Kinetics of glucose decomposition during dilute-acid hydrolysis of lignocellulosic biomass.
Recent research work in-house both at Auburn University and National Renewable Energy Laboratory has demonstrated that extremely low concentrations of acid (e.g., 0.05-0.2 wt% sulfuric acid) and high temperatures (e.g., 200-230 degrees C) are reaction conditions that can be effectively applied for hydrolysis of the cellulosic component of biomass. These conditions are far from those of the conventional dilute-acid hydrolysis processes, and the kinetic data for glucose decomposition are not currently available. We investigated the kinetics of glucose decomposition covering pH values of 1.5-2.2 and temperatures of 180-230 degrees C using glass ampoule reactors. The primary factors controlling glucose decomposition are the reaction medium, acid concentration, and temperature. Based on the experimental data, a kinetic model was developed and the best-fit kinetic parameters were determined. However, a consistent discrepancy in the rate of glucose disappearance was found between that of the model based on pure glucose data and that observed during the actual process of lignocellulosic biomass hydrolysis. This was taken as an indication that glucose recombines with acid-soluble lignin during the hydrolysis process, and this conclusion was incorporated accordingly into the overall model of glucose decomposition.


Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci.
Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed epigenome. Furthermore, large genetic variants alter epigenetic signal dosage. Here, we identify DNA methylation variability between GWAS-SNP risk and non-risk haplotypes. In three subsets comprising 3128 MeDIP-seq peripheral-blood DNA methylomes, we find 7173 consistent and functionally enriched Differentially Methylated Regions. 36.8% can be attributed to common non-SNP genetic variants. CpG-SNPs, as well as facilitative TFBS-motifs, are also enriched. Highlighting their functional potential, CpG-SNPs strongly associate with allele-specific DNase-I hypersensitivity sites. Our results demonstrate strong DNA methylation allelic differences driven by obligatory or facilitative genetic effects, with potential direct or regional disease-related repercussions. These allelic variations require disentangling from pure tissue-specific modifications, may influence array studies, and imply underestimated population variability in current reference epigenomes.


SU-E-T-162: Rapid Assessment of Cyberknife IRIS Variable Collimator Performance Using a Commercial Diode Array.
To describe an efficient method for verifying the size and centering of the radiation field from the Cyberknife IRIS variable collimator with sub-millimeter accuracy using a general purpose commercially available diode array. We present a technique using a conventional diode array (Sun Nuclear Profiler) with the array at an extended distance of 320 cm. The projection of the 4 mm diode spacing back to the 80 cm field definition distance gives an effective spacing of 1 mm, sufficient to confirm proper operation of the IRIS. We describe the data acquisition process and present data comparing the Profiler measurements to scanned measurements for both profile and FWHM analysis and reproducibility of the technique over repeated measurements. Average difference between original water scanner measurements and diode array measurements over the 12 aperture sizes) from 5 mm to 60 mm) were - 0.14 mm (range 0.03 mm to 0.83 mm). Reproducibility and centering measurements had a similar range of accuracy. A general purpose commercially available diode array can be used to quickly and accurately characterize the field size and centering of the Cyberknife IRIS variable collimator system with sub-millimeter accuracy subsequent to service, software recalibration, software upgrades or associated with routine QA. This technique avoids the time consuming and cumbersome water tank scanning with a diode and the difficulties associated with image based measurements (CR or radiochromic film) that require time consuming and careful calibration and choice of threshold values.


Monoallelic expression of MAO-A in skin fibroblasts.
X chromosome inactivation in mammalian females occurs early in embryonic development and renders most genes on the inactive X chromosome transcriptionally silenced. As a consequence, females will display an X chromosomal parent-of-origin mosaicism with regard to which parental allele that is expressed. Some genes however, escape inactivation and will therefore be expressed from both alleles. In this study we have investigated if the X-linked MAO-A gene have bi- or mono-allelic expression. This information would indicate whether or not MAO-A gene dosage could potentially explain the observed gender differences that show functional connections to the serotonin system, such as aggression and impulsiveness. To investigate the X inactivation status of MAO-A we have used primary clonal cell cultures, on which allelic expression was assessed with RFLP analysis. Our results show that the MAO-A gene has mono-allelic expression in these cells. This could have important implications for understanding traits that display gender differences.


Dynamics of anticipatory mechanisms during predictive context processing.
We employed an electroencephalography paradigm manipulating predictive context to dissociate the neural dynamics of anticipatory mechanisms. Subjects either detected random targets or targets preceded by a predictive sequence of three distinct stimuli. The last stimulus in the three-stimulus sequence (decisive stimulus) did not require any motor response but 100% predicted a subsequent target event. We showed that predictive context optimises target processing via the deployment of distinct anticipatory mechanisms at different times of the predictive sequence. Prior to the occurrence of the decisive stimulus, enhanced attentional preparation was manifested by reductions in the alpha oscillatory activities over the visual cortices, resulting in facilitation of processing of the decisive stimulus. Conversely, the subsequent 100% predictable target event did not reveal the deployment of attentional preparation in the visual cortices, but elicited enhanced motor preparation mechanisms, indexed by an increased contingent negative variation and reduced mu oscillatory activities over the motor cortices before movement onset. The present results provide evidence that anticipation operates via different attentional and motor preparation mechanisms by selectively pre-activating task-dependent brain areas as the predictability gradually increases.


Low immigrant mortality in England and Wales: a data artefact?
Previous research shows low mortality for most immigrants compared to natives in host countries. This advantage is often attributed to health selection processes in migration and to protective health behaviours. Little research has examined the role of data quality, especially the registration of moves. Registration errors relating to moves between origin and host countries can mismatch deaths and risk populations, leading to denominator bias and an under-estimation of migrant mortality (data artefact). The paper investigates the mortality of immigrants in England and Wales from 1971 to 2001 using the Office for National Statistics Longitudinal Study (ONS LS), a 1% sample of the population of England and Wales. We apply parametric survival models to study the mortality of 450,000 individuals. We conduct sensitivity analysis to assess the impact of entry and exit uncertainty on immigrant mortality rates. The analysis shows that most international migrants have lower mortality than natives in England and Wales. Differences largely persist when we adjust models to entry and exit uncertainty and they become pronounced once we control for individual socioeconomic characteristics. This study supports low mortality among immigrants and shows that results are not a data artefact.


Management of sterile abdominal pseudocysts related to ventriculoperitoneal shunts.
There are many known complications associated with CSF shunts. One of the more rare ones is a sterile abdominal pseudocyst due to decreased peritoneal absorption. This study was undertaken to detail the presentation, evaluation, and management of this unusual shunt-related event. Patients presenting with ventriculoperitoneal shunt (VPS)-related sterile abdominal pseudocysts treated at two institutions between 2013 and 2018 were included. Patients who had undergone abdominal surgery or shunt revisions within a 12-month period preceding presentation were excluded. Information was collected regarding clinical characteristics; hospital course, including surgical intervention(s); and any subsequent complications. Special attention was given to the eventual surgery after pseudocyst resolution, including the use of laparoscopy for peritoneal catheter placement, distal shunt conversion (i.e., in the atrium or pleural cavity), endoscopic third ventriculostomy, or shunt removal. The timing and nature of any subsequent shunt failures were also noted. Twenty-eight patients met the study criteria, with a mean age of 10 years. The most common etiology of hydrocephalus was intraventricular hemorrhage of prematurity. All shunts were externalized at presentation. One shunt was removed without subsequent internalization. Distal catheters were re-internalized back into the peritoneal cavity in 11 patients (laparoscopy was used in 8 cases). Fourteen shunts were converted to a ventriculoatrial shunt (VAS), and two to a ventriculopleural (VPlS). Two VPSs failed due to a recurrent pseudocyst. The total all-cause failure rates at 1 year were as follows: 18% for VPSs and 50% for VASs. Following treatment of a VPS-related sterile abdominal pseudocyst, laparoscopy-assisted placement of the distal catheter in the peritoneum is a viable and safe option for select patients, compared to a VAS or VPlS.


Dietary sugars, exercise and hepatic carbohydrate metabolism.
The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.


Heredofamilial syndrome of spastic paraplegia, dysarthria and cutaneous lesions in ive siblings.
Five children, three sisters and two brothers aged between three months and 12 years, are described. They all developed a facial desquamating rash of butterfly distribution at the age of about two months, and motor retardation which later was characterized by spasticity, predominantly affecting the lower limbs. The three children who were old enough for speech to be tested had dysarthria. There was no family history of neurological disease, nor was there consanguinity among the parents or grandparents. EEGs were diffusely abnormal in four of the five children, but did not show any specific or diagnostic features. Plasma immunoglobulin tests were normal, and tests for collagen disease were negative. The authors are not aware of previous reports of this condition, but believe that it is a variant of familial spastic paraplegia, with atypical features.


Objective and self-reported factors associated with food-environment perceptions and fruit-and-vegetable consumption: a multilevel analysis.
Few studies have assessed how people's perceptions of their neighborhood environment compare with objective measures or how self-reported and objective neighborhood measures relate to consumption of fruits and vegetables. A telephone survey of 4,399 residents of Philadelphia, Pennsylvania, provided data on individuals, their households, their neighborhoods (self-defined), their food-environment perceptions, and their fruit-and-vegetable consumption. Other data on neighborhoods (census tracts) or "extended neighborhoods" (census tracts plus 1-quarter-mile buffers) came from the US Census Bureau, the Philadelphia Police Department, the Southeastern Pennsylvania Transportation Authority, and the federal Supplemental Nutrition Assistance Program. Mixed-effects multilevel logistic regression models examined associations between food-environment perceptions, fruit-and-vegetable consumption, and individual, household, and neighborhood characteristics. Perceptions of neighborhood food environments (supermarket accessibility, produce availability, and grocery quality) were strongly associated with each other but not consistently or significantly associated with objective neighborhood measures or self-reported fruit-and-vegetable consumption. We found racial and educational disparities in fruit-and-vegetable consumption, even after adjusting for food-environment perceptions and individual, household, and neighborhood characteristics. Having a supermarket in the extended neighborhood was associated with better perceived supermarket access (adjusted odds ratio for having a conventional supermarket, 2.04 [95% CI, 1.68-2.46]; adjusted odds ratio for having a limited-assortment supermarket, 1.28 [95% CI, 1.02-1.59]) but not increased fruit-and-vegetable consumption. Models showed some counterintuitive associations with neighborhood crime and public transportation. We found limited association between objective and self-reported neighborhood measures. Sociodemographic differences in individual fruit-and-vegetable consumption were evident regardless of neighborhood environment. Adding supermarkets to urban neighborhoods might improve residents' perceptions of supermarket accessibility but might not increase their fruit-and-vegetable consumption.


Behavioral modeling of human choices reveals dissociable effects of physical effort and temporal delay on reward devaluation.
There has been considerable interest from the fields of biology, economics, psychology, and ecology about how decision costs decrease the value of rewarding outcomes. For example, formal descriptions of how reward value changes with increasing temporal delays allow for quantifying individual decision preferences, as in animal species populating different habitats, or normal and clinical human populations. Strikingly, it remains largely unclear how humans evaluate rewards when these are tied to energetic costs, despite the surge of interest in the neural basis of effort-guided decision-making and the prevalence of disorders showing a diminished willingness to exert effort (e.g., depression). One common assumption is that effort discounts reward in a similar way to delay. Here we challenge this assumption by formally comparing competing hypotheses about effort and delay discounting. We used a design specifically optimized to compare discounting behavior for both effort and delay over a wide range of decision costs (Experiment 1). We then additionally characterized the profile of effort discounting free of model assumptions (Experiment 2). Contrary to previous reports, in both experiments effort costs devalued reward in a manner opposite to delay, with small devaluations for lower efforts, and progressively larger devaluations for higher effort-levels (concave shape). Bayesian model comparison confirmed that delay-choices were best predicted by a hyperbolic model, with the largest reward devaluations occurring at shorter delays. In contrast, an altogether different relationship was observed for effort-choices, which were best described by a model of inverse sigmoidal shape that is initially concave. Our results provide a novel characterization of human effort discounting behavior and its first dissociation from delay discounting. This enables accurate modelling of cost-benefit decisions, a prerequisite for the investigation of the neural underpinnings of effort-guided choice and for understanding the deficits in clinical disorders characterized by behavioral inactivity.


Positron emission tomography thyroid incidentaloma: Is it different in Indian subcontinent?
Positron emission tomography (PET) forms an integral part in work-up and follow-up of various malignancies. With the increased use of PET in oncology, finding of an incidental focal thyroid uptake (incidentaloma) is not unusual and presents a diagnostic challenge. The aim of the following study is to evaluate the frequency and radio-pathologic correlation of focal 18-fluoro deoxyglucose uptake (FDG) on PET within the thyroid from a large series. Retrospective review of 37,000 consecutive patients who underwent FDG-PET at tertiary cancer center in India. Radiological, pathological, PET scan and follow-up details were evaluated. Statistical analyzes were carried out using Mann Whitney test and Pearson correlation. Abnormal thyroid uptake was seen in 78 (0.2%) patients. Nearly 61 (0.16%) scans had focal and 17 (0.04%) had diffuse FDG uptake. A total of 57 patients with focal uptake were available for further evaluation. No further evaluation was done in 24 (42.1%) patients who had advanced index malignancy. Of the remaining 33 patients 26 were benign and seven were a cause for concern (four primary thyroid cancers, one follicular neoplasm with hurthle cell change and two metastatic cancers). There was no significant correlation in Standardized uptake value (SUV) max of benign and malignant lesion (P = 0.5 on Mann Whitney) or size (r = 0.087 Pearson correlation co-efficient P= 0.667). Incidence of PET incidentaloma is low in this large cohort of Indian patients. Nearly 27% of focal incidentaloma were malignant. There was no correlation between the SUVmax, size and malignancy.


Association of pulse wave velocity with total lung capacity: A cross-sectional analysis of the BOLD London study.
Low lung function, measured using spirometry, has been associated with mortality from cardiovascular disease, but whether this is explained by airflow obstruction or restriction is a question that remains unanswered. To assess the association of total lung capacity (TLC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) with several cardio-metabolic and inflammatory markers. In the follow up of the Burden of Lung Disease (BOLD) study in London, acceptable post-bronchodilator spirometric, pulse rate, pulse wave velocity and blood pressure data were obtained from 108 participants. Blood samples for measurement of cardio-metabolic and inflammatory markers were also collected from these participants. Association of lung function and volume with the different biomarkers was examined in multivariable linear regression models adjusted for potential confounders. Following adjustment for age, sex, height, and ethnicity, TLC (adjusted coefficient = -1.53; 95% CI: -2.57, -0.49) and FVC (adjusted coefficient = -2.66; 95% CI: -4.98, -0.34) were inversely associated with pulse wave velocity, and further adjustment for smoking status, pack-years and body mass index (BMI) did not materially change these results. FEV1 was inversely associated with systolic blood pressure, and adjustment for smoking status, pack-years and BMI made this association stronger (adjusted coefficient = -9.47; 95% CI: -15.62, -3.32). The inverse association of pulse wave velocity, which is a marker of cardiovascular disease, with TLC suggests that the association of the former with low FVC is independent of airflow obstruction. The association between FEV1 with systolic blood pressure after adjustment for FVC suggests an association with airflow obstruction rather than with restricted spirometry.


Phase angle and bioelectrical impedance vectors in adolescent and adult male athletes.
The aim of the current study was to assess phase angle (PA) and bioelectrical impedance vectors (BIVA) in adolescent (n = 105, 12-19 y) and adult (n = 90, 20-50 y) male athletes practicing varied sports modalities. Bioelectrical impedance analysis (BIA) was performed with a single-frequency tetrapolar impedance analyzer after the athletes had fasted overnight for 8 h. PA and BIVA were determined from BIA data. PA presented correlations (P < .01) with body-mass index (r = .58) in all athletes and also with age in adolescent (r = .63) and adult (r = -.27) athletes. Compared with adults, adolescent athletes presented lower PA and higher frequency of PA below the 5th percentile of a reference population (P < .001). The adolescents with low PA were mostly football and basketball players. The BIVA confidence ellipses of adult and adolescent athletes were different (P < .001) between them and from their respective reference populations and were closer than those of adult and adolescent nonathletes. About 80% of the athletes were in the 95th percentile of BIVA tolerance ellipses and in quadrants consistent with adequate body cell mass and total body water. The adolescent athletes outside the 95th percentile ellipse were all football and basketball players who showed indications of decreased water retention and body cell mass and of increased water retention, respectively. PA and BIVA ellipses showed that the intense training routine of the athletes changed functional and hydration parameters and that the magnitude of these changes in adolescents may depend on the sport modality practiced.


Saudi Arabian adult intensive care unit pressure ulcer incidence and risk factors: a prospective cohort study.
The purpose of this study was to identify pressure ulcer (PU) incidence and risk factors that are associated with PU development in patients in two adult intensive care units (ICU) in Saudi Arabia. A prospective cohort study design was used. A total of 84 participants were screened second daily basis until discharge or death, over a consecutive 30-day period, out of which 33 participants with new PUs were identified giving a cumulative hospital-acquired PU incidence of 39·3% (33/84 participants). The incidence of medical devices-related PUs was 8·3% (7/84). Age, length of stay in the ICU, history of cardiovascular disease and kidney disease, infrequent repositioning, time of operation, emergency admission, mechanical ventilation and lower Braden Scale scores independently predicted the development of a PU. According to binary logistic regression analyses, age, longer stay in ICU and infrequent repositioning were significant predictors of all stages of PUs, while the length of stay in the ICU and infrequent repositioning were associated with the development of stages II-IV PUs. In conclusion, PU incidence rate was higher than that reported in other international studies. This indicates that urgent attention is required for PU prevention strategies in this setting.


Practice-Level Variation in Outpatient Cardiac Care and Association With Outcomes.
Utilization of cardiac services varies across regions and hospitals, yet little is known regarding variation in the intensity of outpatient cardiac care across cardiology physician practices or the association with clinical endpoints, an area of potential importance to promote efficient care. We included 7 160 732 Medicare beneficiaries who received services from 5635 cardiology practices in 2012. Beneficiaries were assigned to practices providing the plurality of office visits, and practices were ranked and assigned to quartiles using the ratio of observed to predicted annual payments per beneficiary for common cardiac services (outpatient intensity index). The median (interquartile range) outpatient intensity index was 1.00 (0.81-1.24). Mean payments for beneficiaries attributed to practices in the highest (Q4) and lowest (Q1) quartile of outpatient intensity were: all cardiac payments (Q4 $1272 vs Q1 $581; ratio, 2.2); cardiac catheterization (Q4 $215 vs Q1 $64; ratio, 3.4); myocardial perfusion imaging (Q4 $253 vs Q1 $83; ratio, 3.0); and electrophysiology device procedures (Q4 $353 vs Q1 $142; ratio, 2.5). The adjusted odds ratios (95% CI) for 1 incremental quartile of outpatient intensity for each outcome was: cardiac surgical/procedural hospitalization (1.09 [1.09, 1.10]); cardiac medical hospitalization (1.00 [0.99, 1.00]); noncardiac hospitalization (0.99 [0.99, 0.99]); and death at 1 year (1.00 [0.99, 1.00]). Substantial variation in the intensity of outpatient care exists at the cardiology practice level, and higher intensity is not associated with reduced mortality or hospitalizations. Outpatient cardiac care is a potentially important target for efforts to improve efficiency in the Medicare population.


Murine cytomegalovirus infection: hematological, morphological, and functional study of lymphoid cells.
Mice were studied for 3 to 4 months after murine cytomegalovirus (MCMV) infection. Serial hematological parameters were evaluated. It was found that MCMV infection of mice were accompanied by the appearance of many atypical lymphocytes similar to those seen in association with the hematological features of mononucleosis associated with human CMV infection. Certain functions of splenocytes were studied in infected and uninfected animals during the 4 months after MCMV infection. Three periods were identifiable by the functional response of splenocytes during the course of MCMV infection. The initial phase was characterized by an elevated response of splenocytes to a T cell mitogen and a B cell mitogen (phytohemagglutinin and lipopolysaccharide, respectively). The intermediate phase was marked by productive virus replication in the salivary gland, injury to lymphoid elements, a depressed response of splenocytes to mitogens (phytohemagglutinin and lipopolysaccharide), and decreased humoral splenocytes to phytohemagglutinin stimulation was again increased, and a nonproductive latent infection was established. Study by scanning electron microscopy of splenocytes during the course of infection revealed morphological changes which were correlated with functional alterations.


NQO1 suppresses NF-κB-p300 interaction to regulate inflammatory mediators associated with prostate tumorigenesis.
NADPH reductase quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKKα and NF-κB while decreasing the levels of p53, leading to interactions between NF-κB and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune-associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-κB and p53 function.


Blink or think: can further reflection improve initial diagnostic impressions?
Experienced clinicians derive many diagnoses intuitively, because most new problems they see closely resemble problems they've seen before. The majority of these diagnoses, but not all, will be correct. This study determined whether further reflection regarding initial diagnoses improves diagnostic accuracy during a high-stakes board exam, a model for studying clinical decision making. Keystroke response data were used from 500 residents who took the 2010 American Board of Internal Medicine (ABIM) Internal Medicine Certification Examination. Data included time to initial response on each question, whether the answer was correct, and whether or not the resident changed her or his initial response. The focus was on 80 diagnosis questions that comprised realistic clinical vignettes with multiple-choice single-best answers. Cognitive skill (ability) was measured using overall exam scores. Case complexity was determined using item difficulty (proportion of examinees that correctly answered the question). A hierarchical generalized linear model was used to assess the relationship between time spent on initial responses and the probability of correctly answering the questions. On average, residents changed their responses on 12% of all diagnosis questions (or 9.6 questions out of 80). Changing an answer from incorrect to correct was almost twice as likely as changing an answer from correct to incorrect. The relationship between response time and accuracy was complex. Further reflection appears to be beneficial to diagnostic accuracy, especially for more complex cases.


Phosphatidylglycerolphosphate synthase expression in Schizosaccharomyces pombe is regulated by the phospholipid precursors inositol and choline.
The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 188.8.131.52) catalyzes the committed step in the cardiolipin biosynthetic pathway. To study the regulation of PGPS in Schizosaccharomyces pombe, we characterized the enzyme biochemically. Maximum activity occurred in the presence of 6 mM Triton X-100 at pH 7.5. The apparent Km values for CDP-diacylglycerol and glycerol 3-phosphate were 130 and 26 microM, respectively. Optimal activity was at 35 degrees C, and enzyme activity was labile above 40 degrees C. Thioreactive agents were inhibitory to PGPS activity. To determine whether S. pombe PGPS is regulated by phospholipid precursors, we examined the time-dependent expression of PGPS upon inositol and choline starvation. Starvation for inositol resulted in a threefold increase in PGPS expression in wild-type cells. In cho1 and cho2 mutants, which are blocked in phosphatidylcholine synthesis, starvation for choline resulted in transient derepression of PGPS expression. In choline auxotrophs starved for inositol, PGPS was derepressed 2.5- to 3-fold in the presence of choline and less or not at all in the absence of choline. This is the first description of PGPS regulation in S. pombe and the first demonstration of inositol-mediated regulation in the inositol-requiring yeast species.


A validation sampling approach for consistent estimation of adverse drug reaction risk with misclassified right-censored survival data.
Patient electronic health records, viewed as continuous-time right-censored survival data, can be used to estimate adverse drug reaction risk. Temporal outcome misclassification may occur as a result of errors in follow-up. These errors can be due to a failure to observe the incidence time of the adverse event of interest (due to misdiagnosis or nonreporting, etc) or an actual misdiagnosis of a competing adverse event. As the misclassifying event is often unobservable in the original data, we apply an internal validation sampling approach to produce consistent estimation in the presence of such errors. We introduce a univariate survival model and a cause-specific hazards model in which misclassification may also manifest as a diagnosis of an alternate adverse health outcome other than that of interest. We develop a method of maximum likelihood estimation of the model parameters and establish consistency and asymptotic normality of the estimators using standard results. We also conduct simulation studies to numerically investigate the finite sample properties of these estimators and the impact of ignoring the misclassification error.


Patient-reported outcome data generated in a clinical intervention in community mental health care--psychometric properties.
DIALOG is an intervention to structure the communication between patient and key worker, which has been shown to improve patient outcomes in community mental health care. As part of the intervention, patients provide ratings of their subjective quality of life (SQOL) on eight Likert type items and their treatment satisfaction on three such items. This study explored the psychometric qualities of the outcome data generated in the DIALOG intervention to explore whether they may be used for evaluating treatment outcomes. Data were taken from 271 patients who received the DIALOG intervention. All patients were diagnosed with schizophrenia or a related disorder and treated in community mental health care. For SQOL and treatment satisfaction as assessed in the DIALOG intervention, we established the internal consistency (Cronbach's alpha), the convergent validity of SQOL items (correlation with Manchester Short Assessment of Quality of Life [MANSA]) and treatment satisfaction items (correlation with Client Satisfaction Questionnaire [CSQ]), the concurrent validity (correlations with Positive and Negative Syndrome Scale [PANSS]) and the sensitivity to change (t-test comparing ratings of the first and last intervention). We also explored the factorial structure of the eight SQOL items. The internal consistency of the eight SQOL items was .71 and of the three treatment satisfaction items .57. SQOL scores were correlated with the MANSA (r = .95) and PANSS scores (general psychopathology: r = -.37, positive symptoms: r = -.27, negative symptoms: r = -.27). Treatment satisfaction scores were correlated with the CSQ (r = 0.36) and the PANSS (r = -.29, -.20, -.20). SQOL and treatment satisfaction score improved significantly over time. SQOL items loaded on two meaningful factors, one capturing health and personal safety and one reflecting other life domains. The psychometric qualities of the SQOL scores generated in DIALOG are strong. The properties of the three treatment satisfaction items may be seen as acceptable. Although DIALOG has been designed as a therapeutic intervention, it can generate outcome data on SQOL and treatment satisfaction with acceptable psychometric qualities.


Confronting data sparsity to identify potential sources of Zika virus spillover infection among primates.
The recent Zika virus (ZIKV) epidemic in the Americas ranks among the largest outbreaks in modern times. Like other mosquito-borne flaviviruses, ZIKV circulates in sylvatic cycles among primates that can serve as reservoirs of spillover infection to humans. Identifying sylvatic reservoirs is critical to mitigating spillover risk, but relevant surveillance and biological data remain limited for this and most other zoonoses. We confronted this data sparsity by combining a machine learning method, Bayesian multi-label learning, with a multiple imputation method on primate traits. The resulting models distinguished flavivirus-positive primates with 82% accuracy and suggest that species posing the greatest spillover risk are also among the best adapted to human habitations. Given pervasive data sparsity describing animal hosts, and the virtual guarantee of data sparsity in scenarios involving novel or emerging zoonoses, we show that computational methods can be useful in extracting actionable inference from available data to support improved epidemiological response and prevention.


Effects of finger tapping frequency on regional homogeneity of sensorimotor cortex.
Resting-state functional magnetic resonance imaging (RS-fMRI) has been widely used to investigate temporally correlated fluctuations between distributed brain areas, as well as to characterize local synchronization of low frequency (<0.1 Hz) spontaneous fMRI signal. Regional homogeneity (ReHo) was proposed as a voxel-wise measure of the synchronization of the timecourses of neighboring voxels and has been used in many studies of brain disorders. However, the interpretation of ReHo remains challenging because the effect of high frequency task on ReHo is still not clear. In order to investigate the effect of a high-frequency task on the modulation of local synchronization of resting-state activity, we employed three right-finger movement scanning sessions: slow-event related ('Slow'), fast-event related ('Fast'), and continuous finger pressure ('Tonic'), from 21 healthy participants and compared the ReHo of the three task states with that of resting-state ('Rest'). In the contralateral sensorimotor cortex, 'Slow' task state showed greater ReHo than 'Rest' in low frequency band (0-0.08Hz) fMRI signal, but lower ReHo in high frequency band (0.08-1.67 Hz); 'Fast' task state showed lower ReHo than 'Rest' in both the low and high frequency band; 'Tonic' state did not show any significant difference compared to 'Rest'. The results in the contralateral sensorimotor cortex suggest that local synchronization of BOLD signal varies with different finger tapping speed. In the ipsilateral sensorimotor cortex, all the three task states had lower ReHo than the 'Rest' state both in the low and high frequency, suggesting a similar effect of fast and slow finger tapping frequencies on local synchronization of BOLD signal in the ipsilateral motor cortex.


Abbreviation of larval development and extension of brood care as key features of the evolution of freshwater Decapoda.
The transition from marine to freshwater habitats is one of the major steps in the evolution of life. In the decapod crustaceans, four groups have colonized fresh water at different geological times since the Triassic, the freshwater shrimps, freshwater crayfish, freshwater crabs and freshwater anomurans. Some families have even colonized terrestrial habitats via the freshwater route or directly via the sea shore. Since none of these taxa has ever reinvaded its environment of origin the Decapoda appear particularly suitable to investigate life-history adaptations to fresh water. Evolutionary comparison of marine, freshwater and terrestrial decapods suggests that the reduction of egg number, abbreviation of larval development, extension of brood care and lecithotrophy of the first posthatching life stages are key adaptations to fresh water. Marine decapods usually have high numbers of small eggs and develop through a prolonged planktonic larval cycle, whereas the production of small numbers of large eggs, direct development and extended brood care until the juvenile stage is the rule in freshwater crayfish, primary freshwater crabs and aeglid anomurans. The amphidromous freshwater shrimp and freshwater crab species and all terrestrial decapods that invaded land via the sea shore have retained ocean-type planktonic development. Abbreviation of larval development and extension of brood care are interpreted as adaptations to the particularly strong variations of hydrodynamic parameters, physico-chemical factors and phytoplankton availability in freshwater habitats. These life-history changes increase fitness of the offspring and are obviously favoured by natural selection, explaining their multiple origins in fresh water. There is no evidence for their early evolution in the marine ancestors of the extant freshwater groups and a preadaptive role for the conquest of fresh water. The costs of the shift from relative r- to K-strategy in freshwater decapods are traded-off against fecundity, future reproduction and growth of females and perhaps against size of species but not against longevity of species. Direct development and extension of brood care is associated with the reduction of dispersal and gene flow among populations, which may explain the high degree of speciation and endemism in directly developing freshwater decapods. Direct development and extended brood care also favour the evolution of social systems, which in freshwater decapods range from simple subsocial organization to eusociality. Hermaphroditism and parthenogenesis, which have evolved in some terrestrial crayfish burrowers and invasive open water crayfish, respectively, may enable populations to adapt to restrictive or new environments by spatio-temporal alteration of their socio-ecological characteristics. Under conditions of rapid habitat loss, environmental pollution and global warming, the reduced dispersal ability of direct developers may turn into a severe disadvantage, posing a higher threat of extinction to freshwater crayfish, primary freshwater crabs, aeglids and landlocked freshwater shrimps as compared to amphidromous freshwater shrimps and secondary freshwater crabs.


Development and validation of a real-time microelectrochemical sensor for clinical monitoring of tissue oxygenation/perfusion.
Oxygen is of critical importance to tissue viability and there is increasing demand for its reliable real-time clinical monitoring in order to prevent, diagnose, and treat several pathological disorders, including hypoxia, stroke and reperfusion injury. Herein we report the development and characterisation of a prototype clinical O2 sensor, and its validation in vivo, including proof-of-concept monitoring in patients undergoing surgery for carpal tunnel release. An integrated platinum-based microelectrochemical device was custom designed and controlled using a miniaturised telemetry-operated single channel clinical potentiostat. The in vitro performance of different sensor configurations is presented, with the best sensor design (S2) displaying appropriate linearity (R2 = 0.994) and sensitivity (0.569 ± 0.022 nA μM-1). Pre-clinical validation of S2 was performed in the hind limb muscle of anaesthetised rats; tourniquet application resulted in a significant rapid decrease in signal (90 ± 27%, [ΔO2] ca. 140 ± 18 μM), with a return to baseline within a period of ca. 3 min following tourniquet release. Similar trends were observed in the clinical study; an immediate decrease in signal (39 ± 3%, [ΔO2] ca. 30 ± 20 μM), with basal levels re-established within 2 min of tourniquet release. These results confirm that continuous real-time monitoring of dynamic changes in tissue O2 can serve as an indicator of reperfusion status in patients undergoing carpal tunnel surgery, and suggests the potential usefulness of the developed microelectrochemical sensor for other medical conditions where clinical monitoring of O2 and perfusion is important.


20-Year Nationwide Follow-Up Study on Discontinuation of Antipsychotic Treatment in First-Episode Schizophrenia.
It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that after stabilization, antipsychotic treatment should be continued for 1-5 years, and longer exposure should be avoided if possible. However, there is no published evidence to substantiate this view. The authors used nationwide databases to investigate this issue. Prospectively gathered nationwide register data were used to study the risk of treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment. Multivariate Cox regression was used to assess outcomes among all patients hospitalized for the first time with a schizophrenia diagnosis in Finland during the period of 1996-2014 (N=8,719). The lowest risk of rehospitalization or death was observed for patients who received antipsychotic treatment continuously (adjusted hazard ratio=1.00), followed by patients who discontinued antipsychotic use immediately after discharge from the first hospital treatment (hazard ratio=1.63, 95% CI=1.52-1.75), within 1 year (hazard ratio=1.88, 95% CI=1.57-2.24), within 1-2 years (hazard ratio=2.12, 95% CI=1.43-3.14), within 2-5 years (hazard ratio=3.26, 95% CI=2.07-5.13), and after 5 years (a median of 7.9 years) (hazard ratio=7.28, 95% CI=2.78-19.05). Risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years. Whatever the underlying mechanisms, these results provide evidence that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotic treatment is associated with increased survival.


Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen.
Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.


Association of mild cognitive impairment and characteristic of COPD and overall health status in a cohort study.
Introduction: We evaluated risk factors and demographic characteristics of associated with mild cognitive impairment (MCI) in patients with COPD. Methods: 220 individuals with COPD enrolled in a cohort study designed to evaluate anxiety conducted at 16 clinical centers. Cognitive impairment was assessed with the Montreal Cognitive Assessment (MoCA), a cutoff score of <26 defined as MCI. Data were collected including spirometry, 6-minute walk test, symptom burden by COPD Assessment Test and dyspnea by Modified Medical Research Council, anxiety measured by Anxiety Inventory of Respiratory Disease, Generalized Anxiety Disorder-7 and Hospital Anxiety Depression Scale, depression by Patient Health Questionnaire-9 and health status by Patient Reported Outcomes Measurement Information System and sleep quality by the Pittsburg Sleep Quality Index. Results: The median age was 65 years and 54% of participants were male. 119(54%) of participants had MCI as classified by MoCA. In multivariable logistic regression, higher odds ratios (OR) (95% confidence interval) for MCI (MoCA) <26 were associated with increased years of age, 1.06 (1.02 -1-09, p<0.003); African-American race, 3.68(1.67-8.11, p<0.001); persistent phlegm, 2 (1.12-3.57, p<0.01) and sleep disturbance, 1.04(1.01-1.08, p<0.01). Conclusions: COPD patients commonly screen positive for MCI. Characteristics associated with MCI included age, African-American race, sleep disturbance and persistent phlegm.


Widely assumed phenotypic associations in Cannabis sativa lack a shared genetic basis.
The flowering plant Cannabis sativa, cultivated for centuries for multiple purposes, displays extensive variation in phenotypic traits in addition to its wide array of secondary metabolite production. Notably, Cannabis produces two well-known secondary-metabolite cannabinoids: cannabidiolic acid (CBDA) and delta-9-tetrahydrocannabinolic acid (THCA), which are the main products sought by consumers in the medical and recreational market. Cannabis has several suggested subspecies which have been shown to differ in chemistry, branching patterns, leaf morphology and other traits. In this study we obtained measurements related to phytochemistry, reproductive traits, growth architecture, and leaf morphology from 297 hybrid individuals from a cross between two diverse lineages. We explored correlations among these characteristics to inform our understanding of which traits may be causally associated. Many of the traits widely assumed to be strongly correlated did not show any relationship in this hybrid population. The current taxonomy and legal regulation within Cannabis is based on phenotypic and chemical characteristics. However, we find these traits are not associated when lineages are inter-crossed, which is a common breeding practice and forms the basis of most modern marijuana and hemp germplasms. Our results suggest naming conventions based on leaf morphology do not correspond to the chemical properties in plants with hybrid ancestry. Therefore, a new system for identifying variation within Cannabis is warranted that will provide reliable identifiers of the properties important for recreational and, especially, medical use.


Email for the provision of information on disease prevention and health promotion.
Email is a popular and commonly used method of communication, but its use in health care is not routine. Its application in health care has included the provision of information on disease prevention and health promotion, but the effects of using email in this way are not known. This review assesses the use of email for the provision of information on disease prevention and health promotion. To assess the effects of email for the provision of information on disease prevention and health promotion, compared to standard mail or usual care, on outcomes for healthcare professionals, patients and caregivers, and health services, including harms. We searched: the Cochrane Consumers and Communication Review Group Specialised Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (1950 to January 2010), EMBASE (1980 to January 2010), CINAHL (1982 to February 2010), ERIC (1965 to January 2010) and PsycINFO (1967 to January 2010). We searched grey literature: theses/dissertation repositories, trials registers and Google Scholar (searched July 2010). We used additional search methods: examining reference lists, contacting authors. Randomised controlled trials, quasi-randomised trials, controlled before and after studies and interrupted time series studies examining interventions where email is used by healthcare professionals to provide information to patients on disease prevention and health promotion, and taking the form of 1) unsecured email 2) secure email or 3) web messaging. We considered healthcare professionals or associated administrative staff as participants originating the email communication, and patients and caregivers as participants receiving the email communication, in all settings. Email communication was one-way from healthcare professionals or associated administrative staff originating the email communication, to patients or caregivers receiving the email communication. Two authors independently assessed the risk of bias of included studies and extracted data. We contacted study authors for additional information. We assessed risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. For continuous outcome measures, we report effect sizes as mean differences (MDs). For dichotomous outcome measures, we report effect sizes as odds ratios (ORs). We conducted a meta-analysis for one primary health service outcome, comparing email communication to standard mail, and report this result as an OR. We included six randomised controlled trials involving 8372 people. All trials were judged to be at high risk of bias for at least one domain. Four trials compared email communication to standard mail and two compared email communication to usual care. For the primary health service outcome of uptake of preventive screening, there was no difference between email and standard mail (OR 0.93; 95% CI 0.69 to 1.24). For both comparisons (email versus standard mail and email versus usual care) there was no difference between the groups for patient or caregiver understanding and support. Results were inconclusive for patient or caregiver behaviours and actions. For email versus usual care only, there was no significant difference between groups for the primary outcome of patient health status and well-being. No data were reported relating to healthcare professionals or harms. The evidence on the use of email for the provision of information on disease prevention and health promotion was weak, and therefore inadequate to inform clinical practice. The available trials mostly provide inconclusive, or no evidence for the outcomes of interest in this review. Future research needs to use high-quality study designs that take advantage of the most recent developments in information technology, with consideration of the complexity of email as an intervention.


Structure and dynamics of water in molecular models of hydrated polyvinylamine membranes.
Facilitated transport membranes (FTMs) constitute an emerging class of polymer materials with promising properties for carbon capture applications. The key feature of these membranes is the presence of chemical groups which, in the presence of water, engage in a reaction with dissolved carbon dioxide, thus enhancing the permeability and selectivity of the membrane. Currently, little is known about the organization of these membranes on a molecular level, reaction mechanisms and detailed chemical balance, transport of water, ion species and dissolved gas molecules. The nature of the actual facilitation mechanism and the factors responsible for this effect remain unclear. Here, we use a case of polyvinylamine (PVAm), one of the most studied fixed carrier material for FTMs, to propose molecular models of the hydrated polymers. We aim to understand how transport of water is governed by structural properties of the membrane, such as the free volume, pore limiting diameter, and degree of protonation. We observe that even at the highest experimentally used hydration level, the mobility of water in PVAm matrices is significantly lower than that in bulk water; unlike in bulk systems, chloride ions exhibit much slower diffusion in confined water; this, in turn, affects the diffusion of water, which also diminishes in the presence of chloride ions.


Programming stress-induced altruistic death in engineered bacteria.
Programmed death is often associated with a bacterial stress response. This behavior appears paradoxical, as it offers no benefit to the individual. This paradox can be explained if the death is 'altruistic': the killing of some cells can benefit the survivors through release of 'public goods'. However, the conditions where bacterial programmed death becomes advantageous have not been unambiguously demonstrated experimentally. Here, we determined such conditions by engineering tunable, stress-induced altruistic death in the bacterium Escherichia coli. Using a mathematical model, we predicted the existence of an optimal programmed death rate that maximizes population growth under stress. We further predicted that altruistic death could generate the 'Eagle effect', a counter-intuitive phenomenon where bacteria appear to grow better when treated with higher antibiotic concentrations. In support of these modeling insights, we experimentally demonstrated both the optimality in programmed death rate and the Eagle effect using our engineered system. Our findings fill a critical conceptual gap in the analysis of the evolution of bacterial programmed death, and have implications for a design of antibiotic treatment.


The genotype-phenotype landscape of an allosteric protein.
Allostery is a fundamental biophysical mechanism that underlies cellular sensing, signaling, and metabolism. Yet a quantitative understanding of allosteric genotype-phenotype relationships remains elusive. Here, we report the large-scale measurement of the genotype-phenotype landscape for an allosteric protein: the lac repressor from Escherichia coli, LacI. Using a method that combines long-read and short-read DNA sequencing, we quantitatively measure the dose-response curves for nearly 105 variants of the LacI genetic sensor. The resulting data provide a quantitative map of the effect of amino acid substitutions on LacI allostery and reveal systematic sequence-structure-function relationships. We find that in many cases, allosteric phenotypes can be quantitatively predicted with additive or neural-network models, but unpredictable changes also occur. For example, we were surprised to discover a new band-stop phenotype that challenges conventional models of allostery and that emerges from combinations of nearly silent amino acid substitutions.


Breast Cancer Screening Knowledge and Perceived Health Beliefs among Immigrant Women in Korea.
Recently, through international marriage, immigrant women have rapidly increased throughout Korea. This study was performed to identify health beliefs and practices related to breast cancer screening in immigrant women in Korea. A cross-sectional survey was carried out between March and July 2012, and study population included immigrant females from six other Asian countries (Cambodia, China, Japan, Mongolia, Vietnam, and the Philippines). We surveyed 197 women and categorized them into four groups according to home countries. The questionnaire consisted of 55 items, including demographic and socioeconomic factors, breast cancer-related knowledge regarding risk factors and symptoms, beliefs and attitudes towards health and breast cancer, perceived susceptibility, barriers, and benefits of screening. Japanese participants were significantly older and had resided in Korea for more years than other country-of-origin groups (all p<0.001), and showed higher screening rates without statistical significance (p=0.392). In multivariate analysis, country of origin showed a significant correlation with knowledge (p=0.001), positive beliefs (p=0.002), and perceived benefits (p=0.025) of breast cancer screening. The group with the lowest household income showed a significantly lower score of perceived benefits (p=0.022). Through analysis to identify factors affecting participation in screening mammography, we found that education level (p=0.009), occupation status (p=0.006), and Korean language fluency (p=0.002) were independent predictors for screening behavior. This study identified conditions related to breast cancer screening knowledge, perception, and behavior of immigrant women in Korea. The results reflect the need for increased social aids to remove barriers to medical services and more educational programs to facilitate higher rates of screening.


Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain.
Amyloid-beta, the pathologic protein in Alzheimer's disease, induces chemotaxis and production of reactive oxygen species in phagocytic cells, but mechanisms have not been fully defined. Here we provide three lines of evidence that the phagocyte G protein-coupled receptor (N-formylpeptide receptor 2 (FPR2)) mediates these amyloid-beta-dependent functions in phagocytic cells. First, transfection of FPR2, but not related receptors, including the other known N-formylpeptide receptor FPR, reconstituted amyloid-beta-dependent chemotaxis and calcium flux in HEK 293 cells. Second, amyloid-beta induced both calcium flux and chemotaxis in mouse neutrophils (which express endogenous FPR2) with similar potency as in FPR2-transfected HEK 293 cells. This activity could be specifically desensitized in both cell types by preincubation with a specific FPR2 agonist, which desensitizes the receptor, or with pertussis toxin, which uncouples it from G(i)-dependent signaling. Third, specific and reciprocal desensitization of superoxide production was observed when N-formylpeptides and amyloid-beta were used to sequentially stimulate neutrophils from FPR -/- mice, which express FPR2 normally. Potential biological relevance of these results to the neuroinflammation associated with Alzheimer's disease was suggested by two additional findings: first, FPR2 mRNA could be detected by PCR in mouse brain; second, induction of FPR2 expression correlated with induction of calcium flux and chemotaxis by amyloid-beta in the mouse microglial cell line N9. Further, in sequential stimulation experiments with N9 cells, N-formylpeptides and amyloid-beta were able to reciprocally cross-desensitize each other. Amyloid-beta was also a specific agonist at the human counterpart of FPR2, the FPR-like 1 receptor. These results suggest a unified signaling mechanism for linking amyloid-beta to phagocyte chemotaxis and oxidant stress in the brain.


Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease.
Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-β/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-β, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention.


Early-Stage Mucinous Ovarian Adenocarcinoma with Extensive Clotting in a Previously Healthy Young Female Patient: An Uncommon Presentation of a Relatively Uncommon Disease.
BACKGROUND Mucinous ovarian adenocarcinoma is one of the less common epithelial cancers of the ovaries, and typically does not occur in younger women. Nearly all mucinous ovarian adenocarcinomas present with early-stage disease without significant sequelae of cancer, such as clotting. Anchoring bias is a common problem in medicine that has been shown to significantly affect physician decision-making. CASE REPORT We present the case of a 24-year-old healthy female Chinese immigrant with no significant past medical history, who presented with a subacute history of nonproductive cough and shortness of breath with exertion. Initial workup was directed towards diagnosis of tuberculosis and other infectious etiologies due to anchoring to patient's nationality and her positive family history for tuberculosis. She was eventually diagnosed with extensive bilateral pulmonary emboli and bilateral deep vein thromboses as well as a right ventricular thrombus. This extensive clot burden helped lead to the diagnosis of mucinous ovarian adenocarcinoma. CONCLUSIONS This case is significant not only because the diagnosis of mucinous ovarian adenocarcinoma is uncommon in healthy young females under the age of 25, but, more importantly, because such extensive pulmonary emboli and deep vein thromboses in a young female with local/early-stage ovarian cancer is very rare. This case is also significant because it serves as an important reminder of the risks of anchoring bias in skewing perceptions and delaying the correct diagnosis by physicians.


Shift work and overall and cause-specific mortality in the Danish nurse cohort.
Objectives Evidence of an effect of shift work on all-cause and cause-specific mortality is inconsistent. This study aims to examine whether shift work is associated with increased all-cause and cause-specific mortality. Methods We linked 28 731 female nurses (age ≥44 years), recruited in 1993 or 1999 from the Danish nurse cohort where they reported information on shift work (night, evening, rotating, or day), to the Danish Register of Causes of Death to identify deaths up to 2013. We used Cox regression models with age as the underlying scale to examine the associations between night, evening, and rotating shift work (compared to day shift work) and all-cause and cause-specific mortality in models adjusted for potentially confounding variables. Results Of 18 015 nurses included in this study, 1616 died during the study time period from the following causes: cardiovascular disease (N=217), cancer (N= 945), diabetes (N=20), Alzheimer's disease or dementia (N=33), and psychiatric diseases (N=67). We found that working night [hazard ratio (HR) 1.26, 95% confidence interval 95% CI) 1.05-1.51] or evening (HR 1.29, 95% CI 1.11-1.49) shifts was associated with a significant increase in all-cause mortality when compared to working day shift. We found a significant association of night shift work with cardiovascular disease (HR 1.71, 95% CI 1.09-2.69) and diabetes (HR 12.0, 95% CI 3.17-45.2, based on 8 cases) and none with overall cancer mortality (HR 1.05, 95% CI 0.81-1.35) or mortality from psychiatric diseases (HR 1.17, 95% CI 0.47-2.92). Finally, we found strong association between evening (HR 4.28, 95% CI 1.62-11.3) and rotating (HR 5.39, 95% CI 2.35-12.3) shift work and mortality from Alzheimer's disease and dementia (based on 8 and 14 deaths among evening and rotating shift workers, respectively). Conclusions Women working night and evening shifts have increased all-cause, cardiovascular, diabetes, and Alzheimer's and dementia mortality.


Dietary, behavioural and socio-economic determinants of the metabolic syndrome among adults in Luxembourg: findings from the ORISCAV-LUX study.
The purpose of the present research was to investigate the epidemiological profile of the metabolic syndrome (MetS) and to explore its potential dietary, behavioural and socio-economic determinants among European adults residing in Luxembourg. Cross-sectional, population-based ORISCAV-LUX survey. European adults aged 18-69 years residing in Luxembourg. A total of 1349 Europid adults, who participated in the ORISCAV-LUX survey, were included in the study. The prevalence of MetS was estimated according to the Revised-Adult Treatment Panel (R-ATPIII) criteria. Multivariate logistic regression was used to identify the dietary, behavioural and socio-economic factors independently associated with MetS. The overall prevalence of MetS was 24.7 % with significant gender difference (18.5 % for women v. 30.8 % for men, P < 0.0001). Age, male gender, primary level of education, physical inactivity, family history of diabetes and hypertension and inadequate protein intake were identified as significant determinants of MetS, after adjusting for other socio-economic, family medical history and lifestyle factors. MetS is a common condition among Europid adults in Luxembourg and increases dramatically with age, in both genders. Several dietary, socio-economic and behavioural factors explain the disparity observed. These findings highlight the importance of a comprehensive approach to MetS encompassing dietary, lifestyle and socio-economic aspects, both in clinical and community settings.


Using focus groups in the consumer research phase of a social marketing program to promote moderate-intensity physical activity and walking trail use in Sumter County, South Carolina.
The use of social marketing approaches in public health practice is increasing. Using marketing concepts such as the "four Ps" (product, price, place, and promotion), social marketing borrows from the principles of commercial marketing but promotes beneficial health behaviors. Consumer research is used to segment the population and develop a strategy based on those marketing concepts. In a community-based participatory research study, 17 focus groups were used in consumer research to develop a social marketing program to promote walking and other moderate-intensity physical activities. Two phases of focus groups were conducted. Phase 1 groups, which included both men and women, were asked to respond to questions that would guide the development of a social marketing program based on social marketing concepts. Phase 1 also determined the intervention's target audience, which was irregularly active women aged 35 to 54. Phase 2 groups, composed of members of the target audience, were asked to further define the product and discuss specific promotion strategies. Phase 1 participants determined that the program product, or target behavior, should be walking. In addition, they identified price, place, and promotion strategies. Phase 2 participants determined that moderate-intensity physical activity is best promoted using the term exercise and offered suggestions for marketing walking, or exercise, to the target audience. There have been few published studies of social marketing campaigns to promote physical activity. In this study, focus groups were key to understanding the target audience in a way that would not have been accomplished with quantitative data alone. The group discussions generated important insights into values and motivations that affect consumers' decisions to adopt a product or behavior. The focus group results guided the development of a social marketing program to promote physical activity in the target audience in Sumter County, South Carolina.


Tick-borne pulmonary disease: update on diagnosis and management.
Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man. Several of these tick-borne pathogens can lead to pulmonary disease. Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues. Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features. Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens. A Lyme vaccine has recently become available for use in the United States. Disease prevention depends on the avoidance of tick bites. When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered. Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes.


Color-changing intensified light-emitting multifunctional textiles via digital printing of biobased flavin.
Flavin mononucleotide (biobased flavin), widely known as FMN, possesses intrinsic fluorescence characteristics. This study presents a sustainable approach for fabricating color-changing intensified light-emitting textiles using the natural compound FMN via digital printing technologies such as inkjet and chromojet. The FMN based ink formulation was prepared at 5 different concentrations using water and glycerol-based systems and printed on cotton duck white (CD), mercerized cotton (MC), and polyester (PET) textile woven samples. After characterizing the printing inks (viscosity and surface tension), the photophysical and physicochemical properties of the printed textiles were investigated using FTIR, UV/visible spectrophotometry, and fluorimetry. Furthermore, photodegradation properties were studied after irradiation under UV (370 nm) and visible (white) light. Two prominent absorption peaks were observed at around 370 nm and 450 nm on K/S spectral curves because of the functionalization of FMN on the textiles via digital printing along with the highest fluorescence intensities obtained for cotton textiles. Before light irradiation, the printed textiles exhibited greenish-yellow fluorescence at 535 nm for excitation at 370 nm. The fluorescence intensity varied as a function of the FMN concentration and the solvent system (water/glycerol). With 0.8 and 1% of FMN, the fluorescence of the printed textiles persisted even after prolonged light irradiation; however, the fluorescence color shifted from greenish-yellow color to turquoise blue then to white, with the fluorescence quantum efficiency values (φ) increasing from 0.1 to a value as high as 1. Photodegradation products of the FMN with varying fluorescence wavelengths and intensities would explain the results. Thus, a color-changing light-emitting fluorescent textile was obtained after prolonged light irradiation of textile samples printed using biobased flavin. Furthermore, multifunctional properties such as antibacterial properties against E. coli were observed only for the printed cotton textile while increased ultraviolet protection was observed for both cotton and polyester printed fabrics for the high concentration of FMN water-based and glycerol-based formulations. The evaluation of fluorescence properties using digital printing techniques aimed to provide more sustainable solutions, both in terms of minimum use of biobased dye and obtaining the maximum yield.


Opening the doors a crack wider: palliative care research data in the public domain.
This report builds further on OPCARE9, an EU 7th framework project aiming to identify knowledge gaps in care provision in the last days of life. This study began with curiosity about new ways of generating research questions to meet future challenges in palliative care (PC) and how to better engage disciplines not generally included in PC research. We here describe an innovative methodological approach to generating data; put data relevant for PC research in the public domain; and raise issues about open access in PC research. We aimed to compile research questions from different disciplines, based on raw data consisting of approximately 1000 descriptions of non-pharmacological caregiving activities (NPCAs), generated through previous research. 53 researchers from different fields were sent the full list of NPCAs and asked to generate research questions from their disciplinary perspective. Responses were received from 32 researchers from 9 countries, generating approximately 170 research topics, questions, reflections and ideas, from a wide variety of perspectives, which are presented here. Through these data, issues related to death and dying are addressed in several ways, in line with a new public health approach. By engaging a broader group of disciplines and facilitating availability of data in the public domain, we hope to stimulate more open dialogue about a wider variety of issues related to death and dying. We also introduce an innovative methodological approach to data generation, which resulted in a response rate at least equivalent to that in our Delphi survey of professionals in OPCARE9.


Effects of detraining on anthropometry, aerobic capacity and functional ability in adults with Down syndrome.
Structured exercise has shown to improve parameters of functional fitness in adults with Down syndrome (DS). However, few, if any, continue to exercise after exercise intervention studies. Consequently, the purpose of this study was to determine the effects of detraining on anthropometry, aerobic capacity and functional ability of adults with DS. In a previous study, forty-two participants either performed 12 weeks of interval training, continuous aerobic training or no training (CON). After 3 months of detraining, the same participants were tested again for anthropometry, aerobic capacity, leg strength and functional ability. Significant reductions in maximal aerobic capacity, time to exhaustion and both functional test items were reported for both exercise groups compared to CON (p < .05). No significant differences were reported between the exercise groups concerning aerobic and functional capacity reductions. Detraining occurred significantly in both exercise groups regarding parameters associated with aerobic and functional capacity.


The association between diabetes mellitus, sugar-sweetened beverages, and tooth loss in adults: Evidence from 18 states.
Sugar-sweetened beverages (SSBs) are dietary sources of sugar that are factors in caries development and tooth loss. Dietary sugar also is linked to diabetes mellitus (DM). There is limited research related to SSBs and tooth loss in people with DM. The authors investigated the association between SSBs and tooth loss as it related to the presence or absence of DM. The authors used a cross-sectional design with data reported by adults (18 years and older) who responded to the 2012 Behavior Risk Factor Surveillance System questionnaire, which was used in 18 states (N = 95,897; 14,043 who had DM and 81,854 who did not have DM). The authors conducted χ2 and logistic regression analyses to determine associations related to DM status. Overall, 12.3% of the survey respondents had DM, 15.5% had 6 or more teeth extracted, and 22.6% reported that they consumed 1 or more SSB daily. In the adjusted analyses, among adults who had DM, those who consumed at least 2 SSBs daily were more likely to have had 6 or more teeth extracted than those who reported that they did not consume SSBs (adjusted odds ratio, 2.35; 95% confidence interval, 1.37 to 4.01; P = .0018). Among adults who did not have DM, those who consumed more than 1 but fewer than 2 SSBs per day were more likely to have had at least 6 teeth extracted (adjusted odds ratio, 1.46; 95% confidence interval, 1.21 to 1.77; P < .0001). The authors found that, among adults with DM, consuming 2 or more SSBs per day was associated with having had 6 or more teeth extracted. Dietary sugar is a concern for oral and systemic health; however, a strong, independent relationship between the number of teeth extracted and a single source of dietary sugar is not adequate to explain the complexity of tooth loss. Clinicians should use broadly worded dietary messages when discussing caries assessment with patients.


NIR hyperspectral imaging and multivariate image analysis to characterize spent mushroom substrate: a preliminary study.
Commercial mushroom growth on substrate material produces a heterogeneous waste that can be used for bioenergy purposes. Hyperspectral imaging in the near-infrared (NHI) was used to experimentally study a number of spent mushroom substrate (SMS) packed samples under different conditions (wet vs. dry, open vs. plastic covering, and round or cuboid) and to explore the possibilities of direct characterization of the fresh substrate within a plastic bag. Principal components analysis (PCA) was used to remove the background of images, explore the important studied factors, and identify SMS and mycelia (Myc) based on the pixel clusters within the score plot. Overview PCA modeling indicated high moisture content caused the most significant effects on spectra followed by the uneven distribution of Myc and the plastic cover. There were well-separated pixel clusters for SMS and Myc under different conditions: dry, wet, or wet and plastic covering. The loading peaks of the related component and the second derivative of the mean spectra of pixel clusters of SMS and Myc indicated that there are chemical differences between SMS and Myc. Partial least squares discriminant analysis (PLS-DA) models were calculated and classification of SMS and Myc was successful, whether the materials were dry or wet. Peak shifts because of high moisture content and unexpected peaks from the plastic covering were found. Although the best results were obtained for dried cylinders, it was shown that almost equally good results could be obtained for the wet material and for the wet material covered by plastic. Furthermore, PLS-DA prediction showed that a side face hyperspectral image could represent the information for the entire SMS cylinder when Myc was removed. Thus, the combination of NHI and multivariate image analysis has great potential to develop calibration models to directly predict the contents of water, carbohydrates, lignin, and protein in wet and plastic-covered SMS cylinders.


A new analysis method for disposition kinetics of enterohepatic circulation of diclofenac in rats.
The pharmacokinetics of diclofenac, which is definitely subject to enterohepatic circulation in rats, was evaluated. The pharmacokinetic model for enterohepatic circulation was constructed in the Laplace-transformed domain by means of the transfer function method of the signal flow. The transformed equations were simultaneously fitted to the time courses of plasma concentration averaged over two groups of rats [i.e. one with an intact enterohepatic circulation and the other without an enterohepatic circulation by means of the bile duct cannula (double-lines fitting)]. The transformed equations were also fitted to each plasma time course in the individual rat (single-line fitting). It was demonstrated that the estimated pharmacokinetic parameters by the single-line fitting almost coincided with those by the double-lines fitting. The local moments for a single pass through enterohepatic circulation were also calculated from the time courses of both the plasma concentration and the amount excreted into the bile. In the nonanesthetized group, the recirculation ratio (Fc) and the mean recirculation time (tc) of diclofenac were estimated to be 21.1% and 4.5 hr, respectively. The absorption ratio (Fa) and the mean absorption time (ta) from the intestinal tract were 52.2% and 4.29 hr, respectively. The experiments using bile duct cannulation revealed that the total amounts excreted into the bile were 14.4% in the anesthetized group and 40.4% in the nonanesthetized group of rats, and that diclofenac was excreted 95% as the glucuronide form and 5% as the intact form in both groups.


Effects of Yoga on Attention, Impulsivity, and Hyperactivity in Preschool-Aged Children with Attention-Deficit Hyperactivity Disorder Symptoms.
Behavioral therapies are first-line for preschoolers with attention-deficit hyperactivity disorder (ADHD). Studies support yoga for school-aged children with ADHD; this study evaluated yoga in preschoolers on parent- and teacher-rated attention/challenging behaviors, attentional control (Kinder Test of Attentional Performance [KiTAP]), and heart rate variability (HRV). This randomized waitlist-controlled trial tested a 6-week yoga intervention in preschoolers with ≥4 ADHD symptoms on the ADHD Rating Scale-IV Preschool Version. Group 1 (n = 12) practiced yoga first; Group 2 (n = 11) practiced yoga second. We collected data at 4 time points: baseline, T1 (6 weeks), T2 (12 weeks), and follow-up (3 months after T2). At baseline, there were no significant differences between groups. At T1, Group 1 had faster reaction times on the KiTAP go/no-go task (p = 0.01, 95% confidence interval [CI], -371.1 to -59.1, d = -1.7), fewer distractibility errors of omission (p = 0.009, 95% CI, -14.2 to -2.3, d = -1.5), and more commission errors (p = 0.02, 95% CI, 1.4-14.8, d = 1.3) than Group 2. Children in Group 1 with more severe symptoms at baseline showed improvement at T1 versus control on parent-rated Strengths and Difficulties Questionnaire hyperactivity inattention (β = -2.1, p = 0.04, 95% CI, -4.0 to -0.1) and inattention on the ADHD Rating Scale (β = -4.4, p = 0.02, 95% CI, -7.9 to -0.9). HRV measures did not differ between groups. Yoga was associated with modest improvements on an objective measure of attention (KiTAP) and selective improvements on parent ratings.


Why carers of people with dementia do not utilise out-of-home respite services.
While many people with dementia require institutional care, having a co-resident carer improves the likelihood that people can live at home. Although caregiving can have positive aspects, carers still report a high need for respite. Despite this need, the use of respite services for carers of people with dementia is often low. This article investigates carer beliefs regarding out-of-home respite services and why some carers do not utilise them. A total of 152/294 (51.7%) carers of community-dwelling people with dementia (NSW, Australia) who were sent a survey completed it (November 2009-January 2010). Despite reporting unmet need for both services, 44.2% of those surveyed were not utilising day respite and 60.2% were not utilising residential respite programmes. Binary logistic regression models were used to examine factors associated with non-use using the Theory of Planned Behaviour within an expanded Andersen Behavioural Model on a final sample of 113 (due to missing data). The model explained 66.9% of the variation for day centres, and 42% for residential respite services. Beliefs that service use would result in negative outcomes for the care recipient were strongly associated with non-use of both day care [OR 13.11; 95% CI (3.75, 45.89)] and residential respite care [OR 6.13; 95% CI (2.02, 18.70)] and were more strongly associated with service non-use than other predisposing, impeding and need variables. For some carers who used services despite negative outcome beliefs, the benefits of respite service use may also be diminished. To improve use of out-of-home respite services in this vulnerable group, service beliefs should be addressed through service development and promotion that emphasises benefits for both carer and care recipients. Future research utilising behavioural service models may also be improved via the inclusion of service beliefs in the study of health and social service use.


Nutritional requirements of human malignant (leukemic) cell lines: implications for adjuvant therapy.
Metabolic requirements of malignant cell lines derived from patients with chronic myelogenous and acute lymphoblastic leukemias were compared to those of proliferating normal cells (mitogen-stimulated human lymphocytes) and circulating blasts from acute myeloblastic and acute lymphoblastic leukemias. Requirements were judged by degree of amino acid (AA) utilization in short-term cultures and assessed by the effect of selective AA deprivation on cell growth. Cell growth was measured by DNA synthesis and growth rate analysis. Six AAs (serine, threonine, methionine, valine, phenylalanine, and lysine) were appreciably utilized (52-87%) by IM-9, CEM, MOLT-4, and K-562 cells, but little or no utilization of these or any other AAs were noted in HSB cells, in leukemic blasts, or in mitogen-stimulated normal lymphocytes in short-term culture. Omission of lysine from culture media greatly inhibited cell growth (DNA synthesis by 91%), and cell density (by 83%) of IM-9 cells. However, omission of lysine, valine, serine, threonine, methionine, or phenylalanine had less of an effect on CEM and MOLT-4 cell lines. These observations demonstrate that under the conditions used the IM-9 cell line is uniquely dependent on extracellular lysine levels in contrast to the other cell lines studied. This suggests that human malignancies other than acute lymphoblastic leukemia which exhibits an obligate dependence on extracellular asparagine might be manageable by enzymatic degradation in vivo or by dietary restriction of indispensable AAs.


Amino acid biosynthetic cost and protein conservation.
Protein products of highly expressed genes tend to favor amino acids that have lower average biosynthetic costs (i.e., they exhibit metabolic efficiency). While this trend has been observed in several studies, the specific sites where cost-reducing substitutions accumulate have not been well characterized. Toward that end, weighted costs in conserved and variable positions were evaluated across a total of 9,119 homologous proteins in four mammalian orders (primate, carnivore, rodent, and artiodactyls), which together contain a total of 20,457,072 amino acids. Degree of conservation at homologous positions in these mammalian proteins and average-weighted cost across all positions within a single protein are significantly correlated. Dividing human genes into two classes (those with and those without CpG islands in their promoters) suggests that humans also preferentially utilize less costly amino acids in highly expressed genes. In contrast to the intuitive expectation that the relatively weak selective force associated with metabolic efficiency would be a selection pressure in complex multicellular organisms, the overall level of selective constraint within the variable regions of mammalian proteins allows the metabolic efficiency to derive a reduction of overall biosynthetic cost, particularly in genes with the highest levels of expression.


Medical students' learning orientation regarding interracial interactions affects preparedness to care for minority patients: a report from Medical Student CHANGES.
There is a paucity of evidence on how to train medical students to provide equitable, high quality care to racial and ethnic minority patients. We test the hypothesis that medical schools' ability to foster a learning orientation toward interracial interactions (i.e., that students can improve their ability to successfully interact with people of another race and learn from their mistakes), will contribute to white medical students' readiness to care for racial minority patients. We then test the hypothesis that white medical students who perceive their medical school environment as supporting a learning orientation will benefit more from disparities training. Prospective observational study involving web-based questionnaires administered during first (2010) and last (2014) semesters of medical school to 2394 white medical students from a stratified, random sample of 49 U.S. medical schools. Analysis used data from students' last semester to build mixed effects hierarchical models in order to assess the effects of medical school interracial learning orientation, calculated at both the school and individual (student) level, on key dependent measures. School differences in learning orientation explained part of the school difference in readiness to care for minority patients. However, individual differences in learning orientation accounted for individual differences in readiness, even after controlling for school-level learning orientation. Individual differences in learning orientation significantly moderated the effect of disparities training on white students' readiness to care for minority patients. Specifically, white medical students who perceived a high level of learning orientation in their medical schools regarding interracial interactions benefited more from training to address disparities. Coursework aimed at reducing healthcare disparities and improving the care of racial minority patients was only effective when white medical students perceived their school as having a learning orientation toward interracial interactions. Results suggest that medical school faculty should present interracial encounters as opportunities to practice skills shown to reduce bias, and faculty and students should be encouraged to learn from one another about mistakes in interracial encounters. Future research should explore aspects of the medical school environment that contribute to an interracial learning orientation.


Management of Brown-Sequard syndrome in cervical disc diseases.
To raise the awareness of the appropriate management of unusual clinical presentation of cervical disc herniation. Seven patients with Brown-Sequard syndrome due to cervical disc herniation presented with Brown-Sequard syndrome had been treated surgically as one of them treated with anterior cervical discectomy and three patients treated by anterior cervical discectomy and fusion while three of them have been treated by posterior laminectomy. Patients were 7 three of them were female and four were males and the mean age of our patients is 45.28 ± 16.49 years ranged between 32 and 72 years. History of spinodegenerative disease in the form of chronic neck pain with or without brachialgia was found in 6/7 patients (85.7%) while history of trauma was found in 5/7 patients (71.4%). Most common affected level is C5-C6 disc Outcome after surgical treatment revealed complete recovery in 4/7 patients (57.1%) while incomplete recovery in 2 patients (28.6%) and no improvement in one patient (14.3%). Brown-Sequard syndrome is a rare presentation of cervical disc herniation but accurate diagnosis, and early anterior spinal cord decompression lead to complete recovery of these cases.


Nocturnal slowing of pulsatile luteinizing hormone secretion in women during the follicular phase of the menstrual cycle.
The gonadotropin secretion pattern in normal reproductive age women (n = 5) was evaluated for the presence of a circadian rhythm. The women volunteered for a series of 24-h admissions in different phases of their menstrual cycles (early follicular, late follicular, and midluteal). Plasma LH and FSH levels were determined by RIA in blood samples drawn through indwelling venous catheters at 20-min intervals throughout a normal 24-h sleep-wake cycle. The gonadotropin secretory pattern was subjected to cosine analysis for identifying rhythmicity. The LH interpulse interval fluctuated with a significant 24-h rhythm during the early follicular phase in four of the five women. The maximum interpulse intervals occurred during the early morning between 0100 and 0500 h (mean, 0250 h), with a corresponding increase in LH pulse amplitude occurring within the same time interval (mean, 0320 h). We found no consistent 24-h rhythms in overall mean plasma LH levels during any phase of the menstrual cycle, nor did we find a significant rhythmicity in either LH interpulse interval or LH pulse amplitude during the late follicular or luteal phase. These results demonstrate that the LH pulse-generating system is frequency modulated on a circadian basis during the early follicular phase of the human menstrual cycle.


Humeral head reconstruction for Hill-Sachs defects: a biomechanical comparison of 2 fixation techniques for bone grafting.
The purpose of this biomechanical study was to compare anterograde with retrograde screw fixation for allograft reconstruction of Hill-Sachs defects. In 8 pairs of fresh-frozen humeral heads, a 40% Hill-Sachs defect was created. The resultant wedge-shaped osteochondral fragment was used as allograft. For each technique, two 3.75-mm screws were used for fixation. To test the strength of fixation, a custom tool was used that would apply load to the graft. By use of a materials testing machine, a staircase cyclic loading protocol was performed (500 cycles at 10, 20, 30, and 40 N) and then load to failure. Graft displacement was measured by an optical tracking system. For the 2 techniques, graft displacement increased with increasing load and increasing number of cycles up to a mean of 0.9 ± 0.42 mm for anterograde fixation and 1.1 ± 0.79 mm for retrograde fixation. This increase was significant within each technique across all 4 loading levels (P < .05). However, there were no significant differences in graft displacement between the 2 techniques at any loading level or number of cycles (P = .16 to P = .96). In addition, the load to failure between the anterograde and retrograde techniques (98.5 N and 95.6 N, respectively) was not significantly different (P = .706). The initial fixation and failure strength of anterograde and retrograde graft fixation techniques for substantial Hill-Sachs defects do not significantly differ in a biomechanical cadaveric model. This biomechanical study supports that in an engaging Hill-Sachs defect, both anterograde and retrograde screw fixation techniques can be used for fixation of humeral head allografts.