Dissociable neural patterns of facial identity across changes in viewpoint.
We examined the neural response patterns for facial identity independent of viewpoint and for viewpoint independent of identity. Neural activation patterns for identity and viewpoint were collected in an fMRI experiment. Faces appeared in identity-constant blocks, with variable viewpoint, and in viewpoint-constant blocks, with variable identity. Pattern-based classifiers were used to discriminate neural response patterns for all possible pairs of identities and viewpoints. To increase the likelihood of detecting distinct neural activation patterns for identity, we tested maximally dissimilar "face"-"antiface" pairs and normal face pairs. Neural response patterns for four of six identity pairs, including the "face"-"antiface" pairs, were discriminated at levels above chance. A behavioral experiment showed accord between perceptual and neural discrimination, indicating that the classifier tapped a high-level visual identity code. Neural activity patterns across a broad span of ventral temporal (VT) cortex, including fusiform gyrus and lateral occipital areas (LOC), were required for identity discrimination. For viewpoint, five of six viewpoint pairs were discriminated neurally. Viewpoint discrimination was most accurate with a broad span of VT cortex, but the neural and perceptual discrimination patterns differed. Less accurate discrimination of viewpoint, more consistent with human perception, was found in right posterior superior temporal sulcus, suggesting redundant viewpoint codes optimized for different functions. This study provides the first evidence that it is possible to dissociate neural activation patterns for identity and viewpoint independently.


The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3).
In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid, PDT) is a synthetic dipeptide, which possesses immunomodulatory properties and exerts a well-defined pharmacological activity against infections, but its real mechanism of action is still undefined. Here, we show that PDT is capable of activating tyrosine phosphorylation-based cell signaling in human primary monocytes and triggering rapid adhesion and chemotaxis. PDT-induced monocyte migration requires the activation of the PI3K/Akt signaling pathway and chemokine receptor CXCR3. Indeed, a mAb to CXCR3 and a specific receptor inhibitor suppressed significantly PDT-dependent chemotaxis, and CXCR3-silenced primary monocytes lost responsiveness to PDT chemoattraction. Moreover, our results highlighted that the PDT-induced migratory activity is sustained by the CXCR3A isoform, since CXCR3-transfected L1.2 cells acquired responsiveness to PDT stimulation. Finally, we show that PDT, as CXCR3 ligands, is also able to direct the migration of IL-2 activated T cells, which express the highest levels of CXCR3 among CXCR3-expressing cells. In conclusion, our study defines a chemokine-like activity for PDT through CXCR3A and points on the possible role that this synthetic dipeptide may play in leukocyte trafficking and function. Since recent studies have highlighted diverse therapeutic roles for molecules which activates CXCR3, our findings call for an exploration of using this dipeptide in different pathological processes.


Mobilizing churches for health promotion in Latino communities: Compañeros en la Salud.
Compañeros en la Salud (Partners in Health) is a 3-year project funded by the National Cancer Institute to conduct a church-based health promotion program whose aim is to reduce the risk of breast, cervical, and diet-related cancers in Latino/Hispanic women by increasing their knowledge of preventive behaviors, motivating healthy behavior change, and increasing their access to and utilization of preventive health services. From a systems perspective, churches serve as miniature, dynamic communities that present an opportunity for developing and implementing a program of health promotion. An analysis of church, Promotora (peer health worker), and participant characteristics from the preintervention base-line data revealed a naturally occurring segmentation of churches by congregation size and denomination. The Catholic churches almost exclusively were larger, whereas the Protestant churches almost exclusively were smaller. An analysis of the psychosocial characteristics of the various Latino women, when stratified by church congregation size, revealed that the women from the smaller, Protestant churches were poorer, had a lower level of acculturation, and had lower lifetime rates of clinical breast examinations. These results suggested greater resource deficits and a relatively higher need for Promotora outreach services for women from the smaller, Protestant churches. Implications are presented for differential approaches to effective health promotion among various types of churches.


Feeding Infants and Toddlers Study: do vitamin and mineral supplements contribute to nutrient adequacy or excess among US infants and toddlers?
To report the prevalence of dietary supplement use in a random sample of US infants 4 to 24 months of age, and to compare demographic characteristics, usual nutrient intakes, and food patterns of supplement users and nonusers. Data from 24-hour recalls collected for the 2002 Feeding Infants and Toddlers Study were analyzed. Recalls included nutrient contributions from dietary supplements as well as all foods and beverages. We estimated usual energy and nutrient intakes of supplement users and nonusers, as well as the prevalence of nutrient adequacy and excess in the two groups. We also compared demographic characteristics and food patterns of supplement users and nonusers and, for supplement users, estimated the proportion of total intake provided by foods and the proportion provided by supplements. A national random sample of 3,022 infants and toddlers age 4 to 24 months, including 430 vitamin and/or mineral supplement users and 2,592 nonusers. We compared means, percentile distributions, and proportions by age and supplement subgroup, and applied the Dietary Reference Intakes to assess usual nutrient intakes. We conducted regression analysis to determine which population characteristics predict the use of dietary supplements in this population. Overall, 8% of infants age 4 to 5 months received some type of dietary supplement. The prevalence of supplement use increased with age, to 19% among infants 6 to 11 months and 31% among toddlers 12 to 24 months. The vast majority of supplement users (97%) received only one type of supplement, most commonly a multivitamin and/or mineral supplement. Vitamin/mineral supplement use among infants and toddlers was associated with being a first-born child and being reported by the primary caretaker as being a picky eater. Characteristics that were independent predictors of supplement use were living in the Northeast, being male, and living in a household with fewer children. We found no significant differences between supplement users and nonusers in mean daily intakes of nutrients or nutrient density from foods alone, and few differences in food consumption. Overall, the prevalence of inadequate intakes was low (<1% to 2%). However, 65% of supplement nonusers and 9% of supplement users had vitamin E intakes less than the Estimated Average Requirement. Excessive intakes (ie, intakes above the Tolerable Upper Intake Level) were noted for both supplement users and nonusers for vitamin A (97% and 15% of toddlers) and zinc (60% and 59% of older infants and 68% and 38% of toddlers) as well as for folate among supplement users (18% of toddlers). Generally, healthy infants and toddlers can achieve recommended levels of intake from food alone. Dietetics professionals should encourage caregivers to use foods rather than supplements as the primary source of nutrients in children's diets. Vitamin and mineral supplements can help infants and toddlers with special nutrient needs or marginal intakes achieve adequate intakes, but care must be taken to ensure that supplements do not lead to excessive intakes. This is especially important for nutrients that are widely used as food fortificants, including vitamin A, zinc, and folate.


Prospective validation study of prognostic biomarkers to predict adverse outcomes in patients with COVID-19: a study protocol.
Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers' performance in predicting clinical outcomes of patients with COVID-19. This prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve. This research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.


The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018-2019.
The international response to the evolving Ebola epidemic in eastern Democratic Republic of Congo (DRC) has had interim successes while facing ongoing difficulties. The outbreak has occurred in an area of intractable conflict among multiple armed groups at a time of contentious national elections. Despite porous international borders and considerable population movement, however, transmission has been confined to North Kivu and Ituri provinces. Factors potentially contributing to this containment include conduct of about 55 million screenings, surveillance of contacts (12,591 under surveillance currently), testing of 280 samples per day, provision of safe and dignified burials for most deaths, vaccination of high-risk people (112,485 vaccinated as of May 7, 2019), and medical treatment including four investigational therapies. Major challenges remain. Since late February 2019, a sharp rise in cases and increased transmission have been observed. These coincide with organized attacks by armed groups targeting response teams, deteriorating security, and the population's increasing distrust of the response effort. The risk of local and regional spread remains high given the high proportion of deaths occurring outside treatment facilities, relatively low proportions of new patients who were known contacts, ongoing nosocomial transmission, and persistent delays in detection and reporting. Stopping this epidemic will require the alignment of the principal political and armed groups in eastern DRC in support of the response.


Inhibiting transthyretin amyloid fibril formation via protein stabilization.
Transthyretin (TTR) amyloid fibril formation is observed systemically in familial amyloid polyneuropathy and senile systemic amyloidosis and appears to be the causative agent in these diseases. Herein, we demonstrate conclusively that thyroxine (10.8 microM) inhibits TTR fibril formation efficiently in vitro and does so by stabilizing the tetramer against dissociation and the subsequent conformational changes required for amyloid fibril formation. In addition, the nonnative ligand 2,4,6-triiodophenol, which binds to TTR with slightly increased affinity also inhibits TTR fibril formation by this mechanism. Sedimentation velocity experiments were employed to show that TTR undergoes dissociation (linked to a conformational change) to form the monomeric amyloidogenic intermediate, which self-assembles into amyloid in the absence, but not in the presence of thyroxine. These results demonstrate the feasibility of using small molecules to stabilize the native fold of a potentially amyloidogenic human protein, thus preventing the conformational changes, which appear to be the common link in several human amyloid diseases. This strategy and the compounds resulting from further development should prove useful for critically evaluating the amyloid hypothesis--i.e., the putative cause-and-effect relationship between TTR amyloid deposition and the onset of familial amyloid polyneuropathy and senile systemic amyloidosis.


Evaluation of the validity of the Psychology Experiment Building Language tests of vigilance, auditory memory, and decision making.
Background. The Psychology Experimental Building Language (PEBL) test battery (http://pebl.sourceforge.net/) is a popular application for neurobehavioral investigations. This study evaluated the correspondence between the PEBL and the non-PEBL versions of four executive function tests. Methods. In one cohort, young-adults (N = 44) completed both the Conner's Continuous Performance Test (CCPT) and the PEBL CPT (PCPT) with the order counter-balanced. In a second cohort, participants (N = 47) completed a non-computerized (Wechsler) and a computerized (PEBL) Digit Span (WDS or PDS) both Forward and Backward. Participants also completed the Psychological Assessment Resources or the PEBL versions of the Iowa Gambling Task (PARIGT or PEBLIGT). Results. The between-test correlations were moderately high (reaction time r = 0.78, omission errors r = 0.65, commission errors r = 0.66) on the CPT. DS Forward was significantly greater than DS Backward on the WDS (p < .0005) and the PDS (p < .0005). The total WDS score was moderately correlated with the PDS (r = 0.56). The PARIGT and the PEBLIGTs showed a very similar pattern for response times across blocks, development of preference for Advantageous over Disadvantageous Decks, and Deck selections. However, the amount of money earned (score-loan) was significantly higher in the PEBLIGT during the last Block. Conclusions. These findings are broadly supportive of the criterion validity of the PEBL measures of sustained attention, short-term memory, and decision making. Select differences between workalike versions of the same test highlight how detailed aspects of implementation may have more important consequences for computerized testing than has been previously acknowledged.


Treatment Fidelity Among Family Health Promoters Delivering a Physical Activity and Nutrition Intervention to Immigrant and Refugee Families.
Lack of treatment fidelity can be an important source of variation affecting the credibility and utility of outcomes from behavioral intervention research. Development and implementation of a well-designed treatment fidelity plan, especially with research involving underserved populations, requires careful conceptualization of study needs in conjunction with what is feasible in the population. The purpose of this article is to review a fidelity-monitoring plan consistent with the National Institutes of Health Behavior Change Consortium guidelines (e.g., design, training, delivery, receipt, and enactment) for an intervention trial designed to improve physical activity and nutrition among immigrant and refugee families. Description of the fidelity monitoring plan is provided and challenges related to monitoring treatment fidelity in a community-based participatory intervention for immigrant and refugee families are discussed.


Rediscovering a key interface in dye-sensitized solar cells: guanidinium and iodine competition for binding sites at the dye/electrolyte surface.
We propose a new mechanism by which the common electrolyte additive guanidinium thiocyanate (GdmSCN) improves efficiency in dye-sensitized solar cells (DSSCs). We demonstrate that binding of Gdm(+) to TiO2 is weak and does not passivate recombination sites on the TiO2 surface as has been previously claimed. Instead, we show that Gdm(+) binds strongly to the N719 and D131 dyes and probably to many similar compounds. The binding of Gdm(+) competes with iodine binding to the same molecule, reducing the surface concentration of dye-I2 complexes. This in turn reduces the electron/iodine recombination rate constant, which increases the collection efficiency and thus the photocurrent. We further observe that GdmNO3 can increase efficiency more than the current Gdm(+) source, GdmSCN, at least in some DSSCs. Overall, the results point to an improved paradigm for DSSC operation and development. The TiO2/electrolyte surface has long been held to be the key interface in DSSCs. We now assert that the dye layer/electrolyte interaction is at least, and probably more, important.


The effect of combined hormonal contraceptives use on brain reactivity during response inhibition.
Cognitive control, which can be described as the ability to moderate impulses, has not previously been investigated in users of combined hormonal contraception (CHC). Given the suggested modulatory role of ovarian steroids in prefrontal dopaminergic function, which in turn taps into cognitive control, this randomised, double-blinded, placebo-controlled oral contraceptive trial set out to investigate the brain activity pattern during response inhibition in CHC users. Thirty-four women were randomised to one treatment cycle with a levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo treatment cycle. No differences between CHC and placebo users in number of correct inhibitions were found during treatment, but only women on CHC significantly improved their performance between the baseline and treatment assessments. During the treatment cycle CHC users displayed decreased activity in the right middle frontal gyrus in comparison with placebo users. No other significant activations were evident between treatment groups or within groups. Overall, CHC use had marginal effects on brain activity during response inhibition. If anything, the findings of the study may suggest reduced effort or increased efficiency in maintaining orbitofrontal cortex inhibitory cognitive control when using a combined oral contraceptive.


H-2D (Rfv-1) gene influence on recovery from Friend virus leukemia is mediated by nonleukemic cells of the spleen and bone marrow.
H-2D (Rfv-1)-associated control of recovery from FV leukemia was studied in congenic mice. In irradiation chimeras, the high recovery phenotype was transferred by cells of the spleen, bone marrow, and fetal liver. Furthermore, in cell transfers using unirradiated recipients, spleen and bone marrow cells of the high-recovery genotype were able to mediate recovery from leukemia in mice of the low-recovery genotype. Thus, the H-2D (Rfv-1) influence on recovery appeared to operate via nonleukemic cells of the spleen and bone marrow rather than via leukemic cells. The specific nonleukemic cell type(s) involved in recovery remains unknown. However, the mechanism appears to be complex and probably involves both anti-FV antibody and FV-specific cytotoxic T lymphocytes.


Global dissection of alternative splicing uncovers transcriptional diversity in tissues and associates with the flavonoid pathway in tea plant (Camellia sinensis).
Alternative splicing (AS) regulates mRNA at the post-transcriptional level to change gene function in organisms. However, little is known about the AS and its roles in tea plant (Camellia sinensis), widely cultivated for making a popular beverage tea. In our study, the AS landscape and dynamics were characterized in eight tissues (bud, young leaf, summer mature leaf, winter old leaf, stem, root, flower, fruit) of tea plant by Illumina RNA-Seq and confirmed by Iso-Seq. The most abundant AS (~ 20%) was intron retention and involved in RNA processes. The some alternative splicings were found to be tissue specific in stem and root etc. Thirteen co-expressed modules of AS transcripts were identified, which revealed a similar pattern between the bud and young leaves as well as a distinct pattern between seasons. AS events of structural genes including anthocyanidin reductase and MYB transcription factors were involved in biosynthesis of flavonoid, especially in vegetative tissues. The AS isoforms rather than the full-length ones were the major transcripts involved in flavonoid synthesis pathway, and is positively correlated with the catechins content conferring the tea taste. We propose that the AS is an important functional mechanism in regulating flavonoid metabolites. Our study provides the insight into the AS events underlying tea plant's uniquely different developmental process and highlights the important contribution and efficacy of alternative splicing regulatory function to biosynthesis of flavonoids.


Outcomes and costs associated with initial maintenance therapy with fluticasone propionate-salmeterol xinafoate 250 microg/50 microg combination versus tiotropium in commercially insured patients with COPD.
To compare, in commercially-insured individuals 240 years old, the risk of chronic obstructive pulmonary disease (COPD) exacerbations and COPD-related health care utilization and costs in patients initiating maintenance treatment with fluticasone propionate/salmeterol xinafoate 250 microg/50 microg (FSC) with those in patients initiating treatment with tiotropium bromide (TIO). Retrospective observational cohort study. The risk of COPD exacerbation (moderate, severe, and any), COPD-related health care utilization, and COPD-related costs (overall and by service setting) were assessed over 12 months after the initiation of treatment with FSC or TIO in commercially-insured patients > or =40 years old diagnosed with COPD. After adjusting for covariates, treatment with FSC compared with treatment with TIO was associated with a 14% reduction in risk of severe exacerbation (p = 0.0406), defined as the occurrence of a COPD-related hospitalization; with less health care utilization across several categories of care; with 25% lower COPD-related medical costs ($1814 versus $2258 per patient, p < 0.0001); and with 10% lower COPD-related total costs ($2991 versus $3304 per patient, p < 0.0001) over a 12-month follow-up period. Pharmacy costs were equivalent between FSC and TIO. Initiation of maintenance therapy with FSC compared with TIO was associated with significant reductions in the risk of severe exacerbations, health care utilization, and COPD-related medical and total costs. Considered in the context of other findings, these data suggest that earlier maintenance treatment with FSC offers clinical and economic benefits over maintenance treatment with TIO.


Host specificity of Salmonella infection in chickens and mice is expressed in vivo primarily at the level of the reticuloendothelial system.
By experimental infection, host-specific Salmonella serotypes were shown to demonstrate specificities for chickens, mice, and other laboratory animals. Following oral inoculation, four strains of Salmonella gallinarum and two S. pullorum strains, isolated from diseased poultry, were more virulent for chickens than for mice. By contrast, four strains each of S. choleraesuis and S. dublin, isolated from diseased pigs and cattle, respectively, were more virulent for mice than for chickens. These results were also reflected in the degree of virulence expressed after parenteral inoculation. In addition, S. choleraesuis, but not other serotypes, killed rats, guinea pigs, and rabbits. S. typhimurium strains varied widely in their virulence, and some strains were virulent for both mice and chickens. Four other serotypes isolated from poultry or human food poisoning cases and a nonpathogenic Escherichia coli strain were much less virulent for both experimental host species. Most of the host-specific Salmonella serotypes studied were able to colonize the distal alimentary tract and invade the tissues in both mice and chickens to various degrees. There was, however, a greater difference in the ability to survive and multiply in the visceral organs, particularly the spleen and the liver, once invasion had occurred which correlated with the virulence for the host species involved.


Gemcitabine and CHK1 inhibition potentiate EGFR-directed radioimmunotherapy against pancreatic ductal adenocarcinoma.
To develop effective combination therapy against pancreatic ductal adenocarcinoma (PDAC) with a combination of chemotherapy, CHK1 inhibition, and EGFR-targeted radioimmunotherapy. Maximum tolerated doses were determined for the combination of gemcitabine, the CHK1 inhibitor PF-477736, and Lutetium-177 ((177)Lu)-labeled anti-EGFR antibody. This triple combination therapy was investigated using PDAC models from well-established cell lines, recently established patient-derived cell lines, and fresh patient-derived xenografts. Tumors were investigated for the accumulation of (177)Lu-anti-EGFR antibody, survival of tumor-initiating cells, induction of DNA damage, cell death, and tumor tissue degeneration. The combination of gemcitabine and CHK1 inhibitor PF-477736 with (177)Lu-anti-EGFR antibody was tolerated in mice. This triplet was effective in established tumors and prevented the recurrence of PDAC in four cell line-derived and one patient-derived xenograft model. This exquisite response was associated with the loss of tumor-initiating cells as measured by flow cytometric analysis and secondary implantation of tumors from treated mice into treatment-naïve mice. Extensive DNA damage, apoptosis, and tumor degeneration were detected in the patient-derived xenograft. Mechanistically, we observed CDC25A stabilization as a result of CHK1 inhibition with consequent inhibition of gemcitabine-induced S-phase arrest as well as a decrease in canonical (ERK1/2 phosphorylation) and noncanonical EGFR signaling (RAD51 degradation) as a result of EGFR inhibition. Our study developed an effective combination therapy against PDAC that has potential in the treatment of PDAC.


Collaborative sensing in a distributed PTZ camera network.
The performance of dynamic scene algorithms often suffers because of the inability to effectively acquire features on the targets, particularly when they are distributed over a wide field of view. In this paper, we propose an integrated analysis and control framework for a pan, tilt, zoom (PTZ) camera network in order to maximize various scene understanding performance criteria (e.g., tracking accuracy, best shot, and image resolution) through dynamic camera-to-target assignment and efficient feature acquisition. Moreover, we consider the situation where processing is distributed across the network since it is often unrealistic to have all the image data at a central location. In such situations, the cameras, although autonomous, must collaborate among themselves because each camera's PTZ parameter entails constraints on the others. Motivated by recent work in cooperative control of sensor networks, we propose a distributed optimization strategy, which can be modeled as a game involving the cameras and targets. The cameras gain by reducing the error covariance of the tracked targets or through higher resolution feature acquisition, which, however, comes at the risk of losing the dynamic target. Through the optimization of this reward-versus-risk tradeoff, we are able to control the PTZ parameters of the cameras and assign them to targets dynamically. The tracks, upon which the control algorithm is dependent, are obtained through a consensus estimation algorithm whereby cameras can arrive at a consensus on the state of each target through a negotiation strategy. We analyze the performance of this collaborative sensing strategy in active camera networks in a simulation environment, as well as a real-life camera network.


Mexican American adolescents' sleep patterns: contextual correlates and implications for health and adjustment in young adulthood.
Late adolescence is a period of substantial risk for unhealthy sleep patterns. This study investigated the contextual correlates and health and adjustment implications of sleep patterns among Mexican American youth (N = 246; 51% female). We focused on Mexican American youth because they represent a large and rapidly increasing subgroup of the US population that is at higher risk for health and adjustment problems; this higher risk may be explained, in part, by sleep patterns. Using data from seven phone diary interviews conducted when youth averaged 18 years of age, we assessed average nighttime sleep duration and night-to-night variability in sleep duration. Guided by socio-ecological models, we first examined how experiences in the family context (time spent and quality of relationships with parents, parents' familism values) and in extra-familial contexts (school, work, peers) were related to sleep duration and variability. The findings revealed that time spent in school, work, and with peers linked to less sleep. Further, conflict with mothers was related to greater sleep variability. Next, we tested the implications of sleep in late adolescence for health (perceived physical health, body mass index) and adjustment (depressive symptoms, risky behaviors) in young adulthood. These findings indicated that more sleep variability predicted relative decreases in health and increases in risky behaviors, and shorter sleep duration predicted relative decreases in poorer perceived health for males. The discussion highlights the significance of the transition to young adulthood as a target for sleep research and the importance of studying sleep within its socio-cultural context.


High levels of mercury in wetland resources from three river basins in Ghana: a concern for public health.
Crustaceans, mollusks, and fish are wetland resources that constitute an important source of protein and foreign exchange for the Ghanaian population, and many species of these are sold in the open market and restaurants, yet studies on their heavy metal contents are generally scarce. This paper evaluates the levels of mercury in five species of crustaceans, two species of mollusks, and ten species of fish inhabiting three river basins with different catchment activities in Ghana. These include the Ankobra Basin, characterized with mining and agriculture, Densu Basin, associated with urban waste discharges and agriculture, and Lower Volta River Basin, associated with agricultural activities. Mercury concentration was highest in Ankobra (2.5 ± 2.59 μg g-1) followed by Densu (1.75 ± 1.35 μg g-1) and Volta (0.74 ± 1.46 μg g-1). The mercury load of the organisms range from <0.1 to 4 μg g-1 with the highest load in Cynoglossus senegalensis at Ankobra. Except for Panaeus notialis from Densu and Ankobra, and three other species from Ankobra (Tympanotonus fuscatus, Cardisoma armatum, Callinectes amnicola) in which mercury was not detected, mercury loads of all the organisms were above the permissible limit of 0.5 mg kg-1 established by Commission Regulation-EC (2006) for fishery products and muscle meat of fish. Weekly quantities of crustaceans and mollusks considered safe for consumption by adults ranged from 88 and 1000 g while that of the fishes were between 70 and 700 g (on a dry weight basis) depending on the species. It was clear that some caution needs to be exercised in the consumption of Ghana's fresh and brackish water fisheries.


A headache not to be sneezed at.
A 32-year-old male patient presented to the emergency department (ED) complaining of a headache and vertigo precipitated by sneezing. He had a recent history of neck trauma. Examination revealed horizontal nystagmus and a gait that veered to the left, exacerbated by heel to toe walking. A diagnosis of vertebral artery dissection (VAD) was suspected. A bleed was ruled out in the ED by computerised tomography, after which the patient was loaded with aspirin. The diagnosis was confirmed by magnetic resonance imaging and magnetic resonance angiography. Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing randomised multicentre prospective study comparing antiplatelet therapy with anticoagulation for patients with both carotid artery dissection and VAD. Headache is a very common presentation to the ED and a full neurological examination is essential if rarer causes are not to be missed.


A randomized controlled trial of a smartphone-based application for the treatment of anxiety.
AbstractIntroduction: Generalized anxiety disorder (GAD) is prevalent among college students. Smartphone-based interventions may be a low-cost treatment method. Method: College students with self-reported GAD were randomized to receive smartphone-based guided self-help (n = 50), or no treatment (n = 50). Post-treatment and six-month follow-up outcomes included the Depression Anxiety Stress Scales-Short Form Stress Subscale (DASS Stress), the Penn State Worry Questionnaire (PSWQ-11), and the State-Trait Anxiety Inventory-Trait (STAI-T), as well as diagnostic status assessed by the GAD-Questionnaire, 4th edition. Results: From pre- to post-treatment, participants who received guided self-help (vs. no treatment) experienced significantly greater reductions on the DASS Stress (d = -0.408) and a greater probability of remission from GAD (d = -0.445). There was no significant between-group difference in change on the PSWQ-11 (d = -0.208) or STAI-T (d = -0.114). From post to six-month follow-up there was no significant loss of gains on DASS Stress scores (d = -0.141) and of those who had remitted, 78.6% remained remitted. Yet rates of remitted participants no longer differed significantly between conditions at follow-up (d = -0.229). Conclusion: Smartphone-based interventions may be efficacious in treating some aspects of GAD. Methods for improving symptom reduction and long-term outcome are discussed.


The Influence of Prebiotics on Neurobiology and Behavior.
Manipulating the intestinal microbiota for the benefit of the brain is a concept that has become widely acknowledged. Prebiotics are nondigestible nutrients (i.e., fibers, carbohydrates, or various saccharides) that proliferate intrinsic, beneficial gut bacteria, and so provide an alternative strategy for effectively altering the enteric ecosystem, and thence brain function. Rodent studies demonstrating neurobiological changes following prebiotic intake are slowly emerging, and have thus far revealed significant benefits in disease models, including antiinflammatory and neuroprotective actions. There are also compelling data showing the robust and favorable effects of prebiotics on several behavioral paradigms including, anxiety, learning, and memory. At present, studies in humans are limited, though there is strong evidence for prebiotics modulating emotional processes and the neuroendocrine stress response that may underlie the pathophysiology of anxiety. While the mechanistic details linking the enteric microbiota to the central nervous system remain to be elucidated, there are a number of considerations that can guide future studies. These include the modulation of intestinal endocrine systems and inflammatory cascades, as well as direct interaction with the enteric nervous system and gut mucosa. Our knowledge of gut microbiome-brain communication is steadily progressing, and thorough investigations validating the use of prebiotics in the treatment of neuropsychiatric disorders would be highly valued and are encouraged.


Imaginal disc-autonomous expression of a defect in sensory bristle patterning caused by the lethal(3)ecdysoneless1 (1(3)ecd1) mutation of Drosophila melanogaster.
The temperature-sensitive mutation 1(3)ecd1 of Drosophila melanogaster is known to autonomously impair the ability of the larval prothoracic gland to produce the steroid molting hormone ecdysone in response to stimulation by the tropic neuropeptide prothoracicotropic hormone. It is shown that autonomous expression of the 1(3)ecd1 mutation in metamorphosing imaginal tissues disrupts the spatial pattern of sensory bristles. Transfer of homozygous mutant animals to the restrictive temperature at the time of pupariation resulted in the elimination of sensory microchaetae and macrochaetae. This effect was specific to the sensory bristles; nonsensory bristles were not eliminated, nor were other types of innervated cuticular sense organs. In the case of the dorsal thoracic macrochaetae, normal ecd gene function is required during an early period of bristle development (0-18 h after puparium formation at 20 degrees C). It is during this period that important determinative events take place in developing imaginal tissues that are responsible for the establishment of bristle progenitor cells. It is proposed that the ecd gene product may be required for the response of certain classes of cells to specific, regulatory signals.


The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury.
In this single-center, double-blind, randomized, sham-controlled, prospective trial at the U.S. Air Force School of Aerospace Medicine, the effects of 2.4 atmospheres absolute (ATA) hyperbaric oxygen (HBO₂) on post-concussion symptoms in 50 military service members with at least one combat-related, mild traumatic brain injury were examined. Each subject received 30 sessions of either a sham compression (room air at 1.3 ATA) or HBO₂ treatments at 2.4 ATA over an 8-week period. Individual and total symptoms scores on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) and composite scores on Post-traumatic Disorder Check List-Military Version (PCL-M) were measured just prior to intervention and 6 weeks after completion of intervention. Difference testing of post-intervention means between the sham-control and HBO₂ group revealed no significant differences on the PCL-M composite score (t=-0.205, p=0.84) or on the ImPACT total score (t=-0.943, p=0.35), demonstrating no significant effect for HBO₂ at 2.4 ATA. PCL-M composite scores and ImPACT total scores for sham-control and HBO(2) groups revealed significant improvement over the course of the study for both the sham-control group (t=3.76, p=0.001) and the HBO₂ group (t=3.90, p=0.001), demonstrating no significant HBO₂ effect. Paired t-test results revealed 10 ImPACT scale scores in the sham-control group improved from pre- to post-testing, whereas two scale scores significantly improved in the HBO₂ group. One PCL-M measure improved from pre- to post-testing in both groups. This study showed that HBO₂ at 2.4 ATA pressure had no effect on post-concussive symptoms after mild TBI.


Sodium channel inactivation is impaired in equine hyperkalemic periodic paralysis.
1. Equine hyperkalemic periodic paralysis (E-HPP) is a dominantly inherited disorder of muscle that causes recurrent episodes of stiffness (myotonia) and weakness in association with elevated serum K+. Affected horses carry a mutant allele of the skeletal muscle isoform of the Na channel alpha-subunit. To understand how this mutation may cause the disease phenotype, the functional defect in Na channel behavior was defined physiologically by recording unitary currents from cell-attached patches on normal and affected equine myotubes. 2. The presence of the mutation was confirmed in our cell line by restriction digest of polymerase chain reaction (PCR)-amplified genomic DNA. Myotubes from the affected horse were heterozygous for the point mutation that codes for a Phe to Leu substitution in S3 of domain IV. This assay provides a rapid technique to screen for the mutation in horses at risk. 3. The primary physiological defect in mutant Na channels was an impairment of inactivation. This defect was manifest as bursts of persistent activity during which the channel closed and reopened throughout a maintained depolarization. Disrupted inactivation slowed the decay of the ensemble-averaged current and produced an eightfold increase in the steady-state open probability measured at the end of a 40-ms pulse. This point mutation identifies a new region of the alpha subunit that is important for rapid inactivation of the channel. 4. The persistent Na current was produced by a distinct mode of gating. Failure of a mutant channel to inactivate was infrequent and occurred in groups of consecutive trials.(ABSTRACT TRUNCATED AT 250 WORDS)


Trends in one-year cumulative incidence of death between 2005 and 2013 among patients initiating antiretroviral therapy in Uganda.
Recent ecological data demonstrate improving outcomes for HIV-infected people in sub-Saharan Africa. Recently, Uganda has experienced a resurgence in HIV incidence and prevalence, but trends in HIV-related deaths have not been well described. Data were collected through the Uganda AIDS Rural Treatment Outcomes (UARTO) Study, an observational longitudinal cohort of Ugandan adults initiating antiretroviral therapy (ART) between 2005 and 2013. We calculated cumulative incidence of death within one year of ART initiation, and fit Poisson models with robust variance estimators to estimate the effect enrollment period on one-year risk of death and loss to follow-up. Of 760 persons in UARTO who started ART, 30 deaths occurred within one year of ART initiation (cumulative incidence 3.9%, 95% confidence interval [CI] 2.7-5.6%). Risk of death was highest for those starting ART in 2005 (13.0%, 95% CI 6.0-24.0%), decreased in 2006-2007 to 4% (95% CI 2.0-6.0%), and did not change thereafter ( P = 0.61). These results were robust to adjustment for age, sex, CD4 cell count, viral load, asset wealth, baseline depression, and body mass index. Here, we demonstrate that one-year cumulative incidence of death was high just after free ART rollout, decreased the following year, and remained low thereafter. Once established, ART programs in President's Emergency Fund for AIDS Relief-supported countries can maintain high quality care.


Preliminary results suggest tranexamic acid is safe and effective in arthroplasty patients with severe comorbidities.
Tranexamic acid (TXA) reduces blood loss and transfusion after total joint arthroplasty (TJA) but concerns remain that patients with severe medical comorbidities might be at increased risk for thromboembolic complications. Among patients undergoing primary TJA with severe systemic medical disease, (1) was TXA associated with increased symptomatic thromboembolic events; (2) was TXA associated with decreased blood transfusion rates; and (3) were there differences in symptomatic thromboembolism or transfusions in the subset of patients with a history of, or risk factors for; thromboembolic disease? We performed a retrospective review of 1131 primary TJAs in 1002 patients with American Society of Anesthesiologists score III or IV. Of these, 402 had at least one of seven risk factors for thromboembolic events and were designated as high risk; 240 of those patients received TXA. Outcome measures included 30-day postoperative symptomatic thromboembolic events and postoperative transfusion. There were no differences in symptomatic thromboembolic events within 30 days of surgery between patients who received TXA and those who did not (2.5% versus 2.6%, p = 0.97). Fewer patients treated with TXA received transfusions (11% with versus 41% without; p < 0.0001). In high-risk patients, TXA was not associated with an increase in symptomatic thromboembolic events (6.7% with versus 4.3% without; p = 0.27) and was associated with a decrease in transfusion rates (17% with versus 48% without; p = 0.001). Although TXA seemed safe and effective in this database review of patients with severe medical comorbidities, a larger prospective trial is warranted to confirm these results.


Single nucleotide polymorphisms in cytochrome P450 genes from barley.
Plant cytochrome P450s are known to be essential in a number of economically important pathways of plant metabolism but there are also many P450s of unknown function accumulating in expressed sequence tag (EST) and genomic databases. To detect trait associations that could assist in the assignment of gene function and provide markers for breeders selecting for commercially important traits, detection of polymorphisms in identified P450 genes is desirable. Polymorphisms in EST sequences provide so-called perfect markers for the associated genes. The International Triticeae EST Cooperative data base of 24,344 ESTs was searched for sequences exhibiting homology to P450 genes representing the nine known clans of plant P450s. Seventy five P450 ESTs were identified of which 24 had best matches in Genbank to P450 genes of known function and 51 to P450s of unknown function. Sequence information from PCR products amplified from the genomic template DNA of 11 barley varieties was obtained using primers designed from six barley P450 ESTs and one durum wheat P450 EST. Single nucleotide polymorphisms (SNPs) between barley varieties were identified using five of the seven PCR products. A maximum of five SNPs and three haplotypes among the 11 barley lines were detected in products from any one primer pair. SNPs in three PCR products led to changes between barley varieties in at least one restriction site enabling genotyping and mapping without the expense of a specialist SNP detection system. The overall frequency of SNPs across the 11 barley varieties was 1 every 131 bases.


Reduction of the periplasmic disulfide bond isomerase, DsbC, occurs by passage of electrons from cytoplasmic thioredoxin.
The Escherichia coli periplasmic protein DsbC is active both in vivo and in vitro as a protein disulfide isomerase. For DsbC to attack incorrectly formed disulfide bonds in substrate proteins, its two active-site cysteines should be in the reduced form. Here we present evidence that, in wild-type cells, these two cysteines are reduced. Further, we show that a pathway involving the cytoplasmic proteins thioredoxin reductase and thioredoxin and the cytoplasmic membrane protein DsbD is responsible for the reduction of these cysteines. Thus, reducing potential is passed from cytoplasmic electron donors through the cytoplasmic membrane to DsbC. This pathway does not appear to utilize the cytoplasmic glutathione-glutaredoxin pathway. The redox state of the active-site cysteines of DsbC correlates quite closely with its ability to assist in the folding of proteins with multiple disulfide bonds. Analysis of the activity of mutant forms of DsbC in which either or both of these cysteines have been altered further supports the role of DsbC as a disulfide bond isomerase.


Clinical application of sensory protection of denervated muscle.
Following proximal peripheral nerve injury, motor recovery is often poor due to prolonged muscle denervation and loss of regenerative potential. The transfer of a sensory nerve to denervated muscle results in improved functional recovery in experimental models. The authors here report the first clinical case of sensory protection. Following a total hip arthroplasty, this patient experienced a complete sciatic nerve palsy with no recovery at 3 months postsurgery and profound denervation confirmed electrodiagnostically. He underwent simultaneous neurolysis of the sciatic nerve and saphenous nerve transfers to the tibialis anterior branch of the peroneal nerve and gastrocnemius branch from the tibial nerve. He noted an early proprioceptive response. Electromyography demonstrated initially selective amelioration of denervation potentials followed by improved motor recovery in sensory protected muscles only. The patient reported clinically significant functional improvements in activities of daily living. The authors hypothesize that the presence of a sensory nerve during muscle denervation can improve functional motor recovery.


Organochlorine pesticide level differences among female inhabitants from Veracruz, Puebla and Tabasco, Mexico.
Organochlorine pesticides have been used in Mexico in malaria control programs and against ectoparasites. The objective of this study was to compare the levels of organochlorine pesticides: HCB, α-β-γ-HCH, pp'-DDE, op'-DDT and pp'-DDT in adipose tissue of female inhabitants from three Mexican states: Veracruz, Puebla and Tabasco. Data analyses indicated higher β-HCH levels in Puebla inhabitants. When comparing the mean values of the pp'-DDE concentrations among the three states, no statistically significant differences were noted. A trend of increasing concentrations of op'-DDT from Veracruz to Puebla and Tabasco was observed. Significantly higher pp'-DDT concentrations in Veracruz as compared to Puebla and Tabasco were determined. Using factorial analysis of three age categories (>30, 31-50, <51) organochlorine pesticide concentrations increases with age of participants, indicating time of exposure as a principal factor of organochlorine pesticides accumulation in adipose tissue.


Measuring population transmission risk for HIV: an alternative metric of exposure risk in men who have sex with men (MSM) in the US.
Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. MSM with plasma VL>400 copies/mL were defined as having 'transmission risk'. We calculated HIV prevalence, CVL, PVL, percent of HIV-positive with undetectable viral loads, and prevalence of plasma VL>400 copies/ml (%VL400) for black and white MSM. We used Monte Carlo simulation incorporating data on sexual mixing by race to estimate exposure of black and white HIV-negative MSM to a partner with transmission risk via unprotected anal intercourse (UAI). Of 709 MSM recruited, 42% (168/399) black and 14% (44/310) white MSM tested HIV-positive (p<.0001). No significant differences were seen in CVL, PVL, or percent of HIV positive with undetectable viral loads. The %VL400 was 25% (98/393) for black vs. 8% (25/310) for white MSM (p<.0001). Black MSM with 2 UAI partners were estimated to have 40% probability (95% CI: 35%, 45%) of having ≥1 UAI partner with transmission risk vs. 20% for white MSM (CI: 15%, 24%). Despite similarities in other metrics, black MSM in our cohort are three times as likely as white MSM to have HIV transmission risk. With comparable risk behaviors, HIV-negative black MSM have a substantially higher likelihood of encountering a UAI partner at risk of transmitting HIV. Our results support increasing HIV testing, linkage to care, and antiretroviral treatment of HIV-positive MSM to reduce prevalence of those with transmission risk, particularly for black MSM.


Disentangling disorders of consciousness: Insights from diffusion tensor imaging and machine learning.
Previous studies have suggested that disorders of consciousness (DOC) after severe brain injury may result from disconnections of the thalamo-cortical system. However, thalamo-cortical connectivity differences between vegetative state (VS), minimally conscious state minus (MCS-, i.e., low-level behavior such as visual pursuit), and minimally conscious state plus (MCS+, i.e., high-level behavior such as language processing) remain unclear. Probabilistic tractography in a sample of 25 DOC patients was employed to assess whether structural connectivity in various thalamo-cortical circuits could differentiate between VS, MCS-, and MCS+ patients. First, the thalamus was individually segmented into seven clusters based on patterns of cortical connectivity and tested for univariate differences across groups. Second, reconstructed whole-brain thalamic tracks were used as features in a multivariate searchlight analysis to identify regions along the tracks that were most informative in distinguishing among groups. At the univariate level, it was found that VS patients displayed reduced connectivity in most thalamo-cortical circuits of interest, including frontal, temporal, and sensorimotor connections, as compared with MCS+, but showed more pulvinar-occipital connections when compared with MCS-. Moreover, MCS- exhibited significantly less thalamo-premotor and thalamo-temporal connectivity than MCS+. At the multivariate level, it was found that thalamic tracks reaching frontal, parietal, and sensorimotor regions, could discriminate, up to 100% accuracy, across each pairwise group comparison. Together, these findings highlight the role of thalamo-cortical connections in patients' behavioral profile and level of consciousness. Diffusion tensor imaging combined with machine learning algorithms could thus potentially facilitate diagnostic distinctions in DOC and shed light on the neural correlates of consciousness. Hum Brain Mapp 38:431-443, 2017. © 2016 Wiley Periodicals, Inc.


Seascape genomics reveals population isolation in the reef-building honeycomb worm, Sabellaria alveolata (L.).
Under the threat of climate change populations can disperse, acclimatise or evolve in order to avoid fitness loss. In light of this, it is important to understand neutral gene flow patterns as a measure of dispersal potential, but also adaptive genetic variation as a measure of evolutionary potential. In order to assess genetic variation and how this relates to environment in the honeycomb worm (Sabellaria alveolata (L.)), a reef-building polychaete that supports high biodiversity, we carried out RAD sequencing using individuals from along its complete latitudinal range. Patterns of neutral population genetic structure were compared to larval dispersal as predicted by ocean circulation modelling, and outlier analyses and genotype-environment association tests were used to attempt to identify loci under selection in relation to local temperature data. We genotyped 482 filtered SNPs, from 68 individuals across nine sites, 27 of which were identified as outliers using BAYESCAN and ARLEQUIN. All outlier loci were potentially under balancing selection, despite previous evidence of local adaptation in the system. Limited gene flow was observed among reef-sites (FST = 0.28 ± 0.10), in line with the low dispersal potential identified by the larval dispersal models. The North Atlantic reef emerged as a distinct population and this was linked to high local larval retention and the effect of the North Atlantic Current on dispersal. As an isolated population, with limited potential for natural genetic or demographic augmentation from other reefs, the North Atlantic site warrants conservation attention in order to preserve not only this species, but above all the crucial functional ecological roles that are associated with their bioconstructions. Our study highlights the utility of using seascape genomics to identify populations of conservation concern.


Altered metabolic and stemness capacity of adipose tissue-derived stem cells from obese mouse and human.
Adipose stem cells (ASCs) are an appealing source of cells for therapeutic intervention; however, the environment from which ASCs are isolated may impact their usefulness. Using a range of functional assays, we have evaluated whether ASCs isolated from an obese environment are comparable to cells from non-obese adipose tissue. Results showed that ASCs isolated from obese tissue have a reduced proliferative ability and a loss of viability together with changes in telomerase activity and DNA telomere length, suggesting a decreased self-renewal capacity. Metabolic analysis demonstrated that mitochondrial content and function was impaired in obese-derived ASCs resulting in changes in favored oxidative substrates. These findings highlight the impact of obesity on adult stem properties. Hence, caution should be exercised when considering the source of ASCs for cellular therapies since their therapeutic potential may be impaired.


Follicle capacitation: a meta-analysis to investigate the transcriptome dynamics following follicle-stimulating hormone decline in bovine granulosa cells.
In recent years, exciting progress was made to improve the embryo outcome after ovarian stimulation in domestic animals. The practice of follicle-stimulating hormone (FSH) withdrawal, which is defined as the period of time between the last injection of FSH and oocyte retrieval, resulted in embryo yields significantly superior. Since then, specific changes in the transcriptome of granulosa cells were associated with the increase and also the decline in oocyte developmental competence following the FSH decline. In this study, we integrated large datasets from a public depository using a meta-analysis in order to elucidate the molecular changes occurring in granulosa cells following FSH decline in association with oocyte developmental competence. The meta-analysis revealed that the gene expression patterns observed during this period resulted from the downregulation of proliferative signals, and the upregulation of differentiation signals and early apoptotic signals. Additionally, FSH decline induced cellular hypoxia and triggered the expression of proinflammatory molecules which resulted in early atresia and mimicked the luteinizing hormone (LH) surge signaling to ovulation. To characterize this unique differentiation period, we suggest using the term "follicle capacitation" to refer to the functional changes occurring within the follicle in order to prepare the molecular machinery for the LH surge and ovulation following FSH decline. During this period, the follicle confers the oocyte with developmental competence to become a viable embryo. However, if this period is not rapidly followed by an LH surge, apoptosis signals are increased to generate follicular atresia and decrease oocyte quality.


Determining the architectures of macromolecular assemblies.
To understand the workings of a living cell, we need to know the architectures of its macromolecular assemblies. Here we show how proteomic data can be used to determine such structures. The process involves the collection of sufficient and diverse high-quality data, translation of these data into spatial restraints, and an optimization that uses the restraints to generate an ensemble of structures consistent with the data. Analysis of the ensemble produces a detailed architectural map of the assembly. We developed our approach on a challenging model system, the nuclear pore complex (NPC). The NPC acts as a dynamic barrier, controlling access to and from the nucleus, and in yeast is a 50 MDa assembly of 456 proteins. The resulting structure, presented in an accompanying paper, reveals the configuration of the proteins in the NPC, providing insights into its evolution and architectural principles. The present approach should be applicable to many other macromolecular assemblies.


Disease reactivation following fingolimod withdrawal in multiple sclerosis: Two case reports.
Severe multiple sclerosis reactivation following second line treatment withdrawal, defined "rebound syndrome", is becoming a prominent issue to consider when deciding to discontinue a treatment. In particular disease recurrence after cessation of fingolimod is actually poorly characterized as to date, only case reports and small case series have been described. We herewith describe 2 cases of severe disease reactivation associated to a high number of brain gadolinium enhancing lesions at magnetic resonance imaging (MRI) despite high dose steroid treatment, observed a few weeks after cessation of fingolimod administration, causing a substantial and persistent worsening of patient disability that required long term hospitalization. The severity of the neurological symptom worsening and of the brain lesion largely exceeded the disease activity observed during treatment. Our patients developed a rebound syndrome after ceasing fingolimod treatment, defined as the development of severe neurological symptoms and multiple new or enhancing lesions exceeding previous activity. Further analysis are needed to identify patients at greatest risk of a rebound syndrome.


Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis.
In the fatal disease-amyotrophic lateral sclerosis (ALS)-upper (corticospinal) motor neurons (MNs) and lower somatic MNs, which innervate voluntary muscles, degenerate. Importantly, certain lower MN subgroups are relatively resistant to degeneration, even though pathogenic proteins are typically ubiquitously expressed. Ocular MNs (OMNs), including the oculomotor, trochlear and abducens nuclei (CNIII, IV and VI), which regulate eye movement, persist throughout the disease. Consequently, eye-tracking devices are used to enable paralysed ALS patients (who can no longer speak) to communicate. Additionally, there is a gradient of vulnerability among spinal MNs. Those innervating fast-twitch muscle are most severely affected and degenerate first. MNs innervating slow-twitch muscle can compensate temporarily for the loss of their neighbours by re-innervating denervated muscle until later in disease these too degenerate. The resistant OMNs and the associated extraocular muscles (EOMs) are anatomically and functionally very different from other motor units. The EOMs have a unique set of myosin heavy chains, placing them outside the classical characterization spectrum of all skeletal muscle. Moreover, EOMs have multiple neuromuscular innervation sites per single myofibre. Spinal fast and slow motor units show differences in their dendritic arborisations and the number of myofibres they innervate. These motor units also differ in their functionality and excitability. Identifying the molecular basis of cell-intrinsic pathways that are differentially activated between resistant and vulnerable MNs could reveal mechanisms of selective neuronal resistance, degeneration and regeneration and lead to therapies preventing progressive MN loss in ALS. Illustrating this, overexpression of OMN-enriched genes in spinal MNs, as well as suppression of fast spinal MN-enriched genes can increase the lifespan of ALS mice. Here, we discuss the pattern of lower MN degeneration in ALS and review the current literature on OMN resistance in ALS and differential spinal MN vulnerability. We also reflect upon the non-cell autonomous components that are involved in lower MN degeneration in ALS.


A two-step, PU.1-dependent mechanism for developmentally regulated chromatin remodeling and transcription of the c-fms gene.
Hematopoietic stem cells and multipotent progenitors exhibit low-level transcription and partial chromatin reorganization of myeloid cell-specific genes including the c-fms (csf1R) locus. Expression of the c-fms gene is dependent on the Ets family transcription factor PU.1 and is upregulated during myeloid differentiation, enabling committed macrophage precursors to respond to colony-stimulating factor 1. To analyze molecular mechanisms underlying the transcriptional priming and developmental upregulation of the c-fms gene, we have utilized myeloid progenitors lacking the transcription factor PU.1. PU.1 can bind to sites in both the c-fms promoter and the c-fms intronic regulatory element (FIRE enhancer). Unlike wild-type progenitors, the PU.1(-/-) cells are unable to express c-fms or initiate macrophage differentiation. When PU.1 was reexpressed in mutant progenitors, the chromatin structure of the c-fms promoter was rapidly reorganized. In contrast, assembly of transcription factors at FIRE, acquisition of active histone marks, and high levels of c-fms transcription occurred with significantly slower kinetics. We demonstrate that the reason for this differential activation was that PU.1 was required to promote induction and binding of a secondary transcription factor, Egr-2, which is important for FIRE enhancer activity. These data suggest that the c-fms promoter is maintained in a primed state by PU.1 in progenitor cells and that at FIRE PU.1 functions with another transcription factor to direct full activation of the c-fms locus in differentiated myeloid cells. The two-step mechanism of developmental gene activation that we describe here may be utilized to regulate gene activity in a variety of developmental pathways.


Nestin Mediates Hedgehog Pathway Tumorigenesis.
The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem-like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation, resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Cancer Res; 76(18); 5573-83. ©2016 AACR.


Effects of recombination rate on human endogenous retrovirus fixation and persistence.
Endogenous retroviruses (ERVs) result from germ line infections by exogenous retroviruses. They can proliferate within the genome of their host species until they are either inactivated by mutation or removed by recombinational deletion. ERVs belong to a diverse group of mobile genetic elements collectively termed transposable elements (TEs). Numerous studies have attempted to elucidate the factors determining the genomic distribution and persistence of TEs. Here we show that, within humans, gene density and not recombination rate correlates with fixation of endogenous retroviruses, whereas the local recombination rate determines their persistence in a full-length state. Recombination does not appear to influence fixation either via the ectopic exchange model or by indirect models based on the efficacy of selection. We propose a model linking rates of meiotic recombination to the probability of recombinational deletion to explain the effect of recombination rate on persistence. Chromosomes 19 and Y are exceptions, possessing more elements than other regions, and we suggest this is due to low gene density and elevated rates of human ERV integration in males for chromosome Y and segmental duplication for chromosome 19.


Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinically silent, yet intensive lifestyle intervention with 7% or greater weight loss can improve or resolve NAFLD. Using a Veterans Health Administration (VHA) liver biopsy cohort, we evaluated simple noninvasive fibrosis scoring systems to identify NAFLD with advanced fibrosis (or severe disease) to assist providers. In our retrospective study of a national VHA sample of patients with biopsy-proven NAFLD or normal liver (2005-2015), we segregated patients by fibrosis stage (0-4). Non-NAFLD liver disease was excluded. We evaluated the diagnostic accuracy of the NAFLD fibrosis score (NFS), fibrosis-4 calculator (FIB-4), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), AST-to-platelet ratio index (APRI), and body mass index, AST/ALT ratio, and diabetes (BARD) score by age groups. We included 329 patients with well-defined liver histology (296 NAFLD and 33 normal controls without fibrosis), in which 92 (28%) had advanced (stage 3-4) fibrosis. Across all age groups, NFS and FIB-4 best predicted advanced fibrosis (NFS with 0.676 threshold: AUROC 0.71-0.76, LR + 2.30-22.05, OR 6.00-39.58; FIB-4 with 2.67 threshold: AUROC of 0.62-0.80, LR + 4.70-27.45, OR 16.34-59.65). While NFS and FIB-4 scores exhibit good diagnostic accuracy, FIB-4 is optimal in identifying NAFLD advanced fibrosis in the VHA. Easily implemented as a point-of-care clinical test, FIB-4 can be useful in directing patients that are most likely to have advanced fibrosis to GI/hepatology consultation and follow-up.


Relentless placoid chorioretinitis: A new entity or an unusual variant of serpiginous chorioretinitis?
To characterize an unusual clinical entity resembling acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis but with an atypical clinical course. We describe 6 patients, aged 17 through 51 years, exhibiting this unusual entity who were seen at 6 different centers from 1984 to 1997. The acute retinal lesions in this series were similar to those of APMPPE or serpiginous choroiditis, both clinically and on fluorescein and indocyanine green angiography. However, the clinical course, number of lesions, and location of these lesions were atypical. These patients had evidence of numerous posterior and peripheral retinal lesions predating or occurring simultaneously with macular involvement. Older, healing pigmented lesions were often accompanied by the appearance of new active white placoid lesions. Additionally, these cases all demonstrated prolonged periods of activity resulting in the appearance of more than 50 and sometimes hundreds of lesions scattered throughout the fundus. Growth of subacute lesions and the appearance of new lesions continued for 5 to 24 months after initial examination, and relapses were common. This entity has clinical features similar to APMPPE and serpiginous choroiditis but has a prolonged progressive clinical course and widespread distribution of lesions. It may represent a variant of serpiginous choroiditis or may be a new entity. We call it relentless placoid chorioretinitis. Arch Ophthalmol. 2000;118:931-938


Scurvy in a nonalcoholic person in the United States.
Scurvy is rarely diagnosed in our society today. The authors describe the case of a 31-year-old man with weakness, gingival pain, and a rash over the lower extremities. He had a history of poor nutritional intake, no alcohol consumption, and a 13 pack-year history of cigarette smoking. Laboratory studies revealed an extremely deficient serum ascorbic acid level. Treatment was begun with oral ascorbic acid tablets and, within 3 days after discharge, all clinical symptoms of scurvy had resolved. Scurvy is an easily treated disease and should be considered when there is an appropriate history and classic clinical findings. Because vitamin C deficiency can be seen in many chronic disease states, it is important to recognize some of the early features and clinical manifestations of such nutritional deficiencies.


Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation.
Embelin is a quinone derivative and found in the fruits of Embelia ribes Burm.f. Embelin has been identified as a small molecular inhibitor of X-chromosome-linked inhibitor of apoptosis proteins, and has multiple biological activities, including antioxidation, anti-inflammation, and antitumor effects. However, the effect of embelin in platelets remains unclear. Thus, this study investigated the antiplatelet mechanism of embelin. Our data revealed that embelin could inhibit platelet aggregation induced by various agonists, including the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Embelin, as well as the PKC inhibitor Ro 31-8220, markedly reduced PDBu-mediated phosphorylation of the PKC substrate, suggesting that embelin may be a PKC inhibitor for platelets. Embelin could block PKC downstream signaling and events, including the inhibition of protein kinase B and mitogen-activated protein kinase activation, granule release, and glycoprotein IIbIIIa activation. Moreover, embelin could delay thrombus formation in the mesenteric microvessels of mice, but did not significantly affect the tail bleeding time. In conclusion, we demonstrated that embelin is a PKC inhibitor and possesses antiplatelet and antithrombotic effects. The further analysis is necessary to more accurately determine clinical therapeutic potential of embelin in all clinical thromboembolic events with disturbance of thrombocyte function.


Sea urchin Forkhead gene family: phylogeny and embryonic expression.
Transcription factors of the Forkhead (Fox) family have been identified in many metazoans, and play important roles in diverse biological processes. Here we define the set of fox genes present in the sea urchin genome, and survey their usage during development. This genome includes 22 fox genes, only three of which were previously known. Of the 23 fox gene subclasses identified in vertebrate genomes, the Strongylocentrotus purpuratus genome has orthologues of all but four (E, H, R and S). Phylogenetic analysis suggests that one S. purpuratus fox gene is equally related to foxA and foxB of vertebrates; this gene defines a new class. Two other genes appear to be specific to the sea urchin, with respect to the genomes so far sequenced. Fox genes orthologous with those of vertebrates but lacking in arthropod or nematode genomes may be deuterostome-specific (subclasses I, J1, J2, L1, M and Q1), while the majority are pan-bilaterian. All but one of the S. purpuratus fox genes (SpfoxQ1) are expressed during embryogenesis, most in a very specific temporal and spatial manner. The sea urchin fox genes clearly execute many different regulatory functions, and almost all of them participate in the process of embryonic development.


Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.
Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR.


The alimentary and social instrumental performance in dogs is suppressed by various doses of amphetamine.
Amphetamine was administrated intramuscularly 20-25 min before each experimental session in doses of: 0.2 mg/kg, 0.5 mg/kg and 1.0 mg/kg. Each dose was applied twice and preceded by a regular experimental sessions without any treatment. An instrumental performance consisted of alimentary-social differentiation of two tones reinforced either by food or by sensory-social reward (petting by the experimenter). Amphetamine produced dose dependent decrease of the instrumental performance of both alimentary and social responses. This decrease was however not equal regarding both reactions. The dose of 1 mg/kg produced deep, statistically significant deterioration of alimentary as well as social responses. After the administration of the dose of 0.5 mg/kg the decrease of alimentary responses was equal to that produced by 1 mg/kg, whereas social responses were less deteriorated. After the dose of 0.2 mg/kg the reduction of alimentary responses was smaller than produced by 0.5 mg/kg but still more pronounced than in the case of socially reinforced reactions. The results confirm our previous data that amphetamine suppresses positively motivated instrumental performance in dogs. The results also show that amphetamine-evoked suppression is dose dependent and that it is different for alimentary and social responses. This might indicate that the positive reward system is not homogenous but consists of some subsystems related to different kinds of reward. It is concluded that the suppressing effect of amphetamine is due to the inhibitory effect on motivation, but not on purely instrumental mechanisms nor on hedonic processes.


Monitoring papilledema in a patient with pineal pilocytic astrocytoma by using Heidelberg Retina Tomograph II. Case report.
The Heidelberg Retina Tomograph (HRT) II is a confocal scanning laser device used to acquire images of the optic nerve head. In this paper the authors report a novel use of this device in the assessment of papilledema in a patient with pilocytic astrocytoma of the pineal region. They also present a new technique to objectively produce 3D data of the optic nerve head. An 11-year-old girl presented with headache and bilateral papilledema; magnetic resonance imaging revealed a lesion in the pineal region. A suboccipital craniectomy was performed, and HRT images were obtained both before (baseline) and after (follow-up) the operation. The authors analyzed the height variation of the retinal surface along the vertical and horizontal cross-lines passing the center of the optic nerve head. The postoperative images, studied on the 2nd day after operation, demonstrated visible reduction of the papilledema. The height variation of the retinal surface along the contour line created by the software demonstrated that elevation of the optic nerve head became depressed due to resolved swelling. The height variation of the retinal surface along vertical and horizontal cross-lines demonstrated significant differences between the elevated preoperative curve and the postoperative curve (p < 0.001), consistent with improvement of her symptoms. Initial data suggest that changes in the optic nerve head topography after surgical decompression can be quantitatively documented by 3D data from the HRT II.


Approach to the pruritic horse.
Pruritus in the horse may be due to several causes, the most common being a hypersensitivity response to salivary proteins in the Culicoides genera, which may coexist with atopic dermatitis, also known as an environmental allergy to pollens, molds, dust, storage mites, etc. Less common etiologies are food allergy and contact allergy, the latter often caused by owners applying various products to the skin. Other ectoparasites, such as Chorioptes mites, may also initiate pruritus. Secondary bacterial infections (usually Staphylococcus spp) may be pruritic in and of themselves. This article reviews the questions that need to be asked of owners to obtain a relevant history, always important for any organ system, but perhaps none more so than the skin. The various clinical findings such as alopecia and crusts and their location on the horse, diagnostic methods such as intradermal or serum testing for allergies, and subsequent hyposensitization are also discussed. Therapeutic options currently available for the potential underlying diseases, in particular for the hypersensitivity reactions to Culicoides spp or environmental allergens, are reviewed with the studies of hyposensitization over the last 40 years, as well as medications that may be effective. While the most common causes of pruritus in the horse are known, the current understanding of the pathophysiology still needs to be investigated, and consequently, the most effective treatments for those causes need to be improved. Newer research is discussed that may eventually add to the diagnostic and therapeutic options currently available for the pruritic horse.


Solitary blood cultures as a quality assurance indicator.
For patients with suspected bacteremia, at least two separate blood cultures are recommended to achieve maximum sensitivity and to properly interpret results. Since a single blood collection may signify an improper procedure with serious consequences if the diagnosis of blood stream infection is missed, we investigated this problem with studies at three teaching hospitals (A, B, and C) and by a survey of 38 other hospitals. The incidence of solitary blood cultures ranged from 1 to 99% (median 26%) at the surveyed institutions. Among the cases investigated at hospitals B and C, between 10 and 30% of solitary blood cultures were not clinically indicated, while most of the others were caused by the physician not knowing that one culture was insufficient or by failure to complete the diagnostic plan. Focused concurrent intervention at hospital B was associated with reductions in solitary blood cultures from 40.0 to 24.6% (p = 0.045) and a decline in those not indicated from 38.1 to 12.5% (p = 0.192). Global educational efforts at hospital A were associated with a decrease in solitary blood culture rates from 52 to 37% (p = 0.016). These results show that blood culture practice varies widely among institutions in spite of consensus recommendations for proper specimen collections. We estimate that, nationwide, up to 18,000 etiologic diagnoses of bacteremia are missed annually because of this problem. Monitoring institutional solitary blood cultures is recommended as a test utilization indicator and as the basis for improving blood culture practice.


Isolation, identification and seasonal distribution of soilborne fungi in tea growing areas of Iyidere-Ikizdere vicinity (Rize-Turkey).
This study involves the isolation and identification of soil borne fungi from different altitudes of Iyidere-Ikizdere vicinity in Rize, Turkey. The qualitative and quantitative fungal composition of the soil of Iyidere-Ikizdere vicinity was surveyed seasonally during a year (between summer 2003 and spring 2004). The soil samples were collected from 10 different locations. Some physical and chemical properties of the soil samples were studied. Soil samples were observed to have the proper pH levels (pH 4.00-6.75) for the growth of microfungi. By using a soil dilution technique, the mycological analysis of 40 soil samples were studied at 25 cm depth. The number of microfungi ranged from 2,000-160,000 CFU g(-1). 249 different microfungi belonging to 15 genera were isolated. 45 of the isolates were Mycelia Sterilia. Penicillium, Aspergillus, Trichoderma and Fusarium were the most abundant genera (26.8%, 14.8%, 9.6% and 8.4%, respectively). Penicillium phialosporum, Penicillium trzebinskianum and Gliocladium virens were reported for the first time in Turkey.


Cell-specific expression of the IP(3) receptor gene family in the kidney.
The localization of inositol trisphosphate (IP(3)) receptor isoforms, types 1-3, in the kidney and their role in the regulation of the intracellular calcium concentration - [Ca(2+)](i) - are discussed. Immunohistological studies with isoform-specific antibodies were performed to reveal the localization of IP(3) receptor isoforms. To examine the role of IP(3) receptor type 1 in the glomeruli, the responses of [Ca(2+)](i) to hormonal stimuli were examined in IP(3) receptor type 1 knockout mice. In the immunohistological study, type 1 receptor was present in arteries, afferent arterioles, and mesangial cells. Double staining with antibodies against aquaporin 2 and IP(3) type 2 receptor revealed that type 2 receptor was localized mainly in the intercalated cells. The type 3 receptor showed characteristic intracellular localization in the collecting duct cells of the cortex to the outer medulla. Immunostaining of type 3 receptor was most intense in the cytoplasm on the basolateral membrane side and was not seen on the apical side. The responses of [Ca(2+)](i) to angiotensin II and endothelin in the glomeruli were markedly attenuated in IP(3) receptor type 1 knockout mice. The three isoforms of the IP(3) receptor showed distinctive localization in the kidney, and the type 1 receptor plays a major role in the regulation of [Ca(2+)](i) in the glomeruli. The physiological significance of the cell-specific localization, however, remains to be determined.


Effect of Erica sp. honey against microorganisms of clinical importance: study of the factors underlying this biological activity.
This study aimed to determine the factors (phenolic compounds, flavonoids, sugars or H2O2) that contribute the most to the antimicrobial activity of heather honey samples against four yeasts and four bacteria with medical importance. To discard the effect of H2O2 in the antimicrobial activity, catalase was added. To evaluate the osmotic pressure's effect, artificial honey was also used. Phenolic compounds and flavonoids were determined and Pearson's correlation analysis was performed to assess whether these correlated with antimicrobial activity. The amount of phenolic compounds ranged from 630.89 ± 5.21 GAE kg-1 to 718.92 ± 4.41 GAE kg-1, while the flavonoids varied between 450.72 ± 5.67 CAE kg-1 and 673.98 ± 4.33 CAE kg-1. For the bacteria, the minimum inhibitory concentration (MIC) of the honey without catalase ranged from 1.01 ± 0.50% to 10.00 ± 4.72% and was between 2.00 ± 0.94% and 13.27 ± 5.23% for honey with catalase. Concerning the yeasts, the MICs was between 13.16 ± 4.08% and 20.00 ± 5.09% for honey without catalase and between 14.95 ± 4.16% and 25.67 ± 5.50% for honey with catalase. The elucidation of the antimicrobial factors and action mechanisms is essential for the correct use of honey in therapeutic applications.


Effect of low-level laser therapy on the healing process of donor site in patients with grade 3 burn ulcer after skin graft surgery (a randomized clinical trial).
Skin graft is a standard therapeutic technique in patients with deep ulcers, but managing donor site after grafting is very important. Although several modern dressings are available to enhance the comfort of donor site, using techniques that accelerate wound healing may enhance patient satisfaction. Low-level laser therapy (LLLT) has been used in several medical fields, including healing of diabetic, surgical, and pressure ulcers, but there is not any report of using this method for healing of donor site in burn patients. The protocols and informed consent were reviewed according to Medical Ethics Board of Shahid Beheshti University of Medical Sciences (IR.SBMU.REC.1394.363) and Iranian Registry of Clinical Trials (IRCT2016020226069N2). Eighteen donor sites in 11 patients with grade 3 burn ulcer were selected. Donor areas were divided into 2 parts, for laser irradiation and control randomly. Laser area was irradiated by a red, 655-nm laser light, 150 mW, 2 J/cm2, on days 0 (immediately after surgery), 3, 5, and 7. Dressing and other therapeutic care for both sites were the same. The patients and the person who analyzed the results were blinded. The size of donor site reduced in both groups during the 7-day study period (P < 0.01) and this reduction was significantly greater in the laser group (P = 0.01). In the present study, for the first time, we evaluate the effects of LLLT on the healing process of donor site in burn patients. The results showed that local irradiation of red laser accelerates wound healing process significantly.


Australian Aboriginal women prisoners' experiences of being a mother: a review.
The rise in the incarceration of Aboriginal and Torres Strait Islander mothers is a major public health issue with multiple sequelae for Aboriginal children and the cohesiveness of Aboriginal communities. The purpose of this paper is to review the available literature relating to Australian Aboriginal women prisoners' experiences of being a mother. The literature search covered bibliographic databases from criminology, sociology and anthropology, and Australian history. The authors review the literature on: traditional and contemporary Aboriginal mothering roles, values and practices; historical accounts of the impacts of white settlement of Australia and subsequent Aboriginal affairs policies and practices; and women's and mothers' experiences of imprisonment. The review found that the cultural experiences of mothering are unique to Aboriginal mothers and contrasted to non-Aboriginal concepts. The ways that incarceration of Aboriginal mothers disrupts child rearing practices within the cultural kinship system are identified. Aboriginal women have unique circumstances relevant to the concept of motherhood that need to be understood to develop culturally relevant policy and programs. The burden of disease and cycle of incarceration within Aboriginal families can be addressed by improving health outcomes for incarcerated Aboriginal mothers and female carers. To the authors' knowledge, this is the first literature review on Australian Aboriginal women prisoners' experiences of being a mother.


Driving with hemianopia, II: lane position and steering in a driving simulator.
The hypothesis that drivers with homonymous hemianopia (HH) would take a lane position that increased the safety margin on their blind side was tested with a driving simulator. Twelve participants with HH (six right HH and six left; nine men; mean age, 50 years; range 31-72), and 12 matched current drivers with normal vision (NV) each completed approximately 120 minutes of simulator driving. Lane position and steering stability were evaluated for specific road segment types (straight segments, curves, and turns) in city and rural undivided highway driving. The drivers with right HH held a lane position significantly (P = 0.001) to the left of NV drivers on the straight road segments and to a lesser extent on the curves. The drivers with left HH had a lane position similar to that of the NV drivers on straights and curves, but followed a significantly (P = 0.005) more rightward path on the left turns. The results support the hypothesis that drivers with HH take a lane position that increases the safety margin on their blind side; however, absolute lane position varies as the steering maneuver and location of the risk from oncoming traffic change with road segment type.


Glycosylation site prediction using ensembles of Support Vector Machine classifiers.
Glycosylation is one of the most complex post-translational modifications (PTMs) of proteins in eukaryotic cells. Glycosylation plays an important role in biological processes ranging from protein folding and subcellular localization, to ligand recognition and cell-cell interactions. Experimental identification of glycosylation sites is expensive and laborious. Hence, there is significant interest in the development of computational methods for reliable prediction of glycosylation sites from amino acid sequences. We explore machine learning methods for training classifiers to predict the amino acid residues that are likely to be glycosylated using information derived from the target amino acid residue and its sequence neighbors. We compare the performance of Support Vector Machine classifiers and ensembles of Support Vector Machine classifiers trained on a dataset of experimentally determined N-linked, O-linked, and C-linked glycosylation sites extracted from O-GlycBase version 6.00, a database of 242 proteins from several different species. The results of our experiments show that the ensembles of Support Vector Machine classifiers outperform single Support Vector Machine classifiers on the problem of predicting glycosylation sites in terms of a range of standard measures for comparing the performance of classifiers. The resulting methods have been implemented in EnsembleGly, a web server for glycosylation site prediction. Ensembles of Support Vector Machine classifiers offer an accurate and reliable approach to automated identification of putative glycosylation sites in glycoprotein sequences.


Enhancing electromechanical properties of lead-free ferroelectrics with bilayer ceramic/ceramic composites.
The macroscopic electromechanical behavior of lead-free bilayer composites was characterized at room temperature. One layer consisted of a nonergodic relaxor, (Bi1/2Na1/2)TiO3-7BaTiO3, with an electric-field-induced longrange ferroelectric order, whereas the other is understood to be an ergodic relaxor [(Bi1/2Na1/2)TiO3-25SrTiO3] that undergoes a reversible electric-field-induced macroscopic nonpolar-to-polar transition. Microstructural evidence of a bilayer with low diffusion between the two components is also demonstrated. By taking advantage of the different macroscopic strain- and polarization-electric-field responses of the two constituents, internal mechanical and electrical fields can be developed that enhance the unipolar strain over that expected by a rule of mixtures approximation, thereby improving the properties needed for application of such materials to actuator systems. It is possible through further tailoring of the volume fractions and macroscopic properties of the constituents to optimize the electromechanical properties of multilayer lead-free ferroelectrics.


Schizophrenic subjects with no history of admission to hospital.
It has often been assumed that all subjects with schizophrenia will eventually be admitted to hospital and therefore little bias is introduced by restricting research to hospitalized subjects. Using the Lothian Psychiatric Case Register, 66 subjects were identified who had been diagnosed in Edinburgh as suffering from schizophrenia between 1978 and 1989 but had no history of hospital admission by December 1991. This represented an adjusted average of 6.7% of the estimated annual rate of first diagnosis of schizophrenia: the proportion of such patients did not change over the period. Using a case-control design, the index cases were compared with a control group of schizophrenic patients who had been admitted to hospital within 3 months of diagnosis. At the time of diagnosis, the cases were generally less disturbed with lower levels of violent behaviour and less evidence of neglect or hallucinations. They had a longer duration of illness prior to diagnosis, were more often diagnosed by a consultant and unemployed. In a follow-up study of the index cases, 59 (89%) were traced, of whom 6 (10%) were deceased. The outcome of the illness was heterogeneous although the course was often chronic. The general practitioner provided most of the care they received. The small proportion of such patients suggests that their exclusion from most published series does not seriously bias our picture of the natural history of schizophrenia. Moreover, as there was no increase in the proportion over the period, first admission rates for schizophrenia in Scotland are a reasonable approximation to incidence rates.


Osteochondral Autograft Transfer Versus Microfracture in the Knee: A Meta-analysis of Prospective Comparative Studies at Midterm.
To compare microfracture (MFX) and osteochondral autograft transfer (OAT) surgical techniques to determine (1) postoperative activity level, (2) subjective patient outcomes, (3) failure rates, and (4) assess if any lesion characteristics favored one technique over the other. A comprehensive review of literature was performed of all studies comparing MFX and OAT. Studies included were all prospective studies that reported on activity-based outcome measures such as Tegner activity scores and subjective outcomes such as the International Knee Documentation Committee score. Failure rates, as determined by the publishing authors, were recorded for each study. Meta-analyses were conducted using a random-effects model. Paired standardized mean differences (Hedges's g to account for small sample bias) were used for continuous outcome measures, and risk ratios (Mantel-Haenszel method for small sample bias) for dichotomous outcome measures. Six prospective studies satisfied the eligibility criteria and included 249 patients (186 male, 120 female) with an average age of 26.4 years and follow-up of 67.2 months. Tegner scores were superior in patients treated with OAT compared with MFX (ΔOAT-MFX for pre-post scores = 0.94 Tegner points, standardized mean difference [SMD] = 0.469, P = .005). Failure rates of MFX were higher than OAT (OAT = 11%, MFX = 32%, risk ratio = 2.42, P < .036). OAT was superior to MFX at 3 years in relation to subjective outcome scores (SMD = 0.404, P = .008). When assessing OAT lesions larger than 3 cm2, OAT was superior to MFX with respect to activity level (SMD = 0.506, P = .001). OAT may achieve higher activity levels and lower risk of failure when compared with MFX for cartilage lesions greater than 3 cm2 in the knee, although there was no significant difference for lesions less than 3 cm2 at midterm. However, because of variability in patient-specific factors such as age, preinjury activity level, lesion location and size, the superiority of OAT over MFX cannot be generalized to all patient populations and therefore requires individualized patient care. Level II, meta-analysis of Level I and II studies.