FungiQuant: a broad-coverage fungal quantitative real-time PCR assay.
Fungal load quantification is a critical component of fungal community analyses. Limitation of current approaches for quantifying the fungal component in the human microbiome suggests the need for new broad-coverage techniques. We analyzed 2,085 18S rRNA gene sequences from the SILVA database for assay design. We generated and quantified plasmid standards using a qPCR-based approach. We evaluated assay coverage against 4,968 sequences and performed assay validation following the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. We designed FungiQuant, a TaqMan® qPCR assay targeting a 351 bp region in the fungal 18S rRNA gene. Our in silico analysis showed that FungiQuant is a perfect sequence match to 90.0% of the 2,617 fungal species analyzed. We showed that FungiQuant's is 100% sensitive and its amplification efficiencies ranged from 76.3% to 114.5%, with r(2)-values of >0.99 against the 69 fungal species tested. Additionally, FungiQuant inter- and intra-run coefficients of variance ranged from <10% and <20%, respectively. We further showed that FungiQuant has a limit of quantification 25 copies and a limit of detection at 5 copies. Lastly, by comparing results from human-only background DNA with low-level fungal DNA, we showed that amplification in two or three of a FungiQuant performed in triplicate is statistically significant for true positive fungal detection. FungiQuant has comprehensive coverage against diverse fungi and is a robust quantification and detection tool for delineating between true fungal detection and non-target human DNA.


Eliciting youth and adult recommendations through citizens' juries to improve school based adolescent immunisation programs.
Completion of adolescent immunisation schedules in Australia is sub-optimal despite a well-established school based delivery program. The aim of this study was to seek adolescent and adult views on how existing adolescent school based immunisation policy and program delivery could be improved to increase adolescent immunisation uptake. Two citizens' juries held separately, one with adolescent participants and one with adult participants deliberated on recommendations for public policy. Jury members were selected using a stratified sampling technique and recruited from a standing panel of community research participants through a market research company in South Australia. Juries were conducted in Metropolitan South Australia over two days and used university facilities with all meals and refreshments provided. Fifteen adults and 16 adolescents participated in the adult and youth juries respectively. Similar recommendations were made by both juries including increased ensuring the accuracy of information provided to adolescents and parents; employing a variety of formats for information delivery; and greater consideration of students' physical and emotional comfort in order to improve the experience for adolescents. While the youth jury recommended that it should be compulsory for adolescents to receive vaccines through the school based immunisation program, the adult jury recommended an 'opt-out' system of consent. Both juries also recommended the use of incentives to improve immunisation uptake and immunisation course completion. Eliciting adolescent views and including the perspectives of adolescents in discussions and development of strategies to improve engagement in the school based immunisation program provided valuable insight from the group most impacted by these policies and practices. Specifically, incorporation of adolescent and community views using citizens' juries may lead to greater overall support from the community as their values and needs are more accurately reflected.


Soy isoflavones and breast cancer.
The soybean and its products have been a staple in the Asian diet for centuries. Although intake of soy remains low in most Western populations, the use of soy isoflavone supplements has become commonplace, and an increasing number of food products contain soy ingredients. This review will present an updated summary of the observational results on soy isoflavones and risk of breast cancer development and outcome in patients with breast cancer. Results from soy intervention studies that have specifically examined the effects of soy on breast cell proliferation in breast tissues will be discussed. We will conclude by highlighting gaps in our knowledge on soy and breast cancer and issues that need to be addressed in future studies.


Influence of vasopressin and angiotensin on baroreflexes in the dog.
Cardiovascular responses to step-changes of carotid sinus pressure were evaluated at normal and elevated levels of plasma arginine vasopressin in anesthetized neurohypophysectomized dogs (n = 12). Arginine vasopressin influenced autonomic function in two ways: first, maximum carotid reflex gain increased; second, cardiac output was decreased. The enhancement of reflex strength was observed only in response to decreases of intrasinus pressure below the equilibrium point (pressures of between 60 and 105 mm Hg). Aortic pressure rose twice as high for a given decrease of intrasinus pressure, elevations of total peripheral resistance responses were triple those observed at normal plasma arginine vasopressin. In this way, arginine vasopressin more than doubled the ability of the carotid reflexes to return a drop in arterial pressure to normal. Arginine vasopressin enhancement of reflex gain was not observed with elevations of intrasinus pressures above the equilibrium point. Elevation of aortic pressure expected from the vasoconstrictor actions of infused arginine vasopressin were buffered by associated reductions in cardiac output. Vagally mediated bradycardia was consistently observed with elevated arginine vasopressin, but the reflex response of heart rate to step-changes of intrasinus pressure was unchanged. Time control studies in five neurohypophysectomized dogs indicated no significant change in carotid reflex response over the 3- to 4-hour protocol. Comparison of reflex responses in anephric dogs (n = 8) at low and elevated levels of angiotensin II indicated that this vasoactive peptide did not significantly alter reflex responsiveness. We conclude that arginine vasopressin enhances the ability of the carotid reflexes to normalize decreases of arterial pressure, but buffers a rise in pressure from its own vasoactive properties by initiating a fall of cardiac output.


Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.
Most mitotic homologous recombination (HR) events proceed via a synthesis-dependent strand annealing mechanism to avoid crossing over, which may give rise to chromosomal rearrangements and loss of heterozygosity. The molecular mechanisms controlling HR sub-pathway choice are poorly understood. Here, we show that human RECQ5, a DNA helicase that can disrupt RAD51 nucleoprotein filaments, promotes formation of non-crossover products during DNA double-strand break-induced HR and counteracts the inhibitory effect of RAD51 on RAD52-mediated DNA annealing in vitro and in vivo. Moreover, we demonstrate that RECQ5 deficiency is associated with an increased occupancy of RAD51 at a double-strand break site, and it also causes an elevation of sister chromatid exchanges on inactivation of the Holliday junction dissolution pathway or on induction of a high load of DNA damage in the cell. Collectively, our findings suggest that RECQ5 acts during the post-synaptic phase of synthesis-dependent strand annealing to prevent formation of aberrant RAD51 filaments on the extended invading strand, thus limiting its channeling into potentially hazardous crossover pathway of HR.


Cancer disclosure-account from a pediatric oncology ward in Egypt.
Informing the child about his/her diagnosis and treatment plan is essential; research has shown that it is related to the patient's quality of life and adherence to medication. For 7 months during 2008 (February to September), 2 study-specific questionnaires were constructed and administered to 304 parents of children diagnosed with cancer at the Children's Cancer Hospital Egypt. Among the 313 eligible parents of children diagnosed with cancer, 304 (97%) answered the first questionnaire and 281 (92%) answered the second questionnaire. We found that nearly three-quarters (72%) of the parents had their child's cancer diagnosis communicated by the physician. Among the 72%, the rate of the children present with the parent or parents during the disease disclosure conversation was 39% (n = 85/219). The majority of the children were in the age group 5-18 years (55%). Our findings indicate that cancer disclosure at the Children's Cancer Hospital is to a certain degree common; yet even when disclosure does take place, it is mainly in the absence of the child. Moreover, the information provided during the conversation may not be fully comprehended by the parent or the child because of the physician's misleading use of terms when disclosing the disease. Therefore, better practice should be developed for disease disclosure, and proper communication should be established between the patients and the provider; patient autonomy should also have an influence in the clinical practice.


Prevalence patterns and profile of adolescent tobacco users findings from a youth survey: A cross-sectional study.
To assess the prevalence of smoking and smokeless tobacco use among 16--19-year-old government and private college student of Bhubaneswar city. A cross-sectional descriptive study was designed and data on tobacco usage was collected from 906 students aged 16--19-year old government and private college students of Bhubaneswar city using modified youth tobacco survey (YTS) closed-ended questionnaire. Data was analyzed using descriptive statistics and Chi-square tests were used to determine the significant differences in the variables of interest. Out of 906 study subjects, mean age of initiation of use of tobacco product was found to be 14.8 among males and 15.3 among females. The responses of study subjects upon there believe that tobacco companies try to lure young people to use tobacco products, 54.7% males, 45.3% females reported as yes. 63 (9.9%) of students from private college reported using smokeless tobacco whereas 27 (10%) of students from government college used chewing tobacco. The results were statistically significant. A total of 84 (16.9%) males followed by 18 (4.4%) females reported to have ever tried smoking. The results were statistically significant. It was encouraging to find that during the period of the survey, majority of students did not use tobacco of any form. Regular and systematic education programs catering to teachers, children, and also their parents should be undertaken. Enabling teachers to educate the young impressionable minds regarding lifestyle disorders should be a cornerstone activity in preventing the establishment of lifestyle disorders like tobacco and alcohol use within the community.


Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.
Glucocorticoid (GC) resistance remains a clinical challenge in pediatric acute lymphoblastic leukemia where response to GC is a reliable prognostic indicator. To identify GC resistance pathways, we conducted a genome-wide, survival-based, short hairpin RNA screen in murine T-cell acute lymphoblastic leukemia (T-ALL) cells. Genes identified in the screen interfere with cyclic adenosine monophosphate (cAMP) signaling and are underexpressed in GC-resistant or relapsed ALL patients. Silencing of the cAMP-activating Gnas gene interfered with GC-induced gene expression, resulting in dexamethasone resistance in vitro and in vivo. We demonstrate that cAMP signaling synergizes with dexamethasone to enhance cell death in GC-resistant human T-ALL cells. We find the E prostanoid receptor 4 expressed in T-ALL samples and demonstrate that prostaglandin E2 (PGE2) increases intracellular cAMP, potentiates GC-induced gene expression, and sensitizes human T-ALL samples to dexamethasone in vitro and in vivo. These findings identify PGE2 as a target for GC resensitization in relapsed pediatric T-ALL.


Storage of human corneas in dextran and chondroitin sulfate-based corneal storage medium: changes in stromal free sodium.
To evaluate the hydration and the levels of free and total sodium in human corneal stromata preserved for up to 21 days in a dextran and chondroitin sulfate-based corneal storage medium (Optisol-GS, Chiron IntraOptics, Irvine, Calif) and to evaluate the effect of epithelial removal on stromal sodium and hydration parameters. Stromal hydration was evaluated thermogravimetrically. A sodium-specific electrode and an atomic absorption spectrophotometer were used to determine the amounts of free and of total stromal sodium, respectively, of preserved human corneas. In 50% of the corneas, the epithelium was removed prior to placement in the storage medium. After 3, 7, 14, or 21 days at 4 degrees C, corneas were removed from the storage medium and sodium measurements were taken. In corneas with an intact epithelium, the stromal hydration as well as the stromal free sodium and total sodium levels were relatively constant up to 21 days of storage in the preservation medium. In the absence of the epithelium, the water and sodium contents of the stroma increased significantly during storage. The presence of an intact epithelium is required for maintaining the hydration and sodium levels within the corneal stroma during storage. Removal of the epithelium prior to storage results in increased sodium values and hydration, which may affect postkeratoplasty deturgescence.


Long-term benefit sustained after bilateral pallidal deep brain stimulation in patients with refractory tardive dystonia.
Tardive dystonia (TD) can be a highly disabling, permanent condition related to the use of dopamine-receptor-blocking medications. Our aim was to evaluate the long-term effect of bilateral pallidal deep brain stimulation (DBS) for TD. Five consecutive patients with disabling TD who underwent stereotactic placement of bilateral globus pallidus internus DBS leads were included. All patients had a history of mood disorder or schizophrenia previously treated with neuroleptic medication, with a mean duration of motor symptoms of 10.2 years. Dystonia severity was measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score by a blinded neurologist reviewing pre- and postoperative videotaped examinations. The mean baseline movement BFMDRS score was 49.7 (range 20-88). Overall, we observed a mean reduction of 62% in the BFMDRS movement score within the first year after surgery. Persistent improvement in dystonia (71%) was seen at the last follow-up ranging from 2 to 8 years after surgery. Our experience suggests that pallidal DBS can be an effective therapy with long-term benefits for patients with TD.


Rebalance Without the Balance: A Research Note on the Availability of Community-Based Services in Areas Where Nursing Homes Have Closed.
Policies to "rebalance" funding away from nursing homes and toward home and community-based services (HCBS) have encouraged national trends of nursing home closure and an expansion of the HCBS industry. These changes are unfolding without a clear understanding of what services are available at the local level. The purpose of this study was: (1) to describe the current distribution of community-based services (CBS) in areas where nursing homes have closed and (2) to examine differences in availability of CBS using local market and population characteristics as regressors in a multinomial logistic model. We collected data on and geocoded CBS facilities and then used ArcGIS to define a 5-mile radius around all nursing homes that closed between 2006 and 2010 and compared these local market areas. In rural areas, availability of CBS does not appear to compensate for nursing home closures. Policies encouraging HCBS may be outpacing availability of CBS, especially in rural areas.


The vitamin D-responsive element in the rat bone Gla protein gene is an imperfect direct repeat that cooperates with other cis-elements in 1,25-dihydroxyvitamin D3- mediated transcriptional activation.
The gene for rat bone gla protein (BGP) was isolated and 1250 basepairs (bp), including 1100 bp of 5' flanking DNA, were placed up-stream of the human GH reporter gene. After transient transfection into the osteoblast-like rat osteosarcoma cell line ROS 17/2.8, the BGP promoter demonstrated a low level of basal activity that was increased approximately 10-fold by the addition of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. A single 250-bp fragment (-523 to -274) was sufficient to confer hormone inducibility upon both heterologous and homologous promoters. Deletion studies, complemented by evaluation with synthetic oligomers, enabled localization of the 1,25-(OH)2D3 response element to within 19 bp (-456 to -438), containing an element with an imperfect direct repeat [GGTGA(N4)GGACA] and homology to other steroid-responsive elements. Gel retardation assays demonstrated that partially purified chick intestinal 1,25-(OH)2D3 receptor bound specifically and with high affinity to a DNA fragment containing the putative 1,25-(OH)2D3 response element, and this binding was perturbed by monoclonal antibodies to the 1,25-(OH)2D3 receptor. Surprisingly, the 250-bp fragment, when linked in an antisense orientation with respect to the BGP promoter, blocked basal and hormone-dependent gene expression. However, a 246-bp fragment 5' to the 250-bp element (-1100 to -855) restored 20-fold inducibility when linked to the first fragment in the same orientation, suggesting cooperativity between at least two elements to achieve the hormonal regulation observed in this gene.


Development of an AmpliSeqTM Panel for Next-Generation Sequencing of a Set of Genetic Predictors of Persisting Pain.
Background: Many gene variants modulate the individual perception of pain and possibly also its persistence. The limited selection of single functional variants is increasingly being replaced by analyses of the full coding and regulatory sequences of pain-relevant genes accessible by means of next generation sequencing (NGS). Methods: An NGS panel was created for a set of 77 human genes selected following different lines of evidence supporting their role in persisting pain. To address the role of these candidate genes, we established a sequencing assay based on a custom AmpliSeqTM panel to assess the exomic sequences in 72 subjects of Caucasian ethnicity. To identify the systems biology of the genes, the biological functions associated with these genes were assessed by means of a computational over-representation analysis. Results: Sequencing generated a median of 2.85 ⋅ 106 reads per run with a mean depth close to 200 reads, mean read length of 205 called bases and an average chip loading of 71%. A total of 3,185 genetic variants were called. A computational functional genomics analysis indicated that the proposed NGS gene panel covers biological processes identified previously as characterizing the functional genomics of persisting pain. Conclusion: Results of the NGS assay suggested that the produced nucleotide sequences are comparable to those earned with the classical Sanger sequencing technique. The assay is applicable for small to large-scale experimental setups to target the accessing of information about any nucleotide within the addressed genes in a study cohort.


Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy.
Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.


Systematic comparison of single-cell and single-nucleus RNA-sequencing methods.
The scale and capabilities of single-cell RNA-sequencing methods have expanded rapidly in recent years, enabling major discoveries and large-scale cell mapping efforts. However, these methods have not been systematically and comprehensively benchmarked. Here, we directly compare seven methods for single-cell and/or single-nucleus profiling-selecting representative methods based on their usage and our expertise and resources to prepare libraries-including two low-throughput and five high-throughput methods. We tested the methods on three types of samples: cell lines, peripheral blood mononuclear cells and brain tissue, generating 36 libraries in six separate experiments in a single center. To directly compare the methods and avoid processing differences introduced by the existing pipelines, we developed scumi, a flexible computational pipeline that can be used with any single-cell RNA-sequencing method. We evaluated the methods for both basic performance, such as the structure and alignment of reads, sensitivity and extent of multiplets, and for their ability to recover known biological information in the samples.


Recollection Bias and Its Underpinnings: Lessons from Terrorism Risk Assessments.
Recollection bias is the phenomenon whereby people who observe a highly unexpected event hold current risk beliefs about a similar event that are no higher than their recollection of their prior beliefs. This article replicates and extends the authors' previous study of recollection bias in relation to individuals' perceptions of the risks of terrorism attacks. Over 60% of respondents in a national U.S. sample of over 900 adults believe that the current risk of a future terrorist attack by either an airplane or in a public setting is no higher than they recall having believed, respectively, before the 9/11 attack and before the Boston Marathon bombing. By contrast, a rational Bayesian model would update to a higher currently assessed risk of these previously uncontemplated events. Recollection bias is a persistent trait: individuals who exhibited this bias for the 9/11 attack exhibited it for the Boston Marathon bombing. Only one-fifth of respondents are free of any type of recollection bias. Recollection bias is negatively correlated with absolute levels of risk belief. Recollection bias in relation to highly unexpected terrorist events-the belief that perceived risks did not increase after the surprise occurrence-dampens support for a variety of anti-terrorism measures, controlling for the level of risk beliefs and demographic factors. Persistent recollection bias for both 9/11 and the Boston Marathon bombing is especially influential in diminishing support for protective policy measures, such as surveillance cameras in public places. Given that public attitudes influence policy, educating the public about risk is critical.


The chemistry and biology of RNA editing by adenosine deaminases.
Deamination of adenosines within mRNAs catalyzed by ADAR enzymes generates inosines at the corresponding nucleotide positions. Since inosine is decoded as guanosine, this reaction can lead to codon changes and the introduction of amino acids into a gene product not encoded in the gene. Translation of the different coding strands created by this process leads to protein structural diversity in the parent organism and is necessary for nervous system function in metazoa. The basis for selective editing of adenosines within certain codons is not well understood at the structural/biochemical level. Here we describe the use of synthetic nucleoside analogs incorporated into RNA editing substrates via the protected phosphoramidites to define aspects of the editing reaction mechanism and to carry out mechanism-based trapping of ADAR-RNA complexes. In addition, a high-throughput screen has been developed capable of rapidly identifying functional editing systems.


A literature review of anthropometric studies of school students for ergonomics purposes: Are accuracy, precision and reliability being considered?
Despite offering many benefits, direct manual anthropometric measurement method can be problematic due to their vulnerability to measurement errors. The purpose of this literature review was to determine, whether or not the currently published anthropometric studies of school children, related to ergonomics, mentioned or evaluated the variables precision, reliability or accuracy in the direct manual measurement method. Two bibliographic databases, and the bibliographic references of all the selected papers were used for finding relevant published papers in the fields considered in this study. Forty-six (46) studies met the criteria previously defined for this literature review. However, only ten (10) studies mentioned at least one of the analyzed variables, and none has evaluated all of them. Only reliability was assessed by three papers. Moreover, in what regards the factors that affect precision, reliability and accuracy, the reviewed papers presented large differences. This was particularly clear in the instruments used for the measurements, which were not consistent throughout the studies. Additionally, it was also clear that there was a lack of information regarding the evaluators' training and procedures for anthropometric data collection, which are assumed to be the most important issues that affect precision, reliability and accuracy. Based on the review of the literature, it was possible to conclude that the considered anthropometric studies had not focused their attention to the analysis of precision, reliability and accuracy of the manual measurement methods. Hence, and with the aim of avoiding measurement errors and misleading data, anthropometric studies should put more efforts and care on testing measurement error and defining the procedures used to collect anthropometric data.


Process variation in silicon photonic devices.
An array of passive silicon-on-insulator optical devices is laid out in repeating patterns on four foundry-fabricated wafers. The physical and optical characterization of these microrings, racetrack resonators, and directional couplers are found to exhibit significant variation in optical response. A device-heating experiment carried out on a number of different devices demonstrates that thermal effects are independent of the device's location on the wafer. An analysis of the variation of the optical responses of the room-temperature devices is used to determine the process variation. We find that if we form successive arrays of the values of a quantity of interest (the peak wavelength of a transfer function) at a single device at some point on the wafer, and then increase the size of the array by including the values of the devices at ever greater distances from the original, then the variance of the values of the successive arrays increases linearly with the linear extent of the sample. That is, the process variation exhibits "random walk" pattern with spatial extent. We express the process variation in units of variance per length and find that our measured values agree with others in the literature; that is, the process variation is approximately 1 nm2/cm.


Effect of phasic respiration on left ventricular dimension and performance in a normal population. An echocardiographic study.
Echocardiographic examination of the left ventricle (LV) in 30 normal subjects, 5 to 47 years of age, was performed in order to analyze the effects of phasic respiration on LV dimensions and derived LV function. Peak expiratory and peak inspiratory LV diastolic and systolic dimensions were measured and extrapolated to volume estimates using a standard formula. Although there was wide variation in the individual measurements, and particularly in systolic dimension, the mean peak inspiratory diastolic dimension, derived diastolic volume, and stroke volume all decreased significantly (P less than 0.001); a smaller decrease in ejection fraction was seen (P less than 0.02), while the changes in mean end-systolic dimension and end-systolic volume were not significant. While these observed changes may reflect a true physiologic variation, an artifactual component cannot be excluded. Regardless of their physiologic significance, however, these data show that the effect of phasic respiration is a factor to be considered in correlative echocardiographic studies of LV function in both normal and, possibly, pathologic cardiovascular conditions.


H-2-linked control of resistance to ectromelia virus infection in B10 congenic mice.
Several B10 strains of mice, recombinant at the H-2 locus, have been shown to differ in their resistance to infection with ectromelia virus, a natural mouse pathogen. Of 10 strains, B10, B10.A(2R), B10.A(4R) and B10.D2 were the most resistant, while B10.G and B10.A(5R) were the most susceptible. Other strains were intermediate between these extremes. Several genes conferring resistance have been mapped to Db in B10.A(2R), Kk I-Ak I-Bk in B10.A, I-Jb in B10.A(2R) and to Dd in B10.T(6R). In general, death among susceptible strains was not a consequence of acute liver necrosis as in other non-B10 strains, and occurred randomly from 8-14 days after infection. The exact cause of death is unknown but is characterized by persisting high titers of virus in the spleen and sometimes the liver, despite an ongoing immune response indicated by strong cytotoxic T-cell activity detectable in the spleens of all mice. The most resistant B10 and B10.A(2R) strains cleared virus from the spleen and liver by 8 days after infection. Analysis of infection in chimeric mice indicates that H-2 genes, which determine susceptibility to virus persistence in the spleen, operate via radiosensitive cells of the lymphomyeloid system. This evidence, together with several examples of H-2-linked differences in cytotoxic T-cell responsiveness between resistant and susceptible strains, is consistent with the hypothesis that the mechanism by which H-2 genes control resistance to ectromelia virus in B10 strain mice is by their influence on the effectiveness of a cell-mediated immune response.


Coffee Consumption and Colon Cancer Risk: A Meta- Epidemiological Study of Asian Cohort Studies.
A systematic review reported that coffee consumption would decrease risk of colon cancer in Asian women. But the systematic review arises the issue of duplication, so that a meta-epidemiological study was conducted. The selection criteria were defined that a prospective cohort follow-up study conducted to evaluate coffee consumption and risk of colon cancer in Asian and showed adjusted relative risk and its 95% confidence interval. In order to conduct meta-analysis, the highest versus lowest method was applied to extract relative risk and its 95% confidence intervals of the highest category. Random effect model was applied if I-squared value was over 50%. After avoiding duplication, 9 cohort data were selected for meta-analysis. The summary relative risk (and their 95% confidence intervals) [I-square value] were 0.90 (95% CI: 0.79-1.03) [0.0%] in men, and 0.64 (95% CI: 0.36-1.15) [65.9%] in women, respectively. The results suggest that coffee consumption is not associated with the risk of colon cancer in Asian men and women. The findings of this study are consistent with the results of two systematic reviews conducted under the same hypothesis and selection criteria. Additional epidemiological studies are needed for the inflection of colon cancer risk as the dose of coffee increases and the difference in the protective effect by sex.


Approaching the suicidal patient.
The suicide of a patient can be devastating to the family and to the family physician. The patient's death may shake the physician's confidence, undermine any willingness to work with patients with a mental illness, and provoke professional and legal review. In an attempt to help the family physician prevent suicide, this article reviews known risk factors and offers a strategy for assessing these factors in individual patients. The authors outline interventions that fit the existing level of risk and provide suggestions for the physician in the event of a completed suicide.


A game theoretic model of kleptoparasitism with strategic arrivals and departures of beetles at dung pats.
Dung beetles Onthophagus taurus lay their eggs in brood balls within dung pats. The dung that is used must be sufficiently fresh, and so beetles must keep moving from pat to pat to find fresh dung. If another beetle finds a brood ball it will usually eat the egg inside and lay its own egg in the brood ball instead of constructing its own ball. Thus, beetles will often stay near their eggs to guard them. We model a population of beetles where the times of arrival and departure from pats are strategic choices, and investigate optimal strategies depending upon environmental conditions, which can be reduced to two key parameters, the cost of brood ball construction and the ease of finding balls to parasitise. We predict that beetles should follow one of three distinct behaviors; stay in patches for only short periods, arrive late and be purely parasitic, remain in pats for longer periods in order to guard their brood balls. Under different conditions populations can consist of the first of these types only, a combination of the first and second types, or a combination of all three types.


High-protein-PUFA supplementation, red blood cell membranes, and plasma antioxidant activity in volleyball athletes.
The authors evaluated the role of a high-protein, low-calorie, polyunsaturated fatty-acid (PUFA) -supplemented diet on anthropometric parameters, erythrocyte-membrane fatty-acid composition, and plasma antioxidant defenses of nonprofessional volleyball athletes. The athletes were divided in two groups: One (n = 5) followed the Mediterranean diet, and the other (n = 6) followed a high-protein, low-calorie diet with a 3-g/day fish-oil supplementation. All the athletes had anthropometric measurements taken, both at the beginning and at the end of the study, which lasted for 2 months. Body-mass index and total body fat were significantly diminished in the second group, while they remained unchanged in the first. Plasma total antioxidant activity (TAA) was significantly increased in the plasma of both groups, with no differences between the groups, suggesting that physical activity, not the different diets, is the main contributor to the increase of plasma TAA. The second group showed a significant increase in erythrocyte-membrane PUFA content and in the unsaturation index value (UI) because of the fish-oil supplementation.A high-protein, low-carbohydrate, fish-oil-supplemented diet seems to be useful only when the aim of the diet is to obtain weight loss in a short-term period. The significant increase in the UI of erythrocyte membranes indicates the potential for harm, because a high intake of PUFA might increase susceptibility to lipid peroxidation not counterbalanced by a higher increase in TAA. Adherence to the Mediterranean diet seems to be the better choice.


Numbers of cortical vitreous cells and onset of cataracts in Royal College of surgeons rats.
Royal College of Surgeons (RCS) rats have hereditary retinal degeneration with associated posterior subcapsular opacities. A link between light, retinal degeneration, and cataracts may consist in peroxidation of polyunsaturated fatty acids of rod outer segment lipids to yield water-soluble toxic aldehydes that can traverse the vitreous and react with bow cells and posterior lens fibers. In an immune reaction to the retinal degeneration, macrophages multiply in the retina and in the cortex of the vitreous. In dystrophics, the cortical vitreous separates readily from attachments to retina, ciliary body and lens, and from the vitreous gel. This web-like structure was stained and spread on a counting chamber. Cells were counted at 15-130 postnatal days in pink- and black-eyed RCS dystrophics and in congenic controls to correlate numbers of cells, temporal and geographic patterns of retinal degeneration, and onset of opacities. Rats were reared in cyclic light (10-40 lux inside the cage) and fed a natural ingredient diet (NIH-07). Cortical vitreous cells increased markedly in pink- and black-eyed dystrophics at 50-53 days when slit-lamp detectable opacities occurred in both. The increase was 4.6-fold in pink- and 2.3-fold in black-eyed rats compared with controls. At 50-53 days, the dystrophy affected all quadrants of the retina severely in pink-eyed RCS but only the inferior periphery in black-eyed RCS. Consequently, severe degeneration in one quadrant may suffice to initiate an opacity.(ABSTRACT TRUNCATED AT 250 WORDS)


Lymphocytic bronchiolitis associated with HIV infection.
Patients with the acquired immune deficiency syndrome (AIDS) frequently develop interstitial lung disease. This is due most commonly to opportunistic infections, but malignancy and lymphocytic interstitial pneumonitis have also been associated with the syndrome. In contrast, there has been little reported about airways disease in patients with HIV infection. We describe a patient with AIDS-related complex who presented with symptoms and radiographic evidence of micronodular interstitial lung disease. Transbronchial biopsy revealed a lymphocytic bronchiolitis but no evidence of interstitial lung disease and a marked T-suppressor lymphocytosis was found on analysis of the bronchoalveolar lavage (BAL) specimen. Routine fungal, viral and bacterial cultures did not yield an etiologic agent. This case raises the possibility that lymphocytic bronchiolitis may represent another pulmonary manifestation of HIV infection.


The role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices.
In vivo fluorescence microscopy and electron cryo-tomography have revealed that chemoreceptors self-assemble into extended honeycomb lattices of chemoreceptor trimers with a well-defined relative orientation of trimers. The signaling response of the observed chemoreceptor lattices is remarkable for its extreme sensitivity, which relies crucially on cooperative interactions among chemoreceptor trimers. In common with other membrane proteins, chemoreceptor trimers are expected to deform the surrounding lipid bilayer, inducing membrane-mediated anisotropic interactions between neighboring trimers. Here we introduce a biophysical model of bilayer-chemoreceptor interactions, which allows us to quantify the role of membrane-mediated interactions in the assembly and architecture of chemoreceptor lattices. We find that, even in the absence of direct protein-protein interactions, membrane-mediated interactions can yield assembly of chemoreceptor lattices at very dilute trimer concentrations. The model correctly predicts the observed honeycomb architecture of chemoreceptor lattices as well as the observed relative orientation of chemoreceptor trimers, suggests a series of "gateway" states for chemoreceptor lattice assembly, and provides a simple mechanism for the localization of large chemoreceptor lattices to the cell poles. Our model of bilayer-chemoreceptor interactions also helps to explain the observed dependence of chemotactic signaling on lipid bilayer properties. Finally, we consider the possibility that membrane-mediated interactions might contribute to cooperativity among neighboring chemoreceptor trimers.


Transient Tear Film Dysfunction after Cataract Surgery in Diabetic Patients.
Diabetes mellitus is an increasingly common systemic disease. Many diabetic patients seek cataract surgery for a better visual acuity. Unlike in the general population, the influence of cataract surgery on tear film function in diabetic patients remains elusive. The aim of this study was to evaluate the tear function in diabetic and nondiabetic patients following cataract surgery. In this prospective, interventional case series, 174 diabetic patients without dry eye syndrome (DES) and 474 age-matched nondiabetic patients as control who underwent phacoemulsification were enrolled at two different eye centers between January 2011 and January 2013. Patients were followed up at baseline and at 7 days, 1 month, and 3 months postoperatively. Ocular symptom scores (Ocular Surface Disease Index, OSDI) and tear film function including tear film stability (tear film break-up time, TBUT), corneal epithelium integrity (corneal fluorescein staining, CFS), and tear secretion (Schirmer's I test, SIT) were evaluated. In total, 83.9% of the diabetic patients (146 cases with 185 eyes) and 89.0% of the nondiabetic patients (422 cases with 463 eyes) completed all check-ups after the interventions (P = 0.095). The incidence of DES was 17.1% in the diabetic patients and 8.1% in the nondiabetic patients at 7 days after cataract surgery. In the diabetic patients, the incidence of DES remained 4.8% at 1 month postoperatively and decreased to zero at 3 months after surgery. No DES was diagnosed in nondiabetic patients at either the 1-month or 3-month follow-up. Compared with the baseline, the diabetic patients had worse symptom scores and lower TBUT values at 7 days and 1 month but not at 3 months postoperatively. In the nondiabetic patients, symptom scores and TBUT values had returned to preoperative levels at 1-month check-up. CFS scores and SIT values did not change significantly postoperatively in either group (P = 0.916 and P = 0.964, respectively). Diabetic patients undergoing cataract surgery are prone to DES. Ocular symptoms and tear film stability are transiently worsened in diabetic patients and are restored more slowly than those in nondiabetic patients.


Epimetheus - a multi-profile normalizer for epigenomic sequencing data.
Exponentially increasing numbers of NGS-based epigenomic datasets in public repositories like GEO constitute an enormous source of information that is invaluable for integrative and comparative studies of gene regulatory mechanisms. One of today's challenges for such studies is to identify functionally informative local and global patterns of chromatin states in order to describe the regulatory impact of the epigenome in normal cell physiology and in case of pathological aberrations. Critically, the most preferred Chromatin ImmunoPrecipitation-Sequencing (ChIP-Seq) is inherently prone to significant variability between assays, which poses significant challenge on comparative studies. One challenge concerns data normalization to adjust sequencing depth variation. Currently existing tools either apply linear scaling corrections and/or are restricted to specific genomic regions, which can be prone to biases. To overcome these restrictions without any external biases, we developed Epimetheus, a genome-wide quantile-based multi-profile normalization tool for histone modification data and related datasets. Epimetheus has been successfully used to normalize epigenomics data in previous studies on X inactivation in breast cancer and in integrative studies of neuronal cell fate acquisition and tumorigenic transformation; Epimetheus is freely available to the scientific community.


Apollo 14 active seismic experiment.
Explosion seismic refraction data indicate that the lunar near-surface rocks at the Apollo 14 site consist of a regolith 8.5 meters thick and characterized by a compressional wave velocity of 104 meters per second. The regolith is underlain by a layer with a compressional wave velocity of 299 meters per second. The thickness of this layer, which we interpret to be the Fra Mauro Formation, is between 16 and 76 meters. The layer immediately beneath this has a velocity greater than 370 meters per second. We found no evidence of permafrost.


Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia.
Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged V(H)DJ(H) and V(L)J(L) genes of 25 non-IgM-producing B-CLL cases, we found five IgG(+) cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb's reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG(+) B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both.


Asthma control and adherence in newly diagnosed young and elderly adult patients with asthma in Turkey.
This study aimed to evaluate the factors that affect asthma control and adherence to treatment in newly diagnosed elderly asthmatics in Turkey compared with younger patients. This real-life prospective observational cohort study was conducted at 136 centers. A web-based questionnaire was administered to the patients who were followed up for 12 months. Analysis included 1037 young adult asthma patients (age <65 years) and 79 elderly asthma patients (age ≥65 years). The percentage of patients with total control in the elderly and young groups were 33.9% and 37.1% at visit 1, 20.0% and 42.1% (p = 0.012) at visit 2, and 50.0% and 49.8% at visit 3, respectively. Adherence to treatment was similar for both groups. Visit compliance was better in the elderly group than in the young group at visit 1 (72.2% vs. 60.8%, p = 0.045), visit 2 (51.9% vs. 34.9%, p = 0.002), and visit 3 (32.9% vs. 19.4%, p = 0.004). Adherence to treatment increased with asthma control in both groups (both p < 0.001) but decreased with the presence of gastritis/ulcer, gastroesophageal reflux, and coronary artery disease in the elderly. Asthma control and adherence to treatment were similar for the elderly and young asthma patients, though the follow-up rate was lower in young patients. The presence of gastritis/ulcer, gastroesophageal reflux and coronary artery disease had negative impacts on the adherence to treatment in elderly adult patients.


A proteomic approach to study parathyroid glands.
Parathyroid tumours are heterogeneous and in some cases the diagnosis may be difficult using histological features. In this study we used a two-dimensional electrophoresis (2D)/mass spectrometry (MS)-based approach to examine the global changes of parathyroid adenoma tissues protein profile compared to the parathyroid normal tissues. Validation of protein expression was performed by immunoblotting using specific antibodies. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network. A total of 30 proteins were found to be differentially expressed, of which 22 resulted in being over-expressed. Proteins identified by 2D/MS/MS proteomics were classified into functional categories and a major change (≥ 2-fold) in terms of expression was found in proteins involved in response to biotic stimuli, cell organization and signal transduction. After Ingenuity analysis, 14-3-3 ζ/δ appears to be a key protein in the network of parathyroid adenoma, where it is linked to other proteins such as annexin A2, B box and SPRY domain-containing protein (BSPRY), p53 and epidermal growth factor receptor (EGFR). Our results suggest that the proteomic approach was able to differentiate the protein profiles of normal parathyroid and parathyroid adenoma and identify a panel of proteins which are differentially expressed. The functional role of these proteins in the network of intracellular pathways is discussed.


Bioelectrical Impedance Analysis Overestimates Fat-Free Mass in Breast Cancer Patients Undergoing Treatment.
Bioelectrical impedance analysis (BIA) is commonly used to assess fat-free mass (FFM) and fat mass (FM) in breast cancer patients. However, because of the prevalence of overweight, obesity and variable hydration status in these patients, assumptions for existing prediction equations developed in healthy adults may be violated, resulting in inaccurate body composition assessment. We measured whole-body FFM using single-frequency BIA (50 kHz) and dual-energy x-ray absorptiometry (DXA) in 48 patients undergoing treatment for breast cancer. We applied raw BIA data to 18 previously published FFM prediction equations (FFMBIA ) and compared these estimates to DXA (FFMDXA ; reference method). On average, patients were 52 ± 10 (mean ± SD) years of age and overweight (body mass index: 27.5 ± 5.5 kg/m2 ; body fat by DXA: 40.1% ± 6.6%). Relative to DXA, BIA overestimated FFM by 4.1 ± 3.4 kg (FFMDXA : 42.0 ± 5.9 kg; FFMBIA : 46.1 ± 3.4 kg). Individual equation-generated predictions of FFMBIA ranged from 39.6 ± 6.7 to 52.2 ± 5.6 kg, with 16 equations overestimating and 2 equations underestimating FFMBIA compared with FFMDXA . Based on equivalence testing, no equation-generated estimates were equivalent to DXA. Compared with DXA, BIA overestimated FFM in breast cancer patients during treatment. Although several equations performed better than others, none produced values that aligned closely with DXA. Caution should be used when interpreting BIA measurements in this clinical population, and future studies should develop prediction equations specific to breast cancer patients.


Global myeloma research clusters, output, and citations: a bibliometric mapping and clustering analysis.
International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (>90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care.


Technical challenges of coronary CT angiography: today and tomorrow.
Rapid advancements in multidetector row computed tomography (MDCT) are beginning to revolutionise cardiac imaging applications. As a consequence, coronary CT angiography (CTA) is fast emerging as a highly effective, noninvasive imaging technique for the assessment of coronary artery disease (CAD). Technology is improving at a robust pace, which brings with it the benefits of superior spatial and temporal resolution as well as fast volume coverage, achieved through the development of systems with an increased number of detectors and shorter gantry rotation time, as well as the advent of systems equipped with dual-source X-ray tubes. The main power of CTA was thought to lie in its high negative predictive value in excluding coronary disease with a high degree of accuracy in patients with low probability for CAD. However, this rapid progress has meant that we are also adding to the growing list of additional potential applications of CTA that are possible with the technology. The aim of this review is to present an overview of the technical capabilities of cardiac MDCT relating to coronary CTA and other applications, the limitations of current technologies, as well as discuss political perspectives and how to address these in medical practice.


The influence of Eleuterococcus senticosus on cellular and humoral immunological response of mice.
The influence of Eleuterococcus senticosus on cellular and humoral immune response was evaluated. The experiments were performed on animal models (Balb/c mice and F1 crossbreeds Balb/cxC3H). It was shown that Eleuterococcus has immunomodulatory properties. This substance enhanced the cellular response of the mouse immunological system (chemokinetic activity of mice spleen cells, GvH reaction). A stimulatory effect of Eleuterococcus on the humoral response (antibody production) was also observed. Eleuterococcus did not augment the angiogenic activity of human renal carcinoma cells.


Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives.
Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a "quick and dirty" approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution.


Long-term survival after surgical management of neuroendocrine hepatic metastases.
Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases. Patients (n= 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival. The median age was 56.8 years (range 11.5-80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3-56.8, P= 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P approximately 0.8). Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival.


Chemotaxis in Rhodobacter sphaeroides requires an atypical histidine protein kinase.
Rhodobacter sphaeroides has a complex chemosensory system comprising two classic CheAs, two atypical CheAs, and eight response regulators (six CheYs and two CheBs). The classic CheAs, CheA(1) and CheA(2), have similar domain structures to Escherichia coli CheA, whereas the atypical CheAs, CheA(3) and CheA(4), lack some of the domains found in E. coli CheA. CheA(2), CheA(3), and CheA(4) are all essential for chemotaxis. Here we demonstrate that CheA(3) and CheA(4) are both unable to undergo ATP-dependent autophosphorylation, however, CheA(4) is able to phosphorylate CheA(3). The in vitro kinetics of this phosphorylation reaction were consistent with a reaction mechanism in which CheA(3) associates with a CheA(4) dimer forming a complex, CheA(3)A(4). To the best of our knowledge, CheA(3)A(4) is the first characterized histidine protein kinase where the subunits are encoded by distinct genes. Selective phosphotransfer was observed from CheA(3)-P to the response regulators CheY(1), CheY(6), and CheB(2). Using phosphorylation site and kinase domain mutants of CheA we show that phosphosignaling involving CheA(2), CheA(3), and CheA(4) is essential for chemotaxis in R. sphaeroides. Interestingly, CheA(3) was not phosphorylated in vitro by CheA(1) or CheA(2), although CheA(1) and CheA(2) mutants with defective kinase domains were phosphorylated by CheA(4). Because in vivo CheA(3) and CheA(4) localize to the cytoplasmic chemotaxis cluster, while CheA(2) localizes to the polar chemotaxis cluster, it is likely that the physical separation of CheA(2) and CheA(4) prevents unwanted cross-talk between these CheAs.


From Perception to Metacognition: Auditory and Olfactory Functions in Early Blind, Late Blind, and Sighted Individuals.
Although evidence is mixed, studies have shown that blind individuals perform better than sighted at specific auditory, tactile, and chemosensory tasks. However, few studies have assessed blind and sighted individuals across different sensory modalities in the same study. We tested early blind (n = 15), late blind (n = 15), and sighted (n = 30) participants with analogous olfactory and auditory tests in absolute threshold, discrimination, identification, episodic recognition, and metacognitive ability. Although the multivariate analysis of variance (MANOVA) showed no overall effect of blindness and no interaction with modality, follow-up between-group contrasts indicated a blind-over-sighted advantage in auditory episodic recognition, that was most pronounced in early blind individuals. In contrast to the auditory modality, there was no empirical support for compensatory effects in any of the olfactory tasks. There was no conclusive evidence for group differences in metacognitive ability to predict episodic recognition performance. Taken together, the results showed no evidence of an overall superior performance in blind relative sighted individuals across olfactory and auditory functions, although early blind individuals exceled in episodic auditory recognition memory. This observation may be related to an experience-induced increase in auditory attentional capacity.


Quantifying invasion resistance: the use of recruitment functions to control for propagule pressure.
Invasive species distributions tend to be biased towards some habitats compared to others due to the combined effects of habitat-specific resistance to invasion and non-uniform propagule pressure. These two factors may also interact, with habitat resistance varying as a function of propagule supply rate. Recruitment experiments, in which the number of individuals recruiting into a population is measured under different propagule supply rates, can help us understand these interactions and quantify habitat resistance to invasion while controlling for variation in propagule supply rate. Here, we constructed recruitment functions for the invasive herb Hieracium lepidulum by sowing seeds at five different densities into six different habitat types in New Zealand's Southern Alps repeated over two successive years, and monitored seedling recruitment and survival over a four year period. We fitted recruitment functions that allowed us to estimate the total number of safe sites available for plants to occupy, which we used as a measure of invasion resistance, and tested several hypotheses concerning how invasion resistance differed among habitats and over time. We found significant differences in levels of H. lepidulum recruitment among habitats, which did not match the species' current distribution in the landscape. Local biotic and abiotic characteristics helped explain some of the between-habitat variation, with vascular plant species richness, vascular plant cover, and light availability, all positively correlated with the number of safe sites for recruitment. Resistance also varied over time however, with cohorts sown in successive years showing different levels of recruitment in some habitats but not others. These results show that recruitment functions can be used to quantify habitat resistance to invasion and to identify potential mechanisms of invasion resistance.


A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.
How Canadian practitioners are managing the hypertensive disorders of pregnancy (HDP) is not known, particularly in relation to the 1997 guidelines published by the Canadian Hypertension Society (CHS). A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferroni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. For all types of HDP, most internists, family doctors, and midwives initiate nonpharmacological therapy (most common advice to quit work) at dBP 80-89 mmHg (i.e., primary prevention). Only for preeclampsia do obstetricians most frequently use this threshold; otherwise, dBP 90-99 mmHg is usually chosen. For nonsevere hypertension, antihypertensive drug therapy (most commonly methyldopa or labetalol) is started by most practitioners at dBP 90-99 mmHg, although obstetricians are more likely to choose a higher threshold (p < 0.0001). There is little agreement about dBP treatment goal; most internists and family doctors normalize dBP, whereas obstetricians appear to be divided on dBP goals of 80-89 (46-51%) vs. 90-99 mmHg (41-44%) for all HDP (p = 0.66). Severe hypertension is commonly treated with parenteral hydralazine, labetalol, or magnesium sulphate. Short-acting or sustained release nifedipine is used rarely/never by most practitioners. Approximately one-third of obstetricians and family doctors use diazepam to treat eclampsia. The vast majority use MgSO4 prophylactically in women with preeclampsia. This survey has clarified current stated management of women with HDP, and identified the need for both research into the dBP treatment goal that optimizes pregnancy outcomes among women with HDP, and translation of definitive studies into clinical practice.


Psychophysiological stress induces heat shock cognate protein (HSC) 70 mRNA in the cerebral cortex and stomach of rats.
Families of 70 kDa heat shock proteins have essential roles in cellular coping to noxious stimuli. However, their roles in psychophysiological stress have not been precisely clarified. We tested our hypothesis that heat shock cognate protein (HSC)70 messenger RNA would increase in stress-vulnerable organs under psychophysiological stress. In control rats, cerebral HSC70 mRNAs were constitutively expressed while gastric HSC70 mRNAs were scarcely identified. Restraint-water immersion stress significantly increased the level of cerebral HSC70 mRNAs for 6 h and 12 h. Stress for 6 h with recovery for 6 h induced more gastric HSC70 mRNA levels than that without recovery, while stress for 12 h expressed the highest gastric HSC70 mRNA levels. Hypothermia, induced by water immersion, excluded a possible role of hyperthermia in inducing HSC70 mRNA. Our results point to a crucial cytoprotective role for families of heat shock proteins in stress-vulnerable brain-gut link in mammals under psychophysiological stress.


Biliary atresia.
Biliary atresia (BA) is a cholangiodestructive disease affecting biliary tract, which ultimately leads to cirrhosis, liver failure and death if not treated. The incidence is higher in Asian countries than in Europe. Up to 10% of cases have other congenital anomalies, such as polysplenia, asplenia, situs inversus, absence of inferior vena cava and pre-duodenal portal vein, for which we have coined the term Biliary Atresia Splenic Malformation (BASM) syndrome. For these infants the aetiology lies within the first trimester of gestation. For others affected with BA, aetiology is more obscure and perinatal destruction of fully-formed ducts perhaps by the action of hepatotropic viruses has been suggested. Whatever the cause, the lumen of the extrahepatic duct is obliterated at a variable level and this forms the basis for the commonest classification (Types I, II, III). All patients with BA present with varying degree of conjugated jaundice, pale non-pigmented stools and dark urine. Key diagnostic tests include ultrasonography, biochemical liver function tests, viral serology, and (in our centre) a percutaneous liver biopsy. In some centres, duodenal intubation and measurement of intralumenal bile is the norm. Currently BA is being managed in two stages. The first stage involves the Kasai operation, which essentially excises all extrahepatic biliary remnants leaving a transected portal plate, followed by biliary reconstruction using a Roux loop onto that plate as a portoenterostomy. If bile flow is not restored by Kasai procedure or life-threatening complications of cirrhosis ensue then consideration should be given to liver transplantation as a second stage. The outcome following the Kasai operation can be assessed in two ways: clearance of jaundice to normal values and the proportion who survive with their native liver. Clearance of jaundice (<2 mg/dL or <34 micromol/L) after Kasai has been reported to be around 60%, whereas five years survival with native liver ranges from 40% to 65%.


The TensorMol-0.1 model chemistry: a neural network augmented with long-range physics.
Traditional force fields cannot model chemical reactivity, and suffer from low generality without re-fitting. Neural network potentials promise to address these problems, offering energies and forces with near ab initio accuracy at low cost. However a data-driven approach is naturally inefficient for long-range interatomic forces that have simple physical formulas. In this manuscript we construct a hybrid model chemistry consisting of a nearsighted neural network potential with screened long-range electrostatic and van der Waals physics. This trained potential, simply dubbed "TensorMol-0.1", is offered in an open-source Python package capable of many of the simulation types commonly used to study chemistry: geometry optimizations, harmonic spectra, open or periodic molecular dynamics, Monte Carlo, and nudged elastic band calculations. We describe the robustness and speed of the package, demonstrating its millihartree accuracy and scalability to tens-of-thousands of atoms on ordinary laptops. We demonstrate the performance of the model by reproducing vibrational spectra, and simulating the molecular dynamics of a protein. Our comparisons with electronic structure theory and experimental data demonstrate that neural network molecular dynamics is poised to become an important tool for molecular simulation, lowering the resource barrier to simulating chemistry.


Does a favourable change in the living conditions of young Kenyans affect their body (morphological) structure?
The aim of this study is to describe changes in the body structure of young Kenyans as a result of an upturn in the living conditions. The analyzed changes in their body build were caused by regular lifestyle and nutrition. The research material was male youth aged between 18 and 26. All those young men were students of a basic vocational school in Nairobi (Kenya). The first research was carried out in 1999 (n=121), the second one (n=302) exactly 12 months later and at the same institution. Changes in the body structure were studied on 31 individuals, who were examined twice. The examined parameters included: body height, body weight, chest circumference, waist circumference and thigh circumference. Information was also collected on the period a given student had stayed at that institution, his tribal membership, the number of children in his household and his number in the sequence of births in his family. Also the date of birth (at least the year) was of significance. All the examined men, whose body structure changes were analyzed, belonged to the Bantu language group. The studied individuals were at an age when growth had already finished. A more significant increase was observed in body weight, waist and thigh circumference. A regular schedule of activities and meals served in the dormitory resulted in body weight changes in 87% of those individuals, who were reexamined. As the basic reason for the observed changes one can regard the improvement in the level of nutrition, which was described by the examined individuals as "good".


Ambulance clinicians' perceptions, assessment and management of frailty: thematic analysis of focus groups.
More than half of all patients attended by the South Western Ambulance Service NHS Foundation Trust are over the age of 65. In 2017, 62% of older patients who were the subject of a frailty assessment were believed to have at least mild frailty (1/5 of all patients). Frailty is an increasingly relevant concept/diagnosis and ambulance services are well positioned to identify frailty and influence the 'care pathways' through which patients are directed (thereby influencing health outcomes). Throughout the South Western Ambulance Service NHS Foundation Trust, a mandatory training session regarding frailty was delivered to clinical personnel in 2017 and frailty assessment tools are available on the electronic Patient Clinical Record. To explore and gain insight into the current knowledge, practice and attitudes of ambulance clinicians regarding frailty and patients with frailty. Two focus groups of ambulance clinicians (n = 8; n = 9) recruited from across the South Western Ambulance Service NHS Foundation Trust were held in October 2017. Focus group discussions were analysed thematically. Knowledge of conceptual models of frailty, appropriate assessment of patients with frailty and appropriate care pathways varied substantially among focus group participants. Completion of the 'Rockwood' Clinical Frailty Scale for relevant patients has become routine. However, conflicting opinions were expressed regarding the context and purpose of this. The Timed-Up-and-Go mobility assessment tool is also on the electronic Patient Clinical Record, but difficulties regarding its completion were expressed.Patient management strategies ranged from treatment options which the ambulance service can provide, to referrals to primary/community care which can support the management of patients in their homes, and options to refer patients directly to hospital units or specialists with the aim of facilitating appropriate assessment, treatment and discharge. Perceptions of limited availability and geographical variability regarding these referral pathways was a major feature of the discussions, raising questions regarding awareness, capacity, inter-professional relationships and patient choice. Knowledge, practice and attitudes of ambulance staff, with regard to frailty, varied widely. This reflected the emerging nature of the condition, both academically and clinically, within the ambulance profession and the wider healthcare system.


Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis.
This study was conducted to investigate the chemical component of the hot water (HW) fraction of mycelia of Cordyceps sinensis and its antifatigue and antistress effect against a stimulus in vivo using rats and mice. The growth of mycelia reached a maximum level of 31.6 g/l after 120 h of incubation. The main chemical composition of the HW fraction of mycelia of C. sinensis was found to be carbohydrate (78.9%) with 5% moisture. The swimming endurance capacity of mice orally administered with the HW fraction (150 and 300 mg/kg/d, respectively) was significantly prolonged from 75 to 90 min with a lessening of fatigue. When the HW fraction (150 mg/kg/d) was given to rats for 8 d including a 48 h stress period, the weight changes of the adrenal gland, spleen, thymus, and thyroid, which is an index of stress, were suppressed. The HW fraction also significantly inhibited the increase in total cholesterol and the decrease in alkaline phosphatase levels as biochemical parameters of immobilization stress in rats.


The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases.
We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.


CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial cells.
The establishment and maintenance of epithelial polarity are crucial for tissue organization and function in mammals. Epithelial cadherin (E-cadherin) is expressed in epithelial cell membrane and is important for cell-cell adhesion, intercellular junctions formation, as well as epithelial cell polarization. We report herein that CAS (CAS/CSE 1), the human cellular apoptosis susceptibility protein, interacts with E-cadherin and stimulates polarization of HT-29 human colon epithelial cells. CAS binds with E-cadherin but not with beta-catenin in the immunoprecipitation assays. Interaction of CAS with E-cadherin enhances the formation of E-cadherin/beta-catenin cell-cell adhesive complex. Electron microscopic study demonstrated that CAS overexpression in cells stimulates intercellular junction complex formation. The disorganization of cellular cytoskeleton by cytochalasin D, colchicine, or acrylamide treatment disrupts CAS-stimulated HT-29 cell polarization. CAS-mediated HT-29 cell polarity is also inhibited by antisense E-cadherin DNA expression. Our results indicate that CAS cooperates with E-cadherin and plays a role in the establishment of epithelial cell polarity.


Quality of Health Insurance Coverage and Access to Care for Children in Low-Income Families.
An increasing diversity of children's health coverage options under the US Patient Protection and Affordable Care Act, together with uncertainty regarding reauthorization of the Children's Health Insurance Program (CHIP) beyond 2017, merits renewed attention on the quality of these options for children. To compare health care access, quality, and cost outcomes by insurance type (Medicaid, CHIP, private, and uninsured) for children in households with low to moderate incomes. A repeated cross-sectional analysis was conducted using data from the 2003, 2007, and 2011-2012 US National Surveys of Children's Health, comprising 80,655 children 17 years or younger, weighted to 67 million children nationally, with household incomes between 100% and 300% of the federal poverty level. Multivariable logistic regression models compared caregiver-reported outcomes across insurance types. Analysis was conducted between July 14, 2014, and May 6, 2015. Insurance type was ascertained using a caregiver-reported measure of insurance status and each household's poverty status (percentage of the federal poverty level). Caregiver-reported outcomes related to access to primary and specialty care, unmet needs, out-of-pocket costs, care coordination, and satisfaction with care. Among the 80,655 children, 51,123 (57.3%) had private insurance, 11,853 (13.6%) had Medicaid, 9554 (18.4%) had CHIP, and 8125 (10.8%) were uninsured. In a multivariable logistic regression model (with results reported as adjusted probabilities [95% CIs]), children insured by Medicaid and CHIP were significantly more likely to receive a preventive medical (Medicaid, 88% [86%-89%]; P < .01; CHIP, 88% [87%-89%]; P < .01) and dental (Medicaid, 80% [78%-81%]; P < .01; CHIP, 77% [76%-79%]; P < .01) visits than were privately insured children (medical, 83% [82%-84%]; dental, 73% [72%-74%]). Children with all insurance types experienced challenges in access to specialty care, with caregivers of children insured by CHIP reporting the highest rates of difficulty accessing specialty care (28% [24%-32%]), problems obtaining a referral (23% [18%-29%]), and frustration obtaining health care services (26% [23%-28%]). These challenges were also magnified for privately insured children with special health care needs, whose caregivers reported significantly greater problems accessing specialty care (29% [26%-33%]) and frustration obtaining health care services (36% [32%-41%]) than did caregivers of children insured by Medicaid, and a lower likelihood of insurance always meeting the child's needs (63% [60%-67%]) than children insured by Medicaid or CHIP. Caregivers of privately insured children were also significantly more likely to experience out-of-pocket costs (77% [75%-78%]) than were caregivers of children insured by Medicaid (26% [23%-28%]; P < .01) or CHIP (38% [35%-40%]; P < .01). This examination of caregiver experiences across insurance types revealed important differences that can help guide future policymaking regarding coverage for families with low to moderate incomes.


Age-dependent changes in mitochondrial morphology and volume are not predictors of lifespan.
Mitochondrial dysfunction is a hallmark of skeletal muscle degeneration during aging. One mechanism through which mitochondrial dysfunction can be caused is through changes in mitochondrial morphology. To determine the role of mitochondrial morphology changes in age-dependent mitochondrial dysfunction, we studied mitochondrial morphology in body wall muscles of the nematodeC. elegans. We found that in this tissue, animals display a tubular mitochondrial network, which fragments with increasing age. This fragmentation is accompanied by a decrease in mitochondrial volume. Mitochondrial fragmentation and volume loss occur faster under conditions that shorten lifespan and occur slower under conditions that increase lifespan. However, neither mitochondrial morphology nor mitochondrial volume of five- and seven-day old wild-type animals can be used to predict individual lifespan. Our results indicate that while mitochondria in body wall muscles undergo age-dependent fragmentation and a loss in volume, these changes are not the cause of aging but rather a consequence of the aging process.


Beyond a code of ethics: phenomenological ethics for everyday practice.
Physical therapy, like all health-care professions, governs itself through a code of ethics that defines its obligations of professional behaviours. The code of ethics provides professions with a consistent and common moral language and principled guidelines for ethical actions. Yet, and as argued in this paper, professional codes of ethics have limits applied to ethical decision-making in the presence of ethical dilemmas. Part of the limitations of the codes of ethics is that there is no particular hierarchy of principles that govern in all situations. Instead, the exigencies of clinical practice, the particularities of individual patient's illness experiences and the transformative nature of chronic illnesses and disabilities often obscure the ethical concerns and issues embedded in concrete situations. Consistent with models of expert practice, and with contemporary models of patient-centred care, we advocate and describe in this paper a type of interpretative and narrative approach to moral practice and ethical decision-making based on phenomenology. The tools of phenomenology that are well defined in research are applied and examined in a case that illustrates their use in uncovering the values and ethical concerns of a patient. Based on the deconstruction of this case on a phenomenologist approach, we illustrate how such approaches for ethical understanding can help assist clinicians and educators in applying principles within the context and needs of each patient.


Tissue-specific expression of the rat beta-casein gene in transgenic mice.
The rat beta-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage- and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat beta-casein gene with 3.5 kb of 5' and 3.0 kb of 3' flanking DNA was microinjected into the germline of mice. Eight F0 transgenic mice were generated with copy numbers ranging from 1-10; five transmitted the transgene to their offspring in a Mendelian pattern. A specific RNase protection assay was developed to quantitate the level of expression of the rat beta-casein transgene as compared to the endogenous mouse beta-casein gene. Using this assay expression was demonstrated predominantly in the lactating mammary gland of transgenic mice at a level of 0.01-1% of the endogenous mouse beta-casein gene. The transgene employed the authentic transcription initiation site observed previously in the analogous rat beta-casein gene. In one line, a reduced level of expression of the transgene was also observed in the brain. The site of integration, therefore, plays an important role in influencing the level of expression of the transgene, but not its general pattern of tissue-specificity. The transgene appears to be developmentally-regulated in accordance with the endogenous mouse beta-casein gene. These lines of mice generated carrying the rat beta-casein transgene should provide useful models for studying the developmental and hormonal regulation of milk protein gene expression.


Oral Administration of Tualang and Manuka Honeys Modulates Breast Cancer Progression in Sprague-Dawley Rats Model.
Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.


Sarcoptes scabiei mites modulate gene expression in human skin equivalents.
The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin's protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host's protective response allowing these mites to survive in the skin.


Radioprotective Effect of Sodium Selenite on Mandible of Irradiated Rats.
The purpose of this study was to test the radioprotective effect of selenium in the bone microarchitecture of irradiated rats mandibles. Forty rats were separated into 4 groups with 10 animals: control group (CG), irradiated group (IG), sodium selenite group (SSG) and sodium selenite irradiated group (SSIG). A single dose of 0.8 mg/kg sodium selenite was administered intraperitoneally in the SSG and SSIG groups. One hour later, animals of IG and SSIG groups were irradiated with 15 Gy of x-rays. Forty days after radiation a bilateral extraction of the mandibular first molars was performed. After the extraction procedure, five rats were killed after fifteen days and others five after thirty days. Micro- computed tomography was used to evaluate cortical and trabecular bone of each rat. The mean and standard deviation of each bone microarchitecture parameter were analyzed using the statistical test of two-way Analysis of Variance (ANOVA). At 15 days, the bone volume presented higher values in the CG and SSG groups (p=0.001). The same groups presented statistically significant higher values when bone volume fraction (p<0.001) and trabecular thickness (p<0.001) were analyzed. At 30 days, it was observed that in relation to the bone volume fraction, SSG group presented the highest value while SSIG group had the lowest value, with statistically significant difference (p=0.016). Sodium selenite demonstrated a median radioprotective effect in the bone microarchitecture of irradiated mandibles, which indicates the substance may be a potential radioprotective agent against chronic effects of high doses of ionizing radiation.


Kinetics of organic matter and ammonia removal in horizontal reed beds treating wastewater in Nepal.
In Nepal, both horizontal bed and vertical bed subsurface flow constructed wetlands have been used for wastewater treatment. However, these units were designed based on the empirical findings from other countries. The rational design criteria developed so far has some limitations as the performance of the units is sensitive to the behaviour of the microorganisms, climatic conditions and other attributes pertaining to the local contexts. Secondly, only limited numbers of studies have been carried out to assess the performance of these systems leading to the development of rationale design criteria. Considering these facts, the major objectives of the study were set to: (1) evaluate the performance of the subsurface flow reed bed system in terms of organic matter and ammonia removal; (2) estimate the reaction rate constant and effective specific surface area; (3) assess the relationship between performance and age of the system; and (4) investigate the dynamic behaviour of the reaction rate constant. The study was carried on three full-scale domestic wastewater treatment units and one pilot-scale ranging the age of horizontal beds from 1 to 5 years.


Carcinogenesis Bioassay of C.I. Solvent Yellow 14 (CAS No. 842-07-9) in F344/N Rats and B6C3F1 Mice (Feed Study).
A carcinogenesis bioassay of C.I. Solvent Yellow 14 (94.1% pure), a widely used monoazo dye, was conducted by feeding diets containing 250 or 500 ppm of C.I. Solvent Yellow 14 to groups of 50 F344 rats of either sex for 103 weeks. Similar groups of 50 B6C3F1 mice received diets containing 500 or 1,000 ppm of C.I. Solvent Yellow 14 for 103 weeks. Groups of 50 untreated rats and mice of either sex served as controls. Throughout the bioassay, mean body weights of dosed rats and mice were slightly lower than those of controls. No compound-related clinical signs or effects on survival were observed. Increases in nonneoplastic lesions included cardiac valve fibrosis for male and female rats, lymphoid hyperplasia of the lung for male rats, and for female rats, bile duct hyperplasia, focal atrophy of the pancreatic acinus, and nephropathy. None of these effects were observed in mice. Neoplastic nodules of the liver occurred in rats of either sex with a dose-related trend that was significant (male, P<0.001; female, P=0.005), and the incidences in the high-dose groups were significantly higher than those in the controls (male: control, 5/50; low-dose, 10/50; high-dose, 30/50, P<0.001 and female: control, 2/50; low-dose, 3/49; high-dose, 10/48, P=0.011). Lymphomas or leukemias occurred in low-dose female mice at an incidence significantly (P<0.05) higher than that in the controls (12/50, 23/50, 17/50). Because of the lack of a dose-related trend and because the incidence in the high-dose group was not significant, the association between the increased incidence of hematopoietic tumors in the low-dose group and the administration of C.I. Solvent Yellow 14 is not clearly established. The incidence of lymphomas or leukemias in male mice was higher (not statistically significant) than that in the corresponding controls (5/49, 10/50, 10/50); in both low-and high-dose rats of either sex the incidence was significantly (P<0.001) lower than that in controls. Under the conditions of this bioassay, C.I. Solvent Yellow 14 was carcinogenic in male and female F344/N rats, as evidenced by increased incidences of neoplastic nodules of the liver. C.I. Solvent Yellow 14 was not carcinogenic for B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Negative Female Mice: Negative Synonym: 1-(phenylazo)-2-naphthol


Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential.
Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180 degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP.


Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.
In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.