The long thoracic nerve as a donor for facial nerve reanimation procedures: cadaveric feasibility study: laboratory investigation.
Injury of the facial nerve with resultant facial muscle paralysis may result in other significant complications such as corneal ulceration. To the authors' knowledge, neurotization to the facial nerve using the long thoracic nerve (LTN), a nerve used previously for neurotization to other branches of the brachial plexus, has not been explored previously. In an attempt to identify an additional nerve donor candidate for facial nerve neurotization, 8 adult human cadavers (16 sides) underwent dissection of the LTN, which was passed deep to the clavicle and axillary neurovascular bundle. The facial nerve was localized from the stylomastoid foramen onto the face, and the distal cut end of the previously dissected LTN was tunneled to this location. Measurements were made of the length and diameter of the LTN. Long thoracic nerve innervation to the first and second digitations of the serratus anterior was maintained on all sides. All specimens were found to have an LTN with more than enough length to be tunneled superiorly, tension-free to the extracranial facial nerve. Connections remained tensionless with left and right head rotation of up to 45 degrees . The mean length of this part of the LTN was 18 cm with a range of 15-22 cm. The overall mean diameter of this nerve was 2.5 mm. No evidence of injury to the surrounding neurovascular structures was identified on gross examination. To the authors' knowledge, the LTN has not been previously examined as a donor nerve for facial nerve reanimation procedures. Based on the results of this cadaveric study, the use of the LTN may be considered for such surgical maneuvers.


Aha! Insight experience correlates with solution activation in the right hemisphere.
In one experiment, we tested for an association between semantic activation in the right hemisphere (RH) and left hemisphere (LH) and the Aha! experience when people recognize solutions to insight-like problems. The compound remote associate problems used in this experiment sometimes evoke an Aha! experience and sometimes do not. On each trial, participants (N = 44) attempted to solve these problems and, after 7 sec, named a target word, made a solution decision, and rated their insight experience of recognizing the solution. As in prior studies, the participants demonstrated more solution priming for solutions presented to the left visual field-RH (lvf-RH) than for solutions presented to the right visual field-LH (rvf-LH). As was predicted, following unsolved problems the participants showed greater priming for solutions that they rated as evoking an insight experience on the subsequent solution decision than for solutions that did not evoke an insight experience. This association was stronger for solutions presented to the lvf-RH than for those presented to the rvf-LH. These results tie the subjective experience of insight to an objective measure--semantic priming--and suggest that people have an Aha! experience in part because they already had semantic activation that could lead them to recognize the solution quickly. We believe semantic activation in both hemispheres cooperatively contributes to problem solving, but weak solution activation that contributes to the Aha! experience is more likely to occur in the RH than in the LH.


Examining the global distribution of dominant archaeal populations in soil.
Archaea, primarily Crenarchaeota, are common in soil; however, the structure of soil archaeal communities and the factors regulating their diversity and abundance remain poorly understood. Here, we used barcoded pyrosequencing to comprehensively survey archaeal and bacterial communities in 146 soils, representing a multitude of soil and ecosystem types from across the globe. Relative archaeal abundance, the percentage of all 16S rRNA gene sequences recovered that were archaeal, averaged 2% across all soils and ranged from 0% to >10% in individual soils. Soil C:N ratio was the only factor consistently correlated with archaeal relative abundances, being higher in soils with lower C:N ratios. Soil archaea communities were dominated by just two phylotypes from a constrained clade within the Crenarchaeota, which together accounted for >70% of all archaeal sequences obtained in the survey. As one of these phylotypes was closely related to a previously identified putative ammonia oxidizer, we sampled from two long-term nitrogen (N) addition experiments to determine if this taxon responds to experimental manipulations of N availability. Contrary to expectations, the abundance of this dominant taxon, as well as archaea overall, tended to decline with increasing N. This trend was coupled with a concurrent increase in known N-oxidizing bacteria, suggesting competitive interactions between these groups.


Graphene oxide is degraded by neutrophils and the degradation products are non-genotoxic.
Neutrophils were previously shown to digest oxidized carbon nanotubes through a myeloperoxidase (MPO)-dependent mechanism, and graphene oxide (GO) was found to undergo degradation when incubated with purified MPO, but there are no studies to date showing degradation of GO by neutrophils. Here we produced endotoxin-free GO by a modified Hummers' method and asked whether primary human neutrophils stimulated to produce neutrophil extracellular traps or activated to undergo degranulation are capable of digesting GO. Biodegradation was assessed using a range of techniques including Raman spectroscopy, transmission electron microscopy, atomic force microscopy, and mass spectrometry. GO sheets of differing lateral dimensions were effectively degraded by neutrophils. As the degradation products could have toxicological implications, we also evaluated the impact of degraded GO on the bronchial epithelial cell line BEAS-2B. MPO-degraded GO was found to be non-cytotoxic and did not elicit any DNA damage. Taken together, these studies have shown that neutrophils can digest GO and that the biodegraded GO is non-toxic for human lung cells.


Who Is This "We" You Speak of? Grounding Activist Identity in Social Psychology.
What is an activist identity? Prior answers have focused almost exclusively on collective identity, without a) considering the possibility of role-based identities or b) grounding collective identities in broader social-psychological theories. The present study investigates activist identity through the lens of role-based and category-based identities, and reports two major findings. First, there is a distinct role-based activist identity, one that involves internalizing role responsibilities and the expectations of friends and family. Second, collective identity represents a relationship between a social identity and an injustice frame; it either involves incorporating an injustice frame into a pre-existing social identity, or using the injustice frame to create a new in-group. The present findings help to illuminate the processes underlying collective identity, indicate that a great deal of role-based activist identity is mistaken for collective identity, and suggest new directions for the study of micro-mobilization and organizational forms and tactics in social movements.


Early increase in vegetative symptoms predicts IFN-alpha-induced cognitive-depressive changes.
The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organism's priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-alpha in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions. Sixteen patients eligible for IFN-alpha treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed. Fatigue and depression scores increased significantly during IFN-alpha treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24. During IFN-alpha treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-alpha-induced immune activation.


Quantitative, spectrally-resolved intraoperative fluorescence imaging.
Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the first time. Moreover, we present images from human surgery which detect residual tumor not evident with state-of-the-art vFI. The wide-field qFI technique has broad implications for intraoperative surgical guidance because it provides near real-time quantitative assessment of multiple fluorescent biomarkers across the operative field.


Iron Status in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children. However, the pathogenesis of ADHD remains unclear. Iron, an important trace element, is implicated in brain function and dopaminergic activity. Recent studies have investigated the association between iron deficiency and ADHD, but the results are inconsistent. A systemic search of MEDLINE, EMBASE, Web of Science and Cochrane Library databases was supplemented by manual searches of references of key retrieved articles. Study quality was evaluated using the Newcastle-Ottawa Scale. The standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated using a random-effects model. H2 and I2 were used to evaluate the heterogeneity, and sensitivity, subgroup and meta-regression analyses were conducted to explore the reason of heterogeneity. The search yielded 11 studies published before July 25, 2016. Of these, 10 studies, comprising 2191 participants and 1196 ADHD cases, reported serum ferritin levels, and six studies, comprising 617 participants and 369 ADHD cases, reported serum iron levels. Serum ferritin levels were lower in ADHD cases (SMD = -0.40, 95% CI = -0.66 to -0.14). However, we found no correlation between serum iron levels and ADHD (SMD = -0.026, 95% CI = -0.29 to 0.24). Meta-regression analysis indicated that publication year, age, gender, sample size, and Hb levels did not significantly influence the pooled estimates of serum ferritin. Lower serum ferritin rather than serum iron is associated with ADHD in children.


Sequestration of host plant glucosinolates in the defensive hemolymph of the sawfly Athalia rosae.
Interactions between insects and glucosinolate-containing plant species have been investigated for a long time. Although the glucosinolate-myrosinase system is believed to act as a defense mechanism against generalist herbivores and fungi, several specialist insects use these secondary metabolites for host plant finding and acceptance and can handle them physiologically. However, sequestration of glucosinolates in specialist herbivores has been less well studied. Larvae of the tumip sawfly Athalia rosae feed on several glucosinolate-containing plant species. When larvae are disturbed by antagonists, they release one or more small droplets of hemolymph from their integument. This "reflex bleeding" is used as a defense mechanism. Specific glucosinolate analysis, by conversion to desulfoglucosinolates and analysis of these by high-performance liquid chromatography coupled to diode array UV spectroscopy and mass spectrometry, revealed that larvae incorporate and concentrate the plant's characteristic glucosinolates from their hosts. Extracts of larvae that were reared on Sinapis alba contained sinalbin, even when the larvae were first starved for 22 hr and, thus, had empty guts. Hemolymph was analyzed from larvae that were reared on either S. alba, Brassica nigra, or Barbarea stricta. Leaves were analyzed from the same plants the larvae had fed on. Sinalbin (from S. alba), sinigrin (B. nigra), or glucobarbarin and glucobrassicin (B. stricta) were present in leaves in concentrations less than 1 micromol/g fresh weight, while the same glucosinolates could be detected in the larvae's hemolymph in concentrations between 10 and 31 micromol/g fresh weight, except that glucobrassicin was present only as a trace. In larval feces, only trace amounts of glucosinolates (sinalbin and sinigrin) could be detected. The glucosinolates were likewise found in freshly emerged adults, showing that the sequestered phytochemicals were transferred through the pupal stage.


Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment.
Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the mu-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects. After a 1-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption. Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects. These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.


Dysphagia in severe anorexia nervosa and potential therapeutic intervention: a case series.
In severe anorexia nervosa, there are a litany of medical complications that affect virtually every body system, and severe weakness is a typical characteristic. To our knowledge, aspiration risk, dysphagia recognition, and dysphagia management and intervention have not been well described in the literature in regard to severe anorexia nervosa. The purpose of this case series is to increase awareness among clinicians of possible oropharyngeal dysphagia symptoms that may present in patients with severe anorexia nervosa. We describe the cases of 3 patients with severe anorexia nervosa who presented with symptoms of dysphagia. The speech-language pathology team administered dysphagia therapy to the 3 patients utilizing neuromuscular electrical stimulation (NMES) in conjunction with swallowing therapy tasks that included strengthening exercises and compensatory strategies. After the course of dysphagia treatment intervention, the 3 patients were able to tolerate an oral diet with improved swallowing function and no ongoing aspiration. The use of NMES in conjunction with traditional swallowing exercises in the treatment of dysphagia in patients with anorexia nervosa may reduce the need for enteral feeding and prolonged hospitalization. In regard to dysphagia intervention and management within this population and across other populations, rigorous randomized controlled studies are necessary for determining the efficacy of NMES and traditional swallowing therapy implementation.


A novel sensing technique for measurement of magnitude and polarity of electrostatic charge distribution across individual particles.
Electrostatic charge is generated during powder handling due to particle-particle and particle-wall collisions, rubbing, sliding, and rolling. In case of bipolar charge generation, the electrostatic forces may significantly change the inner forces and increase powder adhesion and cause a serious problem in material handling process. Therefore, the knowledge of distribution of charge across the individual particles is helpful to identify the role of triboelectrification and the effects of various relevant variables especially change in the contact materials, environmental conditions during processing, etc. A novel approach based on inductive sensor has been developed to detect the either polarity of charged particle and to characterise the bipolar charge distribution in the population of particulate material. To achieve this, an amplification unit configured as a pure integrator and signal processing techniques has been used to de-noise and correct the baseline of signal and MATLAB algorithm developed for peak detection. The polarity of charged particles obtained by this method is calibrated with Faraday pail method and the results are promising. Experimental study has been carried out by using two distinct populations of oppositely charged particles (glass beads-PVC, olivine sand, and silica sand). The obtained results indicate that the method is able to detect the distribution of polarities of charged particles.


Glucose entrainment of high-frequency plasma insulin oscillations in control and type 2 diabetic subjects.
Regular high-frequency oscillations of insulin secretion are characteristic of normal beta-cell function. These oscillations are easily entrainable to an exogenous rhythm by small changes in glucose concentration in vitro. We tested whether high-frequency insulin oscillations in vivo would also be entrainable by glucose and whether a lack of entrainment would characterize the diabetic beta-cell. We tested 13 control subjects and 11 patients with type 2 diabetes. Subjects underwent serial blood sampling at 1-min intervals for 60-120 min in the basal state or with small (15 mg/kg) boluses of glucose injected intravenously at exact 29-min intervals. Time series analysis was carried out using spectral analysis. Oscillations of basal plasma glucose concentrations were observed in both control and type 2 diabetic subjects, with a mean period of 11.3 +/- 3.1 and 11.6 +/- 2.0 min, respectively. These oscillations were entrained to mean periods of 15.0 +/- 0.6 and 14.2 +/- 0.9 min, respectively, by exogenous glucose. Regular high-frequency insulin oscillations were observed in control subjects; the mean period of basal plasma insulin oscillations was 10.7 +/- 1.2 min and was entrained to exogenously injected glucose, with a period of 15.2 +/- 0.1 min. In contrast, in the type 2 diabetic subjects, spontaneous insulin oscillations were unchanged by the glucose rhythm; the mean periods were 10.0 +/- 1.0 min during the basal period, and 10.1 +/- 0.0 min during glucose injections. These results demonstrate that spontaneous high-frequency insulin oscillations can be successfully entrained by glucose in control subjects. However, these oscillations in type 2 diabetic subjects are not similarly entrained. We conclude that loss of entrainment of spontaneous high-frequency insulin oscillations in type 2 diabetes is a highly sensitive manifestation of beta-cell secretory dysfunction.


Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer.
Germline NF1, c-RET, SDH, and VHL mutations cause familial pheochromocytoma. Pheochromocytomas derive from sympathetic neuronal precursor cells. Many of these cells undergo c-Jun-dependent apoptosis during normal development as NGF becomes limiting. NF1 encodes a GAP for the NGF receptor TrkA, and NF1 mutations promote survival after NGF withdrawal. We found that pheochromocytoma-associated c-RET and VHL mutations lead to increased JunB, which blunts neuronal apoptosis after NGF withdrawal. We also found that the prolyl hydroxylase EglN3 acts downstream of c-Jun and is specifically required among the three EglN family members for apoptosis in this setting. Moreover, EglN3 proapoptotic activity requires SDH activity because EglN3 is feedback inhibited by succinate. These studies suggest that failure of developmental apoptosis plays a role in pheochromocytoma pathogenesis.


Liaison psychiatry and depression in medical inpatients.
To assess the frequency of depression among hospitalized patients, the socio-demographic variables associated with depression and the number of cases referred by physicians to Psychiatry. A cross-sectional study was carried out at the Aga Khan University Hospital Karachi. An anonymous Urdu version of the WHO-developed self-reporting questionnaire (SRQ) was administered to inpatients meeting the inclusion criteria. Data was analyzed by SPSS version 13.0. Of the 225 patients approached, 178 completed the questionnaire (men= 45.2%, women = 54.8%). The mean age of the sample was 45.2 years. Out of the total 30.5% of patients were identified as having probable depression, among which housewives were more likely to be depressed compared to others (p=0.031). Among variable comparison, there with secondary school education or below and those with psychiatric co-morbidities, showed significantly greater prevalence of depression (p=0.003) and (p=0.005) respectively. Attending physicians correctly diagnosed 7 (13%) patients and referred only 3 patients to Psychiatry over the previous month. The prevalence of depression among inpatients is comparable to that in the general population. Being a housewife, level at or below secondary school education and having a past psychiatric history are significant factors associated with depression in medical inpatients. A very small number of depressed cases were referred to a psychiatrist.


Education Research: A novel resident-driven neurology quality improvement curriculum.
To describe and assess the effectiveness of a neurology resident quality improvement curriculum focused on development of practical skills and project experience. We designed and implemented a quality improvement curriculum composed of (1) a workshop series and (2) monthly resident-led Morbidity, Mortality, & Improvement conferences focused on case analysis and project development. Surveys were administered precurriculum and 18 months postcurriculum to assess the effect on self-assessed confidence with quality improvement skills, attitudes, and project participation. Scholarship in the form of posters, presentations, and manuscripts was tracked during the course of the study. Precurriculum, 83% of neurology residents felt that instruction in quality improvement was important, but most rated their confidence level with various skills as low. Following implementation of the curriculum, residents were significantly more confident in analyzing a patient case (odds ratio, 95% confidence interval) (2.4, 1.9-3.1), proposing system changes (3.1, 2.3-3.9), writing a problem statement (9.9, 6.2-13.5), studying a process (3.1, 2.3-3.8), identifying resources (3.1, 2.3-3.8), identifying appropriate measures (2.5, 1.9-3.0), collaborating with other providers to make improvements (4.9, 3.5-6.4), and making changes in a system (3.1, 2.3-3.8). Project participation increased from the precurriculum baseline (7/18, 39%) to the postcurriculum period (17/22, 77%; p = 0.023). One hundred percent of residents surveyed rated the curriculum positively. Our multifaceted curriculum was associated with increased resident confidence with quality improvement skills and increased participation in improvement projects. With adequate faculty mentorship, this curriculum represents a novel template for preparing neurology residents for meeting the expectations of improvement in practice and offers scholarship opportunities.


Corneal wave aberration from videokeratography: accuracy and limitations of the procedure.
A procedure to calculate the wave aberration of the human cornea from its surface shape measured by videokeratography is presented. The wave aberration was calculated as the difference in optical path between the marginal rays and the chief ray refracted at the surface, for both on- and off-axis objects. The corneal shape elevation map was obtained from videokeratography and fitted to a Zernike polynomial expansion through a Gram-Schmidt orthogonalization. The wave aberration was obtained also as a Zernike polynomial representation. The accuracy of the procedure was analyzed. For calibrated reference surface elevations, a root-mean-square error (RMSE) of 1 to 2 microm for an aperture 4-6 mm in diameter was obtained, and the RMSE associated with the experimental errors and with the fitting method was 0.2 microm. The procedure permits estimation of the corneal wave aberration from videokeratoscopic data with an accuracy of 0.05-0.2 microm for a pupil 4-6 mm in diameter, rendering the method adequate for many applications.


Impact of regional climate change on human health.
The World Health Organisation estimates that the warming and precipitation trends due to anthropogenic climate change of the past 30 years already claim over 150,000 lives annually. Many prevalent human diseases are linked to climate fluctuations, from cardiovascular mortality and respiratory illnesses due to heatwaves, to altered transmission of infectious diseases and malnutrition from crop failures. Uncertainty remains in attributing the expansion or resurgence of diseases to climate change, owing to lack of long-term, high-quality data sets as well as the large influence of socio-economic factors and changes in immunity and drug resistance. Here we review the growing evidence that climate-health relationships pose increasing health risks under future projections of climate change and that the warming trend over recent decades has already contributed to increased morbidity and mortality in many regions of the world. Potentially vulnerable regions include the temperate latitudes, which are projected to warm disproportionately, the regions around the Pacific and Indian oceans that are currently subjected to large rainfall variability due to the El Niño/Southern Oscillation sub-Saharan Africa and sprawling cities where the urban heat island effect could intensify extreme climatic events.


Implementing internet-delivered cognitive behavioural therapy for patients with cardiovascular disease and psychological distress: a scoping review.
Comorbid psychological distress (i.e. insomnia and depression) is experienced by 20-40% of patients with cardiovascular disease. This has a considerable impact on their health and quality of life, leading to frequent re-hospitalisations, higher healthcare costs and a shorter life expectancy. Internet-based cognitive behavioural therapy shows great potential for treating psychological distress in cardiovascular disease. Effective and feasible treatments can, however, only benefit patients if they are fully implemented in clinical care. This scoping review aimed to explore the literature for internet-based cognitive behavioural therapy in cardiovascular disease and for strategies to implement the intervention. We searched electronic databases, journals and internet sources to find original studies about internet-based cognitive behavioural therapy in cardiovascular disease, adhering to scoping methodology guidelines. After identifying 267 titles, we screened 40 abstracts and chose 11 full-text articles for full-text screening. The results sections in four articles were searched for outcomes that related to the effectiveness and implementation of internet-based cognitive behavioural therapy by directed qualitative content analysis using an implementation framework. Three of the four articles fulfilling the inclusion criteria concerned internet-based cognitive behavioural therapy for treating mild to moderate depressive symptoms in cardiovascular disease, and none focused on insomnia. The studies showed evidence for the effectiveness of internet-based cognitive behavioural therapy, and/or described patient factors influencing clinical effectiveness. Our qualitative content analysis showed that many implementation aspects and stakeholder perspectives remain unexplored. Internet-based cognitive behavioural therapy promises to alleviate patient suffering in cardiovascular disease. There is, however, little research about internet-based cognitive behavioural therapy for cardiovascular disease, and about how this evidence-based intervention is implemented.


A 1-Minute Re-warm Up at High-Intensity Improves Sprint Performance During the Loughborough Intermittent Shuttle Test.
Although a 3- to 7-min re-warm up (RW) elicits performance and physiological benefits after half-time (HT), a time-efficient and feasible RW protocol is required for the use of an RW in the athletic setting. This study aimed to investigate the effect of a 1-min RW at high-intensity on the performance and physiological responses during the Loughborough Intermittent Shuttle Test (LIST). In a randomized and counterbalanced cross-over design, 12 male amateur intermittent team sports players (soccer, basketball, handball, and lacrosse; age, 22 ± 2 years; height, 1.70 ± 0.08 m; body mass, 65.1 ± 8.3 kg; body mass index, 22.4 ± 1.9 kg m-2; VO2max, 53.5 ± 4.5 ml kg-1 min-1) performed the LIST. The LIST comprised two 45-min halves separated by a 15-min HT. Each half comprised repetitions of exercise cycles consisting of 3 × 20-m walking, 1 × 20-m maximal sprint, 3 × 20-m jogging, and 3 × 20-m running. During the HT, the participants were assigned to a control trial (CON; 15-min seated rest) or an RW trial (1-min running at 90% of the maximal oxygen uptake after a 14-min seated rest). Compared to the CON, the RW prevents reductions in sprint performance at the fourth and sixth periods of the LIST (fourth: 2.4%, p = 0.002, d = 1.68, sixth: 3.6%, p = 0.012, d = 1.74) and a decrement of gastrointestinal temperature during HT (0.5°C, p = 0.010, d = 1.41). Moreover, the RW decreased the electromyogram amplitude of maximal voluntary contraction (MVC) after HT (12%, p = 0.017, d = 1.12) without a decrease of maximal voluntary contraction force, suggesting an increased neuromuscular efficiency (9%, p = 0.048, d = 0.58). The RW also increased the mean heart rate in the initial part of the second half (4 bpm, p = 0.016, d = 0.38). In conclusion, the RW improved sprint performance, core temperature, muscle activation, and heart rate in the second half of the LIST. The findings suggest that the RW should be recommended for intermittent team sports players when longer RWs are not possible.


Chandra X-Ray Detection of the Radio Hot Spots of 3C 295.
An observation of the radio galaxy 3C 295 during the calibration phase of the Chandra X-Ray Observatory reveals X-ray emission from the core of the galaxy, from each of the two prominent radio hot spots, and from the previously known cluster gas. We discuss the possible emission processes for the hot spots and argue that a synchrotron self-Compton (SSC) model is preferred for most or all of the observed X-ray emission. SSC models with near-equipartition fields thus explain the X-ray emission from the hot spots in the two highest surface brightness FR II radio galaxies, Cygnus A and 3C 295. This lends weight to the assumption of equipartition and suggests that relativistic protons do not dominate the particle energy density.


Orientation-selective contrast adaptation measured with SSVEP.
Exposure to oriented luminance contrast patterns causes a reduction in visual sensitivity specifically for the adapter orientation. This orientation selectivity is probably the most studied aspect of contrast adaptation, but it has rarely been measured with steady-state visually evoked potentials (SSVEPs), despite their becoming one of the more popular methods of human neuroscience. Here, we measured orientation selective adaptation by presenting a plaid stimulus of which the horizontal and vertical grating reversed contrast at different temporal frequencies, while recording EEG signals from occipital visual areas. In three experiments, we compared SSVEP responses to the plaid before and after adaptation. All experiments showed a significant decrease in SSVEP response at the frequency of the adapter orientation, whereas such an effect was absent for the frequency of the orthogonal orientation. Adaptation also led to robust phase delays, selectively for the SSVEP frequency corresponding to the adapter orientation. These results demonstrate the efficiency of SSVEPs for measuring orientation selective adaptation; the method can measure changes in both amplitude and phase, simultaneously for two orientations.


Do the patients read the informed consent?
Informed consent is a process which consists of informing the patient about the medical interventions planned to be applied to the patient's body and making the patient active in the decision making process. The aim of this study was to evaluate whether the patients read the informed consent document or not and if not, to determine why they did not read it. This was achieved via a questionnaire administered at the pre-anaesthetic visit to assess the perception of patients to the informed consent process. Survey study. The patients were given a questionnaire after signing the informed consent document at the pre-anaesthetic visit. We studied whether the patients read the informed consent document or not and asked for their reasons if they did not. A total of 522 patients were included during the two month study (mean age: 38.1 years; 63.8% male, 36.2% female). Overall, 54.8% of patients reported that they did not read the informed consent. Among them, 50.3% did not care about it because they thought they would have the operation anyway, 13.4% did not have enough time to read it, 11.9% found it difficult to understand, 5.9% could not read because they had no glasses with them, and 5.2% found it frightening and gave up reading. Inpatients, older patients and patients with co-morbidities were less likely to read the informed consent document than outpatients, and younger and healthy patients (p<0.05). Also, 57.9% of parents whose children would be operated on had read the document. This study shows that the majority of our patients did not understand the importance of the informed consent. It is therefore concluded that informed consent documents should be rearranged to be easily read and should be supported with visual elements such as illustrations or video presentations, as informed consent is a process rather than just simply signing a form.


Adaptive spectral clustering with application to tripeptide conformation analysis.
A decomposition of a molecular conformational space into sets or functions (states) allows for a reduced description of the dynamical behavior in terms of transition probabilities between these states. Spectral clustering of the corresponding transition probability matrix can then reveal metastabilities. The more states are used for the decomposition, the smaller the risk to cover multiple conformations with one state, which would make these conformations indistinguishable. However, since the computational complexity of the clustering algorithm increases quadratically with the number of states, it is desirable to have as few states as possible. To balance these two contradictory goals, we present an algorithm for an adaptive decomposition of the position space starting from a very coarse decomposition. The algorithm is applied to small data classification problems where it was shown to be superior to commonly used algorithms, e.g., k-means. We also applied this algorithm to the conformation analysis of a tripeptide molecule where six-dimensional time series are successfully analyzed.


Galaxy tools and workflows for sequence analysis with applications in molecular plant pathology.
The Galaxy Project offers the popular web browser-based platform Galaxy for running bioinformatics tools and constructing simple workflows. Here, we present a broad collection of additional Galaxy tools for large scale analysis of gene and protein sequences. The motivating research theme is the identification of specific genes of interest in a range of non-model organisms, and our central example is the identification and prediction of "effector" proteins produced by plant pathogens in order to manipulate their host plant. This functional annotation of a pathogen's predicted capacity for virulence is a key step in translating sequence data into potential applications in plant pathology. This collection includes novel tools, and widely-used third-party tools such as NCBI BLAST+ wrapped for use within Galaxy. Individual bioinformatics software tools are typically available separately as standalone packages, or in online browser-based form. The Galaxy framework enables the user to combine these and other tools to automate organism scale analyses as workflows, without demanding familiarity with command line tools and scripting. Workflows created using Galaxy can be saved and are reusable, so may be distributed within and between research groups, facilitating the construction of a set of standardised, reusable bioinformatic protocols. The Galaxy tools and workflows described in this manuscript are open source and freely available from the Galaxy Tool Shed (http://usegalaxy.org/toolshed or http://toolshed.g2.bx.psu.edu).


Animal models of Listeria infection.
Listeria monocytogenes is an intracellular foodborne pathogen that causes listeriosis, an infection characterized by gastroenteritis, meningitis, encephalitis, and maternofetal infections in humans. L. monocytogenes enters the host via contaminated foods, invades the small intestine, translocates to mesenteric lymph nodes, and spreads to the liver, spleen, brain and, in pregnant women, the fetoplacental unit. Many pathogenicity tests for studying L. monocytogenes have been developed, including tests using laboratory animals. A number of small animal species can be experimentally infected with Listeria. Mice and guinea pigs can be infected either intragastrically or intravenously, and virulence evaluated either by enumerating bacteria within infected target organs or by evaluating the 50% lethal dose (LD50). Although mice and guinea pigs can be infected with Listeria by a variety of routes, the intragastric route is the most relevant to the human foodborne listeriosis.


Detection of magnetic field properties using distributed sensing: a computational neuroscience approach.
Diverse taxa use Earth's magnetic field to aid both short- and long-distance navigation. Study of these behaviors has led to a variety of postulated sensory and processing mechanisms that remain unconfirmed. Although several models have been proposed to explain and understand these mechanisms' underpinnings, they have not necessarily connected a putative sensory signal to the nervous system. Using mathematical software simulation, hardware testing and the computational neuroscience tool of dynamic neural fields, the present work implements a previously developed conceptual model for processing magnetite-based magnetosensory data. Results show that the conceptual model, originally constructed to stimulate thought and generate insights into future physiological experiments, may provide a valid approach to encoding magnetic field information. Specifically, magnetoreceptors that are each individually capable of sensing directional information can, as a population, encode magnetic intensity and direction. The findings hold promise both as a biological magnetoreception concept and for generating engineering innovations in sensing and processing.


Patient Selection by Tumor Markers in Liver Transplantation for Advanced Hepatocellular Carcinoma.
Although far advanced hepatocellular carcinoma (HCC) is generally considered a contraindication for liver transplantation (LT), biologically favorable tumors among them could show acceptable results. However, it is still unclear which tumors can be treated with LT. Data were collected on adult patients who underwent LT for HCC beyond the Milan criteria in 8 Korean LT centers between January 2000 and June 2013. Far advanced HCC was defined as HCC with the largest tumor ≥ 10 cm, 10 or more tumor nodules, or accompanying macrovascular invasion. A total of 688 patients, including 169 with far advanced HCC, were enrolled in this study. The 5-year overall and recurrence-free survival rates were 60.4% and 55.1%, respectively, for all patients but only 28.7% and 24.8%, respectively, for patients with far advanced HCC (P < 0.001). Both preoperative alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) were significant risk factors for HCC recurrence after LT. In particular, AFP + PIVKA-II combined was a better predictor than either marker alone. Of all far advanced HCC patients with available AFP and PIVKA-II levels, 45 (30.8%) had low AFP + PIVKA-II (≤300) and their 5-year overall and recurrence-free survival rate were 47.8% and 53.4%, respectively, which were acceptable and significantly superior to those of patients with AFP (ng/mL) + PIVKA-II (nAU/mL) > 300 (21.0% and 10.8%, respectively; P < 0.001). In conclusion, patients with favorable HCC had acceptable outcomes after LT even when their tumors were extremely advanced. AFP + PIVKA-II gave reliable information about the tumor biology of far advanced HCC. Liver Transplantation 00 000-000 2018 AASLD.


Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight.
Astronauts commonly return from space with altered short-term cardiovascular dynamics and blunted baroreflex sensitivity. Although many studies have addressed this issue, post-flight effects on the dynamic circulatory control remain incompletely understood. It is not clear how long the cardiovascular system needs to recover from spaceflight as most post-flight investigations only extended between a few days and 2 weeks. In this study, we examined the effect of short-duration spaceflight (1-2 weeks) on respiratory-mediated cardiovascular rhythms in five cosmonauts. Two paced-breathing protocols at 6 and 12 breaths min(-1) were performed in the standing and supine positions before spaceflight, and after 1 and 25 days upon return. Dynamic baroreflex function was evaluated by transfer function analysis between systolic pressure and the RR intervals. Post-flight orthostatic blood pressure control was preserved in all cosmonauts. In the standing position after spaceflight there was an increase in heart rate (HR) of approx. 20 beats min(-1) or more. Averaged for all five cosmonauts, respiratory sinus dysrhythmia and transfer gain reduced to 40% the day after landing, and had returned to pre-flight levels after 25 days. Low-frequency gain decreased from 6.6 (3.4) [mean (SD)] pre-flight to 3.9 (1.6) post-flight and returned to 5.7 (1.3) ms mmHg(-1) after 25 days upon return to Earth. Unlike alterations in the modulation of HR, blood pressure dynamics were not significantly different between pre- and post-flight sessions. Our results indicate that short-duration spaceflight reduces respiratory modulation of HR and decreases cardiac baroreflex gain without affecting post-flight arterial blood pressure dynamics. Altered respiratory modulation of human autonomic rhythms does not persist until 25 days upon return to Earth.


Low temperature geomicrobiology follows host rock composition along a geochemical gradient in lau basin.
The East Lau Spreading Center (ELSC) and Valu Fa Ridge (VFR) comprise a ridge segment in the southwest Pacific Ocean where rapid transitions in the underlying mantle chemistry manifest themselves as gradients in seafloor rock geochemistry. We studied the geology and microbial diversity of three silicate rock samples and three inactive sulfide chimney samples collected, from north to south, at the vent fields Kilo Moana, ABE, Tui Malila, and Mariner. This is the first study of microbial populations on basaltic andesite, which was sampled at Mariner vent field. Silicate rock geochemistry exhibits clear latitudinal trends that are mirrored by changes in bacterial community composition. α-proteobacteria, ε-proteobacteria, and Bacteroidetes are most common on a silicate collected from Kilo Moana and their proportions decrease linearly on silicates collected further south. Conversely, a silicate from Mariner vent field hosts high proportions of a unique lineage of Chloroflexi unrelated (<90% sequence similarity) to previously recovered environmental clones or isolates, which decrease at ABE and are absent at Kilo Moana. The exteriors of inactive sulfide structures are dominated by lineages of sulfur oxidizing α-proteobacteria, γ-proteobacteria, and ε-proteobacteria, while the interior of one chimney is dominated by putative sulfur-reducing δ-proteobacteria. A comparison of bacterial communities on inactive sulfides from this and previous studies reveals the presence of a clade of uncultured Bacteroidetes exclusive to sulfidic environments, and a high degree of heterogeneity in bacterial community composition from one sulfide structure to another. In light of the heterogeneous nature of bacterial communities observed here and in previous studies of both active and inactive hydrothermal sulfide structures, the presence of numerous niches may be detected on these structures in the future by finer scale sampling and analysis.


Health and ageing in Nairobi's informal settlements-evidence from the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH): a cross sectional study.
Much of the focus on population ageing has been in high-income counties. Relatively less attention is given to the world's poorest region, Sub-Saharan Africa (SSA) where children and adolescents still comprise a high proportion of the population. Yet the number of adults aged 60-plus in SSA is already twice that in northern Europe. In addition, SSA is experiencing massive rural to urban migration with consequent expansion of informal urban settlements, or slums, whose health problems are usually unrecognised and not addressed. This study aims to improve understanding of functional health and well-being in older adult slum-dwellers in Nairobi (Kenya). The study sample comprised men and women, aged 50 years and over, living in Korogocho and Viwandani, Nairobi, Kenya (n = 1,878). Data from the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) and the WHO Study on global AGEing and adult health (SAGE Wave 1) were analysed. The prevalence of poor self-reported quality of life (QoL) and difficulties in domain-specific function is estimated by age and sex. Logistic regression investigates associations between difficulties in the domains of function and poor QoL, adjusting for age, sex and socio-demographic factors. Statistical significance is set at P<0.05. Women reported poorer QoL and greater functional difficulties than men in all domains except self-care. In the multivariable logistic regression the odds of poor QoL among respondents with problems or difficulties in relation to affect (OR = 7.0; 95%CI = 3.0-16.0), pain/discomfort (OR = 3.6; 95%CI = 2.3-5.8), cognition (OR = 1.8; 95 %CI = 1.2-2.9) and mobility (OR = 1.8; 95%CI = 1.1-2.8) were statistically significant. The findings underscore differences in the domains of functional health that encapsulate women and men's capacities to perform regular activities and the impact of poor functioning on QoL. Investing in the health and QoL of older people in SSA will be crucial in helping the region to realise key development goals and in opening opportunities for improved health outcomes and sustainable economic development.


Regulating Hybrids: 'Making a Mess' and 'Cleaning Up' in Tissue Engineering and Transpecies Transplantation.
This paper explores the institutional regulation of novel biosciences, hybrid technologies that often disturb and challenge existing regulatory frameworks. Developing a conceptual vocabulary for understanding the relationship between material and institutional hybrids, the paper compares human tissue engineering (TE) and xenotransplantation (XT), areas of innovation which regulators have sought to govern separately and in isolation from one another. Contrasting definitional boundaries and regulatory mechanisms partition them socio-institutionally. But despite these attempts at purification, TE and XT have proven increasingly difficult to tell apart in practical and material terms. Human and animal matters, cell cultures and tissue products have much greater corporeal connection than has been institutionally recognized, and are therefore a source of acute instability in the regulation of implants and transplants. This paper tells the story of how the messy worlds of TE and XT have leaked into one another, calling into question the abilities of regulation to adequately control hybrid innovations.


Investigating the behavioural effects of a mobile-phone based home telehealth intervention in people with insulin-requiring diabetes: Results of a randomized controlled trial with patient interviews.
Introduction Evidence supporting home telehealth effects on clinical outcomes in diabetes is available, yet mechanisms of action for these improvements remain poorly understood. Behavioural change is one plausible explanation. This study investigated the behavioural effects of a mobile-phone based home telehealth (MTH) intervention in people with diabetes. It was hypothesized that MTH would improve self-efficacy, illness beliefs, and diabetes self-care. Methods A randomized controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, data transmission, graphical and nurse-initiated feedback, educational calls). Self-report measures of self-efficacy, illness beliefs, and self-care were repeated at baseline, three months, and nine months. MTH effects were based on the group by time interactions in hierarchical linear models and effect sizes with 95% confidence intervals (CIs). Interviews with MTH participants explored the perceived effects of MTH on diabetes self-management. Results Eighty-one participants were randomized to the intervention ( n = 45) and standard care ( n = 36). Significant group by time effects were observed for five out of seven self-efficacy subscales. Effect sizes were large, particularly at nine months. Interaction effects for illness beliefs and self-care were non-significant, but effect sizes and confidence intervals suggested MTH may positively affect diet and exercise. In interviews, MTH was associated with increased awareness, motivation, and a greater sense of security. Improved self-monitoring and diet were reported by some participants. Discussion MTH empowers people with diabetes to manage their condition and may influence self-care. Future MTH research would benefit from investigating behavioural mechanisms and determining patient profiles predictive of greater behavioural effectiveness.


Dual inhibition of akt/mammalian target of rapamycin pathway by nanoparticle albumin-bound-rapamycin and perifosine induces antitumor activity in multiple myeloma.
The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple myeloma (MM) cell proliferation, survival, and development of drug resistance, underscoring the role of mTOR inhibitors, such as rapamycin, with potential anti-MM activity. However, recent data show a positive feedback loop from mTOR/S6K1 to Akt, whereby Akt activation confers resistance to mTOR inhibitors. We confirmed that suppression of mTOR signaling in MM cells by rapamycin was associated with upregulation of Akt phosphorylation. We hypothesized that inhibiting this positive feedback by a potent Akt inhibitor perifosine would augment rapamycin-induced cytotoxicity in MM cells. Perifosine inhibited rapamycin-induced phosphorylated Akt, resulting in enhanced cytotoxicity in MM.1S cells even in the presence of interleukin-6, insulin-like growth factor-I, or bone marrow stromal cells. Moreover, rapamycin-induced autophagy in MM.1S MM cells, as evidenced by electron microscopy and immunocytochemistry, was augmented by perifosine. Combination therapy increased apoptosis detected by Annexin V/propidium iodide analysis and caspase/poly(ADP-ribose) polymerase cleavage. Importantly, in vivo antitumor activity and prolongation of survival in a MM mouse xenograft model after treatment was enhanced with combination of nanoparticle albumin-bound-rapamycin and perifosine. Utilizing the in silico predictive analysis, we confirmed our experimental findings of this drug combination on PI3K, Akt, mTOR kinases, and the caspases. Our data suggest that mutual suppression of the PI3K/Akt/mTOR pathway by rapamycin and perifosine combination induces synergistic MM cell cytotoxicity, providing the rationale for clinical trials in patients with relapsed/refractory MM. Mol Cancer Ther; 9(4); 963-75. (c)2010 AACR.


Treatment of oppositional defiant and conduct problems in young Norwegian children : results of a randomized controlled trial.
The efficacy of the Incredible Years parent training and child therapy programs was examined in a randomized controlled study including 127 Norwegian children aged 4-8 years. Children diagnosed with oppositional defiant disorder (ODD) or conduct disorder (CD) were randomized to parent training (PT), parent training combined with child therapy (PT + CT), or a waiting-list control condition (WLC). Assessments were carried out at baseline, posttreatment and at a one-year follow-up using standardized measures and a semi-structured interview. Both active treatment conditions reduced child conduct problems posttreatment as opposed to the WLC, while differences between the two treatment conditions were small and nonsignificant. About two thirds of the treated children functioned within normal variation after treatment, and the same proportion no longer received an ODD diagnosis at the one-year follow-up. Parental use of positive strategies increased after treatment, and the use of harsh and inconsistent discipline decreased as did mother experience of stress. The outcome of this study emphasizes the importance of offering parent training to young children with severe conduct problems exhibited at home. The findings and usefulness of the Incredible Years program in the present Norwegian replication study further support and extend positive outcomes of previous controlled trials conducted primarily in Anglo-Saxon countries.


Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer.
To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT). Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method. One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9-5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70Gy and D5% (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78-0.88) and 0.89 (IQR, 0.85-0.93) at 2 and 5 years of followup, respectively. A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70Gy and D5%) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.


Physicians infrequently adhere to hepatitis vaccination guidelines for chronic liver disease.
Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines. We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview. HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority. Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines.


Valid items for screening dysphagia risk in patients with stroke: a systematic review.
Screening for dysphagia is essential to the implementation of preventive therapies for patients with stroke. A systematic review was undertaken to determine the evidence-based validity of dysphagia screening items using instrumental evaluation as the reference standard. Four databases from 1985 through March 2011 were searched using the terms cerebrovascular disease, stroke deglutition disorders, and dysphagia. Eligibility criteria were: homogeneous stroke population, comparison to instrumental examination, clinical examination without equipment, outcome measures of dysphagia or aspiration, and validity of screening items reported or able to be calculated. Articles meeting inclusion criteria were evaluated for methodological rigor. Sensitivity, specificity, and predictive capabilities were calculated for each item. Total source documents numbered 832; 86 were reviewed in full and 16 met inclusion criteria. Study quality was variable. Testing swallowing, generally with water, was the most commonly administered item across studies. Both swallowing and nonswallowing items were identified as predictive of aspiration. Neither swallowing protocols nor validity were consistent across studies. Numerous behaviors were found to be associated with aspiration. The best combination of nonswallowing and swallowing items as well as the best swallowing protocol remains unclear. Findings of this review will assist in development of valid clinical screening instruments.


Baseline Factors Associated With 6-Month Visual Acuity and Retinal Thickness Outcomes in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion: SCORE2 Study Report 4.
Macular edema (ME) is the leading cause of decreased visual acuity (VA) associated with retinal vein occlusion (RVO). Identifying factors associated with better outcomes in RVO eyes treated with anti-vascular endothelial growth factor (VEGF) therapy may provide information useful in counseling patients. To investigate baseline characteristics associated with 6-month VA and central subfield thickness (CST) outcomes in participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). A total of 362 patients with central RVO or hemi-RVO were enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in a masked fashion to receive bevacizumab or aflibercept. At month 6, 348 participants (96%) had VA outcomes measured and 335 participants (93%) had spectral domain optical coherence tomography outcomes measured. The current data analysis was conducted from February 27, 2017, to April 7, 2017. Eyes were randomly assigned to receive an intravitreal injection of bevacizumab, 1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary outcome measured at 6 months. Change from baseline in VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST less than 300 µm, and resolution of ME. Baseline factors associated with 6-month outcome at the 0.05 level in univariate regressions were included in multivariate regressions, with those significant after multiplicity control by the Hochberg method reported. The mean (SD) age of patients was 69 (12) years, and 43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95% CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI, 0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater. Compared with bevacizumab, aflibercept treatment was associated with a higher odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than 300 µm (OR, 5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03). In eyes treated with bevacizumab or aflibercept, younger age and worse baseline VALS were associated with better 6-month VA outcomes. Aflibercept treatment was associated with more favorable spectral domain optical coherence tomography outcomes but not VA outcomes. These findings may be useful in assessing expected response at month 6 after monthly injection of anti-VEGF agents for treating ME due to CRVO and HRVO. clinicaltrials.gov Identifier: NCT01969708.


Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.
Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations.


Laser photoexcitation of NAD(P)H induces reduction of P450 BM3 heme domain on the microsecond time scale.
We demonstrate that photoexcitation of NAD(P)H at 355 nm using a Nd:YAG laser leads to rapid reduction of the heme domain of the Bacillus megaterium fatty acid hydroxylase flavocytochrome P450 BM3. An aqueous electron derived from photoexcited NAD(P)H is rapidly transferred to the heme domain, enabling the formation of a carbon monoxy complex of the ferrous P450 (FeII-CO) on the microsecond time scale. Using this approach we have determined the limiting rate constant (1770 s-1 for substrate-free heme domain) for formation of the FeII-CO complex. We find no dependence of the observed rate of FeII-CO complex formation on NAD(P)H concentration but demonstrate a hyperbolic dependence on carbon monoxide concentration. The apparent dissociation constant for the complex of carbon monoxide bound noncovalently to the ferric form of the BM3 heme domain (and with NADH as reductant) is 323 microM. Binding of a P450 substrate (N-palmitoylglycine) weakened the complex between carbon monoxide and the ferric BM3 heme domain (Kd increased to 1404 microM) but enhanced the rate of formation of the FeII-CO complex (3036 s-1 for substrate-free heme domain). This study demonstrates the applicability of NAD(P)H photoexcitation as a method for rapid electron delivery to P450 enzymes and provides a new route to probing the P450 catalytic cycle and its transient intermediates.


Lentiviral Delivery of Small Hairpin RNA Targeting Connective Tissue Growth Factor Blocks Profibrotic Signaling in Tenon's Capsule Fibroblasts.
Trabeculectomy is a surgical procedure for lowering intraocular pressure in glaucoma patients, in which excessive scarring leading to failure of the filtering bleb adversely affects the surgical outcome. Heightened Tenon's capsule fibroblast (TCF) proliferation and extracellular matrix (ECM) deposition are implicated in this process but endogenous factors that regulate TCF functions remain largely elusive. This study sought to elucidate the role of connective tissue growth factor (CTGF) in the regulation of TCF phenotypes and signaling. Expression of CTGF in scarring and nonscarring Tenon's capsules was measured by real-time PCR and immunofluorescence. Knockdown of CTGC was achieved by lentivirus delivery of small-hairpin RNA. Cell proliferation was measured by CCK8, cell cycle progression, and apoptosis by flow cytometry, adhesion, migration, and invasion of TCF by functional assays in vitro. Proteins and cytokines related to fibrosis were measured by Western blot and ELISA, respectively. Expression of CTGF was significantly upregulated in scarring Tenon's capsules and their isolated fibroblasts when compared with the nonfibrotic counterparts. Functionally, targeting CTGF with lentivirus-delivered small-hairpin RNA inhibited the proliferation, adhesion, migration, and invasion of TCFs, accompanied by downregulation of p38 and nuclear factor-κB as well as matrix metalloproteinase-2, cyclin D1, and collagen I. In addition, lentiviral targeting of CTGF reduced the release of fibrosis-related cytokines from TCFs and inhibited TCF-conditioned, medium-induced macrophage chemotaxis. Our study supports a crucial role of CTGF in the regulation of TCF proliferation and ECM deposition. Targeting CTGF using lentiviral vector may be a promising approach for preventing excessive scarring after trabeculectomy.


Muscle-Specific Effective Mechanical Advantage and Joint Impulse in Weightlifting.
Kipp, K, and Harris, C. Muscle-specific effective mechanical advantage and joint impulse in weightlifting. J Strength Cond Res 31(7): 1905-1910, 2017-Lifting greater loads during weightlifting exercises may theoretically be achieved through increasing the magnitudes of net joint impulses or manipulating the joints' effective mechanical advantage (EMA). The purpose of this study was to investigate muscle-specific EMA and joint impulse as well as impulse-momentum characteristics of the lifter-barbell system across a range of external loads during the execution of the clean. Collegiate-level weightlifters performed submaximal cleans at 65, 75, and 85% of their 1-repetition maximum (1-RM), whereas data from a motion analysis system and a force plate were used to calculate lifter-barbell system impulse and velocity, as well as net extensor impulse generated at the hip, knee, and ankle joints and the EMA of the gluteus maximus, hamstrings, quadriceps, and triceps surae muscles. The results indicated that the lifter-barbell system impulse did not change as load increased, whereas the velocity of the lifter-barbell system decreased with greater load. In addition, the net extensor impulse at all joints increased as load increased. The EMA of all muscles did not, however, change as load increased. The load-dependent effects on the impulse-velocity characteristics of the lifter-barbell system may reflect musculoskeletal force-velocity behaviors, and may further indicate that the weightlifting performance is limited by the magnitude of ground reaction force impulse. In turn, the load-dependent effects observed at the joint level indicated that lifting greater loads were due to greater net extensor impulses generated at the joints of the lower extremity and not greater EMAs of the respective extensor muscles. In combination, these results suggest that lifting greater external loads during the clean is due to the ability to generate large extensor joint impulses, rather than manipulate EMA.


Self-concepts and demographic characteristics of battered women in Gauteng, South Africa.
In South Africa, studies have shown that one in every four women are abused or battered. Put graphically, 25% of women in the Republic of South Africa (RSA) are assaulted by their boyfriend/partner or husband and a woman suffer battering on average of 39 times before she seeks outside help. Woman battering can leave women abused, distressed, create fear, limits behaviour, cause psychological damage and physical harms and very often breaks down self-esteem and leaves the individual self-incompetent. Hence the need to understand how women who have been abused rate their pre and post abuse self-concepts, how their demographic characteristics influence their self-concepts and also understand their attitude towards their abuser. Through in-depth interviews using a questionnaire, data were collected from 150 randomly selected abused women attending a respite centre located in Johannesburg. Age of women ranged from 16 years to 49 years with a mean age of 32.2 (SD = 8.27). Abuse or being battered in this study is defined as "women who have been emotionally abused or physically beaten by husband/boyfriend with blows, slapped, kicked and have experienced these over three times in a single relationship. The study was anchored on a three research questions. Results showed that before abuse, women rated themselves positively (X bar = 82.4) and negatively after abuse (X bar = 69.9). The study showed a huge drop in self-concept change (X bar = 23.9) after abuse. At a pre-abuse level, women generally rated themselves positively on almost all dimensions and negatively after abuse on almost all bi-polar items. The study also found that demographics of abused women such as marital status (C2 (1, N = 149) = 7.30, P < .01), educational level (C2 (1, N = 149) = 15.89, P < .001), duration of abuse (C2 (1, N = 149) = 12.71, P < .002), and nature of abuse (C2 (1, N = 149) = 4.502, P < .05) do influence self-concepts of abused women. Age of women was not significant. Finally, results also indicate that majority of the women have negative attitude towards their abuser (C2 (1, N = 149) = 4.051, P < .05). The abuser was described negatively as cold, slow, passive, weak, sick, tense, unpredictable, sad, dangerous, ignorant and bad. Surprisingly, the abuser was also described as rich, wise, clean and valuable. These findings have significant practical implications for intimate partner violence or Gender-based violence and the health and psychological outcomes for battered women. The study also suggests the need for more research in this direction and a need for culturally relevant programmes to help women in abusive relationships and in addition help the abusers deal with myths that have cultural relevance to factors maintaining battering.


Alexander's law in patients with acute vestibular tone asymmetry--evidence for multiple horizontal neural integrators.
Alexander's law (AL) states that the slow-phase velocity of spontaneous nystagmus of peripheral vestibular origin is dependent on horizontal gaze position, with greater velocity when gaze is directed in the fast-phase direction. AL is thought to be a compensatory reaction resulting from adaptive changes in the horizontal ocular motor neural integrator. Until now, only horizontal eye movements have been investigated with respect to AL. Because spontaneous nystagmus usually includes vertical and torsional components, we asked whether horizontal gaze changes would have an effect on the 3D drift of spontaneous nystagmus and, thus, on the vertical/torsional neural integrator. We hypothesized that AL reduces all nystagmus components proportionally. Moreover, we questioned the classical theory of a single bilaterally organized horizontal integrator and searched for nonlinearities of AL implying a network of multiple integrators. Using dual scleral search coils, we measured AL in 17 patients with spontaneous nystagmus. Patients followed a pulsed laser dot at eye level jumping in 5 degrees steps along the horizontal meridian between 25 degrees right and left in otherwise complete darkness. AL was observed in 15 of 17 patients. Whereas individual patients typically showed a change of 3D-drift direction at different horizontal eye positions, the average change in direction was not different from zero. The strength of AL (= rate of change of total velocity with gaze position) correlated with nystagmus slow-phase velocity (Spearman's rho = 0.5; p < 0.05) and, on average, did not change the 3D nystagmus drift direction. In general, eye velocity did not vary linearly with eye position. Rather, there was a stronger dependence of velocity on horizontal position when subjects looked in the slow-phase direction compared to the fast-phase direction. We conclude that the theory of a simple leak of a single horizontal neural integrator is not sufficient to explain all aspects of AL.


Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank.
Coronary artery disease (CAD) is a common complication among individuals with diabetes. A better understanding of the genetic background of CAD in this population has the potential to suggest novel molecular targets for screening, risk assessment and drug development. We performed a genome-wide association study of CAD in 15,666 unrelated individuals (3,968 CAD cases and 11,698 controls) of white British ancestry with diabetes at inclusion in the UK Biobank study. Our results were compared with results from participants without diabetes. We found genome-wide significant evidence for association with CAD at the previously well-established LPA locus (lead variant: rs74617384; OR 1.38 [95% CI 1.26, 1.51], p = 3.2 × 10-12) and at 9p21 (lead variant: rs10811652; OR 1.19 [95% CI 1.13, 1.26], p = 6.0 × 10-11). Moreover, other variants previously associated with CAD showed similar effects in the participants with and without diabetes, indicating that the genetic architecture of CAD is largely the same. Our results indicate large similarities between the genetic architecture of CAD in participants with and without diabetes. Larger studies are needed to establish whether there are important diabetes-specific CAD loci.


A tabu search approach for the NMR protein structure-based assignment problem.
Spectroscopy is an experimental technique which exploits the magnetic properties of specific nuclei and enables the study of proteins in solution. The key bottleneck of NMR studies is to map the NMR peaks to corresponding nuclei, also known as the assignment problem. Structure-Based Assignment (SBA) is an approach to solve this computationally challenging problem by using prior information about the protein obtained from a homologous structure. NVR-BIP used the Nuclear Vector Replacement (NVR) framework to model SBA as a binary integer programming problem. In this paper, we prove that this problem is NP-hard and propose a tabu search (TS) algorithm (NVR-TS) equipped with a guided perturbation mechanism to efficiently solve it. NVR-TS uses a quadratic penalty relaxation of NVR-BIP where the violations in the Nuclear Overhauser Effect constraints are penalized in the objective function. Experimental results indicate that our algorithm finds the optimal solution on NVRBIP's data set which consists of seven proteins with 25 templates (31 to 126 residues). Furthermore, it achieves relatively high assignment accuracies on two additional large proteins, MBP and EIN (348 and 243 residues, respectively), which NVR-BIP failed to solve. The executable and the input files are available for download at http://people.sabanciuniv.edu/catay/NVR-TS/NVR-TS.html.


An atypical anxious-impulsive pattern of social anxiety disorder in an adult clinical population.
An atypical subgroup of Social Anxiety Disorder (SAD) with impulsive rather than inhibited traits has recently been reported. The current study examined whether such an atypical subgroup could be identified in a clinical population of 84 adults with SAD. The temperament dimensions harm avoidance and novelty seeking of the Temperament and Character Inventory, and the Liebowitz Social Anxiety Scale were used in cluster analyses. The identified clusters were compared on depressive symptoms, the character dimension self-directedness, and treatment outcome. Among the six identified clusters, 24% of the sample had atypical characteristics, demonstrating mainly generalized SAD in combination with coexisting traits of inhibition and impulsivity. As additional signs of severity, this group showed low self-directedness and high levels of depressive symptoms. We also identified a typically inhibited subgroup comprising generalized SAD with high levels of harm avoidance and low levels of novelty seeking, with a similar clinical severity as the atypical subgroup. Thus, higher levels of harm avoidance and social anxiety in combination with higher or lower levels of novelty seeking and low self-directedness seem to contribute to a more severe clinical picture. Post hoc examination of the treatment outcome in these subgroups showed that only 20 to 30% achieved clinically significant change.


A role for the septation initiation network in septum assembly revealed by genetic analysis of sid2-250 suppressors.
In the fission yeast Schizosaccharomyces pombe the septation initiation network (SIN) is required for stabilization of the actomyosin ring in late mitosis as well as for ring constriction and septum deposition. In a genetic screen for suppressors of the SIN mutant sid2-250, we isolated a mutation, ace2-35, in the transcription factor Ace2p. Both ace2Delta and ace2-35 show defects in cell separation, and both can rescue the growth defects of some SIN mutants at low restrictive temperatures, where the SIN single mutants lyse at the time of cytokinesis. By detailed analysis of the formation and constriction of the actomyosin ring and septum in the sid2-250 mutant at low restrictive temperatures, we show that the lysis phenotype of the sid2-250 mutant is likely due to a weak cell wall and septum combined with enzymatic activity of septum-degrading enzymes. Consistent with the recent findings that Ace2p controls transcription of genes involved in cell separation, we show that disruption of some of these genes can also rescue sid2-250 mutants. Consistent with SIN mutants having defects in septum formation, many SIN mutants can be rescued at the low restrictive temperature by the osmotic stabilizer sorbitol. The small GTPase Rho1 is known to promote cell wall formation, and we find that Rho1p expressed from a multi-copy plasmid can also rescue sid2-250 at the low restrictive temperature. Together these results suggest that the SIN has a role in promoting proper cell wall formation at the division septa.


Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes.
To compare long-term glycemic control and safety of using insulin aspart (IAsp) with that of regular human insulin (HI). This was a multicenter randomized open-label 6-month study (882 subjects) with a 6-month extension period (714 subjects) that enrolled subjects with type 1 diabetes. Subjects administered IAsp immediately before meals or regular HI 30 min before meals; basal NPH insulin was taken as a single bedtime dose in the majority of subjects. Glycemic control was assessed with HbA1c values and 8-point blood glucose profiles at 3-month intervals. Mean postprandial blood glucose levels (mg/dl +/- SEM) were significantly lower for subjects in the IAsp group compared with subjects in the HI group after breakfast (156 +/- 3.4 vs. 185 +/- 4.7), lunch (137 +/- 3.1 vs. 162 +/- 4.1), and dinner (153 +/- 3.1 vs. 168 +/- 4.1), when assessed after 6 months of treatment. Mean HbA1c values (% +/- SEM) were slightly, but significantly, lower for the IAsp group (7.78% +/- 0.03) than for the regular HI group (7.93% +/- 0.05, P = 0.005) at 6 months. Similar postprandial blood glucose and HbA1c values were observed at 12 months. Adverse events and overall hypoglycemic episodes were similar for both treatment groups. Postprandial glycemic control was significantly better with IAsp compared with HI after 6 and 12 months of treatment. The improvement was not obtained at an increased risk of hypoglycemia. HbA1c was slightly, but significantly, lower for IAsp compared with HI at 6 and 12 months.


Chlamydia pneumoniae induces aponecrosis in human aortic smooth muscle cells.
The intracellular bacterium Chlamydia pneumoniae is suspected to play a role in formation and progression of atherosclerosis. Many studies investigated cell death initiation versus inhibition by Chlamydia pneumoniae in established cell lines but nothing is known in primary human aortic smooth muscle cells, a cell type among others known to be involved in the formation of the atherosclerotic plaque. Type of cell death was analyzed by various methods in primary aortic smooth muscle cells after infection with Chlamydia pneumoniae to investigate a possible pathogenic link in atherosclerosis. Chlamydiae were found to be localized up to 72 h post infection in aortic smooth muscle cells either as single bacteria or inside of large inclusions. Quantification of host cell death by lactate dehydrogenase release assay revealed strictly dose and time dependent lysis for all tested isolates of Chlamydia pneumoniae. Phosphatidylserine exposure was detected by flow cytometry in Chlamydia pneumoniae infected cells. Ultrastructure of Chlamydia pneumoniae infected human aortic smooth muscle cells showed extensive membrane- and organelle damage, chromatin condensation but no nuclear fragmentation. DNA fragmentation as well as cell membrane permeability was analyzed by TUNEL and NHS-biotin staining and occurred exclusively in cells carrying Chlamydia pneumoniae spots but not in smooth muscle cells with inclusions. These morphological features of cell death were not accompanied by an activation of caspase-3 as revealed by analysis of enzyme activity but involved mitochondrial membrane depolarization as shown by TMRE uptake and release of cytochrome c from mitochondria. This study provides evidence that Chlamydia pneumoniae induce a spot like infection in human aortic smooth muscle cells, which results in a chimeric cell death with both apoptotic and necrotic characteristics. This aponecrotic cell death may assist chronic inflammation in atherosclerotic blood vessels.


Predictors of having a dentist among older adults in Iowa.
Oral health plays an important role in the general well-being of older adults, yet older adults experience unique barriers to dental care. In the United States, almost two-thirds of older adults are dentally uninsured - a reflection of the exclusion of dental benefits from Medicare. The aim of this study was to investigate potential predictors of having a dentist among older adults receiving services funded through the Iowa Department on Aging (IDA). This was a cross-sectional analysis on a convenience sample (n = 2692) of adults age 65+ who completed a required survey to determine eligibility to receive services from the IDA. Data from questionnaires completed between March and December 2017 were used to generate multivariable logistic regression models that identified predictors of having a dentist. The dependent variable, having a dentist, was gathered by self-report in the survey. Explanatory variables eligible for inclusion in the models included demographic and geographic factors, indicators of access to dental care, and factors related to activities of daily living. Fewer than half (46.2%) of the respondents reported having a dentist. In the final regression model, individuals with dental insurance were more than twice as likely to have a dentist than those without insurance. Conversely, individuals with a tooth/mouth problem and who need help with housekeeping and with transportation were significantly less likely to have a dentist than their counterparts. These results align with known insurance-related barriers and identify certain activities of daily living that might influence older adults' ability to access care. The finding that individuals with oral health problems were less likely to have a dentist underscores the need to reduce barriers to care for this population.


Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine.
O6-Methylguanine-DNA methyltransferase (MGMT; DNA-O6-methylguanine:protein-L-cysteine S-methyltransferase, EC 22.214.171.124), a unique DNA repair protein present in most organisms, removes the carcinogenic and mutagenic adduct O6-alkylguanine from DNA by stoichiometrically accepting the alkyl group on a cysteine residue in a suicide reaction. The mammalian protein is highly regulated in both somatic and germ-line cells. In addition, the toxicity of certain alkylating drugs in tumor and normal cells is inversely related to the levels of this protein. The cDNA of the human gene, henceforth named MGMT, has been cloned in an expression vector on the basis of its rescue of a methyltransferase-deficient (ada-) Escherichia coli host. A 22-kDa active methyltransferase encoded entirely by the cDNA contains an amino acid sequence of 61 residues that bears 60-65% similarity with segments of E. coli methyltransferase (products of the ada and ogt genes), which encompass the alkyl-acceptor residues. The human cDNA has no sequence similarity with the ada and ogt genes, due in part to differences in codon usage, and shows no detectable homology with E. coli genomic DNA. However, it hybridizes with distinct restriction fragments of human, mouse, and rat DNAs. The lack of methyltransferase observed in many human cell lines is due to the absence of the MGMT gene or to lack of synthesis and/or stability of its 0.95-kilobase poly(A)+ RNA transcript.


YjbH-enhanced proteolysis of Spx by ClpXP in Bacillus subtilis is inhibited by the small protein YirB (YuzO).
The Spx protein of Bacillus subtilis is a global regulator of the oxidative stress response. Spx concentration is controlled at the level of proteolysis by the ATP-dependent protease ClpXP and a substrate-binding protein, YjbH, which interacts with Spx. A yeast two-hybrid screen was carried out using yjbH as bait to uncover additional substrates or regulators of YjbH activity. Of the several genes identified in the screen, one encoded a small protein, YirB (YuzO), which elevated Spx concentration and activity in vivo when overproduced from an isopropyl-β-D-thiogalactopyranoside (IPTG)-inducible yirB construct. Pulldown experiments using extracts of B. subtilis cells producing a His-tagged YirB showed that native YjbH interacts with YirB in B. subtilis. Pulldown experiments using affinity-tagged Spx showed that YirB inhibited YjbH interaction with Spx. In vitro, YjbH-mediated proteolysis of Spx by ClpXP was inhibited by YirB. The activity of YirB is similar to that of the antiadaptor proteins that were previously shown to reduce proteolysis of a specific ClpXP substrate by interacting with a substrate-binding protein.


Improving strategies for detecting genetic patterns of disease susceptibility in association studies.
The analysis of gene interactions and epistatic patterns of susceptibility is especially important for investigating complex diseases such as cancer characterized by the joint action of several genes. This work is motivated by a case-control study of bladder cancer, aimed at evaluating the role of both genetic and environmental factors in bladder carcinogenesis. In particular, the analysis of the inflammation pathway is of interest, for which information on a total of 282 SNPs in 108 genes involved in the inflammatory response is available. Detecting and interpreting interactions with such a large number of polymorphisms is a great challenge from both the statistical and the computational perspectives. In this paper we propose a two-stage strategy for identifying relevant interactions: (1) the use of a synergy measure among interacting genes and (2) the use of the model-based multifactor dimensionality reduction method (MB-MDR), a model-based version of the MDR method, which allows adjustment for confounders.


High-intensity functional exercise in older adults with dementia: A systematic review and meta-analysis.
This study aimed to investigate the efficacy of high-intensity functional exercise among older adults with dementia. In this systematic review and meta-analysis of randomized controlled trials, we collected articles published before August 2020 from PubMed, Embase, and the Cochrane Library to evaluate the effect of high-intensity functional exercise on older adults with dementia. Primary outcomes included improvements in balance function and gait performance (speed, cadence, and stride length). The secondary outcomes included lower limb strength, activities of daily living, psychiatric well-being, depression, and cognition. Furthermore, we performed subgroup analysis with two high-intensity functional exercise programs: the Umeå program and Hauer's program. We identified 15 articles describing six trials including older adults with dementia undergoing high-intensity functional exercise or control activity. The meta-analysis indicated that high-intensity functional exercise, both in Hauer's program and in the Umeå program, significantly improved balance function (pooled standardized mean difference 0.57, 95% confidence interval 0.31-0.83). Hauer's program significantly improved gait speed, cadence, stride length, and lower limb strength. Beneficial effects on speed, cadence, and lower limb strength were retained for several months. The Umeå program facilitated activities of daily living and psychiatric well-being, with effects on activities of daily living lasting several months. In the only eligible trial, no effects on cognition were observed. Adverse effects of high-intensity functional exercise were minimal to none. High-intensity functional exercise is generally safe and is recommended for older individuals with mild or moderate dementia to provide benefits in motor performance and daily functioning.


Surface Laplacian of scalp electrical signals and independent component analysis resolve EMG contamination of electroencephalogram.
The serious impact of electromyogram (EMG) contamination of electroencephalogram (EEG) is well recognised. The objective of this research is to demonstrate that combining independent component analysis with the surface Laplacian can eliminate EMG contamination of the EEG, and to validate that this processing does not degrade expected neurogenic signals. The method involves sequential application of ICA, using a manual procedure to identify and discard EMG components, followed by the surface Laplacian. The extent of decontamination is quantified by comparing processed EEG with EMG-free data that was recorded during pharmacologically induced neuromuscular paralysis. The combination of the ICA procedure and the surface Laplacian, with a flexible spherical spline, results in a strong suppression of EMG contamination at all scalp sites and frequencies. Furthermore, the ICA and surface Laplacian procedure does not impair the detection of well-known, cerebral responses; alpha activity with eyes-closed; ERP components (N1, P2) in response to an auditory oddball task; and steady state responses to photic and auditory stimulation. Finally, more flexible spherical splines increase the suppression of EMG by the surface Laplacian. We postulate this is due to ICA enabling the removal of local muscle sources of EMG contamination and the Laplacian transform being insensitive to distant (postural) muscle EMG contamination.


Health outcomes among patients receiving oseltamivir.
Oseltamivir was approved by the FDA for the treatment of influenza in 1999. The primary objective was to compare health outcomes among influenza patients who were treated with oseltamivir and those who were not. The patient population included UnitedHealthcare members who received an influenza diagnosis during the 1999-2000 influenza season, divided into those who were dispensed oseltamivir on the same day (N = 3211) and those who were not dispensed oseltamivir (N = 19,985). Cardiovascular, neuropsychiatric and respiratory outcomes were assessed from medical claims for a 30-day period. The adjusted incidence rate ratio for major cardiac outcome was 0.56 (95%CI: 0.34-0.93) in those without a positive history of major cardiac disease, indicating that those in the oseltamivir group tended to be at lower risk of cardiac outcomes than those without oseltamivir. The adjusted incidence rate ratio for major neuropsychiatric outcome was 0.72 (95%CI: 0.53-0.97) in the negative history of neuropsychiatric disease stratum. The incidence rate ratios for respiratory events were more variable. There appears to be no increased risk of cardiac or neuropsychiatric outcomes among subjects with influenza who were treated with oseltamivir in comparison with those who were not.


Evidence that HIV budding in primary macrophages occurs through the exosome release pathway.
Lipid rafts are specialized regions of cell membranes enriched in cholesterol and sphingolipids that are involved in immune activation and signaling. Studies in T-cells indicate that these membrane domains serve as sites for release of human immunodeficiency virus (HIV). By budding through lipid rafts in T-cells, HIV selectively incorporates raft markers and excludes non-raft proteins. This process has been well studied in T-cells, but it is unknown whether lipid rafts serve as budding sites for HIV in macrophages. Recently, we proposed a new model of retroviral biogenesis called the Trojan exosome hypothesis (Gould, S. J., Booth, A., and Hildreth, J. E. K. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 10592-10597). This model proposes that retroviruses coopt the existing cellular machinery for exosomal release. Here, we performed the first test designed to differentiate between the lipid raft hypothesis of retroviral biogenesis and the Trojan exosome hypothesis. Using macrophages, we examined the relative abundance of several host proteins on the cell surface, in lipid rafts, and on both HIV particles and exosomes derived from these cells. Our results show significant differences in the abundance of host proteins on the cell surface and in HIV. Moreover, our data demonstrate discordance in the abundance of some proteins in lipid rafts and in HIV. Finally, our data reveal a strong concordance between the host cell protein profile of exosomes and that of HIV. These results strongly support the Trojan exosome hypothesis and its prediction that retroviral budding represents exploitation of a pre-existing cellular pathway of intercellular vesicle trafficking.