Feasibility study of asset mapping with children: identifying how the community environment shapes activity and food choices in Alexander First Nation.
It is estimated that First Nations children living on reserves are 4.5 times more likely to be obese than Canadian children in general. Many First Nations children living on reserves have limited healthy food and physical activity options. Understanding how community factors contribute to First Nations children's lifestyle choices is an understudied area of research. Furthermore, rarely has health research elicited First Nations children's perspectives of their communities. The purpose of this study was to understand the external behavior-shaping factors that influence the lifestyle behaviors of First Nations' children. Asset mapping with children was used to understand how community resources impacted children's activity and eating options. Alexander First Nation is in central Alberta. Asset mapping was one component of a research project in the community to identify risk factors for children developing diabetes. Participants were a convenience sample of two high school students working at the local health centre and seven grade six children. Maps, photographs, and a tour of the town site enabled participants to identify places and spaces where they were active or could obtain food. For each of these assets, a description of how it was used and how it could be modified for better usage was derived from notes and transcripts using content analysis. Assets were grouped into usage categories, which were then mapped onto a layout of the community and presented at a community meeting to address childhood obesity. Twenty-five places and spaces were identified as being activity or food related. Breakfast and/or lunch, concession foods (snack foods, eg chocolate bars, potato crisps) were obtained at school; meals and snack foods where cultural gatherings occur; and snack foods at the local store. Healthy food choices were limited. Children and youth were active at different locations in town, with only two spaces beyond the town site identified as locations for activity. Youth recommended the construction of a leisure centre, that healthier food be sold at the local convenience store, and the development of a community garden and berry farm. In the ecological framework, weight status is considered embedded within the larger ecology of individual lives because of interrelationships between an individual's personal dimensions and other components of an individual's external environment. Asset mapping with children and youth in Alexander First Nation helped to achieve an understanding of the community factors that shaped their health behaviors. Asset mapping not only produced a list of places and spaces where they played, met, and ate, but also showed where they most preferred to be. Further, the exercise enabled children to express how assets could be improved, and the assets they would like in their community, to promote healthy behaviors. The findings enabled adults to contextualize other community data collected about children (ie obesity prevalence, physical activity levels), to better understand how the presence and the condition of places and spaces in the community shaped the physical activity and eating behaviors of children and youth, and how local resources could be modified to be more health promoting.


"Are you at peace?": one item to probe spiritual concerns at the end of life.
Physicians may question their role in probing patients' spiritual distress and the practicality of addressing such issues in the time-limited clinical encounter. Yet, patients' spirituality often influences treatment choices during a course of serious illness. A practical, evidence-based approach to discussing spiritual concerns in a scope suitable to a physician-patient relationship may improve the quality of the clinical encounter. Analysis of the construct of being "at peace" using a sample of patients with advanced cancer, congestive heart failure, or chronic obstructive pulmonary disease. Descriptive statistics were used to compare response distributions among patient subgroups. Construct validity of the concept of being "at peace" was evaluated by examining Spearman rank correlations between the item and existing spirituality and quality-of-life subscales. Variation in patient responses was not explained by demographic categories or diagnosis, indicating broad applicability across patients. Construct validity showed that feeling at peace was strongly correlated with emotional and spiritual well-being. It was equally correlated with faith and purpose subscales, indicating applicability to traditional and nontraditional definitions of spirituality. Asking patients about the extent to which they are at peace offers a brief gateway to assessing spiritual concerns. Although these issues may be heightened at the end of life, research suggests they influence medical decision making throughout a lifetime of care.


Induction of non-lamellar phases in archaeal lipids at high temperature and high hydrostatic pressure by apolar polyisoprenoids.
It is now well established that cell membranes are much more than a barrier that separate the cytoplasm from the outside world. Regarding membrane's lipids and their self-assembling, the system is highly complex, for example, the cell membrane needs to adopt different curvatures to be functional. This is possible thanks to the presence of non-lamellar-forming lipids, which tend to curve the membrane. Here, we present the effect of squalane, an apolar isoprenoid molecule, on an archaea-like lipid membrane. The presence of this molecule provokes negative membrane curvature and forces lipids to self-assemble under inverted cubic and inverted hexagonal phases. Such non-lamellar phases are highly stable under a broad range of external extreme conditions, e.g. temperatures and high hydrostatic pressures, confirming that such apolar lipids could be included in the architecture of membranes arising from cells living under extreme environments.


Natural killer cell function is well preserved in asymptomatic human immunodeficiency virus type 2 (HIV-2) infection but similar to that of HIV-1 infection when CD4 T-cell counts fall.
Natural killer (NK) cells are potent effectors of natural immunity and their activity prevents human immunodeficiency virus type 1 (HIV-1) viral entry and viral replication. We sought to determine whether NK immune responses are associated with different clinical course of HIV-1 and HIV-2 infections. A cross-sectional analysis of NK cell responses was undertaken in 30 HIV-1 and 30 HIV-2 subjects in each of three categories of CD4(+)-T-cell counts (>500, 200 to 500, and <200 cells/microl) and in 50 HIV-uninfected control subjects. Lytic activity and gamma interferon (IFN-gamma) secretion were measured by chromium release and enzyme-linked immunospot assays, respectively. Flow cytometry was used to assess intracellular cytokines and chemokines. Levels of NK cytotoxicity were significantly higher in HIV-2 than in HIV-1 infections in subjects with high CD4(+)-T-cell counts and were similar to that of the healthy controls. In these HIV-2 subjects, cytolytic activity was positively correlated to NK cell count and inversely related to plasma viremia. Levels of intracellular MIP-1beta, RANTES, tumor necrosis factor alpha, and IFN-gamma produced by NK CD56(bright) cells were significantly higher in HIV-2- than HIV-1-infected subjects with high CD4(+)-T-cell counts but fell to similar levels as CD4 counts dropped. The data suggest efficient cytolytic and chemokine-suppressive activity of NK cells early in HIV-2 infection, which is associated with high CD4(+) T-cell counts. Enhancement of these functions may be important in immune-based therapy to control HIV disease.


The average human tooth lengths for black Kenyan population.
Measurement of tooth lengths was carried out on 537 extracted human teeth. The teeth were collected from adults aged 17 years and above and preserved in formalin. The tooth lengths were obtained by taking measurements off calibrated graph paper. The lengths obtained in this study were comparable to previous data reported in the literature. However, this new data will provide useful guidelines in Kenya for the management of endodontic patients especially in the purchase and stocking of the most appropriate endodontic instruments.


Diabetes and periodontal diseases: interplay and links.
The association between diabetes and periodontal diseases is well-established. Diabetes is a risk factor for periodontal disease, with diabetic patients exhibiting an increased prevalence, extent and severity of gingivitis and perio- dontitis compared to healthy adults. Several mechanisms involved in the pathogenesis of diabetes have also been associated with periodontal disease progression. It is recognized today that there is a bidirectional relationship between diabetes and periodontal disease, with recent research showing that periodontal disease may affect the metabolic control of diabetes in diabetic patients. In this review, we present the current knowledge of the interplay between periodontal diseases and diabetes through the evaluation of randomized control and longitudinal cohort studies published in the past 15 years. Current data support the conclusion that diabetic patients are at increased risk for periodontal diseases, and that patients with poorly controlled diabetes are at risk for severe periodontitis. This results in the destruction of oral connective tissue and generalized bone loss, leading ultimately to tooth loss. Although the effect of periodontal disease on glycemic control in type 1 diabetic patients is controversial, evidence does show a direct correlation between periodontal health and glycemic control in type 2 diabetic patients. Furthermore, several studies have demonstrated the beneficial effect of periodontal treatment on metabolic control of type 2 diabetic patients.


Experienced mental workload, perception of usability, their interaction and impact on task performance.
Past research in HCI has generated a number of procedures for assessing the usability of interacting systems. In these procedures there is a tendency to omit characteristics of the users, aspects of the context and peculiarities of the tasks. Building a cohesive model that incorporates these features is not obvious. A construct greatly invoked in Human Factors is human Mental Workload. Its assessment is fundamental for predicting human performance. Despite the several uses of Usability and Mental Workload, not much has been done to explore their relationship. This empirical research focused on I) the investigation of such a relationship and II) the investigation of the impact of the two constructs on human performance. A user study was carried out with participants executing a set of information-seeking tasks over three popular web-sites. A deep correlation analysis of usability and mental workload, by task, by user and by classes of objective task performance was done (I). A number of Supervised Machine Learning techniques based upon different learning strategy were employed for building models aimed at predicting classes of task performance (II). Findings strongly suggests that usability and mental workload are two non overlapping constructs and they can be jointly employed to greatly improve the prediction of human performance.


Host Specificity and Variations in Aggressiveness of North Carolina Isolates of Phytophthora cryptogea and P. drechsleri in Greenhouse Ornamental Plants.
Three isolates of Phytophthora cryptogea and three isolates of P. drechsleri were evaluated for host specificity and variations in aggressiveness on eight floriculture crops commonly grown in North Carolina. Plants were monitored for the development of foliar symptoms stemming from root rot caused by Phytophthora. No isolates of P. cryptogea or P. drechsleri had the same host range, though all P. cryptogea isolates caused foliar symptoms on gerbera daisy and annual stock, and all P. drechsleri isolates incited disease on osteospermum. No African marigold plants developed foliar symptoms of Phytophthora root rot. All P. cryptogea isolates caused foliar symptoms on at least three tested plant species. Isolates of P. drechsleri varied from highly specific and only causing disease on a single host species to relatively nonspecific and causing foliar symptoms on the majority of host plants. This is the first report of host specificity of ornamental isolates of P. drechsleri, and several of the tested plants are not reported hosts of P. drechsleri. Differences in isolate aggressiveness were found and depended on plant species; overall, isolates of P. drechsleri were more aggressive than P. cryptogea isolates. Isolations from nonsymptomatic inoculated plants suggest that these Phytophthora spp. could be moved between growers or from growers to consumers on nonsymptomatic infected ornamentals.


Dynamics of wetting: from inertial spreading to viscous imbibition.
We report the influence of the nature of boundaries on the dynamics of wetting. We review some work recently published and highlight new experimental observations. Our paper begins with the spreading of drops on substrates and demonstrates how the exponents of the spreading laws are affected either by the surface chemistry or by the droplet shape. We then discuss the imbibition of completely and partially wetting fluids into channels and over microtextured surfaces. Starting with the one-dimensional imbibition of completely wetting liquids in tubes and surface textures, we show that (i) shape variations of channels change the power-law response of the imbibition and (ii) the geometrical parameters of a surface roughness change the spreading behavior. For partially wetting fluids, we observe directionally dependent spreading: polygonal wetted domains can be obtained. We conclude with a tabular summary of our findings, allowing us to draw connections between the different systems investigated, and shed light on open questions that remain to be addressed.


Outcomes associated with planned place of birth among women with low-risk pregnancies.
Previous studies have shown that planned home birth is associated with a decreased likelihood of intrapartum intervention with no difference in neonatal outcomes compared with planned hospital birth. The purpose of our study was to evaluate different birth settings by comparing neonatal mortality, morbidity and rates of birth interventions between planned home and planned hospital births in Ontario, Canada. We used a provincial database of all midwifery-booked pregnancies between 2006 and 2009 to compare women who planned home birth at the onset of labour to a matched cohort of women with low-risk pregnancies who had planned hospital births attended by midwives. We conducted subgroup analyses by parity. Our primary outcome was stillbirth, neonatal death (< 28 d) or serious morbidity (Apgar score < 4 at 5 min or resuscitation with positive pressure ventilation and cardiac compressions). We compared 11 493 planned home births and 11 493 planned hospital births. The risk of our primary outcome did not differ significantly by planned place of birth (relative risk [RR] 1.03, 95% confidence interval [CI] 0.68-1.55). These findings held true for both nulliparous (RR 1.04, 95% CI 0.62-1.73) and multiparous women (RR 1.00, 95% CI 0.49-2.05). All intrapartum interventions were lower among planned home births. Compared with planned hospital birth, planned home birth attended by midwives in a jurisdiction where home birth is well-integrated into the health care system was not associated with a difference in serious adverse neonatal outcomes but was associated with fewer intrapartum interventions.


The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency.
Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency. To evaluate the presence of immunodeficiency in a series of 6 patients with JS. Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry. Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found. Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS.


Long-term history and immediate preceding state affect EEG slow wave characteristics at NREM sleep onset in C57BL/6 mice.
The dynamics of cortical activity across the 24-h day and at vigilance state transitions is regulated by an interaction between global subcortical neuromodulatory influences and local shifts in network synchrony and excitability. To address the role of long-term and immediate preceding history in local and global cortical dynamics, we investigated cortical EEG recorded from both frontal and occipital regions during an undisturbed 24-h recording in mice. As expected, at the beginning of the light period, under physiologically increased sleep pressure, EEG slow waves were more frequent and had higher amplitude and slopes, compared to the rest of the light period. Within discrete NREM sleep episodes, the incidence, amplitude and slopes of individual slow waves increased progressively after episode onset in both derivations by approximately 10-30%. Interestingly, at the beginning of NREM sleep episodes slow waves in the frontal and occipital derivations frequently occurred in isolation, as quantified by longer latencies between consecutive slow waves in the two regions. Notably, slow waves during the initial period of NREM sleep following REM sleep episodes were significantly less frequent, lower in amplitude and exhibited shallower slopes, compared to those that occurred in NREM episodes after prolonged waking. Moreover, the latencies between consecutive frontal and occipital NREM slow waves were substantially longer when they occurred directly after REM sleep compared to following consolidated wakefulness. Overall these data reveal a complex picture, where both time of day and preceding state contribute to the characteristics and dynamics of slow waves within NREM sleep. These findings suggest that NREM sleep initiates in a more "local" fashion when it occurs following REM sleep episodes as opposed to sustained waking bouts. While the mechanisms and functional significance of such a re-setting of brain state after individual REM sleep episodes remains to be investigated, we suggest that it may be an essential feature of physiological sleep regulation.


Social Media Listening to Understand the Lived Experience of Presbyopia: Systematic Search and Content Analysis Study.
Presbyopia is defined as the age-related deterioration of near vision over time which is experienced in over 80% of people aged 40 years or older. Individuals with presbyopia have difficulty with tasks that rely on near vision. It is not currently possible to stop or reverse the aging process that causes presbyopia; generally, it is corrected with glasses, contact lenses, surgery, or the use of a magnifying glass. This study aimed to explore how individuals used social media to describe their experience of presbyopia with regard to the symptoms experienced and the impacts of presbyopia on their quality of life. Social media sources including Twitter, forums, blogs, and news outlets were searched using a predefined search string relating to symptoms and impacts of presbyopia. The data that were downloaded, based on the keywords, underwent manual review to identify relevant data points. Relevant posts were further manually analyzed through a process of data tagging, categorization, and clustering. Key themes relating to symptoms, impacts, treatment, and lived experiences were identified. A total of 4456 social media posts related to presbyopia were identified between May 2017 and August 2017. Using a random sampling methodology, we selected 2229 (50.0%) posts for manual review, with 1470 (65.9%) of these 2229 posts identified as relevant to the study objectives. Twitter was the most commonly used channel for discussions on presbyopia compared to forums and blogs. The majority of relevant posts originated in Spain (559/1470, 38.0%) and the United States (426/1470, 29.0%). Of the relevant posts, 270/1470 (18.4%) were categorized as posts written by individuals who have presbyopia, of which 37 of the 270 posts (13.7%) discussed symptoms. On social media, individuals with presbyopia most frequently reported experiencing difficulty reading small print (24/37, 64.9%), difficulty focusing on near objects (15/37, 40.5%), eye strain (12/37, 32.4%), headaches (9/37, 24.3%), and blurred vision (8/37, 21.6%). 81 of the 270 posts (30.0%) discussed impacts of presbyopia-emotional burden (57/81, 70.4%), functional or daily living impacts (46/81, 56.8%), such as difficulty reading (46/81, 56.8%) and using electronic devices (21/81, 25.9%), and impacts on work (3/81, 3.7%). Findings from this social media listening study provided insight into how people with presbyopia discuss their condition online and highlight the impact of presbyopia on individuals' quality of life. The social media listening methodology can be used to generate insights into the lived experience of a condition, but it is recommended that this research be combined with prospective qualitative research for added rigor and for confirmation of the relevance of the findings.


Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.
The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. None. Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4-18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.


SNAP-25a and -25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion.
The tSNARE (the target-membrane soluble NSF-attachment protein receptor, where NSF is N-ethylmaleimide-sensitive fusion protein) synaptosomal-associated protein of 25 kDa (SNAP-25) is expressed in pancreatic B-cells and its cleavage by botulinum neurotoxin E (BoNT/E) abolishes stimulated secretion of insulin. In the nervous system, two SNAP-25 isoforms (a and b) have been described that are produced by alternative splicing. Here it is shown, using reverse transcriptase PCR, that messages for both SNAP-25 isoforms are expressed in primary pancreatic B and non-B cells as well as in insulin-secreting cell lines. After transfection, both isoforms can be detected at the plasma membrane as well as in an intracellular perinuclear region in the insulin-secreting cell line, HIT. To test for the functional role of the two isoforms in insulin secretion, mutant forms of SNAP-25a and b resistant against cleavage by BoNT/E were generated. Such mutant SNAP-25, when expressed in HIT cells, is not inactivated by BoNT/E and its ability to restore insulin secretion can thus be investigated. To obtain the toxin-resistant mutant isoforms, the sequence around the BoNT/E cleavage site (R176QIDRIM182) was changed to P176QIKRIT182. This is the sequence of the equivalent region of human SNAP-23 (P187-T194), which has been shown to be resistant to BoNT/E. The mutant SNAP-25 was resistant to BoNT/E in vitro and in vivo and both mutant isoforms were able to reconstitute insulin secretion from toxin-treated HIT cells.


A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol.
The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Single-centre, single-blind, randomised controlled trial (RCT) stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response). A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed. The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed. Australian New Zealand Clinical Trials Registry ACTRN12610000332022.


Povidone-Iodine Irrigation of Subcutaneous Tissues May Decrease Surgical Site Infections in Elective Colorectal Operations: A Systematic Review.
Postoperative wound infection is the most common complication following abdominal surgery and leads to delayed wound healing, prolonged hospital length of stay (LOS), and causes morbidity. Povidone-Iodine (PVI) is a broad-spectrum anti-septic and disinfectant solution, and can be used intra-operatively to irrigate subcutaneous tissues prior to abdominal skin closure. We systematically reviewed the literature regarding the efficacy of intra-operative PVI irrigation of subcutaneous tissues following elective colorectal surgery. A comprehensive search of electronic databases and various grey literature sources was completed. Unpublished and non-English-language results were included. All clinical controlled trials involving PVI solution in adult colorectal surgery were included. Two independent reviewers assessed the studies for relevance, inclusion, methodological quality and extracted data from the full versions of the manuscripts. Disagreements were resolved by re-extraction or third party adjudication. Data for dichotomous outcomes are reported as relative risks (RR) with 95% confidence intervals (CI). For continuous data, mean differences (MD) are reported with 95% CIs. Five randomized controlled trials (RCTs) involving 205 patients comparing PVI solution or spray to a control group following abdominal fascial closure in elective colorectal or clean-contaminated operations were identified. Pooled results demonstrated a reduction in surgical site infection for patients treated with PVI (RR = 1.97; 95% CI: 1.22 to 3.17) compared to controls. Irrigation of subcutaneous tissues with PVI following abdominal fascial closure is associated with a reduced incidence of surgical site infection. Due to the small number of included trials and patients, additional robust randomized trials are needed.


Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status – The HUNT Study.
The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally. Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood. The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10(-4), adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10(-3), adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10(-4), adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10(-7), adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important. DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.


A rapid appraisal of the status of mental health support in post-rape care services in the Western Cape.
Despite the well-known impact of rape on mental health and the widespread problem of rape in South Africa, mental health services for rape victims are scant and not a priority for acute-phase services. Survivors encounter multiple mental health struggles in this period including adherence to the post-exposure prophylaxis drugs to prevent HIV and finding support from important others. We have little information on what mental health is provided, by whom and how it is integrated into the post-rape package of care. The aim of the study was to do a rapid appraisal of mental health services for rape survivors to gain a better understanding of the current acute and long-term (secondary) mental health services. We conducted a qualitative study using a rapid assessment with a purposive sample of 14 rape survivors and 43 service providers recruited from post-rape sexual assault services in urban and rural Western Cape Province. Data were collected using semi-structured in-depth interviews and observations of survivor sessions with counsellors, nurses and doctors. The data were coded thematically for analysis. Survivors of rape experienced a range of emotional difficulties and presented varying levels of distress and various levels of coping. Receiving support and care from others assisted them, but the poor integration of mental health within post-rape services meant few received formal mental health support or effective referrals. Multiple factors contributed to the poor integration: mental health was not given the same level of priority as other rape services (i.e. clinical care, including forensic management), the inadequate capacity of service providers to provide mental healthcare, including mental health illiteracy, the lack of continuity of care, the poor linkages to ongoing mental healthcare, and the mental health challenges caused by vicarious trauma and compassion fatigue. Providing effective, compassionate mental health services should be seen as essential components of post-rape care. The strengthening of support for providers and linkages to ongoing mental healthcare are essential to improve mental health services within acute post-rape services.


Runx2/Cbfa1-genetically engineered skeletal myoblasts mineralize collagen scaffolds in vitro.
Genetic engineering of progenitor and stem cells is an attractive approach to address cell sourcing limitations associated with tissue engineering applications. Bone tissue engineering represents a promising strategy to repair large bone defects, but has been limited in part by the availability of a sustained, mineralizing cell source. This study examined the in vitro mineralization potential of primary skeletal myoblasts genetically engineered to overexpress Runx2/Cbfa1, an osteoblastic transcriptional regulator essential to bone formation. These cells were viable at the periphery of 3D fibrous collagen scaffolds for 6 weeks of static culture. Exogenous Runx2 expression induced osteogenic differentiation and repressed myogenesis in these constructs relative to controls. Runx2-modified cells deposited significant amounts of mineralized matrix and hydroxyapatite, as determined by microcomputed tomography, histological analysis, and Fourier transform infrared spectroscopy, whereas scaffolds seeded with control cells exhibited no mineralized regions. Although mineralization by Runx2-engineered cells was confined to the periphery of the construct, colocalizing with cell viability, it was sufficient to increase the compressive modulus of constructs 30-fold relative to controls. This work demonstrates that Runx2 overexpression in skeletal myoblasts may address current obstacles of bone tissue engineering by providing a potent cell source for in vitro mineralization and construct maturation. Additionally, the use of genetic engineering methods to express downstream control factors and transcriptional regulators, in contrast to soluble signaling molecules, represents a robust strategy to enhance cellular activities for tissue engineering applications.


Constellation-masked secure communication technique for OFDM-PON.
This paper proposes a novel secure communication technique using constellation masking for applications in orthogonal frequency division multiplexing passive optical network (OFDM-PON). The constellation masking is applied both on each subcarrier and among different subcarriers. The Arnold mapping is utilized as the parameter function for the mask factors. A interleave length is employed to provide a scalable masking granularity for different ONUs. A 15.54 Gb/s constellation-masked 32QAM-OFDM signal has been successfully transmitted over 25-km single mode fiber in the experiment. Experimental results show that the proposed scheme can effectively protect the system from illegal ONU without wasting the bandwidth. The constellation-masked technique suggests an effective solution for the physical secure communication in future OFDM access network.


Vascular and metabolic response to bevacizumab-containing regimens in two patients with colorectal liver metastases measured by dynamic contrast-enhanced MRI and dynamic 18F-FDG-PET.
Early monitoring of response to treatment is one of the cornerstones of personalized treatment. As new and often expensive targeted therapies, which are tumoristatic rather than tumoricidal, become available, new demands are posed on response assessment. Bevacizumab, an antiangiogenic agent causing normalization of the tumor microvasculature, potentiates the effect of cytotoxic agents on colorectal liver metastases. It is known that assessment of glucose metabolism by (dynamic) positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG PET) can be used as an early surrogate endpoint to determine treatment efficacy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to quantify functional tumor vasculature (permeability, vascular surface area). Here, we describe the response of colorectal liver metastases to cytotoxic regimens including bevacizumab using both (18)F-FDG PET and DCE-MRI in 2 cases. In both cases, a large reduction in glucose metabolic rate and functional tumor vasculature are observed after 3 treatment cycles.


Dietary carbohydrate and the progression of age-related macular degeneration: a prospective study from the Age-Related Eye Disease Study.
Cross-sectional studies indicate that diets that provide a higher dietary glycemic index (dGI) are associated with a greater risk of age-related macular degeneration (AMD). No prospective studies have addressed this issue. The objective was to prospectively evaluate the effect of baseline dGI on the progression of AMD. dGI was calculated as the weighted average of GIs from foods and was evaluated as being above or below the sex median (women: 77.9; men: 79.3) for 3977 participants aged 55-80 y (58% women) in the Age-Related Eye Disease Study. The 7232 eligible eyes without advanced AMD were classified into 1 of 3 AMD categories: group 1 (nonextensive small drusen), group 2 (intermediate drusen, extensive small drusen, or pigmentary abnormalities), or group 3 (large drusen or extensive intermediate drusen). With the use of multifailure Cox proportional-hazards regression, we modeled the time to the maximal progression to evaluate the relation between dGI and the risk of AMD. Overall, the multivariate-adjusted risk of progression over 8 y of follow-up (x: 5.4 y) was significantly higher (risk ratio: 1.10; 95% CI: 1.00, 1.20; P = 0.047) in the high-dGI group than in the low-dGI group. The risk of progression for groups 1, 2, and 3 eyes was 5%, 8%, and 17% greater, respectively (P for trend < 0.001). The latter gives an estimate that 7.8% of new advanced AMD cases would be prevented in 5 y if people consumed the low-dGI diet. Persons at risk of AMD progression, especially those at high risk of advanced AMD, may benefit from consuming a smaller amount of refined carbohydrates.


Effect of narcotic agents and of bleeding on systemic and renal haemodynamics in healthy and CCl4-treated cirrhotic rats.
1. The haemodynamic effects of different narcotic agents have been tested in healthy rats and in rats with cirrhosis. 2. Pentobarbital suppresses the sympathetic nervous system. Susceptibility to ketamine is unpredictable, leading to both insufficient pain relief and narcosis related mortality. The combination diazepam-fluanisone induces profound hypotension. After insertion of catheters, awake, freely moving rats are stable and not distressed. This allows repeated measurements after manipulation. Moreover, procedure-related mortality is low and rats have a better stress response. 3. In the awake animal, arterial pressure is 126 +/- 10 for healthy animals, and 111 +/- 16 and 102 +/- 10 mmHg for cirrhotic animals without and with ascites, respectively (P = 0.018). The respective values for portal pressure are 6.9 +/- 1.4, 11.6 +/- 2.5 and 16.2 +/- 2.9 mmHg (P = 0.0001). After a bleeding, arterial pressure is better preserved than portal pressure in the three groups (P < 0.0001). Plasma volume in cirrhotic rats exceeds that of healthy rats. Plasma renin activity, aldosterone and catecholamines do not differ between the groups studied. In cirrhotic rats with and without ascites, glomerular filtration rate tends to be higher (P = 0.12), renal plasma flow is elevated (P = 0.001) and filtration fraction is lower (P = 0.002) than in healthy rats. 4. In conclusion, haemodynamic experiments in the cirrhotic rat should be performed in the awake rat. Arterial hypotension, impaired filtration fraction, enlarged plasma volume and portal hypertension are present in cirrhosis before the development of ascites. This can as well be explained by splanchnic pooling of blood, as by peripheral vasodilatation. The decrease in portal pressure with preserved arterial pressure after a bleeding protects cirrhotic rats from ongoing variceal bleeding.


On the orientation of the catalytic dyad in aspartic proteases.
The recent re-refinement of the X-ray structure of apo plasmepsin II from Plasmodium falciparum suggests that the two carboxylate groups in the catalytic dyad are noncoplanar, (Robbins et al., Acta Crystallogr D Biol Crystallogr 2009;65: 294-296) in remarkable contrast with the vast majority of structures of aspartic proteases. Here, evidence for the noncoplanarity of the catalytic aspartates is provided by analysis of multiple explicit water molecular dynamics (MD) simulations of plasmepsin II, human beta-secretase, and HIV-protease. In the MD runs of plasmepsin II, the angle between the planes of the two carboxylates of the catalytic dyad is almost always in the range 60 degrees -120 degrees , in agreement with the perpendicular orientation in the re-refined X-ray structure. The noncoplanar arrangement is prevalent also in the beta-secretase simulations, as well as in the runs with the inhibitor-bound proteases. Quantum-mechanics calculations provide further evidence that before catalysis the noncoplanar arrangement is favored energetically in eukaryotic aspartic proteases. Remarkably, the coplanar orientation of the catalytic dyad is observed in MD simulations of HIV-protease at 100 K but not at 300 K, which indicates that the noncoplanar arrangement is favored by conformational entropy. This finding suggests that the coplanar orientation in the crystal structures of apo aspartic proteases is promoted by the very low temperature used for data collection (usually around 100 K).


Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome.
The structural organisation of the human IGF2/ICR1/H19 11p15 domain is very complex, and the mechanisms underlying its regulation are poorly understood. The Imprinted Center Region 1 (ICR1) contains seven binding sites for the zinc-finger protein CTCF (CBS: CTCF Binding Sites); three additional differentially methylated regions (DMR) are located at the H19 promoter (H19DMR) and two in the IGF2 gene (DMR0 and DMR2), respectively. Loss of imprinting at the IGF2/ICR1/H19 domain results in two growth disorders with opposite phenotypes: Beckwith-Wiedemann syndrome and Russell Silver syndrome (RSS). Despite the IGF2/ICR1/H19 locus being widely studied, the extent of hypomethylation across the domain remains not yet addressed in patients with RSS. We assessed a detailed investigation of the methylation status of the 11p15 ICR1 CBS1-7, IGF2DMR0 and H19DMR (H19 promoter) in a population of controls (n=50) and RSS carrying (n=104) or not (n=65) carrying a hypomethylation at the 11p15 ICR1 region. The methylation indexes (MI) were balanced at all regions in the control population and patients with RSS without any as yet identified molecular anomaly. Interestingly, patients with RSS with ICR1 hypomethylation showed uneven profiles of methylation among the CBSs and DMRs. Furthermore, normal MIs at CBS1 and CBS7 were identified in 9% of patients. The hypomethylation does not spread equally throughout the IGF2/ICR1/H19 locus, and some loci could have normal MI, which may lead to underdiagnosis of patients with RSS with ICR1 hypomethylation. The uneven pattern of methylation suggests that some CBSs may play different roles in the tridimensional chromosomal looping regulation of this locus.


[Observation on the therapeutic effect of acupuncture treatment of autism children].
To observe the therapeutic effect of acupuncture ("Jin's Sanzhen") treatment for autism patients with different severity. A total of 202 autism children were divided into treatment group (n=118) and control group (n=84) according to their parents' will. Autism children in the treatment group were treated with "Jin's Sanzhen" therapy [for example, Niesanzhen: the point 2 cun superior to the ear tip, and those at the same level 1 cun apart on the left and right sides; Naosanzhen: Naohu (GV 17), bilateral Naokong (GB 19), etc.], while those of control group accepted special training: behavior education (cognition, speech, communication ability, life self-care ability, etc.) and sensory integration training. The treatment was given to the patients in both groups once per day, six times a week for 4 months. Of the 78 and 58 severe patients in the treatment and control groups, 63 (80.8%) and4 (6.9%) experienced marked improvement, 9 (11.5%) and 33 (56.9%) experienced improvement, 6 (7.7%) and 21 (36.2%) failed, with the effective rates being 92.3% and 63.8% respectively. Of the 118 and 84 patients in the treatment and control groups, after the treatment, the no symptoms, mild, moderate and severe cases were 12 (10.2%) and 3 (3.6%), 56 (47.5%) and 25 (29.8%), 45 (38.1%) and 23 (27.4%), 5 (4.2%) and 33 (39.3%), respectively. The total score of Childhood Autism Rating Scale of treatment group was significantly lower than that of control group after the treatment in severe cases (P < 0.01), showing a better therapeutic effect of the treatment group. "Jin's Sanzhen" therapy has a better therapeutic effect for improving the autism patients symptoms at different severity.


A fast algorithm for multidimensional ellipsoid-specific fitting by minimizing a new defined vector norm of residuals using semidefinite programming.
A quadratic surface in n-dimensional space is defined as the locus of zeros of a quadratic polynomial. The quadratic polynomial may be compactly written in notation by an (n+1)-vector and a real symmetric matrix of order n+1, where the vector represents homogenous coordinates of an n-D point, and the symmetric matrix is constructed from the quadratic coefficients. If an n-D quadratic surface is an n-D ellipsoid, the leading n × n principal submatrix of the symmetric matrix would be positive or opposite definite. As we know, to impose a matrix being positive or opposite definite, perhaps the best choice may be to employ semidefinite programming (SDP). From such straightforward and intuitive knowledge, in the literature until 2002, Calafiore first proposed a feasible method for multidimensional ellipsoid-specific fitting using SDP, which minimizes the 2--norm of the algebraic residual vector. However, the runtime of the method is significantly long and memory is often out when the number of fitted points is greater than several thousand. In this paper, we propose a fast and easily implemented algorithm for multidimensional ellipsoid-specific fitting by minimizing a new defined vector norm of the algebraic residual vector using SDP, which drastically decreases the size of the SDP problem while preserving accuracy. The proposed fast method can handle several million fitted points without any difficulty.


Fate of infectious salmon anaemia virus (ISAV) in experimentally challenged blue mussels Mytilus edulis.
In order to investigate the potential role of blue mussels Mytilus edulis as a vector of the fish pathogenic infectious salmon anaemia virus (ISAV), we developed an experimental bioaccumulation system in which mussels can accumulate virus during normal filtration. Detection of virus in mussels was performed by means of real-time RT-PCR. ISAV-RNA was detected in the mussels until 72 h post-challenge. Hepatopancreas homogenate from experimentally challenged mussels was injected into salmon. All the fish injected with homogenate prepared immediately after accumulations were strongly ISAV positive 4 wk post-challenge. In the group injected with homogenate prepared 24 h after the challenge, 1 fish out of 25 was weakly ISAV positive. All of the fish that were challenged with mussel homogenate prepared 96 h after accumulation were ISAV negative. Mussels sampled from a tank with experimentally infected salmon demonstrating clinical signs consistent with ISA (infectious salmon anaemia) and mussels collected on net pen cages during ISA outbreaks in Atlantic salmon were all ISAV negative. The results indicate that the ISAV is rapidly inactivated in mussels and that mussels are not a likely reservoir host or vector for ISAV.


Conservation and variation in the feeding mechanism of the spiny dogfish squalus acanthias
Changes in the feeding mechanism with feeding behavior were investigated using high-speed video and electromyography to examine the kinematics and motor pattern of prey capture, manipulation and transport in the spiny dogfish Squalus acanthias (Squalidae: Squaliformes). In this study, Squalus acanthias used both suction and ram behaviors to capture and manipulate prey, while only suction was used to transport prey. The basic kinematic feeding sequence observed in other aquatic-feeding lower vertebrates is conserved in the spiny dogfish. Prey capture, bite manipulation and suction transport events are characterized by a common pattern of head movements and motor activity, but are distinguishable by differences in duration and relative timing. In general, capture events are longer in duration than manipulation and transport events, as found in other aquatic-feeding lower vertebrates. Numerous individual effects were found, indicating that individual sharks are capable of varying head movements and motor activity among successful feeding events. Upper jaw protrusion in the spiny dogfish is not restricted by its orbitostylic jaw suspension; rather, the upper jaw is protruded by 30 % of its head length, considerably more than in the lemon shark Negaprion brevirostris (Carcharhinidae: Carcharhiniformes) (18 %) with its hyostylic jaw suspension. One function of upper jaw protrusion is to assist in jaw closure by protruding the upper jaw as well as elevating the lower jaw to close the gape, thus decreasing the time to jaw closure. The mechanism of upper jaw protrusion was found to differ between squaliform and carcharhiniform sharks. Whereas the levator palatoquadrati muscle assists in retracting the upper jaw in the spiny dogfish, it assists in protruding the upper jaw in the lemon shark. This study represents the first comprehensive electromyographic and kinematic analysis of the feeding mechanism in a squaliform shark.


Solution structures of alkali metal cyclopentadienides in THF estimated by ECC-DOSY NMR-spectroscopy (incl. software).
In this paper we present the aggregational motifs of the widely used alkali-metal cyclopentadienides (CpLi, CpNa, CpK, CpRb, CpCs) in THF-d8 solution estimated by ECC-DOSY NMR spectroscopy. They form monomeric contact ion pairs (CIPs) in THF-d8 solution, whereas in NH3 solvent-separated ion pairs (SSIPs) are observed. The applicability of ECC-DOSY is further advanced by introducing ECC-MW estimation software.


Dynamics of microfluidic droplets.
This critical review discusses the current understanding of the formation, transport, and merging of drops in microfluidics. We focus on the physical ingredients which determine the flow of drops in microchannels and recall classical results of fluid dynamics which help explain the observed behaviour. We begin by introducing the main physical ingredients that differentiate droplet microfluidics from single-phase microfluidics, namely the modifications to the flow and pressure fields that are introduced by the presence of interfacial tension. Then three practical aspects are studied in detail: (i) The formation of drops and the dominant interactions depending on the geometry in which they are formed. (ii) The transport of drops, namely the evaluation of drop velocity, the pressure-velocity relationships, and the flow field induced by the presence of the drop. (iii) The fusion of two drops, including different methods of bridging the liquid film between them which enables their merging.


Clinical significance of K-ras oncogene activation in ampullary neoplasms.
To investigate the prevalence of K-ras codon 12 point mutations in ampullary neoplasms, to explore their clinical usefulness, and to test whether the detection of these mutations could be used to identify ampullary malignancies at an early stage. Forty one tumour specimens from 28 patients with ampullary neoplasms were analysed for activating point mutations in K-ras codon 12 using a sensitive polymerase chain reaction (PCR) based assay. Eleven (39%) of the 28 primary tumours harboured point mutations in K-ras. Mutations were identified in seven (41%) of the 17 carcinomas and four (36%) of the 11 adenomas. Four of the possible six permutations in codon 12 were found in these 11 samples. This spectrum of mutations is different from pancreatic carcinoma but resembles that of colorectal neoplasms. Cytological brush specimens were available in 11 cases, and in all of these specimens, the K-ras status in the primary tumour and brush specimens was identical. K-ras codon 12 point mutations occur in about 40% of ampullary neoplasms at a relatively early stage in tumorigenesis. The pattern of mutations in these tumours resembles that of the adenoma-carcinoma sequence in the colorectum. These results indicate that ampullary neoplasms can be detected at an early stage by searching for genetic alterations in the K-ras oncogene in cytological brush specimens.


Expanding the Chemical Space of Withaferin A by Incorporating Silicon To Improve Its Clinical Potential on Human Ovarian Carcinoma Cells.
Ovarian cancer represents the seventh most commonly diagnosed cancer worldwide. Herein, we report on the development of a withaferin A (WA)-silyl ether library with 30 analogues reported for the first time. Cytotoxicity assays on human epithelial ovarian carcinoma cisplatin-sensitive and -resistant cell lines identified eight analogues displaying nanomolar potency (IC50 ranging from 1 to 32 nM), higher than that of the lead compound and reference drug. This cytotoxic potency is also coupled with a good selectivity index on a nontumoral cell line. Cell cycle analysis of two potent analogues revealed cell death by apoptosis without indication of cell cycle arrest in G0/G1 phase. The structure-activity relationship and in silico absorption, distribution, metabolism, and excretion studies demonstrated that the incorporation of silicon and a carbonyl group at C-4 in the WA framework enhances potency, selectivity, and drug likeness. These findings reveal analogues 22, 23, and 25 as potential candidates for clinical translation in patients with relapsed ovarian cancer.


Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women.
Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.


Practices and Policies Around Wellness: Insights From the Internet Crimes Against Children Task Force Network.
This article aims to understand what practices and training Internet Crimes Against Children (ICAC) Task Forces and affiliated agencies are currently using to help mitigate distress and promote wellbeing among investigators of child sexual abuse material (CSAM). Data were collected via telephone interviews with Commanders of 54 ICAC Task Forces as well as an online survey of 155 investigators at ICAC-affiliated agencies. Sixty-two percent of respondents said their agency had an Officer Wellness Program. Findings highlighted considerable gaps in protective practices with 46.1% of respondents mentioning the need for more wellness resources in their agency for personnel who have viewed CSAM as a high priority. Stigma created by help-seeking was the most widely acknowledged barrier discussed in relation to police wellness. A large and salient problem was the persistent lack of wellness practices in the affiliated agencies in comparison to the Task Forces themselves. Exposure to CSAM can be a source of stress for personnel and the results indicate concern about the problem and a diffusion of proactive initiatives, but barriers and inconsistent adoption remain.


Hydrophobic substances induce water stress in microbial cells.
Ubiquitous noxious hydrophobic substances, such as hydrocarbons, pesticides and diverse industrial chemicals, stress biological systems and thereby affect their ability to mediate biosphere functions like element and energy cycling vital to biosphere health. Such chemically diverse compounds may have distinct toxic activities for cellular systems; they may also share a common mechanism of stress induction mediated by their hydrophobicity. We hypothesized that the stressful effects of, and cellular adaptations to, hydrophobic stressors operate at the level of water : macromolecule interactions. Here, we present evidence that: (i) hydrocarbons reduce structural interactions within and between cellular macromolecules, (ii) organic compatible solutes - metabolites that protect against osmotic and chaotrope-induced stresses - ameliorate this effect, (iii) toxic hydrophobic substances induce a potent form of water stress in macromolecular and cellular systems, and (iv) the stress mechanism of, and cellular responses to, hydrophobic substances are remarkably similar to those associated with chaotrope-induced water stress. These findings suggest that it may be possible to devise new interventions for microbial processes in both natural environments and industrial reactors to expand microbial tolerance of hydrophobic substances, and hence the biotic windows for such processes.


In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages.
Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)1-3, its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos4. Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis5,6, a high number of embryos containing abnormal cells can pass this strong selection barrier7,8. However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.


Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor contributes to the turnover of multiple proteasome targets.
The polyubiquitin receptor Rpn10 targets ubiquitylated Sic1 to the 26S proteasome for degradation. In contrast, turnover of at least one ubiquitin-proteasome system (UPS) substrate, CPY*, is impervious to deletion of RPN10. To distinguish whether RPN10 is involved in the turnover of only a small set of cell cycle regulators that includes Sic1 or plays a more general role in the UPS, we sought to develop a general method that would allow us to survey the spectrum of ubiquitylated proteins that selectively accumulate in rpn10Delta cells. Polyubiquitin conjugates from yeast cells that express hexahistidine-tagged ubiquitin (H6-ubiquitin) were first enriched on a polyubiquitin binding protein affinity resin. This material was then denatured and subjected to IMAC to retrieve H6-ubiquitin and proteins to which it may be covalently linked. Using this approach, we identified 127 proteins that are candidate substrates for the 26S proteasome. We then sequenced ubiquitin conjugates from cells lacking Rpn10 (rpn10Delta) and identified 54 proteins that were uniquely recovered from rpn10Delta cells. These include two known targets of the UPS, the cell cycle regulator Sic1 and the transcriptional activator Gcn4. Our approach of comparing the ubiquitin conjugate proteome in wild-type and mutant cells has the resolving power to identify even an extremely in abundant transcriptional regulatory protein and should be generally applicable to mapping enzyme substrate networks in the UPS.


Correction of geometrically distorted underwater images using shift map analysis.
In underwater imaging, water waves cause severe geometric distortions and blurring of the acquired short-exposure images. Corrections for these distortions have been tackled reasonably well by previous efforts but still need improvement in the estimation of pixel shift maps to increase restoration accuracy. This paper presents a new algorithm that efficiently estimates the shift maps from geometrically distorted video sequences and uses those maps to restore the sequences. A nonrigid image registration method is employed to estimate the shift maps of the distorted frames against a reference frame. The sharpest frame of the sequence, determined using a sharpness metric, is chosen as the reference frame. A k-means clustering technique is employed to discard too-blurry frames that could result in inaccuracy in the shift maps' estimation. The estimated pixel shift maps are processed to generate the accurate shift map that is used to dewarp the input frames into their nondistorted forms. The proposed method is applied on several synthetic and real-world video sequences, and the obtained results exhibit significant improvements over the state-of-the-art methods.


The measure and significance of Bateman's principles.
Bateman's principles explain sex roles and sexual dimorphism through sex-specific variance in mating success, reproductive success and their relationships within sexes (Bateman gradients). Empirical tests of these principles, however, have come under intense scrutiny. Here, we experimentally show that in replicate groups of red junglefowl, Gallus gallus, mating and reproductive successes were more variable in males than in females, resulting in a steeper male Bateman gradient, consistent with Bateman's principles. However, we use novel quantitative techniques to reveal that current methods typically overestimate Bateman's principles because they (i) infer mating success indirectly from offspring parentage, and thus miss matings that fail to result in fertilization, and (ii) measure Bateman gradients through the univariate regression of reproductive over mating success, without considering the substantial influence of other components of male reproductive success, namely female fecundity and paternity share. We also find a significant female Bateman gradient but show that this likely emerges as spurious consequences of male preference for fecund females, emphasizing the need for experimental approaches to establish the causal relationship between reproductive and mating success. While providing qualitative support for Bateman's principles, our study demonstrates how current approaches can generate a misleading view of sex differences and roles.


The effect of dietary protein on reproduction in the mare. VI. Serum progestagen concentrations during pregnancy.
Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were used, of which 40 were non-lactating and 24 lactating. Foals from these 24 mares were weaned at the age of 6 months. Non-lactating and lactating mares were divided into 4 dietary groups each. The total daily protein intake and the protein quality (essential amino-acid content) differed in the 4 groups of non-lactating and 4 groups of lactating mares. The mares were covered and the effect of the quantity and quality of dietary protein on serum progestagen concentrations during pregnancy was studied. A sharp decline in serum progestagen concentrations was recorded in all dietary groups from Days 18 to 40 of pregnancy, with some individual mares reaching values of less than 4 ng/ml. Serum progestagen concentrations recorded in some of the non-lactating mares on the low-quality protein diet increased to higher values (p < 0.05) than those of mares in the other 3 dietary groups at 35-140 days of pregnancy. A similar trend was observed for the lactating mares on a low-quality protein diet at 30-84 days of pregnancy. No such trends were observed in any of the other dietary groups. High-quality protein supplementation increased serum progestagen concentrations during the 1st 30 days of pregnancy. Lactation depressed serum progestagen concentrations until after the foals were weaned.


New techniques for the evaluation and therapeutic planning of patients with Klippel-Trénaunay syndrome.
Klippel-Trénaunay syndrome (KTS) is a well-known eponym for a capillary-lymphatic-venous malformation which is associated with soft tissue and skeletal hypertrophy, usually of one or more limbs. Plain films, sonograms, conventional venograms, and arteriograms have been employed for the evaluation of the disease. To demonstrate the usefulness of multidetector computed tomography (MDCT) and fast 3-dimensional magnetic resonance imaging (3D-MR) venography for the assessment and therapeutic planning of patients with KTS. A prospective study in 16 consecutive patients with KTS using MDCT and 3D-MR venography, performed between January 2004 and January 2006 in a university hospital in Pamplona, Spain. In nearly all patients, persistent embryologic veins were observed, and in one subject aplasia/atresia of the whole deep venous system of the affected extremity was seen. In four individuals hypoplasia of the femoral vein was observed; one subject had duplication of the femoral vein, and in three patients aplasia/atresia of this vein was found. Only half of the patients had normal popliteal veins. In one patient, aneurysmal dilatation of the popliteal vein was detected, and in six subjects, aplasia of this vein was observed. The presence of geographic stains was suggestive of hypoplasia and/or aplasia of femoral and popliteal veins. The small size of the group of patients with KTS, which is related to low incidence of the disease. MDCT and 3D-MR venography are extremely helpful for the global evaluation of patients with KTS. Information regarding soft tissue and bony anatomy as well as information about superficial and deep venous systems may be obtained with a single exam.


Robotic surgery is the optimal approach for mitral surgery.
This report presented an overview of the patient selection, technical considerations and clinical evidence for robotic mitral valve surgery. A review of comparative outcomes to medical therapy, sternotomy approach, and the MitraClip device suggested that robotic mitral valve surgery is safe and effective in specialized centres. Potential benefits include a reliable and durable repair, with reduced perioperative morbidity and improved quality of life. Future studies should aim to delineate mid- and long-term clinical and echocardiographic outcomes following robotic mitral valve repair compared to the conventional sternotomy approach.


Planar chiral [2.2]paracyclophanes: from synthetic curiosity to applications in asymmetric synthesis and materials.
Planar chiral [2.2]paracyclophane-based ligands and employment of such enantiopure representative ligands to facilitate selective transformation of prochiral or racemic substances into enantiopure products are rarely explored compared to the complex chiral scaffolds such as ferrocenes. This tutorial discusses recent findings and inspiring progress in design, synthetic tunability and applications of planar chiral [2.2]paracyclophane systems as a practical class of catalysts for asymmetric synthesis. Here, we summarize a series of planar chiral [2.2]paracyclophanes that are becoming an important new tool-box in asymmetric synthesis, employed in a variety of synthetic venues such as new chiral ligands and catalysts for stereo-controlled and enantioselective addition of alkyl, alkenyl, alkynyl and aryl zinc reagents to aliphatic and aromatic aldehydes, ketones, imines and many more. Besides, planar chiral [2.2]paracyclophanes are useful synthons, from a material perspective, can be incorporated into conjugated polymeric systems for chiroptical and optoelectronic properties, find broad applications in bio- and materials science, for instance, gold-based cytostatics, surface-mounted chiral MOF thin films for selective adsorption or in functionalized parylene polymer coatings, to name a few. This is an up-to-date tutorial review, written exclusively on planar chiral [2.2]paracyclophane chemistry, covering key aspects of synthesis, structures, properties, applications and future directions of chiral polymeric assemblies and novel biomaterials built with [2.2]paracyclophanes.


Comparative analyses suggest that information transfer promoted sociality in male bats in the temperate zone.
The evolution of sociality is a central theme in evolutionary biology. The vast majority of bats are social, which has been explained in terms of the benefits of communal breeding. However, the causes for segregated male groups remain unknown. In a comparative study, we tested whether diet and morphological adaptations to specific foraging styles, two factors known to influence the occurrence of information transfer, can predict male sociality. Our results suggest that the species most likely to benefit from information transfer--namely, those preying on ephemeral insects and with morphological adaptations to feeding in open habitat--are more likely to form male groups. Our findings also indicate that solitary life was the ancestral state of males and sociality evolved in several lineages. Beyond their significance for explaining the existence of male groups in bats, our findings highlight the importance of information transfer in the evolution of animal sociality.


Mitral valve repair versus revascularization alone in the treatment of ischemic mitral regurgitation.
For patients with ischemic mitral regurgitation (MR), it is not clear whether adjunctive mitral valve (MV) repair at the time of coronary artery bypass graft surgery (CABG) is beneficial. We sought to test the hypothesis that MV repair with CABG is superior to CABG alone in improving MR without increasing operative or long-term mortality. A total of 107 consecutive patients with moderate or severe ischemic MR, as determined by preoperative echocardiography, underwent CABG with concomitant MV repair (repair group, n=50) or CABG only (CABG group, n=57). Degree of MR was graded as none, mild, moderate, or severe by the proximal isovelocity surface area method. The groups were similar with respect to age, gender, baseline New York Heart Association class, ejection fraction, and number of bypass grafts. The repair group had a higher percentage of patients with atrial fibrillation or severe MR than the CABG group. The operative mortality was significantly higher for the repair group (12%) than the CABG group (2%), whereas the 5-year actuarial survival rate of the 2 groups was similar (88%+/-5% versus 87%+/-6%). On multivariate logistic regression analysis, older age, higher New York Heart Association class, and atrial fibrillation were independent predictors of operative mortality (P<0.05). Among patients with severe MR, ischemic MR was improved in all patients of the repair group and in 67% of patients in the CABG group (P<0.001), whereas improvement rates in patients with moderate MR were similar in the 2 groups (75% versus 67%, P=NS). Although MV repair appears to be more effective at reducing ischemic functional MR, CABG alone may be a preferable treatment option for patients with moderate MR and high operative risk factors such as old age or atrial fibrillation.


Ig isotype switching in B lymphocytes. A method for estimating isotype switch frequency in cloned B cell lymphomas.
We have developed a method for enumerating the frequency of Ig isotype switching in clones of B cells. The method adapts Poisson statistics to analyze the distribution of amounts of switched isotype produced by multiple subclones of cells and thus enables one to estimate the probability that a single cell will switch isotype in one cell generation. We have applied this method to determine the spontaneous switch frequency of two Ly-1+ B cell lymphomas of B10-H-2aH-4bp/Wts mice. Both CH12.LX and CH27.LX switch from IgM to IgA at very high frequencies (1 - 5 x 10(-3) switch events per cell division) and from IgM to IgG at low but detectable frequencies (10(-4) - 10(-5) switch events per cell division). Cloned IgG variants of CH12.LX switch to IgA at the same frequency as the IgM-producing cells. Bacterial lipopolysaccharide has a strong inhibitory effect on isotype switching by CH12.LX. Possible explanations for the observed preference for switching to IgA are discussed.


Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.
General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites.


How to activate a plant gravireceptor. Early mechanisms of gravity sensing studied in characean rhizoids during parabolic flights.
Early processes underlying plant gravity sensing were investigated in rhizoids of Chara globularis under microgravity conditions provided by parabolic flights of the A300-Zero-G aircraft and of sounding rockets. By applying centrifugal forces during the microgravity phases of sounding rocket flights, lateral accelerations of 0.14 g, but not of 0.05 g, resulted in a displacement of statoliths. Settling of statoliths onto the subapical plasma membrane initiated the gravitropic response. Since actin controls the positioning of statoliths and restricts sedimentation of statoliths in these cells, it can be calculated that lateral actomyosin forces in a range of 2 x 10(-14) n act on statoliths to keep them in place. These forces represent the threshold value that has to be exceeded by any lateral acceleration stimulus for statolith sedimentation and gravisensing to occur. When rhizoids were gravistimulated during parabolic plane flights, the curvature angles of the flight samples, whose sedimented statoliths became weightless for 22 s during the 31 microgravity phases, were not different from those of in-flight 1g controls. However, in ground control experiments, curvature responses were drastically reduced when the contact of statoliths with the plasma membrane was intermittently interrupted by inverting gravistimulated cells for less than 10 s. Increasing the weight of sedimented statoliths by lateral centrifugation did not enhance the gravitropic response. These results provide evidence that graviperception in characean rhizoids requires contact of statoliths with membrane-bound receptor molecules rather than pressure or tension exerted by the weight of statoliths.


Cryoanalgesia in interventional pain management.
Cryoneuroablation, also known as cryoanalgesia or cryoneurolysis, is a specialized technique for providing long-term pain relief in interventional pain management settings. Modern cryoanalgesia traces its roots to Cooper et al who developed in 1961, a device that used liquid nitrogen in a hollow tube that was insulated at the tip and achieved a temperature of - 190 degrees C. Lloyd et al proposed that cryoanalgesia was superior to other methods of peripheral nerve destruction, including alcohol neurolysis, phenol neurolysis, or surgical lesions. The application of cold to tissues creates a conduction block, similar to the effect of local anesthetics. Long-term pain relief from nerve freezing occurs because ice crystals create vascular damage to the vasonervorum, which produces severe endoneural edema. Cryoanalgesia disrupts the nerve structure and creates wallerian degeneration, but leaves the myelin sheath and endoneurium intact. Clinical applications of cryoanalgesia extend from its use in craniofacial pain secondary to trigeminal neuralgia, posterior auricular neuralgia, and glossopharyngeal neuralgia; chest wall pain with multiple conditions including post-thoracotomy neuromas, persistent pain after rib fractures, and post herpetic neuralgia in thoracic distribution; abdominal and pelvic pain secondary to ilioinguinal, iliohypogastric, genitofemoral, subgastric neuralgia; pudendal neuralgia; low back pain and lower extremity pain secondary to lumbar facet joint pathology, pseudosciatica, pain involving intraspinous ligament or supragluteal nerve, sacroiliac joint pain, cluneal neuralgia, obturator neuritis, and various types of peripheral neuropathy; and upper extremity pain secondary to suprascapular neuritis and other conditions of peripheral neuritis. This review describes historical concepts, physics and equipment, various clinical aspects, along with technical features, indications and contraindications, with clinical description of multiple conditions amenable to cryoanalgesia in interventional pain management settings.


Oxidative stress is the master operator of drug and chemically-induced programmed and unprogrammed cell death: Implications of natural antioxidants in vivo.
ROS, RNS, BRIs and ROS-RNS hybrids are produced during drug or chemical metabolism in vivo. These reactive species are instrumental to the culmination of cellular oxidative stress (OS). OS, once turned on, does not spare any vital intracellular macromolecule, such as glutathione, DNA, RNA, proteins, enzymes, lipids and ATP. Since concentration gradients of such components are very delicately balanced for normal cellular functioning, a gross perturbation leads to cell injury and cell death. Abundant evidence now suggests that intracellular antioxidants keep OS in check and maintain homeostasis. Our laboratory has focused on the role of OS in orchestrating various forms of cell death during drug and chemically-induced target organ toxicity and their counteraction by various natural or synthetic antioxidants in in vivo models. Despite complexity of the in vivo models, results show that metabolism of xenobiotics are invariably associated with different degrees of OS and natural antioxidants such as grape seed extract, bitter melon extract (Momordica charantia) and N-acetylcysteine (NAC) which were very effective in counteracting organ toxicities by minimizing events linked to OS (lipid peroxidation and total glutathione), and CAD-mediated DNA fragmentation. Phytoextract exposure rescued cells from toxic assaults, protected genomic integrity, and minimized apoptotic, necrotic and apocrotic (oncotic necrosis) cell deaths. Pre-exposure mode was more effective than post-exposure route. Overall scenario suggests that OS may have been the prime modulator of death and/or survival programs, whereas, antioxidants may have imparted a dual role in either erasing death signals or reviving survival signals, and a combination of antioxidants may be more beneficial than a single entity to influence a number of intracellular events operating simultaneously to neutralize chaotic toxicological consequences.


Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions.
Niemann-pick type C1 (NPC1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC2. Knowledge-based docking of NPC1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species-specific susceptibility to the virus infection.


Tapping linked to function and structure in premanifest and symptomatic Huntington disease.
Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy. A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded. Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes. Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study.


Blueberry polyphenol-enriched soybean flour reduces hyperglycemia, body weight gain and serum cholesterol in mice.
Defatted soybean flour (DSF) can sorb and concentrate blueberry anthocyanins and other polyphenols, but not sugars. In this study blueberry polyphenol-enriched DSF (BB-DSF) or DSF were incorporated into very high fat diet (VHFD) formulations and provided ad libitum to obese and hyperglycemic C57BL/6 mice for 13 weeks to investigate anti-diabetic effects. Compared to the VHFD containing DSF, the diet supplemented with BB-DSF reduced weight gain by 5.6%, improved glucose tolerance, and lowered fasting blood glucose levels in mice within 7 weeks of intervention. Serum cholesterol of mice consuming the BB-DSF-supplemented diet was 13.2% lower than mice on the diet containing DSF. Compounds were eluted from DSF and BB-DSF for in vitro assays of glucose production and uptake. Compared to untreated control, doses of BB-DSF eluate containing 0.05-10μg/μL of blueberry anthocyanins significantly reduced glucose production by 24-74% in H4IIE rat hepatocytes, but did not increase glucose uptake in L6 myotubes. The results indicate that delivery of blueberry polyphenols stabilized in a high-protein food matrix may be useful for the dietary management of pre-diabetes and/or diabetes.


Acute effect of low dose theophylline on the circulatory disturbances of cirrhosis.
Adenosine is a potent vasoactive substance that may be responsible for mediating the altered haemodynamics found in patients with cirrhosis. The administration of oral theophylline was used to investigate the effect of adenosine receptor antagonism upon the circulation of patients with cirrhosis. Twenty eight patients were given oral theophylline and intravascular haemodynamic measurements obtained over approximately one hour. After 240 mg of oral theophylline elixir the hepatic venous pressure gradient mean fell from 21.8 (2.1) to 19.9 (2.4) mm Hg (p < 0.01), and azygos blood flow fell from 481 (94) to 375 (83) ml/min (p < 0.05). There were no changes in cardiac output or systemic vascular resistance despite a fall in mean arterial pressure (92.2 (2.0) to 89.2 (1.8) mm Hg; p < 0.05) and a rise in heart rate (78.3 (3.0) to 82.4 (3.2); p < 0.001). Left renal vein flow measured by a reverse thermodilution catheter rose from 387 (91) to 601 (119) ml/ min (p < 0.05). The proportion of cardiac output perfusing the left kidney rose from 5.0 (1.3) to 9.7 (2.8)%. These changes indicate a significant role for adenosine in the renal vasoconstriction and a more minor role in the maintenance of portal hypertension.


Spotted fever in Brazil: a seroepidemiological study and description of clinical cases in an endemic area in the state of São Paulo.
During 1985-1995, illnesses clinically and epidemiologically compatible with Brazilian spotted fever were identified in 17 patients in the county of Pedreira, in the state of São Paulo, Brazil. Spotted-fever group rickettsial infection was confirmed by serology and/or immunostaining of tissues in 10 of these patients. Immunostaining confirmed infection in a 37-year-old pregnant patient, although rickettsial antigens were not demonstrable in the tissues of the fetus. A serosurvey was conducted in four localities in the county to determine the prevalence of subclinical or asymptomatic infections with spotted fever group rickettsiae. Five hundred and twenty-five blood samples were tested by an indirect immunofluorescence assay for antibodies reactive with Rickettsia rickettsii. Twenty-two (4.2%) of these samples demonstrated titers > or = 1:64. The results indicate that Brazilian spotted fever is endemic within this region of Brazil.


Mining Gene Expression Data Focusing Cancer Therapeutics: A Digest.
An understanding towards genetics and epigenetics is essential to cope up with the paradigm shift which is underway. Personalized medicine and gene therapy will confluence the days to come. This review highlights traditional approaches as well as current advancements in the analysis of the gene expression data from cancer perspective. Due to improvements in biometric instrumentation and automation, it has become easier to collect a lot of experimental data in molecular biology. Analysis of such data is extremely important as it leads to knowledge discovery that can be validated by experiments. Previously, the diagnosis of complex genetic diseases has conventionally been done based on the non-molecular characteristics like kind of tumor tissue, pathological characteristics, and clinical phase. The microarray data can be well accounted for high dimensional space and noise. Same were the reasons for ineffective and imprecise results. Several machine learning and data mining techniques are presently applied for identifying cancer using gene expression data. While differences in efficiency do exist, none of the well-established approaches is uniformly superior to others. The quality of algorithm is important, but is not in itself a guarantee of the quality of a specific data analysis.


Nitrogen in insects: implications for trophic complexity and species diversification.
Disparities in nutrient content (nitrogen and phosphorus) between herbivores and their plant resources have lately proven to have major consequences for herbivore success, consumer-driven nutrient cycling, and the fate of primary production in ecosystems. Here we extend these findings by examining patterns of nutrient content between animals at higher trophic levels, specifically between insect herbivores and predators. Using a recently compiled database on insect nutrient content, we found that predators exhibit on average 15% greater nitrogen content than herbivores. This difference persists after accounting for variation from phylogeny and allometry. Among herbivorous insects, we also found evidence that recently derived lineages (e.g., herbivorous Diptera and Lepidoptera) have, on a relative basis, 15%-25% less body nitrogen than more ancient herbivore lineages (e.g., herbivorous Orthoptera and Hemiptera). We elaborate several testable hypotheses for the origin of differences in nitrogen content between trophic levels and among phylogenetic lineages. For example, interspecific variation in insect nitrogen content may be directly traceable to differences in dietary nitrogen (including dilution by gut contents), selected for directly in response to the differential scarcity of dietary nitrogen, or an indirect consequence of adaptation to different feeding habits. From some functional perspectives, the magnitude rather than the source of the interspecific differences in nitrogen content may be most critical. We conclude by discussing the implications of the observed patterns for both the trophic complexity of food webs and the evolutionary radiation of herbivorous insects.


Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response.
To investigate the neuropathologic substrate for dementia occurring late in Parkinson disease (PD). We identified 13 patients with a clinical diagnosis of PD who experienced dementia at least 4 years after parkinsonism onset (mean, 10.5 years) and subsequently underwent postmortem examination. Despite levodopa therapy, 9 patients later became severely impaired and nonambulatory, requiring total or near-total care; this included 4 patients treated with 1200 mg/d or more of levodopa (with carbidopa), which was consistent with loss of the levodopa response. These 13 patients were compared with 9 patients clinically diagnosed as having PD, but without dementia, who had undergone autopsies. Twelve of 13 PD patients with dementia had findings of diffuse or transitional Lewy body disease as the primary pathologic substrate for dementia; 1 had progressive supranuclear palsy. This pathology also apparently accounted for the levodopa refractory state. Among the 12 PD patients with dementia, mean and median Lewy body counts were increased nearly 10-fold in neocortex and limbic areas compared with PD patients without dementia (P< or =.002). Alzheimer pathology was modest. Only one patient met the criteria defined by the National Institute on Aging and the Reagan Institute Working Group on the Diagnostic Criteria for the Neuropathologic Assessment of Alzheimer's Disease for "intermediate probability of Alzheimer's disease." There were, however, significant correlations between neocortical Lewy body counts and senile plaques as well as neurofibrillary tangles. Senile plaque counts did not significantly correlate with tangle counts in any of the analyzed nuclei. Arteriolar disease may have contributed to the clinical picture in 2 patients. Diffuse or transitional Lewy body disease is the primary pathologic substrate for dementia developing later in PD. This same pathologic substrate seemed to account for end-stage, levodopa refractory parkinsonism. The occurrence of Alzheimer pathology was modest, but was highly correlated with Lewy body pathology, suggesting common origins or one triggering the other.


Plus disease diagnosis in retinopathy of prematurity: vascular tortuosity as a function of distance from optic disk.
To examine vascular tortuosity as a function of distance from the optic disk in infants with retinopathy of prematurity. Thirty-four wide-angle retinal images from infants with retinopathy of prematurity were reviewed by 22 experts. A reference standard for each image was defined as the diagnosis (plus vs. not plus) given by the majority of experts. Tortuosity, defined as vessel length divided by straight line distance between vessel end points, was calculated as a function of distance from the disk margin for arteries and veins using computer-based methods developed by the authors. Mean cumulative tortuosity increased with distance from the disk margin, both in 13 images with plus disease (P = 0.007 for arterial tortuosity [n = 62 arteries], P < 0.001 for venous tortuosity [n = 58 veins] based on slope of best fit line by regression), and in 21 images without plus disease (P < 0.001 for arterial tortuosity [n = 94 arteries], P <0 .001 for venous tortuosity [n = 85 veins]). Images with plus disease had significantly higher vascular tortuosity than images without plus disease (P < 0.05), up to 7.0 disk diameters from the optic disk margin. Vascular tortuosity was higher peripherally than centrally, both in images with and without plus disease, suggesting that peripheral retinal features may be relevant for retinopathy of prematurity diagnosis.