Short-term thermal acclimation modulates predator functional response.
Phenotypic plastic responses to temperature can modulate the kinetic effects of temperature on biological rates and traits and thus play an important role for species adaptation to climate change. However, there is little information on how these plastic responses to temperature can influence trophic interactions. Here, we conducted an experiment using marbled crayfish and their water louse prey to investigate how short-term thermal acclimation at two temperatures (16 and 24°C) modulates the predator functional response. We found that both functional response parameters (search rate and handling time) differed between the two experimental temperatures. However, the sign and magnitudes of these differences strongly depended on acclimation time. Acclimation to 16°C increased handling time and search rate whereas acclimation to 24°C leads to the opposite effects with shorter handling time and lower search rate for acclimated predators. Moreover, the strength of these effects increased with acclimation time so that the differences in search rate and handing time between the two temperatures were reversed between the treatment without acclimation and after 24 h of acclimation. Overall, we found that the magnitude of the acclimation effects can be as strong as the direct kinetic effects of temperature. Our study highlights the importance of taking into account short-term thermal plasticity to improve our understanding of the potential consequences of global warming on species interactions.


Anthropometric correlates of total body fat, abdominal adiposity, and cardiovascular disease risk factors in a biracial sample of men and women.
To investigate associations between anthropometric measurements and total body fat, abdominal adipose tissue, and cardiovascular disease risk factors in a large biracial sample. This study is limited to cross-sectional analyses of data from participants attending a baseline visit between January 26, 1996, and February 1, 2011. The sample included 2037 individuals aged 18 to 69 years: 488 African American women (24%), 686 white women (34%), 196 African American men (9%), and 667 white men (33%). Anthropometry included weight; hip circumference; waist circumference; waist-hip, waist-height, and weight-height ratios; body adiposity index; and body mass index. Body fat and percentage of fat were measured by dual-energy x-ray absorptiometry, and abdominal visceral and subcutaneous adipose tissue were measured by computed tomography. Bivariate correlations, logistic regression models, and receiver operator characteristic curves were used, and analyses were stratified by sex and race. In each sex-by-race group, all anthropometric measures were highly correlated with percentage of fat, fat mass, and subcutaneous adipose tissue and moderately correlated with visceral adipose tissue, with the exception of the waist-hip ratio. The odds of having an elevated cardiometabolic risk were increased more than 2-fold per SD increase for most anthropometric variables, and the areas under the curve for each anthropometric measure were significantly greater than 0.5. Several common anthropometric measures were moderately to highly correlated with total body fat, abdominal fat, and cardiovascular disease risk factors in a biracial sample of women and men. This comprehensive analysis provides evidence of the linkage between simple anthropometric measurements and the purported pathways between adiposity and health.


Prospective Randomized Comparison of High-pitch CT at 80 kVp Under Free Breathing with Standard-pitch CT at 100 kVp Under Breath-Hold for Detection of Pulmonary Embolism.
To prospectively compare high-pitch computed tomography (HPCT) under free breathing (FB) with standard-pitch CT (SPCT) under breath-hold (BH) for detection of pulmonary embolism (PE). One hundred consecutive patients (47 females; mean age 58.7 ± 16.6) randomly underwent HPCT-FB (n = 50) or SPCT-BH (n = 50). Radiation doses were documented. One reader measured pulmonary artery attenuation and noise; mean signal-to-noise ratio (SNR) was calculated. Two readers assessed image quality, diagnostic confidence for detection of PE, motion artifacts, assessability of anatomical structures, and presence of transient interruption of contrast as sign of Valsalva maneuver. Inter-reader agreement was calculated. Radiation dose was significantly lower in HPCT compared to SPCT (2.68 ± 0.60 mGy vs 6.01 ± 2.26 mGy; P < .001). Mean pulmonary artery attenuation and image noise were significantly higher in HPCT (attenuation: 479 Hounsfield unit (HU) vs 343HU; P < .001; noise: 16 HU vs 10 HU; P < .001) whereas SNR was similar between groups (34 HU vs 38 HU; P = .258). HPCT had significantly higher diagnostic confidence for PE detection (P = .048), less cardiac and breathing artifacts (P < .001), better assessability of anatomical structures, and fewer cases of transient interruption of contrast (P < .001) compared to the SPCT. HPCT-FB allows for a significant reduction of breathing and motion artifacts compared to SPCT-BH. Diagnostic confidence, assessability of vascular and bronchial structures, as well as SNR are maintained.


Renal mineralocorticoid receptor expression is reduced in lipoatrophy.
Obesity is a condition characterized by adipose tissue hypertrophy; it is estimated that the obesity epidemic accounted for 4 million deaths in 2015 and that 70% of these were due to cardiovascular disease (CVD). One of the mechanisms linking obesity to CVD is the ability of adipose tissue to secrete circulating factors. We hypothesized that adipose tissue and its secretory products may influence mineralocorticoid receptor (MR) expression. Here, we showed that expression of MR and its downstream targets (Cnksr3, Scnn1b, and Sgk1) were significantly reduced in the kidneys of peroxisome proliferator-activated receptor-γ null (PpargΔ/Δ ) and A-ZIP/F-1 (AZIPtg/+) lipoatrophic mice with respect to their controls. Intriguingly, MR expression was also found to be significantly reduced in the kidneys of genetically obese ob/ob mice. Our data suggest that adipose tissue contributes to the regulation of MR expression. Given that leptin deficiency seems to be the major feature shared by PpargΔ/Δ , AZIPtg/+, and ob/ob mice, we speculate that adipose tissue modulates MR expression through the leptin system.


Bayesian inference of the sites of perturbations in metabolic pathways via Markov chain Monte Carlo.
Genetic modifications or pharmaceutical interventions can influence multiple sites in metabolic pathways, and often these are 'distant' from the primary effect. In this regard, the ability to identify target and off-target effects of a specific compound or gene therapy is both a major challenge and critical in drug discovery. We applied Markov Chain Monte Carlo (MCMC) for parameter estimation and perturbation identification in the kinetic modeling of metabolic pathways. Variability in the steady-state measurements in cells taken from a population can be caused by differences in initial conditions within the population, by variation of parameters among individuals and by possible measurement noise. MCMC-based parameter estimation is proposed as a method to help in inferring parameter distributions, taking into account uncertainties in the initial conditions and in the measurement data. The inferred parameter distributions are then used to predict changes in the network via a simple classification method. The proposed technique is applied to analyze changes in the pathways of pyruvate metabolism of mutants of Lactococcus lactis, based on previously published experimental data. MATLAB code used in the simulations is available from ftp://firstname.lastname@example.com/pub/Bioinformatics_BJ.zip


G-protein-coupled receptor structure, ligand binding and activation as studied by solid-state NMR spectroscopy.
GPCRs (G-protein-coupled receptors) are versatile signalling molecules at the cell surface and make up the largest and most diverse family of membrane receptors in the human genome. They convert a large variety of extracellular stimuli into intracellular responses through the activation of heterotrimeric G-proteins, which make them key regulatory elements in a broad range of normal and pathological processes, and are therefore one of the most important targets for pharmaceutical drug discovery. Knowledge of a GPCR structure enables us to gain a mechanistic insight into its function and dynamics, and further aid rational drug design. Despite intensive research carried out over the last three decades, resolving the structural basis of GPCR function is still a major activity. The crystal structures obtained in the last 5 years provide the first opportunity to understand how protein structure dictates the unique functional properties of these complex signalling molecules. However, owing to the intrinsic hydrophobicity, flexibility and instability of membrane proteins, it is still a challenge to crystallize GPCRs, and, when this is possible, it is no longer in its native membrane environment and no longer without modification. Furthermore, the conformational change of the transmembrane α-helices associated with the structure activation increases the difficulty of capturing the activation state of a GPCR to a higher resolution by X-ray crystallography. On the other hand, solid-state NMR may offer a unique opportunity to study membrane protein structure, ligand binding and activation at atomic resolution in the native membrane environment, as well as described functionally significant dynamics. In the present review, we discuss some recent achievements of solid-state NMR for understanding GPCRs, the largest mammalian proteome at ~1% of the total expressed proteins. Structural information, details of determination, details of ligand conformations and the consequences of ligand binding to initiate activation can all be explored with solid-state NMR.


Behavioral responses to artificial food colors.
Twenty-two young children, maintained on a diet that excluded certain foods, were challenged intermittently with a blend of seven artificial colors in a double-blind trial. Parents' observations provided the criteria of response. One child that responded mildly to the challenge and one that responded dramatically were detected. The latter, a 34-month-old female, showed a significant increase in aversive behaviors. These results further confirm previous controlled studies.


Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage survey in the Portuguese Island population.
Recent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene-dropping simulations. Significance of genome-wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54-15.71 MB, LOD = 3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32-90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL ≥ 1.98, which was more than would be expected by chance (empirical P = 0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high-density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles.


Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection.
Failure to clear persistent viral infections results from the early loss of T cell activity. A pertinent question is whether the immune response is programmed to fail or if nonresponsive T cells can specifically be fixed to eliminate infection. Although evidence indicates that T cell expansion is permanently programmed during the initial priming events, the mechanisms that determine the acquisition of T cell function are less clear. Herein we show that in contrast to expansion, the functional programming of T cell effector and memory responses in vivo in mice is not hardwired during priming but is alterable and responsive to continuous instruction from the antigenic environment. As a direct consequence, dysfunctional T cells can be functionally reactivated during persistent infection even after an initial program of inactivation has been instituted. We also show that early therapeutic reductions in viral replication facilitate the preservation of antiviral CD4+ T cell activity, enabling the long-term control of viral replication. Thus, dysfunctional antiviral T cells can regain activity, providing a basis for future therapeutic strategies to treat persistent viral infections.


The social environment and suicide attempts in lesbian, gay, and bisexual youth.
To determine whether the social environment surrounding lesbian, gay, and bisexual youth may contribute to their higher rates of suicide attempts, controlling for individual-level risk factors. A total of 31 852 11th grade students (1413 [4.4%] lesbian, gay, and bisexual individuals) in Oregon completed the Oregon Healthy Teens survey in 2006-2008. We created a composite index of the social environment in 34 counties, including (1) the proportion of same-sex couples, (2) the proportion of registered Democrats, (3) the presence of gay-straight alliances in schools, and (4) school policies (nondiscrimination and antibullying) that specifically protected lesbian, gay, and bisexual students. Lesbian, gay, and bisexual youth were significantly more likely to attempt suicide in the previous 12 months, compared with heterosexuals (21.5% vs 4.2%). Among lesbian, gay, and bisexual youth, the risk of attempting suicide was 20% greater in unsupportive environments compared to supportive environments. A more supportive social environment was significantly associated with fewer suicide attempts, controlling for sociodemographic variables and multiple risk factors for suicide attempts, including depressive symptoms, binge drinking, peer victimization, and physical abuse by an adult (odds ratio: 0.97 [95% confidence interval: 0.96-0.99]). This study documents an association between an objective measure of the social environment and suicide attempts among lesbian, gay, and bisexual youth. The social environment appears to confer risk for suicide attempts over and above individual-level risk factors. These results have important implications for the development of policies and interventions to reduce sexual orientation-related disparities in suicide attempts.


Somatic dysfunction and use of osteopathic manual treatment techniques during ambulatory medical care visits: a CONCORD-PBRN study.
Osteopathic manual treatment (OMT) of somatic dysfunction is a unique approach to medical care that may be studied within a practice-based research network. To measure patient characteristics and osteopathic physician practice patterns within the Consortium for Collaborative Osteopathic Research Development-Practice-Based Research Network (CONCORD-PBRN). Cross-sectional card study. Eleven member clinics within the CONCORD-PBRN coordinated by The Osteopathic Research Center. A total of 668 patients seen between January and March 2013. Patient age and sex; primary diagnoses; somatic dysfunction as manifested by tenderness, asymmetry, restricted motion, or tissue texture changes; and use of 14 OMT techniques. Results were stratified by anatomical region and adjusted for clustering within member clinics. Clustering was measured by the intracluster correlation coefficient. Patient ages ranged from 7 days to 87 years (adjusted mean age, 49.2 years; 95% confidence interval [CI], 43.3-55.1 years). There were 450 females (67.4%) and 508 patient visits (76.0%) involved a primary diagnosis of disease of the musculoskeletal system and connective tissue. Structural examination was performed during 657 patient visits (98.4%), and 649 visits (97.2%) involved OMT. Restricted motion and tenderness were the most and least common palpatory findings, respectively. Cranial (1070 [14.5%]), myofascial release (1009 [13.7%]), muscle energy (1001 [13.6%]), and counterstrain (980 [13.3%]) techniques were most commonly used, accounting for more than one-half of the OMT provided. Pediatric patients were more likely than adults to receive OMT within the head (adjusted odds ratio [OR], 9.53; 95% CI, 1.28-71.14). Geriatric patients were more likely than adults to receive a structural examination (adjusted OR, 1.83; 95% CI, 1.09-3.07) and OMT (adjusted OR, 1.62; 1.02-2.59) within the lower extremity. Females were more likely than males to receive a structural examination (adjusted OR, 2.44; 95% CI, 1.44-4.16) and OMT (adjusted OR, 2.11; 95% CI, 1.26-3.52) within the sacrum and OMT within the pelvis (adjusted OR, 1.79; 95% CI, 1.12-2.88). Intracluster correlation coefficients for the 4 most commonly used OMT techniques ranged from 0.34 to 0.72. This study provides proof of concept of the feasibility of studying osteopathic medical practice on a national level by developing and growing the CONCORD-PBRN.


Patterns of treatment response in newly diagnosed epilepsy.
To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: (A) early and sustained seizure freedom; (B) delayed but sustained seizure freedom; (C) fluctuation between periods of seizure freedom and relapse; and (D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year. A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen. Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.


Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model.
Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids.


Mood Disorders and Severity of Addiction in Alcohol-Dependent Patients Could Be Mediated by Sex Differences.
Background: Alcohol dependence is highly prevalent in the general population; some differences in alcohol use and dependence between women and men have been described, including outcomes and ranging from biological to social variables. This study aims to compare the severity of alcohol dependence with clinical and psychopathological characteristics between sexes. Methods: A cross-sectional descriptive study was conducted in alcohol-dependent outpatients; the recruitment period was 7 years. The assessment of these patients was carried out by obtaining sociodemographic characteristics and using the Semi-structured Clinical Interview for Axis I and II (SCID-I and SCID-II), European version of the Addiction Severity Index (EuropASI), Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI) scales. Variables were compared and analyzed. Results: The sample was composed of 178 patients (74.2% males and 25.8% females) with a mean age of 46.52 ± 9.86. No sociodemographic differences were found between men and women. Females had a higher rate of suicide attempts and depression symptoms at the treatment onset. When results of EuropASI were compared, females had worse psychological and employment results than males. According to consumption variables, males had an earlier onset of alcohol use, had more regular alcohol use, and develop alcohol dependence earlier than females. Conclusions: According to results, there are sex-dependent differences (severity and other variables such as mood or suicide) in alcohol dependence. Thus, this may implicate the need of future specific research and treatment programs based on the specific necessities of each sex.


Early Hip Arthroscopy for Femoroacetabular Impingement Syndrome Provides Superior Outcomes When Compared With Delaying Surgical Treatment Beyond 6 Months.
There is literature on the association between chronic preoperative pain and worse outcomes among patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). However, there are few data on whether there is an optimum window that provides the best midterm surgical outcomes. To assess the outcomes of hip arthroscopy for FAIS according to timing of surgical intervention. Cohort study; Level of evidence, 3. Patients undergoing arthroscopic intervention for FAIS with a minimum 2-year follow-up were included. All patients completed the Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sport Specific (HOS-SS), modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (iHOT-12), and visual analog scales for pain and satisfaction. Patients were stratified by preoperative symptom duration. We compared 3 to 6 months of symptoms with other subsequent time frames (>6-12, >12-24, and >24 months). Clinically significant outcome was determined with the minimal clinically important difference and patient acceptable symptomatic state. A total of 1049 patients were included (mean ± SD: age, 32.3 ± 12.4 years; follow-up, 30.8 ± 6.7 months). Patients undergoing surgery at 3 to 6 months of symptoms had no significant differences in outcome when compared with those in the >6- to 12-month group except for the iHOT-12 (P = .028). Patients with symptom duration of >12 to 24 months and >24 months had worse outcomes across all measures (P < .001). Surgery within 3 to 6 months of symptoms was predictive for achieving the minimal clinically important difference on the HOS-ADL (odds ratio [OR], 1.81; 95% CI, 1.20-2.73) and HOS-SS (OR, 1.90; 95% CI, 1.11-3.17), as well as the patient acceptable symptomatic state on the HOS-ADL (OR, 1.85; 95% CI, 1.34-2.56) and HOS-SS (OR, 1.58; 95% CI, 1.14-2.18), when compared with the other groups. In multivariate regression analysis, symptom duration was predictive of visual analog scale for pain (β = 3.10; 95% CI, 1.56-4.63; P < .001) and satisfaction (β = -4.16; 95% CI, -6.14 to -2.18; P < .001). Among patients with FAIS, surgical intervention early after the onset of symptoms (3-6 months) was associated with superior postoperative outcomes when compared with patients who underwent surgical intervention beyond this time frame. This information may help guide preoperative decision making regarding delay of surgery. These findings should be confirmed in a prospective study.


Early Results From the American Joint Replacement Registry: A Comparison With Other National Registries.
The American Joint Replacement Registry (AJRR) was created to capture knee and hip arthroplasty data in the United States. The purpose of this study was to compare early reports from the AJRR to other national registries to identify topics for future analysis. Hip and knee arthroplasty data were extracted from the AJRR, Australia, New Zealand, United Kingdom, Norway, and Sweden from 2014 to 2016. Hip arthroplasty data including femoral and acetabular fixation, bearing surface, head size, dual-mobility bearings, resurfacing, and revision burden were compared. Knee arthroplasty data including polyethylene type, unicondylar arthroplasty, mobile bearings, cruciate-retaining implants, patella resurfacing, and revision burden were compared. Registry characteristics and patient demographics were reported using descriptive statistics. In 2016, the AJRR captured 28% of arthroplasty procedures performed in the United States compared with 95%-98.3% among other registries. Cementless femoral fixation was 96.7% in the AJRR compared with 21.8%-63.4%. Ceramic and 36-mm heads were most common in AJRR; all other registries reported that metal and 32-mm heads were most popular. Dual-mobility articulations were used in 8% of primary and 28% of revision total hip arthroplasty procedures in the AJRR. The AJRR reported a unicondylar knee arthroplasty rate of 3.2% compared with 5.1%-13.3% in other registries, but the highest rates of posterior-stabilized total knee arthroplasties (48.5% compared to 8.2%-28.7%) and patella resurfacing (93.9% compared to 2.4%-51.6%). Several differences in hip and knee arthroplasty practices exist between the United States and other countries. Future studies should focus on understanding why differences in practice trends exist and assess outcomes associated with these practices. Level III, retrospective.


Electrophysiologic assessments of involuntary movements: tremor and myoclonus.
Tremor is defined as a rhythmical, involuntary oscillatory movement of a body part. Although neurological examination reveals information regarding its frequency, regularity, amplitude, and activation conditions, the electrophysiological investigations help in confirming the tremor, in differentiating it from other hyperkinetic disorders like myoclonus, and may provide etiological clues. Accelerometer with surface electromyogram (EMG) can be used to document the dominant frequency of a tremor, which may be useful as certain frequencies are more characteristic of specific etiologies than others hyperkinetic disorders. It may show rhythmic bursts, duration and activation pattern (alternating or synchronous). Myoclonus is a quick, involuntary movement. Electrophysiological studies may helpful in the evaluation of myoclonus, not only for confirming the clinical diagnosis but also for understanding the underlying physiological mechanisms. Electroencephalogram (EEG)-EMG correlates can give us important information about myoclonus. Jerk-locked back-averaging and evoked potentials with recording of the long-latency, long-loop reflexes are currently available to study the pathophysiology of myoclonus.


Managing the common problem of missing data in trauma studies.
To provide guidance for managing the problem of missing data in clinical studies of trauma in order to decrease bias and increase the validity of findings for subsequent use. A thoughtful approach to missing data is an essential component of analysis to promote the clear interpretation of study findings. Integrative review of relevant biostatistics, medical and nursing literature, and case exemplars of missing data analyses using multiple linear regression based upon data from the National Study on the Costs and Outcomes of Trauma (NSCOT) was used as an example. In studies of traumatically injured people, multiple imputed values are often superior to complete case analyses that might have significant bias. Multiple imputation can improve accuracy of the assessment and might also improve precision of estimates. Sensitivity analyses which implements repeated analyses using various scenarios may also be useful in providing information supportive of further inquiry. This stepwise approach of missing data could also be valid in studies with similar types or patterns of missing data. In interpreting and applying findings of studies with missing data, clinicians need to ensure that researchers have used appropriate methods for handling this issue. If suitable methods were not employed, nurse clinicians need to be aware that the findings may be biased.


Transitional Care: Methods and Processes for Transitioning Older Adults With Cancer in a Postacute Setting.
The concept of transitional care and the methods and processes to efficiently and effectively transition patients between a variety of care settings remains a continuous healthcare goal. Despite the numerous transitional care models that have been developed and implemented in a myriad of healthcare settings, increasing healthcare costs and substandard patient outcomes persist. This article will examine the topic of older adults with cancer when transitioned to a skilled nursing setting and the challenges they may face along the care continuum. In addition, it will look at the continuity of care between the hospital and skilled nursing facility, as well as explore some of the clinical difficulties experienced by older adult patients with cancer in the postacute care setting. Keyword searches were conducted in a selected literature review of CINAHL®, Ovid, PubMed, and Google Scholar databases. Successful transitional care models are built around effective communication and often include an interprofessional team approach and/or a nurse navigator to aid in the effective execution of medical treatment and patient care plans.


[Ultrastructure and pathogenesis of vocal nodules on the vocal cords].
Controlled electron microscopy of the epithelium in voice lesions revealed: thickening and destruction of basement membrane, reduplication of the lamina densa, near absence of normal hemidesmosomes and anchoring fibrils, abundant electro-dense vesicles at the basal cell pole (discharging through the cell membrane), abundant mitochondria, euchromatin and nucleolar prominence. These histologic phenomena suggest that the basal cell layer responds to trauma to its anchorages with metabolic hyperactivity. Therefore the traumatic mechanism should be considered as damaging to the basement membrane.


Thermodynamic and structural studies of cavity formation in proteins suggest that loss of packing interactions rather than the hydrophobic effect dominates the observed energetics.
The hydrophobic effect is widely believed to be an important determinant of protein stability. However, it is difficult to obtain unambiguous experimental estimates of the contribution of the hydrophobic driving force to the overall free energy of folding. Thermodynamic and structural studies of large to small substitutions in proteins are the most direct method of measuring this contribution. We have substituted the buried residue Phe8 in RNase S with alanine, methionine, and norleucine. Binding thermodynamics and structures were characterized by titration calorimetry and crystallography, respectively. The crystal structures of the RNase S F8A, F8M, and F8Nle mutants indicate that the protein tolerates the changes without any main chain adjustments. The correlation of structural and thermodynamic parameters associated with large to small substitutions was analyzed for nine mutants of RNase S as well as 32 additional cavity-containing mutants of T4 lysozyme, human lysozyme, and barnase. Such substitutions were typically found to result in negligible changes in DeltaC(p)() and positive values of both DeltaDeltaH degrees and DeltaDeltaS of folding. Enthalpic effects were dominant, and the sign of DeltaDeltaS is the opposite of that expected from the hydrophobic effect. Values of DeltaDeltaG degrees and DeltaDeltaH degrees correlated better with changes in packing parameters such as residue depth or occluded surface than with the change in accessible surface area upon folding. These results suggest that the loss of packing interactions rather than the hydrophobic effect is a dominant contributor to the observed energetics for large to small substitutions. Hence, estimates of the magnitude of the hydrophobic driving force derived from earlier mutational studies are likely to be significantly in excess of the actual value.


Exchange of sterols between myelin and other membranes of developing rat brain.
1. The effect of inhibition of cholesterol synthesis by a hypocholesterolaemic drug (AY-9944) was studied in rat brain during development. 2. At 2 weeks after administration of AY-9944 to young rats 7-dehydrocholesterol accounted for half the total sterol of myelin and other subcellular components. 3. At 4 weeks after injection of the drug 7-dehydrocholesterol had disappeared whereas the cholesterol content of myelin had increased by an equivalent amount. Our studies show that purified myelin has low 7-dehydrocholesterol reductase activity and suggest that 7-dehydrocholesterol is largely converted into cholesterol outside the myelin sheath. 4. Resultant cholesterol may be re-incorporated into myelin by an exchange process. 5. The metabolism of sterols in developing brain is discussed.


Environmental chemical exposures and disturbances of heme synthesis.
Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria.


Efficacy and Survival of Systemic Psoriasis Treatments: An Analysis of the Swiss Registry SDNTT.
The Swiss psoriasis registry SDNTT (Swiss Dermatology Network for Targeted Therapies) records the long-term safety and effectiveness of systemic treatment regimens for psoriasis. Patients with moderate to severe psoriasis are included in the SDNTT when treatment with a conventional systemic agent or biologic is initiated that was not previously used by the respective patient. Patients are followed over a 5-year period. Clinical data are obtained every 3-6 months using standardized case report forms. Here, baseline data and follow-up data for 1 year of patients included from October 2011 until December 2014 were analyzed. Within 39 months, 323 patients from 7 tertiary dermatology centers in Switzerland were recruited in the SDNTT; 165 patients received biologics and 158 conventional systemic therapies. Patients treated with biologics had a significantly higher severity (PASI 11.3 vs. 9.2, BSA 15.6 vs.11.9, psoriatic arthritis 36.4 vs. 10.8%; p ≤ 0.005, p ≤ 0.013, p ≤ 0.001) and a longer duration of illness (19.2 vs. 14.4 years, p ≤ 0.003) compared to patients starting a conventional systemic treatment. PASI reduction was satisfying in both treatment groups, with 60.6% of patients treated with biologics achieving PASI75 after 1 year compared to 54.2% of patients receiving conventional systemic drugs (nonsignificant). On average, the drug survival in patients receiving a biologic therapy was significantly longer than those receiving conventional systemic treatments (30.5 vs. 19.2 months, p ≤ 0.001). In the real-world setting of a prospective national therapy registry, the application of current therapeutic guidelines for patients with moderate to severe psoriasis resulted in a PASI reduction of approximately 70% within the first year of treatment, but current therapeutic targets of PASI75 and PASI90 were reached in only 58 and 36% of patients, respectively, at 1 year, highlighting a gap in efficacy between selective clinical trials and the real-world setting.


Combating poor-quality anti-malarial medicines: a call to action.
The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria-endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development and malaria elimination programmes.


Stability and its manifestation in the chemical and biological worlds.
Bridging between the phenomenologically distinct biological and physical worlds has been a major scientific challenge since Boltzmann's probabilistic formulation of the second law of thermodynamics. In this review we summarize our recent theoretical attempts to bridge that divide through analysis of the thermodynamic-kinetic interplay in chemical processes and the manner in which that interplay impacts on material stability. Key findings are that the term 'stability' manifests two facets - time and energy - and that stability's time facet, expressed as persistence, is more general than its energy facet. That idea, together with the proposed existence of a logical law of nature, the persistence principle, leads to the mathematically-based insight that stability can come about through either Boltzmann's probabilistic considerations or Malthusian kinetics. Two mathematically-based forms of material persistence then lead directly to the physical likelihood of two material forms, animate and inanimate. Significantly, the incorporation of kinetic considerations into the stability concept appears to bring us closer to enabling two of the central theories in science - the second law of thermodynamics and Darwin's theory of evolution - to be reconciled within a single conceptual framework.


A Survey on Mental Health Status of Adult Population Aged 15 and above in the Province of Khouzestan, Iran.
This research aims to determine the mental health status of population aged 15 and over in the province of Khouzestan in 2015. The statistical population of this cross-sectional field survey consisted of residents of urban and rural areas of Khouzestan in Iran. An estimated sample size of 1200 people was chosen using systematic random cluster sampling. The access was provided by the contribution of Geographical Post Office of Ahvaz, Imam khomeini Bandar, and Shooshtar cities. The General Health Questionnaire-28 (GHQ-28) was used as the screening tool for mental disorders. Data analysis in the current study was carried out using the SPSS-18 software. Using GHQ traditional scoring method, 21.8% of the subjects were shown to be at risk of mental disorders (26.2% of females and 23% of males). Urban areas (27.1%) were more at risk of mental disorders compared with rural residents (16.8%). The prevalence of suspected cases of mental disorders in urban areas (25.4%) was higher than rural areas (13.4 %). Anxiety and somatization symptoms were more frequent than depression and social dysfunction among respondents. The obtained data revealed that the prevalence of mental disorders increased with age. Such disorders were more common in females, age group of 65 and above, people living in rural areas, divorced and widowed, illiterate, housewives and unemployed individuals compared with the other groups. The results of this study showed that about a fourth of the people in the province were suspected to have mental disorders and the prevalence of these disorders has increased from 21.3% in 1999 to 21.8% in 2015. Therefore, it is mandatory for the provincial public health authorities to take the needed steps to ensure that necessary requirements encompassing prevention and promotion of mental health are implemented.


Esophageal cancer screening in achalasia: is there a consensus?
Achalasia is an important but relatively uncommon disorder. While highly effective therapeutic options exist, esophageal cancer remains a long-term potential complication. The risk of esophageal cancer in achalasia remains unclear, with current guidelines recommending against routine endoscopic screening. However, given limited data and conflicting opinion, it is unknown whether consensus regarding screening practices in achalasia among experts exists. A 10-question survey to assess screening practices in achalasia was created and distributed to 28 experts in the area of achalasia. Experts were identified based on publications and meeting presentations in the field. Survey responses were received from 17 of 28 (61%) experts. Wide geographic distribution was seen among respondents, with eight (47%) from Europe or Australia, seven (41%) from the United States, and two (12%) from Asia. Screening for esophageal cancer was inconsistent, with nine (53%) experts endorsing the practice and eight (47%) not. Screening practices did not differ among geographic regions. No consensus regarding the risk for esophageal cancer in achalasia was seen, with three experts reporting no increased risk compared with the general population, eight experts a lifetime risk of 0.1-0.5%, three experts a 0.5-1% risk, two experts a 1-2% risk, and one expert a 3-5% risk. However, these differences in perception of risk did not influence screening practices. Upper endoscopy was utilized among all experts who endorsed screening. However, practices still varied with screening commencing at or within 1 year of diagnosis in two practices compared with 5 and 10 years in three respective practices each. Surveillance intervals also varied, performed every 2 years in four practices, every 3 years in four practices, and every 5 years in one practice. Practice variation in the management of achalasia itself was also seen, with initial treatment with Heller myotomy endorsed by eight experts, pneumatic dilation by five experts, and two each endorsing peroral endoscopic myotomy or no specific preference. In addition, while 82% (14/17) of experts endorsed long-term follow up of patients, no consensus regarding long-term follow up existed, with annual follow up in eight practices, every 3-6 months in three practices, and every 2 years in three practices. Large practice variation in the long-term management of achalasia exists among experts in the field. Only a slight majority of experts endorse screening for esophageal cancer in achalasia, and no consensus exists regarding how surveillance should be structured even among this group. Interestingly, the lack of consensus on cancer screening parallels a lack of agreement on initial treatment of achalasia. These findings suggest a need for greater homogeneity in the management of longstanding achalasia and cancer screening. Further, this study highlights the need for more data on this topic to foster greater agreement.


Effects of vitamin K in postmenopausal women: mini review.
Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day.


No improvement in race performance by naps in male ultra-endurance cyclists in a 600-km ultra-cycling race.
Ultra-endurance performance is of increasing popularity. We investigated the associations between anthropometry, training and support during racing, with race performance in 67 male recreational ultra-endurance cyclists participating in the 'Swiss Cycling Marathon' over 600 kilometres, an official qualifier for the cycling ultra-marathon 'Paris-Brest-Paris'. The 54 finishers showed no differences in anthropometry and did not train differently compared to the 13 non-finishers. During the race, the finishers were significantly more frequently racing alone than being followed by a support crew. After bivariate analysis, percent body fat (r = 0.43), the cycling distance per training unit (r = -0.36), the duration per training unit (r = -0.31) and the sleep time during the race (r = 0.50) were related to overall race time. The 23 non-sleepers in the finisher group completed the race within (mean and IQR) 1,567 (1,453-1,606) min, highly significantly faster than the 31 sleepers with 1,934 (1,615-2,033) min (P = 0.0003). No variable of support during the race was associated with race time. After multivariate analysis, percent body fat (P = 0.026) and duration per training unit (P = 0.005) remained predictor variables for race time. To summarize, for a successful finish in a cycling ultra-marathon over 600 kilometres such as the 'Swiss Cycling Marathon', percent body fat and duration per training unit were related to race time whereas equipment and support during the race showed no association. Athletes with naps were highly significantly slower than athletes without naps.


Azithromycin concentrations at the sites of pulmonary infection.
Azithromycin is a new macrolide antimicrobial. The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy. Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing. The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1). In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h. Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations. Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively). The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.


Eliciting Disease Data from Wikipedia Articles.
Traditional disease surveillance systems suffer from several disadvantages, including reporting lags and antiquated technology, that have caused a movement towards internet-based disease surveillance systems. Internet systems are particularly attractive for disease outbreaks because they can provide data in near real-time and can be verified by individuals around the globe. However, most existing systems have focused on disease monitoring and do not provide a data repository for policy makers or researchers. In order to fill this gap, we analyzed Wikipedia article content. We demonstrate how a named-entity recognizer can be trained to tag case counts, death counts, and hospitalization counts in the article narrative that achieves an F1 score of 0.753. We also show, using the 2014 West African Ebola virus disease epidemic article as a case study, that there are detailed time series data that are consistently updated that closely align with ground truth data. We argue that Wikipedia can be used to create the first community-driven open-source emerging disease detection, monitoring, and repository system.


Cultural specificity of emotional overinvolvement: a systematic review.
Understanding cross-cultural aspects of emotional overinvolvement (EOI) on psychosis outcomes is important for ensuring cultural appropriateness of family interventions. This systematic review explores whether EOI has similar impact in different cultural groups and whether the same norms can be used to measure EOI across cultures. Thirty-four studies were found that have investigated the impact of EOI on outcomes across cultures or culturally adapted EOI measures. The relationship between high EOI and poor outcome is inconsistent across cultures. Attempts to improve predictive ability by post hoc adjustment of EOI norms have had varied success. Few studies have attempted a priori adaptations or development of culture-specific norms. Methodological differences such as use of different expressed emotions (EE) measures and varying definitions of relapse across studies may explain a lack of EOI outcome relationship across cultures. However, our findings suggest that the construct and measurement of EOI itself are culture-specific. EOI may not necessarily be detrimental in all cultures. The effect of high EOI may be moderated by the unexplored dimension of warmth and high levels of mutual interdependence in kin relationships. Researchers should reevaluate the prevailing concepts of the impact of family relations on the course and outcome of psychotic disorders, specifically focusing on the protective aspects of family involvement. Clinically, family interventions based on EE reduction should take cultural differences into account when treating families from different ethnocultural groups.


Circulatory dynamics during dental operations in patients with heart transplants.
Twelve patients with heart transplants and who needed dental operations were studied. At the same time, a group of normal subjects was enrolled as control. Blood pressure and heart rate were recorded in all subjects when they sat in the chair, after 5 minutes of relaxation, 5 minutes after administration of local anesthetic, and immediately after each dental extraction or curettage. No statistically significant difference was found between the values recorded during the different situations and the basal values in transplanted patients. Conversely, in the normal subjects, the values recorded when they sat in the chair, at the end of curettage, and at the end of dental extractions were significantly different from the basal values. The slight and dulled cardiovascular reaction to stress in patients with heart transplants suggests that the management of these patients is relatively uncomplicated and certainly easier than treatment of subjects with heart disease.


Mapping the knowledge and understanding of menarche, menstrual hygiene and menstrual health among adolescent girls in low- and middle-income countries.
Menstruation is a natural physiological process that requires proper management. Unlike other normal bodily processes, menstruation is linked with religious and cultural meanings that can affect the perceptions of young girls as well as the ways in which the adults in the communities around them respond to their needs. This review aims to answer the following questions: (1) how knowledgeable are adolescent girls in low- and middle-income countries about menstruation and how prepared are they for reaching menarche, (2) who are their sources of information regarding menstruation, (3) how well do the adults around them respond to their information needs, (4) what negative health and social effects do adolescents experience as a result of menstruation, and (5) how do adolescents respond when they experience these negative effects and what practices do they develop as a result? Using a structured search strategy, articles that investigate young girls' preparedness for menarche, knowledge of menstruation and practices surrounding menstrual hygiene in LMIC were identified. A total of 81 studies published in peer-reviewed journals between the years 2000 and 2015 that describe the experiences of adolescent girls from 25 different countries were included. Adolescent girls in LMIC are often uninformed and unprepared for menarche. Information is primarily obtained from mothers and other female family members who are not necessarily well equipped to fill gaps in girls' knowledge. Exclusion and shame lead to misconceptions and unhygienic practices during menstruation. Rather than seek medical consultation, girls tend to miss school, self-medicate and refrain from social interaction. Also problematic is that relatives and teachers are often not prepared to respond to the needs of girls. LMIC must recognize that lack of preparation, knowledge and poor practices surrounding menstruation are key impediments not only to girls' education, but also to self-confidence and personal development. In addition to investment in private latrines with clean water for girls in both schools and communities, countries must consider how to improve the provision of knowledge and understanding and how to better respond to the needs of adolescent girls.


A 100,000-year-old ochre-processing workshop at Blombos Cave, South Africa.
The conceptual ability to source, combine, and store substances that enhance technology or social practices represents a benchmark in the evolution of complex human cognition. Excavations in 2008 at Blombos Cave, South Africa, revealed a processing workshop where a liquefied ochre-rich mixture was produced and stored in two Haliotis midae (abalone) shells 100,000 years ago. Ochre, bone, charcoal, grindstones, and hammerstones form a composite part of this production toolkit. The application of the mixture is unknown, but possibilities include decoration and skin protection.


Effects of Bacillus cereus var. toyoi on immune parameters of pregnant sows.
Changing immune parameters during pregnancy have previously been reported in humans and cattle, and have been suggested to contribute to increased susceptibility to infections. However, data regarding immune parameters during pregnancy in sows are rare. In this study, we investigated the peripartal immune status of sows using phenotypical (FACS analysis) as well as functional (proliferation assays, cytokine analysis) parameters of peripheral blood mononuclear cells (PBMCs) in pregnant sows. In previous studies, we reported a modulation of the immune system after feed supplementation of the probiotic Bacillus cereus var. toyoi in piglets [Schierack, P., Wieler, L.H., Taras, D., Herwig, V., Tachu, B., Hlinak, A., Schmidt, M.F., Scharek, L., 2007. Bacillus cereus var. toyoi enhanced systemic immune response in piglets. Vet. Immunol. Immunopathol. 118, 1-11]. Here, we extended these previous studies to include investigations of possible probiotic effects on the peripartal immune status of sows and their reproductivity. We show that immune parameters of sows change during pregnancy, the proliferative response of PBMCs to several bacterial antigens in control animals decreased from days 90 to 30 ante partum. Relative numbers (%) of CD3+CD8+, CD4+, cytotoxic T, CD14+ and CD21+ cells were reduced compared to non-pregnant sows. In contrast, the proliferative response of PBMCs of probiotic-treated sows increased during pregnancy. Bacterial antigens primarily stimulated the proliferation of naïve CD21+ cells and the relative CD21+ cell numbers were elevated in the probiotic group in the absence of effects on other immune cell populations. The clinical and microbial status of both control and probiotic sows was similar, excluding pre-existing health problems or infections as responsible for the immunological changes, and feed supplementation also had no significant effects on reproductivity. The results suggest that the probiotic B. cereus var. toyoi can alter the proliferative response of lymphocytes and affects the immune cell population ratios of pregnant sows. How and to what extent this may affect health and reproductivity should be the focus of further studies.


Individual prediction of white matter injury following traumatic brain injury.
Traumatic brain injury (TBI) often results in traumatic axonal injury (TAI). This can be difficult to identify using conventional imaging. Diffusion tensor imaging (DTI) offers a method of assessing axonal damage in vivo, but has previously mainly been used to investigate groups of patients. Machine learning techniques are increasingly used to improve diagnosis based on complex imaging measures. We investigated whether machine learning applied to DTI data can be used to diagnose white matter damage after TBI and to predict neuropsychological outcome in individual patients. We trained pattern classifiers to predict the presence of white matter damage in 25 TBI patients with microbleed evidence of TAI compared to neurologically healthy age-matched controls. We then applied these classifiers to 35 additional patients with no conventional imaging evidence of TAI. Finally, we used regression analyses to predict indices of neuropsychological outcome for information processing speed, executive function, and associative memory in a group of 70 heterogeneous patients. The classifiers discriminated between patients with microbleeds and age-matched controls with a high degree of accuracy, and outperformed other methods. When the trained classifiers were applied to patients without microbleeds, patients having likely TAI showed evidence of greater cognitive impairment in information processing speed and executive function. The classifiers were also able to predict the extent of impairments in information processing speed and executive function. The work provides a proof of principle that multivariate techniques can be used with DTI to provide diagnostic information about clinically significant TAI.


A scoring matrix approach to detecting miRNA target sites.
Experimental identification of microRNA (miRNA) targets is a difficult and time consuming process. As a consequence several computational prediction methods have been devised in order to predict targets for follow up experimental validation. Current computational target prediction methods use only the miRNA sequence as input. With an increasing number of experimentally validated targets becoming available, utilising this additional information in the search for further targets may help to improve the specificity of computational methods for target site prediction. We introduce a generic target prediction method, the Stacking Binding Matrix (SBM) that uses both information about the miRNA as well as experimentally validated target sequences in the search for candidate target sequences. We demonstrate the utility of our method by applying it to both animal and plant data sets and compare it with miRanda, a commonly used target prediction method. We show that SBM can be applied to target prediction in both plants and animals and performs well in terms of sensitivity and specificity. Open source code implementing the SBM method, together with documentation and examples are freely available for download from the address in the Availability and Requirements section.


Apocynin protects mesangial cells from lipopolysaccharide-induced inflammation by exerting heme oxygenase 1-mediated monocyte chemoattractant protein-1 suppression.
Renal failure is observed in the pathological progression of sepsis and septic shock. Renal mesangial cells (RMCs) have been implicated in renal failure as a result of producing mediators, such as monocyte chemoattractant protein-1 (MCP-1) in response to lipopolysaccharide (LPS). Mitogen-activated protein kinases (MAPKs) have been demonstrated to mediate the LPS-induced inflammatory response in RMCs. Although previous studies indicated a promising effect of apocynin in various inflammatory conditions, its antiseptic efficacy in mesangial cells remains to be clearly determined. In the present study, the anti-inflammatory effects of apocynin and its underlying mechanism were examined in LPS-challenged RMCs. Apocynin significantly inhibited nitric oxide (NO) production in LPS-challenged RMCs and the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, the level of LPS-induced MCP-1 expression was significantly attenuated with apocynin. Furthermore, apocynin significantly suppressed the activation of MAPKs, such as extracellular signal-regulated kinases 1/2 and p38, but not c-Jun N-terminal kinases. Apocynin exhibited significantly increased expression of heme oxygenase-1 (HO-1) induction via nuclear factor (erythroid-derived 2)-like-2 (Nrf-2) phosphorylation. Inhibition of HO-1 with zinc protoporphyrin significantly abolished apocynin-induced suppression of MCP-1, indicating that HO-1 is significant in the suppression of MCP-1. Thus, apocynin exerts antiseptic activity via the suppression of pro-inflammatory signaling pathways and the activation of cytoprotective signaling pathways, such as HO-1/Nrf-2 in RMCs, indicating that apocynin may present as a promising candidate for in vivo evaluation of a therapeutic agent for inflammation-associated renal disorders.


The Configurations of Informal Institutions to Promote Men's and Women's Entrepreneurial Activities.
While previous studies have examined the impact of informal institutions to determine entrepreneurial activities, this paper explores the different configurational paths of informal institutions to promote men's and women's entrepreneurial activities across factor-driven and efficiency-driven economies. We collected data from the Global Entrepreneurship Monitor for 56 countries for the years 2008-2013 and employed fuzzy-set qualitative comparative analysis to conduct the empirical analysis. The results confirm that a single antecedent condition is unable to produce an outcome while combination of different conditions can produce an outcome. We find that cultural-cognitive institutional antecedents in combination with social-normative antecedents create configurations of conditions that lead to the higher levels of men's and women's entrepreneurial activities in factor-driven and efficiency-driven economies. Moreover, this study shows that these causal conditions configure differently to promote men's and women's entrepreneurial activities in factor-driven and efficiency-driven nations. This paper may create awareness in potential entrepreneurs regarding specific sets of institutional antecedents that can increase the emergence of entrepreneurship in different economic clusters. We show that institutional antecedents which are essential to promote entrepreneurship combine distinctly for men's and women's entrepreneurship and this combination varies in different stages of economic development.


Are optical aberrations during accommodation a significant problem for refractive surgery?
To study the limits to a perfect ideal customized wavefront correction due to the change of aberrations during accommodation. METHODS. We measured the dynamic changes of ocular aberrations during accommodation in normal eyes with a real-time Hartmann-Shack wavefront sensor. Those results were used in computer simulations to predict the benefit of a perfect customized correction. Due to the continuous changes of the aberrations over time, an ideal perfect static correction will not provide stable aberration-free optics. For example, when the eye accommodates to near objects, due to the changing aberrations, the eye will become aberrated again. An alternative correction using the aberration pattern for a slightly accommodated condition could provide a better-correction in a larger accommodative range, although at the cost of non-perfect correction for far vision. Due to the dynamic nature of ocular optics, a static perfect correction, for instance performed in customized refractive surgery, would not remain perfect for every condition occurring during normal accommodation.


The semi-permeability of silicone: a saline-filled breast implant with intraluminal and pericapsular Aspergillus flavus.
Fungal infection of breast implants is a rare complication. Growth of fungi within the lumen of saline-filled implants has previously been demonstrated in laboratory studies, however, clinical infections are rare. We report a case of Aspergillus flavus growth within and around a saline-filled breast implant that was inserted 18 months previously. This was successfully treated with implant removal and wound irrigation. Possible routes of microbial contamination as well as survival mechanisms of organisms within saline-filled implants are discussed. This case re-iterates that the silicone envelope of a saline-filled implant is selectively permeable and we believe this is instrumental in facilitating intraluminal microbial growth. This also emphasises the importance of stringent asepsis when dealing with saline-filled breast implants including avoiding contamination of the saline filling fluid.


Anovaginal fistulas: evaluation with endoanal MR imaging.
To evaluate endoanal magnetic resonance (MR) imaging in the assessment of anovaginal fistulas and associated findings. In a retrospective descriptive study, two radiologists systematically reviewed MR findings in 20 patients with a clinically proved anovaginal fistula and looked for the main fistula tract, the internal opening in the anal canal and/or vagina, secondary fistula tracts, abscesses within the rectovaginal septum, and sphincter damage. Interobserver variability was calculated, and clinical records were searched for possible underlying causes that could explain the complexity of anovaginal fistulas. The kappa value was calculated. Patients with or without a complex anovaginal fistula were compared in regard to the presence of any underlying disease or condition. Statistical significance was calculated with the Fisher exact test. In all 20 patients, anovaginal fistulas were identified on T2-weighted MR images as predominantly high-signal-intensity linear abnormalities extending between the anal canal and the vagina. In all patients, the fistulas were typically located in the sagittal plane, and the mean distance from the anal verge to the fistula was 25.0 mm (range, 13-32 mm). The internal opening in the anal canal was detected in all patients. The internal opening in the vagina was detected in 19 (95%) patients. In seven (35%) patients, an anovaginal fistula with an additional abnormality was found and included an abscess within the rectovaginal septum (n = 1), a perianal fistula (n = 3), and a perianal fistula in combination with an abscess (n = 3). Defects of the external anal sphincter were present in three (15%) patients. There was complete agreement between observers for all items on endoanal MR images, except for the presence of secondary fistula extensions (agreement, 90%; kappa, 0.74). History of obstetric trauma, pelvic floor surgery, or Crohn disease was present in 10 (50%) patients. Of these patients, six (60%) had a complex anovaginal fistula and four (40%) had a simple anovaginal fistula. In the remaining 10 patients without relevant medical history, one (10%) had a complex anovaginal fistula. This difference tended toward statistical significance (P =.057). Endoanal MR imaging allows evaluation of anovaginal fistulas and additional abnormalities, such as abscesses within the rectovaginal septum, secondary perianal fistula tracts, and sphincter damage.


Determinants of medical expenditures in the last 6 months of life.
End-of-life medical expenditures exceed costs of care during other years, vary across regions, and are likely to be unsustainable. Identifying determinants of expenditure variation may reveal opportunities for reducing costs. To identify patient-level determinants of Medicare expenditures at the end of life and to determine the contributions of these factors to expenditure variation while accounting for regional characteristics. It was hypothesized that race or ethnicity, social support, and functional status are independently associated with treatment intensity and controlling for regional characteristics, and that individual characteristics account for a substantial proportion of expenditure variation. Using data from the Health and Retirement Study, Medicare claims, and The Dartmouth Atlas of Health Care, relationships were modeled between expenditures and patient and regional characteristics. United States, 2000 to 2006. 2394 Health and Retirement Study decedents aged 65.5 years or older. Medicare expenditures in the last 6 months of life were estimated in a series of 2-level multivariable regression models that included patient, regional, and patient and regional characteristics. Decline in function (rate ratio [RR], 1.64 [95% CI, 1.46 to 1.83]); Hispanic ethnicity (RR, 1.50 [CI, 1.22 to 1.85]); black race (RR, 1.43 [CI, 1.25 to 1.64]); and certain chronic diseases, including diabetes (RR, 1.16 [CI, 1.06 to 1.27]), were associated with higher expenditures. Nearby family (RR, 0.90 [CI, 0.82 to 0.98]) and dementia (RR, 0.78 CI, 0.71 to 0.87]) were associated with lower expenditures, and advance care planning had no association. Regional characteristics, including end-of-life practice patterns (RR, 1.09 [CI, 1.06 to 1.14]) and hospital beds per capita (RR, 1.01 [CI, 1.00 to 1.02]), were associated with higher expenditures. Patient characteristics explained 10% of overall variance and retained statistically significant relationships with expenditures after regional characteristics were controlled for. The study limitations include the decedent sample, proxy informants, and a large proportion of unexplained variation. Patient characteristics, such as functional decline, race or ethnicity, chronic disease, and nearby family, are important determinants of expenditures at the end of life, independent of regional characteristics. The Brookdale Foundation.


Interaction of a salivary mucin-secretory immunoglobulin A complex with mucosal pathogens.
This study examined the interaction of a human salivary low-molecular-weight mucin (MG2) with Staphylococcus aureus and Pseudomonas aeruginosa by using both solution-phase and solid-phase assays. In solution phase, MG2 in human submandibular-sublingual saliva (HSMSL) bound to the bacterial surface; however, the highly purified mucin isoforms (MG2a and MG2b) did not. Mucin binding appeared to be dependent on heterotypic complexing between MG2 and secretory immunoglobulin A (IgA), although other salivary molecules may also be involved. In contrast, in a solid-phase assay in which HSMSL, MG2-containing fractions with secretory IgA, and purified MG2 were immobilized onto a solid surface, there was minimal adherence of S. aureus. The collective results suggest that mucin binding to S. aureus and P. aeruginosa may be predicated on the formation of an MG2-secretory IgA complex. Such interactions may facilitate microbial clearance from the oral cavity and play an important role in preventing colonization of the oral cavity and the respiratory tract by potential pathogens.


Stereocontrolled Self-Assembly and Self-Sorting of Luminescent Europium Tetrahedral Cages.
Coordination-directed self-assembly has become a well-established technique for the construction of functional supramolecular structures. In contrast to the most often exploited transition metals, trivalent lanthanides Ln(III) have been less utilized in the design of polynuclear self-assembled structures despite the wealth of stimulating applications of these elements. In particular, stereochemical control in the assembly of lanthanide chiral cage compounds is not easy to achieve in view of the usually large lability of the Ln(III) ions. We report here the first examples of stereoselective self-assembly of chiral luminescent europium coordination tetrahedral cages and their intriguing self-sorting behavior. Two pairs of R and S ligands are designed on the basis of the pyridine-2,6-dicarboxamide coordination unit, bis(tridentate) L1 and tris(tridentate) L2. Corresponding chiral Eu4(L1)6 and Eu4(L2)4 topological tetrahedral cages are independently assembled via edge- and face-capping design strategies, respectively. The chirality of the ligand is transferred during the self-assembly process to give either Δ or Λ metal stereochemistry. The self-assembled cages are characterized by NMR, high-resolution ESI-TOF-MS, and in one case by X-ray crystallography. Strict control of stereoselectivity is confirmed by CD spectroscopy and NMR enantiomeric differentiation experiments. Narcissistic self-sorting is observed in the self-assembly process when two differently shaped ligands L1 and L2 are mixed. More impressively, distinct self-sorting behavior between Eu4(L1)6 and Eu4(L2)4 coordination cages is observed for the first time when racemic mixtures of ligands are used. We envisage that chiral luminescent lanthanide tetrahedral cages could be used in chiroptical probes\sensors and enantioselective catalysis.


Occupational exposure to noise and the attributable burden of hearing difficulties in Great Britain.
To determine the prevalence of self reported hearing difficulties and tinnitus in working aged people from the general population, and to estimate the risks from occupational exposure to noise and the number of attributable cases nationally. A questionnaire was mailed to 22 194 adults of working age selected at random from the age-sex registers of 34 British general practices (21 201 subjects) and from the central pay records of the British armed services (993 subjects). Information was collected on years of employment in a noisy job; and whether the respondent wore a hearing aid, had difficulty in hearing conversation, or had experienced persistent tinnitus over the past year. Associations of hearing difficulty and tinnitus with noise exposure were examined by logistic regression, with adjustment for age, sex, smoking habits, and frequent complaints of headaches, tiredness, or stress. The findings were expressed as prevalence ratios (PRs) with associated 95% confidence intervals (CIs). Attributable numbers were calculated from the relevant PRs and an estimate of the prevalence of occupational exposure to noise nationally. Some 2% of subjects reported severe hearing difficulties (wearing a hearing aid or having great difficulty in both ears in hearing conversation in a quiet room). In men, the prevalence of this outcome rose steeply with age, from below 1% in those aged 16-24 years to 8% in those aged 55-64. The pattern was similar in women, but severe hearing loss was only about half as prevalent in the oldest age band. Tinnitus was far more common in subjects with hearing difficulties. In both sexes, after adjustment for age, the risk of severe hearing difficulty and persistent tinnitus rose with years spent in a noisy job. In men older than 35 years with 10 or more years of exposure, the PR for severe hearing difficulty was 3.8 (95% CI 2.4 to 6.2) and that for persistent tinnitus 2.6 (95% CI 2.0 to 3.4) in comparison with those who had never had a noisy job. Nationally, some 153 000 men and 26 000 women aged 35-64 years were estimated to have severe hearing difficulties attributable to noise at work. For persistent tinnitus the corresponding numbers were 266 000 and 84 000. Significant hearing difficulties and tinnitus are quite common in men from the older working age range. Both are strongly associated with years spent in a noisy occupation--a predominantly male exposure. The national burden of hearing difficulties attributable to noise at work is substantial.


Phylogenetic relationships among members of the Fusarium solani species complex in human infections and the descriptions of F. keratoplasticum sp. nov. and F. petroliphilum stat. nov.
Fusarium species are frequently associated with mycotic keratitis and, to a lesser extent, cases of localized and disseminated infections. The Fusarium solani species complex (FSSC) is the most common group of fusaria associated with human infectious diseases. Several studies to date have revealed dozens of strongly supported phylogenetic species within this important evolutionary clade, though little work has been done to improve the taxonomy and understanding of the reproductive mode and phenotypes of the predominant clinically relevant species. Here we described Fusarium keratoplasticum sp. nov., and Fusarium petroliphilum stat. nov., two phylogenetic species that are among the most frequently isolated fusaria in plumbing drain biofilms and outbreaks of contact lens-associated mycotic keratitis. F. keratoplasticum isolates were highly variable and showed a range of morphological characteristics typical for most classical concepts of 'F. solani.' Many isolates failed to produce sporodochia and macroconidia. Although most attempts to sexually cross F. keratoplasticum isolates failed, a heterothallic sexual stage typical for the FSSC was discovered by pairing isolates of opposite mating type on V-8 agar, the ascospores of which showed molecular evidence of recombination. Secondary metabolite profiles of FSSC species defined through molecular data were compared for the first time and revealed the production of bioactive compounds including cyclosporines and several novel compounds of unknown function. We speculate that the inferred phenotypic variability in these species is the result of the almost entirely anthropogenic sources from which they are derived, including biofilms on plumbing systems.


Effects of hydrochlorothiazide and diltiazem on reflex vasoconstriction in hypertension.
The purpose of our study was to determine the effects of treatment with hydrochlorothiazide (n = 10) or diltiazem (n = 8) on reflex humoral, hemodynamic, and vascular responses to graded lower body negative pressure in subjects with mild to moderate hypertension (supine diastolic pressure, 95-114 mm Hg). All subjects received placebo for 2 to 4 weeks followed by either hydrochlorothiazide (25-50 mg b.i.d.) or diltiazem (120-180 mg b.i.d.) to achieve a reduction in supine diastolic pressure of 10 mm Hg or more and a final pressure below 90 mm Hg. Mean arterial pressure, forearm vascular resistance, plasma norepinephrine, and renin responses to graded lower body negative pressure (-10, -20, -40 mm Hg) and head-up tilt were examined before and after 12 weeks of treatment with either drug. Pretreatment basal values of mean arterial pressure (114 +/- 2 vs 117 +/- 2 mm Hg), forearm vascular resistance (29 +/- 3 vs 35 +/- 7 units), and plasma renin activity (0.7 +/- 0.2 vs 0.6 +/- 0.2 ng angiotensin I/ml/hr) were not significantly different between groups. There were no significant differences in basal plasma norepinephrine or in the increases of norepinephrine in response to lower body negative pressure before and after treatment in either group. Forearm vascular resistance responses to lower body negative pressure were virtually abolished in the diltiazem-treated group but not in the hydrochlorothiazide-treated group despite similar levels of mean arterial pressure and basal forearm vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)


In situ analytical techniques for battery interface analysis.
Lithium-ion batteries, simply known as lithium batteries, are distinct among high energy density charge-storage devices. The power delivery of batteries depends upon the electrochemical performances and the stability of the electrode, electrolytes and their interface. Interfacial phenomena of the electrode/electrolyte involve lithium dendrite formation, electrolyte degradation and gas evolution, and a semi-solid protective layer formation at the electrode-electrolyte interface, also known as the solid-electrolyte interface (SEI). The SEI protects electrodes from further exfoliation or corrosion and suppresses lithium dendrite formation, which are crucial needs for enhancing the cell performance. This review covers the compositional, structural and morphological aspects of SEI, both artificially and naturally formed, and metallic dendrites using in situ/in operando cells and various in situ analytical tools. Critical challenges and the historical legacy in the development of in situ/in operando electrochemical cells with some reports on state-of-the-art progress are particularly highlighted. The present compilation pinpoints the emerging research opportunities in advancing this field and concludes on the future directions and strategies for in situ/in operando analysis.


Computational discovery and characterization of new B2O phases.
We present computational discoveries of new structural phases of the B2O compound exhibiting novel bonding networks and electronic states at ambient and elevated pressures. Our advanced crystal structure searches in conjunction with density functional theory calculations have identified an orthorhombic phase of B2O that is energetically stable at ambient pressure and contains an intriguing bonding network of icosahedral B12 clusters bridged by oxygen atoms. As pressure increases above 1.9 GPa, a structural transformation takes the orthorhombic B2O into a pseudo-layered trigonal phase. We have performed extensive studies to investigate the evolution of chemical bonds and electronic states associated with the B12 icosahedral unit in the orthorhombic phase and the covalent B-O bonds in the trigonal phase. We have also examined the nature of the charge carriers and their coupling to the lattice vibrations in the newly identified B2O crystals. Interestingly, our results indicate that both B2O phases become superconducting at low temperatures, with transition temperatures of 6.4 K and 5.9 K, respectively, in the ambient and high-pressure phase. The present findings establish new B2O phases and characterize their structural and electronic properties, which offer insights and guidance for exploration toward further fundamental understanding and potential synthesis and application.


Papular elastorrhexis: clinical perspectives.
First described by Bordas in 1987, papular elastorrhexis (PE) is a rare elastic fiber disorder of the skin characterized by multiple, discrete, asymptomatic, firm, nonfollicular, monomorphous, 1-5 mm, circumscribed, hypopigmented, oval to round papules, symmetrically distributed on the chest, abdomen, back, shoulders, arms, and thighs. The onset of the condition is usually in the first or second decade of life. PE appears to be an exceedingly rare entity, with 33 cases reported in the literature until now. However, the disorder might be underestimated probably because of its subtlety, asymptomatic course, and benign nature of clinical alterations, which can easily be confused with other dermatoses such as acne scars. Clinical and histopathological differential diagnosis of PE is broad and includes papular acne scars, eruptive collagenoma, disseminated lenticular dermatofibrosis (as a component of Buschke-Ollendorff syndrome), white fibrous papulosis of the neck, pseudoxanthoma elasticum, pseudoxanthoma elasticum-like papillary dermal elastolysis, middermal elastolysis, and perifollicular elastolysis. Treatment of PE is a matter of debate and no reliable curative option exists.


Comparison of two clinical severity scoring systems in two multi-center, developing country rotavirus vaccine trials in Africa and Asia.
Clinical severity scoring systems are used in rotavirus vaccine efficacy and effectiveness studies to define the primary endpoint, severe rotavirus gastroenteritis (RVGE). Understanding how scoring systems perform in diverse settings is critical for proper design and interpretation. This investigation aims to understand how the Vesikari scoring system (VSS) and Clark scoring system (CSS) categorize severe disease among children under 2 years of age using data from two Phase III efficacy trials conducted in five developing countries in Africa and Asia. Signs and symptoms were collected on trial participants who presented to a medical facility with study-defined gastroenteritis. Severity scores were calculated using pre-established VSS and CSS criteria and compared to identify differences in the proportions of severe RVGE within regions and sites, and by gender and age. In Africa and Asia, 40.6% and 56.0% of rotavirus-positive episodes were severe according to the VSS, while 9.5% and 6.3% of episodes were severe according to the CSS (Fisher's Exact, p ≤ 0.001). Using the mean scores in these trials (VSS: ≥ 10 Africa, ≥ 11 Asia; CSS: Africa and Asia ≥ 10) as the severity thresholds, agreement between scoring system severity classifications improved substantially within each region (Africa: kappa = 0.67; Asia: kappa = 0.78) as compared to the original severity classification (Africa: kappa = 0.27; Asia: kappa = 0.10). Using the mean score, 17.1% and 9.5% of severe VSS cases in Africa and Asia, respectively, were classified as not severe according to the CSS and 14.7% and 9.5% of severe CSS cases in Africa and Asia were classified as not severe according to the VSS. The two scoring systems performed differently among developing country populations in Africa and Asia, with the VSS classifying more cases as severe in both regions. One accurate and reliable scoring system should be developed and implemented for all trials so that results may be more comparable.


Neuroimaging predictors of brain amyloidosis in mild cognitive impairment.
To identify a neuroimaging signature predictive of brain amyloidosis as a screening tool to identify individuals with mild cognitive impairment (MCI) that are most likely to have high levels of brain amyloidosis or to be amyloid-free. The prediction model cohort included 62 MCI subjects screened with structural magnetic resonance imaging (MRI) and (11) C-labeled Pittsburgh compound B positron emission tomography (PET). We identified an anatomical shape variation-based neuroimaging predictor of brain amyloidosis and defined a structural MRI-based brain amyloidosis score (sMRI-BAS). Amyloid beta positivity (Aβ(+) ) predictive power of sMRI-BAS was validated on an independent cohort of 153 MCI patients with cerebrospinal fluid Aβ1-42 biomarker data but no amyloid PET scans. We compared the Aβ(+) predictive power of sMRI-BAS to those of apolipoprotein E (ApoE) genotype and hippocampal volume, the 2 most relevant candidate biomarkers for the prediction of brain amyloidosis. Anatomical shape variations predictive of brain amyloidosis in MCI embraced a characteristic spatial pattern known for high vulnerability to Alzheimer disease pathology, including the medial temporal lobe, temporal-parietal association cortices, posterior cingulate, precuneus, hippocampus, amygdala, caudate, and fornix/stria terminals. Aβ(+) prediction performance of sMRI-BAS and ApoE genotype jointly was significantly better than the performance of each predictor separately (area under the curve [AUC] = 0.88 vs AUC = 0.70 and AUC = 0.81, respectively) with >90% sensitivity and specificity at 20% false-positive rate and false-negative rate thresholds. Performance of hippocampal volume as an independent predictor of brain amyloidosis in MCI was only marginally better than random chance (AUC = 0.56). As one of the first attempts to use an imaging technique that does not require amyloid-specific radioligands for identification of individuals with brain amyloidosis, our findings could lead to development of multidisciplinary/multimodality brain amyloidosis biomarkers that are reliable, minimally invasive, and widely available.


TRPV1 Antagonist Prevents Neonatal Sevoflurane-Induced Synaptic Abnormality and Cognitive Impairment in Mice Through Regulating the Src/Cofilin Signaling Pathway.
Long-term neurodevelopmental disorders following neonatal anesthesia have been reported both in young animals and in children. The activation of transient receptor potential vanilloid 1 (TRPV1) channels in hippocampus adversely affects neurodevelopment. The current study explored the underlying mechanism of TRPV1 channels on long-lasting cognitive dysfunction induced by anesthetic exposure to the developing brain. we demonstrated that TRPV1 expression was increased after sevoflurane exposure both in vitro and in vivo. Sevoflurane exposure to hippocampal neurons decreased the synaptic density and the surface GluA1 expression, as well as increased co-localization of internalized AMPAR in early and recycling endosomes. Sevoflurane exposure to newborn mice impaired learning and memory in adulthood, and reduced AMPAR subunit GluA1, 2 and 3 expressions in the crude synaptosomal fractions from mouse hippocampus. The inhibition of TRPV1 reversed the phenotypic changes induced by sevoflurane. Moreover, sevoflurane exposure increased Src phosphorylation at tyrosine 416 site thereby reducing cofilin phosphorylation. TRPV1 blockade reversed these suppressive effects of sevoflurane. Our data suggested that TRPV1 antagonist may protect against synaptic damage and cognitive dysfunction induced by sevoflurane exposure during the brain developing stage.


Perioperative treatment of gastrointestinal stromal tumors.
This review describes the current multidisciplinary management of gastrointestinal stromal tumor (GIST), which is the most common sarcoma of the gastrointestinal tract. Before 2001, surgery was the only effective therapy for GIST. The discovery of the central role of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of specific inhibitors of KIT tyrosine kinase (TK) function, has changed the paradigm of treatment for GISTs. Imatinib and sunitinib are TK inhibitors with activity against GISTs. Their major established role in GIST is in the treatment of advanced disease. A growing body of literature and clinical experience support the potential perioperative use of these drugs. The adjuvant use of imatinib is based on retrospective series and limited prospective studies demonstrating that imatinib reduces the risk of recurrence. Ongoing studies are further defining the length of adjuvant therapy, as well as identifying the patients that could achieve the best results. Neoadjuvant treatment often decreases the tumor size, allowing a less morbid surgery, appears to be safe and beneficial for some patients, and therefore deserves further study.


Systematic review of qualitative evaluations of reentry programs addressing problematic drug use and mental health disorders amongst people transitioning from prison to communities.
The paper presents a systematic review and metasynthesis of findings from qualitative evaluations of community reentry programs. The programs sought to engage recently released adult prison inmates with either problematic drug use or a mental health disorder. Seven biomedical and social science databases, Cinahl, Pubmed, Scopus, Proquest, Medline, Sociological abstracts and Web of Science and publisher database Taylor and Francis were searched in 2016 resulting in 2373 potential papers. Abstract reviews left 140 papers of which 8 were included after detailed review. Major themes and subthemes were identified through grounded theory inductive analysis of results from the eight papers. Of the final eight papers the majority (6) were from the United States. In total, the papers covered 405 interviews and included 121 (30%) females and 284 (70%) males. Findings suggest that the interpersonal skills of case workers; access to social support and housing; and continuity of case worker relationships throughout the pre-release and post-release period are key social and structural factors in program success. Evaluation of community reentry programs requires qualitative data to contextualize statistical findings and identify social and structural factors that impact on reducing incarceration and improving participant health. These aspects of program efficacy have implications for reentry program development and staff training and broader social and health policy and services.


A little bias goes a long way: the effects of feedback on the strategic regulation of accuracy on formula-scored tests.
Under formula-scoring rules for multiple-choice exams, a penalty is applied to incorrect responses to reduce noise in the observed score. To avoid the penalty individuals are allowed to "pass," and therefore they must be able to strategically regulate the accuracy of their reporting by deciding which and how many questions to answer. To investigate the effect of bias within this framework, Higham (2007) introduced bias profiles, which show the score obtained under formula scoring (corrected score) as a function of the omission rate. Bias profiles estimate the optimal number of questions that should be answered to maximize the corrected score (i.e., optimal bias). Our initial research showed that individuals tend to be too conservative when setting reporting criteria, "omitting" too many answers. The present three experiments introduced a feedback manipulation whereby participants were informed of the optimal omission rate after completing a test and asked to alter their reporting decisions accordingly. This feedback and concomitant alteration of reporting decisions led to improved corrected scores on true/false (Experiment 1), 2-alternative tests (Experiments 2), and 4-alternative tests (Experiment 3). Importantly, corrected scores at optimal bias also were higher than at forced-report for both true/false and 2-alternative tests. Furthermore, in Experiment 3, feedback based on one test improved scores on a second test, and participants were more likely to perform optimally on a third test without feedback. These effects suggest that optimal-bias feedback may have long-term effects and generalize to new tests.