Using quantitative PCR, the abundances of six phytoplankton viruses DNA polymerase (polB) gene fragments were estimated in water samples collected from Lake Ontario, Canada over 26 months. Four of the polB fragments were most related to marine prasinoviruses, while the other two were most closely related to cultivated chloroviruses. Two Prasinovirus-related genes reached peak abundances of >1000 copies ml−1 and were considered ‘high abundance', whereas the other two Prasinovirus-related genes peaked at abundances <1000 copies ml−1 and were considered ‘low abundance'. Of the genes related to chloroviruses, one peaked at ca 1600 copies ml−1, whereas the other reached only ca 300 copies ml−1. Despite these differences in peak abundance, the abundances of all genes monitored were lowest during the late fall, winter and early spring; during these months the high abundance genes persisted at 100–1000 copies ml−1 while the low abundance Prasinovirus- and Chlorovirus-related genes persisted at fewer than ca 100 copies ml−1. Clone libraries of psbA genes from Lake Ontario revealed numerous Chlorella-like algae and two prasinophytes demonstrating the presence of candidate hosts for all types of viruses monitored. Our results corroborate recent metagenomic analyses that suggest that aquatic virus communities are composed of only a few abundant populations and many low abundance populations. Thus, we speculate that an ecologically important characteristic of phycodnavirus communities is seed-bank populations with members that can become numerically dominant when their host abundances reach appropriate levels.

Purpose

Training numbers for colonoscopy vary among specialties. Tracking colonoscopy quality indicators for program graduates may provide reliable outcome data to improve educational programs and establish training requirements. The purpose of this study was to measure specific colonoscopy quality indicators for a family medicine graduate to determine if outcome can be used to assess the quality of procedure training and contribute to more objective means of establishing training numbers.

Methods

We present a case series of the first 800 colonoscopies performed by a newly credentialed family physician who had performed 101 procedures during residency training. Procedure reports and medical records were reviewed for all patients receiving a colonoscopy by this physician from September 2003 to September 2007. Selected quality indicators were compared to recommended colonoscopy standards.

Results

The overall reach-the-cecum rate was 98.6%. Adenomas were detected in 21.6% of females and 33.7% of males. All polyps measuring less than 2 cm were removed. Epinephrine was used for 3 patients with hemostasis after polypectomy. There were no perforations.

Conclusions

Quality indicators for colonoscopy were met after 101 supervised procedures. Postgraduate tracking of nationally recognized colonoscopy quality indicators can provide valuable outcome data to improve residency training and assist in establishing uniform training requirements among specialties.

OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.

RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot.

RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals.

CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.

The cyclic AMP (cAMP)-inducible promoter from the rat lactate dehydrogenase A subunit gene (LDH A) is associated with a distal negative regulatory element (LDH-NRE) that represses inherent basal and cAMP-inducible promoter activity. The element is of dyad symmetry, consisting of a palindromic sequence with two half-sites, 5'-TCTTG-3'. It represses the expression of an LDH A/chloramphenicol acetyltransferase (CAT) reporter gene in a dose-dependent, orientation- and position-independent fashion, suggesting that it is a true silencer element. Uniquely, it selectively represses cAMP-responsive element (CRE)-dependent transcription but has no effect on promoters lacking a CRE sequence. The repressing action of LDH-NRE could be overcome by cotransfection with LDH A/CAT vector oligonucleotides containing either the LDH-NRE or CRE sequence. This suggests that the reversal of repression was caused by the removal of functional active, limiting transacting factors which associate with LDH-NRE as well as with CRE. Gel mobility shift, footprinting, and Southwestern blotting assays demonstrated the presence of a 69-kDa protein with specific binding activity for LDH-NRE. Additionally, gel supershift assays with anti-CREB and anti-Fos antibodies indicate the presence of CREB and Fos or antigenically closely related proteins with the LDH-NRE/protein complex. We suggest that the LDH-NRE and CRE modules functionally interact to achieve negative modulation of cAMP-responsive LDH A transcriptional activity.

Background:

Neo-angiogenesis is a hallmark of cancer. The aim of this study was to test the hypothesis, in a prospective patient cohort, that in low-risk gestational trophoblastic neoplasia (LR-GTN) the uterine artery pulsatility index (UAPI), a measure of tumour vascularity, can predict resistance to methotrexate chemotherapy (MTX-R).

Methods:

286 LR-GTN patients (Charing Cross Hospital (CXH) score 0–8, or FIGO score 0–6) were treated with methotrexate between January 2008 and June 2011 at CXH. During staging investigations, patients underwent a Doppler ultrasound to assess the UAPI.

Results:

239 patients were assessable for both UAPI and MTX-R. The median UAPI was lower (higher vascularity) in MTX-R compared with MTX-sensitive patients (0.8 vs 1.4, P<0.0001). In multivariate logistic regression, UAPI⩽1 predicted MTX-R, independent of both CXH and FIGO scores. The risk of MTX-R in patients with a FIGO score of 6 and UAPI⩽1 was 100% vs 20% in patients with UAPI>1 (χ2 P<0.0001).

Conclusion:

UAPI represents an independently validated clinically useful predictor of MTX-R in LR-GTN. Further, consideration of whether to incorporate UAPI into the FIGO scoring system is now warranted so that patients with a score of 6 and a UAPI ⩽1 might be upstaged and offered combination chemotherapy rather than MTX.

Objective

To assess the effect of prenatal cocaine exposure on mental health symptoms in 9-year old children controlling for potential confounders.

Methods

332 children (170 prenatally cocaine-exposed (PCE), 162 non cocaine-exposed (NCE) were assessed using self (Dominic Interactive; DI) and caregiver report (Child Behavior Checklist; CBCL).

Results

Higher levels of PCE were associated with caregiver report of clinically elevated aggressive and delinquent behavior. With each increased unit of PCE, children were 1.3 times more likely to be rated as aggressive (OR=1.30, 95% CI: 1.02–1.67, p<0.04). For each increased unit of PCE, girls were 2 times more likely to be rated as having delinquent behavior (OR=2.08, 95% CI: 1.46–2.96, p<0.0001). PCE status was also associated with increased odds of delinquent behavior (OR=2.41; 95% CI: 1.16–4.97, p=0.02), primarily due to the increased risk among girls with PCE. While girls with PCE status were 7 times more likely than NCE girls to have delinquent behaviors (OR=7.42; 95% CI: 2.03–27.11, p<0.002) boys with PCE did not demonstrate increased risk (OR=0.98; 95% CI: 0.36–2.65, p>0.97). Foster or adoptive parents were more likely to rate their PCE children as having more thought problems, inattention, delinquent behavior, aggression, externalizing and overall problems (p<0.05) than biologic mothers or relative caregivers. Higher 2nd trimester tobacco exposure was associated with increased odds of caregiver reported anxiety (OR=1.73; 95% CI 1.06–2.81, p<0.03) and marijuana exposure increased the odds of thought problems (OR=1.68; 95% CI 1.01–2.79, p<0.05). Children with PCE self-reported fewer symptoms of oppositional defiant disorder (ODD) compared to NCE children (OR=0.44, 95% CI: 0.21–0.92, p<0.03). Greater tobacco exposure was associated with increased odds of child reported ODD (OR=1.24; 95% CI 1.03–1.78, p<0.03).

Conclusion

Higher PCE was associated with disruptive behaviors including aggression and delinquent behavior among girls by caregiver report, but not child report. These findings highlight the need for early behavioral assessment using multiple informants in multi-risk children.

There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, p<0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, p = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, p<0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.

Structural equation modeling was used to simultaneously examine maternal psychological distress and social support as mediators linking maternal childhood trauma (MCT) to both maternal and child-reported behavior at 9 years of age in 231 birth mother-child dyads, who were primarily poor, urban, and African American. One half of the mothers (n = 116) reported a history of childhood abuse and neglect. Although MCT was associated with both increased maternal psychological distress and limited social support at 6 years, the pathway to child behavior ratings at 9 years was informant dependent. MCT influenced maternal ratings of her child’s behavior, with some effects mediated through psychological distress. MCT indirectly influenced children’s self-perception of behavior through maternal experience of social support. Maternal ratings and child self-ratings of child behavior problems were moderately correlated. No significant gender interaction was found. Findings suggest a need for understanding trauma histories in the lives of mothers who seek assistance for parenting and child behavior problems, especially in urban low income communities. Interventions targeting both increasing maternal social support and reducing psychological distress may promote competency and resiliency among children for whom MCT poses a risk to optimal development.

Study reveals how SUMOylation converts a transcriptional activator into a repressor.

Study reveals how SUMOylation converts a transcriptional activator into a repressor.

Background

Children prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions.

Objective

To assess behavioral outcomes of cocaine (CE) and non-cocaine exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors.

Methods

Low socioeconomic status (SES), primarily African-American children (n = 381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10 years of age, controlling for confounders.

Results

Prenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR=1.93, CI: 1.09-3.42, p<.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR=3.57, CI: 1.67-7.60, p<.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4, 9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions.

Conclusion

Prenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.

Background

Transitional Year (TY) programs meet an important need by preparing residents for specialties that accept individuals after an initial preparatory year. To our knowledge, no surveys to date have been conducted to identify attributes of TY programs and concerns of TY program directors.

Purpose

The purpose of this study was to review TY program characteristics and identify critical issues and concerns of TY program directors (TYPDs).

Methods

A web-based, 22-question survey was sent to all 114 TYPDs of programs accredited by the Accreditation Council for Graduate Medical Education between January and April 2011. The survey included open-formatted and closed-formatted questions addressing program and institution demographics, program director time, administrative support, satisfaction, and future plans.

Results

The survey response rate was 86%. The median age of TY programs was 28 years, with few new programs. More than 80% of TY programs were conducted at community hospitals and university-affiliated community hospitals. Of the responding TYPDs, 17% had served less than 2 years, and 32% had served 10 years or more. Common sponsoring TY programs included internal medicine (88%), general surgery (42%), family medicine (25%), emergency medicine (24%), and pediatrics (18%). Overall, TYPDs were satisfied with their positions. They expressed concerns about inadequate time to complete duties, salary support, and administrative duties assigned to program coordinators. Forty-nine percent of TYPDs reported they planned to leave the position within the next 5 years.

Conclusions

Our survey provides useful information to assist institutions and the graduate medical education community in meeting the needs of TYPDs and strengthening TY programs.

The human face provides a wealth of information pertaining to the internal state and life-stage history of an individual. Facial width-to-height ratio is a size-independent sexually dimorphic trait, and estimates of aggression made by untrained adults judging own-race faces were positively associated with both facial width-to-height ratio and actual aggressive behavior. Given the significant adaptive value of accurately detecting aggressiveness based on facial appearance, we hypothesized that aggression estimates made by adults and 8-year-olds would be highly correlated with male facial width-to-height ratio even for a face category with which they had minimal experience—other-race faces. For each of the four race and age groups, estimates of aggression were positively correlated with facial width-to-height ratio irrespective of rating own-or other-race faces. Overall, the correlations between facial width-to-height ratio and ratings of aggression were stronger for adults than for children. Sensitivity to facial width-to-height ratio appears to be part of an evolved mechanism designed to detect threats in the external environment. This mechanism is likely broadly tuned and functions independently of experience.

Inactivating clathrin in S phase reveals the protein's involvement in centrosome maturation.

Inactivating clathrin in S phase reveals the protein's involvement in centrosome maturation.

Background

Despite high rates of self-reported crime victimisation, no study to date has compared official victimisation records of people with severe mental illness with a random community sample. Accordingly, this study sought to determine whether persons with schizophrenia-spectrum disorders have higher rates of recorded victimisation than the general population, and to explore whether there have been changes in rates of recorded victimisation over a period of deinstitutionalisation.

Methods

The schizophrenia-spectrum cases were drawn from a state-wide public mental health register, comprising all persons first diagnosed with a schizophrenic illness in five year cohorts between 1975 – 2005. The criminal histories of 4,168 persons diagnosed with schizophrenic-spectrum disorders were compared to those of a randomly selected community sample of 4,641 individuals.

Results

Compared to community controls, patients with schizophrenia-spectrum disorders were significantly more likely to have a record of violent (10.1% vs. 6.6%, odds ratio 1.4) and sexually violent victimisation (1.7% vs. 0.3%, odds ratio 2.77), but less likely to have an official record of victimisation overall (28.7% vs. 39.1%, odds ratio 0.5). Over the approximate period of deinstitutionalisation, the rate of recorded victimisation has more than doubled in schizophrenia-spectrum patients, but stayed relatively constant in the general community.

Conclusions

People with schizophrenic-spectrum disorders are particularly vulnerable to violent crime victimisation; although co-morbid substance misuse and criminality both heighten the chances of victimisation, they cannot fully account for the increased rates. Deinstitutionalisation may have, in part, contributed to an unintended consequence of increasing rates of victimisation amongst the seriously mentally ill.

Parkinson’s disease (PD), an age-related movement disorder, is characterized by severe catecholaminergic neuron loss in the substantia nigra pars compacta-ventral tegmental area (SNPC-VTA) and locus coeruleus (LC). To assess the stability of these central catecholaminergic neurons following an acute episode of severe inflammation, 6 to 22 month-old C57/Bl6 mice received a maximally tolerated dose of LPS followed by euthanasia two hours later to assay peak levels of peripheral and central cytokines; and, 14 weeks later for computerized stereology of tyrosine hydroxylase-immunopositive (TH+) neurons in the SNPC-VTA and LC. Two hours after LPS, cytokine levels varied in an age-related manner, with the greatest peripheral and central elevations in old and young mice, respectively. Severe inflammation failed to cause loss of TH+ neurons in SNPC-VTA or LC; however, there was an age-related decline in these TH+ neurons in LPS-treated and control groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against catecholaminergic neuron loss during an acute episode of severe inflammation, while catecholaminergic neuron loss occurs during normal aging.

In Southern Africa, high adult HIV prevalence has fueled concern about the welfare of children losing parents to the epidemic. A growing body of evidence indicates that parental, particularly maternal, death is negatively associated with child outcomes. However, a better understanding of the mechanisms is needed. In addition, the way orphan disadvantage and the mechanisms giving rise to it are understood on the ground is essential for the successful translation of research into policies and programs. This study employs data from 89 in-depth interviews with caregivers and key informants in Lesotho, a setting where approximately one-quarter of adults is infected with HIV, to elaborate understandings of orphan disadvantage. Our analysis focuses on two questions: (i) Do local actors perceive orphans to be disadvantaged compared to non-orphans, and if so, in what ways; and (ii) How do they explain orphans’ differential disadvantage?

Analyses suggest that orphans were widely perceived to be disadvantaged; respondents described this disadvantage in material as well as affective domains. Thematic analyses reveal five broad categories of explanation: poverty, love and kin connection, caregiver character, perceptions of orphans, and community norms related to orphan care. These results underscore the need for research and policy to address (i) multiple types of disadvantage, including deficits in kindness and attention; and (ii) the social embeddedness of disadvantage, recognizing that poverty, kinship, and community interact with individual attributes to shape caregiving relationships and child experiences. The findings suggest limited success for programs and policies that do not address the emotional needs of children, or that focus on child or caregiver support to the exclusion of community outreach.

It is widely believed that adults cannot learn a foreign language in the same way that children learn a first language. However, recent evidence suggests that adult learners of a foreign language can come to rely on native-like language brain mechanisms. Here, we show that the type of language training crucially impacts this outcome. We used an artificial language paradigm to examine longitudinally whether explicit training (that approximates traditional grammar-focused classroom settings) and implicit training (that approximates immersion settings) differentially affect neural (electrophysiological) and behavioral (performance) measures of syntactic processing. Results showed that performance of explicitly and implicitly trained groups did not differ at either low or high proficiency. In contrast, electrophysiological (ERP) measures revealed striking differences between the groups’ neural activity at both proficiency levels in response to syntactic violations. Implicit training yielded an N400 at low proficiency, whereas at high proficiency, it elicited a pattern typical of native speakers: an anterior negativity followed by a P600 accompanied by a late anterior negativity. Explicit training, by contrast, yielded no significant effects at low proficiency and only an anterior positivity followed by a P600 at high proficiency. Although the P600 is reminiscent of native-like processing, this response pattern as a whole is not. Thus, only implicit training led to an electrophysiological signature typical of native speakers. Overall, the results suggest that adult foreign language learners can come to rely on native-like language brain mechanisms, but that the conditions under which the language is learned may be crucial in attaining this goal.

Phospholipid directs polarized growth by targeting actin-polymerizing formins to the cortex of plant cells.

Phospholipid directs polarized growth by targeting actin-polymerizing formins to the cortex of plant cells.