesthetic on a paediatric dental list. A prospective study of paediatric dental general anaesthetic procedures was undertaken at Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK. Data were collected prospectively for 71 operating lists over a 3-year period from April 2003 to March 2006. Both operator status and the procedure being undertaken were recorded. In addition, pre-anaesthetic, anaesthetic, operating and disconnection times were recorded. Of the 71 lists examined, 61 either finished early or on time, with a median unused time of 32.50 min (interquartile range = 19.50, 50.00 min), whilst 10 lists finished late with a median overrun time of 30.50 min (interquartile range = 9.25, 45.50 min). Comparing lists which finished late with those which were completed within time, the median pre-anaesthetic time was significantly longer (Mann-Whitney U-test, W = 20.05, P = 0.048). Overall, the theatre was in use for 78.22% of time combining pre-anaesthetic, anaesthetic, operating and disconnection times; hence, there was poor time utilization of theatre for 21.78% of the total theatre time. Overall, 85.9% of theatre sessions for dental procedures under general anaesthetic in children finished early or on time. Where lists finished late, the duration of the pre-anaesthetic time appeared to be the significant factor.


Ligation and mucopexy for prolapsing hemorrhoids--a ten year experience.
The aim of this study is to clinically test the efficacy of author's approach of suture ligation and mucopexy for patients having symptomatic and prolapsing hemorrhoids. 616 patients (255 females) complaining of symptoms of hemorrhoids were included in the study. The hemorrhoids were suture ligated with an absorbable suture material under vision. Operating time, postoperative complications, time to return to work, and outcome of the procedure were analyzed. Follow-up was planned following discharge after 1 month, 6 months and after at least 1 year. Patient satisfaction was also assessed. The mean procedure time was 8 +/- 0 minutes (range, 6-15 minutes), and the total admission period was 12 +/- 4 Hours. Perianal thrombosis and skin tags were the commonest post-operative complications. The mean total analgesic dose and duration of pain control using analgesics was 19 +/- 4 tablets, and 9 +/- 3 days respectively.The postoperative follow up after 4 weeks revealed therapeutic success in 589 patients (95.6%), who presented with hemorrhoidal bleeding. Prolapse was no longer observed in 98% of patients and 96% patients experienced no pain after defecation. 93% patients completed the one-year follow-up and 89 percent of them were asymptomatic. The patient satisfaction scoring was 8.2% on visual analogue scale. Suture ligation and mucopexy of hemorrhoids is an easy-to-perform technique that is well accepted by patients and has good results for prolapsing hemorrhoids.


Risk factors for obstetrical anal sphincter lacerations.
The objective of this study was to identify the rate of anal sphincter lacerations in a large population-based database and analyze risk factors associated with this condition. Data were obtained from Pennsylvania Healthcare Cost Containment Council (PHC4) regarding all cases of obstetrical third and fourth degree perineal lacerations that occurred during a 2-year period from January 1990 to December 1991. Modifiable risk factors associated with this condition were analyzed, specifically episiotomy, forceps-assisted vaginal delivery, forceps with episiotomy, vacuum-assisted vaginal delivery, and vacuum with episiotomy. There were a total of 168,337 deliveries in 1990 and 165,051 deliveries in 1991 in Pennsylvania. Twenty-two percent (n = 74,881) of the deliveries were by cesarean section and were excluded from analysis. Among the remaining 258,507 deliveries, there were 18,888 (7.3%) third and fourth degree lacerations. Instrumental vaginal delivery, particularly with use of episiotomy, increased the risk of laceration significantly [forceps odds ratio (OR): 3.84, forceps with episiotomy OR: 3.89, vacuum OR: 2.58, vacuum with episiotomy OR: 2.93]. Episiotomy on the whole was associated with a threefold increase in the risk of sphincter tears. However, episiotomy in the absence of instrumental delivery seems to be protective with an OR of 0.9 [95% confidence interval (CI): 0.88-0.93]. Instrumental vaginal delivery, particularly forceps delivery, appears to be an important risk factor for anal sphincter tears. The risk previously attributed to episiotomy is probably due to its association with instrumental vaginal delivery. Forceps delivery is associated with higher occurrence of anal sphincter injury compared to vacuum delivery.