Prevalence, Incidence, and Clearance of Human Papillomavirus Types Covered by Current Vaccines in Men With Human Immunodeficiency Virus in the SUN Study.
High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized. We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. Baseline prevalence of any anal 9v HR-HPV type among men who have sex with men (MSM) and men who have sex with women (MSW) was 74% and 25% (P < .001), respectively. Among 299 MSM, abnormal cytology was detected in 161 (54%) MSM and was associated with the presence of any 9v HR-HPV (relative risk [RR], 1.8 [95% confidence interval {CI}, 1.3-2.6]; P < .001). Among 61 MSW, abnormal anal cytology was detected in 12 (20%) and was associated with the presence of any 9v HR-HPV (RR, 4.3 [95% CI, 1.6-11.5]; P < .001). Among men with HIV, the prevalence of the 7 HR-HPV types in the 9v vaccine was high and was associated with abnormal cytology. These findings indicate that men with HIV could benefit from prophylactic administration of the 9v HPV vaccine.


Associations between lifestyle patterns and body mass index in a sample of Greek children and adolescents.
Although eating and physical activity behaviors have been previously individually investigated with regard to overweight in children, multidimensional lifestyle patterns, based on these behaviors, have not been explored. To assess lifestyle patterns in relation to body mass index (BMI), in a nationally representative sample of the Greek pediatric population Cross-sectional study. Data were collected from May through July 2007. The sample consisted of 1,305 children and adolescents (ages 3 to 18 years). Information on participants' dietary intake, eating behaviors, physical activity habits, and BMI were collected. Adherence to the Mediterranean diet guidelines was evaluated using the KIDMED Mediterranean diet quality index; the higher the score in this index the more favorable the dietary pattern. The Goldberg cut-off limits for the ratio of energy intake/basal metabolic rate were used to evaluate dietary low energy reporting and participants were accordingly classified as low-energy reporters. Principal component analysis was performed to identify participants' lifestyle patterns. Associations between BMI and lifestyle patterns were further evaluated using multiple linear regression analyses, after controlling for potential confounders. Principal component analysis identified seven lifestyle patterns explaining 85% of the total variance of lifestyle habits. A lifestyle pattern characterized by higher eating frequency, breakfast consumption and higher KIDMED score was negatively associated with BMI (standardized beta=-.125, P<0.001), after controlling for age, sex, and parental education. The association remained significant even when low-energy reporters were excluded from the analysis. Results from the study suggest a potential intercorrelation and protective action of selected eating behaviors, namely eating frequency, breakfast consumption, and adherence to the Mediterranean diet, against overweight and obesity in children and adolescents.


The role of rubella in the etiology of supravalvular aortic stenosis.
The possibility of an etiological relationship between rubella embryopathy and sporadic forms of supravalvular aortic stenosis is considered. A case is presented of a patient with rubella embryopathy and supravalvular aortic stenosis associated with pulmonary valvular and peripheral pulmonary artery stenosis, bicuspid aortic valve, aortic valve stenosis and subendothelial myocardial fibrosis. A review of the literature revealed many clinical and pathological features common to both syndromes. The hypothesis that rubella virus produced germ-cell mutation and subsequent persistence of rubella in the zygote produced further fetal damage is presented to explain these observations.


New college data may shed light on issue of sexual abuse by physicians.
During a recent conference on physician health that was cosponsored by the CMA and American Medical Association, physicians learned that there had been an increase in the number of reported cases of abuse of patients by physicians in Ontario. The increase occurred after new legislation made the reporting of suspected sexual abuse mandatory in the province in 1994. Dr. Laurel Dempsey said there was "a considerable body of opinion" at the College of Physicians and Surgeons of Ontario that there would be a backlog of cases waiting to be reported once the new law took effect. However, it won't be possible to tell if this backlog actually exists until data have been gathered for at least a few more years.


Radiomics Predicts for Distant Metastasis in Locally Advanced Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.
(1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics for risk stratification in this patient population to guide treatment. (2) Methods: the study population consisted of 225 patients with locally advanced HPV+ OPSCC treated with curative-intent radiation or chemoradiation therapy. Appearance of distant metastasis was used as the endpoint event. Radiomics data were extracted from the gross tumor volumes (GTVs) identified on the planning CT, with gray level being discretized using three different bin widths (8, 16, and 32). The data extracted for the groups with and without distant metastasis were subsequently balanced using three different algorithms including synthetic minority over-sampling technique (SMOTE), adaptive synthetic sampling (ADASYN), and borderline SMOTE. From these different combinations, a total of nine radiomics datasets were derived. Top features that minimized redundancy while maximizing relevance to the endpoint were selected individually and collectively for the nine radiomics datasets to build support vector machine (SVM) based predictive classifiers. Performance of the developed classifiers was evaluated by receiver operating characteristic (ROC) curve analysis. (3) Results: of the 225 locally advanced HPV+ OPSCC patients being studied, 9.3% had developed distant metastases at last follow-up. SVM classifiers built for the nine radiomics dataset using either their own respective top features or the top consensus ones were all able to differentiate the two cohorts at a level of excellence or beyond, with ROC area under curve (AUC) ranging from 0.84 to 0.95 (median = 0.90). ROC comparisons further revealed that the majority of the built classifiers did not distinguish the two cohorts significantly better than each other. (4) Conclusions: radiomics demonstrated discriminative ability in distinguishing patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone and may serve to risk stratify this patient population with the purpose of guiding the appropriate therapy.


Levetiracetam effect on adult-onset temporal lobe epilepsy with positive voltage-gated potassium channel antibody.
Temporal lobe epilepsy is considered to be the most frequent of all epileptic syndromes. Recently, several retrospective studies suggest that limbic encephalitis (LE) may be a cause for adult onset unexplained seizure disorders in patients. This report describes two cases of adult onset epilepsy with voltage-gated potassium channel antibodies (VGKC-abs)-associated LE that responded well to levetiracetam (LEV). As demonstrated by these two cases and reviewing previous reports, we propose that the therapeutic regimen for VGKC-abs associated seizures still needs to be determined and LEV may be effective in treating this kind of disorders.


Covalent binding of radioactivity from [14C]rofecoxib, but not [14C]celecoxib or [14C]CS-706, to the arterial elastin of rats.
Rofecoxib is a cyclooxygenase-2 (COX-2) inhibitor that has been withdrawn from the market because of an increased risk of cardiovascular (CV) events. With a special focus on the arteries, the distribution profiles of radioactivity in rats orally administered [14C]rofecoxib were investigated in comparison with two other COX-2 inhibitors, [14C]celecoxib and [14C]CS-706 (2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole), a novel selective COX-2 inhibitor. Whole-body autoradioluminography and quantitative determination of the tissue concentrations showed that considerable radioactivity is retained by and accumulated in the thoracic aorta of rats after oral administration of [14C]rofecoxib, but not [14C]celecoxib or [14C]CS-706. Acid, organic solvent, and proteolytic enzyme treatments of aorta retaining high levels of radioactivity from [14C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. In agreement with this result, the radioactivity was found to be highly localized on the elastic fibers in the aorta by microautoradiography. The retention of radioactivity on the elastic fibers was also observed in the aortic arch and the coronary artery. These findings indicate that [14C]rofecoxib and/or its metabolite(s) are covalently bound to elastin in the arteries. These data are consistent with the suggestion of modified arterial elasticity leading to an increased risk of CV events after long-term treatment with rofecoxib.


Sex hormones during alcohol withdrawal: a longitudinal study of 29 male alcoholics during detoxification.
It is a well-known fact that alcohol affects sex hormone levels in males. Even in the absence of liver dysfunction, there is still a direct toxic effect of ethanol on testosterone synthesis resulting in acutely decreased values. This study is based on 29 male alcoholics without severe signs of liver disease treated on the alcohol detoxification ward at Huddinge hospital in Stockholm, Sweden during 1995. The aim was to study levels of sex hormones in male alcoholics during detoxification with benzodiazepines and after 3 weeks of sobriety. Blood samples were taken three times: one day after admission (day 2) when the patient was sober, at discharge (day 5) and after 3 weeks of sobriety (day 21). Levels of testosterone and sex hormone-binding globulin (SHBG) showed the same pattern during detoxification and follow-up. They were both low, but generally within normal limits, on days 2 and 5, but raised after 3 weeks of sobriety. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were initially high, but were substantially depressed during detoxification. Levels of FSH recovered after 3 weeks, whereas LH remained at the same level. Most patients exhibited generally low levels of both FSH and LH, however. Levels of oestrone decreased steadily. There were no correlations between levels of sex hormones and the number of milligrams of oxazepam administered to the patients during detoxification either at admission, at discharge or at follow-up. In summary, the endocrinological response to alcohol intake is complex. This study suggests that the duration of endocrinological recovery after drinking is a quite long-lasting process, that different hormones need different times to recover and that the normal glandular-pituitary feed-back processes may be partly put out of order.


Nanoscale organization in piperidinium-based room temperature ionic liquids.
Here we report on the complex nature of the phase diagram of N-alkyl-N-methylpiperidinium bis(trifluoromethanesulfonyl)imide ionic liquids using several complementary techniques and on their structural order in the molten state using small-wide angle x-ray scattering. The latter study indicates that the piperidinium aliphatic alkyl chains tend to aggregate, forming alkyl domains embedded into polar regions, similar to what we recently highlighted in the case of other ionic liquids.


Lithium therapy in aggressive mentally subnormal patients.
In a series of fifteen aggressive mentally subnormal patients treated with lithium carbonate, there was an improvement in aggressive behaviour in eleven cases, three patients showed no change and one patient became worse during lithium treatment. The response to lithium therapy was assessed by clinical observation and retrospective analysis of daily ward reports. Treatment had to be discontinued in one patient who developed tardive dyskinesia, but otherwise side effects were not a problem.


Adverse effects of lactational exposure to chlorpyrifos in suckling rats.
The present study was undertaken to evaluate the oxidative damage, biochemical and histopathological alterations in sucking rats whose mothers were exposed to the insecticide chlorpyrifos (CPF). Dams were administered CPF, via oral route. Doses equalled 0.01 mg kg(-1) body weight (b.wt.; acceptable daily intake, ADI), 1.00 mg kg(-1) b.wt. (no observed adverse effects level, NOAEL) and 1.35 mg kg(-1) b.wt. (1/100 lethal dose [LD(50)]) from postnatal day 1 until day 20 after delivery. At two high doses of CPF, the body weight gain and relative liver and kidney weight of suckling pups were significantly decreased. Exposure of the mothers to CPF caused increase in lipid peroxidation (LPO) and decrease in superoxide dismutase (SOD) and glutathione-s-transferase (GST) in lactating pups. CPF altered the level of the marker parameters related to the liver and kidneys. Consistent histological changes were found in the liver and kidneys of the subjected pups, especially at the higher doses. The results suggested that the transfer of CPF intoxication through the mother's milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. The data of this study may be considered as a contribution to the problem of lactational transfer of the relatively less persistent OP pesticides, such as CPF.


Multivisceral robotic resection: a glimpse into the future of minimally invasive abdominal surgery.
A 62-year-old man was referred to the Hepato-Pancreato-Biliary (HPB) surgeons with left upper quadrant discomfort. The initial investigations and CT scans revealed a tumour in the pancreatic tail with liver metastases, confirmed on MRI. It was initially thought to be an adenocarcinoma; however, further investigations found that it was a grade 1 neuroendocrine tumour with Ki 67 at 1% and it was agreed that he would undergo a total robotic surgery involving resection of the locally advanced tumour of the tail of pancreas, with the involvement of the stomach, and splenic flexure of the colon with liver metastases. The resulting procedure was a total robotic distal pancreatectomy, splenectomy, sleeve resection of stomach, cholecystectomy, atypical resection of two liver lesions and microwave ablation of multiple liver lesions. Four days post-operatively, he was discharged from hospital and commenced adjuvant chemotherapy. He currently enjoys a good quality of life.


Prevalence of resurgence during thinning of multiple schedules of reinforcement following functional communication training.
The current study examined resurgence of problem behavior during thinning of multiple schedules of reinforcement following functional communication training replicating previous research (Briggs et al., 2018). Data were analyzed at each thinning step from subjects enrolled in an intensive day treatment program over a 5-year period. Results indicated that of the 239 thinning steps analyzed, resurgence was observed in 97 of those steps (40.6%), similar to results of Briggs et al. (2018). The data were also analyzed to estimate the magnitude of resurgence when it was observed. In the first session after the thinning step, the rate of problem behavior observed was 7 times higher than the average of the 5 sessions pre-thinning step.


Fear of hypoglycemia in patients with type 1 and 2 diabetes: a systematic review.
To summarize and thematize fear of hypoglycemia (FOH) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) to provide a theoretical basis for the development of effective interventions. FOH is common in this population and can reduce quality of life(QOL) and adversely impact upon diabetes self-care management. a systematic review METHODS: Articles published between 2000 and 2019 were searched in PubMed, MEDLINE, EMBASE, Web of Science and three Chinese databases (CNKI, Wan-fang data and VIP). Eligible articles were selected using the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. The quality of all articles finally included was evaluated by the Joanna Briggs Institute (JBI) Critical Appraisal tools. Eighteen studies from 8654 papers were included. The sample size of each study ranged from 48 to 3812 subjects. FOH negatively impacted QOL, particularly psychosocial functioning, daily life and sleep quality. FOH is a common and serious problem for patients, leading to poor QOL. It has been suggested that psychological concerns, QOL and effective countermeasures in individuals with T1D and T2D should be taken seriously. Advanced technology should be evaluated for its benefits before being used by patients. The review highlights that FOH negatively impacts QOL, including psychosocial factors, daily life and sleep quality. Healthcare providers should develop targeted and professional assessment tools for FOH and QOL for patients with T2D, especially for patients who are about 60 years old. Advanced technology should be evaluated for its benefits before being used by patients.


Immunologic dysfunction in the pathogenesis of periodontal diseases.
Despite significant progress in our understanding of the pathogenesis and etiology of periodontal diseases, the nature and contribution of the immune system to this disorder remains unclear. Several studies provide evidence for either a protective or destructive rôle. These conflicting findings are difficult to reconcile, since most interpretations tend to argue for a static contributory rôle (i.e., either protective or destructive) of the immune system. Current theories on the rôle of the immune response do not address these conflicting findings as well as the contradictory observation of a detectable immune response in the face of persistent infection in these patients. In this article, we present a model, based on available data, for the contribution of the immune system to the pathogenesis of periodontal disease. This model ascribes a dynamic rôle for the immune response. As documented in other infectious diseases, it is entirely possible, for example, that a state of immunologic dysfunction may occur in the earliest stages of periodontal disease progression; this may then be followed by a period of active immune reactivity (humoral and/or cellular) that would represent either a delayed or depressed response. This model is discussed in conjunction with recent findings that several suspected periodontal pathogens are capable of producing immunosuppressive agents. Many of the apparently contradictory clinical observations concerning the host immune response to oral pathogens and its correlation (or lack of) with both the progression and severity of periodontal disease may be accounted for in this model.


Is it possible to improve the outcome of transanal advancement flap repair for high transsphincteric fistulas by additional ligation of the intersphincteric fistula tract?
Transanal advancement flap repair is successful in 2 of every 3 patients with a cryptoglandular fistula passing through the middle or upper third of the external anal sphincter. It has been suggested that ongoing disease in the remaining fistula tract contributes to failure. Ligation of the intersphincteric fistula tract might be a useful tool to eradicate this ongoing disease. The aim of the present study was to evaluate the effect of an additional ligation of the fistula tract on the outcome of transanal advancement flap repair. This investigation was designed as a prospective clinical study. The study took place in a university hospital. A consecutive series of 41 patients with a high transsphincteric fistula of cryptoglandular origin were included. Ligation of the intersphincteric fistula tract was performed in addition to flap repair. Early and late complications were recorded. Continence scores were determined with the use of the Fecal Incontinence Severity Index. Median duration of follow-up was 15 months. Primary healing was observed in 21 patients (51%). Of the 20 patients with a failure, the original transsphincteric fistula persisted in 12 patients. In 8 patients, the transsphincteric fistula was converted into an intersphincteric fistula. These patients underwent subsequent fistulectomy, which was successful in all of them. The overall healing rate was 71%. This was a preliminary observational study with no control group. : The ligation of the intersphincteric fistula tract procedure is prone to infection and does not enhance the outcome of flap repair.


REEP6 knockout leads to defective β-adrenergic signaling in adipocytes and promotes obesity-related metabolic dysfunction.
The mobilization and catabolism of lipid energy is a central function of adipocytes that is under the control of the β-adrenergic signaling pathway, and defects in β-adrenergic signaling in adipocytes have been linked to obesity and obesity-related metabolic diseases. Receptor expression-enhancing proteins (REEPs) are endoplasmic reticulum (ER) proteins that play critical roles in subcellular targeting of receptor signaling complexes. Examination of gene expression profiles indicates that, among REEPs expressed in adipocytes, REEP6 expression is uniquely upregulated by sympathetic nervous system activation, suggesting involvement in regulating adrenergic signal transduction. The aim of this study was to assess the contribution of REEP6 to the thermogenic activation of adipocytes and characterize the metabolic consequences of REEP6 deficiency in vivo. Expression levels of Reep6 in adipose tissue were examined by using public transcriptomic data and validated by Western blot and qPCR analyses. Adipocyte-specific regulatory roles of REEP6 were investigated in vitro in C3H10T1/2 adipocytes and in primary adipocytes obtained from REEP6 KO mice. Effects of in vivo REEP6 deficiency on energy expenditure were measured by indirect calorimetry. Mitochondrial content in adipose tissue was accessed by immunoblot, mitochondrial DNA analysis, and confocal and electron microscopy. Effects of REEP6 KO on obesity-induced metabolic dysfunction were tested in a high-fat diet-induced obesity mouse model by glucose tolerance test, Western blot, and histological analyses. REEP6 expression is highly enriched in murine adipocytes and is sharply upregulated upon adipocyte differentiation and by cold exposure. Inactivation of REEP6 in mice increased adiposity, and reduced energy expenditure and cold tolerance. REEP6 KO severely reduced protein kinase A-mediated signaling in BAT and greatly reduced mitochondrial mass. The effect of REEP6 inactivation on diminished β-adrenergic signaling was reproduced in cultured adipocytes, indicating that this effect is cell-autonomous. REEP6 KO also suppressed expression of adenylate cyclase 3 (Adcy3) in brown adipose tissue and knockdown of REEP6 in adipocytes reduced targeting of ADCY3 to the plasma membrane. Lastly, REEP6 KO exacerbated high-fat diet-induced insulin resistance and inflammation in adipose tissue. This study indicates that REEP6 plays an important role in β-adrenergic signal transduction in adipocytes involving the expression and trafficking of Adcy3. Genetic inactivation of REEP6 reduces energy expenditure, increases adiposity, and the susceptibility to obesity-related metabolic dysfunction.


Versatile Optofluidic Solid-Core/Liquid-Cladding Waveguide Based on Evanescent Wave Excitation.
In this paper, we present the design and operation of a solid-core/liquid-cladding (SL) waveguide excited by an evanescent wave. To do this, an optical fiber is integrated into a microfluidic channel and pumped along the fiber axis, ensuring the cladding solution is excited by the evanescent field of the guided mode at the core/cladding interface. The pump beam is guided by the total internal reflection in the fiber, providing a uniform excitation along the microfluidic channel. The evanescent wave provides precise excitation to the dye molecules in close proximity to the core/cladding interface, which significantly reduces the background fluorescence and increases the signal-to-noise ratio. Fluorescence intensity measurements of different dye concentrations and refractive indices of the cladding solution are conducted to evaluate their influences on the propagation loss, which shows that the peak intensity propagation loss can be as low as about 0.1 dB/cm. We further exemplify that the intensity of the fluorescence emission and the dye concentration show good linearity when the dye is in the low concentration region (<250 μM). A broad-band and simultaneous light source with a single pump light is also demonstrated by employing cascade SL waveguide segments through fluorescence resonance energy transfer. The proposed SL waveguide demonstrates excellent robustness and is easy to fabricate and use, providing a versatile platform for a variety of applications, such as high-sensitivity detection of low-concentration samples, multiband on-chip light sources, and simultaneous measurement of multiplexed parameters.


A comparison of thoracolumbosacral orthoses and SpineCor treatment of adolescent idiopathic scoliosis patients using the Scoliosis Research Society standardized criteria.
SpineCor is a relatively new bracing system that uses dynamic bracing concepts in the treatment of adolescent idiopathic scoliosis (AIS). Limited data are available regarding its effectiveness. This study compared treatment outcomes of 2 groups of AIS patients treated via either a conventional rigid thoracolumbosacral orthoses (TLSO) or a SpineCor nonrigid orthosis. We identified 2 scoliosis patient cohorts: 35 patients treated with a TLSO and 32 patients treated with a SpineCor orthosis. All patients included in these groups conformed with the Scoliosis Research Society (SRS) standardized criteria for AIS bracing: (1) Risser < or =2, (2) curve magnitude 25 to 40 degrees, (3) age > or =10 years. Outcomes were SRS standardized with failure being defined as curve progression > or =6 degrees, or ever exceeding 45 degrees, or having surgery recommended before skeletal maturity. All patients were followed through the completion of brace treatment or attainment of other treatment end points. The Yates corrected chi test and unpaired t test were used for data analysis. The 35 patients (32 girls, 3 boys) in the TLSO group had an average age of 13 years (range: 11.1-16.8) and an average primary curve magnitude of 33 degrees (range: 25-40 degrees). Follow-up averaged 2 years (range: 8-61 m) from the beginning of brace treatment. The 32 patients (28 girls, 4 boys) in the SpineCor group had an average age of 13 years (range: 11-15.2) and an average primary curve magnitude of 31 degrees (range: 25-40 degrees). Follow-up for this group averaged 2 years and 6 months (range: 13-73 mo) from the beginning of brace treatment. No significant difference (P=0.75) was found using the more strict outcome measure (< or =5-degree curve progression) as the success rates were 60% (21/35) for TLSO and 53% (17/32) for SpineCor. Similarly, no significant difference (P=0.62) was found using the more liberal outcome measure (never reached 45 degrees) as the success rates were 80% (28/35) for TLSO and 72% (23/32) for SpineCor. We were unable to identify any significant differences in brace treatment outcomes when comparing TLSO and SpineCor treated patients.


Establishing normal values of moving two-point discrimination in children and adolescents.
To establish normal values of moving two-point discrimination (2pd) in children and adolescents, bilateral median and ulnar nerve distribution in 313 subjects aged 4 to 18 years was evaluated. A moving 2pd of 2 to 3mm for both the median and ulnar nerve distributions bilaterally was found in 270 subjects. 2% (N = 5) had moving 2pds of 4mm for both right and left median nerve distributions. There was a significant increase in mean age with 2, 3 and 4mm of moving 2pd for median and ulnar nerves bilaterally. There was no significant difference between sexes for ulnar nerves bilaterally or left median nerve. A borderline difference was found between the sexes for the right median nerve. Multivariate logistic regression revealed age as a significant predictor of discrimination for all variables. Significantly more subjects had a moving 2pd of 4mm in the ulnar nerve distribution than in the median nerve distribution.


An evolutionary framework outlining the integration of individual social and spatial ecology.
Behaviour is the interface between an organism and its environment, and behavioural plasticity is important for organisms to cope with environmental change. Social behaviour is particularly important because sociality is a dynamic process, where environmental variation influences group dynamics and social plasticity can mediate resource acquisition. Heterogeneity in the ecological environment can therefore influence the social environment. The combination of the ecological and social environments may be interpreted collectively as the "socioecological environment," which could explain variation in fitness. Our objective was to outline a framework through which individual social and spatial phenotypes can be integrated and interpreted as phenotypes that covary as a function of changes in the socioecological environment. We propose the socioecological environment is composed of individual behavioural traits, including sociality and habitat selection, both of which are repeatable, potentially heritable and may reflect animal personality traits. We also highlight how ecological and social niche theory can be applied to the socioecological environment framework, where individuals occupy different socioecological niches. Individual sociality and habitat selection are also density-dependent, and theory predicts that density-dependent traits should affect reproduction, survival, and therefore fitness and population dynamics. We then illustrate the proximate links between sociality, habitat selection and fitness as well as the ultimate, and possibly adaptive, consequences associated with changes in population density. The ecological, evolutionary and applied implications of our proposed socioecological environment framework are broad and changes in density could influence individual fitness and population dynamics. For instance, human-induced environmental changes can influence population density, which can affect the distribution of social and spatial phenotypes within a population. In summary, we outline a conceptual framework that incorporates individual social and spatial behavioural traits with fitness and we highlight a range of ecological and evolutionary processes that are likely associated with the socioecological environment.


Di(hydroperoxy)cycloalkane Adducts of Triarylphosphine Oxides: A Comprehensive Study Including Solid-State Structures and Association in Solution.
Four new di(hydroperoxy)cycloalkane adducts (Ahn adducts) of p-Tol3PO (1) and o-Tol3PO (2), namely, p-Tol3PO·(HOO)2C(CH2)5 (3), o-Tol3PO·(HOO)2C(CH2)5 (4), p-Tol3PO·(HOO)2C(CH2)6 (5), and o-Tol3PO·(HOO)2C(CH2)6 (6), have been synthesized and fully characterized. Their single crystal X-ray structures have been determined and analyzed. The 31P NMR data are in accordance with hydrogen bonding of the di(hydroperoxy)alkanes to the P═O groups of the phosphine oxides. Due to their high solubility in organic solvents, natural abundance 17O NMR spectra of 1-6 could be recorded, providing the signals for the P═O groups and additionally the two different oxygen nuclei in the O-OH groups in the adducts 3-6. The association and mobility of 3-6 were explored by 1H DOSY (diffusion ordered spectroscopy) NMR, which indicated persistent hydrogen bonding of the adducts in solution. Competition experiments with phosphine oxides allowed ranking of the affinities of the di(hydroperoxy)cycloalkanes for the different phosphine oxide carriers. On the basis of variable temperature 31P NMR investigations, the Gibbs energies of activation ΔG‡ for the adduct dissociation processes of 3-6 at different temperatures, as well as the enthalpy ΔH‡ and entropy ΔS‡ of activation, have been determined. IR spectroscopy of 3-6 corroborated the hydrogen bonding, and in the Raman spectra, the ν(O-O) stretching bands have been identified, confirming the presence of peroxy groups in the solid materials. The high solubilities in selected organic solvents have been quantified.


HIV-1 TAR RNA spontaneously undergoes relevant apo-to-holo conformational transitions in molecular dynamics and constrained geometrical simulations.
We report all-atom molecular dynamics and replica exchange molecular dynamics simulations on the unbound human immunodeficiency virus type-1 (HIV-1) transactivation responsive region (TAR) RNA structure and three TAR RNA structures in bound conformations of, in total, approximately 250 ns length. We compare the extent of observed conformational sampling with that of the conceptually simpler and computationally much cheaper constrained geometrical simulation approach framework rigidity optimized dynamic algorithm (FRODA). Atomic fluctuations obtained by replica-exchange molecular dynamics (REMD) simulations agree quantitatively with those obtained by molecular dynamics (MD) and FRODA simulations for the unbound TAR structure. Regarding the stereochemical quality of the generated conformations, backbone torsion angles and puckering modes of the sugar-phosphate backbone were reproduced equally well by MD and REMD simulations, but further improvement is needed in the case of FRODA simulations. Essential dynamics analysis reveals that all three simulation approaches show a tendency to sample bound conformations when starting from the unbound TAR structure, with MD and REMD simulations being superior with respect to FRODA. These results are consistent with the experimental view that bound TAR RNA conformations are transiently sampled in the free ensemble, following a conformation selection model. The simulation-generated TAR RNA conformations have been successfully used as receptor structures for docking. This finding has important implications for RNA-ligand docking in that docking into an ensemble of simulation-generated RNA structures is shown to be a valuable means to cope with large apo-to-holo conformational transitions of the receptor structure.


Unusual timing of CD127 expression by mouse uterine natural killer cells.
Decidualization, a progesterone-dependent process that alters endometrial stromal cells at implantation sites in humans and rodents, is accompanied by a highly regulated, NK cell-dominated leukocyte influx into decidual basalis (DB). Whether uNK cells differentiate from uterine progenitor cells is unknown, as are the mechanisms restricting leukocytes to DB. We asked if cells expressing the early NK lineage marker CD127 (IL-7Rα) occurred in mouse decidua. CD127 was absent from gd6.5 decidual lymphoid cells but became expressed by a mature uNK cell subset in gd10.5 DB. DB and transient myometrial structures (MLAp) that ring maternal blood vessels supplying placentae expressed IL-7 and TSLP, the CD127 ligands, but with differing temporal and spatial patterns. UNK cells expressed TSLPR, and study of gd10.5 implantation sites from mice deleted for IL-7, CD127, or TSLPR suggested that IL-7 and its receptor have physiological roles in limiting expansion of immature uNK cells within MLAp, while the TSLP signaling pathway is used in DB to sustain IFN-γ production from a subset of mature uNK cells. Regionalized, dynamic expression of the additional lymphoid organ stromal markers gp38/podoplanin and ER-TR7, but not CD157, were seen by immunohistochemistry in implantation sites, and DB and MLAp contained transcripts for Aire, a tolerance-promoting factor. These observations suggest that CD127(+) NK lineage progenitors are not present in the early postimplantation period of mouse uterus and that decidualized endometrial stroma has key immunoregulatory properties.


[[Population, birth, and death in Japan for the period 1890-1920]].
"Japanese mortality statistics since 1872 show upward [trends] in overall mortality until 1920, and thereafter mortality goes down. Whether this was true or just...caused by improvement in [the] death registration rate has been a matter of debate. The author tried to examine the accuracy and completeness of death registration data for the period 1890-1920....[It is found that] registered mortality data for the period 1890-1920 are believed to be highly reliable and would be a valuable source of data for the study of the early stage of mortality transition." (SUMMARY IN ENG)


Integrating life stages into ecological niche models: a case study on tiger beetles.
Detailed understanding of a species' natural history and environmental needs across spatial scales is a primary requisite for effective conservation planning, particularly for species with complex life cycles in which different life stages occupy different niches and respond to the environment at different scales. However, niche models applied to conservation often neglect early life stages and are mostly performed at broad spatial scales. Using the endangered heath tiger beetle (Cicindela sylvatica) as a model species, we relate presence/absence and abundance data of locally dispersing adults and sedentary larvae to abiotic and biotic variables measured in a multiscale approach within the geographic extent relevant to active conservation management. At the scale of hundreds of meters, fine-grained abiotic conditions (i.e., vegetation structure) are fundamental determinants of the occurrence of both life stages, whereas the effect of biotic factors is mostly contained in the abiotic signature. The combination of dense heath vegetation and bare ground areas is thus the first requirement for the species' preservation, provided that accessibility to the suitable habitat is ensured. At a smaller scale (centimetres), the influence of abiotic factors on larval occurrence becomes negligible, suggesting the existence of important additional variables acting within larval proximity. Sustained significant correlations between neighbouring larvae in the models provide an indication of the potential impact of neighbourhood crowding on the larval niche within a few centimetres. Since the species spends the majority of its life cycle in the larval stage, it is essential to consider the hierarchical abiotic and biotic processes affecting the larvae when designing practical conservation guidelines for the species. This underlines the necessity for a more critical evaluation of the consequences of disregarding niche variation between life stages when estimating niches and addressing effective conservation measures for species with complex life cycles.


[Significance of diagnostic aspects in general practice].
The role of the 'diagnosis' in general practice is different from that in teaching hospitals, but a broader definition is needed. In general practice the spectrum of diagnoses appears to be almost unlimited ('for every patient his own diagnosis'). Therefore, the author calls in question any classification system. In a personal study of 300 consultations in the offices of six Swiss general practitioners, no main diagnosis was reported in 16%, and in one third the main diagnosis was uncertain. The impact of the diagnosis on the therapeutic consequences or on prognosis seems to be overestimated. Of the stated diagnoses most were somatic, but not in the sense of 'clinical' entities. Only few patients are interested in our diagnostic terms. Significant inter-practitioner variations in the diagnostic approach are discussed.


Methyl/allyl monolayer on silicon: efficient surface passivation for silicon-conjugated polymer hybrid solar cell.
We demonstrate a hybrid Schottky junction solar cell based on methyl/allyl groups terminated silicon nanowire arrays (SiNWs) and poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) with a power conversion efficiency (PCE) of 10.2%. The methyl/allyl organic monolayer on silicon can act as an excellent passivation layer for suppressing surface charge recombination, which is characterized by grazing angle attenuated total reflectance Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements. The transient and steady electric output characteristics measurements indicate that the density of trap states of SiNWs are dramatically suppressed by methyl/allyl surface modification. In addition, the device based on methyl/allyl passivated SiNWs exhibits improved stable electrical output over those based on either methyl or allyl passivated ones. The improved PCE and good stability of the device are ascribed to efficient functionalization of the SiNW surface.


Mitroflow bioprosthesis stent deformation: a rare cause of early prosthetic stenosis.
We report the case of a severe prosthetic aortic stenosis in a 61-year-old male patient with an aortic Mitroflow LF bioprosthesis (Sorin Group) at early (6 months) postoperative echocardiographic follow-up. At reintervention, we found significant stent deformation, asymmetric orientation of the posts, and subsequent central kinking and prolapse of one leaflet. Maldistribution of pledgeted mattress sutures over the flexible stent was found to be the origin of its permanent deformation. Simple technical preventive strategies of this previously unreported complication are suggested.


Health education: message and medium.
During 1979, 1980 and 1981, the Scottish Health Education Unit of the Scottish Health Service Common Services Agency is funding a research project involving the production and evaluation of six video recorded health education programmes. The project is being undertaken by the Department of Community Medicine of the Forth Valley Health Board and the Department of Continuing Medicine, Stirling University. In the first of two articles, Dr J.L. Graham, Chief Administrative Medical Officer, Forth Valley Health Board, and Chairman of the project's steering committee, describes the benefits of this approach.


Characteristics of older adults with self-reported stooping, crouching, or kneeling difficulty.
Stooping, crouching, and kneeling (SCK) are fundamental components of daily living tasks, and nearly a quarter of older adults report a lot of difficulty or inability to perform these movements. This study examined characteristics associated with SCK difficulty to explore underlying mechanisms and remediation strategies. One hundred eighty-four older adults with no, low, or high SCK difficulty underwent a comprehensive laboratory visit at the University of Michigan. Twenty-one percent of participants (n = 39) reported a lot of difficulty or inability to stoop, crouch, or kneel. Characteristics independently associated with increasing SCK difficulty were self-reported leg joint limitations, (odds ratio [OR] = 3.84; 95% confidence interval [CI], 1.64-9.01), Activities-specific Balance Confidence Scale score (OR = 0.97; 95% CI, 0.95-0.99), and knee extension strength (OR = 0.72; 95% CI, 0.55-0.94). Increasing SCK difficulty is associated with balance confidence as well as leg limitations. Remediation of SCK difficulty will likely require a program that encompasses both behavioral and physical issues.


Electrochemical Synthesis of Dimeric 2-Oxindole Sharing Vicinal Quaternary Centers Employing Proton-Coupled Electron Transfer.
Dimerization of 3-substituted 2-oxindoles has been developed under a mild electrochemical condition, avoiding toxic chemical oxidants and metal by-products. This methodology forms a C(sp3)-C(sp3) bond at the pseudobenzylic position of two partners of 2-oxindoles with a broad substrate scope. These dimeric structural motifs are important building blocks for the total synthesis of pyrroloindoline alkaloids. Furthermore, this work demonstrates in-depth mechanistic insights employing electrochemistry, which suggests a stepwise one proton transfer (PT) and two electron transfer (ET) processes. Most significantly, reaction rate acceleration has been demonstrated by exploiting the base-assisted proton-coupled electron transfer (PCET) pathway. Hence, this work brings a new dimension in the field of electro-organic synthesis with the help of nature's favorite kinetic route, i.e., PCET, to lower the kinetic barrier.


Ethanol injection of hepatic tumors.
To assess the efficacy of intratumoral injections of absolute ethanol in the treatment of hepatic tumors, 18 New Zealand White rabbits underwent implantation of two 1-mm3 fragments of the VX-2 carcinoma. The animals were reexplored 2 weeks postimplant and the tumors measured. One nodule was treated by intratumoral injections of 2.28 +/- 0.72 mL of absolute ethanol; the second was injected with an equal amount of normal saline. The animals were sacrificed 4 weeks postimplant, and the tumors were measured and microscopically examined. On gross inspection, tumor size, expressed as the product of the largest and smallest diameters, was 4.59 +/- 3.4 cm2 for the ethanol-injected tumors vs 6.73 +/- 2.1 cm2 for the saline-treated nodules (p = .01). Histologic sections through the largest tumor diameter were microscopically examined using a computerized image analyzer. The mean cross-sectional area of viable tumor was 0.51 +/- 0.3 cm2 for the ethanol-treated nodules vs 2.01 +/- 0.5 cm2 for the saline-treated nodules (p less than .001). Contrast-enhanced CT and MRI studies were able to provide valuable information in terms of tissue characterization, which will be useful in differentiating viable tumor from necrotic tumor and infarcted liver. We conclude that intratumoral ethanol injection inhibits growth of liver tumors in this experimental model and deserves further study.


Substance P-induced respiratory excitation is blunted by delta-receptor specific opioids in the rat medulla oblongata.
The effects of substance P (SP) and the naturally occurring met-enkephalin and the synthetic mu-specific opioid agonist, DAGO (Tyr-D-Ala-Gly-N-Methy-Phe-Gly-ol) and the delta-specific opioid agonist DADL (Tyr-D-Ala-Gly-Phe-D-Leu) on basal ventilation were investigated in halothane-anaesthetized rats. Local injections of SP (0.75-1.5 nmol) in the ventrolateral medulla oblongata (VLM), e.g. nucleus paragigantocellularis, and nucleus reticularis lateralis increased ventilation because of an elevation of tidal volume. Met-enkephalin induced a short-lasting ventilatory depression mainly because of a depression of tidal volume. Activation of delta- and mu-opioid receptors in the VLM by local application of DADL and DAGO, respectively, induced ventilatory depression, which was later in onset and more long-lasting. Local administration of met-enkephalin into the VLM also produced a long-lasting inhibition of the SP-induced ventilatory excitation. A similar blockade of the SP-induced excitatory ventilatory response could be elicited by DADL but not by DAGO. This antagonistic effect was attenuated by local application of the delta-opioid receptor antagonist ICI 154. 129. We conclude that the naturally occurring met-enkephalin as well as synthetic mu- and delta-specific enkephalin analogues (DAGO and DADL, respectively) in VLM depress basal ventilation by an effect on inspiratory drive. There is a functional antagonism between activation of delta-opioid receptors and SP receptors into the VLM in respect to respiratory regulation.


Deletion of exons 1a-2 of BRCA1: a rather frequent pathogenic abnormality.
Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk of developing breast and/or ovarian cancer. The majority of mutations in these genes are small point mutations. Since the development of multiplex ligation-dependent probe amplification, an increasing number of large genomic rearrangements have been detected. Here, we describe the characterization of pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of heterozygosity, array comparative genomic hybridization, and sequence analyses. Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1, encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an 8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This observation, together with the previously described families with exon 1a-2 deletions of BRCA1, demonstrates that this type of deletions is relatively frequent in breast/ovarian cancer families.


The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling.
SignificanceTranscription-coupled repair (TCR) involves four core proteins: CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB. We deleted the UVSSA protein using CRISPR-Cas9 in an aneuploid cell line, HEK293, and determined the functional consequences. The knockout cell line was sensitive to transcription-blocking lesions but not sensitive to oxidative agents or PARP inhibitors, unlike CSB. Knockout of UVSSA also activated ATM, like CSB, in transcription-arrested cells. The phenotype of UVSSA, especially its rarity, suggests that many TCR-deficient patients and tumors fail to be recognized clinically.


A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.
Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE-/-) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE-/- mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE-/- mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.


Pressure-jump studies of the folding/unfolding of trp repressor.
The dimeric protein, trp apo-repressor of Escherichia coli has been subjected to high hydrostatic pressure under a variety of conditions, and the effects have been monitored by fluorescence spectroscopic and infra-red absorption techniques. Under conditions of micromolar protein concentration and low, non-denaturing concentrations of guanidinium hydrochloride (GuHCl), tryptophan and 8-anilino-1-naphthalene sulfonate (ANS) fluorescence detected high pressure profiles demonstrate that pressures below 3 kbar result in dissociation of the dimer to a monomeric species that presents no hydrophobic binding sites for ANS. The FTIR-detected high pressure profile obtained under significantly different solution conditions (30 mM trp repressor in absence of denaturant) exhibits a much smaller pressure dependence than the fluorescence detected profiles. The pressure-denatured form obtained under the FTIR conditions retains about 50 % alpha-helical structure. From this we conclude that the secondary structure present in the high pressure state achieved under the conditions of the fluorescence experiments is at least as disrupted as that achieved under FTIR conditions. Fluorescence-detected pressure-jump relaxation studies in the presence of non-denaturing concentrations of GuHCl reveal a positive activation volume for the association/folding reaction and a negative activation volume for dissociation/unfolding reaction, implicating dehydration as the rate-limiting step for association/folding and hydration as the rate-limiting step for unfolding. The GuHCl concentration dependence of the kinetic parameters place the transition state at least half-way along the reaction coordinate between the unfolded and folded states. The temperature dependence of the pressure-jump fluorescence-detected dissociation/unfolding reaction in the presence of non-denaturing GuHCl suggests that the curvature in the temperature dependence of the stability arises from non-Arrhenius behavior of the folding rate constant, consistent with a large decrease in heat capacity upon formation of the transition state from the unfolded state. The decrease in the equilibrium volume change for folding with increasing temperature (due to differences in thermal expansivity of the folded and unfolded states) arises from a decrease in the absolute value for the activation volume for unfolding, thus indicating that the thermal expansivity of the transition state is similar to that of the unfolded state.


Artesunate Suppresses the Proliferation and Development of Estrogen Receptor-α-Positive Endometrial Cancer in HAND2-Dependent Pathway.
Endometrial cancer (EC) is a common leading cause of cancer-related death in women, which is associated with the increased level of estrogen in the body. Artesunate (ART), an active compound derived from Artemisia annua L., exerted antitumor properties in several cancer types. However, the role of artesunate and the molecular basis on EC remains unclear. Here, we aimed to explore the effects and mechanisms of artesunate. Our results identified that estrogen receptor-α (ER-α) was a key factor for the type I EC (ER-α-positive), which might suppress the downstream LKB1/AMPK/mTOR pathway. Besides, we found ART significantly inhibited tumor proliferation in a dose-dependent manner. Mechanistic studies identified that ART led to tumor cell apoptosis and cell cycle arrest by downregulating the ER-α expression and activating the LKB1/AMPK/mTOR pathway. In addition, we found ART could increase the expression of heart and neural crest derivatives expressed 2 (HAND2) in the ER-α-positive EC cells, which could interact with ER-α. Through the gain-and loss-function experiments, we showed that over expression of HAND2 repressed the proliferation and migration of ER-α-positive EC cells via inhibition of ER-α expression. HAND2 knockdown increased ER-α expression and alleviated the antitumor effect of ART in vitro and in vivo. Overall, our study first showed that ART could be an effective antitumor agent through modulating ER-α-mediated LKB1/AMPK/mTOR pathway in the HAND2 dependent manner. Our findings provide an effective therapeutic agent for ER-α-positive EC treatment.


A new 3D mesoporous carbon replicated from commercial silica as a catalyst support for direct conversion of cellulose into ethylene glycol.
Tungsten carbide nanoparticles were supported on a new 3D mesoporous carbon replicated from commercial silica and exhibited selectivity as high as 72.9% for the catalytic conversion of cellulose into ethylene glycol.


Using the Rasch measurement model in psychometric analysis of the Family Effectiveness Measure.
Valid assessment of family functioning can play a vital role in optimizing client outcomes. Because family functioning is influenced by family structure, socioeconomic context, and culture, existing measures of family functioning-primarily developed with nuclear, middle-class European American families-may not be valid assessments of families in diverse populations. The Family Effectiveness Measure was developed to address this limitation. The aim of this study was to test the Family Effectiveness Measure with data from a primarily low-income African American convenience sample using the Rasch measurement model. A sample of 607 adult women completed the measure. Rasch analysis was used to assess unidimensionality, response category functioning, item fit, person reliability, differential item functioning by race and parental status, and item hierarchy. Criterion-related validity was tested using correlations with five other variables related to family functioning. The Family Effectiveness Measure measures two separate constructs: The Effective Family Functioning construct was a psychometrically sound measure of the target construct that was more efficient because of the deletion of 22 items. The Ineffective Family Functioning construct consisted of 16 of those deleted items but was not as strong psychometrically. Items in both constructs evidenced no differential item functioning by race. Criterion-related validity was supported for both. In contrast to the prevailing conceptualization that family functioning is a single construct, assessed by positively and negatively worded items, use of the Rasch analysis suggested the existence of two constructs. Whereas the Effective Family Functioning scale is a strong and efficient measure of family functioning, the Ineffective Family Functioning scale will require additional item development and psychometric testing.


Disaster and emergency management: Canadian nurses' perceptions of preparedness on hospital front lines.
Three years following the global outbreak of severe acute respiratory syndrome (SARS), a national, Web-based survey of Canadian nurses was conducted to assess perceptions of preparedness for disasters and access to support mechanisms, particularly for nurses in emergency and critical care units. The following hypotheses were tested: (1) nurses' sense of preparedness for infectious disease outbreaks and naturally occurring disasters will be higher than for chemical, biological, radiological, and nuclear (CBRN)-type disasters associated with terrorist attacks; (2) perceptions of preparedness will vary according to previous outbreak experience; and (3) perceptions of personal preparedness will be related to perceived institutional preparedness. Nurses from emergency departments and intensive care units across Canada were recruited via flyer mailouts and e-mail notices to complete a 30-minute online survey. A total of 1,543 nurses completed the survey (90% female; 10% male). The results indicate that nurses feel unprepared to respond to large-scale disasters/attacks. The sense of preparedness varied according to the outbreak/disaster scenario with nurses feeling least prepared to respond to a CBRN event. A variety of socio-demographic factors, notably gender, previous outbreak experience (particularly with SARS), full-time vs. part-time job status, and region of employment also were related to perceptions of risk. Approximately 40% of respondents were unaware if their hospital had an emergency plan for a large-scale outbreak. Nurses reported inadequate access to resources to support disaster response capacity and expressed a low degree of confidence in the preparedness of Canadian healthcare institutions for future outbreaks. Canadian nurses have indicated that considerably more training and information are needed to enhance preparedness for frontline healthcare workers as important members of the response community.


Conservation of the northern spotted owl under the Northwest Forest Plan.
Development of the Northwest Forest Plan (NWFP) was motivated by concerns about the over-harvest of late-seral forests and the effects of intensive forest management on the long-term viability of the Northern Spotted Owl (Strix occidentalis caurina). Following several years of intense political and legal debates, the final NWFP was approved in 1994. Even though the plan evolved with a broad ecosystem perspective, it remained anchored in the Spotted Owl reserve design proposed in 1990. Based on a criterion of stable or increasing populations, a decade later it remains unclear whether the enactment of the NWFP has improved the conservation status of Spotted Owls. The results of intensive monitoring of several Spotted Owl populations for over a decade suggest a continuing range-wide decline even though rates of timber harvest have declined dramatically on federal lands. The cause of the decline is difficult to determine because the research needed to establish cause and effect relations has not been done. One plausible hypothesis is that the owl's life history greatly constrains its rate of population growth even when habitat is no longer limiting. Since enactment of the NWFP, new threats have arisen, including the movement of Barred Owls (S. varia) into the range of the Spotted Owl, political pressure to increase levels of timber harvest, and recent changes to forest laws that eliminate the requirement to assess the viability of wildlife populations on U.S. Department of Agriculture Forest Service lands. At this time is appears that Spotted Owl conservation rests critically on continued implementation of the protections afforded by the NWFP and the U.S. Endangered Species Act.


Cancer Pain Assessment and Classification.
More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional ways of classifying pain in the cancer population include distinguishing pain etiology, clinical characteristics related to pain and the patient, pathophysiology, and the use of already validated classification systems. Concepts like breakthrough, nociceptive, neuropathic, and mixed pain are very important in the assessment of pain in this population of patients. When dealing with patients affected by cancer pain it is also very important to be familiar to the characteristics of specific pain syndromes that are usually encountered. In this article we review methods presently applied for classifying cancer pain highlighting the importance of an accurate clinical evaluation in providing adequate analgesia to patients.


Glycosite-deleted mRNA of SARS-CoV-2 spike protein as a broad-spectrum vaccine.
Development of the messenger RNA (mRNA) vaccine has emerged as an effective and speedy strategy to control the spread of new pathogens. After vaccination, the mRNA is translated into the real protein vaccine, and there is no need to manufacture the protein in vitro. However, the fate of mRNA and its posttranslational modification inside the cell may affect immune response. Here, we showed that the mRNA vaccine of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with deletion of glycosites in the receptor-binding domain (RBD) or especially the subunit 2 (S2) domain to expose more conserved epitopes elicited stronger antibody and CD8+ T cell responses with broader protection against the alpha, beta, gamma, delta, and omicron variants, compared to the unmodified mRNA. Immunization of such mRNA resulted in accumulation of misfolded spike protein in the endoplasmic reticulum, causing the up-regulation of BiP/GRP78, XBP1, and p-eIF2α to induce cell apoptosis and strong CD8+ T cell response. In addition, dendritic cells (DCs) incubated with S2-glysosite deleted mRNA vaccine increased class I major histocompatibility complex (MHC I) expression. This study provides a direction for the development of broad-spectrum mRNA vaccines which may not be achieved with the use of expressed proteins as antigens.


Does surgical treatment within 4 hours after trauma have an influence on neurological remission in patients with acute spinal cord injury?
The proper timing for surgery in patients with acute spinal cord injury is controversial. This study was conducted to detect if there is an advantage in early (within the first 4 hours after trauma) compared to late (between 4 and 24 hours after trauma) surgery on neurological outcome. In this single institution prospective cohort study, data were analyzed from 51 spinal cord injured patients with an average age of 43.4 (±19.2) years. The influence of early (29 patients within the first 4 hours) as opposed to late (22 patients between 4 and 24 hours) decompression was evaluated by comparing data for neurological outcome. Patients of the study collectively suffered acute spinal fractures from C2 to L3 (cervical 39.2%, thoracic 29.4%, and lumbal 21.6%) or nonosseous lesions (9.8%). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades were assessed at time of admission and 6 months after trauma or longer depending on the time of release. Surgical treatment included early stabilization and decompression within 24 hours. No significant difference between improved neurological function, measured with the AIS, and an early or late surgery time can be seen (P=0.402). Furthermore, binary logistic regression shows no significant difference between sex or age, and AIS improvement as possible confounders. In our study, all patients with spinal cord injury were treated with spine stabilization and decompression within the first 24 hours after trauma. Surgical decompression within the first 4 hours after trauma was not associated with improved neurological outcome compared to treatment between 4 and 24 hours. In a clinical context, this indicates that there is a time frame of at least 1 day in which optimal care is possible.


Compressive preload reduces segmental flexion instability after progressive destabilization of the lumbar spine.
Biomechanical human cadaveric study. We hypothesized that increasing compressive preload will reduce the segmental instability after nucleotomy, posterior ligament resection, and decompressive surgery. The human spine experiences significant compressive preloads in vivo due to spinal musculature and gravity. Although the effect of destabilization procedures on spinal motion has been studied, the effect of compressive preload on the motion response of destabilized, multisegment lumbar spines has not been reported. Eight human cadaveric spines (L1-sacrum, 51.4 ± 14.1 yr) were tested intact, after L4-L5 nucleotomy, after interspinous and supraspinous ligaments transection, and after midline decompression (bilateral laminotomy, partial medial facetectomy, and foraminotomy). Specimens were loaded in flexion (8 Nm) and extension (6 Nm) under 0-N, 200-N, and 400-N compressive follower preload. L4-L5 range of motion (ROM) and flexion stiffness in the high-flexibility zone were analyzed using repeated-measures analysis of variance and multiple comparisons with the Bonferroni correction. With a fixed set of loading conditions, a progressive increase in segmental ROM along with expansion of the high-flexibility zone (decrease of flexion stiffness) was noted with serial destabilizations. Application of increasing compressive preload did not substantially change segmental ROM, but did significantly increase the segmental stiffness in the high-flexibility zone. In the most destabilized condition, 400-N preload did not return the segmental stiffness to intact levels. Anatomical alterations representing degenerative and iatrogenic instabilities are associated with significant increases in segmental ROM and decreased segmental stiffness. Although application of compressive preload, mimicking the effect of increased axial muscular activity, significantly increased the segmental stiffness, it was not restored to intact levels; thereby suggesting that core strengthening alone may not compensate for the loss of structural stability associated with midline surgical decompression. This suggests that there may be a role for surgical implants or interventions that specifically increase flexion stiffness and limit flexion ROM to counteract the iatrogenic instability resulting from surgical decompression. N/A.


Histone-tryptase interaction: H2A N-terminal tail removal and inhibitory activity.
The involvement of tryptase, the trypsin-like serine proteinase of mast cell granules, in many (patho)physiological conditions is now recognized. In vitro this enzyme is known to act as a potent growth factor for fibroblasts and epithelial cells. Moreover, a role in inflammatory diseases and in dermatological disorders characterized by increased cell turnover has been suggested for this protease. In an attempt to understand the molecular basis of tryptase activity, we have investigated the interaction in vitro between bovine tryptase and histones. Here we show that tryptase cleaves histone H2A at a specific site (Arg20-Ala21), resulting in the removal of the N-terminal flexible fragment of the molecule. Furthermore, we demonstrate that the H2A major fragment (H2A*, 109 residues) generated by hydrolysis and lacking the N-terminal domain, is a noncompetitive, reversible and highly specific inhibitor (Ki = 29 nM) of tryptase enzymatic activity. H2A* is able to inhibit the hydrolysis of a small substrate as well as the cleavage of fibronectin, a high-molecular-weight substrate of tryptase.


Moderating effects and maintenance of lung cancer cellular immune functions by CIK cell therapy.
To study the CIK cell treatment effects on regulation of cellular immune function disorders in patients with lung cancer, and to analyze the time characteristics. Cellular immune function was assessed by FCM, and patients with functional disorders were randomly divided into two groups, one given CIK cell therapy within 18 months (5 courses) and the other the controls, which were followed up for 1 year with cellular immune functions tested once a month. There were 5 types of cellular immunity, 4 of which are disorders; after CIK treatment, the improvement rate of the 4 groups were 79.1%, 70.8%, 76.0% and 70.0%, intergroup differences not being statistically significant (P=0.675), all significantly higher than in the control group (P=0.000). The median maintenance times for the 4 groups were 10.4 months (9.76-11.04), 8.4 months (7.86-8.94), 9.8 months (9.20-10.4) and 7.9 months (6.25-9.55), respectively. CIK cells were able to improve the immune functions of patients with lung cancer, the rate of improvement and maintenance time being related to the immune function before the treatment and CIK-cell-therapy courses.


Exploring rape myths, gendered norms, group processing, and the social context of rape among college women: a qualitative analysis.
The purpose of this research is to explore the negotiation strategies of college women as they interpret ambiguous rape scenarios. In focus groups, 1st- and 4th-year college women were presented with a series of three vignettes depicting incidents that meet the legal criteria for rape yet are ambiguous due to the presence of cultural rape myths, contexts involving alcohol consumption, varying degrees of consent, and a known perpetrator. These contexts are critical in understanding how college women define rape. Key findings indicated many of these college women utilized rape myths and norms within their peer groups to interpret rape scenarios.


Calcium-activated nucleotides 1 (CANT1)-driven nuclear factor-k-gene binding (NF-ĸB) signaling pathway facilitates the lung cancer progression.
Dysregulation of calcium-activated nucleotides 1 (CANT1) has been observed in different organs. Thus, its biological function in cancer has increasingly attracted researchers. The current work aims to study the CANT1 role in lung cancer and understand the underlying pathological mechanisms. High amplification of CANT1 was observed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared to normal tissues. The high-CANT1 patients showed a dismal prognosis in comparison with the low-CANT1 patients. Highly expressed CANT1 was significantly associated with the N stage of LUSC patients. Ectopic expression of CANT1 conspicuously increased the proliferation and viability of A549 cells. Conversely, CANT1 depletion resulted in adverse effects in H1299 cells. CANT1 depletion also resulted in the retardation of tumor growth in vivo. Mechanically, we found that CANT1 could elevate NF-ĸB (nuclear factor-k-gene binding) transcriptional activity in a concentration-dependent manner. This regulatory relationship was also established by the Western blot technique. Inhibiting NF-ĸB can significantly blunt the increased NF-κ-B Inhibitor-α (IκBα) expression caused by CANT1 overexpression in A549 cells. In conclusion, highly amplified CANT1 promotes the proliferation and viability of lung cancer cells. We also elucidate a new signaling axis of CANT1-NF-ĸB in lung cancer. This approach might be a promising strategy for lung cancer treatment.


Mediators of the inflammatory response to joint replacement devices.
Joint replacement surgery is one of the success stories of modern medicine, restoring mobility, diminishing pain and improving the overall quality of life for millions of people. Unfortunately, wear of these prostheses over time generates debris, which activates an innate immune response that can ultimately lead to periprosthetic resorption of bone (osteolysis) and failure of the implant. Over the past decade, the biological interactions between the particulate debris from various implant materials and the immune system have begun to be better understood. The wear debris induces a multifaceted immune response encompassing the generation of reactive oxygen species and damage-associated molecular patterns, Toll-like receptor signaling and NALP3 inflammasome activation. Acting alone or in concert, these events generate chronic inflammation, periprosthetic bone loss and decreased osteointegration that ultimately leads to implant failure.


[The influence of anamorphotic image formation on the visual evoked cortical potential].
The correction of astigmatism by spectacle lenses involves anamorphotic image formations and produces distortion of retinal images, putting strain on the sensory part of fusion. These distortions were artificially produced by anamorphotic telescopes in a group of emmetropic volunteers. In binocular visually evoked cortical potential (VECP), a transient increase in amplitudes was recordable after application of the anamorphotic distortions. The removal of anamorphotic telescopes resulted in a distinct decrease in amplitude, followed by an overshoot increase before recompensation to pretest values occurred. The amplitude reactions observed are suggested as being an objective indicator of the cortical fusion mechanism.


Elastic Tethers Between Separating Anaphase Chromosomes Regulate the Poleward Speeds of the Attached Chromosomes in Crane-Fly Spermatocytes.
Elastic "tethers" connect separating anaphase chromosomes in most (or all) animal cells. We tested whether tethers are involved in coordinating movements of separating anaphase chromosomes in crane-fly spermatocytes. In these cells the coupled movements of separating chromosomes become uncoupled after the tethers are severed by laser microbeam irradiation of the interzone region between the chromosomes (Sheykhani et al., 2017). While this strongly suggests that tethers are involved with coordinating the poleward chromosome movements, the experiments are open to another interpretation: laser irradiations that cut the tethers also might damage something else in the interzone, and those non-tether components might regulate chromosome movements. In the experiments reported herein we distinguish between those two possibilities by disabling the tethers without cutting the interzone. We cut the arms from individual chromosomes, thereby severing the mechanical connection between separating chromosomes, disconnecting them, without damaging components in the interzone. Disabling tethers in this way uncoupled the movements of the separating chromosomes. We thus conclude that tethers are involved in regulating the speeds of separating anaphase chromosomes in crane-fly spermatocytes.


Extracorporeal Membrane Oxygenation in Infarct-Related Cardiogenic Shock.
Mortality in infarct-related cardiogenic shock (CS) remains high, reaching 40-50%. In refractory CS, active mechanical circulatory support devices including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are rapidly evolving. However, supporting evidence of VA-ECMO therapy in infarct-related CS is low. The current review aims to give an overview on the basics of VA-ECMO therapy, current evidence, ongoing trials, patient selection and potential complications.


Penetrating trauma to the facial skeleton by pickaxe - case report.
Number of deaths related with injuries suffered as a result of experienced traumas is increasing. Penetrating traumas of the facial skeleton occur relatively rarely and much more often concern rather children than adults. Epidemiology relating this kind of trauma differs depending on the region of the world. In Poland, gunshot injuries as well as traumas caused by explosions of firecrackers or fireworks amount only to a slight percentage among all facial skeleton traumas, and the most common reason for penetrating traumas lies in accidents or assault with the use of sharp, narrow and long objects that easily enter bones of the facial skeleton. The present study reported the case of 50-year-old man who suffered from trauma of the facial skeleton, which resulted from foreign body (pickaxe) penetration into the subtemporal area, zygomatic arch and the right orbital cavity. The surgical treatment method and final outcome was presented and discussed.


In situ detection of cyclosporin A: evidence for nuclear localization of cyclosporine and cyclophilins.
The immunosuppressant cyclosporin A (CsA) forms a trimolecular complex with cyclophilin (CPH) and calcineurins (CN) and inhibits CN phosphatase activity. Inhibition of CN phosphatase by CsA prevents the dephosphorylation of a nuclear factor in the cytosol and its nuclear translocation to the nucleus. The intracellular distribution of CPH and CN was investigated in permeabilized Jurkat T lymphocytes and MRC fibroblasts using biochemical techniques and confocal microscopy. The site of CsA binding was identified in situ using a photoaffinity label derivative of CsA followed by immunodetection. Cyclophilin A (CPH-A) and CN display essentially a cytosolic localization by immunofluorescence, and additional nuclear CPH-A and CN are evidenced by Western blot analysis of purified nuclei and immunofluorescence. By contrast, cyclophilin B (CPH-B) has a punctuate and reticular distribution pattern in cytoplasm, indicating an association with the endoplasmatic reticulum, but its main location is in the nuclear matrix, sparing the nucleolar region. For the in situ detection of CsA binding sites, a photolabile cyclosporine derivative (PL-CS) was used that allowed the detection of covalently bound CsA by Ab. Using the biologically active PL-CS, a punctate cytoplasmatic and nuclear immunoreactivity was obtained, which was specific and competed only with active cyclosporine derivatives. Nuclear CPH-A and -B were labeled by PL-CS, and trimolecular complexes of labeled CPH and CN were obtained by chemically cross-linking nuclear extracts. We describe herein the accessibility of CsA to the nucleus, the presence and labeling in situ of nuclear CPH and CN. The current models of CsA action predict that CsA-CPH complexes inhibit CN activity in the cytosol. However, our present findings invite the hypothesis that CPH may capture the drug into the nucleus and target regulatory proteins or transcriptional control elements.


Implementing ward based clinical pharmacy services in an Ethiopian University Hospital.
Clinical pharmacy practice has developed internationally to expand the role of a pharmacist well beyond the traditional roles of compounding, dispensing and supplying drugs to roles more directly in caring for patients. Studies on the activities of the clinical pharmacist in an inpatient ward in resource constrained settings are scarce, however. To assess ward based clinical pharmacy services in an internal medicine ward of Jimma University Specialized Hospital. The study was carried out in the internal medicine ward from March to April, 2011 at Jimma University Specialized Hospital. The study design was a prospective observational study where pharmaceutical care services provided by clinical pharmacists for inpatients were documented over a period of two months. Interventions like optimization of rational drug use and physician acceptance of these recommendations were documented. Clinical significance of interventions was evaluated by an independent team (1 internist, 1 clinical pharmacologist) using a standardized method for categorizing drug related problems (DRPs). A total of 149 drug related interventions conducted for 48 patients were documented; among which 133(89.3%) were clinical pharmacists initiated interventions and 16(10.7%) interventions were initiated by other health care professionals. The most frequent DRPs underlying interventions were unnecessary drug therapy, 36(24.2%); needs additional drug therapy, 34(22.8%) and noncompliance, 29(19.5%). The most frequent intervention type was change of dosage/instruction for use, 23(15.4%). Acceptance rate by physicians was 68.4%. Among the interventions that were rated as clinically significant, 46(48.9%) and 25(26.6%) had major and moderate clinical importance respectively. Involving trained clinical pharmacists in the healthcare team leads to clinically relevant and well accepted optimization of medicine use in a resource limited settings. This approach can likely be generalized to other health care settings in the country to improve medication outcomes.


A novel prokaryotic L-arginine:glycine amidinotransferase is involved in cylindrospermopsin biosynthesis.
We report the first characterization of an L-arginine:glycine amidinotransferase from a prokaryote. The enzyme, CyrA, is involved in the pathway for biosynthesis of the polyketide-derived hepatotoxin cylindrospermopsin from Cylindrospermopsis raciborskii AWT205. CyrA is phylogenetically distinct from other amidinotransferases, and structural alignment shows differences between the active site residues of CyrA and the well-characterized human L-arginine:glycine amidinotransferase (AGAT). Overexpression of recombinant CyrA in Escherichia coli enabled biochemical characterization of the enzyme, and we confirmed the predicted function of CyrA as an L-arginine:glycine amidinotransferase by (1) H NMR. As compared with AGAT, CyrA showed narrow substrate specificity when presented with substrate analogs, and deviated from regular Michaelis-Menten kinetics in the presence of the non-natural substrate hydroxylamine. Studies of initial reaction velocities and product inhibition, and identification of intermediate reaction products, were used to probe the kinetic mechanism of CyrA, which is best described as a hybrid of ping-pong and sequential mechanisms. Differences in the active site residues of CyrA and AGAT are discussed in relation to the different properties of both enzymes. The enzyme had maximum activity and maximum stability at pH 8.5 and 6.5, respectively, and an optimum temperature of 32 °C. Investigations into the stability of the enzyme revealed that an inactivated form of this enzyme retained an appreciable amount of secondary structure elements even on heating to 94 °C, but lost its tertiary structure at low temperature (T(max) of 44.5 °C), resulting in a state reminiscent of a molten globule. CyrA represents a novel group of prokaryotic amidinotransferases that utilize arginine and glycine as substrates with a complex kinetic mechanism and substrate specificity that differs from that of the eukaryotic L-arginine:glycine amidinotransferases.


An exploration of group-based compassion-focused therapy for adolescents and their parents.
The long-term negative consequences of mental health problems during adolescence highlight the need for effective treatments. Compassion-focused therapy (CFT) aims to help individuals to enhance their ability to support and care for themselves and to alleviate shame and self-stigmatization. This non-randomized controlled trial examined the effectiveness of group-based CFT on perceived stress and the extent of self-compassion in a clinical sample of adolescents receiving psychiatric care for complex mental health difficulties and their parents. The participants were 43 adolescents (ages 14-17; 83.7 % female) under treatment at a child and adolescent psychiatric outpatient clinic in Sweden and their parents (n = 77; 61 % female). The adolescents volunteered for group-based CFT (n = 19); if they did not want to participate, they were asked to join the control group receiving treatment as usual (TAU, n = 24). The CFT parents were given the same treatment as their children in parallel parent groups. The participants completed questionnaires measuring self-compassion and perceived stress before and after treatment. Paired samples t-tests and independent samples t-tests assessed the within-group and between-group differences via change scores. The fathers scored highest on self-compassion and had less perceived stress at both times than the adolescents or mothers. There were no significant differences between the CFT and TAU groups in self-compassion or perceived stress at either time, and the effect sizes were small (g ≤ 0.25). The TAU mother group was the only group with a significantly changed mean self-compassion score post-treatment. Some patients seem to benefit from group-based CFT in ways similar to the benefits of specialized therapeutic approaches. Further research into the utility of CFT for adolescents with MH problems and their parents, as well as the long-term clinical effects of CFT for this group is needed.


Do postal questionnaires change GPs' workload and referral patterns?
We aimed to determine changes in workload in general practice associated with the postal administration of a health needs questionnaire. We carried out controlled before-and-after intervention study of the effects of delivering a postal questionnaire to assess needs for care for patients with arthropathies of the hip and knee, groin hernia and varicose veins, and to assess health service utilization, general health status and risk factors for cardiovascular disease. The setting was a seven-partner, fundholding, group practice in Avon. The subjects were patients registered with an NHS group practice situated in Backwell and Nailsea, Avon. The outcome measures were the frequency of consultation, home visits and night visits, reasons for consultation, referral to specialist agencies and patterns of prescribing. There was no significant difference between the study and control group in the year before and the year after the postal administration of the questionnaire with respect to changes in overall frequency of consultation, frequency of referral (including type of referral) and frequency of prescribing of non-steroidal anti-inflammatory drugs. In the study group there was a significant (P<0.05) reduction in the number of daytime home visits and prescriptions written for analgesics. Analysis of the records of those who had received a medical examination, in addition to a postal questionnaire, showed that there was no significant difference between the study and control group with respect to frequency of consultation, referral to outside agencies or items prescribed. Administration of a health needs questionnaire to patients registered with this general practice was not associated with an increase in consultation frequency or referral, or a change in prescribing patterns. No plausible explanation could be identified for the significant reduction in the number of home visits and prescriptions written for analgesics. It was concluded that these results were a statistical artefact. On the basis of the evidence from this study, GPs can be reassured that the administration of health needs questionnaires of the type used in this study will not result in any increase in workload or costs of care incurred by increased referrals to outside agencies or increased prescribing.


Precision of verbal feedback affects accuracy of motor skill performance.
The study sought to determine whether the precision of verbal feedback on knowledge of results affected the accuracy of motor skill performance with various parameters. Eighty-eight male young healthy adults (21.55±1.13 years) participated in the study. They were randomly assigned to two groups (44 people each one). They had to perform standing long jump test. Three types of feedback and three distances that the participants jumped were used in the experiment. The types of feedback in both groups were provided in the same order, whilst jumps were performed from the shortest to the longest distance in the first group and from the longest to the shortest one in the other group. Each participant performed the tasks individually. The results demonstrated that participants performed significantly more accurate tasks when they were provided with more precise feedback on the distance to the target. The study revealed that in the case of trials with no feedback the results improved after changing the task parameters (i.e. the distance of a jump). It is recommended that teachers and coaches should provide clear and accurate feedback on results achieved in trials. It enables task performers to assess their position in relation to the target. In practice, trials without feedback should not be omitted since, as the results showed, they are an important source of experience that affects the performance of tasks with different parameters.


Subdural empyema and group C Streptococcus.
We have described a case of subdural empyema in a 13-year-old boy whose presentation was not atypical for the disease. The unusual organism cultured from his blood, frontal sinuses, middle ear, meninges, and epidura was group C beta-hemolytic Streptococcus.


Molar Heat Capacity (Cv) for Saturated and Compressed Liquid and Vapor Nitrogen from 65 to 300 K at Pressures to 35 MPa.
Molar heat capacities at constant volume (Cv ,) for nitrogen have been measured with an automated adiabatic calorimeter. The temperatures ranged from 65 to 300 K, while pressures were as high as 35 MPa. Calorimetric data were obtained for a total of 276 state conditions on 14 isochores. Extensive results which were obtained in the saturated liquid region (Cv(2) and Cσ ) demonstrate the internal consistency of the Cv (ρ,T) data and also show satisfactory agreement with published heat capacity data. The overall uncertainty of the Cv values ranges from 2% in the vapor to 0.5% in the liquid.


Somatosensory Test Responses and Physical and Psychological Functioning of Children and Adolescents with Chronic Non-neuropathic Pain: An Exploratory Study.
This study was designed to establish preliminary feasibility testing of a set of inherently benign somatosensory stimulus-response tests (to cutaneous and deep stimuli) for bedside or office evaluation of pain disorders in children and adolescents. Associations between, and the relative influence of, cutaneous somatosensory testing (SST) responses, deep SST responses, and psychological factors (depression, pain-related catastrophizing) on pain outcomes (worst pain intensity, pain-related disability) were considered. Sixty participants (6 to 18 y) were recruited from the pediatric chronic pain clinic. SST responses were assessed at the pain site (PS) and control sites to diverse stimuli (static/dynamic touch, punctate pressure, vibration, cool, deep pressure) using Colored Analogue Scales (CAS) with modified anchors. Validated measures of depression, pain-related catastrophizing, and pain-related functional interference were administered. Responses at the PS were more frequently hypersensitive than hyposensitive for all SST measures except vibration. Deep pressure responses were the only statistically significant predictor of worst pain intensity. Depression and pain-related catastrophizing accounted for a statistically significant amount of variance of pain-related disability, over and above that which was accounted for by SST responses. Preliminary feasibility of a set of somatosensory stimulus-response tests for bedside or office evaluation of pain disorders in children and adolescents was established. Deep pressure responses contributed unique information in predicting worst pain intensity but not functional interference. Although cutaneous SST responses at the PSs were frequently abnormal, cutaneous SST responses were not confirmed in this study to have clinical utility, but rather might be centrally mediated epiphenomena.


Improving the accuracy of protein stability predictions with multistate design using a variety of backbone ensembles.
Multistate computational protein design (MSD) with backbone ensembles approximating conformational flexibility can predict higher quality sequences than single-state design with a single fixed backbone. However, it is currently unclear what characteristics of backbone ensembles are required for the accurate prediction of protein sequence stability. In this study, we aimed to improve the accuracy of protein stability predictions made with MSD by using a variety of backbone ensembles to recapitulate the experimentally measured stability of 85 Streptococcal protein G domain β1 sequences. Ensembles tested here include an NMR ensemble as well as those generated by molecular dynamics (MD) simulations, by Backrub motions, and by PertMin, a new method that we developed involving the perturbation of atomic coordinates followed by energy minimization. MSD with the PertMin ensembles resulted in the most accurate predictions by providing the highest number of stable sequences in the top 25, and by correctly binning sequences as stable or unstable with the highest success rate (≈90%) and the lowest number of false positives. The performance of PertMin ensembles is due to the fact that their members closely resemble the input crystal structure and have low potential energy. Conversely, the NMR ensemble as well as those generated by MD simulations at 500 or 1000 K reduced prediction accuracy due to their low structural similarity to the crystal structure. The ensembles tested herein thus represent on- or off-target models of the native protein fold and could be used in future studies to design for desired properties other than stability.


Extraction and mapping of drug names from free text to a standardized nomenclature.
Free text fields are often used to store clinical drug data in electronic health records. The use of free text facilitates rapid data entry by the clinician. Errors in spelling, abbreviations, and jargon, however, limit the utility of these data. We designed and implemented an algorithm, using open source tools and RxNorm, to extract and normalize drug data stored in free text fields of an anesthesia electronic health record. The algorithm was developed using a training set containing drug data from 49,518 cases, and validated using a validation set containing data from 14,655 cases. Overall sensitivity and specificity for the validation set were 92.2% and 95.7% respectively. The mains sources of error were misspellings and unknown but valid drug names. These preliminary results demonstrate that free text clinical drug data can be efficiently extracted and mapped to a controlled drug nomenclature.


Regulation of Chloroplast Development and Function at Adverse Temperatures in Plants.
The chloroplast is essential for photosynthesis, plant growth and development. As semiautonomous organelles, the biogenesis and development of chloroplasts need to be well-regulated during plant growth and stress responses. Low or high ambient temperatures are adverse environmental stresses that affect crop growth and productivity. As sessile organisms, plants regulate the development and function of chloroplasts in a fluctuating temperature environment to maintain normal photosynthesis. This review focuses on the molecular mechanisms and regulatory factors required for chloroplast biogenesis and development under cold or heat stress conditions and highlights the importance of chloroplast gene transcription, RNA metabolism, ribosome function and protein homeostasis essential for chloroplast development under adverse temperature conditions.


Significance of Matrix Metalloproteinase 9 Expression as Supporting Marker to Cytokeratin 19 mRNA in Sentinel Lymph Nodes in Breast Cancer Patients.
One-step nucleic acid amplification (OSNA) detects and quantifies, with the use of a polymerase chain reaction, the presence of cytokeratin 19 mRNA in sentinel lymph nodes. The main advantage of the OSNA assay is the avoidance of second surgery in case of positive sentinel lymph node diagnosis. The objective of this study was to evaluate the significance of matrix metalloproteinase 9 expression by immunohistochemistry as supporting marker to cytokeratin 19 mRNA in sentinel lymph nodes in breast cancer patients and to relate this expression with clinicopathological data. This study was conducted on fresh sentinel lymph nodes obtained from 40 patients with tumors classified as carcinoma of no special type. The presence of metastatic cells in the slices of lymph nodes was evaluated by immunohistochemistry using antibodies for CK19 and MMP-9. Expression of CK19 and MMP-9 in lymph nodes was also confirmed by means of Western blot analysis. Results indicated that the strongest correlation with CK19 mRNA was displayed by MMP-9, CK19 (by immunohistochemistry, IHC), and nodal metastases (p < 0.001). Higher histological grading also positively correlated with CK19 mRNA, however that correlation was less significant. Since MMP-9 shows very strong correlation with CK19 mRNA in breast carcinoma of no special type metastases, expression of MMP-9 in sentinel lymph nodes should be considered as useful method whenever OSNA analysis is not available.