Exposure to overprotective parenting and psychopathology in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW; <1,000 g) infants are the most vulnerable babies and are at higher risk for experiencing overprotective (i.e., controlling and intrusive) parenting, which is hypothesized to contribute to the risk for mental disorders. Despite the increased risk for anxiety disorders and decreased risk for alcohol or substance use disorders seen in ELBW survivors, no research has examined the impact of parenting. This study investigated if overprotective parenting mediates links between ELBW birth status and psychiatric disorders in adulthood. STUDY DESIGN: Participants included ELBW survivors born in 1977-1982 and matched normal birth weight (≥2,500 g) control participants (ELBW n = 81; normal birth weight n = 87) prospectively followed in Ontario, Canada. These individuals retrospectively reported on whether either of their parents was overprotective using the Parental Bonding Instrument. Presence of a current anxiety disorder and of current alcohol or substance use disorders was assessed using the Mini International Neuropsychiatric Interview at age 29-36 years. RESULTS: Path analysis showed that overprotective parenting was a significant mediator of the association between ELBW status and risk for an anxiety disorder in adulthood and the risk for an alcohol or substance use disorder in adulthood in ELBW survivors. Overprotective parenting accounted for 53% of the association between ELBW status and the risk for an anxiety disorder in adulthood and 26% of the association between ELBW status and alcohol or substance use disorders. CONCLUSIONS: Overprotective parenting accounted for a substantial proportion of the increased risk for anxiety and alcohol or substance use disorders in adulthood in ELBW survivors. Despite their perceived vulnerabilities, it is important that the parents of ELBW survivors be supported in their attempts to facilitate their children's pursuit of independence during childhood and beyond.

An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis.

Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease. In the absence of relevant animal models and patient brain specimens, we took advantage of induced pluripotent stem cell (iPSC) technology to model the disease. We established human iPSCs from two males with mutated DCX and classical lissencephaly including smooth brain and abnormal cortical morphology. The disease was recapitulated by differentiation of iPSC into neural cells followed by expression profiling and dissection of DCX-associated functions. Here we show that neural stem cells, with absent or reduced DCX protein expression, exhibit impaired migration, delayed differentiation and deficient neurite formation. Hence, the patient-derived iPSCs and neural stem cells provide a system to further unravel the functions of DCX in normal development and disease.

Can teamwork and situational awareness (SA) in ED resuscitations be improved with a technological cognitive aid? Design and a pilot study of a team situation display.

Effective teamwork in ED resuscitations, including information sharing and situational awareness, could be degraded. Technological cognitive aids can facilitate effective teamwork. OBJECTIVE: This study focused on the design of an ED situation display and pilot test its influence on teamwork and situational awareness during simulated resuscitation scenarios. MATERIAL AND METHODS: The display design consisted of a central area showing the critical dynamic parameters of the interventions with an events time-line below it. Static information was placed at the sides of the display. We pilot tested whether the situation display could lead to higher scores on the Clinical Teamwork Scale (CTS), improved scores on a context-specific Situational Awareness Global Assessment Technique (SAGAT) tool, and team communication patterns that reflect teamwork and situational awareness. RESULTS: Resuscitation teamwork, as measured by the CTS, was overall better with the presence of the situation display as compared with no situation display. Team members discussed interventions more with the situation display compared with not having the situation display. Situational awareness was better with the situation display only in the trauma scenario. DISCUSSION: The situation display could be more effective for certain ED team members and in certain cases. CONCLUSIONS: Overall, this pilot study implies that a situation display could facilitate better teamwork and team communication in the resuscitation event.

Fibulin-3 promotes muscle-invasive bladder cancer.

Urothelial carcinoma is the most common type of bladder cancer and can be categorized as either non-muscle-invasive (Ta-T1) or muscle-invasive (⩾T2). The majority of bladder cancers are non-muscle-invasive at presentation; however, the recurrence rate for these tumors is high and a subset can progress to T2. In this study, we aimed to identify genes differentially expressed between T1 vs T2 bladder cancer to identify key regulators of bladder cancer progression and/or invasion. We performed RNA-Seq on T1 and T2 bladder cancer tissues and used publicly available bladder cancer profiling studies to prioritize differentially expressed genes for validation and functional assessment. This integrative approach nominated an extracellular matrix glycoprotein, fibulin-3 (FBLN3, also known as EFEMP1), as being highly expressed in T2 vs T1 bladder cancer and aggressive vs indolent disease. We confirmed the overexpression of fibulin-3 in ⩾T2 vs non-muscle-invasive bladder cancer (NMIBC) by quantitative reverse transcriptase-PCR. Consistent with these findings, fibulin-3 expression level correlated with the invasive ability of several bladder cancer cell lines and modulation of fibulin-3 expression directly affected invasion. Fibulin-3 knockdown in bladder cancer cells decreased the incidence of MIBCs in a murine orthotopic bladder cancer model and decreased the expression of insulin-like growth factor-binding protein-5 (IGFBP5). Restoring IGFBP5 in these cells rescued their invasive and migratory potential. These results indicate that fibulin-3 serves as a pro-invasive factor in bladder cancer, which may be mediated through modulation of IGFBP5 expression. This also suggests fibulin-3 and IGFBP5 may have potential as biomarkers of aggressive bladder cancer or therapeutic targets.

Adult social outcomes of extremely low birth weight survivors of childhood sexual abuse.

Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW; 2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29-36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.

Prevalence and determinants of white coat effect in a large UK hypertension clinic population.

White coat hypertension (WCH) is common and termed white coat effect (WCE) in those on treatment for hypertension. The UK guideline suggests that all patients in stage 1 and 2 hypertension, but not stage 3 hypertension, should have ambulatory blood pressure monitoring (ABPM) performed before commencing treatment. The relationship between office blood pressure (BP) and ABPM and the factors that influence the WCE were examined in a large British cohort (n=2056) from 2 hypertension clinics (1998-2011). Data were collected prospectively: the median age was 56 years: 53% were female, 76% Caucasian, 9% African Caribbean, 15% South Asian and 86% taking antihypertensives. Fifty-one percent had WCE and differences between clinic BP and ABPM measurements increased with the stage of hypertension varying from 2/4 (normotensive), 13/10 (stage 1 hypertension), 24/14 (stage 2) and 40/20 mm Hg (stage 3). The degree of difference is greater in this study than described in other populations. A positive correlation was found between clinic systolic and diastolic BP and the WCE (r=0.74 and r=0.56, respectively, P<0.0001). Significant (P<0.05) independent associations of systolic WCE were clinic systolic BP (ß=0.707), Caucasian ethnicity (South Asian ß=-0.06; African Caribbean ß=-0.043), female gender (male ß=-0.047), nonsmoking status (smoker ß=-0.100) and reduced renal function (estimated glomerular filtration rate ß=-0.036). Significant independent associations of diastolic WCH were clinic diastolic BP (ß=0.624), age (ß=0.207), female gender (male ß=-0.104), Caucasian ethnicity (South Asian ß=-0.052, African Caribbean ß=-0.079) and being a nonsmoker (ß=-0.082) or ex-smoker (ß=0.046). The results support current UK guidelines but suggest those with stage 3 hypertension would also benefit from ABPM.

Medical student clerkship performance and career selection after a junior medical student surgical mentorship program.

BACKGROUND: The impact of early medical school mentorship in students' clerkships performance and career selection is unknown. METHODS: We administered Introduction to Surgery, a resident-directed, semester-long, preclinical elective to junior medical students who answered a Likert-type survey after residency application. Elective participants (EPs) were compared with nonparticipant applicants (EAs), medical school class (MS), and national match outcomes (USA). RESULTS: All 18 EPs (7 M1's, 11 M2's) completed the elective and survey. EP reported more confidence and improved surgical skills, especially attributed to resident mentorship (F(13,237) = 2.3, P = 8*10(-3)). EP "honored" the clerkship more than MS (P = .05); 55.6% of EP, 37.5% of EA, and 27.7% of MS chose surgical fields, yielding a relative risk of 2.0 for EP vs MS (95% confidence interval: 1.3 to 3.2, P = 4*10(-3)). EP "strongly agree" with future mentorship programs (4.6/5), and 1 EP reported the course to be the "main reason" for applying to general surgery. CONCLUSIONS: Introduction to Surgery provides a model for a multifaceted junior medical student mentorship program, which has the potential to retain interested students for surgical career selection.

Evaluation of a new chromogenic medium, chromID OXA-48, for recovery of carbapenemase-producing Enterobacteriaceae from patients at a university hospital in Turkey.

The purpose of this study was to evaluate a new chromogenic medium, chromID OXA-48, for the isolation of carbapenemase-producing Enterobacteriaceae (CPE) directly from rectal swabs. chromID CARBA and chromID OXA-48 are two chromogenic media that have been commercialized for the isolation of CPE directly from clinical samples. Both media were evaluated alongside a broth enrichment method recommended by the CDC for isolation of CPE, with rectal swabs from 302 unique hospitalized patients at the Hacettepe University Hospital, Ankara, Turkey. A total of 33 patients (11 %) were found to be colonized with CPE using a combination of all methods, and all CPE produced OXA-48 carbapenemase. Klebsiella pneumoniae was by far the most dominant species of CPE and was isolated from 31 patients. Culture on chromID OXA-48 offered the highest sensitivity (75.8 %) for detection of CPE compared with the other two methods (sensitivity for both other methods was 57.6 %) and also offered the highest specificity (99.3 %). However, a combination of methods (either chromID OXA-48 plus CDC method or chromID OXA-48 plus chromID CARBA) was necessary to achieve an acceptable sensitivity (90.9 %). For isolation of CPE, in a setting where OXA-48 carbapenemase is the dominant type of carbapenemase, chromID OXA-48 is a highly useful medium but using a combination of methods is optimal for adequate detection. The combined use of two chromogenic media offered acceptable sensitivity (90.9 %) and the highest specificity (98.5 %) and also allowed for isolation of CPE within 18-20 h.

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: II. Comparison of responses to diesel and gasoline engine exhausts, hardwood smoke and simulated downwind coal emissions.

The NERC Program conducted identically designed exposure-response studies of the respiratory and cardiovascular responses of rodents exposed by inhalation for up to 6 months to diesel and gasoline exhausts (DE, GE), wood smoke (WS) and simulated downwind coal emissions (CE). Concentrations of the four combustion-derived mixtures ranged from near upper bound plausible to common occupational and environmental hotspot levels. An "exposure effect" statistic was created to compare the strengths of exposure-response relationships and adjustments were made to minimize false positives among the large number of comparisons. All four exposures caused statistically significant effects. No exposure caused overt illness, neutrophilic lung inflammation, increased circulating micronuclei or histopathology of major organs visible by light microscopy. DE and GE caused the greatest lung cytotoxicity. WS elicited the most responses in lung lavage fluid. All exposures reduced oxidant production by unstimulated alveolar macrophages, but only GE suppressed stimulated macrophages. Only DE retarded clearance of bacteria from the lung. DE before antigen challenge suppressed responses of allergic mice. CE tended to amplify allergic responses regardless of exposure order. GE and DE induced oxidant stress and pro-atherosclerotic responses in aorta; WS and CE had no such effects. No overall ranking of toxicity was plausible. The ranking of exposures by number of significant responses varied among the response models, with each of the four causing the most responses for at least one model. Each exposure could also be deemed most or least toxic depending on the exposure metric used for comparison. The database is available for additional analyses.

Prevalence of NDM-1 carbapenemase in patients with diarrhoea in Pakistan and evaluation of two chromogenic culture media.

AIMS: To evaluate two chromogenic media, Brilliance CRE and chromID CARBA, with stool samples referred to the Public Health Laboratories Division of the National Institute of Health in Islamabad, and assess the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in this population. METHODS AND RESULTS: One hundred and fifty-two stool samples from patients with diarrhoea were referred to the Microbiology Department and were investigated for the presence of CPE using two chromogenic culture media, Brilliance CRE and chromID CARBA. Thirteen patients (8·6%) were found to be colonized with CPE and all produced NDM-1 carbapenemase. Twelve of these patients (92%) were found to be colonized by culture on chromID CARBA compared with seven (54%) using Brilliance CRE. CONCLUSIONS: If only coloured colonies were considered as presumptive CPE, the sensitivity, specificity and positive predictive value were 54, 23 and 6% for Brilliance CRE and 85, 85 and 36% for chromID CARBA, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: We conclude that Enterobacteriaceae that produce NDM-1 carbapenemase can be found in patients from all major provinces of Pakistan and that chromID CARBA was the most effective of the two chromogenic media in this setting.

The potential impact of washing machines on laundry malodour generation.

A multidisciplinary approach has been adopted to investigate and identify the source of malodour in washing machines and the potential for cross-contamination of laundry. Four washing machines were olfactively graded, and the number of colony-forming units (CFUs) bacteria was determined in four specific locations. Then, samples of terry-towel and fleece were washed, without the use of detergent, in the machines, and the occurrence of malodour over a 52-h period was assessed. Analysis of the scrapings from the four locations in the two malodorous machines identified a plethora of volatile organic compounds (VOCs) by either olfactory detection or mass spectral identification post-gas chromatographic separation. In addition, microbiological analysis from the swabs from the four locations within all four washing machines was carried out. Quantitative analysis of VOCs from 66 microbiological isolates from either the washing machines or fabrics was carried out. In total, 10 VOCs were identified: dimethyl disulfide, 3-methyl-1-butanol, 2,4-dithiapentane, dimethyl trisulfide, 2-tridecanone, indole, 2-phenylethanol, isovaleric acid, isobutyric acid and 1-undecene.

Device use, locomotor training and the presence of arm swing during treadmill walking after spinal cord injury.

STUDY DESIGN: Observational, cross-sectional study from a convenience sample with pretest/posttest data from a sample subset. OBJECTIVES: Determine the presence of walking-related arm swing after spinal cord injury (SCI), its associated factors and whether arm swing may change after locomotor training (LT). SETTING: Malcom Randall VAMC and University of Florida, Gainesville, FL. METHODS: Arm movement was assessed during treadmill stepping, pre-LT, in 30 individuals with motor incomplete SCI (iSCI, American Spinal Injury Association Impairment Scale grade C/D, as defined by the International Standards for Neurological Classifications of SCI, with neurological level of impairment at or below C4). Partial body weight support and manual-trainer assistance were provided, as needed, to achieve stepping and allow arm swing. Arm swing presence was compared on the basis of cervical versus thoracic neurological levels of impairment and device type. Leg and arm strength and walking independence were compared between individuals with and without arm swing. Arm swing was reevaluated post-LT in the 21 out of 30 individuals who underwent LT. RESULTS: Of 30 individuals with iSCI, 12 demonstrated arm swing during treadmill stepping, pre-LT. Arm movement was associated with device type, lower extremity motor scores and walking independence. Among the 21 individuals who received LT, only 5 demonstrated arm swing pre-LT. Of the 16 individuals lacking arm swing pre-LT, 8 integrated arm swing post-LT. CONCLUSION: Devices routinely used for walking post-iSCI appeared associated with arm swing. Post-LT, arm swing presence increased. Therefore, arm swing may be experience dependent. Daily neuromuscular experiences provided to the arms may produce training effects, thereby altering arm swing expression.

Introduction of electronic referral from community associated with more timely review by secondary services.

BACKGROUND: Electronic referral (eReferral) from community into public secondary healthcare services was introduced to 30 referring general medical practices and 28 hospital based services in late 2007. OBJECTIVES: To measure the extent of uptake of eReferral and its association with changes in referral processing. METHODS: Analysis of transactional data from the eReferral message service and the patient information management system of the affected hospital; interview of clinical, operational and management stakeholders. RESULTS: eReferral use rose steadily to 1000 transactions per month in 2008, thereafter showing moderate growth to 1200 per month in 2010. Rate of eReferral from the community in 2010 is estimated at 56% of total referrals to the hospital from general practice, and as 71% of referrals from those having done at least one referral electronically. Referral latency from letter date to hospital triage improves significantly from 2007 to 2009 (p<0.001), from a paper referral median of 8 days (inter-quartile range, IQR: 4-14) in 2007 to an eReferral median of 5 days (IQR: 2-9) and paper referral median of 6 days (IQR: 2-12) in 2009. Specialists upgrade the referrer-assigned eReferral priority in 19.2% of cases and downgrade it 18.6% of the time. Clinical users appreciate improvement of referral visibility (status and content access); however, both general practitioners and specialists point out system usability issues. DISCUSSION: With eReferrals, a referral's status can be checked, and its content read, by any authorized user at any time. The period of eReferral uptake was associated with significant speed-up in referral processing without changes in staffing levels. The eReferral system provides a foundation for further innovation in the community-secondary interface, such as electronic decision support and shared care planning systems. CONCLUSIONS: We observed substantial rapid voluntary uptake of eReferrals associated with faster, more reliable and more transparent referral processing.

Defining the transcriptional signature of skeletal muscle stem cells.

Satellite cells, the main source of myoblasts in postnatal muscle, are located beneath the myofiber basal lamina. The myogenic potential of satellite cells was initially documented based on their capacity to produce progeny that fused into myotubes. More recently, molecular markers of resident satellite cells were identified, further contributing to defining these cells as myogenic stem cells that produce differentiating progeny and self-renew. Herein, we discuss aspects of the satellite cell transcriptional milieu that have been intensively investigated in our research. We elaborate on the expression patterns of the paired box (Pax) transcription factors Pax3 and Pax7, and on the myogenic regulatory factors myogenic factor 5 (Myf5), myogenic determination factor 1 (MyoD), and myogenin. We also introduce original data on MyoD upregulation in newly activated satellite cells, which precedes the first round of cell proliferation. Such MyoD upregulation occurred even when parent myofibers with their associated satellite cells were exposed to pharmacological inhibitors of hepatocyte growth factor and fibroblast growth factor receptors, which are typically involved in promoting satellite cell proliferation. These observations support the hypothesis that most satellite cells in adult muscle are committed to rapidly entering myogenesis. We also detected expression of serum response factor in resident satellite cells prior to MyoD expression, which may facilitate the rapid upregulation of MyoD. Aspects of satellite cell self-renewal based on the reemergence of cells expressing Pax7, but not MyoD, in myogenic cultures are discussed further herein. We conclude by describing our recent studies using transgenic mice in which satellite cells are traced and isolated based on their expression of green fluorescence protein driven by regulatory elements of the nestin promoter (nestin-green fluorescence protein). This feature provides us with a novel means of studying satellite cell transcriptional signatures, heterogeneity among muscle groups, and the role of the myogenic niche in directing satellite cell self-renewal.

Supporting information technology across health boards in New Zealand: the role of learning in adapting to complex change.

This article describes a study of a major change management project involving the establishment of a shared services organization to align the information services functions for two district health boards in New Zealand. The research uncovered a capability crisis that many people experienced when they realized the magnitude of the task they were involved in. Not everyone experienced the crisis and it seems that learning, especially in a complex healthcare environment, plays an important role in reducing the negative impact of change.

Supporting information technology across health boards in New Zealand: themes emerging from the development of a shared services organization.

Shared services organizations are ascribed with adding value to business in several ways but especially by sharing resources and leading to economies of scale. However, these gains are not automatic and in some instances, particularly healthcare, they are difficult to achieve. This article describes a project to develop a shared services information technology infrastructure across two district health boards in New Zealand. The study reveals valuable insight into the crisis issues that accompany change management and identifies emergent themes that can be used to reduce negative impact.

Coamplification of Leucocytozoon by PCR diagnostic tests for avian malaria: a cautionary note.

A number of PCR assays have now been described for detecting species of the avian malaria parasites Plasmodium and Haemoproteus from blood samples. The published protocols amplify both genera simultaneously, owing to the high degree of sequence similarity between them in target genes. However, the potential for coamplification in these assays of a third, closely related hematozoan parasite, Leucocytozoon spp. has been largely overlooked. In this paper, we highlight the importance of this issue, showing that coamplification of Leucocytozoon spp. occurs in several of the protocols designed to amplify avian malaria parasites. This leads not only to scoring of false positives but, in cases of mixed Leucocytozoon/malaria infections, may also lead to scoring of false negatives. We, therefore, advocate the use of a post-PCR diagnostic step, such as RFLP analysis or sequencing, to assess the contribution of Leucocytozoon spp. to overall prevalence.

Zebrafish: a genetic model for hemostasis and thrombosis.

Here we review the zebrafish hemostatic system, its relevance to mammalian hemostasis, and its efficacy as a vertebrate genetic model to further the understanding of hemostasis and thrombosis.