On the use of in silico tools for prioritising toxicity testing of the low-volume industrial chemicals in REACH.
This study was conducted to evaluate the utility of a selection of commercially and freely available non-testing tools and to analyse how REACH registrants can apply these as prioritisation tool for low-volume chemicals. The analysis was performed on a set of organic industrial chemicals and pesticides with extensive peer-reviewed risk assessment data. Analysed in silico model systems included Derek Nexus, Toxtree, QSAR Toolbox, LAZAR, TEST and VEGA, and results from these were compared with expert-judged risk classification according to the classifying, labelling and packaging (CLP) regulation. The most reliable results were obtained for carcinogenicity; however, less reliable predictions were derived for mutagenicity and reproductive toxicity. A group of compounds frequently predicted as false negatives was identified. These were relatively small molecules with low structural complexity, for example benzene derivatives with hydroxyl-, amino- or aniline-substituents. A rat liver S9 metabolite simulator was applied to illustrate the importance of considering metabolism in the risk assessment procedure. We also discuss outcome of combining predictions from multiple model systems and advise how to apply in silico tools. These models are proposed to be used to prioritise low-volume chemicals for testing within the REACH legislation, and we conclude that further guidance is needed so that industry can select and apply models in a reliable, systematic and transparent way.


Bite Wound Infections.
Patients with mammalian bite wounds account for hundreds of thousands of emergency department, urgent care center, and physician office visits in the United States each year. The types of wounds encountered by physicians range from insignificant scratches to life-threatening neck and facial injuries. Infectious complications of bite wounds are common, and the consequences of these infections are significant and sometimes disabling. This article reviews the infectious complications of cat, dog, and human bite wounds. The prevention of tetanus and rabies virus infection, the appropriate antimicrobial treatment of bacterial infections, and the frequent need for surgical consultation and intervention are emphasized.


Flexible magnetic filaments under the influence of external magnetic fields in the limit of infinite dilution.
In the present work we use Langevin dynamics computer simulations to understand how the presence of a constant external magnetic field modifies the conformational phase diagram of magnetic filaments in the limit of infinite dilution. We have considered the filaments immersed in either a good (non-sticky filaments) or a poor (Stockmayer polymers) solvent. It has been found that in the presence of an applied field, filaments turn out to be much more susceptible to parameters such as temperature and solvent conditions. Filaments owe this increased susceptibility to the fact that the external magnetic field tends to level the free energy landscape as compared to the zero-field case. The field induces equalization in the free energy of competing conformational states that were separated by large energy differences in the zero-field limit. In this new scenario multistability arises, and manifests itself in the existence of broad regions in the phase diagram where two or more equilibrium configurations coexist. The existence of multistability greatly enhances the possibility of tuning the properties of the filament.


Health behind bars: utilization and evaluation of medical care among jail inmates.
Jail and prison inmates experience disproportionately high levels of chronic and acute physical health problems, resulting in increased utilization of health services in correctional institutions. Variations in both health status and health care utilization are likely, although several important factors have been under-researched. Gender, in particular, is presumed to influence health outcomes and use of medical care in correctional facilities. The current study explores the physical health status of a systematic sample of 198 male and female inmates incarcerated in a large county jail located in a medium-sized Southern city. Using multiple regression analysis, predictors of physical health status, utilization of medical care, and inmates' evaluations of the accessibility and quality of health care are identified. The results indicate that gender and age are the most consistent demographic predictors of health status and medical care utilization, with females and older inmates reporting higher morbidity and concomitantly higher numbers of medical encounters. The experience of incarceration also appears to influence the physical health of inmates, as self-reported health problems increase with inmates' duration of incarceration. Evaluations of jail medical care differ significantly by gender, with female inmates reporting more difficulty accessing health services, yet higher satisfaction with the quality of services received. The results suggest a need for medical care in correctional settings to adapt to the medical needs of older inmates and women, in addition to improving treatment for chronic conditions and preventive services.


Single-pulse ultrafast-laser machining of high aspect nano-holes at the surface of SiO2.
Use of high numerical aperture focusing with negative longitudinal spherical aberration is shown to enable deep (> microm), high aspect ratio, nano-scale-width holes to be machined into the surface of a fused-silica (SiO(2)) substrate with single pulses from a 200 fs, 4 microJ Ti-Sapphire laser source. The depths of the nano-holes are characterized by use of a non-destructive acetate replication technique and are confirmed by imaging of sectioned samples with a dual focused ion beam/scanning electron microscope.


Clinicians' perceptions of challenges and strategies of transition from assertive community treatment to less intensive services.
The study aimed to identify clinical strategies and challenges around transition from Assertive Community Treatment (ACT) to less intensive services. Six focus groups were conducted with ACT team leaders (n = 49). Themes were grouped under four intervention-focused domains: (1) client/clinical, (2) family and natural supports, (3) ACT staff and team, and (4) public mental health system. Barriers to transition included beliefs that clients and families would not want to terminate services (due to loss of relationships, fear of failure, preference for ACT model), clinical concerns that transition would not be successful (due to limited client skills, relapse without ACT support), systems challenges (clinic waiting lists, transportation barriers, eligibility restrictions, stigma against ACT clients), and staff ambivalence (loss of relationship with client, impact on caseload). Strategies to support transition included building skills for transition, engaging supports, celebrating success, enhanced coordination with new providers, and integrating and structuring transition in ACT routines.


MiR-150 Inhibits Cell Growth In Vitro and In Vivo by Restraining the RAB11A/WNT/β-Catenin Pathway in Thyroid Cancer.
BACKGROUND Emerging evidence has shown that downregulation or upregulation of microRNAs (miRNAs) plays an important role in the development and progression of thyroid cancer (TC). However, the potential role of miR-150 and its biological function in TC remains largely unclear. MATERIAL AND METHODS Real-time polymerase chain reaction (RT-qPCR) was employed to detect the expression level of miR-150 and RAB11A in human TC tissue and human normal thyroid tissue. MTT assay, colony formation assay, flow cytometry cell cycle, and apoptosis assay were used to investigate the role of miR-150 and RAB11A on the malignant phenotypes in vitro. Nude mouse xenograft assay and western blot assay was used to verify the function of miR-150 in vivo. Western blot assay and immunofluorescence assay were used to detect the activation of WNT/β-catenin pathway mediated by miR-150 and RAB11A. EGFP reporter assay, RT-qPCR assay, and western blot assay were used to validate the regulation relationship. RESULTS This study demonstrated that miR-150 expression in human TC tissues was markedly downregulated. Moreover, overexpression of miR-150 markedly inhibited cell proliferation via inducing the cell cycle arrest and promoting cell apoptosis by directly targeting RAB11A in vitro and suppressing tumor growth in vivo. However, overexpression of RAB11A promoted cell malignant phenotypes. In addition, miR-150 restrained the RAB11A mediated WNT/β-catenin activation in TC cells. CONCLUSIONS miR-150 may function as a suppressor gene in TC cells by inhibiting the RAB11A/WNT/β-catenin pathway.


Food Reference Budgets as a Potential Policy Tool to Address Food Insecurity: Lessons Learned from a Pilot Study in 26 European Countries.
The aim of this article is to present the development of cross-country comparable food reference budgets in 26 European countries, and to discuss their usefulness as an addition to food-based dietary guidelines (FBDG) for tackling food insecurity in low-income groups. Reference budgets are illustrative priced baskets containing the minimum goods and services necessary for well-described types of families to have an adequate social participation. This study was conducted starting from national FBDG, which were translated into monthly food baskets. Next, these baskets were validated in terms of their acceptability and feasibility through focus group discussions, and finally they were priced. Along the paper, we show how that food reference budgets hold interesting contributions to the promotion of healthy eating and prevention of food insecurity in low-income contexts in at least four ways: (1) they show how a healthy diet can be achieved with limited economic resources, (2) they bring closer to the citizen a detailed example of how to put FBDG recommendations into practice, (3) they ensure that food security is achieved in an integral way, by comprising the biological but also psychological and social functions of food, and (4) providing routes for further (comparative) research into food insecurity.


Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease.
Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course. Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses. The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4+ terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4+ terminally differentiated effector memory T cells and an increased frequency of NK CD56bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4+ terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls. Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology.


When another assessment attempt is bad for progress.
This article was migrated. The article was marked as recommended. The history and current practice of resit tests are briefly reviewed. The evidence supporting resits and also the problems associated with resits are evaluated. In addition, the financial implications of resits for both students and institutions are explored, along with the need to ensure assessments establish currency of ability and are a reflection of the long-term capability of students. Although resit outcomes are typically capped at the passing score we argue that they still afford an unfair advantage. We conclude that where resit opportunities are provided then they should have higher pass marks than first sit attempts. However, we recommend that the stress of high stakes exams, and thus resits, should be avoided. Consequently, a case is made for an alternative to resits whereby multiple lower stakes assessment results are aggregated.


The ability of adenosine to decrease the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. A cyclic AMP-mediated effect.
The presence of adenosine (25-250 microM) or of 2-chloroadenosine (2.5-100 microM) in the incubation medium caused a marked decrease in the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. This effect was accompanied by an increase in the concentration of cyclic AMP, an activation of phosphorylase and of fructose 2,6-bisphosphatase, and an inactivation of pyruvate kinase and of 6-phosphofructo-2-kinase. As a rule, the changes in the fructose 2,6-bisphosphate-modifying system were slower but more persistent than those in the activities of phosphorylase and pyruvate kinase. The effect of the nucleoside to decrease the concentration of fructose 2,6-bisphosphate was not affected by an inhibitor of adenosine transport and could not be obtained in a liver high-speed supernatant. These data indicate that the effect of adenosine to decrease the concentration of fructose 2,6-bisphosphate is mediated by the stimulation of adenylate cyclase, secondary to the binding of adenosine to membranous receptors. Like glucagon, 2-chloroadenosine stimulated gluconeogenesis in isolated hepatocytes, whereas adenosine had an opposite effect.


Validity of food frequency questionnaire-based estimates of long-term long-chain n-3 polyunsaturated fatty acid intake.
To evaluate how long-term dietary intake of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs), estimated by repeated food frequency questionnaires (FFQs) over 15 years, is correlated with LCn-3 PUFAs in adipose tissue (AT). Subcutaneous adipose tissue was obtained in 2003-2004 (AT-03) from 239 randomly selected women, aged 55-75 years, after completion of a 96-item FFQ (FFQ-03). All participants had previously returned an identical FFQ in 1997 (FFQ-97) and a 67-item version in 1987-1990 (FFQ-87). Pearson product-moment correlations were used to evaluate associations between intake of total and individual LCn-3 PUFAs as estimated by the three FFQ assessments and AT-03 content (% of total fatty acids). FFQ-estimated mean relative intake of LCn-3 PUFAs (% of total fat intake) increased between all three assessments (FFQ-87, 0.55 ± 0.34; FFQ-97, 0.74 ± 0.64; FFQ-03, 0.88 ± 0.56). Validity, in terms of Pearson correlations between FFQ-03 estimates and AT-03 content, was 0.41 (95% CI 0.30-0.51) for total LCn-3 PUFA and ranged from 0.29 to 0.48 for individual fatty acids; lower correlation was observed among participants with higher percentage body fat. With regard to long-term intake estimates, past dietary intake was also correlated with AT-03 content, with correlation coefficients in the range of 0.21-0.33 and 0.21-0.34 for FFQ-97 and FFQ-87, respectively. The correlations were improved by using average estimates from two or more FFQ assessments. Exclusion of fish oil supplement users (14%) did not alter the correlations. These data indicate reasonable validity of FFQ-based estimates of long-term (up to 15 years) LCn-3 PUFA intake, justifying their use in studies of diet-disease associations.


DNA fingerprinting of Enterococcus faecium by pulsed-field gel electrophoresis may be a useful epidemiologic tool.
Pulsed-field gel electrophoresis was used to compare 34 isolates of Enterococcus faecium from six different geographic locations. This procedure generated an average of 13 discernible fragment bands per isolate (range, 10 to 19 fragment bands) of 34 to 485 kb. The resulting restriction endonuclease digestion patterns were quite heterogeneous and were able to differentiate 27 of 34 isolates from each other, as defined by one or more mismatched fragment bands. Five patterns were shared by two or more isolates, and each set of isolates with matching patterns (shared pattern) originated in the same medical center, suggesting a common epidemiologic background, including highly penicillin resistant isolates in Richmond and Philadelphia. We conclude that pulsed-field gel electrophoresis of DNA digested with low-frequency-cleavage restriction enzymes offers a relatively simple method of comparing E. faecium for the purpose of epidemiologic study.


Co-drivers of Air Pollutant and CO2 Emissions from On-Road Transportation in China 2010-2020.
Co-controlling the emissions of air pollutants and CO2 from automobiles is crucial for addressing the intertwined challenges of air pollution and climate change in China. Here, we analyze the synergetic characteristics of air pollutant and CO2 emissions from China's on-road transportation and identify the co-drivers influencing these trends. Using detailed emission inventories and employing index decomposition analysis, we found that despite notable progress in pollution control, minimizing on-road CO2 emissions remains a formidable task. Over 2010-2020, the estimated sectoral emissions of VOCs, NOx, PM2.5, and CO declined by 49.9%, 25.9%, 75.2%, and 63.5%, respectively, while CO2 emissions increased by 46.1%. Light-duty passenger vehicles and heavy-duty trucks have been identified as the primary contributors to carbon-pollution co-emissions, highlighting the need for tailored policies. The driver analysis indicates that socioeconomic changes are primary drivers of emission growth, while policy controls, particularly advances in emission efficiency, can facilitate co-reductions. Regional disparities emphasize the need for policy refinement, including reducing dependency on fuel vehicles in the passenger subsector and prioritizing co-reduction strategies in high-emission provinces in the freight subsector. Overall, our study confirms the effectiveness of China's on-road control policies and provides valuable insights for future policy makers in China and other similarly positioned developing countries.


Comparison of Patent Ductus Arteriosus Stent and Blalock-Taussig Shunt as Palliation for Neonates with Sole Source Ductal-Dependent Pulmonary Blood Flow: Results from the Congenital Catheterization Research Collaborative.
Patent ductus arteriosus (PDA) stenting is an accepted method for securing pulmonary blood flow in cyanotic neonates. In neonates with pulmonary atresia and single source ductal-dependent pulmonary blood flow (SSPBF), PDA stenting remains controversial. We sought to evaluate outcomes in neonates with SSPBF, comparing PDA stenting and surgical Blalock-Taussig shunt (BTS). Neonates with SSPBF who underwent PDA stenting or BTS at the four centers of the Congenital Catheterization Research Collaborative from January 2008 to December 2015 were retrospectively reviewed. Reintervention on the BTS or PDA stent prior to planned surgical repair served as the primary endpoint. Additional analyses of peri-procedural complications, interventions, and pulmonary artery growth were performed. A propensity score was utilized to adjust for differences in factors. Thirty-five patients with PDA stents and 156 patients with BTS were included. The cohorts had similar baseline characteristics, procedural complications, and mortality. Interstage reintervention rates were higher in the PDA stent cohort (48.6% vs. 15.4%, p < 0.001).


Allosteric modulation of neurotoxin binding to voltage-sensitive sodium channels by Ptychodiscus brevis toxin 2.
The effects of Ptychodiscus brevis toxin 2 (PbTx-2) on the binding of neurotoxins at four different neurotoxin receptor sites on voltage-sensitive sodium channels in rat brain synaptosomes were examined. Binding of saxitoxin at neurotoxin receptor site 1 and Leiurus quinquestriatus alpha-scorpion toxin (LqTx) at neurotoxin receptor site 3 was unaffected. PbTx-2 enhanced binding of batrachotoxinin A 20-alpha-benzoate (BTX-B) to neurotoxin receptor site 2 and Centruroides suffusus suffusus beta-scorpion toxin (CsTx II) to site 4 on sodium channels. These results support the proposal that PbTx-2 and related toxins act at a new receptor site (site 5) that has not been previously analyzed in binding experiments. Half-maximal effects of PbTx-2 were observed in the range of 20-50 nM PbTx-2. The enhancement of BTX-B binding was reduced by depolarization. Saturating concentrations of PbTx-2 reduced KD values for binding of BTX-B and CsTx-II 2.9-fold and 2.6-fold, respectively. The effects of PbTx-2 and LqTx in enhancing BTX-B binding were synergistic. A model involving both preferential binding of BTX-B, PbTx-2, LqTx, and CsTx II to active states of sodium channels and allosteric interactions among the four receptor sites at which these toxins act accommodates these and previous results.


Improving oral health behavior: a social psychological approach.
The authors describe social psychological research that has found consistent beneficial effects of framing health messages to be congruent with personality factors in encouraging preventive oral health behaviors. The authors describe several studies in which they administered health messages to young adults who did not floss and who were classified as predominantly approach-oriented or avoidance-oriented on the basis of a short personality questionnaire. They framed the messages to emphasize the benefits of dental flossing or the costs of not flossing. The authors assessed the effectiveness in terms of flossing efficacy and flossing behavior. When patients received a dental health message that was congruent with their motivational orientation-approach or avoidance-they had a stronger belief that they were capable of flossing, expressed greater intentions to floss and exhibited increased flossing behavior (flossing 50 to 65 percent more often in the following week). Two factors that dental practitioners should consider when delivering information are whether the patient is more approach- or avoidance-oriented and whether to frame the message in terms of gains or losses. Practitioners can use these theory-based findings in dental practice to promote positive oral health behaviors by administering brief personality assessments to patients and by framing the message accordingly.


The impact of COVID-19 on dual career athletes: Three typologies of coping.
This research aimed to understand the coping and wellbeing of dual-career athletes during the COVID-19 pandemic. A total of 159 dual-career athletes completed a series of questionnaires that aimed to identify the coping strategies and their impact on the wellbeing of respondents during COVID-19 restrictions. The survey included measures of coping, wellbeing, burnout, and identity along with open-ended questions with the focus of change, coping, and support. Findings identified three coping approaches that have been employed by dual-career athletes: positive coping, negative coping, and acceptance. The three coping approaches also showed distinct wellbeing and burnout profiles. The negative coping group showed high indicators of burnout and poor wellbeing, whereas the acceptance group showed the highest scores on wellbeing and low indications of burnout. Based on the findings, it is recommended that dual-career support providers and stakeholders consider how best to support athletes that have not coped well and have experienced wellbeing issues during this time. It is also important to recognise the benefit a dual-career has provided to some individuals during this period.


A recurrent outbreak of nosocomial legionnaires' disease detected by urinary antigen testing: evidence for long-term colonization of a hospital plumbing system.
In 1994, a hospital reported an increase in nosocomial legionnaires' disease after implementing use of a rapid urinary antigen test for Legionella pneumophila serogroup 1 (Lp-1). This hospital was the site of a previous nosocomial legionnaires' disease outbreak during 1980 to 1982. Infection control records were reviewed to compare rates of nosocomial pneumonia and the proportion of cases attributable to legionnaires' disease during the 1994 outbreak period with those during the same period in 1993. Water samples were collected for Legionella culture from the hospital's potable water system and cooling towers, and isolates were subtyped by monoclonal antibody (MAb) testing and arbitrarily primed polymerase chain reaction (AP-PCR). Nosocomial pneumonia rates were similar from April through October 1993 and April through October 1994: 5.9 and 6.6 per 1,000 admissions, respectively (rate ratio [RR], 1.1; P=.56); however, 3.2% of nosocomial pneumonias were diagnosed as legionnaires' disease in 1993, compared with 23.9% in 1994 (RR, 9.4; P<.001). In 1994, most legionnaires' disease cases were detected by the urinary antigen testing alone. MAb testing and AP-PCR demonstrated identical patterns among Lp-1 isolates recovered from a patient's respiratory secretions, the hospital potable water system, and stored potable water isolates from the 1980 to 1982 outbreak. There may have been persistent transmission of nosocomial legionnaires' disease at this hospital that went undiscovered for many years because there was no active surveillance for legionnaires' disease. Introduction of a rapid urinary antigen test improved case ascertainment. Legionella species can be established in colonized plumbing systems and may pose a risk for infection over prolonged periods.


[Temporal study in AIDS-associated disease in Brazil, 1980-1999].
Trends in annual incidence of reported AIDS-associated opportunistic infections (OI/100 adults > 12 years old) among AIDS cases were estimated at the national level in Brazil from 1980 through May 1999. The analysis included chi-square and linear regression modeling. The opportunistic infections included: candidiasis (CD), tuberculosis (TB), Pneumocystis carinii pneumonia (PCP), neurotoxoplasmosis (NT), Kaposi sarcoma (KS), cryptococcal meningitis (CM), and protozoa infections (PI). The overall cumulative incidence rates/100 reported AIDS cases were: CD = 59, TB = 26, PCP = 23, NT = 15, KS = 5, CM = 4, and PI = 4. Annual trends indicated a statistically significant decline in all OIs. However, in the Northeast and Central-West regions there were increases in TB (b = 0.39) and NT (b = 0.20), respectively. TB showed a higher incidence among individuals with less schooling (< 8 years), while PCP and KS had higher incidence rates among those with 8 or more years of schooling, despite similar downward trends. Access to antiretroviral therapy and OI prophylaxis may partially explain these results. However, data reliability, delay in reporting, OI incidence after AIDS, and reporting and diagnostic criteria are factors that also need to be carefully assessed.


Current insights into the mechanisms and management of infection stones.
Infection stones are complex aggregates of crystals amalgamated in an organic matrix that are strictly associated with urinary tract infections. The management of patients who form infection stones is challenging owing to the complexity of the calculi and high recurrence rates. The formation of infection stones is a multifactorial process that can be driven by urine chemistry, the urine microenvironment, the presence of modulator substances in urine, associations with bacteria, and the development of biofilms. Despite decades of investigation, the mechanisms of infection stone formation are still poorly understood. A mechanistic understanding of the formation and growth of infection stones - including the role of organics in the stone matrix, microorganisms, and biofilms in stone formation and their effect on stone characteristics - and the medical implications of these insights might be crucial for the development of improved treatments. Tools and approaches used in various disciplines (for example, engineering, chemistry, mineralogy, and microbiology) can be applied to further understand the microorganism-mineral interactions that lead to infection stone formation. Thus, the use of integrated multidisciplinary approaches is imperative to improve the diagnosis, prevention, and treatment of infection stones.


Floricoccus tropicus gen. nov., sp. nov. and Floricoccus penangensis sp. nov. isolated from fresh flowers of durian tree and hibiscus.
Three strains of Gram-staining-positive, coccus-shaped, lactic acid bacteria, designated as HibF3T, HibF2 and HibF5 were isolated from fresh flowers of hibiscus, and a fourth, DF1T, was isolated from fresh flowers of durian tree, in Penang, Malaysia. Taxonomic characterisation was performed by polyphasic analysis. Sequence similarities of the 16S rRNA gene and the housekeeping rpoA and pheS genes of these strains with their closely-related lactococcal and streptococcal relatives were 92-94, 78 and 81 %, respectively. The results of phylogenetic analysis indicated that strains DF1T, HibF2, HibF5 and HibF3T were clustered together but were clearly separated from species of the genera Streptococcus and Lactococcus, indicating that they represent members of a novel genus of the family Streptococcaceae. Calculation of average nucleotide identity (ANI) values between the genomes of DF1T and HibF3T yielded values of 92.50-92.93 %. ANI values below the cut-off value and distinctive chemotaxonomic characteristics supported the hypothesis that these strains represented two novel species. Major cellular fatty acids in DF1T, HibF2 and HibF5 were C18 : 1ω7c and C16 : 0, while C12 : 0 and C14 : 0 were also dominant, in addition to C18 : 1ω7c and C16 : 0, in HibF3T. A novel genus is proposed with the name Floricoccus gen. nov. which consists of two species, Floricoccus tropicus sp. nov as the type species, and Floricoccus penangensis sp. nov. The respective type strains are DF1T (=LMG 29833T=JCM 31733T) and HibF3T (=LMG 29831T=DSM 31735T).


Anterior organization of the Caenorhabditis elegans embryo by the labial-like Hox gene ceh-13.
The Caenorhabditis elegans lin-39, mab-5 and egl-5 Hox genes specify cell fates along the anterior-posterior body axis of the nematode during postembryonic development, but little is known about Hox gene functions during embryogenesis. Here, we show that the C. elegans labial-like gene ceh-13 is expressed in cells of many different tissues and lineages and that the rostral boundary of its expression domain is anterior to those of the other Hox genes. By transposon-mediated mutagenesis, we isolated a zygotic recessive ceh-13 loss-of-function allele, sw1, that exhibits an embryonic sublethal phenotype. Lineage analyses and immunostainings revealed defects in the organization of the anterior lateral epidermis and anterior body wall muscle cells. The epidermal and mesodermal identity of these cells, however, is correctly specified. ceh-13(sw1) mutant embryos also show fusion and adhesion defects in ectodermal cells. This suggests that ceh-13 plays a role in the anterior organization of the C. elegans embryo and is involved in the regulation of cell affinities.


A kinetic study of ferrocenium cation decomposition utilizing an integrated electrochemical methodology composed of cyclic voltammetry and amperometry.
A novel, easy, quick, and inexpensive integrated electrochemical methodology composed of cyclic voltammetry and amperometry has been developed for the determination of the kinetic stability of higher oxidation states for inorganic complexes. In this study, ferrocene and its derivatives have been used as model systems and the corresponding ferrocenium cations were generated in situ during the electrochemical experiments to determine their kinetic stabilities. The study found that the ferrocenium cations decompose following the first-order kinetics at 27 ± 3 °C in the presence of ambient oxygen and water. The half-lives of the ferrocenium, carboxylate ferrocenium, and decamethyl ferrocenium cations were found to be 1.27 × 10(3), 1.52 × 10(3), and ≫11.0 × 10(3) s, respectively, in acetonitrile solvent having a 0.5 M tetrabutylammonium hexafluorophosphate electrolyte. These results are in agreement with the previous reports, i.e. the ferrocenium cation is unstable whereas the decamethyl ferrocenium cation has superior stability. The new methodology has been established by performing various experiments using different concentrations of ferrocene, variable scan rates in cyclic voltammetry, different time periods for amperometry, and in situ spectroelectrochemical experiments.


Feasibility Testing of Wearable Device for Musculoskeletal Monitoring during Aquatic Therapy and Rehabilitation.
The objectives of this study were to test the feasibility of the developed waterproof wearable device with a Surface Electromyography (sEMG) sensor and Inertial Measurement Unit (IMU) sensor by (1) comparing the onset duration of sEMG recordings from maximal voluntary contractions (MVC), (2) comparing the acceleration of arm movement from IMU, and (3) observing the reproducibility of onset duration and acceleration from the developed device for bicep brachii (BB) muscle between on dry-land, and in aquatic environments. Five healthy males participated in two experimental protocols with the activity of BB muscle of the left and right arms. Using the sEMG of BB muscle, the intra-class correlation coefficient (ICC) and typical error (CV%) were calculated to determine the reproducibility and precision of onset duration and acceleration, respectively. In case of onset duration, no significant differences were observed between land and aquatic condition (p = 0.9-0.98), and high reliability (ICC = 0.93-0.98) and precision (CV% = 2.7-6.4%) were observed. In addition, acceleration data shows no significant differences between land and aquatic condition (p = 0.89-0.93), and high reliability (ICC = 0.9-0.97) and precision (CV% = 7.9-9.2%). These comparable sEMG and acceleration values in both dry-land and aquatic environment supports the suitability of the proposed wearable device for musculoskeletal monitoring during aquatic therapy and rehabilitation as the integrity of the sEMG and acceleration recordings maintained during aquatic activities.Clinical Relevance-This study and relevant experiment demonstrate the feasibility of the developed wearable device to support clinicians and therapists for musculoskeletal monitoring during aquatic therapy and rehabilitation.


Development of enzyme-inorganic hybrid nanoflower-modified electrodes and a smartphone-controlled electrochemical analyzer for point-of-care testing of salivary amylase in saliva.
Quantitation of salivary alpha-amylase (sAA) plays a significant role in not only theoretical studies but also clinical practice. This study reports a quantitative point-of-care testing (POCT) system for sAA quantitation anywhere, anytime and by anyone, which consists of customized electrodes and a smartphone-controlled electrochemical analyzer. Organic-inorganic hybrid nanoflowers (NFs) encapsulating α-glucosidase (AG) and glucose dehydrogenase (GDH) have been synthesized and modified onto screen-printed electrodes (SPCEs) to fabricate the customized electrodes. The SPCEs integrated with the smartphone-controlled electrochemical analyzer exhibit good analytical performance for sAA with a low detection limit of 5.02 U mL-1 and a wide dynamic range of 100-2000 U mL-1 using chronoamperometry. The reported POCT system has been successfully demonstrated for quantitation of sAA in clinical saliva samples, and the quantitation results correlated well with those of the Bernfeld method which is extensively used in clinics. More importantly, this study reveals the great potential of sAA as an early warning indicator of abnormal glucose metabolism in obese individuals. Considering the non-invasive saliva sampling process as well as the easy-to-use and cost-effectiveness features of this quantitative POCT system, quantitation of salivary sAA at home by laypersons might become an appealing choice for obese individuals to monitor their glucose metabolism status anytime.


A reconditioning program to lower the recurrence rate of brachial plexus neurapraxia in collegiate football players.
To present clinical techniques for managing class I brachial plexus neurapraxia (BPN) in collegiate football players. During a football career, up to 50% of college football players develop BPN. It is difficult to return the player to practice and competition without many recurrences during the same season. Postseason reconditioning programs may improve the outcome by allowing the injured nerves a chance to heal adequately. Flexibility and strength of the neck and shoulder girdle are the focus of this proposed postseason BPN reconditioning program. This clinical technique is designed to reduce or eliminate inflammation, weakness, and hypomobility that contribute to reinjury of the brachial plexus and the resulting class I BPN. After the football season, the team physician performs a mandatory follow-up examination. Any pathology that may be exacerbated is ruled out before beginning this program. Conservative management is prescribed during the first 4 weeks postseason. Then an 8-week period of aggressive reconditioning is initiated. Players begin manual resistance and Nautilus neck machine exercises 3 times per week. A cervical spine mobilization and modified shoulder resistance program is performed 2 days per week. Subsequently, players proceed with modification of the general neck and shoulder program used by the rest of the squad. Shoulder pad and neck orthoses selection should be reviewed to ensure that the best protection against reinjury is used when the athlete returns to play. To minimize any chance of recurrence, a progressive pattern of gradually increasing collision work is employed after the athlete is cleared by the physician. Postseason observation of players after 1 year should reveal decreased recurrence of brachial plexus injury. The reconditioning program format, together with protective equipment considerations, may have a significant effect in reducing or eliminating the recurrence of BPN in football players.


Centrosomal and ciliary targeting of CCDC66 requires cooperative action of centriolar satellites, microtubules and molecular motors.
Mammalian centrosomes and cilia play key roles in many cellular processes and their deregulation is linked to cancer and ciliopathies. Spatiotemporal regulation of their biogenesis and function in response to physiological stimuli requires timely protein targeting. This can occur by different pathways, including microtubule-dependent active transport and via centriolar satellites, which are key regulators of cilia assembly and signaling. How satellites mediate their functions and their relationship with other targeting pathways is currently unclear. To address this, we studied retinal degeneration gene product CCDC66, which localizes to centrosomes, cilia, satellites and microtubules and functions in ciliogenesis. FRAP experiments showed that its centrosomal pool was dynamic and the ciliary pool associated with the ciliary axoneme and was stable. Centrosomal CCDC66 abundance and dynamics required microtubule-dependent active transport and tethering, and was inhibited by sequestration at satellites. Systematic quantitation of satellite dynamics identified only a small fraction to display microtubule-based bimodal motility, consistent with trafficking function. Majority displayed diffusive motility with unimodal persistence, supporting sequestration function. Together, our findings reveal new mechanisms of communication between membrane-less compartments.


[DNA-dependent RNA polymerase I from human placental nuclei].
This paper describes a large-scale method for solubilisation and purification of DNA-dependent RNA-Polymerase I from mature human placenta. The solubilisation method involves homogenization of the whole human placenta, isolation of cell nuclei, sonication of separated nuclei at high ionic strength and ammonium sulfate precipitation. The purification method consists of chromatography of RNA-Polymerase I activity on DEAE-Sephadex A-25 and Phosphocellulose P-11, and glycerol-density gradient centrifugation. In result, RNA-Polymerase I of human placenta nuclei has been shown to be completely resistant to alpha-amanitin. Besides dependence of RNA-Polymerase I on different Mg2+ and Mn2+ concentrations, glycerol concentration and ionic strength was studied. Using our results, an optimal RNA-Polymerase I assay mixture was developed. The subunit composition of RNA-Polymerase I was investigated by dodecylsulfate-gel electrophoresis. The RNA-Polymerase I molecule of human placenta consists of 13-14 polypeptides.


Age distribution and seasonal dynamics of abomasal helminths in wild red deer from central Spain.
A study on age distribution and seasonal dynamics of abomasal helminths in wild red deer was conducted in central Spain, by monthly samplings of fawns (<1 yr), subadult (1-2 yr), and adult (>2 yr) animals. Both intensity and prevalence of abomasal parasitism were higher in older animals, particularly in males. A bimodal pattern for intensity of infection by gastrointestinal parasites was observed. Maximum values attained in winter and summer may be related to variation in climate and the shifting availability of forage resources. The pattern was largely due to the contribution of Spiculopteragia asymmetrica/Spiculopteragia quadrispiculata, whereas the other species found (Ostertagia leptospicularis/Ostertagia kolchida and Ostertagia drozdzi/Ostertagia ryjikovi) occurred with lower prevalence and intensity of infection. Among these ostertagiines, the ratio for major and minor morphotypes of males of respective species and the relative abundance of males and females were stable through the annual cycle.


[Role of GABA receptors in pathological processes].
The review presents data indicative that both qualitative and quantitative changes in the structure of GABA--receptor complexes can lead to neurologic, mental, vegetotropic, somatic, hormonal and other disorders. The knowledge of structure of GABA receptors, their functions, and participation in the development of pathological states can promote the search for new selective synthetic substances capable of affecting receptor target, which opens ways to creating new highly effective and safe preparations for the treatment of various diseases.


Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule cell apoptosis and interstitial fibrosis in rats.
Unilateral ureteral obstruction (UUO) results in a number of pathophysiological and morphological changes in the renal parenchyma, including interstitial inflammation and fibrosis, apoptotic changes of tubular and interstitial cells. Recent studies have indicated an association between renin-angiotensin system and apoptotic alterations in the kidney after unilateral obstructive nephropathy. In this study, the effect of ACE inhibitors and AT1 receptor antagonists on tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy after UUO in rats was investigated. The study was conducted on Wistar rats with unilaterally ligated ureter and sham operated animals (control group). The rats with UUO were treated with ACE inhibitor (cilazapril) or AT1 receptor antagonists (losartan) and control group was treated with H2O. Sham-operated animals were treated in the same way. Tubular and interstitial cell apoptosis was detected morphologically by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). The area of intersitial fibrosis was determined using computer-assisted image processing after Gomory silver impregnation of paraffin sections. All experimental animal groups with unilateral ureter ligation showed a significantly increased number of apoptotic tubular and interstitial cells in the obstructed kidney compared with the contralateral, unobstructed kidney. Histomorphometric analysis of renal interstitial fibrotic changes in the groups of rats treated with losartan or water showed a statistically significant difference (p < 0.05) between the operated and sham--operated animals. In conclusion, following UUO there is a significantly increased number of apoptotic tubular cells and interstitial fibrosis in the ipsilateral kidney compared with the contralateral kidney. ACE inhibitors and AT1 receptor antagonists could not decrease the extent of renal cells apoptosis and interstitial fibrosis after UUO.


Single center experiences with telemetric intracranial pressure measurements in patients with CSF circulation disturbances.
Hydrocephalus may present with heterogeneous signs and symptoms. The indication for its treatment and the optimal drainage in complex cases may be challenging. Telemetric intracranial pressure measurements (TICPM) may open new perspectives for those circumstances. We report our experiences using the Neurovent-P-tel and the Sensor Reservoir in a retrospective study. A series of 21 patients (age range 10-39.5 years) treated in our Pediatric Neurosurgical Unit receiving a TICPM was analyzed. In 8 patients, a Neurovent-P-Tel was implanted; 13 patients received a Sensor Reservoir, 6 of which as a stand-alone implant, while 7 were already shunted. TICPM were performed on an outpatient basis. Possible complications, follow-up surgeries, and TICPM were analyzed. Concerning the complications, one infection was seen in each group and one postoperative seizure was observed in the P-tel group. TICPM-assisted shunt adjustments lead to clinical improvements in six patients in the P-tel group and six patients in the Sensor Reservoir group. In four out of six non-shunted patients, TICPM contributed to the indication toward shunt implantation. TICPM seems to be a promising tool to improve clinical management of shunted patients with complex hydrocephalus. The two available systems will need further technical improvements, concerning implantation time, measurements, and data analysis in order to optimize handling and interpretation of the data.


Toward the recognition of structure-function relationships in galactomannans.
In this paper the determination of the physical/rheological characteristics is described for a series of commercial galactomannans of which the structural details have been reported previously. Both solubility of the galactomannans and rheological properties of galactomannan solutions and galactomannan/xanthan mixtures were determined. Using a statistical analysis approach an attempt was undertaken to recognize correlations between structural and rheological data. The best correlation found was between the abundance of galactose substituents at a regular distance (type of galactomannan) and the storage modulus (G') of mixed galactomannan/xanthan gels, underscoring the hypothesis that branching hinders the formation of a network with xanthan gum. Also, the G' for the group of locust bean gums correlated with the degree of blockiness, that is, the size and occurrence of nonsubstituted regions on the mannose backbone. In addition, galactomannans displayed an apparent decrease in gelling ability with increasing average molecular weight. That G' also relates to the type of galactomannan can therefore partly be attributed to differences in average molecular weight for the various galactomannan types. However, within the series of locust bean gums tested, also an increase of G' with molecular weight was observed. This can be explained by the decreasing number of loose ends of the polymers and the concomitant increasing efficiency in network participation with increasing molecular weight.


Distribution and fate of anthropogenic nitrogen in the Calamagrostis angustifolia wetland ecosystem of Sanjiang Plain, Northeast China.
Wetlands are important for the protection of water quality of rivers and lakes, especially those adjacent to agricultural landscapes, by intercepting and removing nutrients in runoff. In this study, the 15N tracer technique was applied to study the distribution and fate of anthropogenic nitrogen (15N-fertilizer) in Calamagrostis angustifolia Kom wetland plant-soil microcosms to identify the main ecological effects of it. 15NH415NO3 solution (14.93 mg N/L, 20.28 at.%15N) was added to each microcosm of the first group, which was approximate to the current nitrogen concentration (CNC) of farm drainage, and 29.86 mg N/L 15NH415NO3 solution was added to another group, which was approximate to the double nitrogen concentration (DNC) of farm drainage, while no nitrogen (NN) was added to the third group. The results suggest that the input of anthropogenic nitrogen has positive effects on the biomass and total nitrogen content of plant, and the positive effects will be elevated as the increase of its input amount. The increase of 15N-fertilizer can also elevate its amounts and proportions in plant nitrogen. Soil nitrogen is still the main source of plant nitrogen, but its proportion will be reduced as the increase of 15N-fertilizer. The study of the fate of 15N-fertilizer indicates that, in CNC treatment, only a small proportion is water-dissolved (0.13 +/- 0.20%), a considerable proportion is soil-immobilized (17.02 +/- 8.62%), or plant-assimilated (23.70 +/- 0.92%), and most is lost by gaseous forms (59.15 +/- 8.35%). While in DNC treatment, about 0.09 +/- 0.15% is water-dissolved, 15.33 +/- 7.46% is soil-immobilized, 23.55 +/- 2.86% is plant-assimilated, and 61.01 +/- 5.59% is lost by gaseous forms. The double input of anthropogenic nitrogen can not elevate the proportions of plant-assimilation, soil-immobilization and water-dissolution, but it can enhance the gaseous losses.


Two simple questions to assess outcome after stroke: a European study.
The "2 simple questions" were designed as an efficient way of measuring outcome after stroke. We assessed the sensitivity and specificity of this tool, adapted for use in 8 European centers, and used it to compare outcomes across centers. Data were taken from the Biomed II prospective study of stroke care and outcomes. Three-month poststroke data from 8 European centers were analyzed. Sensitivity and specificity were assessed by comparing responses to the 2 simple questions with Barthel Index and modified Rankin scale scores. Adjusting for case mix, logistic regression was used to compare patients in each center with "good" outcome (not dependent and fully recovered) at 3 months. Data for 793 patients were analyzed. For the total sample, the dependency question had a sensitivity of 88% and a specificity of 77%; the recovery question had a sensitivity of 78% and a specificity of 90%. Dependency data from Riga had much lower sensitivity. There was variation in good outcome between centers (P:=0.0015). Compared with the reference center (Kaunas), patients in Dijon, Florence, and Menorca were more likely to have good outcome, after adjusting for case mix. Dependency and recovery questions showed generally high sensitivity and specificity. There were significant differences across centers in outcome, but reasons for these are unclear. Such differences raise particular questions about how patients interpreted and answered the simple questions and the extent to which expectations of recovery and perceived needs for assistance vary cross-culturally.


P-Selectin Is Critical for De Novo Pulmonary Arterial Thrombosis Following Blunt Thoracic Trauma.
Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.


Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: implications for human motor neuron disease.
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown but hypotheses about disease mechanisms include oxidative stress, defective axonal transport, mitochondrial dysfunction and disrupted RNA processing. Whereas familial ALS is well represented by transgenic mutant SOD1 mouse models, the mouse mutant wobbler (WR) develops progressive motor neuron degeneration due to a point mutation in the Vps54 gene, and provides an animal model for sporadic ALS. VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS. In motor neurons of homozygous symptomatic WR mice, a massive number of endosomal vesicles significantly enlarged (up to 3 μm in diameter) were subjected to ultrastructural analysis and immunohistochemistry for the endosome-specific small GTPase protein Rab7 and for amyloid precursor protein (APP). Enlarged vesicles were neither detected in heterozygous WR nor in transgenic SOD1(G93A) mice; in WR motor neurons, numerous APP/Rab7-positive vesicles were observed which were mostly LC3-negative, suggesting they are not autophagosomes. We conclude that endosomal APP/Rab7 staining reflects impaired vesicle trafficking in WR mouse motor neurons. Based on these findings human ALS tissues were analysed for APP in enlarged vesicles and were detected in spinal cord motor neurons in six out of fourteen sporadic ALS cases. These enlarged vesicles were not detected in any of the familial ALS cases. Thus our study provides the first evidence for wobbler-like aetiologies in human ALS and suggests that the genes encoding proteins involved in vesicle trafficking should be screened for pathogenic mutations.


[Serotypes of herpes simplex virus and their association with cervical cancer].
Comparative studies of some properties of Herpes simplex viruses type I and II and their ability to reproduce latent infection in vitro revealed no essential differences between them. Virus-neutralizing and hemagglutinating antibodies to the virus type II are detected reliably more frequently in cervical cancer patients than in healthy ones. Forty six per cent of cervical cancer patients and thirty nine per cent of healthy females along with antibodies against the virus of serotype II showed a specific cellular response, which was demonstrated in the reaction of leucocyte migration inhibition. In patients with dissemination of the disease there is an inhibited cell immunity to Herpes virus without changing of the humoral resistance.


Consensus Development of a Core Content for a Standardized Medical Toxicology Curriculum for Medical Students.
Currently, no standardized core content in medical toxicology exists for medical students. The goals of this study were to (1) assess the current state and needs of medical toxicology clerkships and (2) develop a consensus-derived list of core topics that should be covered during a medical toxicology clerkship. We assembled a task force established by the American College of Medical Toxicology (ACMT) of nine experts in medical toxicology or emergency medicine. We developed a needs assessment survey that was sent to all medical student clerkship directors in medical toxicology. Based on their responses, we used a modified Delphi process to develop a consensus of core topics that should be covered during a medical student clerkship. Nineteen out of 42 (45%) clerkship directors completed the survey; 18 met inclusion criteria. The majority of clerkships were 4 weeks in duration with an average of 15 students/year. The three most common teaching methods used were bedside teaching (n = 17/18), classroom teaching (n = 17/18), and journal club (n = 14/18). All the clerkship directors (n = 18/18) reported they would use a standardized curriculum as well as educational content developed by ACMT. There was overwhelming consensus on the core topics which included, but were not limited to, pharmacology/toxicology; drugs; drugs of abuse; natural products; pharmacological basis of antidote use; toxicologic syndromes; vital sign abnormalities; initial management; supportive and other care; withdrawal syndrome management; industrial, household, and environmental toxins; differential diagnosis by clinical findings; and ABCs-resuscitation. The ACMT task force developed a medical toxicology clerkship core content. The task force also identified a need for shared resources among clerkships.


An unusual case of xanthogranulomatous pyelonephritis in a leukemia patient.
We report a 65-year-old woman with leukemia who presented with urinary tract infection, splenic abscess, and a renal mass. Both urine and pus culture of the splenic abscess yielded Klebsiella pneumoniae. The differential diagnosis of the renal mass by radiological findings included unliquefied renal abscess, xanthogranulomatous pyelonephritis, and renal cell carcinoma. Percutaneous biopsy of the renal mass confirmed the diagnosis of xanthogranulomatous pyelonephritis. Because of high surgical risk, the patient received medical treatment with prolonged antibiotic therapy. With antibiotic therapy only, not only the splenic abscess was cured but also follow-up ultrasonography showed progressive resolution of the renal mass. The occurrence of xanthogranulomatous pyelonephritis has rarely been reported in the absence of urinary tract obstruction or nephrolithiasis. Furthermore, this is the first report of xanthogranulomatous pyelonephritis occurring in patients with leukemia and concurrent with splenic abscess. In addition to describing this unusual case, we provide a short review of xanthogranulomatous pyelonephritis successfully treated with antibiotics only.


Effects of an 8-week multimodal exercise program on strength, flexibility, and golf performance in 55- to 79-year-old men.
Substantial research has indicated the beneficial effect of physical activity on physical fitness and activities of daily living in older adults, but none have investigated the effects on performance of recreational activities. This investigation studied the effect of an exercise program on fitness and golf-clubhead speed in older men. Thirty-one golfers (mean age 65.1 +/- 6.2 years) were randomly assigned to a treatment (n = 19) or control (n = 12) group. The treatment group completed an 8-week strength and flexibility program. Assessments included 10-RM muscle strength; selected range-of-motion (ROM) measurements; and golf-clubhead speed (CHS). ANCOVA revealed significant differences between groups (p <.005) for all strength measurements and several ROM measurements. CHS was significantly different (p <.05) between groups after the intervention. Mean CHS improved from 85.0 to 87.1 miles/hr (136.8 to 140.2 km/hr). These results indicate that a strength and flexibility program can improve golf performance in older adults.


Larger core size has superior technical and analytical accuracy in bladder tissue microarray.
The construction of tissue microarrays (TMAs) with cores from a large number of paraffin-embedded tissues (donors) into a single paraffin block (recipient) is an effective method of analyzing samples from many patient specimens simultaneously. For the TMA to be successful, the cores within it must capture the correct histologic areas from the donor blocks (technical accuracy) and maintain concordance with the tissue of origin (analytical accuracy). This can be particularly challenging for tissues with small histological features such as small islands of carcinoma in situ (CIS), thin layers of normal urothelial lining of the bladder, or cancers that exhibit intratumor heterogeneity. In an effort to create a comprehensive TMA of a bladder cancer patient cohort that accurately represents the tumor heterogeneity and captures the small features of normal and CIS, we determined how core size (0.6 vs 1.0 mm) impacted the technical and analytical accuracy of the TMA. The larger 1.0 mm core exhibited better technical accuracy for all tissue types at 80.9% (normal), 94.2% (tumor), and 71.4% (CIS) compared with 58.6%, 85.9%, and 63.8% for 0.6 mm cores. Although the 1.0 mm core provided better tissue capture, increasing the number of replicates from two to three allowed with the 0.6 mm core compensated for this reduced technical accuracy. However, quantitative image analysis of proliferation using both Ki67+ immunofluorescence counts and manual mitotic counts demonstrated that the 1.0 mm core size also exhibited significantly greater analytical accuracy (P=0.004 and 0.035, respectively, r2=0.979 and 0.669, respectively). Ultimately, our findings demonstrate that capturing two or more 1.0 mm cores for TMA construction provides superior technical and analytical accuracy over the smaller 0.6 mm cores, especially for tissues harboring small histological features or substantial heterogeneity.


Detection of blood pressure in general practice screening or case finding?
An attempt has been made to show that there is still a need to evaluate screening for moderate hypertension (i.e. diastolic blood pressure equal or above 110 mm Hg). At present it has not been satisfactorily shown that treatment reduces mortality and morbidity. It is suggested that in the meantime individual general practitioners can be encouraged to find cases and that this method is probably the most suitable for identifying patients with diastolic blood pressure levels above 110 mm Hg (diastolic IV).In addition it has been indicated that at present we have little knowledge about how to make treatment acceptable and that this in itself needs further study. The question has also been raised as to who will do the work of screening and treating, and whether those earmarked to do this will find it acceptable. Finally, the need for accurate costing of the benefits and disadvantages before the wide-scale implementation of a screening service has been discussed.


Surgical Therapy for Colitis Cystica Profunda and Solitary Rectal Ulcer Syndrome.
The initial treatment for patients with colitis cystica profunda is aimed at re-education of bowel habits to avoid straining. Patients are instructed to spend the minimum time on the commode. A high-fiber diet with bulk laxatives is recommended. If fiber does not work, polyethylene glycol solutions and surface-active stool softeners such as docusate sodium are tried. Conservative therapy resolves most symptoms. Biofeedback is offered to patients who fail dietary therapy. For patients with associated rectal prolapse, an operation designed to correct the intussusception is considered. For full-thickness prolapse (procidentia) a mucosal resection (Delorme) or perineal proctectomy (Altemeier) is recommended. Surgical treatment of internal (occult) prolapse is problematic. If attempted, a resection and suture rectopexy has the most support. In the absence of procidentia, transanal excision may be used in selected patients. If other measures fail, a mucosal sleeve resection with coloanal pull-through or a diverting colostomy may be considered.


Inhibition of WY-14,643 induced hepatic lesion growth in mice by rotenone.
The effect of rotenone treatment on [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (WY-14,643) hepatic lesion growth in male B6C3F1 mice was investigated. Following induction of hepatic focal lesions by diethylnitrosamine (DEN) 35 mg/kg twice a week for 8 weeks, mice were placed into one of the four treatment groups: group I, control NIH-07 diet (control diet), group II, rotenone (600 mg/kg diet), group III NIH-07 diet containing WY-14,643 (1000 mg/kg diet), and group IV, NIH-07 diet containing WY-14,643 (1000 mg/kg diet) and rotenone (600 mg/ kg diet). Mice were killed after 30 and 60 days of dietary treatment. The effect of treatment with WY-14,643 and rotenone on hepatic lesion growth was examined by estimating the number of focal lesions per liver and the relative volume of focal lesions. WY-14,643 (group III) increased both the number and the volume of focal lesions. In particular, an increase in number and volume of basophilic lesions was seen. Co-treatment with WY-14,643 and rotenone (group IV) decreased both the number and the volume of the total number of focal lesions and basophilic foci compared with WY-14,643 treatment alone (group II). Alterations in the growth of hepatic focal lesions was further investigated by examining DNA synthesis and apoptosis within individual lesions. WY-14,643 (group III) treatment increased the DNA synthetic labeling index in all foci. Co-treatment of rotenone and WY-14,643 (group IV) decreased focal DNA synthesis and mitosis and increased the incidence of apoptotic hepatocytes. These data suggest that rotenone's ability to inhibit WY-14,643-induced hepatic focal lesion growth was mediated through a decrease in hepatic focal proliferation and an increase in focal apoptosis.


The beaten copper cranium: a correlation between intracranial pressure, cranial radiographs, and computed tomographic scans in children with craniosynostosis.
The beaten copper appearance of the cranium, as well as other cranial radiographic and computed tomographic findings in children with craniosynostosis, is often interpreted by clinicians as evidence of elevated intracranial pressure (ICP). However, a correlation between radiological findings and ICP measurements has not been previously demonstrated, and their usefulness in detecting elevated ICP has not been defined. To address those issues, 123 children with craniosynostosis who had cranial radiographs and ICP monitoring were studied. To assess the specificity of certain radiological findings to patients with craniosynostosis, cranial radiographs of patients with craniosynostosis were compared to those of age- and sex-matched controls. In patients with craniosynostosis, findings on cranial radiographs were compared to computed tomographic scans of the brain. Radiographic findings were then correlated with ICP measurements obtained while the patient was sleeping, which was measured using a Camino fiberoptic ICP monitor (Camino Laboratories, San Diego, CA). All radiographs were independently analyzed by two radiologists who were blinded to clinical and ICP data. A diffuse beaten copper pattern, erosion of the dorsum sellar, and suture diastasis were seen more commonly in patients with craniosynostosis than in controls (P < 0.05), but the presence of the beaten copper pattern was no more common in children with craniosynostosis. ICP was greater when a diffuse beaten copper pattern, dorsum sellar erosion, suture diastasis, or narrowing of basal cisterns was present (P < 0.05). Although this study demonstrates that some cranial radiographic and computed tomographic findings do correlate with elevated ICP, the sensitivity of radiological methods for detecting elevated ICP is universally low and they are not recommended to screen for elevated ICP in children with craniosynostosis.


Extension of bactericidal effect of sodium hypochlorite into dentinal tubules.
The aim of this study was to determine the extent of disinfection mediated by 2 concentrations of sodium hypochlorite for bacteria-laden dentin wall of a root canal. A dual-species film, Enterococcus faecalis and Porphyromonas gingivalis, was cultivated on root canal dentin for 7 days. The canal wall was irrigated with 0.5% or 3% sodium hypochlorite (n = 8 each), with a control group (n = 2) irrigated with sterile saline. The roots were then split horizontally at 5-, 7-, and 9-mm levels from root apex and examined under confocal laser scanning microscope and then scanning electron microscope. The proportions of viable cells situated on different depths into root canal dentin were compared at a significance level of P = .05. Both concentrations of sodium hypochlorite significantly reduced the amount of live bacteria in the most superficial layer (first 0.1 mm) of root canal dentin, compared with the control; however, the difference was not significant between the 2 concentrations. For the next 2 layers (0.1-0.3 mm into dentinal tubules), irrigation with 3% hypochlorite resulted in significantly lower amounts of viable bacteria than 0.5% hypochlorite or saline. No significant difference between 0.5% or 3% sodium hypochlorite and the positive control was observed in deeper (>0.3 mm) regions into the root canal wall. Increasing the concentration of sodium hypochlorite improves the penetration depth of its antibacterial action into dentinal tubules, but that seemed unable to completely eradicate bacteria residing there. Total elimination of bacteria from dentinal tubules cannot be achieved by irrigation with sodium hypochlorite alone.


Ex-ante evaluation of promising soybean innovations for sub-Saharan Africa.
This study undertakes an ex-ante evaluation of the effects of alternative technology and policy options on soybean supply and demand in sub-Saharan Africa (SSA) to 2050. Current soybean consumption in SSA is dominated by cooking oil followed by soybean cake used as animal feed. Due to weak processing sectors and low soybean yields, the region is currently importing about 70% of its consumption requirements. Based on the results from a geospatial bio-economic modeling framework, soybean consumption in SSA is projected to more than double by 2050 compared to 2010 due in part to a rising population and rising incomes. On the other hand, supply from domestic production is projected to increase by 80% over the same period. Hence, by 2050, net imports into SSA would be nearly 4 times higher than supply from domestic production. Under a future drier climate, some of the production gains achieved through soybean research and extension would be lost and this would further worsen the soybean demand gap in SSA relative to the baseline. This study shows that relying on conventional breeding alone to increase soybean yields in SSA would not be enough to substantially reduce the future demand gap. A combination of promising innovations affecting the soybean value chain across SSA would be needed to close the soybean demand gap in SSA by 2050 under a drier future climate.


Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast.
Nonsense-mediated mRNA decay (NMD) in mammalian cells is restricted to newly synthesized mRNA that is bound at the 5' cap by the major nuclear cap-binding complex and at splicing-generated exon-exon junctions by exon junction complexes. This messenger ribonucleoprotein has been called the pioneer translation initiation complex and, accordingly, NMD occurs as a consequence of nonsense codon recognition during a pioneer round of translation. Here, we characterize the nature of messenger ribonucleoprotein that is targeted for NMD in Saccharomyces cerevisiae. Data indicate that NMD targets both cap-binding complex (Cbc)1p- and eukaryotic translation initiation factor (eIF)4E-bound mRNAs, unlike in mammalian cells, where NMD does not detectably target eIF4E-bound mRNA. First, intron-containing pre-mRNAs in yeast are detectably bound by either Cbc1p, or, unlike in mammalian cells, eIF4E, indicating that mRNAs can be derived from either Cbc1p- or eIF4E-bound pre-mRNAs. Second, the ratio of nonsense-containing Cbc1p-bound mRNA to nonsense-free Cbc1p-bound mRNA, which was < 0.4 for those mRNAs tested here, is essentially identical to the ratio of the corresponding nonsense-containing eIF4E-bound mRNA to nonsense-free eIF4E-bound mRNA, and both ratios increase in cells treated with the translational inhibitor cycloheximide (CHX). These data, together with data presented here and elsewhere showing that Cbc1p-bound transcripts are precursors to eIF4E-bound transcripts, demonstrate that Cbc1p-bound mRNA is targeted for NMD. In support of the idea that eIF4E-bound mRNA is also targeted for NMD, eIF4E-bound mRNA is targeted for NMD in strains that lack Cbc1p. These results suggest that both Cbc1p- and eIF4E-mediated pioneer rounds of translation occur in yeast.


[Phraseology of disk herniation: an inevitable revision renaming the posterior disk prolapse--retrolapse is better].
Etymology teaches us to use the term prolapse exclusively for describing the part of the intervertebral disk that has slipped forwards, that is, towards the anterior longitudinal ligament. Consequently, the word retrolapse has to be introduced as the corresponding term in order to designate the posterior slipped disk. The common use of matching pairs like propulsion/retropulsion or prognathism/retrognathia is another justification for the recommended revision.


The Food Contaminant Mycotoxin Deoxynivalenol Inhibits the Swallowing Reflex in Anaesthetized Rats.
Deoxynivalenol (DON), one of the most abundant mycotoxins found on cereals, is known to be implicated in acute and chronic illnesses in both humans and animals. Among the symptoms, anorexia, reduction of weight gain and decreased nutrition efficiency were described, but the mechanisms underlying these effects on feeding behavior are not yet totally understood. Swallowing is a major motor component of ingestive behavior which allows the propulsion of the alimentary bolus from the mouth to the esophagus. To better understand DON effects on ingestive behaviour, we have studied its effects on rhythmic swallowing in the rat, after intravenous and central administration. Repetitive electrical stimulation of the superior laryngeal nerve or of the tractus solitarius, induces rhythmic swallowing that can be recorded using electromyographic electrodes inserted in sublingual muscles. Here we provide the first demonstration that, after intravenous and central administration, DON strongly inhibits the swallowing reflex with a short latency and in a dose dependent manner. Moreover, using c-Fos staining, a strong neuronal activation was observed in the solitary tract nucleus which contains the central pattern generator of swallowing and in the area postrema after DON intravenous injection. Our data show that DON modifies swallowing and interferes with central neuronal networks dedicated to food intake regulation.


Multicolor Flow Cytometry and High-Dimensional Data Analysis to Probe Complex Questions in Vaccinology.
Vaccines induce a highly complex immune reaction in secondary lymphoid organs to generate immunological memory against an antigen or antigens of interest. Measurement of post immunization immune responses generated by specialized lymphocyte subsets requires time-dependent sampling, usually of the blood. Several T and B cell subsets are involved in the reaction, including CD4 and CD8 T cells, T follicular helper cells (Tfh), and germinal center B cells alongside their circulating (c) counterparts; cTfh and antibody secreting cells. Multicolor flow cytometry of peripheral blood mononuclear cells (PBMC) coupled with high-dimensional analysis offers an opportunity to study these cells in detail. Here we demonstrate a method by which such data can be generated and analysed using software that renders multidimensional data on a two dimensional map to identify rare vaccine-induced T and B cell subsets.


Assessment of the usefulness of semipermeable membrane devices for long-term watershed monitoring in an urban slough system.
Semipermeable membrane devices (SPMDs) were deployed at eight sites within the Buffalo Slough, near Portland, Oregon, to (1) measure the spatial and seasonal distribution of dissolved polycyclic aromatic hydrocarbon (PAH) and organochlorine (OC) compounds in the slough, (2) assess the usefulness of SPMDs as a tool for investigating and monitoring hydrophobic compounds throughout the Columbia Slough system, and (3) evaluate the utility of SPMDs as a tool for measuring the long-term effects of watershed improvement activities. Data from the SPMDs revealed clear spatial and seasonal differences in water quality within the slough and indicate that for hydrophobic compounds, this time-integrated passive-sampling technique is a useful tool for long-term watershed monitoring. In addition, the data suggest that a spiking rate of 2-5 microg/SPMD of permeability/performance reference compounds, including at least one compound that is not susceptible to photodegradation, may be optimum for the conditions encountered here.


Identification of an immunogenic 18-kDa protein of Helicobacter pylori by alkaline phosphatase gene fusions.
The use of alkaline phosphatase fusion methodology to identify Helicobacter pylori exported proteins enabled the identification of an open reading frame (ORF) encoding a highly immunogenic, previously uncharacterised exported protein. The predicted aminoacid sequence displays a typical N-terminal signal peptide and contains regions of C-terminal hydrophobicity consistent with a membrane-associated protein. Southern blot analysis revealed that the gene encoding the protein was absent in several Helicobacter spp. and a combination of PCR and sequence analysis of the amplified gene showed that it is highly conserved amongst isolates of H. pylori. To obtain pure recombinant protein, the gene encoding the protein was cloned and expressed as a beta-galactosidase (beta-gal) fusion in Escherichia coli and the protein was purified by affinity chromatography and proteolytic cleavage of the beta-gal portion. The purified protein, which has an apparent mol. wt of 18 kDa, was recognised by antibody present in 71% of sera from patients infected with H. pylori, but in only 16% of sera from patients with unrelated or no gastrointestinal disease, by Western blot assays. These results indicate that the 18-kDa protein from H. pylori is immunogenic and is expressed in vivo.


Reproductive biology and pollination mechanisms of Epidendrum secundum (Orchidaceae). Floral variation: a consequence of natural hybridization?
The phenology, flower morphology, pollination mechanism and reproductive biology of Epidendrum secundum were studied in a semi-deciduous forest at the Serra do Japi (SJ), and in the Atlantic rain forest of Picinguaba, both natural reserves in the State of São Paulo, southeastern Brazil. E. secundum flowers all year round, with a flowering peak between September and January. This species is either a lithophytic or terrestrial herb in the SJ, whereas, in Picinguaba, it grows mainly in disturbed areas along roadsides. E. secundum is pollinated by several species of diurnal Lepidoptera at both study sites. In Picinguaba, where E. secundum is sympatric with E. fulgens and both share the same pollinators, pollen transference between these two species was recorded. E. secundum is self-compatible but pollinator-dependent. It is inter-compatible with E. fulgens, producing fertile seeds. In contrast to the population of the SJ, in the Picinguaba region, floral morphology is quite variable among plants and some individuals present flowers with characteristics in-between both sympatric species, suggesting that natural hybridization occasionally occurs. The anthropogenic perturbation is probably the cause of the occurrence of E. secundum in the Picinguaba region, enabling its contact with E. fulgens.


Structural insights into neutrophilic migration revealed by the crystal structure of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1.
Neutrophil plays an essential role in host defense against infection, but uncontrolled neutrophilic infiltration can cause inflammation and severe epithelial damage. We recently showed that CXCR2 formed a signaling complex with NHERF1 and PLC-2, and that the formation of this complex was required for intracellular calcium mobilization and neutrophilic transepithelial migration. To uncover the structural basis of the complex formation, we report here the crystal structure of the NHERF1 PDZ1 domain in complex with the C-terminal sequence of CXCR2 at 1.16 Å resolution. The structure reveals that the CXCR2 peptide binds to PDZ1 in an extended conformation with the last four residues making specific side chain interactions. Remarkably, comparison of the structure to previously studied PDZ1 domains has allowed the identification of PDZ1 ligand-specific interactions and the mechanisms that govern PDZ1 target selection diversities. In addition, we show that CXCR2 can bind both NHERF1 PDZ1 and PDZ2 in pulldown experiments, consistent with the observation that the peptide binding pockets of these two PDZ domains are highly structurally conserved. The results of this study therefore provide structural basis for the CXCR2-mediated neutrophilic migration and could have important clinical applications in the prevention and treatment of numerous neutrophil-dependent inflammatory disorders.


[Investigation of the content of carcinogenic compounds in commercial smoked fish].
The authors performed investigations of the content of polycyclic aromatic hydrocarbons (PAH) (n = 17) and their nitro derivatives (n = 5) in commercial cold and hot smoked herrings and greenlings. The level of benz(a)pyrene in all fish samples was found to be well below the current sanitary and hygienic limits. The concentration of N-nitrosoamines in cold smoked fish was slightly below that in hot smoked one. The content of nitro derivatives of PAH in fish is indicative of the low significance of these compounds in the total negative potential of smoked fish.


Long noncoding RNA polymorphisms in gynecological cancers.
Gynecological malignancies are one of the main causes of cancer-induced mortality. Despite remarkable recent therapeutic advances, current therapeutic options are not sufficient. Regarding the effect of long noncoding RNAs (lncRNAs) on cell differentiation, proliferation and apoptosis, variations in their expression cause different anomalies, such as tumorigenesis. SNPs influence lncRNA function and expression. LncRNA polymorphisms can predict cancer risk and are effective for early diagnosis and customized therapy. In this literature review, we comprehensively investigate the effect of lncRNA polymorphisms on gynecological cancers. LncRNA-related variants are proposed to evaluate cancer incidence, early detection and management of personalized therapy. Nonetheless, more studies are required to validate the consistency of current findings in numerous samples and across various ethnic groups.


Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO) Radar Based on the Elements of the Covariance Matrix.
In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.


Hepatic artery reconstruction and biliary stricture formation after living donor adult liver transplantation using the left lobe.
Biliary complications, including bile leak, biliary stricture, and cholangitis, are seen in 15% to 29% of all cases after living related liver transplantation. We investigate risk factors and discuss the management of biliary complications after living related liver transplantation in adults using left-lobe grafts. We studied 37 adult patients who underwent living related liver transplantation using left-lobe grafts. Perioperative variables were evaluated as risk factors for biliary strictures. The overall incidence of biliary complications was 43.2% (16 of 37 patients). Anastomotic strictures occurred in 8 patients, whereas bile leaks and cholangitis occurred in 9 and 8 patients, respectively. Anastomotic stricture was strongly related to a partial artery reconstruction (P <.02) and cholangitis (P <.01). Anastomotic biliary stricture was not associated with bile leak, acute cellular rejection, or infection. Our results suggest that an important risk factor for biliary anastomotic biliary strictures is a partial artery reconstruction. To minimize the risk for biliary anastomotic strictures, we will reconstruct both the middle and left hepatic artery.


The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation.
The impact of residual vein thrombosis (RVT) on the long-term outcome of patients with deep vein thrombosis (DVT) is unknown. We assessed the incidence of recurrent venous thromboembolism (VTE), postthrombotic syndrome (PTS), arterial thrombotic events, and cancer in patients with DVT with and without RVT. For this purpose, we evaluated up to 3 years 869 consecutive patients with acute proximal DVT who had conventional anticoagulation. RVT, defined as ultrasound incompressibility of at least 4 mm in the common femoral and/or the popliteal vein after 3 months, was detected in 429 (49.4%) patients, and was more likely in males (adjusted odds ratio [OR], 1.82; 95% confidence interval [CI], 1.37-2.04), in patients with previous VTE (OR, 1.64; 95% CI, 1.06-2.54), and in those with extensive thrombosis (OR, 3.58; 95% CI, 2.19-5.86). During the 3-year follow-up, recurrent VTE developed in 84 (19.6%) patients with RVT and 43 (9.8%) patients without RVT (adjusted hazard ratio [HR], 2.03; 95% CI, 1.40-2.94); PTS in 225 (52.4%) and 118 (26.8%), respectively (HR, 2.34; 95% CI, 1.87-2.93); arterial thrombosis in 29 (6.7%) and 14 (3.2%), respectively (HR, 2.05; 95% CI, 1.08-3.88); and cancer in 21 (4.9%) and 8 (1.8%), respectively (HR, 3.09; 95% CI, 1.31-7.28). In conclusion, in patients treated with vitamin K antagonists for prevention of recurrent VTE, RVT doubles the risk of recurrent VTE, PTS, arterial thrombosis, and cancer. Males, patients with previous VTE, and those with extensive thrombosis are independent risk factors of RVT development. Studies addressing the impact of the novel direct anticoagulants on the development of RVT as well as the long-term complications of DVT are needed.


Application of the Theoretical Domains Framework and the Behaviour Change Wheel to Understand Physicians' Behaviors and Behavior Change in Using Temporary Work Modifications for Return to Work: A Qualitative Study.
Purpose Applying the theoretical domains framework (TDF) and the Behaviour Change Wheel (BCW) to understand physicians' behaviors and behavior change in using temporary work modifications (TWMs) for return to work (RTW). Methods Interviews and focus group discussions were conducted with 15 occupational physicians (OPs). Responses were coded using the TDF and the BCW. Results Key behaviors related to applying TWMs were initiating the process with the employee, making recommendations to the workplace, and following up the process. OP behaviors were influenced by several factors related to personal capability and motivation, and opportunities provided by the physical and social environment. Capability comprised relevant knowledge and skills related to applying TWMs, remembering to initiate TWMS and monitor the process, and being accustomed to reflective practice. Opportunity comprised physical resources (e.g., time, predefined procedures, and availability of modified work at companies), and social pressure from stakeholders. Motivation comprised conceptions of a proper OP role, confidence to carry out TWMs, personal RTW-related goals, beliefs about the outcomes of one's actions, feedback received from earlier cases, and feelings related to applying TWMs. OPs' perceived means to target these identified factors were linked to the following BCW intervention functions: education, training, persuasion, environmental restructuring, and enablement. The results suggest that at least these functions should be considered when designing future interventions. Conclusions Our study illustrates how theoretical frameworks TDF and BCW can be utilized in a RTW context to understand which determinants of physicians' behavior need to be targeted, and how, to promote desired behaviors.


[Severe and malignant arterial hypertension: the optimal treatment].
54 patients were treated with a combination of capoten and diuretics for 40 to 250 days. Some patients had been subjected to the "nitroprusside test" prior to medication. The relation between the clinical state, the perilimbal and eye fundus microcirculation and degree of BP decrease were studied using fluorescent angiography. An adequate (for this group of patients) effect was observed when blood pressure decreased by 25-30% as compared to the initial level. For this capoten, up to 150 mg per day, is sufficient. However, when the BP during the "nitroprusside test" and capoten "overdosage" fell by 35-40% or more as compared to the basal level, undesirable changes were observed. The angioarchitecture deteriorated considerably due to a significant increase in the number of non-perfused vessels and vast ischemic zones as compared to the initial state.


Liposomes as carriers of poorly water-soluble substrates: linear modelling of membrane systems with catalytic or binding sites of different facedness. Significance of experimental membrane partition coefficients and of kinetic and equilibrium parameters.
1. A multiphasic modelling approach to systems containing membrane-bound receptors or catalytic sites and a liposomal preparation as a substrate carrier is described. Kinetic expressions are derived for a single-substrate enzymic reaction operating at constant liposome concentration or at a fixed substrate/liposome concentration ratio. 2. The assumption that accumulation of exchangeable components into the phospholipid bilayers can be described by linear bulk-phase partition leads to simple relationships between the initial reaction rate and (a) two kinetic coefficients (V and K'm), (b) the partition coefficients of the solutes for the lipid compartments of the membrane (Pms) and liposomal preparations (P1s) and (c) the total concentrations of substrate, membrane lipid and liposomal lipid. K'm is called the effective Michaelis constant. 3. For correct estimation of the coefficients V, K', Pms and P1s extrapolation to zero lipid concentration is required. 4. The distinction is introduced between hydrophilic and hydrophobic aqueous-faced sites, lipid-faced sites and mixed sites, i.e. sites overlapping an aqueous and a lipid region. For hydrophilic aqueous-faced sites K'm is equal to the true Km and for the other types of site to Km/Ps. For lipid-faced and for mixed sites Ps corresponds to the membrane partition coefficient Pms. For binding of homologous compounds to a hydrophobic aqueous-faced binding pocket Ps is the incremental site partition coefficient Pbss, which takes into account the energetic contribution to the binding process due to the hydrophobic tail of the ligands. 5. K'm accounts for any effects due to the facedness and nature of the enzymic sites. The dependence of the systems on the size of the lipidic partition compartment(s) is expressed exclusively by a distribution function F.6. When enzyme assays are performed with a series of chemically different substrates containing the same catalytically sensitive group, independence of K'm from partition indicates a hydrophilic aqueous-faced binding site. For the low-molecular-mass members of the homologous series a linear increase in -log (K'm) with the logarithm of the partition coefficient will be observed with any of the other site types considered 7. Equilibrium relationships for binding of a ligand to a membrane-bound receptor are also derived. 8. The significance of experimental membrane partition coefficients is discussed.


Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals.
The majority of maturing T lymphocytes that recognize self-antigens is eliminated in the thymus upon exposure to their target antigens. This physiological process of negative selection requires that tissue-specific antigens be expressed by thymic cells, a phenomenon that has been well studied in experimental animals. Here, we have examined the expression in human thymi of four retinal antigens, that are capable of inducing autoimmune ocular disease retinal S-antigen (S-Ag), recoverin, RPE65 and inter-photoreceptor retinoid-binding protein (IRBP)], as well as four melanocyte-specific antigens, two of which are used as targets for melanoma immunotherapy [gp100, melanoma antigen recognized by T cells 1, tyrosinase-related protein (TRP)-1 and TRP-2]. Using reverse transcription (RT)-PCR, we found that all thymic samples from the 18 donors expressed mRNA transcripts of most or all the eight tested tissue antigens. Yet, the expression of the transcripts varied remarkably among the individual thymic samples. In addition, S-Ag, RPE65 and IRBP were detected by immunostaining in rare cells in sections of human thymi by antibodies against these proteins. Quantitative real-time RT-PCR analysis revealed that the retinal antigen transcripts in the human thymus are present at trace levels, that are lower by approximately five orders of magnitude than those in the retina. Our observations thus support the notions that thymic expression is a common feature for all tissue-specific antigens and that the levels of expression play a role in determining the susceptibility to autoimmunity against these molecules.


Selection of reliable reference genes for qPCR studies on chondroprotective action.
Chondroprotective agents (CPA) such as glucosamine, curcumin and diacerein represent potential remedies for the management of osteoarthritis and several studies have been performed on their effects in-vitro and in-vivo. For the investigation of chondroprotective action on chondrocyte gene expression, quantitative real-time RT-PCR is the method of choice. However, validation of applied normalization strategies represents a crucial and sometimes neglected step in the analysis process. Therefore, the present study aimed to determine the expression stability of common reference genes (ACTB, Beta actin; GAPDH, Glyceraldehyde-3-phosphate; B2M, Beta-2-microglobulin; HPRT1, Hypoxanthine phosphoribosyl-transferase I; SDHA, Succinate dehydrogenase complex, subunit A; YWHAZ, Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide) under the influence of glucosamine, curcumin and diacerein in the IL-1beta-stimulated C-28/I2 chondrocyte model, using the geNorm software tool. CPA treatment of C-28/I2 chondrocytes significantly affected the expression level of many reference genes (p < 0.05). According to their expression stability, geNorm analysis revealed rankings of the 3 most stable genes (from most stable to least stable) as follows: GAPDH, B2M and SDHA in glucosamine treated samples and HPRT1, GAPDH and B2M in curcumin or diacerein treated samples. Interestingly, ACTB was one of the most variably expressed genes throughout all experiments. Our study points out the problem of relying on commonly used reference genes without an accurate validation process. For normalization purposes in gene profiling studies on glucosamine action, the genes GAPDH, B2M and SDHA are recommended as single reference genes depending on the expression level of the target gene or more favourably in combination. For experiments with curcumin and diacerein the use of HPRT1, GAPDH and B2M should be considered.


Radial Organization in the Mammalian Nucleus.
In eukaryotic cells, most of the genetic material is contained within a highly specialized organelle-the nucleus. A large body of evidence indicates that, within the nucleus, chromatinized DNA is spatially organized at multiple length scales. The higher-order organization of chromatin is crucial for proper execution of multiple genome functions, including DNA replication and transcription. Here, we review our current knowledge on the spatial organization of chromatin in the nucleus of mammalian cells, focusing in particular on how chromatin is radially arranged with respect to the nuclear lamina. We then discuss the possible mechanisms by which the radial organization of chromatin in the cell nucleus is established. Lastly, we propose a unifying model of nuclear spatial organization, and suggest novel approaches to test it.