The Intestinal Gas Questionnaire: development of a new instrument for measuring gas-related symptoms and their impact on daily life.
Although gas-related symptoms (GRS) are common and intrusive, there are no questionnaires to quantitate this problem. This study aimed to develop an instrument to rectify this gap in our knowledge. Concepts were initially identified from the literature and interviews with gastroenterologists. Exploratory one-to-one interviews and focus groups with irritable bowel syndrome (IBS) patients (n = 28) and non-IBS subjects (n = 27) with GRS were conducted in UK, France, and Spain leading to a conceptual framework for the questionnaire. Last, iterative rounds of cognitive debriefing were performed with IBS (n = 16) and non-IBS subjects (n = 14). From the first three steps, nine GRS (bloating, distension, flatulence, odorous flatulence, difficult gas evacuation, stomach rumbling, belching, bad breath, and abdominal movement) were identified although abdominal movement was subsequently excluded. Twelve quality of life domains affected by these symptoms were identified as: Clothing, emotional, physical appearance, diet, daily living, work, social life, physical activity, relationships, sex life, sleep, and cognitive function. A 24-h recall for symptoms and a 7-day recall for impact assessment were supported by the qualitative findings. Cognitive debriefing confirmed the understanding of the instrument. Across the three languages, the instrument was conceptually and linguistically consistent. The International Gas Questionnaire is a 2-part instrument, developed rigorously and simultaneously in three languages assessing seven symptoms (17 items) and their impact on 12 domains (26 items) in IBS and general population. It is now undergoing psychometric validation and should provide a unique tool for epidemiological surveys and clinical trials for developing new treatments for these symptoms.


Whitebark pine stand condition, tree abundance, and cone production as predictors of visitation by Clark's nutcracker.
Accurately quantifying key interactions between species is important for developing effective recovery strategies for threatened and endangered species. Whitebark pine (Pinus albicaulis), a candidate species for listing under the Endangered Species Act, depends on Clark's nutcracker (Nucifraga columbiana) for seed dispersal. As whitebark pine succumbs to exotic disease and mountain pine beetles (Dendroctonus ponderosae), cone production declines, and nutcrackers visit stands less frequently, reducing the probability of seed dispersal. We quantified whitebark pine forest structure, health metrics, and the frequency of nutcracker occurrence in national parks within the Northern and Central Rocky Mountains in 2008 and 2009. Forest health characteristics varied between the two regions, with the northern region in overall poorer health. Using these data, we show that a previously published model consistently under-predicts the proportion of survey hours resulting in nutcracker observations at all cone density levels. We present a new statistical model of the relationship between whitebark pine cone production and the probability of Clark's nutcracker occurrence based on combining data from this study and the previous study. Our model clarified earlier findings and suggested a lower cone production threshold value for predicting likely visitation by nutcrackers: Although nutcrackers do visit whitebark pine stands with few cones, the probability of visitation increases with increased cone production. We use information theoretics to show that beta regression is a more appropriate statistical framework for modeling the relationship between cone density and proportion of survey time resulting in nutcracker observations. We illustrate how resource managers may apply this model in the process of prioritizing areas for whitebark pine restoration.


Clinical analysis of 28 children suffering from intracranial hematoma and multiple injuries following traffic accidents.
To evaluate the result of diagnosis and treatment of intracranial hematoma and multiple injuries caused by road traffic accidents. Twenty-eight patients, aged from 1 to 14 years, receiving craniotomy and other surgical treatments were retrospectively reviewed. Among the 28 cases, 23 cured with the recovery rate of 82.3%, 2 had a sequel of moderate disability, and 3 died from severe brain injury, hemorrhagic shock, and other visceral complications. The clinical symptoms and signs were severe and perplexing. The major characters included: severe head injury, usually combined by multiple injuries, and easy of access to missed diagnosis and misdiagnosis. The occurrence of infection is high after traffic accidents as a result of depression of humoral and cellular immunity, long-term bed rest, and fractures of limbs. Hence, on the basis of maintaining vital signs, the management of primary wound is essential to reduce infection and underlying death. In addition to the management of brain injury, concurrent injuries should also be highlighted so as to reach a good result for their patients.


Low maternal awareness of fetal movement is associated with small for gestational age infants.
Our aim was to identify associations between information given to pregnant women about fetal activity, level of maternal awareness of fetal activity, maternal concern about decreased fetal movement, and pregnancy outcomes. This was a population-based cross-sectional study. Mothers with a singleton delivery were invited to answer an anonymous structured questionnaire before discharge from the delivery unit. Six hundred and ninety-one mothers participated (60.4% of eligible women). Women were highly aware of fetal activity. Yet, 25% did not receive any information from care providers about expected normal fetal activity. Receiving information about fetal activity was associated with increased maternal awareness (odds ratio, 2.0; 95% confidence interval [CI], 1.2-3.4). Low maternal awareness of fetal activity was associated with an increased risk of having a small for gestational age infant (odds ratio, 6.5; 95% CI, 3.5-12.3). Expectations about the normal frequency of fetal movements, as reported by the mothers, varied from 25 kicks/hour to 3 kicks/24 hours. Receiving information about expected fetal activity was associated with maternal concerns about decreased fetal movement, but not with improved outcomes. We conclude that receiving information about expected fetal activity was associated with maternal concerns, but not with improved outcomes.


Child abuse and neglect--is it time for a public health approach?
Australia is seeing an unprecedented increase in the rate of child protection notifications and children being taken into care. The burden of such high levels of notifications and removals impact not only the children and families but also the system which is trying to resource them. The concern is that these increases are unsustainable and overloaded child protection systems can be dangerous for the vulnerable families and children they are trying to protect and support. This paper hopes to raise some alternative thinking as to the overall approaches to child abuse and neglect with a greater focus on prevention. Is it time to consider a public health approach, using population-based measures of child abuse and neglect to accurately describe the epidemiology of population risk and protective factors? Should we investigate the potential of universal health, welfare and education services as platforms for prevention? And should we investigate whether the provision of secondary prevention for vulnerable families which address major contributing factors, such as parental substance dependence and mental health issues are effective in reducing abuse of children in these families?


Hyaluronidases and CD44 undergo differential modulation during chondrogenesis.
Hyaluronan, a high-molecular-weight glycosaminoglycan of cartilage, is deposited directly into the extracellular space by hyaluronan synthases, while hyaluronan catabolism is mediated by the hyaluronidases. An in vitro cell culture system has been established in which human dermal fibroblasts are induced to undergo chondrogenesis. Here, we describe the differential modulation of the hyaluronidases and the up-regulation of the hyaluronan receptor, CD44, during such chondrogenesis. Dermal fibroblasts, plated in micromass cultures in the presence of lactic acid and staurosporine for 24 h, were then placed in serum-free, chemically defined medium. At 3 days, RNA was extracted and RT-PCR performed using primers for the hyaluronidase genes. Marked increase in HYAL1 expression was observed, with only moderate increases occurring in HYAL2 and HYAL3. No expression of HYAL4 and PH-20, the sperm-associated hyaluronidase, was detected. RNA levels correlated well with changes in hyaluronidase enzyme activity. Finally, greater expression and staining for the hyaluronan receptor, CD44s, the standard form, were detected. Differential expression of the somatic hyaluronidases and CD44-mediated hyaluronan turnover play a critical role in cartilage development from mesenchymal precursors.


Clinical and descriptive genetic study of polydactyly: a Pakistani experience of 313 cases.
Polydactyly, a common hereditary condition with additional digits in hands and/or feet, is a very attractive model to appreciate clinical and genetic heterogeneity. In order to get an insight into its phenotypic manifestations, we ascertained a cohort of 313 independent families with polydactyly from Pakistan; 35% cases turned out to be familial while 65% were sporadic. In majority of the index cases, polydactyly was presented as an isolated digit defect. Preaxial polydactyly types were 48.24% and postaxial were 51.8%. Familial polydactylies mainly had bilateral and symmetrical presentations, whereas sporadic cases were mostly unilateral and less often symmetrical. In the 313 index subjects a total of 508 limbs with additional digits were recorded. Variable expression was evident as the involvement of upper limbs was more common than the lower, right hand than the left, and left foot than the right. The present cohort establishes interesting epidemiological attributes of polydactyly in the Pakistani population and highlights its extraordinary clinical heterogeneity. Molecular analyses of this cohort are anticipated to elucidate novel genetic factors involved in the origin of additional digits in the growing limb and may provide clues to the role of stochastic factors in the etiology of phenotypic variability in polydactyly.


Robot-assisted vitreoretinal surgery: current perspectives.
Vitreoretinal microsurgery is among the most technically challenging of the minimally invasive surgical techniques. Exceptional precision is required to operate on micron scale targets presented by the retina while also maneuvering in a tightly constrained and fragile workspace. These challenges are compounded by inherent limitations of the unassisted human hand with regard to dexterity, tremor and precision in positioning instruments. The limited human ability to visually resolve targets on the single-digit micron scale is a further limitation. The inherent attributes of robotic approaches therefore, provide logical, strategic and promising solutions to the numerous challenges associated with retinal microsurgery. Robotic retinal surgery is a rapidly emerging technology that has witnessed an exponential growth in capabilities and applications over the last decade. There is now a worldwide movement toward evaluating robotic systems in an expanding number of clinical applications. Coincident with this expanding application is growth in the number of laboratories committed to "robotic medicine". Recent technological advances in conventional retina surgery have also led to tremendous progress in the surgeon's capabilities, enhanced outcomes, a reduction of patient discomfort, limited hospitalization and improved safety. The emergence of robotic technology into this rapidly advancing domain is expected to further enhance important aspects of the retinal surgery experience for the patients, surgeons and society.


The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP.
The SSX gene family is composed of at least five functional and highly homologous members, SSX1 to SSX5, that are normally expressed in only the testis and thyroid. SSX1, SSX2, or SSX4 may be fused to the SYT gene as a result of the t(X;18) translocation in synovial sarcoma. In addition, the SSX1, SSX2, SSX4, and SSX5 genes were found to be aberrantly expressed in several other malignancies, including melanoma. The SSX proteins are localized in the nucleus and are diffusely distributed. In addition, they may be included in polycomb-group nuclear bodies. Other studies have indicated that the SSX proteins may act as transcriptional repressors. As a first step toward the elucidation of the cellular signaling networks in which the SSX proteins may act, we used the yeast two-hybrid system to identify SSX2-interacting proteins. By doing so, two novel human proteins were detected: RAB3IP, the human homolog of an interactor of the Ras-like GTPase Rab3A; and a novel protein, SSX2IP. RAB3IP did not interact with either SSX1, SSX3, or SSX4 in the yeast two-hybrid system, whereas SSX2IP interacted with SSX3 but not with either SSX1 or SSX4. Further analysis of deletion mutants showed that both RAB3IP and SSX2IP interact with the N-terminal moiety of the SSX2 protein. Immunofluorescence analyses of transfected cells revealed that the RAB3IP protein is normally localized in the cytoplasm. However, coexpression of both RAB3IP and SSX2 led to colocalization of both proteins in the nucleus. Likewise, the SSX2IP protein was found to be colocalizing with SSX2 in the nucleus. By performing glutathione-S-transferase pull-down assays, we found that both RAB3IP and SSX2IP interact directly with SSX2 in vitro. These newly observed protein/protein interactions may have important implications for the mechanisms underlying normal and malignant cellular growth.


The Antimicrobial Index: a comprehensive literature-based antimicrobial database and reference work.
Although the ever-growing usage of antimicrobials in the fields of medicine, pharmacology, and microbiology have undoubtedly allowed for unprecedented advances in the scientific world, these advances are nevertheless accompanied by unprecedented challenges. Sharp increases in antibiotic usages have led to inefficient and wasteful usage practices. Bacterial resistances have dramatically increased and therefore hindered the effectiveness of traditional antibiotics, thus forcing many life-science professionals to turn to plant extracts and synthetic chemicals [1]. The Antimicrobial Index (TAMI) seeks to alleviate some of these mounting difficulties through the collection and centralization of relevant antimicrobial susceptibility data from journals. Data compiled for antimicrobials include: method of action, physical properties, resistance genes, side effects, and minimal inhibitory concentrations (MIC50, MIC90 and/or ranges). TAMI currently contains data on 960 antimicrobials and over 24,000 microorganisms (3,500 unique strains) which were collected from over 400 pieces of published literature. Volume and scope of the index have been and will continue to increase and it is hoped that such an index will further foster international cooperation and communication of antimicrobial-related knowledge. TAMI can be accessed at: http://antibiotics.toku-e.com/.


Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission.
Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC-Kpn), are an increasing threat to patient safety. To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI. Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC-Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn4401a), except one KPC-Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC-Kpn (ST491) with Tn4401a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC-Kpn (ST14,ST661) including clonal spread of KPC-Kpn (ST661) from a symptomatic case to nine ward contacts. WGS of outbreak KPC isolates demonstrated blaKPC dissemination via horizontal transposition (Tn4401a), plasmid spread (pKpQIL-D2) and clonal spread (K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of blaKPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts.


Workplace Physical Activity Barriers and Facilitators: A Qualitative Study Based on Employees Physical Activity Levels.
Lack of time, management support, insufficient facilitates, workload balance, and culture are often reported as common barriers to physical activity (PA) participation in the workplace. In comparison, identifying facilitators of PA in the workplace are scarce. A 'one-size-fits-all' approach to overcoming the barriers may also be unsuccessful within university settings where multidisciplinary workforce exists due to the heterogeneity nature of job roles. Thus, the aim of this study was to understand the perceived barriers and facilitators of PA of university employees who were classified as active or inactive based on their job roles. Forty-one employees (female = 17; male = 24) participated in focus groups to discuss their perceived barriers and facilitators to PA in the workplace. Participants were categorised based on their PA levels as active and inactive prior analysing the semi-structured focus groups data via using thematic analysis. The results showed that a lack of time was reported by 80% of the participants as a barrier to PA, including 63% inactive and 17% of the active participants. This included 27% administrators' staff, 23% academics, 19% senior management, and 11% professional service staff. Over 75% participants reported a lack of management support as one of the perceived barriers to their PA engagement in the workplace. Approximately 58% also reported workplace culture as a barrier to PA participation. Open access to a gym on campus was perceived to be the main facilitator to engaging in PA in the future. Similarly, increased management support for engaging in PA and having flexibility during working days were perceived as facilitators for PA engagement and a way to reduced sedentary behaviour in the workplace. These findings contribute to the limited literature in terms of evaluating obstacles and facilitators of university employees to encourage engagement with PA in the workplace. These findings can be applied to form PA, health, and wellbeing-related interventions specifically targeting these identified barriers that are experienced in the workplace and thereby potentially reducing absenteeism and increasing productivity.


Ventricular function in norepinephrine-induced cardiomyopathic rabbits.
Catecholamine cardiomyopathy (CM) was produced in rabbits by a 90-min infusion of norepinephrine (NE, 2 micrograms . kg-1 . min-1). Left ventricular (LV) contractility and pump function (VF) were examined 2 days later and compared with control animals. The effects of hypercapnia [CO2 tension (PCO2) greater than 70 mmHg] and inotropic responsiveness to NE were also determined. VF was assessed by means of left ventricular function curves obtained with constant aortic pressure and heart rate and quantified by determining stroke volume at left ventricular end-diastolic pressure of 10 cmH2O (SV10). Mean SV10 was 1.16 +/- 0.06 ml in controls but averaged only 0.93 +/- 0.05 in CM (P less than 0.02). Hypercapnia caused significantly greater depression of VF in CM than in controls. NE dose-response curves demonstrated increases in both LV dP/dtmax and SV10 in each group. The percent increase in LV dP/dtmax was markedly attenuated n CM, but the increments in SV10 did not differ. The mean histological score in the CM animals was 1.6 +/- 0.1, indicating extensive myofiber injury. No histological abnormalities were observed in the controls. Thus functional defects correlated with the presence of histopathological changes. In addition, a dissociation of velocity (dP/dtmax) and force (SV10) responsiveness to inotropic stimulation was identified in the CM group.


Myelomatosis: comparison of melphalan and cyclophosphamide therapy.
UNTREATED PATIENTS SUFFERING FROM MYELOMATOSIS WERE ALLOCATED AT RANDOM FOR TREATMENT BY THE DAILY ORAL ADMINISTRATION OF EITHER CYCLOPHOSPHAMIDE OR MELPHALAN: 141 received cyclophosphamide and 133 melphalan. The trial began on 1 October 1964 and the intake of patients continued until 31 July 1968. The statistical analysis includes follow-up of the surviving patients to 31 May 1970.The most important single factor affecting the prognosis was the blood urea concentration at presentation. The median survival of the 125 patients whose blood urea concentration was less than 40 mg/100 ml was 33 months, compared with 20 months for the 96 patients whose blood urea concentration was 40-79 mg/100 ml and two months for the 55 patients whose blood urea concentration was 80 mg/100 ml or more.The median survival periods of the 114 patients in the cyclophosphamide group and of the 105 in the melphalan group whose blood urea concentration at presentation was less than 80 mg/100 ml were 27 and 23 months respectively. The difference is not statistically significant.


Sexual Self-Concept Ambiguity and the Interpersonal Theory of Suicide Risk.
Mechanisms (i.e., thwarted belongingness, perceived burdensomeness, hopelessness) derived from the interpersonal theory of suicide which are hypothesized to account for the relation between sexual orientation self-concept ambiguity and active suicide ideation were examined. Participants included 349 women, among whom 42% currently self-ascribed a non-exclusively heterosexual sexual identity. Among women reporting higher levels of sexual self-concept ambiguity, greater risk for active suicide ideation is found when perceptions of burden and feelings of thwarted belonging co-occur with feelings of hopelessness. Results support relevant theory useful for understanding suicide risk among sexual minority women who acknowledge ambiguity with regard to their sexual orientation.


Time management strategies in nursing practice.
With the increasing emphasis on efficiency and effectiveness in health care, how a nurse manages her time is an important consideration. Whilst time management is recognized as an important component of work performance and professional nursing practice, the reality of this process in nursing practice has been subject to scant empirical investigation. To explore how nurses organize and manage their time. A qualitative study was carried out, incorporating narratives (22 nurses), focus groups (24 nurses) and semi-structured interviews (22 nurses). In my role as practitioner researcher I undertook observation and had informal conversations, which provided further data. Study sites were five health care organizations in the United Kingdom during 1995-1999. Time management is complex, with nurses using a range of time management strategies and a repertoire of actions. Two of these strategies, namely routinization and prioritizing, are discussed, including their implications for understanding time management by nurses in clinical practice. Ignoring the influence of 'others', the team and the organization perpetuates a rather individualistic and self-critical perspective of time management. This may lead to a failure to address problems in the organizing of work, and the co-ordinating of care involving other health care workers.


Climate change and health beliefs, knowledge, and educational needs among disaster providers.
Climate change has been called the greatest public health threat of our time. Increasing morbidity and mortality is expected to continue as climate-associated disasters become more prevalent. Disaster health professionals are on the front lines of addressing these health sequalae, making the need to assess their knowledge of climate change and health and their perceived need for a policy response critically important. The purpose of this study is to examine the knowledge, opinions, and educational needs of disaster health providers surrounding climate change and health. A web-based questionnaire assessing disaster health professionals' attitudes and knowledge on the health effects of climate change and associated policy recommendations was administered to a sample of disaster health professionals. Among the study's 150 participants, 95% responded affirmatively that climate change exists and is largely caused by humans. Two-thirds (67%) indicated climate change affects their patient's health and 93% indicated climate change will continue to affect patients in the future. Respondents also believed climate change will impact vulnerable populations such as children under four years old (75%), the elderly (72%) and those living in poverty (71%). Three-quarters (76%) indicated educating patients about climate change and its association with health outcomes should be integrated into health professions education. Disaster health professionals need access to education on climate-change related health impacts, materials for patients and relevant policy information. This research provides evidence from front-line disaster and emergency health professionals that can inform policy on climate change and health.


In situ augmentation of class I major histocompatibility antigen expression on immunogenic variants of a spontaneous murine mammary carcinoma.
The relationship between expression of cell surface glycoproteins encoded by the major histocompatibility complex (MHC) and immunogenicity of a recently obtained spontaneous murine mammary adenocarcinoma (designated CBA.SP1) was examined. Immunogenic and nonimmunogenic variant clones were isolated from a subclone of the parent tumor after treatment with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or the DNA hypomethylating agent and "gene activator," 5-aza-2'-deoxycytidine (5-aza-dCyd). All clones from the untreated tumor population were tumorigenic in normal syngeneic recipients. In contrast, immunogenic variant clones, isolated at high frequencies after drug treatment [ranging from 5% (5-aza-dCyd treated) to greater than 90% (MNNG treated)], were rejected in normal syngeneic mice but grew progressively in T-cell deficient nude mice. Consistent with our previous report (J. Natl. Cancer Inst., 75: 291, 1985), all 5-aza-dCyd induced immunogenic clones expressed elevated levels of class I (particularly Dk) MHC antigens. However some (three out of nine) nonimmunogenic clones also showed enhanced class I MHC expression, implying that not all high MHC expressors were immunogenic. In contrast to 5-aza-dCyd induced variants, only 50% of MNNG induced immunogenic variants showed elevated levels of Dk or Dk and Kk antigens in vitro. Strong augmentation of class I MHC antigens in situ was observed on all immunogenic, but not nonimmunogenic, clones following transplant into syngeneic mice; no increase in MHC expression on variants during progressive growth in athymic nude mice occurred. Although no class II (Ak or Ek) antigens were detected on the parent line or any of the immunogenic variants, a strong infiltration of host I-A bearing cells occurred during immune rejection of SP1 variants. These results are consistent with the hypothesis that induction of class I MHC antigen expression on certain low MHC expressing tumors, although not the sole requirement for immunogenicity, can facilitate immune rejection of the SP1 tumor and, conversely, that the reduced level of MHC observed in certain clinical cancers may significantly affect the immunological aspects of the tumor-host relationship.


Adaptive control of a wheelchair mounted robotic arm with neuromorphically integrated velocity readings and online-learning.
Wheelchair-mounted robotic arms support people with upper extremity disabilities with various activities of daily living (ADL). However, the associated cost and the power consumption of responsive and adaptive assistive robotic arms contribute to the fact that such systems are in limited use. Neuromorphic spiking neural networks can be used for a real-time machine learning-driven control of robots, providing an energy efficient framework for adaptive control. In this work, we demonstrate a neuromorphic adaptive control of a wheelchair-mounted robotic arm deployed on Intel's Loihi chip. Our algorithm design uses neuromorphically represented and integrated velocity readings to derive the arm's current state. The proposed controller provides the robotic arm with adaptive signals, guiding its motion while accounting for kinematic changes in real-time. We pilot-tested the device with an able-bodied participant to evaluate its accuracy while performing ADL-related trajectories. We further demonstrated the capacity of the controller to compensate for unexpected inertia-generating payloads using online learning. Videotaped recordings of ADL tasks performed by the robot were viewed by caregivers; data summarizing their feedback on the user experience and the potential benefit of the system is reported.


Crossed renal ectopia with fusion: report of two patients.
Crossed renal ectopia is one of the rarest urinary system anomalies. It is more often seen at autopsy than in clinical practice. Most cases of renal ectopia remain asymptomatic during life and are diagnosed incidentally. Renal ultrasonography, intravenous pyelography, computerized tomography, and renal scintigraphy (technetium-based tests) are the imaging methods used for diagnosis. Demonstration of crossed renal ectopia is important because it is a predisposing factor for obstruction, infection, and neoplasia of the urinary system. We report two male patients who had unremarkable clinical findings. Both had left-to-right inferior crossed renal ectopia with fusion. Additionally, the first patient had a history of surgery for a recurrent inguinal hernia, whereas the second had crossed fused renal ectopia associated with nephroptosis. Surgeons should be aware of ectopic and fused kidneys to minimize perioperative complications because of the uncertain anatomy.


Ovarian Cancer in Elderly Patients: Patterns of Care and Treatment Outcomes According to Age and Modified Frailty Index.
The present study assessed the predictive value of age and Modified Frailty Index (mFI) on the management of primary epithelial ovarian cancer (EOC) patients aged 70 years or older (elderly). A retrospective multicenter study selected elderly EOC patients treated between 2006 and 2014. Treatments were analyzed according to the following age group categories: (1) 70 to 75 years versus (2) older than 75 years, and mFI of less than 4 (low frailty) versus greater than or equal to 4 (high frailty). Seventy-eight patients were identified (40 in age group 1 and 38 in age group 2). The mFI was greater than or equal to 4 in 23 women. Median age of low frailty and high frailty was not significantly different (75.6 vs 75.3). Comorbidities were equally distributed according to age, whereas diabetes, hypertension, obesity, and chronic renal failure were more frequent in the high-frailty group. Performance status was different only according to mFI. Twenty percent of age group 1 versus 55.3% of age group 2 underwent none or only explorative surgical approach (P = 0.003), whereas surgical approaches were similar in the 2 frailty groups. The rate of postoperative complications was higher in high-frailty patients compared with low-frailty patients (23.5% vs 4.3%; P = 0.03). Chemotherapy was administered to all the patients, a monotherapy regimen to 50% of them. No differences in toxicity were registered, except more hospital recovery in the high-frailty cohort. Median survival time was in favor of younger patients (98 versus 30 months) and less-frailty patients (56 vs 27 months). Elderly EOC patients can receive an adequate treatment, but patients who are older than 75 years can be undertreated, if not adequately selected. The pretreatment assessment of frailty through mFI could be suggested in the surgical and medical management.


Ejection has both positive and negative effects on left ventricular isovolumic relaxation.
In isovolumically beating hearts, the speed of left ventricular (LV) relaxation is uniquely determined by peak active stress (sigma max). In contrast, such a succinct description of relaxation is lacking for the ejection beats, although ejection is generally thought to hasten relaxation. We set out to determine how ejection modifies the relaxation-sigma max relationship obtained in the isovolumically beating hearts. Experiments were performed on five isolated rabbit hearts subjected to various loading conditions. Instantaneous LV pressure and volume were recorded and converted to active stress, from which isovolumic relaxation time (Tr) was defined as the time for stress to fall from 75 to 25% of sigma max (isovolumic beats) or its end-ejection value (ejection beats). Steady-state and transient isovolumic beat and steady-state ejection beat data were used to develop a multiple regression model. This model identified stress, current beat ejection, and previous beat ejection history as independent predictor variables of Tr and fit the data well in all hearts (r2 > 0.98). Furthermore, this model could predict relaxation in transient ejection beats (r2 = 0.30 for all hearts). Whereas the coefficient for the current beat ejection was negative (i.e., negative effect or hastening relaxation), the ejection history coefficient was positive (i.e., positive effect or slowing relaxation). The sum of these two coefficients was negative, corresponding to the commonly observed net negative effect of ejection on relaxation. The expected positive inotropic effect of ejection was also observed. The dissipations of both positive inotropic and relaxation effects were slow, suggesting a nonmechanical underlying mechanism(s). We postulate that these two effects are linked and caused by ejection-mediated changes in myofilament Ca2+ sensitivity.


A Fragment-Based Approach for the Computational Prediction of the Nonspecific Binding of Drugs to Hepatic Microsomes.
Correction for the nonspecific binding (NSB) of drugs to liver microsomes is essential for the accurate measurement of the kinetic parameters Km and Ki, and hence in vitro-in vivo extrapolation to predict hepatic clearance and drug-drug interaction potential. Although a number of computational approaches for the estimation of drug microsomal NSB have been published, they generally rely on compound lipophilicity and charge state at the expense of other physicochemical and chemical properties. In this work, we report the development of a fragment-based hologram quantitative structure activity relationship (HQSAR) approach for the prediction of NSB using a database of 132 compounds. The model has excellent predictivity, with a noncross-validated r2 of 0.966 and cross-validated r2 of 0.680, with a predictive r2 of 0.748 for an external test set comprising 34 drugs. The HQSAR method reliably predicted the fraction unbound in incubations of 95% of the training and test set drugs, excluding compounds with a steroid or morphinan 4,5-epoxide nucleus. Using the same data set of compounds, performance of the HQSAR method was superior to a model based on logP/D as the sole descriptor (predictive r2 for the test set compounds, 0.534). Thus, the HQSAR method provides an alternative approach to laboratory-based procedures for the prediction of the NSB of drugs to liver microsomes, irrespective of the drug charge state (acid, base, or neutral).


The inter-relationship of symptom severity and quality of life in 2055 patients with primary biliary cholangitis.
Age at presentation with primary biliary cholangitis (PBC) is associated with differential response to ursodeoxycholic acid (UDCA) therapy. Younger-presenting patients are less likely to respond to treatment and more likely to need transplant or die from the disease. PBC has a complex impact on quality of life (QoL), with systemic symptoms often having significant impact. To explain the impact of age at presentation on perceived QoL and the inter-related symptoms which impact upon it. Using the UK-PBC cohort, symptoms were assessed using the PBC-40 and other validated tools. Data were available on 2055 patients. Of the 1990 patients reporting a global PBC-QoL score, 66% reported good/neutral scores and 34% reported poor scores. Each 10-year increase in age at presentation was associated with a 14% decrease in risk of poor perceived QoL (OR = 0.86, 95% CI: 0.75-0.98, P < 0.05). All symptom domains were similarly age-associated (P < 0.01). Social dysfunction was the symptom factor with the greatest impact on QoL. Median (interquartile range) PBC-40 social scores for patients with good perceived QoL were 18 (14-23) compared with 34 (29-39) for those with poor QoL. The majority of patients with primary biliary cholangitis do not feel their QoL is impaired, although impairment is reported by a sizeable minority. Age at presentation is associated with impact on perceived QoL and the symptoms impairing it, with younger patients being more affected. Social dysfunction makes the greatest contribution to QoL impairment, and it should be targeted in trials aimed at improving life quality.


[Effect of aeration and redox potential on the biosynthesis of the antibiotic imbricin].
The relationship between imbricin biosynthesis by Streptomyces imbricatus and the medium aeration and redox potential (Eh) was studied. The influence of the oxygen dissolution velocity within the ranges of 2.9 to 0.5 g O2/l.h was investigated and it was shown that the highest yield of the antibiotic was provided by the maximum velocity. At the background of the intensive aeration (2.9 g O2/l.h) decreasing of Eh by reducing agents such as ascorbic acid, L-thyrosin or K4Fe(CN)6 stimulated the biosynthesis whereas at the lower velocities the process proved to be inhibited. Under conditions of insufficient aeration the biosynthesis stimulation could be provided by increasing the medium Eh by acidifying agents such as K2Cr2O7, K3Fe(CN)6 or KMnO4. It was concluded that intensive synthesis of imbricin required not only efficient aeration but also definite levels of the medium redox potential.


The changes in active and inactive renin induced by various maneuvers in hypertensive patients.
The changes in active and inactive renin after captopril (n = 29) or furosemide administration (n = 10) were studied in hypertensive patients. Furthermore, after percutaneous transluminal angioplasty (PTA) in 3 cases of renovascular hypertension (RVH), and after nephrectomy in a case of juxtaglomerular cell tumor, the time course of the changes in these two types of renin was investigated. Inactive renin was activated by trypsin treatment. Plasma renin concentration was measured by using an excess of sheep substrate. In patients with essential hypertension or primary aldosteronism, inactive renin was unchanged, irrespective of response in active renin, after the administration of captopril and furosemide. In patients with RVH, inactive renin was markedly decreased by furosemide but unchanged by captopril, in spite of significant increase in active renin. After PTA and nephrectomy, inactive renin decreased slower than active renin. These data support the idea that in patients with RVH, the increase in active renin by furosemide is at least partly due to the activation of inactive renin. It is also suggested that the increase in active renin by captopril is mainly due to the promoted release of active renin from the kidney. Furthermore, it seems likely that the metabolic clearance of inactive renin is slower than that in active renin.


Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog.
Multiple unrelated polymer systems have evolved to partition DNA molecules between daughter cells at division. To better understand polymer-driven DNA segregation, we reconstituted the three-component segregation system of the R1 plasmid from purified components. We found that the ParR/parC complex can construct a simple bipolar spindle by binding the ends of ParM filaments, inhibiting dynamic instability, and acting as a ratchet permitting incorporation of new monomers and riding on the elongating filament ends. Under steady-state conditions, the dynamic instability of unattached ParM filaments provides the energy required to drive DNA segregation.


ABO Blood Group and Cochlear Status: Otoacoustic Emission Markers.
There are an increasing number of research studies examining the effects of ABO blood group on susceptibility to disease. However, little is known regarding the potential relationship between blood group and hearing. Higher risk of noise-induced hearing loss was linked to blood group O in several occupational health studies. Based on this finding, a recent study of cochlear status was conducted with normal-hearing female participants representing equal numbers of the four blood groups in the ABO blood group system. ABO blood group was associated with cochlear characteristics, including the prevalence of spontaneous otoacoustic emissions (SOAEs) and the amplitudes of transient-evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs). Females with blood group O showed significantly lower amplitudes of DPOAEs at some frequencies and lower prevalence of SOAEs compared with participants with blood group B. There was a general trend of reduced TEOAE and DPOAE amplitudes in blood group O individuals compared with participants with non-O blood groups. Following from this finding, and based on known sex differences in otoacoustic emission characteristics, the present study examined the possible effects of blood group on otoacoustic emission status in males. Sixty clinically normal-hearing males aged between 18 and 26 years, with equal numbers of participants in each of the ABO blood groups, were recruited by purposive sampling. SOAE, DPOAE, and linear and nonlinear TEOAE recordings were collected from all participants, as well as tympanometric data related to external and middle ear characteristics. The male blood group O participants exhibited significantly lower SOAE prevalence and reduced amplitudes of DPOAEs on average, and in the midfrequency range, than participants with blood group B, and lower nonlinear and linear TEOAE amplitudes at a number of frequencies when compared with participants with blood groups A and B. A consistent trend of lower TEOAE and DPOAE response amplitudes was observed in participants with blood group O. No significant difference was noted among blood groups for outer or middle ear characteristics. These results were consistent with previous findings of reduced otoacoustic emission responses in female blood group O individuals. Results support the hypothesis that blood group O individuals may be at increased risk of cochlear damage from noise exposure. Further investigation on the potential link between ABO blood group and auditory status, including potentially differential effects of noise exposure on cochlear function, is needed. The possible effects of ABO blood group on other aspects of audition, such as hearing sensitivity, speech understanding, and auditory processing, should be evaluated.


What's the Use? Disparate Purposes of U.S. Federal Bioethics Commissions.
In the forty-year history of U.S. bioethics commissions, these government-sanctioned forums have often demonstrated their power to address pressing problems and to enable policy change. For example, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, established in 1974, left a legacy of reports that were translated into regulations and had an enormous practical impact. And the 1982 report Splicing Life, by the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, became the basis for the National Institutes of Health's Recombinant DNA Advisory Committee as well as for the Food and Drug Administration's developing "Points to Consider" when contemplating the introduction of recombinant DNA into human beings. Some efforts of bioethics commissions, however, are not tightly connected to policy change or to outcomes directly linked to a specific report. While direct policy impact is indeed a useful metric for government bioethics commissions, it is not their only legitimate utility. For instance, bioethics commissions can also be incubators for deliberation on a hot topic, giving policy-makers time to think through options while the political heat has some time to dissipate. Or a bioethics commission may stake out a position that enables a politician to take action while not necessarily following its recommendations.


Trends in pesticide use on soybean, corn and cotton since the introduction of major genetically modified crops in the United States.
Genetically modified (GM) varieties of soybean, corn and cotton have largely replaced conventional varieties in the United States. The most widely used applications of GM technology have been the development of crops that are resistant to a specific broad-spectrum herbicide (primarily glyphosate) or that produce insecticidal compounds within the plant itself. With the widespread adoption of GM crops, a decline in the use of conventional pesticides was expected. There has been a reduction in the annual herbicide application rate to corn since the advent of GM crops, but the herbicide application rate is mostly unchanged for cotton. Herbicide use on soybean has increased. There has been a substantial reduction in the amount of insecticides used on both corn and cotton since the introduction of GM crops. The observed changes in pesticide use are likely to be the result of many factors, including the introduction of GM crops, regulatory restrictions on some conventional pesticides, introduction of new pesticide technologies and changes in farming practices. In order to help protect human and environmental health and to help agriculture plan for the future, more detailed and complete documentation on pesticide use is needed on a frequent and ongoing basis. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.


Night cough and general practice research.
Thirty-four children, aged between three and nine years, presenting with nocturnal cough, were studied on successive nights using an automatic voice activated tape recorder system. Children with a family history of atopy coughed significantly more than children without such a family history. A wide variation in cough frequency was found both between and within subjects. No effects of treatment on cough frequency were demonstrated. Some of the physiological and pathological mechanisms underlying night cough are discussed.


Nicotine effects and the endogenous opioid system.
Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.


Assessment and introduction of quantitative resistance to Fusarium head blight in elite spring barley.
Breeding for resistance is a key task to control Fusarium head blight (FHB), a devastating disease of small cereals leading to economic losses and grain contamination with mycotoxins harmful for humans and animals. In the present work, FHB resistance of the six-rowed spring barley 'Chevron' to FHB in Germany was compared with those of adapted German spring barley cultivars. Both under natural infection conditions and after spray inoculation with conidia of Fusarium culmorum, F. sporotrichioides, and F. avenaceum under field conditions, Chevron showed a high level of quantitative resistance to the infection and contamination of grain with diverse mycotoxins. This indicates that Chevron is not only a little susceptible to deoxynivalenol-producing Fusarium spp. but also to Fusarium spp. producing type A trichothecenes and enniatins. Monitoring the initial infection course of F. culmorum on barley lemma tissue by confocal laser-scanning microscopy provided evidence that FHB resistance of Chevron is partially mediated by a preformed penetration resistance, because direct penetration of floral tissue by F. culmorum was observed rarely on Chevron but was common on susceptible genotypes. Alternatively, F. culmorum penetrated Chevron lemma tissue via stomata, which was unusual for susceptible genotypes. We generated double-haploid barley populations segregating for the major FHB resistance quantitative trait loci (QTL) Qrgz-2H-8 of Chevron. Subsequently, we characterized these populations by spray inoculation with conidia of F. culmorum and F. sporotrichioides. This suggested that Qrgz-2H-8 was functional in the genetic background of European elite barley cultivars. However, the degree of achieved resistance was very low when compared with quantitative resistance of the QTL donor Chevron, and the introgression of Qrgz-2H-8 was not sufficient to mediate the cellular resistance phenotype of Chevron in the European backgrounds.


Near-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostics.
This contribution describes the design and synthesis of multifunctional micelles based on amphiphilic brush block copolymers (BBCPs) for imaging and selective drug delivery of natural anticancer compounds. Well-defined BBCPs were synthesized via one-pot multi-step sequential grafting-through ring-opening metathesis polymerization (ROMP) of norbornene-based macroinitiators. The norbornenes employed contain a poly(ethylene glycol) methyl ether chain, an alkyl bromide chain, and/or a near-infrared (NIR) fluorescent cyanine dye. After block copolymerization, post-polymerization transformations using bromide-azide substitution, followed by the strain-promoted azide-alkyne cycloaddition (SPAAC) allowed for the functionalization of the BBCPs with the piplartine (PPT) moiety, a natural product with well-documented cytotoxicity against cancer cell lines, via an ester linker between the drug and the polymer side chain. The amphiphilic BBCPs self-assembled in aqueous media into nano-sized spherical micelles with neutral surface charges, as confirmed by dynamic light scattering analysis and transmission electron microscopy. During self-assembly, paclitaxel (PTX) could be effectively encapsulated into the hydrophobic core to form stable PTX-loaded micelles with high loading capacities and encapsulation efficiencies. The NIR fluorescent dye-containing micelles exhibited remarkable photophysical properties, excellent colloidal stability under physiological conditions, and a pH-induced disassembly under slightly acidic conditions, allowing for the release of the drug in a controlled manner. The in vitro studies demonstrated that the micelles without the drug (blank micelles) are biocompatible at concentrations of up to 1 mg mL-1 and present a high cellular internalization capacity toward MCF-7 cancer cells. The drug-functionalized micelles showed in vitro cytotoxicity comparable to free PPT and PTX against MCF-7 and PC3 cancer cells, confirming efficient drug release into the tumor environment upon cellular internalization. Furthermore, the drug-functionalized micelles exhibited higher selectivity than the pristine drugs and preferential cellular uptake in human cancer cell lines (MCF-7 and PC3) when compared to the normal breast cell line (MCF10A). This study provides an efficient strategy for the development of versatile polymeric nanosystems for drug delivery and image-guided diagnostics. Notably, the easy functionalization of BBCP side chains via SPAAC opens up the possibility for the preparation of a library of multifunctional systems containing other drugs or functionalities, such as target groups for recognition.


Changes in leukocytes caused by tritium contamination.
Tritium is a radionuclide uniformly absorbed by the body. The purpose of cytomorphological and cytochemical leukocytes examination in tritium-affected workers was early detection of initial health disorder caused by tritium contamination. Cytoplasm and nuclear morphological changes were analyzed by colored blood smear microscopy. The enzyme activity (APL, MPO) in granulocytes was examined by cytochemical methods. Morphological changes were found in 47.17% of the subjects (N = 53) and in 2% (N = 52) of the controls. Chromosomal aberrations in lymphocytes were found in 49.05% of the exposed workers and in 2% of the controls. The granulocytes enzyme activities were significantly diminished in the exposed workers (p < or = 0.001). The average level of beta radiation found in the urine of those affected by tritium was 3.46 kBq L(-1), while it was significantly lower in the others: 0.35 kBq L(-1). The enzyme activity decreases after 5 y of tritium exposure. Nuclear and cytoplasm changes as well as lowered enzyme activity in granulocytes were found in tritium-contaminated workers. Interdependence of cytomorphological and cytochemical changes was established. There was no correlation between cytochemical changes and granulocytes count.


Clinician perspectives on considering radiation exposure to patients when ordering imaging tests: a qualitative study.
Increased computer tomography (CT) scan use has contributed to a rise in medically-associated radiation exposure. The extent to which clinicians consider radiation exposure when ordering imaging tests is unknown. We examined (1) outpatient clinician attitudes towards considering radiation exposure when ordering CT scans; and (2) clinician reactions to displaying radiation exposure information for CT scans at clinician electronic order entry. We conducted nine focus groups with primary care clinicians and subspecialty physicians (nephrology, pulmonary and neurology) (n=50) who deliver outpatient care across 12 hospital-based clinics and community health centres in an urban safety-net health system, which use a common electronic order entry system. We analysed focus group transcripts using an inductive framework to identify emergent themes and illustrative quotations. Clinicians felt they had limited knowledge of the clinical implications of radiation exposure. Many believed clinically relevant information such as the increased risk of malignancy from CT scans would be useful to inform decision-making and patient-clinician discussions. Clinicians noted that patient vulnerability and long wait times for tests with less radiation exposure (such as MRI or ultrasound) often acted as barriers to minimise patient radiation exposure from CT scans. Clinicians suggested providing patients' cumulative radiation exposure or formal decision aids to improve the usefulness of the radiation exposure information. Displaying clinically relevant radiation exposure information at order entry may improve clinician knowledge and inform patient-clinician discussions regarding risks and benefits of imaging. However, limited access to tests with lower radiation exposure in safety-net settings may trump efforts to minimise patient radiation exposure.


Mineral trioxide aggregate for obturation of maxillary central incisors with necrotic pulp and open apices.
There are few reports on treatment of necrotic pulps with mineral trioxide aggregate (MTA) for apexification. Five immature teeth with necrotic pulps were treated with the use of an apical plug of MTA for apexification. All teeth were central incisors that had premature interruption of root development caused by a previous trauma. According to the treatment protocol, the root canals were rinsed with 5% NaOCl; then calcium hydroxide paste was placed in the canals for 1-6 weeks. The apical portion of the canals were filled with MTA. The rest of the canals were obturated with lateral condensation of the gutta-percha applied with a canal sealer. At 6 months, 1 year and 2 year follow-up periods the clinical and radiographic appearance of the teeth showed the resolution of the periapical lesions and continued root end development in all except in the one case in which the MTA was extruded out the apex. MTA can be considered a very effective option for apexification with the advantage of reduced treatment time, good sealing ability and high biocompatibility.


Automatic gait recognition based on statistical shape analysis.
Gait recognition has recently gained significant attention from computer vision researchers. This interest is strongly motivated by the need for automated person identification systems at a distance in visual surveillance and monitoring applications. The paper proposes a simple and efficient automatic gait recognition algorithm using statistical shape analysis. For each image sequence, an improved background subtraction procedure is used to extract moving silhouettes of a walking figure from the background. Temporal changes of the detected silhouettes are then represented as an associated sequence of complex vector configurations in a common coordinate frame, and are further analyzed using the Procrustes shape analysis method to obtain mean shape as gait signature. Supervised pattern classification techniques, based on the full Procrustes distance measure, are adopted for recognition. This method does not directly analyze the dynamics of gait, but implicitly uses the action of walking to capture the structural characteristics of gait, especially the shape cues of body biometrics. The algorithm is tested on a database consisting of 240 sequences from 20 different subjects walking at 3 viewing angles in an outdoor environment. Experimental results are included to demonstrate the encouraging performance of the proposed algorithm.


Chagas disease in 2 geriatric rhesus macaques (Macaca mulatta) housed in the Pacific Northwest.
Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission.


Cervical cancer incidence and patient survival in Manizales, Colombia, 2008-2012.
To estimate the cervical cancer incidence and survival rates by histological subtype and stage in Manizales, Colombia during 2008-2012; and to compare the survival rate to the one from the previous five years. Using population-based data, incidence rates by age were standardized for each histological subtype. Active and passive follow-up was performed to determine vital status and cause of death at 60 months. The Kaplan-Meier method and Cox models were adjusted to estimate overall survival by each covariant. A total of 217 new cases were observed; with a mean incidence of 17.8 per 100,000 woman-years. Stages III-IV were more frequently observed in patients of medium and low socioeconomic status. At 5 years, the survival rate was 68.9%; ages over 70 years were associated with lower survival rates (p<0.001). Risk of death was 90% higher in patients with undifferentiated or unknown histological samples, when compared with those with squamous cell carcinoma (HR 1.9, 95% CI: 1.1-3.3). Likewise, the risk of death was 1.7 times higher for patients aged over 70 years (HR 2.7, 95% CI 1.6-4.8); and it was also found to be 3 times higher for stage III (HR 4.3, 95% CI: 1.8-10.2) and 7 times higher for stage IV (HR 8.7, 95% CI: 3.6-20.1), when compared with stage I. The incidence rate of cervical cancer in Manizales was found to be similar to the global and continental rates and lower than those from other Colombian cities with similar characteristics. Advanced stages were more frequent in women of low socioeconomic status. Survival was associated with age, histological subtype and staging.


The optokinetic response in zebrafish and its applications.
The optokinetic response (OKR) is a stereotyped eye movement in response to movement in he surround. The OKR serves to stabilize the visual image on the retina, and allows for high resolution vision. Due to its high selection value, all vertebrates display this basic behavior. Here, we review the properties of the OKR with a focus on the zebrafish, including methodological aspects of measuring eye movements in small larvae. The genetic amenabilities of the zebrafish model permit the use of this reflexive behavior in genetic screens. Such approaches have led to the isolation of mutant strains with specific defects in the visual pathway. In addition to the use of the OKR as a screening assay, mutations with characteristic abnormalities in the execution of this behavior will enable the analysis of sensory-motor control in great detail. A case in point is the belladonna mutation, where an axonal misrouting effect at the optic chiasm leads to a reversed OKR with a number of interesting properties.


Quantifying transmission dynamics of acute hepatitis C virus infections in a heterogeneous population using sequence data.
Opioid substitution and syringes exchange programs have drastically reduced hepatitis C virus (HCV) spread in France but HCV sexual transmission in men having sex with men (MSM) has recently arisen as a significant public health concern. The fact that the virus is transmitting in a heterogeneous population, with different transmission routes, makes prevalence and incidence rates poorly informative. However, additional insights can be gained by analyzing virus phylogenies inferred from dated genetic sequence data. By combining a phylodynamics approach based on Approximate Bayesian Computation (ABC) and an original transmission model, we estimate key epidemiological parameters of an ongoing HCV epidemic among MSMs in Lyon (France). We show that this new epidemic is largely independent of the previously observed non-MSM HCV epidemics and that its doubling time is ten times lower (0.44 years versus 4.37 years). These results have practical implications for HCV control and illustrate the additional information provided by virus genomics in public health.


Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer.
Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.


Convergence Analysis of the Hessian Estimation Evolution Strategy.
The class of algorithms called Hessian Estimation Evolution Strategies (HE-ESs) update the covariance matrix of their sampling distribution by directly estimating the curvature of the objective function. The approach is practically efficient, as attested by respectable performance on the BBOB testbed, even on rather irregular functions. In this article, we formally prove two strong guarantees for the (1 + 4)-HE-ES, a minimal elitist member of the family: stability of the covariance matrix update, and as a consequence, linear convergence on all convex quadratic problems at a rate that is independent of the problem instance.


Multi-exposure laser speckle contrast imaging using a video-rate multi-tap charge modulation image sensor.
Multi-exposure laser speckle contrast imaging (MELSCI) systems based on high frame rate cameras are suitable for wide-field quantitative measurement of blood flow. However, high-speed camera-based MELSCI requires high power consumption, large memory, and high processing capability, which may lead to relatively large and expensive hardware. To realize a compact and cost-efficient MELSCI system, we discuss an application of the multi-tap CMOS image sensor originally designed for time-of-flight range imaging. This image sensor operated in the global shutter mode and every pixel was provided with multiple charge-storage diodes. Multiple images for different exposures were acquired simultaneously because exposure patterns were programmable to implement an arbitrary exposure duration for each tap. The frame rate was close to video frame rates (30 frames per second (fps)) regardless of the exposure pattern. The feasibility of the proposed method was verified by simulations that were performed with real speckle images captured by a high-speed camera at 40 kfps. Experiments with a four-tap CMOS image sensor demonstrated that a flow speed map was obtained at a moderate frame rate such as 35 fps for a moving ground glass plate and 45 fps for flowing Intralipose, which were linearly moved at speeds of 1-5 mm/s.


[The basal concentration and characteristics of the diurnal secretory rate of prolactin in women with primary hypothyroidism].
Basal concentration was measured of prolactin (PRL) as were its diurnal fluctuations in blood depending on the clinical association of primary hypothyrosis (PH) with lactorrhea-amenorrhea, lactorrhea only or lactorrhea associated with disturbances in menstrual and reproductive functions that differ from those in amenorrhea, and without such disturbances. Patients with lactorrhea-amenorrhea syndrome present with continual hyperprolactinemia and no physiological diurnal rythm of PRL secretion. In patients presenting without amenorrhea, and basal hyperprolactinemia, lactorrhea and disordered menses result from transitory "night-time" hyperprolactinemia. PH patients who do not present with lactorrhea and disordered menstrual and reproductive function show physiological diurnal rythm of PRL secretion, with its parameters corresponding to those in healthy women. The development of hyperprolactinemia in PH is not age-related; neither is it associated with severity of hypothyrosis.


RING finger E3 ubiquitin ligase gene TaAIRP2-1B controls spike length in wheat.
E3 ubiquitin ligase genes play important roles in the regulation of plant development. They have been well studied in plants, but have not been sufficiently investigated in wheat. Here, we identified a highly expressed RING finger E3 ubiquitin ligase gene TaAIRP2-1B (ABA-insensitive RING protein 2) in wheat spike. Sequence polymorphism and association analysis showed that TaAIRP2-1B is significantly associated with spike length under various conditions. The genotype with haplotype Hap-1B-1 of TaAIRP2-1B has a longer spike than that of Hap-1B-2, and was positively selected in the process of wheat breeding in China. Moreover, the TaAIRP2-1B-overexpressing rice lines have longer panicles compared with wild-type plants. The expression levels of TaAIRP2-1B in Hap-1B-1 accessions were higher than in Hap-1B-2 accessions. Further study revealed that the expression of TaAIRP2-1B was negatively regulated by TaERF3 (ethylene-responsive factor 3) via binding to the Hap-1B-2 promoter, but not via binding of Hap-1B-1. Additionally, several candidate genes interacting with TaAIRP2-1B were obtained by screening the cDNA library of wheat in yeast cells. It was found that TaAIRP2-1B interacted with TaHIPP3 (heavy metal-associated isoprenylated protein 3) and promoted TaHIPP3 degradation. Our study demonstrates that TaAIRP2-1B controls spike length, and the haplotype Hap-1B-1 of TaAIRP2-1B is a favorable natural variation for spike length enhancement in wheat. This work also provides genetic resources and functional markers for wheat molecular breeding.


Effects of Pseudomonas aureofaciens 63-28 on defense responses in soybean plants infected by Rhizoctonia solani.
The objective of this work was to investigate the ability of the plant growth-promoting rhizobacterium Pseudomonas aureofaciens 63-28 to induce plant defense systems, including defense-related enzyme levels and expression of defense-related isoenzymes, and isoflavone production, leading to improved resistance to the phytopathogen Rhizoctonia solani AG-4 in soybean seedlings. Seven-dayold soybean seedlings were inoculated with P. aureofaciens 63-28, R. solani AG-4, or P. aureofaciens 63-28 plus R. solani AG-4 (P+R), or not inoculated (control). After 7 days of incubation, roots treated with R. solani AG-4 had obvious damping-off symptoms, but P+R-treated soybean plants had less disease development, indicating suppression of R. solani AG-4 in soybean seedlings. Superoxide dismutase (SOD) and catalase (CAT) activities of R. solani AG-4-treated roots increased by 24.6% and 54.0%, respectively, compared with control roots. Ascorbate peroxidase (APX) and phenylalanine ammonia lyase (PAL) activities of R. solani AG-4-treated roots were increased by 75.1% and 23.6%, respectively. Polyphenol oxidase (PPO) activity in soybean roots challenged with P. aureofaciens 63-28 and P+R increased by 25.0% and 11.6%, respectively. Mn-SOD (S1 band on gel) and Fe-SOD (S2) were strongly induced in P+R-treated roots, whereas one CAT (C1) and one APX (A3) were strongly induced in R. solani AG-4- treated roots. The total isoflavone concentration in P+Rtreated shoots was 27.2% greater than the control treatment. The isoflavone yield of R. solani AG-4-treated shoots was 60.9% less than the control.


Estrogen and bone-muscle strength and mass relationships.
The largest voluntary loads on bones come from muscles. To adapt bone strength and mass to them, special strain threshold ranges determine where modeling adds and strengthens bone, and where remodeling conserves or removes it, just as different thermostat settings control the heating and cooling systems in a house. If estrogen lowers the remodeling threshold, two things should occur. First, at puberty in girls, bone mass should begin to increase more than in boys with similar muscle strengths, owing to reduced remodeling-dependent bone losses, while gains from longitudinal bone growth and bone modeling continue normally. That increase in bone mass in girls should plateau when their muscle strength stops increasing, since their stronger bones could then reduce bone strains enough to turn modeling off, but could let remodeling keep conserving existing bone. Second, decreased estrogen secretion [or a related factor(s)], as during menopause, should raise the remodeling threshold and make remodeling begin removing that extra bone. That removal should also tend to plateau after the remaining and weaker bone lets bone strains rise to the higher threshold. Postmenopausal bone loss shows the second effects. Previously unremarked relationships in the data of a 1995 Argentine study showed the first effects. This supports the idea that estrogen can affect human bone strength and mass by lowering the remodeling threshold, and loss of estrogen would raise the threshold and help cause postmenopausal bone loss even if other factors help to do it. The Argentine study also suggested ways to study those things and the roles of muscle strength and other factors in controlling bone strength and mass in children and adult humans. Those factors included, in part, hormones, vitamins, calcium, diet, sex, race, age, medications, cytokines, genetic errors, gene expression patterns, and disease.


Regulation of MSC and macrophage functions in bone healing by peptide LL-37-loaded silk fibroin nanoparticles on a titanium surface.
Titanium-based materials have been long regarded as effective bone implants for clinical use, yet the corresponding osteointegration ability needs to be optimized. This challenge can be overcome by fabricating titanium (Ti) materials with physiological functions. In this study, peptide LL-37-loaded silk fibroin nanoparticles (SFNPs) were immobilized on a titanium surface to facilitate osteointegration by regulating the physiological functions of mesenchymal stem cells (MSCs) and macrophages. According to our results, the cell viability, recruitment and paracrine responses of MSCs and macrophages were improved by the modified Ti samples. MSC differentiation was promoted by the macrophages incubated on the modified Ti samples, and the phenotype switch of macrophages was also modulated by the MSCs incubated on the modified Ti samples. In vivo studies proved that the modified Ti implant induced MSC and macrophage recruitments to injury sites and the inflammatory response was positively regulated. Moreover, better bone formation was achieved around the modified Ti implant 28 days after surgery. This suggested that the immobilization of peptide LL-37-loaded SFNPs on a titanium surface improves osteointegration via the regulation of physiological functions of MSCs and macrophages.


Children's hospitals do not acutely respond to high occupancy.
High hospital occupancy may lead to overcrowding in emergency departments and inpatient units, having an adverse impact on patient care. It is not known how children's hospitals acutely respond to high occupancy. The objective of this study was to describe the frequency, direction, and magnitude of children's hospitals' acute responses to high occupancy. Patients who were discharged from 39 children's hospitals that participated in the Pediatric Health Information System database during 2006 were eligible. Midnight census data were used to construct occupancy levels. Acute response to high occupancy was measured by 8 variables, including changes in hospital admissions (4 measures), transfers (2 measures), and length of stay (2 measures). Hospitals were frequently at high occupancy, with 28% of midnights at 85% to 94% occupancy and 42% of midnights at > or =95% occupancy. Whereas half of children's hospitals used occupancy-mitigating responses, there was variability in responses and magnitudes were small. When occupancy was >95%, no more than 8% of hospitals took steps to reduce admissions, 13% increased transfers out, and up to 58% reduced standardized length of stay. Two-day lag response was more common but remained of too small a magnitude to make a difference in hospital crowding. Additional modeling techniques also revealed little response. We found a low rate of acute response to high occupancy. When there was a response, the magnitude was small.


Complementary medicine use by patients with inflammatory bowel disease.
The purpose of this study was to establish the degree and determinants of the use of complementary therapies by patients with inflammatory bowel disease (IBD) and their reasons for seeking them. The first phase was a cross-sectional survey of 134 patients with IBD (98 with Crohn's disease, 34 with ulcerative colitis, and two indeterminate) using a mailed, structured questionnaire (response rate 70%). Determinants of complementary medicine use were examined using logistic regression. The second phase was an in-depth exploration using personal interviews of the beliefs and perceptions of 14 complementary medicine users about the management of their disease. Analysis was performed using standard qualitative techniques and the identification of important, patient-identified themes about the management of IBD. Complementary therapies had been used by 51% of patients in the previous 2 yr. Current use was reported by 33%, of whom one-half were using it for their IBD. Vitamins and herbal products were the most commonly reported therapies. In multivariate analysis, duration of disease > 10 yr and a history of hospitalization were independent predictors of complementary medicine use. The side effects and lack of effectiveness of standard therapies were the most commonly cited reasons for seeking complementary medicine. Sixty-two percent had told their doctor about their use of complementary medicine. Complementary medicine use is common in patients with IBD, especially among those with a longer duration of disease or a history of hospitalization.


A global health training model for teaching pediatric clinical decision making skills to Rwandan physical therapists: A case report.
Background and Purpose: There is increasing interest among physical therapists from high-income countries to participate in education development projects in low-income countries. However, there are few examples in the literature of effective developmental models or projects. This case report describes a model for improving pediatric clinical decision making skills among Rwandan physical therapists using best practices in clinical decision making, evidence-based practice where possible, and use of the International Classification of Functioning and Disability (ICF) model. Case Description: A 48-hour continuing professional development course based on the pediatric section of the Advancement of Rwandan Rehabilitation Services Project (ARRSP) was presented to 66 Rwandan physical therapists in the form of classroom lectures, laboratory and case study practice, and clinical visits to the course participant's work place. Interactive teaching and learning was emphasized. Outcomes: Course participants completed a pre- and post-course assessment addressing course content. There was a 53% improvement in post-course assessment scores. A post-course evaluation eliciting participants' confidence in eight clinical decision making skills emphasized in course material was also administered. Comments were strongly positive (92%) for the value of clinical visits in reinforcing the participant's new clinical skills. Discussion: This case report documents a global health continuing professional development project that improved pediatric rehabilitation knowledge and clinical skill confidence. The project incorporated sustainability by soliciting both input and involvement of the target audience from start to finish; from the needs assessment to classroom teaching. Building on these two aspects promotes a sense of ownership and longevity.


The vasa nervorum: microcorrosion casts for scanning electron microscopy.
Studies on the vasa nervorum have a long history, not least because of their beneficial application in surgical practice and in understanding the pathogenesis of some neuropathies. In the present study a method is described for the preparation of microcorrosion casts of the vasa nervorum suitable for examination by scanning electron microscopy. The results confirm the findings of earlier investigations but also demonstrate the advantages of an immediate three-dimensional representation of the vascular architecture together with the additional magnification and resolving power of electron microscopy.


Standoff monitoring of aqueous aerosols using nanosecond laser-induced breakdown spectroscopy: droplet size and matrix effects.
Nanosecond laser-induced breakdown spectroscopy has been examined for the analysis of suspended matter in a free stream of air. The real-time monitoring of this scenario poses major challenges for an accurate categorization due to its changing characteristics such as composition, size, and density of particles. The effects of particle size and matrix in the optical emission responses registered from such scenarios have been evaluated. Distant (10 m) plasmas of saline solutions, containing either NaCl or Na2SO4 at different concentrations, have been induced by nanosecond laser pulses at a wavelength of 1064 nm. The effects of the droplet size and its concentration on differences in the laser-induced breakdown probability, the intensity of the characteristic lines, and the plasma emission continuum have been discussed. The quantification of sodium in distant water droplets has been proved. However, an initial knowledge on the average droplet size is required. The average droplet size could be determined from the slope of H I and O I lines versus the continuum plasma emission, which is only weakly influenced by the salt content in the droplets.


[Topographic and histological study of the sinoatrial node in the Jaffarabadi buffalo (Babalus bubalis Linnaeus, 1758)].
A topographic and histologic study of the sinuatrial node was made in the hearts of 12 buffalo of the Jaffarabadi breed, 8 adults (5 females and 3 males) and 4 term fetuses (3 female and 1 male). The nodal tissue was localized at the junction of the vena cava superior with the right atrium, occupying, more precisely, the entire extent of the terminal groove, the dihedral cavoatrial angle and the first part of the auricular surface of the junction, which is contiguous with this angle. This structure contains cells with single or double nuclei, round or oval in shape, surrounded by a light halo, with scattered chromatin and a well-defined nucleolus, acidophilic cytoplasm containing, in comparison with the common myocardium, few sinuous myofibrils with transverse striations and a larger amount of glycogen. We also observed arteries of small and medium caliber, with veins and nerves accompanying the nodal mass, while the nerve ganglia were situated opposite the sinuatrial node.


Soil organic carbon across scales.
Mechanistic understanding of scale effects is important for interpreting the processes that control the global carbon cycle. Greater attention should be given to scale in soil organic carbon (SOC) science so that we can devise better policy to protect/enhance existing SOC stocks and ensure sustainable use of soils. Global issues such as climate change require consideration of SOC stock changes at the global and biosphere scale, but human interaction occurs at the landscape scale, with consequences at the pedon, aggregate and particle scales. This review evaluates our understanding of SOC across all these scales in the context of the processes involved in SOC cycling at each scale and with emphasis on stabilizing SOC. Current synergy between science and policy is explored at each scale to determine how well each is represented in the management of SOC. An outline of how SOC might be integrated into a framework of soil security is examined. We conclude that SOC processes at the biosphere to biome scales are not well understood. Instead, SOC has come to be viewed as a large-scale pool subjects to carbon flux. Better understanding exists for SOC processes operating at the scales of the pedon, aggregate and particle. At the landscape scale, the influence of large- and small-scale processes has the greatest interaction and is exposed to the greatest modification through agricultural management. Policy implemented at regional or national scale tends to focus at the landscape scale without due consideration of the larger scale factors controlling SOC or the impacts of policy for SOC at the smaller SOC scales. What is required is a framework that can be integrated across a continuum of scales to optimize SOC management.


Clinical efficacy of apple polyphenol for treating cedar pollinosis.
A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.


Astroviruses as a cause of gastroenteritis in children.
Infection with astroviruses has been associated with gastroenteritis in children, and serologic surveys indicate that this infection may be frequent. The importance of astroviruses as agents of gastroenteritis has not been shown in a controlled study, however. We used monoclonal antibody-based enzyme immunoassays to detect astroviruses, enteric adenoviruses, and rotaviruses in stool samples obtained from age-matched children with and children without gastroenteritis. The samples were obtained in two studies, three years apart, among patients attending an outpatient clinic in Bangkok, Thailand. In the first study, astroviruses were detected in 8.6 percent (96 of 1111) of the children with gastroenteritis and in 2.0 percent (19 of 947) of the children without gastroenteritis. In the second study the rates were 8.6 percent (50 of 580) and 2.1 percent (11 of 512), respectively. For both studies combined, enteric adenoviruses were detected in 2.6 percent of those with gastroenteritis and in 0.5 percent of the controls, whereas rotaviruses were detected in 19 percent of those with gastroenteritis and in 1.0 percent of the controls. The clinical findings associated with astrovirus infection were similar to those associated with rotavirus infection, except for a trend toward greater dehydration in the children infected with rotaviruses. These two controlled studies involving a total of 3150 Thai children provide evidence that astroviruses are a common cause of viral gastroenteritis. Astroviruses were found in association with gastroenteritis more frequently than were enteric adenoviruses, and with nearly half the frequency of rotaviruses.


Estimating the heritability of female lifetime fecundity in a locally adapted Drosophila melanogaster population.
The heritability of genome-wide fitness that is expected in finite populations is poorly understood, both theoretically and empirically, despite its relevance to many fundamental concepts in evolutionary biology. In this study, we used two independent methods of estimating the heritability of lifetime female fecundity (the predominant female fitness component in this population) in a large, outbred population of Drosophila melanogaster that had adapted to the laboratory environment for over 400 generations. Despite strong directional selection on adult female fecundity, we uncovered high heritability for this trait that cannot be explained by antagonistic pleiotropy with juvenile fitness. The evolutionary significance of this high heritability of lifetime fecundity is discussed.


Vernier and grating acuity in adult hooded rats: the influence of sex.
Although morphological sex differences are pervasive in the primary visual cortex of hooded rats, it is not known whether sex differences occur in vision in these rats. In this study, grating acuity was measured in a forced-choice Y maze and a jumping stand in adult hooded rats, and vernier acuity thresholds were established in the jumping stand. With a criterion of 34 correct/50 trials, the number of correct choices for both sexes was high (1.0-1.6 cycles per degree [c/deg]) for spatial gratings. Female rats made more correct identifications of the coarse gratings (0.125 and 0.25 c/deg) than male rats, but no sex differences were found for higher spatial frequencies. In contrast, male rats were better at detecting smaller vernier offsets in both the individual criterion and group averages than female rats, and all of the rats detected vernier misalignments at 34.1 min (equivalent to 1.75 c/deg), which is above their grating acuity. Vernier acuity may mirror some sex differences in visual cortex anatomy.


Big-Loop Recurrence within the Hippocampal System Supports Integration of Information across Episodes.
Recent evidence challenges the widely held view that the hippocampus is specialized for episodic memory, by demonstrating that it also underpins the integration of information across experiences. Contemporary computational theories propose that these two contrasting functions can be accomplished by big-loop recurrence, whereby the output of the system is recirculated back into the hippocampus. We use ultra-high-resolution fMRI to provide support for this hypothesis, by showing that retrieved information is presented as a new input on the superficial entorhinal cortex-driven by functional connectivity between the deep and superficial entorhinal layers. Further, the magnitude of this laminar connectivity correlated with inferential performance, demonstrating its importance for behavior. Our findings offer a novel perspective on information processing within the hippocampus and support a unifying framework in which the hippocampus captures higher-order structure across experiences, by creating a dynamic memory space from separate episodic codes for individual experiences.


Essential fatty acids and phospholipase A2 in autistic spectrum disorders.
A health questionnaire based on parental observations of clinical signs of fatty acid deficiency (FAD) showed that patients with autism and Asperger's syndrome (ASP) had significantly higher FAD scores (6.34+/-4.37 and 7.64+/-6.20, respectively) compared to controls (1.78+/-1.68). Patients with regressive autism had significantly higher percentages of 18:0,18:2n-6 and total saturates in their RBC membranes compared to controls, while 24:0, 22:5n-6, 24:1 and the 20:4n-6/20:5n-3 ratio were significantly higher in both regressive autism and ASP groups compared to controls. By comparison, the 18:1n-9 and 20:4n-6 values were significantly lower in patients with regressive autism compared to controls while 22:5n-3, total n-3 and total dimethyl acetals were significantly lower in both regressive autism and ASP groups compared to controls. Storage of RBC at -20 degrees C for 6 weeks resulted in significant reductions in highly unsaturated fatty acid levels in polar lipids of patients with regressive autism, compared to patients with classical autism or ASP, or controls. Patients diagnosed with both autism and ASP showed significantly increased levels of EPA ( approximately 200%) and DHA ( approximately 40%), and significantly reduced levels of ARA ( approximately 20%), 20:3n-6 and ARA/EPA ratio in their RBC polar lipids, when supplemented with EPA-rich fish oils, compared to controls and non-supplemented patients with autism. Patients with both regressive autism and classical autism/Asperger's syndrome had significantly higher concentrations of RBC type IV phospholipase A2 compared to controls. However, patients with autism/ASP, who had taken EPA supplements, had significantly reduced PLA2 concentrations compared to unsupplemented patients with classical autism or ASP.


Determination of the structure of the catabolic N-succinylornithine transaminase (AstC) from Escherichia coli.
Escherichia coli possesses two acyl ornithine aminotransferases, one catabolic (AstC) and the other anabolic (ArgD), that participate in L-arginine metabolism. Although only 58% identical, the enzymes have been shown to be functionally interchangeable. Here we have purified AstC and have obtained X-ray crystal structures of apo and holo-AstC and of the enzyme complexed with its physiological substrate, succinylornithine. We compare the structures obtained in this study with those of ArgD from Salmonella typhimurium obtained elsewhere, finding several notable differences. Docking studies were used to explore the docking modes of several substrates (ornithine, succinylornithine and acetylornithine) and the co-substrate glutamate/α-ketogluterate. The docking studies support our observations that AstC has a strong preference for acylated ornithine species over ornithine itself, and suggest that the increase in specificity associated with acylation is caused by steric and desolvation effects rather than specific interactions between the substrate and enzyme.


Wound healing properties of Indian propolis studied on excision wound-induced rats.
In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.


[Multiplexed peroperative mapping in unstable rhythm disorders].
Since the introduction and development of mapping methods in clinical practice, some arrhythmias can now be treated surgically. We studied an automatized method of epicardial mapping necessitating only a single ventricular complex for the definition of epicardial activation; the signal was acquired from 35 monopolar electrodes spread out over the whole of the ventricular epicardium or concentrated in the zone of epicardial break through to localise its site more accurately. The acquisition, elaboration and tracing of these maps were performed with a computer; the activation can be presented as isochrones or isopotentials. The main value of this method of automatic mapping is the possibility of studying irregular arrhythmias whose potentials are difficult to obtain beat manually. This method has already been applied to 21 patients with ventricular tachycardia unresponsive to medical treatment and referred for surgery.