Search

The aim of this study was to investigate the relationship between mitochondrial content and respiratory function and whole-body insulin resistance in high-fat diet (HFD) fed rats. Male Wistar rats were given either a chow diet or an HFD for 12 weeks. After 4 weeks of the dietary intervention, half of the rats in each group began 8 weeks of interval training. In vivo glucose and insulin tolerance were assessed. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by the measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS). We found HFD rats had impaired glucose and insulin tolerance but increased mitochondrial respiratory function and increased protein expression of components of the ETS. This was accompanied by an increase in CS activity in WG. Exercise training improved glucose and insulin tolerance in the HFD rats. Mitochondrial respiratory function was increased with exercise training in the chow-fed animals in soleus muscle. This exercise effect was absent in the HFD animals. In conclusion, exercise training improved insulin resistance in HFD rats but without changes in mitochondrial respiratory function and content. The lack of an association between mitochondrial characteristics and whole-body insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that improvements in mitochondrial respiratory function and content are not responsible for improvements in whole-body insulin resistance in HFD rats.

BACKGROUND Colorectal cancer (CRC) rates are increasing in individuals below the age of 50 and this trend has been projected to continue for the foreseeable future. Health officials are calling for increased awareness of rising rates in affected populations to promote discussion and early detection. METHODS In May 2018, we surveyed an online purposive sample of adults below the age of 50 (N = 624). We conducted an exploratory analysis examining knowledge of current CRC screening guidelines, knowledge of available CRC screening methods, perceived risk of CRC, and perceived importance of screening for CRC by gender, race, and previous CRC screening activity. RESULTS The sample was 56% female, averaged 36 years of age, largely identified as Caucasian (84%), married (48%), and well educated (70% with some college or a college degree). 36% correctly identified the current age of recommended CRC screening initiation. Few (8%) correctly identified all CRC screening options presented. Genetics was thought to be the most relevant determinant of CRC. African American or black participants perceived themselves to be at lower risk of CRC, while women rated the importance of screening significantly lower than men. CONCLUSION We identified a lack of CRC knowledge in individuals below the age of 50. Interventions should correct perceptions of risk of CRC and highlight the importance of screening. Complete knowledge of the range of screening options may reduce barriers to screening while a greater knowledge of modifiable risk factors of CRC can promote healthy behaviors.

Key points Paternal obesity negatively influences metabolic outcomes in adult rat offspring.Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers.Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring.Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers.This paper presents a feasible, low‐cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity. Abstract We investigated whether maternal exercise before and during gestation could attenuate the negative metabolic effects of paternal high‐fat diet‐induced obesity in female adult rat offspring. Fathers consumed a normal chow or high‐fat diet before mating. Mothers exercised on a treadmill before and during gestation or remained sedentary. In adulthood, female offspring were assessed using intraperitoneal insulin and glucose tolerance tests (IPITT and IPGTT, respectively), pancreatic morphology, ex vivo skeletal muscle insulin‐stimulated glucose uptake and mitochondrial respiratory function. Paternal obesity impaired whole‐body and skeletal muscle insulin sensitivity and insulin secretion in adult offspring. Maternal exercise attenuated the lower insulin‐stimulated glucose uptake in offspring sired by obese fathers but distal insulin signalling components (p‐AKT Thr308 and Ser473, p‐TBC1D4 Thr642 and GLUT4) remained unchanged (P > 0.05). Maternal exercise increased citrate synthase activity only in offspring sired by obese fathers. Maternal exercise also reversed the lower insulin secretion in vivo observed in offspring of obese fathers, probably due to an attenuation of the decrease in pancreatic beta cell mass. In summary, maternal exercise before and during pregnancy in rats attenuated skeletal muscle insulin resistance and attenuated the decrease in pancreatic beta cell mass and insulin secretion observed in the female offspring of obese fathers., Key points Paternal obesity negatively influences metabolic outcomes in adult rat offspring.Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers.Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring.Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers.This paper presents a feasible, low‐cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity.

Objective The aim of this study was to compare diurnal salivary cortisol among high-risk occupational police specialties and the general population (n = 18,698). Methods Tactical and frontline officers provided salivary cortisol samples for 2 days (four times: wake, 30 minutes, 11 hours, and 17 hours post-awakening) and were compared with a general population sample of group field studies utilizing similar methodology. Samples were analyzed for free cortisol concentrations (nmol/L) using chemiluminescence immunoassay. Results Repeated-measures mixed-model analysis of variance (ANOVA) revealed significantly greater salivary diurnal cortisol among tactical than frontline officers. Furthermore, both tactical and frontline officers had higher cortisol levels on average at all time points than the general population sample. Conclusion Results suggest that diurnal cortisol response may be associated with level of risk exposure in hazardous occupational subspecialties within policing compared with the general population.

KEY POINTS A paternal high-fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect with respect to reprogramming adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance as a result of having a high-fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalize the reduced adult pancreatic beta cell mass as a result of having a high-fat fed/obese father. Early-life exercise training may be able to reprogram an individual whose father was obese, inducing long-lasting beneficial effects on health. ABSTRACT A paternal high-fat diet (HFD) impairs female rat offspring glucose tolerance, pancreatic morphology and insulin secretion. We examined whether only 4 weeks of exercise early in life could reprogram these negative effects. Male Sprague-Dawley rats consumed a HFD for 10 weeks before mating with chow-fed dams. Female offspring remained sedentary or performed moderate intensity treadmill exercise (5 days week-1 , 60 min day-1 , 20 m min-1 ) from 5 to 9 weeks of age. Paternal HFD impaired (P < 0.05) adult offspring whole body insulin sensitivity (i.p. insulin sensitivity test), as well as skeletal muscle ex vivo insulin sensitivity and TBC1D4 phosphorylation. It also lowered β-cell mass and reduced in vivo insulin secretion in response to an i.p. glucose tolerance test. Early-life exercise in offspring reprogrammed the negative effects of a paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin-stimulated glucose uptake and TBC1D4 phosphorylation and also increased glucose transporter 4 protein. However, early exercise did not normalize the reduced pancreatic β-cell mass or insulin secretion. In conclusion, only 4 weeks of exercise early in life in female rat offspring reprograms reductions in insulin sensitivity in adulthood caused by a paternal HFD without affecting pancreatic β-cell mass or insulin secretion.

Aim Exercise is able to increase both muscle protein synthesis and mitochondrial biogenesis. However, acidosis, which can occur in pathological states as well as during high‐intensity exercise, can decrease mitochondrial function, whilst its impact on muscle protein synthesis is disputed. Thus, the aim of this study was to determine the effect of a mild physiological decrease in pH, by administration of ammonium chloride, on myofibrillar and mitochondrial protein synthesis, as well as associated molecular signaling events. Methods Male Wistar rats were given either a placebo or ammonium chloride prior to a short interval training session. Rats were killed before exercise, immediately after exercise, or 3 h after exercise. Results Myofibrillar (p = 0.036) fractional protein synthesis rates was increased immediately after exercise in the soleus muscle of the placebo group, but this effect was absent in the ammonium chloride group. However, in the gastrocnemius muscle NH4Cl increased myofibrillar (p = 0.044) and mitochondrial protein synthesis (0 h after exercise p = 0.01; 3 h after exercise p = 0.003). This was accompanied by some small differences in protein phosphorylation and mRNA expression. Conclusion This study found ammonium chloride administration immediately prior to a single session of exercise in rats had differing effects on mitochondrial and myofibrillar protein synthesis rates in soleus (type I) and gastrocnemius (type II) muscle in rats., Ammonium chloride administration immediately prior to a single session of exercise in rats had differing effects on mitochondrial and myofibrillar protein synthesis rates in soleus (type I) and gastrocnemius (type II) muscle in rats.

IntroductionSex hormone binding globulin (SHBG) levels are reported to be inversely associated with diabetes risk. It is unknown whether diabetes prevention interventions increase SHBG and whether resultant changes in SHBG affect diabetes risk. The purpose of this analysis was to determine whether intensive lifestyle intervention (ILS) or metformin changed circulating SHBG and if resultant changes influenced diabetes risk in the Diabetes Prevention Program (DPP).Research design and methodsThis is a secondary analysis from the DPP (1996–2001), a randomized trial of ILS or metformin versus placebo on diabetes risk over a mean follow-up of 3.2 years. The DPP was conducted across 27 academic study centers in the USA. Men, premenopausal and postmenopausal women without hormone use in the DPP were evaluated. The DPP included overweight/obese persons with elevated fasting glucose and impaired glucose tolerance. Main outcomes measures were changes in SHBG levels at 1 year and risk of diabetes over 3 years.ResultsILS resulted in significantly higher increases (postmenopausal women: pConclusionsLifestyle intervention may be associated with favorable changes in circulating SHBG, which is largely due to changes in adiposity. Changes in circulating SHBG do not independently predict reductions in diabetes incidence.

Studies suggest protein intake may be associated with lower body weight, but protein has also been associated with preservation of lean body mass. Understanding the role of protein in maintaining health for older adults is important for disease prevention among this population. Cross-sectional study of the relationship of dietary protein on body composition. New York City community centers. 1,011 Black, White, and Latino urban men and women 60-99 years of age. Protein intake was assessed using two interviewer-administered 24-hour recalls, and body composition was assessed using bioelectrical impedance analysis (BIA) of fat mass (kg) (FM), fat free mass (kg) (FFM), and impedance resistance (Ohms). Indices of FM and FFM were calculated by dividing BIA measurements by height squared (m2), and percent FFM was calculated by dividing FFM by the sum of FM and FFM. Log linear models adjusting for age (continuous), race/ethnicity, education, physical activity (dichotomized at the median), hypertension, diabetes, and total calories (continuous). Just 33% of women and 50% of men reported meeting the RDA for protein. Both fat free mass index (FFMI) and fat mass index (FMI) were negatively associated with meeting the RDA for protein (Women: FFMI -1.78 95%CI [-2.24, -1.33], FMI -4.12 95% CI [-4.82, -3.42]; Men: FFMI -1.62 95% CI [-2.32, -0.93] FMI -1.80 95% CI [-2.70, -0.89]). After accounting for confounders, women and men consuming at least 0.8 g/kg/day had a 6.2% (95% CI: 5.0%, 7.4%) and a 3.2% (95% CI 1.1%, 5.3%) higher percent fat free mass, respectively. FFM, FFMI, FM, and FMI were inversely related to meeting the RDA for protein. Meeting the RDA for protein of at least 0.8g/kg/day was associated with a higher percentage of fat free mass among older adults. These results suggest meeting the protein recommendations of at least 0.8 g/kg/day may help to promote lower overall body mass, primarily through loss of fat mass rather than lean mass.

To determine the prevalence of glaucoma among patients referred to a glaucoma service with suspicious disc photographs from the diabetic retinopathy (DR) screening program.A clinical audit of all patients attending a single-center DR screening program in the Mater Misericordiae University Hospital, Dublin, between July 2010 and October 2011 was conducted with a minimum follow-up of 30 months. The DR screening service uses trained technician graders to assess 2-field color retinal photographs for the features of DR. Recently, the service was enhanced so that optic discs are also assessed for signs of glaucoma.In the 16-month study period, 3,697 diabetic patients were photographed. Following photograph grading, 91 (2.46%) were judged to require referral for assessment at the glaucoma clinic. Of these, 63 (69.23%) presented for assessment. Thirteen patients (20.63%) were diagnosed with glaucoma, comprising 7 cases of low-tension glaucoma and 6 cases of primary open-angle glaucoma. Thirty-six patients (57.14%) were classified as glaucoma suspects and 14 patients (22.22%) were discharged back to the DR screening program following normal ocular examination. Only 6 (9.52%) of the 63 patients examined had an intraocular pressure greater than 21 mm Hg.The assessment of DR screening photographs for signs of glaucomatous optic nerve damage should be considered as part of a strategy to improve glaucoma case detection and to reduce the burden of this disease on society.

Objectives: The aim of this study was to test an intervention modifying officer physiology to reduce lethal force errors and improve health. Methods: A longitudinal, within-subjects intervention study was conducted with urban front-line police officers (n = 57). The physiological intervention applied an empirically validated method of enhancing parasympathetic engagement (ie, heart rate variability biofeedback) during stressful training that required lethal force decision-making. Results: Significant post-intervention reductions in lethal force errors, and in the extent and duration of autonomic arousal, were maintained across 12 months. Results at 18 months begin to return to pre-intervention levels. Conclusion: We provide objective evidence for a physiologically focused intervention in reducing errors in lethal force decision-making, improving health and safety for both police and the public. Results provide a timeline of skill retention, suggesting annual retraining to maintain health and safety gains.

Odontomas are the most common odontogenic tumors, typically diagnosed during the first two decades of life. 1 The purpose of this paper was to report an interesting case of an eight-year-old Caucasian boy who presented with an asymptomatic, progressive, firm swelling of the right maxilla with no eruption of the permanent maxillary right lateral incisor. Radiographic investigation revealed a mixed radiolucent and radiopaque lesion measuring 28 by 24 by 17 mm with a corticated border causing expansion and thinning of the buccal cortical plate. This large bag-of-marbles-like appearance representing odontoids was impeding his adult teeth from erupting; hence, complete surgical removal under general anesthesia was the treatment of choice. Removal of the lesion resulted in an unexpected loss of the embedded permanent maxillary right lateral incisor. Histopathological investigations gave a diagnosis of compound odontoma; due to their low growth potential, recurrence after removal is not expected.

Adolescents' neural substrates of emotional reactions to the consequences of risky decisions are poorly understood. In this functional magnetic resonance imaging study, 30 late adolescents and 30 young adults made risky and neutral decisions in social scenarios and received valenced outcomes. Negative outcomes in risky decisions eliciting regret, as compared with negative outcomes in neutral decisions eliciting disappointment, activated executive control (orbitofrontal cortex) and self-relevance regions (middle temporal gyrus [MTG], posterior cingulate cortex, and precuneus) for both age groups. Young adults showed more activation than adolescents in regret and disappointment as compared with relief and elation conditions in the avoidance (insula), action monitoring (inferior frontal gyrus, pre-SMA, and caudate), and social-cognition regions (superior temporal sulcus and MTG). These late socio-emotional developments may pave the way for more adaptive decision-making behavior in social contexts.

PurposeTo evaluate the clinical outcome of patients with venous malformation (VM) involving the eyelid treated with bleomycin sclerotherapy.MethodsA retrospective review was performed of 18 consecutive patients with VM involving the eyelid who underwent bleomycin sclerotherapy. Patients’ clinical presentation, details of sclerotherapy, and post-sclerotherapy resolution of the lesion as well as any procedure-related complications were evaluated.ResultsTwelve women and six men of mean age 34.3±20.4 years underwent sclerotherapy with bleomycin. Chief complaints were cosmetic disfigurations with or without hemifacial deformity (n=2), pain in engorgement area (n=2), pain and swelling from venous thrombosis (n=2), swelling or engorgement obstructing their eyesight (n=2), or eyelid dysfunction (n=1). The lesions were only in the eyelid in three patients; otherwise they were extended out of the eyelid either superiorly (n=3), laterally (n=8), inferiorly (n=8), and/or posteriorly to the orbit (n=8) to various extents. Conjunctival involvement was present in 13 patients. 14 patients had received prior treatments including surgery, laser therapy, or non-bleomycin sclerotherapy. With an average three sessions of bleomycin sclerotherapy (average total dose 34.5 mg), more than 80% shrinkage was observed in seven patients (38.9%), 50–80% shrinkage in eight patients (44.4%), and 30–50% shrinkage in two patients (11.1%). One patient had recurrence, which was successfully treated again with bleomycin. No procedure-related complications were noted.ConclusionsThe use of bleomycin appears to be a simple, safe, and effective treatment for venous malformations involving the eyelid, avoiding more elaborate and challenging surgical or laser interventions, and is even effective in full thickness lesions.

Background Patients and families can make discriminatory comments leading to physician distress. Residents receive little training in appropriate responses to such comments and may be ill equipped to respond to intolerance without alienating the individual(s) making the comments. Objective We assessed whether a simulated curriculum would enhance pediatrics residents' ability to effectively respond to discriminatory comments. Methods In the 2016–2017 academic year, we modified an existing communication skills curriculum for senior pediatrics residents. Residents engaged a simulated parent who used discriminatory speech in 4 scenarios, followed by a group debriefing. We conducted anonymous surveys to assess residents' preparedness to respond to these comments before and immediately following participation and examined their experience with discriminatory comments in the workplace. Results The majority of residents reported prior experience with discriminatory comments (32 of 45 [71%] witnessed such comments, and 27 of 48 [56%] were targeted by such comments), most often regarding age, race, and ethnicity. Mean precourse scores ranged from 2.1 to 3.1 (on a 5-point scale) regarding ability to engage in a firm yet respectful dialogue, to reference the hospital code of conduct, to coach a learner to respond, and to facilitate a team debrief. Mean postcourse scores improved significantly for these questions (range 3.8–4.1). The greatest improvement was in referencing the code of conduct (2.1 versus 4.0, P < .001). Conclusions Immediately after participating in simulation, pediatrics residents reported a significant improvement in self-reported readiness to respond to discriminatory comments made by a parent and reported the simulation experience was beneficial.

Objectives Assess differences in perceived health status among individuals receiving colonoscopy screening based on smoking status. Study design Cross-sectional data were collected as part of a larger study investigating whether verbal and non-verbal communication and behaviors of gastroenterologists and nurses. Method Data for this study were collected between 2011 and 2013 among receiving colonoscopy screenings. Data were collected as part of a study assessing patients ( n = 1785) undergoing colonoscopy screenings about their expectations, concerns, understanding of the procedure, and perceived health status. Differences between current, former and never smokers were analyzed using a one-way between subjects ANOVA, with a Scheffe post hoc. Results Post hoc analyses revealed that current smokers were significantly different from former or never smokers on the following variables: days their physical health was not good, days their mental health was not good, days health influenced their activities, days pain influenced their ability to perform activities, perceived general health, and current anxiety. Conclusion This study looked at perceived health among individuals receiving colonoscopy screening by on smoking status, a relevant population based on the recent Surgeon Generals link. Former smokers reported similar health status across all variables as never smokers, suggesting the effect of quitting smoking on self-perceived health. With this link, tailored smoking cessation messages to smokers receiving colonoscopy screenings may be an excellent vantage point for a smoking cessation intervention.

Objectives. We aimed to highlight sociodemographic differences in how patients access colonoscopy. Methods. We invited all eligible patients (n = 2500) from 2 academy-affiliated colonoscopy centers in Alachua County, Florida (1 free standing, 1 hospital based), to participate in a precolonoscopy survey (September 2011–October 2013); patients agreeing to participate (n = 1841, response rate = 73.6%) received a $5.00 gift card. Results. We found sociodemographic differences in referral pathway, costs, and reasons associated with obtaining the procedure. Patients with the ideal pathway (referred by their regular doctor for age-appropriate screening) were more likely to be Black (compared with other minorities), male, high income, employed, and older. Having the colonoscopy because of symptoms was associated with being female, younger, and having lower income. We found significant differences for 1 previously underestimated barrier, having a spouse to accompany the patient to the procedure. Conclusions. Patients’ facilitators and barriers to colonoscopy differed by sociodemographics in our study, which implies that interventions based on a single facilitator will not be effective for all subgroups of a population.

Parasitic helminths are extremely resilient in their ability to maintain chronic infection burdens despite (or maybe because of) their hosts’ immune response. Explaining how parasites maintain these lifelong infections, identifying the protective immune mechanisms that regulate helminth infection burdens, and designing prophylactics and therapeutics that combat helminth infection, while preserving host health requires a far better understanding of how the immune system functions in natural habitats than we have at present. It is, therefore, necessary to complement mechanistic laboratory-based studies with studies on wild populations and their natural parasite communities. Unfortunately, the relative paucity of immunological tools for non-model species has held these types of studies back. Thankfully, recent progress in high-throughput ‘omics platforms provide powerful and increasingly practical means for immunologists to move beyond traditional lab-based model organisms. Yet, assigning both metabolic and immune function to genes, transcripts, and proteins in novel species and assessing how they interact with other physiological and environmental factors requires identifying quantitative relationships between their expression and infection. Here, we used supervised machine learning to identify gene networks robustly associated with burdens of the gastrointestinal nematode Heligmosomoides polygyrus in its natural host, the wild wood mice Apodemus sylvaticus. Across 34 mice spanning two wild populations and across two different seasons, we found 17,639 transcripts that clustered in 131 weighted gene networks. These clusters robustly predicted H. polygyrus burden and included well-known effector and regulatory immune genes, but also revealed a number of genes associated with the maintenance of tissue homeostasis and hematopoiesis that have so far received little attention. We then tested the effect of experimentally reducing helminth burdens through drug treatment on those putatively protective immune factors. Despite the near elimination of H. polygyrus worms, the treatment had surprisingly little effect on gene expression. Taken together, these results suggest that hosts balance tissue homeostasis and protective immunity, resulting in relatively stable immune and, consequently, parasitological profiles. In the future, applying our approach to larger numbers of samples from additional populations will help further increase our ability to detect the immune pathways that determine chronic gastrointestinal helminth burdens in the wild.

Microbial keratitis (MK) is a sight-threatening emergency. Delayed diagnosis and treatment may exacerbate the condition and infection may spread to the posterior segment with resultant endophthalmitis. We describe the presentation, management, visual outcomes and microbial profiles of MK-associated endophthalmitis presenting to a tertiary referral centre.Prospective collection of data on all patients presenting with presumed MK-associated endophthalmitis from 1997 to 2007, to the Royal Victorian Eye and Ear Hospital. Outcome measures included: visual acuity, microbial profiles, and management strategy.Thirty-seven cases of MK-associated endophthalmitis were identified over the study period, with a mean age of 73 years and 19 were male. Presenting acuities ranged from Snellen 2/60 to no perception of light (NPL). Thrity-four (91.9%) patients had a prior history of ocular disease. Identifiable non-ocular risk factors were present in 31 (83.8%), including steroid use, dementia, nursing home care or relative systemic immunosuppression. A culture positivity rate of 83.8% was recorded. The most common organisms identified included: Streptococcal species in 12 (32.4%), Pseudomonas aeruginosa in 11 (29.7%), and Staphylococcus aureus in eight (21.6%). Final acuities ranged from 6/36 to NPL. Sixteen (43.2%) eyes were eviscerated/enucleated as primary treatment. Overall, 23 (62.2%) patients required evisceration/enucleation, of which nine (39.1%) were due to Pseudomonas aeruginosa and seven (30.4%) to Streptococcal species (Streptococcal pneumonia).MK-associated endophthalmitis is a serious ocular condition occurring more frequently in elderly populations, and those with long standing severe pre-existing ocular disease. Visual outcomes are poor, often requiring evisceration/enucleation.

Some studies have reported that understanding concrete action-related words and sentences elicits activations of motor areas in the brain. The present fMRI study goes one step further by testing whether this is also the case for comprehension of nonfactual statements. Three linguistic structures were used (factuals, counterfactuals, and negations), referring either to actions or, as a control condition, to visual events. The results showed that action sentences elicited stronger activations than visual sentences in the SMA, extending to the primary motor area, as well as in regions generally associated with the planning and understanding of actions (left superior temporal gyrus, left and right supramarginal gyri). Also, we found stronger activations for action sentences than for visual sentences in the extrastriate body area, a region involved in the visual processing of human body movements. These action-related effects occurred not only in factuals but also in negations and counterfactuals, suggesting that brain regions involved in action understanding and planning are activated by default even when the actions are described as hypothetical or as not happening. Moreover, some of these regions overlapped with those activated during the observation of action videos, indicating that the act of understanding action language and that of observing real actions share neural networks. These results support the claim that embodied representations of linguistic meaning are important even in abstract linguistic contexts.

A growing body of literature shows that the emotional content of verbal material affects reading, wherein emotional words are given processing priority compared to neutral words. Human emotions can be conceptualised within a two-dimensional model comprised of emotional valence and arousal (intensity). These variables are at least in part distinct, but recent studies report interactive effects during implicit emotion processing and relate these to stimulus-evoked approach-withdrawal tendencies. The aim of the present study was to explore how valence and arousal interact at the neural level, during implicit emotion word processing. The emotional attributes of written word stimuli were orthogonally manipulated based on behavioural ratings from a corpus of emotion words. Stimuli were presented during an fMRI experiment while 16 participants performed a lexical decision task, which did not require explicit evaluation of a word′s emotional content. Results showed greater neural activation within right insular cortex in response to stimuli evoking conflicting approach-withdrawal tendencies (i.e., positive high-arousal and negative low-arousal words) compared to stimuli evoking congruent approach vs. withdrawal tendencies (i.e., positive low-arousal and negative high-arousal words). Further, a significant cluster of activation in the left extra-striate cortex was found in response to emotional than neutral words, suggesting enhanced perceptual processing of emotionally salient stimuli. These findings support an interactive two-dimensional approach to the study of emotion word recognition and suggest that the integration of valence and arousal dimensions recruits a brain region associated with interoception, emotional awareness and sympathetic functions., Highlights • Emotional valence and arousal affect reading interactively. • Positive high-arousal and negative low-arousal words evoke conflicting reactions. • Enhanced right insula activation was found in response to conflicting stimuli. • Insula integrates viscero-sensory and cognitive/evaluative information. • Enhanced extra-striate cortex activation was found for emotional than neutral words.

Clinical guidelines for prostate cancer screening (PCS) advise physicians to discuss the potential harms and benefits of screening. However, there is a lack of training programs for informed decision-making (IDM), and it is unknown which IDM behaviors physicians have the most difficulty performing. Identifying difficult behaviors can help tailor training programs. In the context of developing a physician-IDM program for PCS, we aimed to describe physicians’ use of nine key IDM behaviors for the PCS discussion and to examine the relation between the behaviors and physician characteristics. A cross-sectional sample of The American Academy of Family Physicians National Research Network completed surveys about their behavior regarding PCS (N = 246; response rate = 58 %). The surveys included nine physician key IDM behaviors for PCS and a single-item question describing their general practice style for PCS. The most common IDM behavior was to invite men to ask questions. The two least common reported behaviors concerned patients uncertain about screening (i.e., arrange follow-up and provide additional information for undecided men). Physicians reported difficulty with these two behaviors regardless whether they reported to discuss or not to discuss PCS with patients. Reported use of key IDM behaviors was associated with a general practice style for PCS and being affiliated with a residency-training program. Physician training programs for IDM should include physician skills to address the needs of patients uncertain about screening. Future research should determine if actual behavior is associated with self-reported behavior for the PCS discussion.

Immune function is an important component of host fitness, and high investment in immunity should occur when the benefits outweigh the costs, such as when risk of parasitism is high. We sampled two rodent hosts, white-footed mice (Peromyscus leucopus), and prairie voles (Microtus ochrogaster), and their tick, flea, and mite ectoparasites. A bacterial killing assay was used to measure the host's innate immune function. We hypothesized that classes of hosts (species, sexes, or age classes) with overall higher tick burdens would have a higher innate immune function as an evolutionary response to historically greater exposure. We hypothesized a weaker relationship between the fleas and mites and immune function because of high host specificity in fleas and the absence of known vector function in North American mites. Ectoparasites were significantly overdispersed on hosts. In accordance with our hypothesis, Peromyscus that had higher tick burdens also exhibited significantly higher bacterial killing ability compared to Microtus. There was no significant difference in total flea burden between rodent species and no relationship with bacterial killing ability. Microtus had higher burdens of mites in each order than Peromyscus, and female rodents had higher mite burdens than males. The benefits of maintaining high levels of innate immune factors appear to be greater than the energetic costs for Peromyscus compared to Microtus.

Homonymous visual field defects (HVFD) are common and frequently occur after cerebrovascular accidents. They significantly impair visual function and cause disability particularly with regard to visual exploration. The purpose of this study was to assess a novel interventional treatment of monocular prism therapy on visual functioning in patients with HVFD of varied etiology using vision targeted, health-related quality of life (QOL) questionnaires. Our secondary aim was to confirm monocular and binocular visual field expansion pre- and posttreatment.Twelve patients with acquired, documented HVFD were eligible to be included. All patients underwent specific vision-targeted, health-related QOL questionnaire and monocular and binocular Goldmann perimetry before commencing prism therapy. Patients were fitted with monocular prisms on the side of the HVFD with the base-in the direction of the field defect creating a peripheral optical exotropia and field expansion. After the treatment period, QOL questionnaires and perimetry were repeated.Twelve patients were included in the treatment group, 10 of whom were included in data analysis. Overall, there was significant improvement within multiple vision-related, QOL functioning parameters, specifically within the domains of general health (p0.01), general vision (p0.05), distance vision (p0.01), peripheral vision (p0.05), role difficulties (p0.05), dependency (p0.05), and social functioning (p0.05). Visual field expansion was shown when measured monocularly and binocularly during the study period in comparison with pretreatment baselines.Patients with HVFD demonstrate decreased QOL. Monocular sector prisms can improve the QOL and expand the visual field in these patients.

This study provides implicit verb causality norms for a corpus of 305 English verbs. A web-based sentence completion study was conducted, with 96 respondents completing fragments such as "John liked Mary because..." The resulting bias scores are provided as supplementary material in the Psychonomic Society Archive, where we also present lexical and semantic verb features, such as the frequency, semantic class and emotional valence. Our results replicate those of previous studies with much smaller numbers of verbs and respondents. Novel effects of gender and its interaction with verb valence illustrate the type of issues that can be investigated using stable norms for a large number of verbs. The corpus will facilitate future studies in a range of areas, including psycholinguistics and social psychology.

Endogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre. A prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate. In total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiellaspecies. Better visual outcome was documented in fungal cases. EE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.

Aim The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Methods Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively. Results Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L−1; P = .001) and insulin sensitivity decreased (25 ± 7%, P < .05) following the night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II‐V) or insulin‐stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). Conclusion Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D.

Objective To assess the content of counseling about prostate-specific antigen (PSA) screening. Guidelines recommend informed consent before screening because of concerns about benefits versus risks. As part of the professional practice standard for informed consent, clinicians should include content customarily provided by experts. Methods 40 transcripts of conversations between medicine residents and standardized patients were abstracted using an instrument derived from an expert Delphi panel that ranked 10 “facts that experts believe men ought to know.” Results Transcripts contained definite criteria for an average of 1.7 facts, and either definite or partial criteria for 5.1 facts. Second- and third-year residents presented more facts than interns (p = 0.01). The most common facts were “false positive PSA tests can occur” and “use of the PSA test as a screening test is controversial.” There was an r = 0.88 correlation between inclusion by residents and the experts’ ranking. Conclusion Counseling varied but most transcripts included some expert-recommended facts. The absence of other facts could be a quality deficit or an effort to prioritize messages and lessen cognitive demands on the patient. Practice implications Clinicians should adapt counseling for each patient, but our abstraction approach may help to assess the quality of informed consent over larger populations.

OBJECTIVE To compare the weight and height gain and the frequency of clinical complications in preterm newborns weighing less than 1,500 g, exclusively fed human milk or fortified human milk until reaching 1,800 g. METHODS Prospective double-blind randomized controlled trial involving 40 preterm infants weighing < 1,500 g at birth and

Inferences during discourse comprehension are needed to connect subsequent sentences to each other. Previous studies have implicated the dorso-medial prefrontal cortex (dmPFC) as important for successful coherence building. The present study addressed the question of whether the dmPFC activation could be modulated by the task instructions or whether it was a function of stimulus properties. In a graded coherence judgment task, participants rated on a 4-point scale the closeness of the pragmatic connection between subsequent sentences. 75% of the sentence pairs had previously been identified as incoherent, so that some creativity was needed for finding a pragmatic connection. Of particular interest were the incoherent sentence pairs rated as somewhat related, because this novel condition allowed to separate stimulus properties from the inference success. Compared to the unrelated sentence pairs, this condition elicited increased activation in fronto-parietal regions related to executive functions, reflecting the difficulty of the search for coherence. Compared to coherent sentence pairs, activations in the bilateral fusiform gyri were found. This suggests a role for visual and spatial situation model building during inferencing. Most importantly, the time course of the signal change in the fronto-medial cortex confirmed that all rating conditions engaged this brain region to an equal degree, and that the process extended throughout the relatively long decision period. These results confirm that the dmPFC activation can be modulated by task instructions and that it reflects non-automatic cognitive processes, subserving the integration between external stimulation and idiosyncratic response criteria.

Background. A 7-year old boy was referred with retained maxillary right primary central and lateral incisors. Radiographic exam revealed a large calcified radio-opaque mass overlying the roots of these primary teeth preventing the permanent teeth from erupting. Case Report. The purpose of this paper is to describe the pre-operative use of multi-directional cross-sectional tomography in establishing the relationship between a large complex odontome that was preventing the eruption of a maxillary permanent central incisor. Conclusion. Low dose, multi-directional cross-sectional tomography was beneficial in visualisation of the precise relationship between the large complex odontome and the unerupted permanent incisor. This allowed correct judgement of the position on the odontome prior to its surgical removal.

Objective Colonoscopy is a complex procedure that requires bowel preparation, sedation, and has the potential for substantial risk. Given this, we investigated colonoscopy patients' perceived and actual understanding of the procedure. Methods Consecutive colonoscopy patients were enrolled and surveyed, with their caregivers, immediately prior to their procedure. Demographics, health literacy, socioeconomic status and perceived risks/benefits were assessed. Thematic analysis was conducted on open-ended responses and a 3-level outcome variable was created to categorize correctness of patients' and caregivers' understanding. Multinomial logistic regression was used to determine predictors of response level. Results Patients ( N =1821) were 77% White, 60% female, and averaged 54 years old; caregivers were demographically similar. Among patients, bivariate analysis revealed that younger age, minority race, and low income, education, and health literacy were associated with incomplete understanding. Multinomial regression revealed that age, education, health literacy, first-time colonoscopy, and perceived risk-benefit difference discriminated among groups. Bivariate and multinomial results for caregivers were similar. Conclusion Patients and caregivers varied on information, understanding and misconceptions about colonoscopy. Implications are discussed for inadequate: 1. informed consent, 2. bowel preparation, and 3. emotional preparation for cancer detection or adverse events. Practice Implications Attention should be paid to patients' understanding of the purpose, anatomy, and logistics of colonoscopy, preferably prior to bowel preparation.

Veillonella spp. are predominant bacteria found in all oral biofilms. In this study, a metatranscriptomic approach was used to investigate the gene expression levels of three oral Veillonella spp. (V. parvula, V. dispar and V. atypica) in whole stimulated saliva from caries-free volunteers and in carious lesions (n = 11 for each group). In the lesions the greatest proportion of reads were assigned to V. parvula and genes with the highest level of expression in carious samples were those coding for membrane transport systems. All three Veillonella spp. increased expression of genes involved in the catabolism of lactate and succinate, notably the alpha- and beta-subunits of L(+)-tartrate dehydratase (EC 4.2.1.32). There was also significantly increased expression of histidine biosynthesis pathway in V. parvula, suggesting higher intra-cellular levels of histidine that could provide intra-cellular buffering capacity and, therefore, assist survival in the acidic environment. Various other systems such as potassium uptake systems were also up regulated that may aid in the survival and proliferation of V. parvula in carious lesions.

Continuous peripheral nerve block (CPNB) is an optimal choice for analgesia after orthopedic procedures, but is not commonly used in outpatients because of concern regarding the possibility of catheter-related complications. In addition, it may be difficult to provide adequate patient access to physicians in this setting. We present 620 outpatients who were treated with CPNB using an established protocol.All catheters were placed using direct ultrasound visualization. These patients received extensive oral and written preoperative instruction and were provided continuous telephone access to the anesthesiologist during the postoperative period. All patients were also contacted at home by telephone on the first postoperative day. In addition, each patient was seen and examined by the surgeon within 2 wk of hospital discharge.Of the 620 patients, there were 190 interscalene (brachial plexus), 206 fascia iliaca (femoral nerve), and 224 popliteal fossa (sciatic nerve) catheters. Two patients (0.3%) had complications related to the nerve block. In both of these patients, the symptoms resolved within 6 wk of surgery. Twenty-six patients (4.2%) required postoperative interventions by the anesthesiologist. One patient returned to the hospital for catheter removal.In this large series of outpatients treated with CPNB, there were surprisingly few interventions requiring an anesthesiologist. Likewise, patients were able to manage and remove their catheters at home without additional follow-up. This suggests that with adequate instruction and telephone access to health care providers, patients are comfortable with managing and removing CPNB catheters at home.

Summary. Sotos syndrome, or cerebral gigantism, is a rare genetic condition characterized by tall stature, gigantism, dolichocephaly, advanced bone age and learning disability. The purpose of this case report is to highlight the dental management of a 10-year-old boy with Sotos syndrome who presented with hypodontia and dental caries.

Two experiments tested text comprehension skills in adults varying in age from 20 to 69 years. A coherence judgment task (n = 39), in which the pragmatic connection of two sentences had to be evaluated, did not yield any age effects. Both error rates and reaction times were largely independent of age. In a word recognition paradigm (n = 60), testing the strength of different text representation levels, there was a gradual, linear decrease in performance with age, accompanied by a similarly gradual increase in processing times. The results confirm that aging affects comprehension under high memory demands, but spares the conceptual, situation-based levels. Most importantly, it was shown that these changes become apparent during middle age already. Implications for education and neuropsychology are discussed.

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 +/- 6.7 years) with DM (mean duration 8.2 +/- 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 microg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 microg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.

A 54-year-old man with diabetes mellitus, peripheral vascular disease, and hypertension was admitted to the hospital for an acute exacerbation of chronic heart failure. Therapy with intravenous furosemide and oral losartan 100 mg twice/day was begun. Ten days later, the patient's blood urea nitrogen and serum creatinine levels rose and peaked at 110 and 6.0 mg/dl, respectively. His serum potassium level increased to 5.7 mg/dl, urine output dropped to 400 ml over 24 hours, and mental status changes occurred. Magnetic resonance angiography revealed bilateral renal artery stenosis. After losartan was discontinued and hemodialysis was performed for 3 consecutive days, the patient's renal function returned to his baseline level. Reports in the medical literature reinforce the importance of recognizing that angiotensin-converting enzyme inhibitors should be used with caution in patients with bilateral renal artery stenosis. However, the literature is not as definitive about using of angiotensin II receptor blockers (ARBs) in these patients. Our patient's experience suggests that ARBs should be used with caution in patients with bilateral renal artery stenosis. Clinicians should be aware that renal failure might occur when using ARBs in these patients.

Objectives. This study examined knowledge about prostate-specific antigen (PSA) screening among African Americans and Whites. Because PSA screening for prostate cancer is controversial, professional organizations recommend informed consent for screening. Methods. Men (n = 304) attending outpatient clinics were surveyed for their knowledge about and experience with screening. Results. Most men did not know the key facts about screening with PSA. African Americans appeared less knowledgeable than Whites, but these differences were mediated by differences in educational level and experience with prostate cancer screening. Conclusions. Public health efforts to improve informed consent for prostate cancer screening should focus on highlighting the key facts and developing different approaches for men at different levels of formal education and prior experience with screening.

This study investigated the functional neuroanatomy of the anterior medial prefrontal cortex (aMPFC). Previous studies have shown that the aMPFC is involved in evaluative judgment and self-referential processes. Specifically, different sections of the aMPFC are differentially influenced by attention demanding processes. Whereas the dorsal section is supposed to be involved in self-referential processes, the ventral section is assumed to be attenuated during attention demanding processes. The present study investigates the involvement of the dorsal and ventral aMPFC in evaluative judgment by using functional magnetic resonance imaging with spin-echo echo-planar-imaging. Processes involved in evaluative judgment are attention-demanding, self-referential and activate regions in the dorsal and ventral section of the aMPFC. Attention demanding tasks do not necessarily lead to an attenuation of the ventral section of the aMPFC, a region mainly involved in emotional and affective processing.

Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%.To evaluate an intervention to increase childhood influenza vaccination across age and racial groups.In 2011-2012, a total of 20 primary care practices treating children were randomly assigned to the intervention and control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity.The average vaccination differences from pre-intervention to the intervention year were significantly larger in the intervention arm (n=10 practices) than the control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts intervention vs 4.3 pct pts control, p0.05); for non-white children (16.7 pct pts intervention vs 4.6 pct pts control, p0.001); and overall (9.9 pct pts intervention vs 4.2 pct pts control, p0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race, and intervention, the likelihood of vaccination increased with younger age group (6-23 months); white race; commercial insurance; the practice's pre-intervention vaccination rate; and being in the intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9-18 years.A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large percentages of minority children.

Purpose Understanding job satisfaction in academia is important in order to recruit and retain faculty. Faculty members with greater job dissatisfaction are more likely to leave than faculty members who are satisfied. Physician assistant (PA) faculty job satisfaction needs to be assessed to determine which job facets are satisfying or dissatisfying. Methods A quantitative descriptive study was done using a Web-based survey sent to PA faculty. The Job Descriptive Index (JDI), a validated survey, was used to measure levels of job satisfaction. The means for each facet were calculated to indicate levels of satisfaction with the job overall, work, supervision, co-workers, pay, promotion, levels of stress, and trustworthiness in management. Correlations were run among demographic factors, salary, and overall job satisfaction. Results Of the 1,241 PA faculty that received the survey, 239 responses (19.3% response rate) met the criteria for study inclusion. The highest level of satisfaction was with one's co-workers (mean 46.83, range 0 to 54). The promotion facet received the lowest mean level of satisfaction with a 22.2 (range 0 to 54). A small correlation was found between job satisfaction and academic rank (r = -.153, P = .020). Conclusion Job satisfaction is linked to increased productivity and performance. It is important to understand job satisfaction to make improvements in the appropriate areas. Overall, the results indicate that PA faculty are satisfied with their jobs. Further research is needed to understand the factors that contribute to satisfaction among PA faculty.

Text processing requires inferences for establishing coherence between successive sentences. In neuropsychological studies and brain imaging studies, these coherence-building processes have been ascribed to the right hemisphere. On the other hand, there is evidence for prefrontal brain damage causing non-aphasic language disorders, in which text level processes are impaired. In this study, we used an event-related, whole-head fMRI methodology to evaluate the contributions of prefrontal areas and the right hemisphere to coherence building. We scanned 12 participants while they read 120 sentence pairs and judged their coherence. Four conditions were used, resulting from crossing coherence and cohesion (i.e. the presence of a lexical connection). A behavioral pretest confirmed that cohesion aided establishing coherence, whereas it hindered the detection of coherence breaks. In the fMRI study, all language conditions yielded activation in left frontolateral and temporolateral regions, when compared to a physical control task. The differences due to coherence of the sentence pairs were most evident in larger activation for coherent as compared to incoherent sentence pairs in the left frontomedian wall, but also in posterior cingulate and precuneal regions. Finally, a left inferior prefrontal area was sensitive to the difficulty of the task, and in particular to the increase in processing costs when cohesion falsely indicated coherence. These results could not provide evidence for a special involvement of the right hemisphere during inferencing. Rather, they suggest that the left frontomedian cortex plays an important role in coherence building.

Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV-shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.

S100 proteins are calcium-binding proteins of the EF-hand superfamily and are involved in the regulation of a number of cellular processes. The present study deals with the immunohistochemical expression of S100A1 and S10100A6 in the rat submandibular and sublingual glands during postnatal development from day 0 to 12 weeks. Expression of S100A1 was particularly concentrated in pillar and transition cells in the granular convoluted tubule (GCT) and in striated duct cells of the submandibular gland age 4 weeks to maturity. None or only weak staining for S100A1 was observed in the duct segment at 0-5 days. On the contrary, immunostaining of S100A6 was present in proacinar cells in undifferentiated submandibular gland at age 3 days to 2 weeks. S100A6 immunoreactivity in rat submandibular gland coexisted with chromogranin reactivity. It is possible that S100A6 regulates secretion of chromogranin in proacinar cells. Secretion of growth factors and biologically active peptides in the GCT are regulated by calcium signals, and S100A1 may be involved in the secretory mechanism of granular cells. S100A1 and S100A6 are potentially of great importance in secretory functions of granular cells and proacinar cells, as well as in rat salivary glands.

Purpose: Since prostate-specific antigen (PSA) screening is controversial, some authorities recommend that patients give informed consent before testing. We identified and compared what facts experts and patients thought men should know. Subjects and Methods: We recruited a Delphi panel of national experts (6 urologists and 6 non-urologists) and conducted 6 focus groups of couples (48 subjects) with 24 screened and unscreened men from a university hospital. We ranked key facts that experts and couples thought men ought to know before consenting to PSA screening and conducted a multidisciplinary focus group to help interpret the findings. Results: All participants would disclose that false positive and false negative results can occur and that it is not known whether PSA screening reduces prostate cancer mortality. The 12 experts would disclose the uncertain benefits of treating early, localized prostate cancer. All 24 couples would disclose that the PSA test is a blood test and that patients may worry about results. The 6 urologists would disclose that prostate cancer is often incurable when symptoms appear; the 6 non-urologists, that it can be asymptomatic. The 12 couples with screened men would disclose that the PSA test can detect cancer sooner than the digital rectal examination; the 12 couples with unscreened men, that PSA testing is controversial. Conclusions: Physicians and patients agree upon some facts that men should know about PSA screening before giving informed consent. However, physicians fail to emphasize other facts that patients find important. Physicians may differ by expertise; patients, by experience. Our findings provide content for informed consent for PSA screening, and our method may be useful for other controversial tests.

There is inconclusive evidence that prostate cancer screening with prostate-specific antigen (PSA) reduces mortality. Although PSA testing is widespread, it is unknown how many physicians have taken the PSA test themselves.To determine the prevalence of PSA testing among physicians.Cross-sectional survey.A nationwide stratified random sample of urologists (response rate 61%, n=247), Internists (response rate 51%, n=273), and family physicians (response rate 64%, n=249) were surveyed by mail in 2000. After excluding female respondents and men who either reported a positive history of prostate cancer or did not respond to that query, there were 146 urologists, 96 Internists, and 118 family physicians.Whether physicians had undergone prostate cancer screening with PSA.Eighty-seven percent (155/178) of male physicians aged, 50 and older and 21% (31/150) of white male physicians under age 50 reported having had a PSA test. More urologists than nonurologists in both age groups reported having had a screening PSA test.Most physicians aged 50 and older report undergoing PSA testing. This may reflect a belief in its efficacy and contribute to its widespread use.

A capillary zone electrophoresis method has been developed for the determination of p-aminosalicylic acid (PAS) and its metabolite, N-acetyl-p-aminosalicylic acid (N-acetyl-PAS), in urine. A linear relationship was observed between time-normalized peak area and the concentration of the parent and metabolite with correlation coefficients greater than 0.9990. The method could be applied to the determination of PAS and N-acetyl-PAS in human urine without any sample pretreatment. A good separation of the analytes is achieved in a run time of 12 min (15 min total, including capillary wash). Using PAS as a probe for N-acetyltransferase 1 activity, 20 healthy volunteers were phenotyped after oral administration of a 1 g dose. The preliminary results seem to indicate a bimodal distribution of N-acetyl-PAS/PAS molar ratios.

Purpose: Commercially available polyclonal antibodies against a mixture of bovine brain S100 proteins have become an established marker for immunohistochemical characterization of malignant melanoma. However, the commercially available antibodies used are undefined and to date, 13 different human S100 proteins are known. The purpose of this study was to examine the expression of 4 newly available polyclonal antibodies against the human recombinant Ca 2+ -binding S100 proteins, S100A1, S100A2, S100A4 and S100A6, in cutaneous melanoma and to correlate these findings with the standard S100 staining as well as with the metastatic potential of the primary. Methods: 39 formalin-fixed paraffin-embedded primary cutaneous melanomas were incubated with polyclonal antibodies against recombinant human S100 proteins using the APAAP method. The extent of staining was qualitatively assessed and a staining index was calculated. Findings were correlated to the metastatic potential and the overall survival in all patients. Results: Staining with antibodies against human S100A6 as well as with antibodies against conventional bovine S100 proteins was positive in all specimens. No correlation was found between the extent of protein expression and patients' outcome for standard S100 staining as well as for S100A6. S100A1, S100A2 and S100A4 stainings could not be used for statistical analysis due to their low expression in melanoma. Conclusion: Staining was positive using S100A6 antibodies in all specimens, the quality being inferior to the commercially available S100 antibody. Highly specific and well characterized antibodies against the individual S100 proteins are now available for future immunohistochemical characterization studies in melanomas.

Purpose To determine whether frailty can be measured within 4 days prior to hospital discharge in older intensive care unit (ICU) survivors of respiratory failure and whether it is associated with post-discharge disability and mortality. Materials and Methods We performed a single-center prospective cohort study of 22 medical ICU survivors age 65 years or older who had received noninvasive or invasive mechanical ventilation for at least 24 hours. Frailty was defined as a score of ≥3 using Fried's 5-point scale. We measured disability with the Katz Activities of Daily Living. We estimated unadjusted associations between Fried's frailty score and incident disability at 1-month and 6-month mortality using Cox proportional hazard models. Results The mean (SD) age was 77 (9) years, mean Acute Physiology and Chronic Health Evaluation II score was 27 (9.7), mean frailty score was 3.4 (1.3), and 18 (82%) were frail. Nine subjects (41%) died within 6 months, and all were frail. Each 1-point increase in frailty score was associated with a 90% increased rate of incident disability at 1-month (rate ratio: 1.9, 95% CI 0.7-4.9) and a threefold increase in 6-month mortality (rate ratio: 3.0, 95% CI 1.4-6.3). Conclusions Frailty can be measured in older ICU survivors near hospital discharge and is associated with 6-month mortality in unadjusted analysis. Larger studies to determine if frailty independently predicts outcomes are warranted.

Models of affect assume a two-dimensional framework, composed of emotional valence and arousal. Although neuroimaging evidence supports a neuro-functional distinction of their effects during single word processing, electrophysiological studies have not yet compared the effects of arousal within the same category of valence (positive and negative). Here we investigate effects of arousal and valence on written lexical decision. Amplitude differences between emotion and neutral words were seen in the early posterior negativity (EPN), the late positive complex and in a sustained slow positivity. In addition, trends towards interactive effects of valence and arousal were observed in the EPN, showing larger amplitude for positive, high-arousal and negative, low-arousal words. The results provide initial evidence for interactions between arousal and valence during processing of positive words and highlight the importance of both variables in studies of emotional stimulus processing. Crown Copyright (C) 2012 Published by Elsevier Ireland Ltd. All rights reserved.