Association between left ventricular global longitudinal strain and adverse left ventricular dilatation after ST-segment-elevation myocardial infarction.
Myocardial infarct size is a major determinant of left ventricular (LV) remodeling after ST-segment-elevation myocardial infarction. We evaluated whether LV global longitudinal strain (GLS), proposed as a novel marker of infarct size, is associated with 3- and 6-month LV dilatation after ST-segment-elevation myocardial infarction. In the first ST-segment-elevation myocardial infarction patients treated with primary percutaneous coronary intervention, baseline LVGLS was measured with 2-dimensional speckle-tracking echocardiography. Patients were dichotomized according to median value. The independent relationship between GLS groups and LV end-diastolic volume at 3 and 6 months (adjusted for clinical and echocardiographic variables) was assessed. The final study population comprised 1041 patients (60±12 years; 76% men). Median LVGLS was -15.0%. Patients with baseline LVGLS>-15.0% exhibited greater LV dilatation at 3 and 6 months compared with patients with GLS≤-15.0% (LV end-diastolic volume 123±44 versus 106±36 mL and 121±43 versus 102±34 mL, respectively; global group-time interaction P<0.001). This association retained the same statistical significance after adjustment for various relevant demographic, clinical, and echocardiographic characteristics. Further, net reclassification improvement index demonstrated significant incremental value of LVGLS for prediction of LV end-diastolic volume increase (0.14 [95% confidence interval, 0.00034-0.29]; P=0.04). LVGLS before discharge after ST-segment-elevation myocardial infarction is independently associated with LV dilatation at follow-up.


Obesity and risk of thyroid cancer: evidence from a meta-analysis of 21 observational studies.
Several studies have evaluated the association between obesity and thyroid cancer risk. However, the results remain uncertain. In this study, we conducted a meta-analysis to assess the association between obesity and thyroid cancer risk. Published literature from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were retrieved before 10 August 2014. We included all studies that reported adjusted risk ratios (RRs), hazard ratios (HRs) or odds ratios (ORs), and 95% confidence intervals (CIs) of thyroid cancer risk. Thirty-two studies (n=12 620 676) were included in this meta-analysis. Obesity was associated with a significantly increased risk of thyroid cancer (adjusted RR=1.33; 95% CI, 1.24-1.42; I2=25%). In the subgroup analysis by study type, increased risk of thyroid cancer was found in cohort studies and case-control studies. In subgroup analysis by sex, both obese men and women were at significantly greater risk of thyroid cancer than non-obese subjects. When stratified by ethnicity, significantly elevated risk was observed in Caucasians and in Asians. In the age subgroup analysis, both young and old populations showed increased thyroid cancer risk. Subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers and in non-smokers. In the histology subgroup analyses, increased risks of papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer were observed. However, obesity was associated with decreased risk of medullary thyroid cancer. Our results indicate that obesity is associated with an increased thyroid cancer risk, except medullary thyroid cancer.


Generalist and subspecialist physicians' knowledge, attitudes, and practices regarding influenza and pneumococcal vaccinations for elderly and other high-risk patients: a nationwide survey.
Influenza and pneumococcal vaccination rates remain too low. This survey assessed generalist and subspecialist physicians' knowledge, attitudes, and practices regarding influenza and pneumococcal vaccinations for high-risk patients. A self-administered questionnaire was mailed to 6000 physicians randomly selected from a national database. After 3 mailings, 1874 physicians (32%) of the 5858 eligible responded. Although most physicians thought that it was very important for their high-risk patients be current on influenza and pneumococcal vaccinations, only 86% and 75% of generalists and subspecialists, respectively, very strongly recommended influenza vaccinations to their elderly patients and only 81% and 64%, respectively, very strongly recommended pneumococcal vaccinations to their elderly patients (P<.001 for both). After multivariate logistic regression, factors significantly associated with strongly recommending vaccinations to elderly patients in the influenza and pneumococcal vaccination models included female sex of provider, the provider having received an influenza vaccination, the provider's beliefs about vaccine effectiveness and cost-effectiveness, a patient's risk for illness, and ease of targeting patients. In addition, generalists were more likely than subspecialists to strongly recommend pneumococcal vaccinations to their patients. Patient reminders, special clinics, and standing orders were each used by fewer than 30% of respondents, although generalists were more likely than subspecialists to use such strategies. Nontrivial proportions of generalist and subspecialist physicians fail to strongly recommend influenza and pneumococcal vaccinations to their elderly and high-risk patients. Other effective strategies for promoting vaccine delivery are also used relatively infrequently. These findings suggest areas for improvement if vaccination rates are to reach national goals.


Molecular characteristics of CTA056, a novel interleukin-2-inducible T-cell kinase inhibitor that selectively targets malignant T cells and modulates oncomirs.
Interleukin-2-inducible T-cell kinase (Itk) is a member of the Btk (Bruton's tyrosine kinase) family of tyrosine kinases. Itk plays an important role in normal T-cell functions and in the pathophysiology of both autoimmune diseases and T-cell malignancies. Here, we describe the initial characterization of a selective inhibitor, 7-benzyl-1-(3-(piperidin-1-yl)propyl)-2-(4-(pyridin-4-yl)phenyl)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (CTA056), that was developed through screening a 9600-compound combinatorial solution phase library, followed by molecular modeling, and extensive structure-activity relationship studies. CTA056 exhibits the highest inhibitory effects toward Itk, followed by Btk and endothelial and epithelial tyrosine kinase. Among the 41 cancer cell lines analyzed, CTA056 selectively targets acute lymphoblastic T-cell leukemia and cutaneous T-cell lymphoma. Normal T cells are minimally affected. Incubation of Jurkat and MOLT-4 cells with CTA056 resulted in the inhibition of the phosphorylation of Itk and its effectors including PLC-γ, Akt, and extracellular signal-regulated kinase, as well as the decreased secretion of targeted genes such as interleukin-2 and interferon-γ. Jurkat cells also underwent apoptosis in a dose-dependent manner when incubated with CTA056. The potent apoptosis-inducing potential of CTA056 is reflected by the significant modulation of microRNAs involved in survival pathways and oncogenesis. The in vitro cytotoxic effect on malignant T cells is further validated in a xenograft model. The selective expression and activation of Itk in malignant T cells, as well as the specificity of CTA056 for Itk, make this molecule a potential therapeutic agent for the treatment of T-cell leukemia and lymphoma.


Air Pollution and Maximum Temperature Are Associated with Neurodevelopmental Regressive Events in Autism Spectrum Disorder.
Neurodevelopmental regression (NDR) is an enigmatic event associated with autism spectrum disorder (ASD) during which a child loses previously acquired skills and develops ASD symptoms. In some, a trigger which precedes the NDR event, such as a fever, can be identified, but in many cases no trigger is obvious. We hypothesize that air pollution (PM2.5) may trigger NDR, especially in those children without an identified trigger. Average daily PM2.5, ozone, precipitation and maximum temperature (Tmax) were derived from Environmental Protection Agency models and National Oceanic and Atmospheric Administration monitors based on zip-code information from 83 ASD participants during the six-weeks following the onset month of an NDR event and a reference period defined as one year before and one year after the event. Seasonally adjusted logistic regression (LR) and linear mixed models (LMM) compared cases (with a history of NDR) and matched controls (without a history of NDR). LR models found that the risk of NDR was related to higher PM2.5 during 3 to 6 weeks of the NDR event period, particularly in those without a trigger. Overall, both models converged on NDR being related to a higher PM2.5 and lower Tmax both during the NDR event period as well as the reference period, particularly in those without a known trigger. This temporal pattern suggests that environmental triggers, particularly PM2.5, could be related to NDR, especially in those without an identifiable trigger. Further studies to determine the underlying biological mechanism of this observation could help better understand NDR and provide opportunities to prevent NDR.


Electrocardiographic left atrial abnormalities and risk of incident stroke in hypertensive patients with electrocardiographic left ventricular hypertrophy.
Recent findings in population-based studies suggest that abnormal P wave terminal force in lead V1 (PTFV1), a marker of left atrial abnormalities such as fibrosis, dilatation and elevated filling pressures, is associated with incident ischemic stroke, even in the absence of atrial fibrillation. However, whether PTFV1 predicts incident stroke in hypertensive patients during blood pressure lowering has not been examined. Risk of incident stroke was examined in relation to abnormal PTFV1 on a baseline ECG in 7778 hypertensive patients with ECG left ventricular hypertrophy, no history of atrial fibrillation, in sinus rhythm on their baseline ECG with no incident atrial fibrillation during follow-up, who were randomly assigned to losartan-based or atenolol-based treatment. Results focused on the subset of patients between 55 and 60 years old (n = 1879) because of a significant interaction between PTFV1 and age in Cox analyses. Abnormal PTFV1 was defined by the presence of a negative terminal P wave in lead V1 with amplitude × duration ≥ 4000 μV ms. During mean follow-up of 4.8 ± 0.9 years, 364 patients (4.7%) of the overall study population and 45 patients (2.4%) in the subset of patients aged 60 years or less experienced a definite stroke. In the overall population, abnormal PTFV1 was not a significant predictor of incident stroke [hazard ratio 1.12, 95% confidence interval (CI) 0.91-1.38, P = 0.301], but there was a highly significant interaction of PTFV1 with age stratified at 60 (P = 0.009, hazard ratio 2.30, 95% CI 1.27-4.13, P = 0.006 for abnormal PTFV1 in the interaction model). Further analyses in the subset of patients aged 60 years or less revealed a higher incidence of stroke occurred in those with abnormal than normal baseline PTFV1: incidence rate per 1000 person-years, 7.8 (95% CI 5.2-11.4) vs 3.4 (95% CI 2.2-5.2; P = 0.004); a greater than two-fold increased risk of incident stroke (hazard ratio 2.31, 95% CI 1.28-4.16, P = 0.005) in univariate Cox analysis; and in multivariable Cox regression models that adjusted for other significant predictors of incident stroke in this population (sex, history of stroke or transient ischemic attack, ischemic heart disease or diabetes, baseline creatinine and in-treatment SBP), that abnormal PTFV1 remained associated with a greater than two-fold increased risk of incident stroke (hazard ratio 2.06; 95% CI 1.14-3.74, P = 0.017). Abnormal PTFV1, a marker of left atrial abnormality, was strongly associated with incident stroke in hypertensive patients, independent of in-treatment SBP and other predictors of incident stroke. This association, in the absence of detectable atrial fibrillation, suggests that an underlying atrial cardiopathy may cause left atrial thrombus formation and a subsequent stroke without intervening clinically recognized atrial fibrillation.


Design, Synthesis and Biological Evaluation of Biphenylglyoxamide-Based Small Molecular Antimicrobial Peptide Mimics as Antibacterial Agents.
There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure-activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.


Herbal hepatotoxicity: suspected cases assessed for alternative causes.
Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI). We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes. The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient. In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI.


Global Analysis of Transcription Start Sites and Enhancers in Endometrial Stromal Cells and Differences Associated with Endometriosis.
Identifying tissue-specific molecular signatures of active regulatory elements is critical to understanding gene regulatory mechanisms. In this study, transcription start sites (TSS) and enhancers were identified using Cap analysis of gene expression (CAGE) across endometrial stromal cell (ESC) samples obtained from women with (n = 4) and without endometriosis (n = 4). ESC TSSs and enhancers were compared to those reported in other tissue and cell types in FANTOM5 and were integrated with RNA-seq and ATAC-seq data from the same samples for regulatory activity and network analyses. CAGE tag count differences between women with and without endometriosis were statistically tested and tags within close proximity to genetic variants associated with endometriosis risk were identified. Over 90% of tag clusters mapping to promoters were observed in cells and tissues in FANTOM5. However, some potential cell-type-specific promoters and enhancers were also observed. Regions of open chromatin identified using ATAC-seq provided further evidence of the active transcriptional regions identified by CAGE. Despite the small sample number, there was evidence of differences associated with endometriosis at 210 consensus clusters, including IGFBP5, CALD1 and OXTR. ESC TSSs were also located within loci associated with endometriosis risk from genome-wide association studies. This study provides novel evidence of transcriptional differences in endometrial stromal cells associated with endometriosis and provides a valuable cell-type specific resource of active TSSs and enhancers in endometrial stromal cells.


Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis.
Lipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far. SAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies. Lipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype. In summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.


Vascular Stem Cells and the Role of B-Raf Kinase in Survival, Proliferation, and Apoptosis.
Neovascularization is an essential process in organismal development and aging. With aging, from fetal to adult life, there is a significant reduction in neovascularization potential. However, the pathways which play a role in increased neovascularization potential during fetal life are unknown. Although several studies proposed the idea of vascular stem cells (VSCs), the identification and essential survival mechanism are still not clear. In the present study, we isolated fetal VSCs from the ovine carotid artery and identified the pathways involved in their survival. We tested the hypothesis that fetal vessels contain a population of VSCs, and that B-Raf kinase is required for their survival. We conducted viability, apoptotic, and cell cycle stage assays on fetal and adult carotid arteries and isolated cells. To determine molecular mechanisms, we conducted RNAseq, PCR, and western blot experiments to characterize them and identify pathways essential for their survival. Results: A stem cell-like population was isolated from fetal carotid arteries grown in serum-free media. The isolated fetal VSCs contained markers for endothelial, smooth muscle, and adventitial cells, and formed a de novo blood vessel ex vivo. A transcriptomic analysis that compared fetal and adult arteries identified pathway enrichment for several kinases, including B-Raf kinase in fetal arteries. Furthermore, we demonstrated that B-Raf- Signal Transducer and Activator of Transcription 3 (STAT3)-Bcl2 is critical for the survival of these cells. Fetal arteries, but not adult arteries, contain VSCs, and B-Raf-STAT3-Bcl2 plays an important role in their survival and proliferation.


Guilty by stereotypic association: Country animosity and brand prejudice and discrimination.
This research tests the proposition that brands suffer prejudice and discrimination due to animosity toward a country with which they have a strong stereotypic association. In the first study, attitudinal data collected across a range of brands that vary in terms of the strength of the brand-country association indicate that brands with strong stereotypic association with a country suffer direct prejudice, in the form of more negative attitudes, related to animosity. When the brand-country association is less strong, the relationship between animosity and brand attitudes is moderated by the strength of the stereotypic association. In the second study, the level of brand-country association is manipulated experimentally to provide additional evidence of its moderating role on the relationship between country animosity and both prejudice toward (more negative brand attitudes) and discrimination against (less choice) a new brand.


Mapping urban-rural gradients of settlements and vegetation at national scale using Sentinel-2 spectral-temporal metrics and regression-based unmixing with synthetic training data.
The increasing impact of humans on land and ongoing global population growth requires an improved understanding of land cover (LC) and land use (LU) processes related to settlements. The heterogeneity of built-up areas and infrastructures as well as the importance of not only mapping, but also characterizing anthropogenic structures suggests using a sub-pixel mapping approach for analysing related LC from space. We implement a regression-based unmixing approach for mapping built-up surfaces and infrastructure, woody vegetation and non-woody vegetation for all of Germany and Austria at 10 m resolution to demonstrate the potential of sub-pixel mapping. We map LC fractions for one point in time, using all available Sentinel-2 data from 2017 and 2018 (<70% cloud cover). We combine the concept of synthetically mixed training data with statistical aggregations from spectral-temporal metrics (STM) derived from Sentinel-2 reflectance time series. We specifically examine how STM can be used for creating synthetically mixed training data. STM are known to facilitate large area mapping by being largely independent of image acquisition dates and inherently incorporate phenological information. Vegetation is an important part of settlements and time series information supports its mapping. Synthetically mixed training data facilitates a streamlined training by using pure reference spectra to generate artificial mixtures as input to regression modelling of LC fractions in mixed pixels. We here show how combining both offers great potential for wall-to-wall LC fraction mapping. We further investigate the positive effect of STM on map results by comparing the performance of different subsets of STM combinations. Our results indicate that many STM combinations containing spectral variability and vegetation indices provide suitable input to creating synthetic training data for regression-based fraction mapping. Results for built-up surfaces and infrastructure (MAE 0.13/RMSE 0.18 at 20 m resolution), woody vegetation (0.18, 0.22) and non-woody vegetation (0.14, 0.19) are highly consistent across Germany and Austria. Only a few surface types were not accurately predicted in our nation-wide mapping. Further research is required to optimize mapping of temporally invariant bare soil and rock surfaces that show spectral similarity to built-up surfaces and infrastructure. The proposed methodology combines benefits of both regression-based modelling with synthetically mixed training data and STM, and thus facilitates mapping of LC fractions on a national scale and at high resolution. Such information will allow to better characterize settlements and identifying processes such as densification that are best represented by continuous LC mapping.


Oral Signs and HLA-DQB1∗02 Haplotypes in the Celiac Paediatric Patient: A Preliminary Study.
Celiac disease (CD) diagnosis can be extremely challenging in the case of atypical patterns. In this context, oral signs seem to play a decisive role in arousing suspicion of these forms of the disease. At the same time, the different expressions of the HLA-DQB1∗02 allele apparently seem to facilitate the interpretation of signs and highlighted symptoms. The aim of this work was to verify whether it is possible to identify a correlation between the development of oral signs and different DQ2 haplotypes in celiac pediatric patients. 44 celiac patients with a medium age of 9.9 were studied. Oral examinations were performed in order to identify recurrent aphthous stomatitis (RAS) and dental enamel defects (DED). The diagnosis of DED resulted as being related to allele expression (P value = 0.042) while it was impossible to find a similar correlation with RAS. When both oral signs were considered, there was an increase in correlation with HLA-DQB1∗02 expression (P value = 0.018). The obtained results identified both the fundamental role that dentists can play in early diagnosis of CD, as well as the possible role of HLA haplotype analysis in arousing suspicion of atypical forms of the disease.


Cholinergic microstimulation of the peribrachial nucleus in the cat. I. Immediate and prolonged increases in ponto-geniculo-occipital waves.
The cholinergic agonist carbachol was injected into the pontine Pb area where PGO bursting cells have been recorded. When microinjections were localized to the ventrolateral aspect of the caudal Pb nucleus near aggregates of ChAT immunolabeled cholinergic neurons, carbachol produced an immediate onset of state-independent PGO waves in the ipsilateral LGB. These state-independent PGO waves persisted for 3-4 days. After the first 24 hrs PGO wave activity increasingly became associated with REM sleep and with REM transitional SP sleep as both of these PGO-related states increased in amount to 3-4 times baseline levels. The increase in amount of PGO-related states peaked on days 2-4 following one carbachol injection and persisted for 10-12 days. These results suggest a two stage process: stage one, PGO enhancement, is the direct consequence of the membrane activation of cholinoceptive PGO burst neurons by carbachol; stage two, REM enhancement, is the consequence of metabolic activation of endogenous cholinergic neurons. This experimental preparation is a useful model for the study of the electrophysiology and functional significance of PGO wave and REM sleep generation.


Experiences of first wave general practice fundholders in South East Thames Regional Health Authority.
The purchasing power given to general practitioner fundholders has important longterm implications. A study was undertaken to investigate the experiences of a group of fundholders. All 15 first wave fundholders in South East Thames Regional Health Authority were sent a questionnaire asking about their experiences towards the end of the first year of fundholding. The practices varied considerably in the degree of changes made. Nine had developed consultant outreach clinics in the surgery and four had made major changes in their use of providers. Advantages mentioned by respondents were the outreach consultant clinics, increased practice facilities, increased provider responsiveness, greater direct access and facilities for investigations, reduced waiting times for outpatient appointments, increased computerization and a new awareness of practice and provider activity. A number of difficulties were also mentioned, including provider resistance and time spent on administration. It is important to view these changes in the context of other National Health Service and general practice reforms: practice based innovations are not unique to fundholding and other initiatives could have brought about these changes. In addition, developments such as outreach consultant clinics which may benefit the practice still need to be evaluated in terms of cost effectiveness and health outcomes, as well as their impact on services elsewhere.


[Prostate cancer centres / prostate centres--certified by DKG or DVPZ].
In Germany, ambitious efforts for the implementation of well-defined quality standards in the diagnosis of and therapy for prostate cancer have resulted in the creation of certified centres over the past years. This development is in analogy to that of certified breast and intestinal centres. Concerning the prostate, there are two different models for the certification of centres. The model of the Dachverband der Prostatazentren e. V. (DVPZ) includes the most common kinds of dis-eases of the prostate, namely BPH, prostate cancer and prostatitis. On the other hand prostate cancer centres are certified by the Deutsche Krebsgesellschaft (DKG). Among German urologists there is a controversial discussion concerning this process. The present paper gives a review of the two models and discusses the chances as well as the risks which come along with certified centres.


Knee osteoarthritis alters peri-articular knee muscle strategies during gait.
The primary role of muscles is to move, and control joints. It is therefore important to understand how degenerative joint disease changes this role with the resulting effect on mechanical joint loading. Muscular control strategies can vary depending on strength and coordination which in turn influences joint control and loading. The purpose of this study was to investigate the variation in neuromuscular control mechanisms and joint biomechanics for three subject groups including those with: uni-compartmental knee osteoarthritis (OA), listed for high tibial osteotomy surgery (pre-HTO, n = 10); multi-compartmental knee OA listed for total knee replacement (pre-TKR, n = 9), and non-pathological knees (NP, n = 11). Lower limb kinematics and electromyography (EMG) data for subjects walking at self-selected speed, were input to an EMG-driven musculoskeletal knee model which was scaled and calibrated to each individual to estimate muscle forces. Compared to NP, the peak gastrocnemius muscle force reduced by 30% and 18% for pre-HTO and pre-TKR respectively, and the peak force estimated for hamstring muscle increased by 25% for pre-HTO. Higher quadriceps and hamstring forces suggest that co-contraction with the gastrocnemius could lead to higher joint contact forces. Combined with the excessive loading due to a high external knee adduction moment this may exacerbate joint destruction. An increased lateral muscle co-contraction reflects the progression from NP to uni-compartmental OA (pre-HTO). Pre-TKR patients adopt a different gait pattern to pre-HTO patients. Increased medial muscle co-activation could potentially differentiate between uni- or multi-compartmental OA.


Secretin Amino-Terminal Structure-Activity Relationships and Complementary Mutagenesis at the Site of Docking to the Secretin Receptor.
Class B1 G protein-coupled receptors are activated by peptides, with amino-terminal regions critical for biologic activity. Although high resolution structures exist, understanding of key features of the peptide activation domain that drive signaling is limited. In the secretin receptor (SecR) structure, interactions are observed between peptide residues His1 and Ser2 and seventh transmembrane segment (TM7) receptor residue E373. We interrogated these interactions using systematic structure-activity analysis of peptide and receptor. His1 was critical for binding and cAMP responses, but its orientation was not critical, and substitution could independently modify affinity and efficacy. Ser2 was also critical, with all substitutions reducing peptide affinity and functional responses proportionally. Mutation of E373 to conserved acidic Asp (E373D), uncharged polar Gln (E373Q), or charge-reversed basic Arg (E373R) did not alter receptor expression, with all exhibiting secretin-dependent cAMP accumulation. All position 373 mutants displayed reduced binding affinities and cAMP potencies for many peptide analogs, although relative effects of position 1 peptides were similar whereas position 2 peptides exhibited substantial differences. The peptide including basic Lys in position 2 was active at SecR having acidic Glu in position 373 and at E373D while exhibiting minimal activity at those receptors in which an acidic residue is absent in this position (E373Q and E373R). In contrast, the peptide including acidic Glu in position 2 was equipotent with secretin at E373R while being much less potent than secretin at wild-type SecR and E373D. These data support functional importance of a charge-charge interaction between the amino-terminal region of secretin and the top of TM7. SIGNIFICANCE STATEMENT: This work refines our molecular understanding of the activation mechanisms of class B1 G protein-coupled receptors. The amino-terminal region of secretin interacts with the seventh transmembrane segment of its receptor with structural specificity and with a charge-charge interaction helping to drive functional activation.


Selenium nanoparticles as anti-infective implant coatings for trauma orthopedics against methicillin-resistant Staphylococcus aureus and epidermidis: in vitro and in vivo assessment.
Background: Bacterial infection is a common and serious complication in orthopedic implants following traumatic injury, which is often associated with extensive soft tissue damage and contaminated wounds. Multidrug-resistant bacteria have been found in these infected wounds, especially in patients who have multi trauma and prolonged stay in intensive care units.Purpose: The objective of this study was to develop a coating on orthopedic implants that is effective against drug-resistant bacteria. Methods and results: We applied nanoparticles (30-70nm) of the trace element selenium (Se) as a coating through surface-induced nucleation-deposition on titanium implants and investigated the antimicrobial activity against drug resistant bacteria including Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus epidermidis (MRSE) in vitro and in an infected femur model in rats.The nanoparticles were shown in vitro to have antimicrobial activity at concentrations as low as 0.5ppm. The nanoparticle coatings strongly inhibited biofilm formation on the implants and reduced the number of viable bacteria in the surrounding tissue following inoculation of implants with biofilm forming doses of bacteria. Conclusion: This study shows a proof of concept for a selenium nanoparticle coatings as a potential anti-infective barrier for orthopedic medical devices in the setting of contamination with multi-resistant bacteria. It also represents one of the few (if only) in vivo assessment of selenium nanoparticle coatings on reducing antibiotic-resistant orthopedic implant infections.


Alternative greater saphenous vein-sparing surgery: valvuloplasty combined with axial transposition of a competent tributary vein for the treatment of primary valvular incompetence---18-month follow-up.
The greater saphenous vein (GSV) is one of the best grafts for vascular reconstruction, and a variety of sparing methods in patients with primary varicose veins have been performed. Of these, valvuloplasty of the subterminal valve is useful, but reflux in the proximal GSV via a competent tributary vein still remains. To minimize the subsequent reflux, we propose a new method, "valvuloplasty combined with axial transposition of a competent tributary vein" for the treatment of GSV incompetence. To compare this new method with single valvuloplasty. Seventy-eight limbs in 65 patients with GSV incompetence were included. Of these limbs, 38 underwent angioscopic valvuloplasty of the subterminal valve alone (V group). The remaining 40 were treated by angioscopic valvuloplasty combined with axial transposition of a competent tributary vein (V + T group). A competent tributary vein was identified by duplex scan in the thigh before surgery. After angioscopic valvuloplasty had been done, a competent tributary vein was exposed, and was cut 1.5 cm distal to its insertion. The distal cut end of the vein was then transposed to the GSV and end-to-side anastomosis was performed using 8-0 nylon under magnification. The incompetent GSV was ligated between the insertion and the anastomosed region. Venous hemodynamic changes were analyzed using air plethysmography (APG). Values obtained by9 APG included venous volume (VV), venous filling index (VFI), ejection fraction (EF), and residual venous function (RVF). The follow-up period was 18 months. Intergroup differences were analyzed with the Wilcoxon ranked sum test for nonparametric distribution. There were no statistical differences in age, gender, or clinical presentation between the two groups. In the V group, 27 limbs had reflux in the proximal GSV (67.4%). On the other hand, only 6 limbs (13.3%) showed minor reflux in the V + T group. A significant difference was seen in VFI at 1 year, and a continuous increase was observed in the V group during the follow-up examinations (P =.0035, VFI = 2.50 plus minus 1.21, 1.14 plus minus 0.42 at 18 months, respectively). Valvuloplasty combined with axial transposition of a competent tributary vein gives a better result than valvuloplasty alone at the 18-month follow-up. A competent valve in this location can be expected to improve VFI to a normal range.


The N-terminal extracellular domain 23-60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1.
The calcitonin receptor-like receptor (CLR) requires the associated receptor activity-modifying protein (RAMP)1 to reveal a calcitonin gene-related peptide (CGRP) receptor. Here, the subdomain of the CLR that associates with RAMP1 has been identified in chimeras between the CLR and the parathyroid hormone (PTH) receptor 1 (PTHR). The PTHR alone does not interact with RAMP1. RAMP1 requires the CLR for its transport to the cell surface. Thus, receptor-dependent RAMP1 delivery to the plasma membrane and coimmunoprecipitation from the cell surface were used as measures for receptor/RAMP1 interaction. Several chimeric CLR-PTHR included the N-terminal amino acids 23-60 of the CLR transported RAMP1 to the surface of COS-7 cells much like the intact CLR. Moreover, RAMP1 coimmunoprecipitated with these receptors from the cell surface. A CLR deletion mutant, consisting of the N-terminal extracellular domain, the first transmembrane domain, and the C-terminal intracellular region, revealed the same results. Cyclic AMP was stimulated by CGRP in CLR/RAMP1 expressing cells (58 +/- 19-fold, EC(50) = 0.12 +/- 0.03 nM) and by PTH-related protein in cells expressing the PTHR (50 +/- 10-fold, EC(50) = 0.25 +/- 0.03 nM) or a PTHR with the N-terminal amino acids 23-60 of the CLR (23 +/- 5-fold, EC(50) > 1000 nM). Other chimeric CLR-PTHR were inactive. In conclusion, structural elements in the extreme N-terminus of the CLR between amino acids 23-60 are required and sufficient for CLR/RAMP1 cotransport to the plasma membrane and heterodimerization.


Impaired family functioning in psychosis and its relevance to relapse: a two-year follow-up study.
The aim of the present study was to investigate whether dysfunctional family functioning contributes to relapse over a two-year follow-up period in patients experiencing their first episode of psychosis (FEP) and chronic patients with psychosis. The sample consisted of 100 remitted patients (50 FEP and 50 chronic) diagnosed with schizophrenia (82%) or bipolar disorder with most recent episode manic severe with psychotic features (18%) recruited from the Inpatient Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece, and their family caregivers. Family functioning was assessed in terms of cohesion and flexibility (FACES-IV), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Relapse was defined as patient rehospitalisation due to acute psychotic exacerbation, while number, length, and type of hospitalisations were also evaluated. Dysfunctional family functioning in terms of cohesion and flexibility was not found to be a significant risk factor for relapse in psychosis. High expressed emotion, as indexed primarily by increased levels of criticism rather than emotional over-involvement, was associated with increased risk of relapse and shorter time to relapse (HR=0.48, 95% CI: 0.24, 0.98, p=0.043). Similarly, high levels of family burden were related to shorter time to relapse (HR=0.47, 95% CI: 0.23, 0.95, p=0.037), whereas there was no significant difference in survival curves based on caregivers' psychological distress. No significant interaction effect of illness chronicity was observed in the aforementioned associations. These findings highlight caregivers' criticism and burden of care as long-term predictors of the course of psychosis from the early stages of the illness and later on. In contrast, unbalanced levels of cohesion and flexibility in the family, as well as caregivers' high emotional over-involvement and psychological distress do not appear to be factors that contribute to patient relapse. Family psychoeducational interventions focusing at ameliorating caregivers' negativity toward the patient, and easing the burden of care should be considered as means in reducing relapse.


Examining the Association Between a Modified Quan-Charlson Comorbidity Index and HIV Viral Suppression: A Cross-Sectional Analysis of DC Cohort Participants.
With the advancement of effective antiretroviral therapy, people with HIV live longer, and many are developing non-AIDS comorbidities. It is important to assess how comorbidities are associated with HIV-related health outcomes, such as viral suppression (VS). The aim of this study was to analyze the association between comorbidity burden, measured using a modified Quan-Charlson Comorbidity Index (QCCI), and VS (viral load result of <200 copies/mL). We hypothesized that an increase in QCCI score, indicating a higher risk for mortality, would correlate with lower likelihood of VS because of the burden of comorbidity treatment, possibly leading to worse antiretroviral adherence. Our analysis included participants from the DC Cohort Longitudinal HIV Study in Washington, DC. Eligible participants were aged ≥18 years and enrolled in the cohort as of January 1, 2018 (n = 2,471). A modified QCCI score, which weighs selected comorbidities (not including HIV/AIDS) and predicts mortality, was calculated using International Classification of Disease-9/10 codes from electronic health records. Multivariable logistic regressions were used to characterize the association between QCCI composite scores and VS. Participants were predominantly virally suppressed (89.6%), male (73.9%), non-Hispanic Black (74.7%), and between 18 and 55 years (59.3%). The median QCCI score was 1 (range = 1-12, interquartile range = 0-2), demonstrating predominately low mortality risk. We did not establish a statistically significant association between QCCI score and VS (adjusted odds ratio = 1.06, 95% confidence interval 0.96-1.17). Our findings suggest that a higher QCCI score was not associated with lower VS in this population, which may be partly due to the high retention in care among cohort participants.


Myocardial Bridging in Cases of Sudden Death and its Association with Clinicopathologic Characteristics.
Myocardial bridging (MB) is the course of the epicardial segment of a coronary artery within the myocardium. The systolic compression of this segment called the tunneled segment may lead to alterations in blood flow to the heart. We have studied the gross and microscopic features of MB in cases of sudden cardiac death and analyzed its characteristics and whether there is any association with other clinicopathological characteristics which may help us to understand the pathogenesis and risk stratification. This is a retrospective descriptive study of 132 postmortem heart specimens of sudden cardiac death. The coronary arteries were dissected, and MB and its characteristics were studied. Statistical analysis was performed using the Chi-square and Fisher's exact tests (P < 0.05 significant). MB was present in 28 cases (21.2%), with a mean age of 49.5 years and male:female ratio of 27:1. MB was seen in the left anterior descending artery in 86.2% of cases, the right coronary artery in 10%, and left circumflex artery in 3.5% of cases. Atherosclerosis was seen in the segment proximal to the tunneling in 89.2% of cases leading to infarction in four cases. Left ventricular hypertrophy (LVH) was significantly associated with MB cases (19/68%) (P < 0.05). MB causes turbulence of blood in the proximal segment leading to coronary atherosclerosis, thereby predisposing the heart to ischemic changes and LVH and may lead to infarction in a few cases.


Implementation, feasibility, and acceptability of 99DOTS-based supervision of treatment for drug-susceptible TB in Uganda.
99DOTS is a low-cost digital adherence technology that allows people with tuberculosis (TB) to self-report treatment adherence. There are limited data on its implementation, feasibility, and acceptability from sub-Saharan Africa. We conducted a longitudinal analysis and cross-sectional surveys nested within a stepped-wedge randomized trial at 18 health facilities in Uganda between December 2018 and January 2020. The longitudinal analysis assessed implementation of key components of a 99DOTS-based intervention, including self-reporting of TB medication adherence via toll-free phone calls, automated text message reminders and support actions by health workers monitoring adherence data. Cross-sectional surveys administered to a subset of people with TB and health workers assessed 99DOTS feasibility and acceptability. Composite scores for capability, opportunity, and motivation to use 99DOTS were estimated as mean Likert scale responses. Among 462 people with pulmonary TB enrolled on 99DOTS, median adherence was 58.4% (inter-quartile range [IQR] 38.7-75.6) as confirmed by self-reporting dosing via phone calls and 99.4% (IQR 96.4-100) when also including doses confirmed by health workers. Phone call-confirmed adherence declined over the treatment period and was lower among people with HIV (median 50.6% vs. 63.7%, p<0.001). People with TB received SMS dosing reminders on 90.5% of treatment days. Health worker support actions were documented for 261/409 (63.8%) people with TB who missed >3 consecutive doses. Surveys were completed by 83 people with TB and 22 health workers. Composite scores for capability, opportunity, and motivation were high; among people with TB, composite scores did not differ by gender or HIV status. Barriers to using 99DOTS included technical issues (phone access, charging, and network connection) and concerns regarding disclosure. 99DOTS was feasible to implement and highly acceptable to people with TB and their health workers. National TB Programs should offer 99DOTS as an option for TB treatment supervision.


[Fat-suppressing STIR sequences with and without contrast media in the MRT of ENT tumors].
Fat-suppressed STIR (short TI inversion recovery) sequences were compared to plain and contrast-enhanced T1-weighted SE sequences of head and neck tumors. 19 patients underwent MR imaging on a 0.5 Telsa system (T5-II, Philips). STIR imaging parameters: TR/TE = 1000/20 ms, inversion pulse 100 ms. All films were read by four radiologists. The image quality was graded: score from 0 to 5, by means that grade 5 = optimal quality. Sensitivity was 89% in STIR, 96% in SE sequences. Tumor delineation was graded good in the enhanced T1-weighted and enhanced fat suppression images. The unenhanced imaging was superior in STIR (STIR/T1 = 2.8/2.43). The tumor contrast was best in contrast enhanced and plain STIR sequences (STIR contrast = 3.41), and in the contrast enhanced T1-weighted SE (3.33). STIR almost equaled T1 post-contrast in respect of tumour conspicuity, but the sensitivity was lower. STIR can be a supplement to SE, but cannot substitute T1 postcontrast. The combined use is expected to have the highest assessment value.


Winning, losing, and violence.
Although international sports events attract huge interest, and results can be a barometer of popular national standing, their impact on violent behaviour has not been investigated. Associations between assault related emergency department (ED) attendances and international sporting events (home and away rugby and soccer matches) in a European capital city (Cardiff) served by one ED, between 1 May 1995 and 30 April 2002 were investigated. The frequency of assault related ED attendances were studied relative to whether the national team won or lost, controlling for potential covariates: match attendance, match location (home/away), results (win/lose), net scores, and day of match (weekend/weekday). Multiple linear regression was used to identify significant associations with ED assault related attendances. Matches which the Wales team won (p = 0.03), match attendance (p<0.001), and weekend matches (p<0.001) were positively associated with ED assault related injury attendances. Assault frequency measured in this way was no different for home and away matches. Assault injury resulting in ED treatment was more frequent when national teams won than when they lost. Sport type made no difference. Violence prevention efforts should be increased on international match days, when the national team is expected to win, when match attendance is large, and for away as well as home matches.


Photoactivity and optical applications of organic materials containing selenium and tellurium.
Sulfur-containing compounds, particularly derivatives of thiophene, are well studied for organic optoelectronic applications. Incorporating selenium or tellurium in place of sulfur imparts different physical properties due to the fundamental differences of these atoms relative to their lighter analogues. This has a profound influence on the properties of molecules and materials that incorporate chalcogens that may ultimately lead to new opportunities and applications. This mini-review will focus on the quantitative and qualitative photophysical characteristics of organic materials containing selenium and tellurium as well as their emerging applications as molecular photoactive species, including light-emitting sensors, triplet sensitizers, and beyond.


A putative 3-hydroxyisobutyryl-CoA hydrolase is required for efficient symbiotic nitrogen fixation in Sinorhizobium meliloti and Sinorhizobium fredii NGR234.
We report that the smb20752 gene of the alfalfa symbiont Sinorhizobium meliloti is a novel symbiotic gene required for full N2 -fixation. Deletion of smb20752 resulted in lower nitrogenase activity and smaller nodules without impacting overall nodule morphology. Orthologs of smb20752 were present in all alpha and beta rhizobia, including the ngr_b20860 gene of Sinorhizobium fredii NGR234. A ngr_b20860 mutant formed Fix- determinate nodules that developed normally to a late stage of the symbiosis on the host plants Macroptilium atropurpureum and Vigna unguiculata. However an early symbiotic defect was evident during symbiosis with Leucaena leucocephala, producing Fix- indeterminate nodules. The smb20752 and ngr_b20860 genes encode putative 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolases. HIB-CoA hydrolases are required for l-valine catabolism and appear to prevent the accumulation of toxic metabolic intermediates, particularly methacrylyl-CoA. Evidence presented here and elsewhere (Curson et al., , PLoS ONE 9:e97660) demonstrated that Smb20752 and NGR_b20860 can also prevent metabolic toxicity, are required for l-valine metabolism, and play an undefined role in 3-hydroxybutyrate catabolism. We present evidence that the symbiotic defect of the HIB-CoA hydrolase mutants is independent of the inability to catabolize l-valine and suggest it relates to the toxicity resulting from metabolism of other compounds possibly related to 3-hydroxybutyric acid.


The specificity properties that distinguish members of a set of homologous anti-digoxin antibodies are controlled by H chain mutations.
Five murine A/J strain anti-digoxin mAb (35-20, 40-40, 40-120, 40-140, and 40-160) have highly homologous H and L chain V regions, only differing by somatic mutation, yet differ in affinity and specificity. The availability of the VH and VL genomic clones from one hybridoma, 40-140, has now allowed studies involving in vitro mutagenesis and chain recombination among these five hybridomas. To determine the relative contributions of the mutations found in either VH or VL to the overall binding properties of these antibodies, we recombined the 40-140VH with the VL of each hybridoma. The 40-140VH gene was transfected into hybridoma variants that produce only VL. The recombinant antibodies show that the mutations present in VH, rather than in VL, affect the fine specificity properties of these antibodies, whereas, the mutations among both VH and VL chains are important in determining antigen affinity. From mutations present in VH that affect fine specificity properties, the comparison of the antibody sequences, and from the previously measured binding properties, we predicted and tested selected VH mutations for their ability to alter specificity or affinity by doing site-directed in vitro mutagenesis. The results for the somatic mutations found in this group of antibodies show: 1) VH mutations control the fine specificity properties that distinguish different members of this group; 2) in particular, VH residues 54 and 55 in CDR2 control the distinguishing characteristics of specificities between these antibodies; and 3) by mutagenesis, we had the unusual result of being able to alter Ag specificity without affecting affinity. A computer model of the 40-140 antibody binding site was generated which indicates that VH residues 54 and 55 are highly accessible.


The Prognostic Value of HRAS mRNA Expression in Cutaneous Melanoma.
This study aimed to investigate the prognostic value of HRAS mRNA expression in cutaneous melanoma. Cutaneous melanoma is an aggressive cancer with an increasing incidence. Few studies have focused on the transcriptional level of RAS isoforms (KRAS, NRAS, and HRAS) in cutaneous melanoma. To gain further insight into RAS isoforms at transcriptional level, we obtained the cutaneous melanoma data from cBioPortal and investigated the RAS mRNA expression levels in different stages of melanoma and evaluated their correlation with clinical characteristics and patients' survival. Furthermore, we retrieved and analyzed the coexpression data and performed pathway enrichment analysis. Totally, 452 cutaneous melanoma cases were included in this study. We found that lower HRAS expression level was associated with longer patient survival. 206 genes that negatively correlated with HRAS expression were positively correlated with KRAS and NRAS expression. In contrast, no gene that positively correlated with HRAS expression was positively correlated with KRAS and NRAS expression. In conclusion, our data showed that transcriptional regulation was different for the three RAS isoforms in cutaneous melanoma. This study highlighted the prognostic value of HRAS mRNA expression and revealed that HRAS greatly differs from KRAS and NRAS at the transcriptional level.


Assessment of Management Options on Striga Infestation and Maize Grain Yield in Kenya.
The parasitic purple witchweed [Striga hermonthica (Del.) Benth.] is a serious constraint to maize production in sub-Saharan Africa, especially in poor soils. Various Striga spp. control measures have been developed, but these have not been assessed in an integrated system. This study was conducted to evaluate a set of promising technologies for S. hermonthica management in western Kenya. We evaluated three maize genotypes either intercropped with peanut (Arachis hypogaea L.), soybean [Glycine max (L.) Merr.], or silverleaf desmodium [Desmodium uncinatum (Jacq.) DC] or as a sole crop at two locations under artificial S. hermonthica infestation and at three locations under natural S. hermonthica infestation between 2011 and 2013. Combined ANOVA showed significant (P < 0.05) cropping system and cropping system by environment interactions for most traits measured. Grain yield was highest for maize grown in soybean rotation (3,672 kg ha-1) under artificial infestation and in D. uncinatum and peanut cropping systems (3,203 kg ha-1 and 3,193 kg ha-1) under natural infestation. Grain yield was highest for the Striga spp.-resistant hybrid under both methods of infestation. A lower number of emerged S. hermonthica plants per square meter were recorded at 10 and 12 wk after planting on maize grown under D. uncinatum in the artificial S. hermonthica infestation. A combination of herbicide-resistant maize varieties intercropped with legumes was a more effective method for S. hermonthica control than individual component technologies. Herbicide-resistant and Striga spp.-resistant maize integrated with legumes would help reduce the Striga spp. seedbank in the soil. Farmers should be encouraged to adopt an integrated approach to control Striga spp. for better maize yields.


Common themes among morale and depression scales.
This paper reports on the intra- and interbattery scaling of three morale and depression batteries comprised of self-reported items: PGC, G-H, and ZUNG. Responses to the three scales were sought from a sample of long-term residents of a state mental hospital. First, the batteries were factor analyzed separately to identify the intrabattery scales; then the resultant scales were compared using canonical correlation and super matrix factor analysis to identify the interbattery themes. These analyses resulted in the identification of a Clinical Depression domain across all three batteries and single independent themes in both the Zung and PGC batteries.


Inhibition of hyaluronate synthesis.
UDP-GlcNAc (UDP-N-acetylglucosamine) and UDP-GlcA (UDP-glucuronic acid) were oxidized by periodate in the ribose ring and utilized as inhibitors for hyaluronate synthase in membrane fractions from the B6 cell line and in cell cultures of B6 cells and human fibrosarcoma HT 1080. Inhibition was irreversible and concentration-dependent and could be prevented in the case of periodate-oxidized UDP-GlcNAc by UDP-GlcNAc. Periodate-oxidized UDP-GlcNAc was shown to block chain elongation of hyaluronate. Introduction of periodate-oxidized UDP-GlcA into B6 cells by hypo-osmotic lysis of pinocytotic vesicles decreased hyaluronate synthesis by direct inhibition of the synthase. In HT 1080 cells the synthesis of hyaluronate, chondroitin sulphate and heparan sulphate was inhibited simultaneously.


An Exploratory Study of Residents' Perception of Place Image: The Case of Kavala.
Studies on place image have predominantly focused on the tourists' destination image and have given limited attention to other stakeholders' perspectives. This study aims to address this gap by focusing on the notion of residents' place image, whereby it reviews existing literature on residents' place image in terms of whether common attributes can be identified, and examines the role of community-focused attributes in its measurement. Data collected from a sample of 481 Kavala residents (Greece) were subjected to exploratory and confirmatory factor analysis. The study reveals that the existing measurement tools have typically emphasized destination-focused attributes and neglected community-focused attributes. This study contributes to the residents' place image research by proposing a more holistic measurement, which consisted of four dimensions: physical appearance, community services, social environment, and entertainment opportunities. The study also offers practical insights for developing and promoting a tourist place while simultaneously enhancing its residents' quality of life.


Diversity and functionality of arbuscular mycorrhizal fungi in three plant communities in semiarid Grasslands National Park, Canada.
Septate endophytes proliferating in the roots of grasslands' plants shed doubts on the importance of arbuscular mycorrhizal (AM) symbioses in dry soils. The functionality and diversity of the AM symbioses formed in four replicates of three adjacent plant communities (agricultural, native, and restored) in Grasslands National Park, Canada were assessed in periods of moisture sufficiency and deficiency typical of early and late summer in the region. The community structure of AM fungi, as determined by polymerase chain reaction-denaturing gradient gel electrophoresis, varied with sampling time and plant community. Soil properties other than soil moisture did not change significantly with sampling time. The DNA sequences dominating AM extraradical networks in dry soil apparently belonged to rare taxa unreported in GenBank. DNA sequences of Glomus viscosum, Glomus mosseae, and Glomus hoi were dominant under conditions of moisture sufficiency. In total, nine different AM fungal sequences were found suggesting a role for the AM symbioses in semiarid areas. Significant positive linear relationships between plant P and N concentrations and active extraradical AM fungal biomass, estimated by the abundance of the phospholipid fatty acid marker 16:1 omega 5, existed under conditions of moisture sufficiency, but not under dry conditions. Active extraradical AM fungal biomass had significantly positive linear relationship with the abundance of two early season grasses, Agropyron cristatum (L.) Gaertn. and Koeleria gracilis Pers., but no relationship was found under dry conditions. The AM symbioses formed under conditions of moisture sufficiency typical of early summer at this location appear to be important for the nutrition of grassland plant communities, but no evidence of mutualism was found under the dry conditions of late summer.


Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma.
KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis. The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6. KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.


Mechanism behind augmentation in baroreflex sensitivity after acute exercise in spontaneously hypertensive rats.
A single bout of dynamic exercise increases baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). We examined whether change in hemodynamics (increases in blood pressure and heart rate) associated with dynamic exercise contribute to the post-exercise modulation of BRS. SHR aged 12 weeks were chronically instrumented with a carotid artery catheter and jugular vein catheter. They were then allocated to three groups submitted to 40 min of 1) running on a treadmill at 12 m/min (Run), 2) concomitant infusion of isoproterenol and a relatively high dose of phenylephrine (Iso+Phe(high)), or 3) concomitant infusion of isoproterenol and a relatively low dose of phenylephrine (Iso+Phe(low)). Arterial pressure and heart rate were continuously recorded throughout the experiments. BRS estimated by heart rate responses to phenylephrine injection and systolic blood pressure-low frequency power amplitude (SBP-LFamp) evaluated by power spectral analysis of SBP, a marker of sympathetic activity, were examined before and after running (Run group), or administration of drugs (Iso+Phe(high) or Iso+Phe(low) groups). BRS increased significantly from 1.4 to 1.9 bpm/mmHg after running, but not after administration of Iso+Phe(high) or Iso+Phe(low). Blood pressure and SBP-LFamp significantly decreased in each of the Run, Iso+Phe(high) and Iso+Phe(low) groups. These results suggest that hemodynamic change alone does not contribute to post-exercise modulation of BRS, while hemodynamic change or sympathetic activation during exercise contributes to post-exercise hypotension associated with a reduction of sympathetic activity.


Human papillomavirus type 56: a new virus detected in cervical cancers.
A new human papillomavirus type (HPV-56) was identified by low stringency Southern blot analysis with an HPV-31 DNA probe, in a cervical intraepithelial neoplasm (CIN). The DNA of this virus was molecularly cloned and shown to be a new HPV type based on the absence of cross-reactivity to HPV types 1 to 55 under high-stringency hybridization conditions. At low stringency, HPV-56 was most related to HPV types 30 and 45. The deduced organization of the open reading frames of HPV-56, from hybridization and partial nucleotide sequence analyses, reveals a typical HPV genome. HPV-56 was detected in two of 464 normal cervical tissues, in five of 227 cervical condylomas and CIN, and in two of 84 invasive cancers of the cervix.


Nitric oxide. I. Physiological chemistry of nitric oxide and its metabolites:implications in inflammation.
The role of nitric oxide (NO) in inflammation represents one of the most studied yet controversial subjects in physiology. A number of reports have demonstrated that NO possesses potent anti-inflammatory properties, whereas an equally impressive number of studies suggest that NO may promote inflammation-induced cell and tissue dysfunction. The reasons for these apparent paradoxical observations are not entirely clear; however, we propose that understanding the physiological chemistry of NO and its metabolites will provide a blueprint by which one may distinguish the regulatory/anti-inflammatory properties of NO from its deleterious/proinflammatory effects. The physiological chemistry of NO is complex and encompasses numerous potential reactions. In an attempt to simplify the understanding of this chemistry, the physiological aspects of NO chemistry may be categorized into direct and indirect effects. This type of classification allows for consideration of timing, location, and rate of production of NO and the relevant targets likely to be affected. Direct effects are those reactions in which NO interacts directly with a biological molecule or target and are thought to occur under normal physiological conditions when the rates of NO production are low. Generally, these types of reactions may serve regulatory and/or anti-inflammatory functions. Indirect effects, on the other hand, are those reactions mediated by NO-derived intermediates such as reactive nitrogen oxide species derived from the reaction of NO with oxygen or superoxide and are produced when fluxes of NO are enhanced. We postulate that these types of reactions may predominate during times of active inflammation. Consideration of the physiological chemistry of NO and its metabolites will hopefully allow one to identify which of the many NO-dependent reactions are important in modulating the inflammatory response and may help in the design of new therapeutic strategies for the treatment of inflammatory tissue injury.


Dielectric spectroscopy in benzophenone: the beta relaxation and its relation to the mode-coupling Cole-Cole peak.
We report a thorough characterization of the glassy dynamics of benzophenone by broadband dielectric spectroscopy. We detect a well-pronounced beta relaxation peak developing into an excess wing with increasing temperature. A previous analysis of results from Optical-Kerr-effect measurements of this material within the mode-coupling theory revealed a high-frequency Cole-Cole peak. We address the question if this phenomenon also may explain the Johari-Goldstein beta relaxation, a so-far unexplained spectral feature inherent to glass-forming matter, mainly observed in dielectric spectra. Our results demonstrate that according to the present status of theory, both spectral features seem not to be directly related.


Phosphonomethyl analogues of hexose phosphates.
The analogue of fructose 1,6-bisphosphate in which the phosphate group, -O-PO3H2, on C-6 is replaced by the phosphonomethyl group, -CH2-PO3H2, was made enzymically from the corresponding analogue of 3-phosphoglycerate. It was a substrate for aldolase, which was used to form it, but not for fructose 1,6-bisphosphatase. It was hydrolysed chemically to yield the corresponding analogue of fructose 6-phosphate [i.e. 6-deoxy-6-(phosphonomethyl)-D-fructose, or, more strictly, 6,7-dideoxy-7-phosphono-D-arabino-2-heptulose]. This proved to be a substrate for the sequential actions of glucose 6-phosphate isomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Thus seven out of the nine enzymes of the glycolytic and pentose phosphate pathways so far tested catalyse the reactions of the phosphonomethyl isosteres of their substrates.


Mass gathering events and undetected transmission of SARS-CoV-2 in vulnerable populations leading to an outbreak with high case fatality ratio in the district of Tirschenreuth, Germany.
In early March 2020, a COVID-19-outbreak occurred in the district of Tirschenreuth, Germany. The outbreak was characterised by a rapid increase in case numbers and a comparatively high crude case fatality ratio (CFR; 11%). Until the beginning of May 2020, 1122 cases were reported in the district. To investigate the outbreak, we analysed surveillance and other data available at the district health department, including data on cases living in care facilities and public health measures applied. Furthermore, we compared the number of tests performed in Tirschenreuth and in Germany as a whole. We interviewed the first 110 cases in order to investigate potential exposures at the beginning of the outbreak. We found that returning ski-travellers from Austria and Italy and early undetected community transmission likely initiated the outbreak which was then accelerated by Bavarian beer festivities. Testing of mainly acute cases in the district of Tirschenreuth resulted in a higher rate of positive tests compared to the whole of Germany. Despite adjustment for age, the CFR continued to exceed the German mean which was due to spread to vulnerable populations. Strict public health measures likely contributed to control the outbreak by mid-April 2020.


Urethral atrophy is now a rare cause for artificial urinary sphincter revision surgery in the contemporary 3.5 cm cuff era.
Urethral atrophy has long been suggested as the leading cause of artificial urinary sphincter (AUS) revision. Since the introduction of the 3.5 cm AUS cuff in 2010, precise cuff sizing primarily has been suggested to reduce revisions due to urethral atrophy. We evaluated a large contemporary series of reoperative AUS cases to determine reasons for revision surgery. We retrospectively reviewed our tertiary referral center database of male AUS procedures performed by a single surgeon from 2007-2019. AUS revision or replacement procedures were included for analysis. Cuff sizes and reasons for reoperation were recorded based on intraoperative findings and evaluated for temporal trends. Patients with cuff erosion or lacking follow-up were excluded. Among 714 AUS cases, 177 revisions or replacements were identified. Of these, 137 met inclusion criteria [mean age 71.7 years, median follow-up 52.7 months (IQR 22.3-94.6 months)]. Urethral atrophy was cited as the cause of AUS failure in 8.0% (11/137) of cases overall, virtually never among those with a 3.5 cm cuff placement (1/51, 2.0%). In those with ≥4.0 cm cuffs, urethral atrophy was the reason for revision in 10/86 (11.6%). Pressure regulating balloon (PRB) failure was the most frequently cited cause of failure (47/137, 34.3%). Cuff-related failure (23/137, 16.8%) and mechanical failure of unspecified device component (16/137, 11.8%) were the next most frequent causes of failure. Urethral atrophy has become a rare cause of AUS revision surgery since the availability of smaller cuffs. PRB-related failure is now the leading cause of AUS reoperation.


From linear care plan through concept map to Concepto-Plan: The creation of an innovative and holistic care plan.
Linear care plans have traditionally been used in nursing education to support nursing students in identifying potential and actual health care problems, and to follow up on those issues with nursing interventions. However, the linear care plan does not support the nursing student with learning in-depth critical thinking, clinical reasoning, creative thinking, and other ways of thinking. Concept mapping was introduced as a way to support the nursing student to improve upon critical thinking and clinical reasoning and to identify relationships among the patient's health care problems. The present manuscript features the development and evaluation of the Concepto-Plan (C-P), an innovative, holistic care plan that moves away from the linear care plan and improves upon the concept map care plan. The C-P focuses on the relationships among the data clusters and the nursing diagnoses and can be used to enhance the therapeutic relationship between the patient and the nursing student. Quality improvement data supports the effectiveness of the C-P for nursing students to organize and prioritize client-centred care while experiencing meaningful learning, professional self-reflection, clinical reasoning, creative and critical thinking skills and the ability to provide an individualized holistic care plan. As a result, the C-P has been integrated into the curriculum in two different nursing programs in two Canadian provinces.


Serum IL-1, IL-2, TNFalpha and INFgamma levels of patients with type 1 diabetes mellitus and their siblings.
Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p < 0.05) and the siblings (S) (p < 0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p < 0.05), PD (p < 0.001), S (p < 0.05), and control (C) (p < 0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p< 0.005) and C (p < 0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p < 0.005) and C (p < 0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p < 0.01 for both) and C (p < 0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p < 0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p < 0.05) INFgamma (r = 0.796, p < 0.001) and IL-2 (r = 0.862, p < 0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p < 0.05) and INFgamma (r = 0.754, p < 0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL-1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus.


Mortality and cancer risk among workers exposed to man-made mineral fibers in Finland.
A cohort of 941 workers in the glass-wool producing industry in Finland was followed for deaths in 1953-1981, the mean duration of follow-up being 12.1 years. The overall mortality and mortality from individual causes of death did not differ significantly from those expected. Similarly, the cohort was followed for cancer incidence through the Finnish Cancer Registry. No excess cancer risks were observed. There were four cases of lung cancer versus 6.6 expected.


Percutaneous transnasal sphenoidotomy with sphenoid window.
Ten percutaneous transnasal sphenoidotomies were performed in nine children; and in seven, a sphenoid window was also created. All procedures were performed in the special procedures laboratory, with biplane fluoroscopic guidance used in each case. Under general anesthesia, with the child in the supine position, a 14-gauge antral trocar was placed transnasally into the sphenoid sinus. The sinus was aspirated and material was obtained for culture. A Takahashi forceps was placed via the same tract into the sphenoid sinus. The cusps were centered across the anterior cortex, and under fluoroscopic visualization, opened and rotated 360 degrees, creating a sphenoid window. All procedures were completed without complication, and no child required further surgery.


IrML - a gene encoding a new member of the ML protein family from the hard tick, Ixodes ricinus.
Blood intake causes significant changes in ticks, triggering vital physiological processes including differential gene expression. A gene encoding Ixodes ricinus ML-domain containing protein (IrML) is one of the set of the genes that are strongly induced by blood meals. IrML belongs to the ML protein family that commonly occurs in diverse organisms and is involved in lipid binding and transport, pathogen recognition or in immune response. An IrML gene was amplified from cDNA of engorged I. ricinus females using the gene-specific primers designed on a basis of partial sequences of related genes for ML domain protein. IrML was shown to be expressed mainly in the gut, but also in salivary glands and hemolymph of all tick developmental stages. Using in situ hybridization, IrML transcripts were detected in type II and III salivary glands acini. Analysis of the predicted structure of I. ricinus ML-domain containing protein and its localization in the tick body could suggest that IrML is a secreted protein and is possibly involved in tick innate immunity.


Lateral hypothalamic modulation of oral sensory afferent activity in nucleus tractus solitarius neurons of rats.
This study was designed to examine whether the sensory afferents from the anterior part of the tongue are modulated by activity of the lateral hypothalamic area (LHA) at the level of the nucleus tractus solitarius (NTS) in rats. The electrical activity of the NTS neurons was recorded extracellularly, and they were classified as gustatory, thermal, or mechanical neurons in accordance with their responsiveness to tongue stimulation by taste solutions, by warm and cool water, and by stroking the tongue surface. Sixty-two percent of the neurons were polysynaptically activated by electrical stimulation of the LHA. When a single conditioning stimulus of the LHA was applied prior to the test electrical stimulation of the tongue at various conditioning-test intervals, the activity of the gustatory neurons was facilitated by 30 to 80% of their control level for a period of approximately 20 to 150 msec. The activity of the mechanical and thermal neurons was suppressed for a 50- to 300-msec period. These results demonstrate the existence of modulatory effects from the LHA on the NTS neurons, which receive sensory information from the tongue.


Chemical characterization methods for the analysis of structural extracellular polymeric substances (EPS).
Biofilm structure and functionality depend on extracellular polymeric substances (EPS), but analytical methods for EPS often lack specificity which limits progress of biofilm research. EPS were extracted from aerobic granular sludge and analyzed with frequently applied colorimetric methods. The colorimetric methods were evaluated based on their applicability for EPS analysis. EPS fractions of interest were proteins, sugars, uronic acids and phenolic compounds. The applied methods (Lowry method, bicinchoninic acid assay, phenol sulfuric acid method, carbazole sulfuric acid method) were investigated in terms of their sensitivity towards the selected standard compound. Interference of compounds present in EPS with the colorimetric methods was further evaluated. All methods showed to be highly depending on the choice of standard compound and susceptible towards interference by compounds present in EPS. This study shows that currently used colorimetric methods are not capable of accurately characterizing EPS. More advanced methods are needed to be able to draw conclusions about biofilm composition, structure and functionality.


Thromboelastography in healthy, sick non-septic and septic neonatal foals.
To evaluate citrated recalcified thromboelastography (TEG) in healthy newborn foals, and to determine intra-assay, inter-individual and intra-individual (at 12 h, 24 h and 7 days after birth) variations. Additionally, to compare TEG variables, haematological values and conventional coagulation profiles from healthy, sick non-septic, and septic foals. Prospective study. The study group comprised 18 healthy, 15 sick non-septic and 17 septic foals. Two citrated (3.2%; 1 : 9 anticoagulant : blood ratio) blood samples were submitted for haemostatic evaluation using a TEG analyser and conventional coagulation profile. TEG values (R time (R), K time (K), angle (α), maximum amplitude (MA) and G value (G)), complete blood count (CBC) and conventional coagulation profile (prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration (Fib) and antithrombin (AT)) were evaluated. Signalment, presenting complaint, sepsis scores, blood culture results and outcome were taken from the medical records of the sick foals. Mean values ± SD for TEG variables in healthy neonatal foals were: R = 11.82 ± 5.35 min, K = 3.06 ± 1.34 min, α= 51.19 ± 12.66 degrees, MA = 55.06 ± 6.67 mm and G = 6361 ± 1700 dyn/cm(2) . Mean coefficients of variation for intra-assay/inter-individual/intra-individual in healthy foals were: R = 3.5/45.2/43.1%; K = 5.3/58.7/28.7%; α= 1.5/24.7/11.9%; MA = 0.3/12.1/6.1%; G = 1.6/26.7/14.7%. Septic foals had significantly greater α, MA and G values than sick non-septic foals, and significantly greater MA and G than healthy foals, changes that are consistent with hypercoagulability. Weak correlations were detected between TEG variables and haematological or haemostatic values. TEG could be used to provide additional information about the haemostatic system in equine neonates.


Basic FGF regulates interstitial collagenase gene expression in human smooth muscle cells.
Basic fibroblast growth factor (bFGF) is a mitogenic factor that is implicated in smooth muscle cell growth in atherosclerosis and vascular restenosis. In this study, we examined the effect of bFGF on the expression of the interstitial collagenase gene in human vascular smooth muscle cells. Results from Northern transfer analysis showed that bFGF increased collagenase mRNA levels greater than threefold as early as 24 h. Collagenase pre-mRNA levels were elevated approximately threefold by bFGF, according to RT-PCR analysis. Transient transfections of the smooth muscle cells with a 4.4-kb human collagenase promoter-CAT reporter gene, however, failed to show upregulation of the promoter activity by bFGF. Interestingly, transfections with deleted fragments containing promoter sequences from -1047 to -2271 resulted in modest stimulation of the collagenase-CAT promoter activity by bFGF, bFGF did not alter the stability of the collagenase mRNA, as demonstrated by degradation studies. The enhanced collagenase mRNA levels elicited by bFGF were reflected in increased amounts of collagenase protein that were detected by Western blot analysis. In summary, bFGF upregulates the interstitial collagenase expression, resulting in turnover of the extracellular matrix, an event that could facilitate smooth muscle cell migration and proliferation during the early stages of atherosclerosis and restenosis.


Incidence of Vibrio parahaemolyticus bacteriophages and other Vibrio bacteriophages in marine samples.
Vibrio bacteriophages were isolated by enrichment from 177 of 643 samples of marine molluscan shellfish, crustaceans, seawater, and sediments. The predominant bacteriophage types isolated were specific for some strains of Vibrio parahaemolyticus. A high frequency of phage isolations was also observed with strains of agar-digesting vibrios (21 of 56) and psychrophilic vibrios (14 of 72) that were originally isolated from non-shellfish growing areas. No bacteriophages were isolated against V. alginolyticus and only rarely for V. anguillarum even though these were the two most abundant species found in near-shore environments. No V. cholerae phages were isolated. It was also determined from quantitative studies on the Pacific oyster (Crassostrea gigas) obtained from two environments in Washington and Oregon that the titers of V. parahaemolyticus bacteriophages increased with increasing seasonal water temperatures and that this was proportional to the increase in numbers of mesophilic vibrios and not with the incidence of V. parahaemolyticus. Titers of V. parahaemolyticus bacteriophages occasionally exceeded 10(6) per g of oyster during the summer months. Specific V. parahaemolyticus bacteriophages were also isolated from market seafoods and other marine samples that originated in cold environments where no mesophilic vibrios are expected to be found. The possibility that V. parahaemolyticus bacteriophages originate from Vibrio spp. other than V. parahaemolyticus and the role of these bacteriophages in the ecology of marine vibrios are discussed.


Synergistic selection between ecological niche and mate preference primes diversification.
The ecological niche and mate preferences have independently been shown to be important for the process of speciation. Here, we articulate a novel mechanism by which ecological niche use and mate preference can be linked to promote speciation. The degree to which individual niches are narrow and clustered affects the strength of divergent natural selection and population splitting. Similarly, the degree to which individual mate preferences are narrow and clustered affects the strength of divergent sexual selection and assortative mating between diverging forms. This novel perspective is inspired by the literature on ecological niches; it also explores mate preferences and how they may contribute to speciation. Unlike much comparative work, we do not search for evolutionary patterns using proxies for adaptation and sexual selection, but rather we elucidate how ideas from niche theory relate to mate preference, and how this relationship can foster speciation. Recognizing that individual and population niches are conceptually and ecologically linked to individual and population mate preference functions will significantly increase our understanding of rapid evolutionary diversification in nature. It has potential to help solve the difficult challenge of testing the role of sexual selection in the speciation process. We also identify ecological factors that are likely to affect individual niche and individual mate preference in synergistic ways and as a consequence to promote speciation. The ecological niche an individual occupies can directly affect its mate preference. Clusters of individuals with narrow, differentiated niches are likely to have narrow, differentiated mate preference functions. Our approach integrates ecological and sexual selection research to further our understanding of diversification processes. Such integration may be necessary for progress because these processes seem inextricably linked in the natural world.


[Pathogenetic justification of organ-preserving operations and their role in improving the effectiveness of the comprehensive treatment of renal tuberculosis].
Some experimental data concerning the pathogenesis of tuberculous injury to the kidneys have been obtained from a complex study of the microcirculatory blood bed on a model of tuberculosis of the kidneys in 112 rabbits. Clinical investigations and clinico-experimental correlations have provided pathogenetic grounds for a surgical method of the treatment of tuberculosis of the kidneys complicated with strictures or the ureter. The pathogenetic association of the main tuberculous focus in the renal parenchyma with the tuberculous injury to the ureter and perivascular expansion of specific infection has been pointed to. The effectiveness of pathogenetically grounded surgical intervention has been proved in 52 patients followed-up from 1.5 to 7 years.


Absence of the peroneus tertius muscle: cadaveric study with clinical considerations.
Peroneus tertius (PT) is a muscle of the anterior compartment of the leg. The PT muscle originates from the anterior surface of the fibula and the interosseous membrane and inserts into the medial side of the dorsal region of the fifth metatarsal bone. During routine dissection, we observed the absence of PT on the left lower limb of a cadaver. Usually, the PT is involved in dorsiflexion and eversion of the foot. In many cases, the absence of PT maybe asymptomatic and it may be incidentally detected during cadaveric dissections or autopsies. The existence of PT may help in the swing phase of bipedal walking. The PT may be used for tendon graft surgeries. The pull of the PT may be responsible for causing stress on the fifth metacarpal and account for all stress fractures in any individual. The absence of the PT may puzzle any transplant and foot surgeons performing graft operations. We as anatomists discuss the clinical implications of the absence of PT.


Expanding anchored hybrid enrichment to resolve both deep and shallow relationships within the spider tree of life.
Despite considerable effort, progress in spider molecular systematics has lagged behind many other comparable arthropod groups, thereby hindering family-level resolution, classification, and testing of important macroevolutionary hypotheses. Recently, alternative targeted sequence capture techniques have provided molecular systematics a powerful tool for resolving relationships across the Tree of Life. One of these approaches, Anchored Hybrid Enrichment (AHE), is designed to recover hundreds of unique orthologous loci from across the genome, for resolving both shallow and deep-scale evolutionary relationships within non-model systems. Herein we present a modification of the AHE approach that expands its use for application in spiders, with a particular emphasis on the infraorder Mygalomorphae. Our aim was to design a set of probes that effectively capture loci informative at a diversity of phylogenetic timescales. Following identification of putative arthropod-wide loci, we utilized homologous transcriptome sequences from 17 species across all spiders to identify exon boundaries. Conserved regions with variable flanking regions were then sought across the tick genome, three published araneomorph spider genomes, and raw genomic reads of two mygalomorph taxa. Following development of the 585 target loci in the Spider Probe Kit, we applied AHE across three taxonomic depths to evaluate performance: deep-level spider family relationships (33 taxa, 327 loci); family and generic relationships within the mygalomorph family Euctenizidae (25 taxa, 403 loci); and species relationships in the North American tarantula genus Aphonopelma (83 taxa, 581 loci). At the deepest level, all three major spider lineages (the Mesothelae, Mygalomorphae, and Araneomorphae) were supported with high bootstrap support. Strong support was also found throughout the Euctenizidae, including generic relationships within the family and species relationships within the genus Aptostichus. As in the Euctenizidae, virtually identical topologies were inferred with high support throughout Aphonopelma. The Spider Probe Kit, the first implementation of AHE methodology in Class Arachnida, holds great promise for gathering the types and quantities of molecular data needed to accelerate an understanding of the spider Tree of Life by providing a mechanism whereby different researchers can confidently and effectively use the same loci for independent projects, yet allowing synthesis of data across independent research groups.


Treatment of allergic rhinitis: effects of allergic rhinitis and antihistamines on performance.
Antihistamines are the most commonly used drugs for allergic rhinitis, and many antihistamines may cause subclinical side effects which are not noticeable by the patient. These include impaired driving performance, impaired work performance, reduced coordination, reduced motor skills, sleepiness and impaired information processing (arithmetic, verbal, and office skills). The newer nonsedating antihistamines should be used for the treatment of allergic rhinitis because they do not produce these effects. Recent studies have shown that children's learning in school may also be negatively affected by traditional antihistamines, and therefore, school children should definitely be given the nonsedating antihistamines. Not only does the treatment cause some impaired performance, but allergic rhinitis itself may result in changes in the patient's mood affect, and other aspects of personality. Physicians who treat allergic rhinitis should be aware of the potential performance effects of medications that they prescribe and the potential effects of the disease itself on the patient's personality.


Upper extremity salvage with a flow-through free flap.
In complex extremity injuries, which include composite tissue lost with devascularization caused by segmental vascular damage, simultaneous coverage of the defects with revascularizations should be required. One-stage reconstruction of both soft tissue coverage and vascular damage can be performed by a flow-through-type free flap. In this series, 5 patients between 13 and 36 years of age with wide composite tissue defects in the cubital region and segmental defects in brachial arteries were operated at our clinic between 1996 and 2003. With the aim of reconstructing the wide tissue defects in the cubital region as well as that of the brachial artery, a radial arterial flow-through flap was applied. The radial artery of the flow-through flap was anastomosed to the proximal ends of the brachial and ulnar arteries in an end-to-end fashion. In 4 of the patients, the radial arterial flow-through flap was prepared from the distal aspect of the wounded forearm and in 1 patient from the contralateral forearm. In the postoperative period, no complications related to the anastomosis were encountered in the flap with all anastomoses found to be patent, and distal circulation was restored. The radial arterial flow-through flap is very useful in the clinical field of major trauma of the cubital region with brachial artery damage with numerous advantages that include the opportunity to work in one single surgical area, shorter dissection times resulting from simple and fixed anatomy, perfect color and tissue adaptation, and the suitability of the vessel caliber and length.