HIV knowledge and its contribution to sexual health behaviors of low-income African American adolescents.
Although many factors contribute to racial disparities in human immunodeficiency virus (HIV)/AIDS among young African Americans, knowledge is a particularly modifiable factor. However, little information has been published about the current HIV knowledge of African American teens or to what extent knowledge independently contributes to their sexual behavior and health. This study aimed to describe the level of knowledge among this at-risk population and determine whether knowledge contributes to variance in sexual behavior and health beyond that of sociodemographic and psychological factors. African American adolescents (n = 1658) were recruited in 2 northeastern and 2 southeastern US cities (74% eligible for free or reduced-price school lunch). Analyses utilized data gathered from adolescents using an audio computer-assisted self-interview program. On average, participants answered only 50% of HIV knowledge items correctly and were least accurate concerning effective condom use and HIV testing. Controlling tor associated sociodemographic and psychological factors, greater knowledge was associated with sexual experience and, among experienced adolescents, with sexually transmitted infection/HIV testing and--unexpectedly--less condom use. HIV knowledge, which is modifiable, is limited among at-risk African American adolescents and is an important contributor to sexual behavior and health. Findings indicate a need for more comprehensive HIV/AIDS education, particularly with regard to condom use and the benefits of routine sexually transmitted infection/HIV testing. Although knowledge might not be sufficiently protective in and of itself, having accurate information about HIV may benefit sexual health by impacting health-promoting attitudes necessary for successful engagement in health care-seeking behavior.


Can Reduction of NO to N2O in Cytochrome c Dependent Nitric Oxide Reductase Proceed through a Trans-Mechanism?
As part of microbial denitrification, NO is reduced to N2O in the membrane bound enzyme nitric oxide reductase, NOR. The N-N coupling occurs in the diiron binuclear active site, BNC, and different mechanisms for this reaction step have been suggested. Computational studies have supported a so-called cis:b3-mechanism, in which the hyponitrite product of the reductive N-N bond formation coordinates with one nitrogen to the heme iron and with both oxygens to the non-heme iron in the BNC. In contrast, experimental results have been interpreted to support a so-called trans-mechanism, in which the hyponitrite intermediate coordinates with one nitrogen atom to each of the two iron ions. Hybrid density functional theory is used here to perform an extensive search for possible intermediates of the NO reduction in the cNOR enzyme. It is found that hyponitrite structures coordinating with their negatively charged oxygens to the positively charged iron ions are the most stable ones. The hyponitrite intermediate involved in the suggested trans-mechanism, which only coordinates with the nitrogens to the iron ions, is found to be prohibitively high in energy, leading to a too slow reaction, which should rule out this mechanism. Furthermore, intermediates binding one NO molecule to each iron ion in the BNC, which have been suggested to initiate the trans-mechanism, are found to be too high in energy to be observable, indicating that the experimentally observed electron paramagnetic resonance signals, taken to support such an iron-nitrosyl dimer intermediate, should be reinterpreted.


Adenosine and glutamate signaling in neuron-glial interactions: implications in alcoholism and sleep disorders.
Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. Especially, astrocytes are essential for neuronal activity in the brain. Astrocytes actively participate in synapse formation and brain information processing by releasing or uptaking gliotransmitters such as glutamate, d-serine, adenosine 5'-triphosphate (ATP), and adenosine. In the central nervous system, adenosine plays an important role in regulating neuronal activity as well as in controlling other neurotransmitter systems such as GABA, glutamate, and dopamine. Ethanol (EtOH) increases extracellular adenosine levels, which regulates the ataxic and hypnotic/sedative (somnogenic) effects of EtOH. Adenosine signaling is also involved in the homeostasis of major inhibitory/excitatory neurotransmission (i.e., GABA or glutamate) through neuron-glial interactions, which regulates the effect of EtOH and sleep. Adenosine transporters or astrocytic SNARE-mediated transmitter release regulates extracellular or synaptic adenosine levels. Adenosine then exerts its function through several adenosine receptors and regulates glutamate levels in the brain. This review presents novel findings on how neuron-glial interactions, particularly adenosinergic signaling and glutamate uptake activity involving glutamate transporter 1 (GLT1), are implicated in alcoholism and sleep disorders.


Temporal changes of under-reporting of cigarette consumption in population-based studies.
To monitor trends in under-reporting of smoking in Italy over the last two decades. A total of 9 representative population-based surveys on smoking conducted in Italy in 1990 and annually between 2001 and 2008, covering 26,397 individuals, were studied. The number of cigarettes per day per person aged 15 years or over, obtained from these interview-based surveys, was compared with official data from legal sales. Over the last two decades, self-reported smoking prevalence progressively decreased from 32% in 1990 to 22% in 2008. Self-reported daily per capita consumption of cigarettes also showed a reduction between 1990 and 2008, notably so over the last few years (from 5.2 in 1990 to 4.0 in 2004 to 3.2 in 2008). According to data from legal sales, number of cigarettes per day per person decreased from 5.3 in 1990 to 5.0 in 1992, levelled off from 1992 to 1997, subsequently increased from 5.0 in 1997 to 5.8 in 2002 (likely due to control of smuggling), and decreased over the last 6 years (to 4.9 in 2008). These figures correspond to an under-reporting of approximately 1% in 1990, 25% in 2001 and up to 35% in 2008. The difference in cigarette consumption between legal sale and self-reported data has substantially increased over the last two decades in Italy, reflecting increasing under-reporting of cigarette consumption mainly due to a decreasing social acceptability of smoking. Comparisons between interview-based and legal sale data are complicated by factors such as smuggling control and changes in the population (eg, increased proportion of immigrants); however these are able to justify only a small proportion of the gap found in Italy.


Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity.
Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens. By comparing the results of these two assays across various stimuli, we found that genetic screens tend to identify response regulators, whereas mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We used this approach to reveal cellular pathways responding to the toxicity of alpha-synuclein, a protein implicated in several neurodegenerative disorders including Parkinson's disease. For this we screened an established yeast model to identify genes that when overexpressed alter alpha-synuclein toxicity. Bridging these data and data from mRNA profiling provided functional explanations for many of these genes and identified previously unknown relations between alpha-synuclein toxicity and basic cellular pathways.


Molecular characterization of Legionella populations present within slow sand filters used for fungal plant pathogen suppression in horticultural crops.
The total bacterial community of an experimental slow sand filter (SSF) was analyzed by denaturing gradient gel electrophoresis (DGGE) of partial 16S rRNA gene PCR products. One dominant band had sequence homology to Legionella species, indicating that these bacteria were a large component of the SSF bacterial community. Populations within experimental and commercial SSF units were studied by using Legionella-specific PCR primers, and products were studied by DGGE and quantitative PCR analyses. In the experimental SSF unit, the DGGE profiles for sand column, reservoir, storage tank, and headwater tank samples each contained at least one intense band, indicating that a single Legionella strain was predominant in each sample. Greater numbers of DGGE bands of equal intensity were detected in the outflow water sample. Sequence analysis of these PCR products showed that several Legionella species were present and that the organisms exhibited similarity to strains isolated from environmental and clinical samples. Quantitative PCR analysis of the SSF samples showed that from the headwater sample through the sand column, the number of Legionella cells decreased, resulting in a lower number of cells in the outflow water. In the commercial SSF, legionellae were also detected in the sand column samples. Storing prefilter water or locating SSF units within greenhouses, which are often maintained at temperatures that are higher than the ambient temperature, increases the risk of growth of Legionella and should be avoided. Care should also be taken when used filter sand is handled or replaced, and regular monitoring of outflow water would be useful, especially if the water is used for misting or overhead irrigation.


Effect of various process parameters on morphology, rheology, and polygalacturonase production by Aspergillus sojae in a batch bioreactor.
The effects of pH, agitation speed, and dissolved oxygen tension (DOT), significant in common fungal fermentations, on the production of polygalacturonase (PG) enzyme and their relation to morphology and broth rheology were investigated using Aspergillus sojae in a batch bioreactor. All three factors were effective on the response parameters under study. An uncontrolled pH increased biomass and PG activity by 27% and 38%, respectively, compared to controlled pH (pH 6) with an average pellet size of 1.69 +/- 0.48 mm. pH did not significantly affect the broth rheology but created an impact on the pellet morphology. Similarly, at constant agitation speed the maximum biomass obtained at 500 rpm and at 30 h was 3.27 and 3.67 times more than at 200 and 350 rpm, respectively, with an average pellet size of 1.08 +/- 0.42 mm. The maximum enzyme productivity of 0.149 U mL-1 h-1 was obtained at 200 rpm with an average pellet size of 0.71 +/- 0.35 mm. Non-Newtonian and pseudoplastic broth rheology was observed at 500 rpm agitation speed, broth rheology exhibited dilatant behavior at the lower agitation rate (200 rpm), and at the medium agitation speed (350 rpm) the broth was close to Newtonian. Furthermore, a DOT range of 30-50% was essential for maximum biomass formation, whereas only 10% DOT was required for maximum PG synthesis. Non-Newtonian shear thickening behavior (n > 1.0) was depicted at DOT levels of 10% and 30%, whereas non-Newtonian shear thinning behavior (n < 1.0) was dominant at 50% DOT. The overall fermentation duration (50-70 h) was considerably shorter compared to common fungal fermentations, revealing the economic feasibility of this particular process. As a result this study not only introduced a new strain with a potential of producing a highly commercially significant enzyme but also provided certain parameters significant in the design and mathematical modeling of fungal bioprocesses.


Identifying the Hidden Population: Former Intravenous Drug Users Who Are No Longer in Contact with Services. "Ask a Friend".
People who, after a period of drug use, have changed their lifestyle and left substance use behind them are a hidden population within our communities. Lack of contact with drug services may mean that they are not tested for hepatitis C (HCV) infection through service-led initiatives and, therefore, may be exposed to the chronic morbidity and risk of death inherent with a legacy of HCV infection. This study utilized respondent-driven sampling (RDS) in a novel fashion to find those at historical risk of HCV. The social networks of people with a history of drug use were mapped, and individuals not currently in contact with services were invited to come forward for testing by members of their social network. The study used a reference group to inform study methodology and communication methods to reach out to this hidden population. One hundred and nine individuals received dry blood spot tests for HCV, 17.4% were antibody positive. Fifty one individuals met the inclusion criteria for this study. One hundred and twenty three invite-to-test coupons were issued; however, only one wave of recruitment consisting of one participant resulted from this method. Using RDS in historical social networks was not effective in this study and did not reach this hidden population and increase testing for HCV. This study is registered with clinicaltrials.gov (Ref NCT03697135).


Sacral region massage as an alternative to the urinary catheter used to prevent urinary retention after cesarean delivery.
The aim of the study was to determine the effect of massage to the sacral region after cesarean delivery instead of employing a urinary catheter for the prevention of urinary retention. Cross sectional study. This interventional study population consisted of 60 women who were divided into two intervention groups and one control group. For the first intervention group, the sacral region was massaged every hour 10-15 minutes after cesarean delivery and every 30 minutes after a voiding sensation for the second intervention group. No interventions were made in the control group, although routine hospital services were provided. Socio-demographic data were collected using a questionnaire developed by the researchers. Other data were collected via observation. Fifteen percent (15%) of the women in the first intervention group needed to void 2 hours after cesarean delivery, 35% after 3 hours, and the mean time to void after delivery was 3.4±0.8 hours. Forty percent (40%) of the women in the second intervention group needed to void after 5 hours, and the mean time to void after delivery was 5.5±0.8 hours. Sixty percent (60%) of the women in the control group needed to void 6 hours later, and the mean time to void after delivery was 6.2±0.7 hours. Urinary retention was not observed in the first intervention group. Our statistical analysis showed a significant difference between the three groups in terms of mean times to void after cesarean delivery (p<0.05). In order to facilitate voiding and to prevent urinary retention, which is seen as a post-cesarean complication, massaging the sacral region could be recommended instead of urinary catheter insertion. Additional studies with larger groups are also recommended.


Anemia of inflammation: the cytokine-hepcidin link.
The anemia of inflammation, commonly observed in patients with chronic infections, malignancy, trauma, and inflammatory disorders, is a well-known clinical entity. Until recently, we understood little about its pathogenesis. It now appears that the inflammatory cytokine IL-6 induces production of hepcidin, an iron-regulatory hormone that may be responsible for most or all of the features of this disorder.


Contribution behavior of 401(k) plan participants.
This Issue Brief examines the 1999 contribution behavior of 1.7 million 401(k) plan participants drawn from the EBRI/ICI Participant-Directed Retirement Plan Data Collection Project. The findings in this paper build on previous academic research examining the contribution activity of 401(k) participants, by using a large sample of participants in a wide range of plan sizes and by examining in detail the factors that influence contribution activity. Eighty-five percent of participants in the sample only made before-tax contributions to their plans, and 97 percent of all dollars contributed by employees were contributed on a before-tax basis. On average, participants contributed 6.8 percent of their salaries on a before-tax basis. Before-tax contribution activity varied among participants. About 61 percent of participants contributed more than 5 percent of their salaries on a before-tax basis and about 21 percent set aside more than 10 percent of their salaries on a before-tax basis. Eleven percent of participants analyzed in this study earning more than $40,000 a year contributed at the $10,000 before-tax IRC limit in 1999. Thirteen percent of participants with salaries between $70,000 and $80,000 contributed at the cap, and 18 percent of those with salaries between $80,000 and $90,000 were at the limit. However, it appears that among participants not contributing at the IRC limit, 52 percent could not have done so because of formal plan-imposed contribution limits below the IRC limit. Older participants tended to contribute a higher percentage of their salaries to plans than did younger participants, even after factoring out differences in salary and job tenure. Participants tended to increase the share of their salary (and amounts) contributed to their 401(k) plan as their salaries rose until salaries reached $80,000. For individuals with salaries above $80,000, before-tax contribution rates (though not the amounts contributed) tended to fall as salaries rose because IRC, and possibly plan sponsor, contribution limits became binding for some participants. Giving employees the option of borrowing from their 401(k) accounts increased participant contribution rates. On average, a participant in a plan offering loans appeared to contribute 0.6 percentage point more of his or her salary to the plan than a participant in a plan with no loan provision. Total contributions--the sum of employee and employer contributions--were higher for participants who received an employer contribution as part of their 401(k) plan than for those who did not. The average total contribution rate was 10 percent of salary for employees in plans offering an employer contribution, compared with 7.4 percent for those in plans not offering an employer contribution.


Gene Expression Analysis of Immunomagnetically Enriched Circulating Tumor Cell Fraction in Castration-Resistant Prostate Cancer.
Molecular characterization of tumors could be a key to therapeutic decision-making with regards to targeted therapies in castration-resistant prostate cancer (CRPC). A convenient solution may be non-invasive liquid biopsy testing of circulating tumor cells (CTCs). For this reason, CTC-enriched samples obtained by immunomagnetic separation (AdnaTest®) were studied as a source material for high-throughput gene expression analysis using BioMark™. CTC-enriched samples from 41 CRPC patients previously determined to be CTC positive using the AdnaTest® were retrospectively re-analysed for androgen receptor (AR) messenger RNA (mRNA), using the updated AdnaTest®. Blood samples were drawn two times from each patient: at the time of CRPC diagnosis and after the third docetaxel cycle. A gene expression panel of 27 genes related to CRPC therapeutic decision-making, including AR full length (ARFL) and splice variant 7 (ARV7), was retrospectively analyzed on a BioMark™ platform in 29 of 41 patients. The AdnaTest® detected AR mRNA in three-quarters of CTC-positive samples taken at the time of CRPC diagnosis and after the third docetaxel cycle. AR detection was associated with a shorter disease-specific survival (45.0 vs. 20.4 months) at the time of CRPC diagnosis. ARFL expression at the time of CRPC diagnosis, measured on the BioMark™ platform, was associated with a lower decrease of serum level of prostate-specific antigen (sPSA) (p = 0.029), i.e., worse therapy response. ARV7 was found in 38% of the ARFL--positive samples at both analyzed timepoints. Detection of AR expression by AdnaTest® in CTC-enriched samples may help predict patients' survival. These AdnaTest® CTC-enriched samples can be used in a high-throughput quantitative polymerase chain reaction (qPCR) analysis of gene expression, provided that the specificity of the assay for each individual gene is properly validated. The BioMark™ platform can be used for the simultaneous detection of ARFL and ARV7 and other genes in CTC-enriched samples from CRPC patients.


The effects of reduced copayments on discontinuation and adherence failure to statin medication in Australia.
This paper assesses whether the concession card, which offers discounted out-of-pocket costs for prescription medicines in Australia, affects discontinuation and adherence to statin therapy. The analysis uses data from the Australian Hypertension and Absolute Risk Study (AusHEART), which involves patients aged 55 years and over who visited a GP between April and June 2008. Socioeconomic and clinical information was collected and linked to administrative data on pharmaceutical use. Patients without a concession card were 63% more likely (hazard ratio (HR) 95% confidence interval (CI): 1.14-2.33) to discontinue and 60% (odds ratio (OR) CI: 1.04-2.44) more likely to fail to adhere to therapy compared to concessional patients. Smokers were 2.12 (HR CI: 1.39-3.22) times more likely to discontinue use and 2.23 (OR CI: 1.35-3.71) times more likely to fail to adhere compared to non-smokers. Patients who had recently initiated statin medication were also 2.28 (HR CI: 1.22-4.28) times more likely to discontinue use. In conclusion, higher copayments act as a disincentive for persistent and adherent use of statin medication.


Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: First qualitative data.
This work assessed sexual and neurobehavioral parameters after ovarian treatment with autologous PRP. Questionnaire study. Patients receiving ovarian PRP injection (n=80) due to low ovarian reserve and/or at least 1 prior failed IVF cycle were sampled. Pre- and post-treatment levels in self-reported daily energy, sleep quality, skin tone/hair thickness/nail growth, cognitive clarity, menstrual pattern, cervical mucus/vaginal lubrication, libido, sexual activity, ability to achieve orgasm, and overall sexual experience were measured. Mean±SD age and baseline BMI among patients were 45.5±6yrs and 25±5.1kg/m2, respectively. Average weight loss after ovarian PRP was 1kg (p=0.056). After ovarian PRP, superior nail growth, skin tone, and hair thickness was observed by 46.3% of patients [95%CI=35%,57.8%]; the same ratio experienced increased "clarity of thinking" following the procedure. Irregular or absent menses affected 56.3% of patients at enrollment, and menses returned or cyclicity improved in 24.4% after treatment [95%CI=12.9%,39.5%]. Increased post-treatment vaginal lubrication/cervical mucus production was reported by 51.3% of women [95%CI=39.8%, 62.6%] accompanied by increased libido in 55% [95%CI=43.5%,66.2%]. More frequent sexual activity after ovarian PRP was noted from 46.3% of subjects [95%CI=35%, 57.8%] coinciding with a 45% improvement in overall sexual experience before vs. after ovarian PRP [95%CI=33.9%, 56.5%]. This investigation is the first to document responses across neurobehavioral and metabolic parameters after ovarian PRP. Injection of PRP-derived growth factors directly into ovarian tissue seems to enable a local signaling milieu favoring development of hormonally active ovarian elements, thus "re-potentiating" low or absent reserve.


Enhancing the functional properties of thermophilic enzymes by chemical modification and immobilization.
The immobilization of proteins (mostly typically enzymes) onto solid supports is mature technology and has been used successfully to enhance biocatalytic processes in a wide range of industrial applications. However, continued developments in immobilization technology have led to more sophisticated and specialized applications of the process. A combination of targeted chemistries, for both the support and the protein, sometimes in combination with additional chemical and/or genetic engineering, has led to the development of methods for the modification of protein functional properties, for enhancing protein stability and for the recovery of specific proteins from complex mixtures. In particular, the development of effective methods for immobilizing large multi-subunit proteins with multiple covalent linkages (multi-point immobilization) has been effective in stabilizing proteins where subunit dissociation is the initial step in enzyme inactivation. In some instances, multiple benefits are achievable in a single process. Here we comprehensively review the literature pertaining to immobilization and chemical modification of different enzyme classes from thermophiles, with emphasis on the chemistries involved and their implications for modification of the enzyme functional properties. We also highlight the potential for synergies in the combined use of immobilization and other chemical modifications.


AMSH is an endosome-associated ubiquitin isopeptidase.
The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif has been proposed to provide the active site for isopeptidase activity associated with the Rpn11/POH1 subunit of the 19S-proteasome and the Csn5-subunit of the signalosome. We have looked for similar activity in associated molecule with the SH3 domain of STAM (AMSH), a JAMM domain-containing protein that associates with the SH3-domain of STAM, a protein, which regulates receptor sorting at the endosome. We demonstrate isopeptidase activity against K48-linked tetraubiquitin and K63-linked polyubiquitin chains to generate di-ubiquitin and free ubiquitin, respectively. An inactivating mutation (D348A) in AMSH leads to accumulation of ubiquitin on endosomes and the concomitant stabilization of a ubiquitinated form of STAM, which requires an intact ubiquitin interaction motif (UIM) within STAM. Short interfering RNA knockdown of AMSH enhances the degradation rate of EGF receptor (EGFR) following acute stimulation and ubiquitinated EGFR provides a substrate for AMSH in vitro. We propose that AMSH is a deubiquitinating enzyme with functions at the endosome, which oppose the ubiquitin-dependent sorting of receptors to lysosomes.


Use of Spectroscopic Techniques for a Rapid and Non-Destructive Monitoring of Thermal Treatments and Storage Time of Sous-Vide Cooked Cod Fillets.
In this work, the potential of spectroscopic techniques was studied to investigate heat-induced changes occurring during the application of thermal treatments on cod (Gadus morhua L.) fillets. Vacuum-packed samples were thermally treated in a water bath at 50, 60, 70 and 80 °C for 5 and 10 min, and further stored for one, four, and eight days at 4 ± 1 °C before analysis. Several traditional (including cooking loss, drip loss, texture, protein solubility, protein oxidation, and color) and spectroscopic (fluorescence and diffuse reflectance hyperspectral imaging) measurements were conducted on the same samples. The results showed a decrease in fluorescence intensity with increasing cooking temperature and storage time, while the impact of cooking time was only noticeable at low temperatures. Diffuse reflectance data exhibited a decrease in absorbance, possibly as a result of protein denaturation and increased scattering at higher cooking temperatures. Both fluorescence and diffuse reflectance data were highly correlated with color parameters, whereas moderate correlations were observed with most other traditional parameters. Support vector machine models performed better than partial least square ones for both classification of cod samples cooked at different temperatures and in prediction of the cooking temperature. The best classification result was obtained on fluorescence data, achieving an accuracy of 92.5%, while the prediction models resulted in a root mean square error of prediction of cooking temperature lower than 5 °C. Overall, the classification and prediction models showed good results, indicating that spectroscopic techniques, especially fluorescence hyperspectral imaging, have a high potential for monitoring thermal treatments in cod fillets.


A methodological investigation of the Intermodal Preferential Looking paradigm: Methods of analyses, picture selection and data rejection criteria.
The Intermodal Preferential Looking paradigm provides a sensitive measure of a child's online word comprehension. To complement existing recommendations (Fernald, Zangl, Portillo, & Marchman, 2008), the present study evaluates the impact of experimental noise generated by two aspects of the visual stimuli on the robustness of familiar word recognition with and without mispronunciations: the presence of a central fixation point and the level of visual noise in the pictures (as measured by luminance saliency). Twenty-month-old infants were presented with a classic word recognition IPL procedure in 3 conditions: without a fixation stimulus (No Fixation - noisiest condition), with a fixation stimulus before trial onset (Fixation, intermediate), and with a fixation stimulus, a neutral background and equally salient images (Fixation Plus - least noisy). Data were systematically analyzed considering a range of data selection criteria and dependent variables (proportion of looking time towards the target, longest look, and time-course analysis). Critically, the expected pronunciation and naming interaction was only found in the Fixation Plus condition. We discuss the impact of data selection criteria and the dependent variable choice on the modulation of these effects across the different conditions.


Popliteal artery aneurysms treatments: early midterm results of the use of endovascular stent grafts
Popliteal artery aneurysms (PAAs) are abnormal bulgings, which account for 70% of all peripheral artery aneurysms. They are usually asymptomatic. In this study, we present our long-term results of endovascular stent grafts in the treatment of PAA in the light of literature data. A total of 63 legs of 63 patients with PAA, who were treated with endovascular techniques in our clinic between July 2010 and July 2019, were retrospectively analyzed. All patients underwent color Doppler ultrasound (DUS), magnetic resonance angiography (MRA), or computed tomography angiography (CTA) to identify the diameter and length of PAAs, vessel tortuosity, the presence and degree of thrombus, and diameter in the healthy landing zone and to visualize tibioperoneal vascular structures. A Viabahn stent graft was inserted in all patients. 57 patients (90.5%) were males with a mean age of 76.35 ± 7 years. 24 patients (38.1%) were symptomatic, while 11 patients (17.5%) had a concomitant abdominal aortic aneurysm (AAA). The mean follow-up period was 46.05 ± 25.01 months. The primary patency rate was 79.3%. A graft thrombosis was observed in 13 patients (20.6%) during a mean follow-up period of 8.31 ± 5.91 months. The number of distal arteries was significantly lower in the patients with thrombosis than those without. Endovascular treatment of PAA using stentgrafts is safe in selected cases. However, it is reasonable to avoid endovascular treatment due to an increased risk for thrombosis in patients with a low number of patent distal arteries or impaired distal flow.


Inoculation with arbuscular mycorrhizal fungi improves the nutritional value of tomatoes.
Arbuscular mycorrhizal (AM) fungi can affect many different micronutrients and macronutrients in plants and also influence host volatile compound synthesis. Their effect on the edible portions of plants is less clear. Two separate studies were performed to investigate whether inoculation by AM fungi (Rhizophagus irregularis, Funneliformis mosseae, or both) can affect the food quality of tomato fruits, in particular common minerals, antioxidants, carotenoids, a suite of vitamins, and flavor compounds (sugars, titratable acids, volatile compounds). It was found that AM fungal inoculation increased the nutrient quality of tomato fruits for most nutrients except vitamins. Fruit mineral concentration increased with inoculation (particularly N, P, and Cu). Similarly, inoculated plants had fruit with higher antioxidant capacity and more carotenoids. Furthermore, five volatile compounds were significantly higher in AM plants compared with non-AM controls. Taken together, these results show that AM fungi represent a promising resource for improving both sustainable food production and human nutritional needs.


A national survey of practicing psychologists' use and attitudes toward homework in psychotherapy.
Homework assignments have been studied extensively in psychotherapy research, but there is little data on the way in which homework is transferred to clinical practice. A survey was conducted of 827 practicing psychologists nationwide regarding their use and attitudes toward homework. Overall, 68% of the present sample indicated that they "often" or "almost always" used homework assignments. Factor analysis revealed that practitioners have a range of attitudes that can be classified as reflecting the notion that homework has (a) a negative impact on in-session therapeutic work and (b) a positive effect on therapy outcomes. More positive attitudes were reported among those with a cognitive-behavioral theoretical orientation. Nevertheless, the use of homework among psychodynamic/analytic practitioners reported in the present sample was unexpected and suggests that theoretical and empirical work is required to examine homework's effects in a range of psychotherapy approaches.


Tuberculous meningitis in adults in Turkey: epidemiology, diagnosis, clinic and laboratory [corrected].
A retrospective study was performed to assess the epidemiology, diagnosis, clinic, and laboratory of the patients with tuberculous meningitis (TBM) in a multicentral study. The medical records of adult cases with TBM treated at 12 university hospitals throughout Turkey, between 1985 and 1998 were reviewed using a standardized protocol. The diagnosis of TMB was established with the clinical and laboratory findings and/or microbiological confirmation in cerebrospinal fluid (CSF). The non-microbiologically confirmed cases were diagnosed with five diagnostic sub-criteria which CSF findings, radiological findings, extra-neural tuberculosis, epidemiological findings and response to antituberculous therapy. A total of 469 patients were included in this study. Majority of the patients were from Southeast Anatolia (164 patients, 35.0%) and (108 patients, 23.0%) from East Anatolia regions. There was a close contact with a tuberculous patient in 88 of 341 patients (25.8%) and with a tuberculous family member in 53 of 288 patients (18.4%). BCG scar was positive in 161 of 392 patients (41.1%). Tuberculin skin test was done in 233 patients and was found to be negative in 75. Totally 115 patients died (24.5%) of whom 23 died in 24 hour after admittance. The diagnosis was confirmed with clinical findings and CSF culture and/or Ziehl-Nelson staining in 88 patients (18.8%). Besides clinical criteria, there were three or more diagnostic sub-criteria in 252 cases (53.7%), two diagnostic sub-criteria in 99 cases (21.1%), and any diagnostic sub-criteria in 30 patients (6.4%). Since TBM is a very critical disease, early diagnosis and treatment may reduce fatal outcome and morbidity.


Using Optimal Control to Disambiguate the Effect of Depression on Sensorimotor, Motivational and Goal-Setting Functions.
Differentiating the ability from the motivation to act is of central importance to psychiatric disorders in general and depression in particular. However, it has been difficult to develop quantitative approaches to relate depression to poor motor performance in goal-directed tasks. Here, we use an inverse optimal control approach to provide a computational framework that can be used to infer and factorize performance deficits into three components: sensorimotor speed, goal setting and motivation. Using a novel computer-simulated driving experiment, we found that (1) severity of depression is associated with both altered sensorimotor speed and motivational function; (2) moderately to severely depressed individuals show an increased distance from the stop sign indicating aversive learning affecting goal setting functions. Taken together, the inverse optimal control framework can disambiguate on an individual basis the sensorimotor from the motivational dysfunctions in depression, which may help to develop more precisely targeted interventions.


Biomonitoring of herbicides in Ontario farm applicators.
Biomonitoring of pesticide residues in urine offers the advantages of integrating exposure due to all routes of entry and accounting for individual differences in several factors such as pharmacokinetics. The study was designed to measure the body burden of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) in farm applicators and to measure compliance with label recommendations regarding the use of personal protective gear and the impact of such use on exposure. Farmers (N=126) from Ontario, Canada, collected a preexposure spot sample of urine and then two consecutive 24-hour urine samples immediately following the farmers' first use of these herbicides during 1996. Details on the pesticides used and handling practices were collected by questionnaire. For the farmers who reported using 2,4-D, the mean urinary concentration was 27.6 microg/l in the day-1 sample and 40.8 microg/l in the day-2 sample. The comparable figures for MCPA were 44.4 microg/l and 58.0 microg/l, respectively. Adherence to all of the recommended personal protective gear was rare (3%). Wearing goggles or a face shield during mixing and loading was associated with the lowest exposures. The urinary concentrations of 2,4-D and MCPA of these farm applicators were of the same order of magnitude as those published in the past decade, but lower than earlier studies, indicating that improvements in education, equipment, and labeling have likely had an impact on the degree of exposure in occupational settings.


Neuroimaging abnormalities in adults with sickle cell anemia: associations with cognition.
This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = -2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = -3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.


Musculoskeletal MRI findings of juvenile localized scleroderma.
Juvenile localized scleroderma comprises a group of autoimmune conditions often characterized clinically by an area of skin hardening. In addition to superficial changes in the skin and subcutaneous tissues, juvenile localized scleroderma may involve the deep soft tissues, bones and joints, possibly resulting in functional impairment and pain in addition to cosmetic changes. There is literature documenting the spectrum of findings for deep involvement of localized scleroderma (fascia, muscles, tendons, bones and joints) in adults, but there is limited literature for the condition in children. We aimed to document the spectrum of musculoskeletal magnetic resonance imaging (MRI) findings of both superficial and deep juvenile localized scleroderma involvement in children and to evaluate the utility of various MRI sequences for detecting those findings. Two radiologists retrospectively evaluated 20 MRI studies of the extremities in 14 children with juvenile localized scleroderma. Each imaging sequence was also given a subjective score of 0 (not useful), 1 (somewhat useful) or 2 (most useful for detecting the findings). Deep tissue involvement was detected in 65% of the imaged extremities. Fascial thickening and enhancement were seen in 50% of imaged extremities. Axial T1, axial T1 fat-suppressed (FS) contrast-enhanced and axial fluid-sensitive sequences were rated most useful. Fascial thickening and enhancement were the most commonly encountered deep tissue findings in extremity MRIs of children with juvenile localized scleroderma. Because abnormalities of the skin, subcutaneous tissues and fascia tend to run longitudinally in an affected limb, axial T1, axial fluid-sensitive and axial T1-FS contrast-enhanced sequences should be included in the imaging protocol.


Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography.
The purpose of this study was to determine whether myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD) during rest and pharmacological stress in humans through the use of venous injections of contrast. Thirty patients with known or suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1)) infusion. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the two sets of images using both methods were scored for myocardial perfusion as follows: 1=normal, 0.5=mildly reduced, and 0=severely reduced. The information from baseline and postdipyridamole images was then used to determine whether an abnormal segment was irreversible (similar abnormal perfusion at baseline and after dipyridamole) or reversible (perfusion better at baseline compared with after dipyridamole). Concordance between segmental scores was 92% (kappa=.99) for both methods. Concordance between normal perfusion and reversible or irreversible segmental defects was 90% (kappa=.80). Agreem between the two methods for each of the three vascular territories in each patient was 90% (kappa=.77), while agreement for the presence or absence of CAD in each patient was 86% (kappa=.86). In the 4 patients with disagreement, the perfusion scores were 0.5 for SPECT and 1.0 for MCE. This study shows that MCE, with venous injection of contrast, can define the presence of CAD during rest and pharmacological stress. The location of perfusion abnormalities and their physiologic relevance (reversible or irreversible) by MCE is similar to that provided by SPECT. MCE, therefore, holds promise for the noninvasive assessment of myocardial perfusion in humans.


Broadband parametric frequency comb generation with a 1-μm pump source.
We report the first experimental demonstration of broadband frequency comb generation from a single-frequency pump laser at 1-μm using parametric oscillation in a high-Q silicon-nitride ring resonator. The resonator dispersion is engineered to have a broad anomalous group velocity dispersion region near the pump wavelength for efficient parametric four-wave mixing. The comb spans 55 THz with a 230-GHz free spectral range. These results demonstrate the powerful advantage of dispersion engineering in chip-based devices for producing combs with a wide range of pump wavelengths.


Mortality in adult offspring of immigrants: a Swedish national cohort study.
Higher risks of psychiatric disorders and lower-than-average subjective health in adulthood have been demonstrated in offspring of immigrants in Sweden compared with offspring of native Swedes, and linked to relative socioeconomic disadvantage. The present study investigated mortality rates in relation to this inequity from a gender perspective. We used data from national registers covering the entire Swedish population aged 18-65 years. Offspring of foreign-born parents who were either Swedish born or had received residency in Sweden before school age (<7 years) were defined as "offspring of immigrants." We used Cox regression models to examine the association between parental country of birth and mortality between 1990 and 2008, with adjustment for education, income, age and family type. Male offspring of immigrants from the Middle East (HR:2.00, CI:1.66-2.26), other non-European countries (HR:1.80, CI:1.36-2.36) and Finland (HR:1.56, CI:1.48-1.65) showed an age-adjusted excess mortality risk from all causes of death when compared to offspring with Swedish-born parents. Income, but not education, greatly attenuated these increased mortality risks. No excess mortality rates were found among female offspring of immigrants, with the exception of external cause of death among offspring of Finnish immigrants. The study demonstrates high mortality rates in male offspring of immigrants from Finland and non-European countries that are associated with economic, but not educational, disadvantage. No increased mortality rates were found among female offspring of immigrants. Future studies are needed to explain this gender differential and why income, but not education, predicts mortality in male offspring of immigrants.


The statistics of synergism.
Biological scientists often want to determine whether two agents or events, for example, extracellular stimuli and/or intracellular signaling pathways, act synergistically when eliciting a biological response. When setting out to study whether two experimental treatments act synergistically, most biologists design the correct experiment--they administer four treatment combinations consisting of (1) the first treatment alone, (2) the second treatment alone, (3) both treatments together, and (4) neither treatment (i.e. the control). Many biologists are less clear about the correct statistical approach to determining whether the data collected in such an experimental design support a conclusion regarding synergism, or lack thereof. The non-additivity of two experimental treatments that is central to the definition of synergism leads to an algebraic formulation corresponding to the statistical null hypothesis appropriate for testing whether or not there is synergism. The resulting complex contrast among the four treatment group means is identical to the interaction effect tested in a two-way analysis of variance (ANOVA). This should not be surprising, because synergism, by definition, occurs when two treatments interact, rather than act independently, to influence a biological response. Hence, in the most readily implemented approach, the correct statistical analysis of a question of synergism is based on testing the interaction effect in a two-way ANOVA. This review presents the rationale for this correct approach to analysing data when the question is of synergism, and applies this approach to a recent published example. In addition, a common incorrect approach to analysing data with regards to synergism is presented. Finally, several associated statistical issues with regard to correctly implementing a two-way ANOVA are discussed.


Properties of the internal clock: first- and second-order principles of subjective time.
Humans share with other animals an ability to measure the passage of physical time and subjectively experience a sense of time passing. Subjective time has hallmark qualities, akin to other senses, which can be accounted for by formal, psychological, and neurobiological models of the internal clock. These include first-order principles, such as changes in clock speed and how temporal memories are stored, and second-order principles, including timescale invariance, multisensory integration, rhythmical structure, and attentional time-sharing. Within these principles there are both typical individual differences--influences of emotionality, thought speed, and psychoactive drugs--and atypical differences in individuals affected with certain clinical disorders (e.g., autism, Parkinson's disease, and schizophrenia). This review summarizes recent behavioral and neurobiological findings and provides a theoretical framework for considering how changes in the properties of the internal clock impact time perception and other psychological domains.


Protection of repetitive DNA borders from self-induced meiotic instability.
DNA double strand breaks (DSBs) in repetitive sequences are a potent source of genomic instability, owing to the possibility of non-allelic homologous recombination (NAHR). Repetitive sequences are especially at risk during meiosis, when numerous programmed DSBs are introduced into the genome to initiate meiotic recombination. In the repetitive ribosomal DNA (rDNA) array of the budding yeast Saccharomyces cerevisiae, meiotic DSB formation is prevented in part through Sir2-dependent heterochromatin formation. Here we show that the edges of the rDNA array are exceptionally susceptible to meiotic DSBs, revealing an inherent heterogeneity in the rDNA array. We find that this localized DSB susceptibility necessitates a border-specific protection system consisting of the meiotic ATPase Pch2 and the origin recognition complex subunit Orc1. Upon disruption of these factors, DSB formation and recombination increased specifically in the outermost rDNA repeats, leading to NAHR and rDNA instability. Notably, the Sir2-dependent heterochromatin of the rDNA itself was responsible for the induction of DSBs at the rDNA borders in pch2Δ cells. Thus, although the activity of Sir2 globally prevents meiotic DSBs in the rDNA, it creates a highly permissive environment for DSB formation at the junctions between heterochromatin and euchromatin. Heterochromatinized repetitive DNA arrays are abundant in most eukaryotic genomes. Our data define the borders of such chromatin domains as distinct high-risk regions for meiotic NAHR, the protection of which may be a universal requirement to prevent meiotic genome rearrangements that are associated with genomic diseases and birth defects.


The Complete Genome and Physiological Analysis of the Microbialite-Dwelling Agrococcus pavilionensis sp. nov; Reveals Genetic Promiscuity and Predicted Adaptations to Environmental Stress.
Members of the bacterial genus Agrococcus are globally distributed and found across environments so highly diverse that they include forests, deserts, and coal mines, as well as in potatoes and cheese. Despite how widely Agrococcus occurs, the extent of its physiology, genomes, and potential roles in the environment are poorly understood. Here we use whole-genome analysis, chemotaxonomic markers, morphology, and 16S rRNA gene phylogeny to describe a new isolate of the genus Agrococcus from freshwater microbialites in Pavilion Lake, British Columbia, Canada. We characterize this isolate as a new species Agrococcus pavilionensis strain RW1 and provide the first complete genome from a member of the genus Agrococcus. The A. pavilionensis genome consists of one chromosome (2,627,177 bp) as well as two plasmids (HC-CG1 1,427 bp, and LC-RRW783 31,795 bp). The genome reveals considerable genetic promiscuity via mobile elements, including a prophage and plasmids involved in integration, transposition, and heavy-metal stress. A. pavilionensis strain RW1 differs from other members of the Agrococcus genus by having a novel phospholipid fatty acid iso-C15:1Δ4, β-galactosidase activity and amygdalin utilization. Carotenoid biosynthesis is predicted by genomic metabolic reconstruction, which explains the characteristic yellow pigmentation of A. pavilionensis. Metabolic reconstructions of strain RW1 genome predicts a pathway for releasing ammonia via ammonification amino acids, which could increase the saturation index leading to carbonate precipitation. Our genomic analyses suggest signatures of environmental adaption to the relatively cold and oligotrophic conditions of Pavilion Lake microbialites. A. pavilionensis strain RW1 in modern microbialites has an ecological significance in Pavilion Lake microbialites, which include potential roles in heavy-metal cycling and carbonate precipitation (e.g., ammonification of amino acids and filamentation which many trap carbonate minerals).


"It's got to be on this page": age and cognitive style in a study of online health information seeking.
The extensive availability of online health information offers the public opportunities to become independently informed about their care, but what affects the successful retrieval and understanding of accurate and detailed information? We have limited knowledge about the ways individuals use the Internet and the personal characteristics that affect online health literacy. This study examined the extent to which age and cognitive style predicted success in searching for online health information, controlling for differences in education, daily Internet use, and general health literacy. The Online Health Study (OHS) was conducted at Johns Hopkins School of Public Health and Stanford University School of Medicine from April 2009 to June 2010. The OHS was designed to explore the factors associated with success in obtaining health information across different age groups. A total of 346 men and women aged 35 years and older of diverse racial and ethnic backgrounds participated in the study. Participants were evaluated for success in searching online for answers to health-related tasks/questions on nutrition, cancer, alternative medicine, vaccinations, medical equipment, and genetic testing. Cognitive style, in terms of context sensitivity, was associated with less success in obtaining online health information, with tasks involving visual judgment most affected. In addition, better health literacy was positively associated with overall success in online health seeking, specifically for tasks requiring prior health knowledge. The oldest searchers were disadvantaged even after controlling for education, Internet use, general health literacy, and cognitive style, especially when spatial tasks such as mapping were involved. The increasing availability of online health information provides opportunities to improve patient education and knowledge, but effective use of these resources depends on online health literacy. Greater support for those who are in the oldest cohorts and for design of interfaces that support users with different cognitive styles may be required in an age of shared medical decision making.


Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: a systematic review.
The aim of this study was to systematically review the findings of publications addressing the epidemiology of anal human papillomavirus (HPV) infection, anal intraepithelial neoplasia, and anal cancer in women. We conducted a systematic review among publications published from Jan. 1, 1997, to Sept. 30, 2013, to limit to publications from the combined antiretroviral therapy era. Three searches were performed of the National Library of Medicine PubMed database using the following search terms: women and anal HPV, women anal intraepithelial neoplasia, and women and anal cancer. Publications were included in the review if they addressed any of the following outcomes: (1) prevalence, incidence, or clearance of anal HPV infection, (2) prevalence of anal cytological or histological neoplastic abnormalities, or (3) incidence or risk of anal cancer. Thirty-seven publications addressing anal HPV infection and anal cytology remained after applying selection criteria, and 23 anal cancer publications met the selection criteria. Among HIV-positive women, the prevalence of high-risk (HR)-HPV in the anus was 16-85%. Among HIV-negative women, the prevalence of anal HR-HPV infection ranged from 4% to 86%. The prevalence of anal HR-HPV in HIV-negative women with HPV-related pathology of the vulva, vagina, and cervix compared with women with no known HPV-related pathology, varied from 23% to 86% and from 5% to 22%, respectively. Histological anal high-grade squamous intraepithelial lesions (anal intraepithelial neoplasia 2 or greater) was found in 3-26% of the women living with HIV, 0-9% among women with lower genital tract pathology, and 0-3% for women who are HIV negative without known lower genital tract pathology. The incidence of anal cancer among HIV-infected women ranged from 3.9 to 30 per 100,000. Among women with a history of cervical cancer or cervical intraepithelial neoplasia 3, the incidence rates of anal cancer ranged from 0.8 to 63.8 per 100,000 person-years, and in the general population, the incidence rates ranged from 0.55 to 2.4 per 100,000 person-years. This review provides evidence that anal HPV infection and dysplasia are common in women, especially in those who are HIV positive or have a history of HPV-related lower genital tract pathology. The incidence of anal cancer continues to grow in all women, especially those living with HIV, despite the widespread use of combined antiretroviral therapy.


Virulence factors of Moraxella catarrhalis outer membrane vesicles are major targets for cross-reactive antibodies and have adapted during evolution.
Moraxella catarrhalis is a common human respiratory tract pathogen. Its virulence factors associated with whole bacteria or outer membrane vesicles (OMVs) aid infection, colonization and may induce specific antibodies. To investigate pathogen-host interactions, we applied integrated bioinformatic and immunoproteomic (2D-electrophoresis, immunoblotting, LC-MS/MS) approaches. We showed that OMV proteins engaged exclusively in complement evasion and colonization strategies, but not those involved in iron transport and metabolism, are major targets for cross-reacting antibodies produced against phylogenetically divergent M. catarrhalis strains. The analysis of 31 complete genomes of M. catarrhalis and other Moraxella revealed that OMV protein-coding genes belong to 64 orthologous groups, five of which are restricted to M. catarrhalis. This species showed a two-fold increase in the number of OMV protein-coding genes relative to its ancestors and animal-pathogenic Moraxella. The appearance of specific OMV factors and the increase in OMV-associated virulence proteins during M. catarrhalis evolution is an interesting example of pathogen adaptation to optimize colonization. This precisely targeted cross-reactive immunity against M. catarrhalis may be an important strategy of host defences to counteract this phenomenon. We demonstrate that cross-reactivity is closely associated with the anti-virulent antibody repertoire which we have linked with adaptation of this pathogen to the host.


Structural basis of slow activation gating in the cardiac I Ks channel complex.
Accessory β-subunits of the KCNE gene family modulate the function of various cation channel α-subunits by the formation of heteromultimers. Among the most dramatic changes of biophysical properties of a voltage-gated channel by KCNEs are the effects of KCNE1 on KCNQ1 channels. KCNQ1 and KCNE1 are believed to form nativeI(Ks) channels. Here, we characterize molecular determinants of KCNE1 interaction with KCNQ1 channels by scanning mutagenesis, double mutant cycle analysis, and molecular dynamics simulations. Our findings suggest that KCNE1 binds to the outer face of the KCNQ1 channel pore domain, modifies interactions between voltage sensor, S4-S5 linker and the pore domain, leading to structural modifications of the selectivity filter and voltage sensor domain. Molecular dynamics simulations suggest a stable interaction of the KCNE1 transmembrane α-helix with the pore domain S5/S6 and part of the voltage sensor domain S4 of KCNQ1 in a putative pre-open channel state. Formation of this state may induce slow activation gating, the pivotal characteristic of native cardiac I(Ks) channels. This new KCNQ1-KCNE1 model may become useful for dynamic modeling of disease-associated mutant I(Ks) channels.


Mendelian and complex genetics of susceptibility and resistance to parasitic infections.
Uncovering the complex genetic basis of susceptibility and resistance to parasitic infectious diseases is an enormous challenge. It probably involves many different host genes, interacting with multiple parasite genetic and environmental factors. Several genes of interest have been identified by family and association studies in humans and by using mouse models, but more robust epidemiological studies and functional data are needed to authenticate these findings. With new technologies and statistical tools for whole-genome association analysis, the next few years are likely to see acceleration in the rate of gene discovery, which has the potential to greatly assist drug and vaccine development.


A Qualitative Analysis of How Online Access to Mental Health Notes Is Changing Clinician Perceptions of Power and the Therapeutic Relationship.
As part of the national OpenNotes initiative, the Veterans Health Administration (VHA) provides veterans online access to their clinical progress notes, raising concern in mental health settings. The aim of this study was to examine the perspectives and experiences of mental health clinicians with OpenNotes to better understand how OpenNotes may be affecting mental health care. We conducted individual semi-structured interviews with 28 VHA mental health clinicians and nurses. Transcripts were analyzed using a thematic analysis approach, which allows for both inductive and deductive themes to be explored using an iterative, constant comparative coding process. OpenNotes is changing VHA mental health care in ways that mental health clinicians perceive as both challenging and beneficial. At the heart of these changes is a shifting power distribution within the patient-clinician relationship. Some clinicians view OpenNotes as an opportunity to better partner with patients, whereas others feel that it has the potential to undo the therapeutic relationship. Many clinicians are uncomfortable with OpenNotes, but acknowledge that this discomfort could both improve and diminish care and documentation practices. Specifically, we found that (1) OpenNotes is empowering patients, (2) OpenNotes is affecting how clinicians build and maintain the therapeutic relationship, and (3) mental health clinicians are adjusting their practices to protect patients and themselves from adverse consequences of OpenNotes. Our findings suggest that future research should monitor whether OpenNotes notes facilitates stronger patient-clinician relationships, enhancing patient-centered mental health care, or diminishes the quality of mental health care through disruptions in the therapeutic relationship and reduced documentation.


Muscle cell attachment in Caenorhabditis elegans.
In the nematode Caenorhabditis elegans, the body wall muscles exert their force on the cuticle to generate locomotion. Interposed between the muscle cells and the cuticle are a basement membrane and a thin hypodermal cell. The latter contains bundles of filaments attached to dense plaques in the hypodermal cell membranes, which together we have called a fibrous organelle. In an effort to define the chain of molecules that anchor the muscle cells to the cuticle we have isolated five mAbs using preparations enriched in these components. Two antibodies define a 200-kD muscle antigen likely to be part of the basement membrane at the muscle/hypodermal interface. Three other antibodies probably identify elements of the fibrous organelles in the adjacent hypodermis. The mAb IFA, which reacts with mammalian intermediate filaments, also recognizes these structures. We suggest that the components recognized by these antibodies are likely to be involved in the transmission of tension from the muscle cell to the cuticle.


The striatum and cerebral cortex express different muscarinic receptor mRNAs.
The existence of four distinct muscarinic acetylcholine receptor genes (m1-mr) has recently been demonstrated. cDNAs for three of these receptors have been cloned from brain (m1, m3, m4) and one from heart (m2). To gain some understanding of the physiological role of the brain muscarinic receptors, we mapped the distribution of their mRNAs in rat brain by in situ hybridization. These mRNAs are barely detectable in the hindbrain and cerebellum. Within forebrain, each mRNA has a strikingly different pattern of distribution. The highest levels of m1 mRNA are in the cerebral cortex and hippocampus followed by the striatum. m3 mRNA is also prominent in the cerebral cortex, but has very low levels in the striatum. Conversely, the levels of m4 mRNA are highest in the striatum. Since the cognitive effects of muscarinic drugs have been localized to the cerebral cortex and hippocampus, and their psychomotor effects to the striatum, these data suggest that the muscarinic receptors which subserve these responses may be different gene products. Finally, we show that these muscarinic receptors can be distinguished pharmacologically, suggesting that it may be possible to develop drugs for the selective treatment of the psychomotor vs cognitive difficulties of Parkinson's and Alzheimer's disease, respectively.


Conservative management of mallet injuries: A national survey of current practice in the UK.
Mallet injuries are common and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding the best management, and it is unclear whether this uncertainty is reflected in current UK practice. An online survey was developed to determine the current practice for the conservative treatment of mallet injury among specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician's views of study outcome selection were also explored to improve future trials. In total, 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for 6 weeks (n = 228, 78%) and soft tissue injuries for either 8 weeks (n = 172, 56%) or 6 weeks (n = 119, 39%). Post-immobilisation splinting was frequently recommended, but duration varied between 2 and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence-based protocol is required. Clinicians' opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.


What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models.
Statistical models, such as linear or logistic regression or survival analysis, are frequently used as a means to answer scientific questions in psychosomatic research. Many who use these techniques, however, apparently fail to appreciate fully the problem of overfitting, ie, capitalizing on the idiosyncrasies of the sample at hand. Overfitted models will fail to replicate in future samples, thus creating considerable uncertainty about the scientific merit of the finding. The present article is a nontechnical discussion of the concept of overfitting and is intended to be accessible to readers with varying levels of statistical expertise. The notion of overfitting is presented in terms of asking too much from the available data. Given a certain number of observations in a data set, there is an upper limit to the complexity of the model that can be derived with any acceptable degree of uncertainty. Complexity arises as a function of the number of degrees of freedom expended (the number of predictors including complex terms such as interactions and nonlinear terms) against the same data set during any stage of the data analysis. Theoretical and empirical evidence--with a special focus on the results of computer simulation studies--is presented to demonstrate the practical consequences of overfitting with respect to scientific inference. Three common practices--automated variable selection, pretesting of candidate predictors, and dichotomization of continuous variables--are shown to pose a considerable risk for spurious findings in models. The dilemma between overfitting and exploring candidate confounders is also discussed. Alternative means of guarding against overfitting are discussed, including variable aggregation and the fixing of coefficients a priori. Techniques that account and correct for complexity, including shrinkage and penalization, also are introduced.


Sleep-disordered breathing, sleep duration, and childhood overweight: a longitudinal cohort study.
To examine independent associations between sleep-disordered breathing (SDB), sleep duration from birth through 6.75 years, and body mass index (BMI) through 15 years of age in a population-based cohort. The Avon Longitudinal Study of Parents and Children collected parent questionnaire data on child sleep duration and SDB symptoms from birth through 6.75 years and child BMI from the Avon Longitudinal Study of Parents and Children research clinics (n = 1899). For SDB, logistic regression models-minimal, confounder, and confounder + sleep duration adjusted-examined associations with BMI at 7, 10, and 15 years of age. For short sleep duration (≤10th percentile), comparable SDB-adjusted models examined associations with BMI at 15 years of age. Children with the worst SDB symptoms vs asymptomatic children, had increased odds of overweight at 7 (OR = 2.08, 95% CI = 1.04-4.17), 10 (OR = 1.79, 95% CI = 1.02-3.16), and 15 years of age (OR = 2.25, 95% CI = 1.27-3.97) in models adjusted for sleep duration. Similarly, short sleep duration at ≈5-6 years was associated with overweight at 15 years, independent of SDB. Children with short sleep duration at 4.75 years were more likely to be overweight at 15 years in minimally (OR = 2.21, 95% CI = 1.52-3.20), confounder (OR = 1.99, 95% CI = 1.34-2.96), and SDB-adjusted (OR = 2.04, 95% CI = 1.36-3.04) models. Both SDB and short sleep duration significantly and independently increase children's odds of becoming overweight. Findings underscore the potential importance of early identification and remediation of SDB, along with insufficient sleep, as strategies for reducing childhood obesity.


Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes.
Recent evidence suggests that higher vitamin D intakes beyond current recommendations may be associated with better health outcomes. In this chapter, evidence is summarized from different studies that evaluate threshold levels for serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity function, dental health, risk of falls, admission to nursing home, fractures, cancer prevention and incident hypertension. For all endpoints, the most advantageous serum levels for 25(OH)D appeared to be at least 75 nmol/l (30 ng/ml) and for cancer prevention, desirable 25(OH)D levels are between 90-120 nmol/l (36-48 ng/ml). An intake of no less than 1000 IU (25 mcg) of vitamin D3 (cholecalciferol) per day for all adults may bring at least 50% of the population up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most individuals into the desired range. While estimates suggest that 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of 2000 IU or higher doses for the total adult population need to be addressed in future studies.


Recording the sound of musical instruments with FBGs: the photonic pickup.
Fiber Bragg gratings (FBGs) have previously found many applications as strain and vibration sensors. Here we demonstrate that they may also be employed as pickups for musical instruments and, specifically, for acoustic guitars and solid-body electric guitars. By fixing the FBG to a vibrating part of the instrument's body, e.g., near the bridge of an acoustic guitar or on the headstock of a solid-body guitar, a number of sound recordings were made and compared to those obtained with either piezoelectric pickups or with magnetic induction pickups. The change in attenuation at the FBG's midreflection point is found to be correlated to the amplitude of vibration of the vibrating structure of the instrument. Acoustic frequency spectrum analysis supports the observation that the FBG acoustic transducer has a frequency response range that is comparable to those of commercial piezoelectric pickups. The recordings made with FBG pickups were of comparable quality to those obtained with other recording methods.


Urinary tract infections in children with prenatal hydronephrosis: A risk assessment from the Society for Fetal Urology Hydronephrosis Registry.
Risk factors for urinary tract infection (UTI) in children with prenatal hydronephrosis (PNH) are not clearly defined. Our study aim was to describe incidence and identify factors associated with UTI among a cohort of children diagnosed with PNH. Patients with confirmed PNH from four medical centers were prospectively enrolled in the Society for Fetal Urology (SFU) hydronephrosis registry between 9/2008 and 10/2015. Exclusion criteria included enrollment because of UTI, associated congenital anomalies, and less than 1-month follow-up. Univariate analysis was performed using Fisher's Exact test or Mann-Whitney U. Probability for UTI was determined by Kaplan-Meier curve. Median follow-up was 12 (IQR 4-20) months in 213 patients prenatally diagnosed with hydronephrosis. The majority of the cohort was male (72%), Caucasian (77%), and 26% had high grade (SFU 3 or 4) hydronephrosis. Circumcision was performed in 116/147 (79%) with known status, 19% had vesicoureteral reflux (VUR), and 11% had ureteral dilatation. UTI developed in 8% (n = 18), 89% during their first year of life. Univariate analysis found UTI developed more frequently in females (p < 0.001), uncircumcised males (p < 0.01), and the presence of parenchymal renal cyst (p < 0.05). Logistic regression found renal cyst to no longer be significant, but female gender a significant risk factor for development of UTI (p < 0.001). Regression analysis stratified by gender found neither hydronephrosis grade nor parenchymal renal cyst to be significant risk factors for UTI development among females. However, hydronephrosis grade and circumcision status were significant risk factors for development of UTI among males (p < 0.05 and p < 0.01, respectively). Identification of factors associated with UTI in patients with PNH is still progressing; however, several observational studies have identified groups that may be at increased risk of UTI. Use of prophylactic antibiotics (PA), degree of kidney dilation, gender, and circumcision status all have been reported to have some degree of impact on UTI. A previous study identified risk factors for UTI as female gender, uncircumcised status, hydroureteronephrosis, and VUR, and reported that prophylaxis provided a protective effect on prevention of UTI. Our data mirror those in some respect, identifying an association of UTI with female gender and, among males, uncircumcised status, and high grade hydronephrosis. However, we were unable to demonstrate an association between UTI and the use of PA, presence of VUR, dilated ureter, or renal duplication in this observational registry.


An evaluation of an educational intervention to reduce inappropriate cannulation and improve cannulation technique by paramedics.
Intravenous cannulation enables administration of fluids or drugs by paramedics in prehospital settings. Inappropriate use and poor technique carry risks for patients, including pain and infection. We aimed to investigate the effect of an educational intervention designed to reduce the rate of inappropriate cannulation and to improve cannulation technique. We used a non-randomised control group design, comparing two counties in the East Midlands (UK) as intervention and control areas. The educational intervention was based on Joint Royal Colleges Ambulance Liaison Committee guidance and delivered to paramedic team leaders who cascaded it to their teams. We analysed rates of inappropriate cannulation before and after the intervention using routine clinical data. We also assessed overall cannulation rates before and after the intervention. A sample of paramedics was assessed post-intervention on cannulation technique with a "model" arm using a predesigned checklist. There was a non-significant reduction in inappropriate (no intravenous fluids or drugs given) cannulation rates in the intervention area (1.0% to 0%) compared with the control area (2.5% to 2.6%). There was a significant (p<0.001) reduction in cannulation rates in the intervention area (9.1% to 6.5%; OR 0.7, 95% CI 0.48 to 1.03) compared with an increase in the control area (13.8% to 19.1%; OR 1.47, 95% CI 1.15 to 1.90), a significant difference (p<0.001). Paramedics in the intervention area were significantly more likely to use correct hand-washing techniques post-intervention (74.5% vs. 14.9%; p<0.001). The educational intervention was effective in bringing about changes leading to enhanced quality and safety in some aspects of prehospital cannulation.


High-speed reconfigurable card-to-card optical interconnects based on hybrid free-space and multi-mode fiber propagations.
In this paper, a high-speed reconfigurable card-to-card optical interconnect architecture based on hybrid free-space and multi-mode fiber (MMF) propagation is proposed. The use of free-space signal transmission provides flexibility and reconfigurability and the MMF extends the achievable interconnection range. A printed-circuit-board (PCB) based integrated optical interconnect module is designed and developed and proof-of-concept demonstration experiments are carried out. Results show that 3 × 10 Gb/s reconfigurable optical interconnect is realized with ~12 cm free-space propagation and a 10 m MMF length. In addition, since air turbulence due to high temperature of electronic components and heat dissipation fans always exists in typical interconnect environments and it normally results in system performance degradation, its impact on the proposed reconfigurable optical interconnect scheme is also experimentally investigated. Results indicate that even with comparatively strong air turbulence, 3 × 10 Gb/s optical interconnects with flexibility can still be achieved and the power penalty is <0.7 dB.


First Evidence of Purely Extreme-Ultraviolet Four-Wave Mixing.
The extension of nonlinear optical techniques to the extreme-ultraviolet (EUV), soft and hard x-ray regime represents one of the open challenges of modern science since it would combine chemical specificity with background-free detection and ultrafast time resolution. We report on the first observation of a four-wave-mixing (FWM) response from solid-state samples stimulated exclusively by EUV pulses. The all-EUV FWM signal was generated by the diffraction of high-order harmonics of the FERMI free-electron laser (FEL) from the standing wave resulting from the interference of two crossed FEL pulses at the fundamental wavelength. From the intensity of the FWM signal, we are able to extract the first-ever estimate of an effective value of ∼6×10^{-24} m^{2} V^{-2} for the third-order nonlinear susceptibility in the EUV regime. This proof of principle experiment represents a significant advance in the field of nonlinear optics and sets the starting point for a manifold of techniques, including frequency and phase-resolved FWM methods, that are unprecedented in this photon-energy regime.


Nicotine and synaptic plasticity in prefrontal cortex.
Nicotinic receptor activation enhances working memory and attention. The prefrontal cortex is a key brain area involved in working memory, and plasticity of excitatory synaptic transmission within the cortex is likely an important cellular mechanism of memory. A recent study has explored the cellular and synaptic basis of nicotine's effects on excitability within the prefrontal cortex. The findings suggest that nicotine enhances inhibitory synaptic inputs to layer V pyramidal cells, which suppresses induction of long-term potentiation (LTP). This inhibitory effect can be overcome by stimulating the pyramidal cells in bursts, which suggests a modification in the signal-to-noise ratio for synaptic input. Thus, the impact of strong stimuli on working memory would be enhanced when combined with nicotinic receptor activity. These findings may lead to novel and more effective treatments for memory disorders.


Brainstem mechanisms of persistent pain following injury.
Nerve signals arising from sites of tissue or nerve injury lead to long-term changes in the central nervous system and contribute to hyperalgesia and the amplification and persistence of pain. These nociceptor activity-dependent changes are referred to as central sensitization. Central sensitization involves an increase in the excitability of medullary dorsal horn (subnucleus caudalis) and spinal dorsal horn neurons brought about by a series of events including neuronal depolarization; removal of the voltage-dependent magnesium block of the N-methyl-D-aspartate (NMDA) receptor; release of calcium from intracellular stores; phosphorylation of the NMDA, alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), and neurokinin (NK) 1 receptors via activation of protein kineses; a change in the neuron's excitability; and an increase in synaptic strength. Central sensitization occurs in trigeminal nociceptive pathways, and more robust neuronal hyperexcitability occurs following deep tissue stimulation than cutaneous stimulation. Utilizing Fos protein immunocytochemistry, it has been found that 2 distinct regions are activated in the trigeminal brainstem sensory nuclei, the subnuclei interpolaris/caudalis transition zone (Vi/Vc) and the caudal part of the subnucleus caudalis. The latter is very similar to the spinal dorsal horn and is involved in the sensory discriminative aspects of pain. In contrast, the ventral pole of the Vi/Vc is unique. In addition to its role in the nociceptive sensory processing of deep tissues, it is involved bilaterally in somatovisceral and somatoautonomic processing, activation of the pituitary-adrenal axis, and descending modulatory control. The findings support our overall hypothesis that the ventral pole of Vi/Vc is involved in the coordination of bilateral sensorimotor functions of the trigeminal system associated with the response to deep tissue injury.


Recognition of a mycobacteria-specific epitope in the 65-kD heat-shock protein by synovial fluid-derived T cell clones.
Adjuvant arthritis in rats is induced by a T cell clone specific for amino acids 180-188 of the mycobacterial 65-kD heat-shock protein, and synovial T cell responses to this same Ag have been noted in human arthritis. We have isolated 65-kD Ag-specific T cell clones from synovial fluid mononuclear cells of a patient with acute arthritis, which, unlike the corresponding PBMC, showed a marked proliferative response to the 65-kD Ag. Using synthetic peptides corresponding to the whole sequence of the 65-kD Ag, all the clones were shown to recognize an epitope present in the first NH2-terminal peptide (amino acids 1-15), with no response to the adjacent peptide (amino acids 6-22) or to any other peptide. The complete dominance of this epitope in the response to the 65-kD Ag was shown by documenting responses to the peptide in PBMC obtained after recovery from the arthritis. This epitope, like that recognized by the rat arthritogenic T cell clone, is in a portion of the 65-kD sequence that is not conserved between bacteria and eukaryotes, so that in this case, joint inflammation could not be attributed to bacteria-induced T cell clones cross-reacting with the self 65-kD Ag.


Electrocardiographic features of arrhythmogenic right ventricular dysplasia.
The purpose of this study was to reevaluate the ECG features of arrhythmogenic right ventricular dysplasia (ARVD). The second objective was to evaluate the sensitivity and specificity of the standard and newly proposed diagnostic ECG markers in the presence of a right bundle-branch block (RBBB). One hundred patients with ARVD (57 men; aged 39+/-15 years) and 57 controls (21 men; aged 40+/-17 years) were included. Among the 100 patients with ARVD, a complete RBBB was present in 17 patients, and 15 patients had an incomplete RBBB. T-wave inversion through V(3) demonstrated optimal sensitivity and specificity in both ARVD patients without a complete RBBB or incomplete RBBB (71% [95% confidence interval, 58% to 81%] and 96% [95% confidence interval, 81% to 100%], respectively) and in ARVD patients with incomplete RBBB (73% [95% confidence interval, 45% to 92%] and 95% [95% confidence interval, 77% to 100%], respectively). Between ARVD patients and controls with a complete RBBB, the only 2 parameters that differed were the prevalence of T-wave inversion through V(4) (59% versus 12%, respectively; P<0.05) and an r'/s ratio in V(1) <1 (88% versus 14%, respectively; P<0.005). In ARVD patients with complete RBBB, the most sensitive and specific parameter was an r'/s ratio <1. We evaluated comprehensively the diagnostic value of ECG markers for ARVD. On the basis of the findings, we propose an algorithm, with examination of QRS morphology being the first step, for ECG evaluation of ARVD patients. Definite criteria are then applied on the basis of the presence of no RBBB, incomplete RBBB, and complete RBBB to obtain the best diagnostic utility of the ECG.


Evidence TRPV4 contributes to mechanosensitive ion channels in mouse skeletal muscle fibers.
We recorded the activity of single mechanosensitive (MS) ion channels from membrane patches on single muscle fibers isolated from mice. We investigated the actions of various TRP (transient receptor potential) channel blockers on MS channel activity. 2-aminoethoxydiphenyl borate (2-APB) neither inhibited nor facilitated single channel activity at submillimolar concentrations. The absence of an effect of 2-APB indicates MS channels are not composed purely of TRPC or TRPV1, 2 or 3 proteins. Exposing patches to 1-oleolyl-2-acetyl-sn-glycerol (OAG), a potent activator of TRPC channels, also had no effect on MS channel activity. In addition, flufenamic acid and spermidine had no effect on the activity of single MS channels. By contrast, SKF-96365 and ruthenium red blocked single-channel currents at micromolar concentrations. SKF-96365 produced a rapid block of the open channel current. The blocking rate depended linearly on blocker concentration, while the unblocking rate was independent of concentration, consistent with a simple model of open channel block. A fit to the concentration-dependence of block gave k(on) = 13 x 10 ( 6) M (-1) s (-1) and k(off) = 1609 sec (-1) with K(D) = ~124 µM. Block by ruthenium red was complex, involving both reduction of the amplitude of the single-channel current and increased occupancy of subconductance levels. The reduction in current amplitude with increasing concentration of ruthenium red gave a K(D) = ~49 µM. The high sensitivity of MS channels to block by ruthenium red suggests MS channels in skeletal muscle contain TRPV subunits. Recordings from skeletal muscle isolated from TRPV4 knockout mice failed to show MS channel activity, consistent with a contribution of TRPV4. In addition, exposure to hypo-osmotic solutions increases opening of MS channels in muscle. Our results provide evidence TRPV4 contributes to MS channels in skeletal muscle.


Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer's Disease.
Alzheimer's disease (AD) is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD) and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA) levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.


Genetic parameters of a random regression model for daily feed intake of performance tested French Landrace and Large White growing pigs.
Daily feed intake data of 1 279 French Landrace (FL, 1 039 boars and 240 castrates) and 2 417 Large White (LW, 2 032 boars and 385 castrates) growing pigs were recorded with electronic feed dispensers in three French central testing stations from 1992-1994. Male (35 to 95 kg live body weight) or castrated (100 kg live body weight) group housed, ad libitum fed pigs were performance tested. A quadratic polynomial in days on test with fixed regressions for sex and batch, random regressions for additive genetic, pen, litter and individual permanent environmental effects was used, with two different models for the residual variance: constant in model 1 and modelled with a quadratic polynomial depending on the day on test d(m) as follows in model 2: sigma(epsilon(m))(2) = exp (gamma(0) + gamma(1) d(m) + gamma(2) d(m)(2)). Variance components were estimated from weekly means of daily feed intake by means of a Bayesian analysis using Gibbs sampling. Posterior means of (co)variances were calculated using 800 000 samples from four chains (200 000 each). Heritability estimates of regression coefficients were 0.30 (FL model 1), 0.21 (FL model 2), 0.14 (LW1) and 0.14 (LW2) for the intercept, 0.04 (FL1), 0.04 (FL2), 0.11 (LW1) and 0.06 (LW2) for the linear, 0.03 (FL1), 0.04 (FL2) 0.11 (LW1) and 0.06 (LW2) for the quadratic term. Heritability estimates for weekly means of daily feed intake were the lowest in week 4 (FL1: 0.11, FL2: 0.11) and week 1 (LW1: 0.09, LW2: 0.10), and the highest in week 11 (FL1: 0.25, FL2: 0.24) and week 8 (LW1: 0.19, LW2: 0.18), respectively. Genetic eigenfunctions revealed that altering the shape of the feed intake curve by selection is difficult.


Multivalency at Interfaces: Supramolecular Carbohydrate-Functionalized Graphene Derivatives for Bacterial Capture, Release, and Disinfection.
A supramolecular carbohydrate-functionalized two-dimensional (2D) surface was designed and synthesized by decorating thermally reduced graphene sheets with multivalent sugar ligands. The formation of host-guest inclusions on the carbon surface provides a versatile strategy, not only to increase the intrinsic water solubility of graphene-based materials, but more importantly to let the desired biofunctional binding groups bind to the surface. Combining the vital recognition role of carbohydrates and the unique 2D large flexible surface area of the graphene sheets, the addition of multivalent sugar ligands makes the resulting carbon material an excellent platform for selectively wrapping and agglutinating Escherichia coli (E. coli). By taking advantage of the responsive property of supramolecular interactions, the captured bacteria can then be partially released by adding a competitive guest. Compared to previously reported scaffolds, the unique thermal IR-absorption properties of graphene derivatives provide a facile method to kill the captured bacteria by IR-laser irradiation of the captured graphene-sugar-E. coli complex.


Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.
Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA), an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01 μg/ml, 0.1 μg/ml) significantly inhibited platelet aggregation induced by collagen (P<0.001) and CRP (P<0.01), a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent.


Reflections on bioethics: consolidation of the principle of autonomy and legal aspects.
The author highlights the importance of emotions in all ethical reflections. He describes the most common positions of ethicists employing duties and rights as the basis for ethical thought. The author, goes to Freudian theory as viewed by the utilitarians, stating that the 'quest for pleasure' is not necessarily egocentric, especially for adults. For example, the feeling of solidarity emerges 'from the inside out', making irrelevant all the emphasis laid on obedience to duty (from the outside in). The article questions the essence of Kantian theory, based exclusively on 'reason' with disregard for feelings, by establishing what he considers a 'positivist' view of rational thought. It emphasizes the principle of autonomy, which it seen as basically opposing the principles of beneficence and fairness. It is proposed that the latter should be seen as what he calls heteronomy (a concept different from that of the rational ethicists). In theory, autonomy is not assigned to anyone on the basis of an external assessment. Any intervention in individual autonomy must be made (by the intervenor) when it becomes imperative in the defense of social or cultural values. The article distinguishes between ethics and morals) and states that the sole acceptable ethical principle is that ethics (theoretically) has no principle.


Identification and characterization of circular RNAs in Qinchuan cattle testis.
Circular RNA (circRNA) is a new class of non-coding RNA that has recently attracted researchers' interest. Studies have demonstrated that circRNA can function as microRNA sponges or competing endogenous RNAs. Although circRNA has been explored in some species and tissues, the genetic basis of testis development and spermatogenesis in cattle remains unknown. We performed ribo-depleted total RNA-Seq to detect circRNA expression profiles of neonatal (one week old) and adult (4 years old) Qinchuan cattle testes. We obtained 91 112 596 and 80 485 868 clean reads and detected 21 753 circRNAs. A total of 4248 circRNAs were significantly differentially expressed between neonatal and adult cattle testes. Among these circRNAs, 2225 were upregulated, and 2023 were downregulated in adult cattle testis. Genomic feature, length distribution and other characteristics of the circRNAs in cattle testis were studied. Moreover, Gene Ontology and KEGG pathway analyses were performed for source genes of circRNAs. These source genes were mainly involved in tight junction, adherens junction, TGFβ signalling pathway and reproduction, such as PIWIL1, DPY19L2, SLC26A8, IFT81, SMC1B, IQCG and TTLL5. CircRNA expression patterns were validated by RT-qPCR. Our discoveries provide a solid foundation for the identification and characterization of key circRNAs involved in testis development or spermatogenesis.


A family of promoter probe vectors incorporating autofluorescent and chromogenic reporter proteins for studying gene expression in Gram-negative bacteria.
A series of promoter probe vectors for use in Gram-negative bacteria has been made in two broad-host-range vectors, pOT (pBBR replicon) and pJP2 (incP replicon). Reporter fusions can be made to gfpUV, gfpmut3.1, unstable gfpmut3.1 variants (LAA, LVA, AAV and ASV), gfp+, dsRed2, dsRedT.3, dsRedT.4, mRFP1, gusA or lacZ. The two vector families, pOT and pJP2, are compatible with one another and share the same polylinker for facile interchange of promoter regions. Vectors based on pJP2 have the advantage of being ultra-stable in the environment due to the presence of the parABCDE genes. As a confirmation of their usefulness, the dicarboxylic acid transport system promoter (dctA(p)) was cloned into a pOT (pRU1097)- and a pJP2 (pRU1156)-based vector and shown to be expressed by Rhizobium leguminosarum in infection threads of vetch. This indicates the presence of dicarboxylates at the earliest stages of nodule formation.