Predictors of drug use during pregnancy: The relative effects of socioeconomic, demographic, and mental health risk factors.

BACKGROUND: With limited Canadian research on predictors of drug use during pregnancy, the primary objective was to assess the relative effects of socioeconomic, demographic, and mental health risk factors associated with drug use during pregnancy. Predictors of an Apgar score < 7 and fetal macrosomia were examined as secondary outcomes. METHODS: This retrospective cohort study consisted of 25,734 pregnant women from Southwestern Ontario. Data were prospectively obtained from perinatal and neonatal databases at a tertiary hospital in London, Ontario. Using a Geographic Information System, neighborhood-level socioeconomic variables were obtained by mapping maternal postal codes. Separate logistic regressions were computed for all outcome variables. RESULTS: The rates of alcohol, tobacco, and cannabis use during pregnancy were 1.9%, 16.2%, and 2.3%, respectively. The mean maternal age was 29.4±5.4 years. Maternal age was inversely associated with alcohol, tobacco and cannabis use, whereas lone-parent household, depression, and anxiety increased the odds of substance use. Depression was the top risk factor of all three substances. Compared to women who were not depressed during pregnancy, women who were depressed were 2.15 times more likely to use alcohol (95% CI: 1.60, 2.90), 1.70 times more likely to smoke tobacco (95% CI: 1.48, 1.95), and 2.56 times more likely to use cannabis (95% CI: 1.95, 3.35). Adverse birth outcomes were also associated with overweight and obesity, gestational diabetes and insulin-dependent diabetes. CONCLUSIONS: Maternal depression is the primary risk factor of drug use during pregnancy. Policy interventions that target at-risk women are important considerations to improve maternal mental health.

Is Breast Best? Examining the effects of alcohol and cannabis use during lactation.

Maternal drug use during lactation may have adverse effects on the health of their children. Two common drugs used during this period are alcohol and cannabis. A literature search was conducted using PubMed, CINAHL, Nursing and Allied Health, and Google Scholar with the following search terms: marijuana, cannabis, THC, alcohol, ethanol, breastfeeding, lactation, and breastmilk. The search strategy was restricted to papers since the year 2000, and limited to English language journals. Reference lists were also used to capture any articles that were missed from the database searches. In total, 19 articles were found related to alcohol and breastfeeding (n = 17 original research papers; n = 2 systematic reviews), and 4 articles were specific to cannabis (n = 2 original papers; n = 2 systematic reviews). The most common outcomes associated with alcohol consumption and breastfeeding included changes in sleep patterns, reduced milk production and flow, lower milk intake, and impaired immune function. Maternal outcomes related to cannabis consumption included panic attacks, delayed response time, increased heart rate, reduced short-term memory, dizziness, and impaired motor performance; infant outcomes associated with maternal cannabis use and breastfeeding were reduced muscular tonus, poor sucking, and growth delay and restriction. Mothers should be advised to refrain from substance use during the lactation period for the health and safety of their children.

A novel system for expansion and delivery of human keratinocytes for the treatment of severe cutaneous injuries using microcarriers and compressed collagen.

Cell therapy with autologous or allogeneic keratinocytes applied as a single-cell suspension is well established in clinical practice in the treatment of severe burn injuries to augment epithelial barrier restoration. Yet, the application of cell sprays can lead to significant cell loss owing to lack of adhesion of cell suspension to the wound bed. The development of a robust and controllable method of transplanting cells onto the wound bed is yet to be established. The ability to control adhesion and distribution of cells by using a cell carrier embedded in a biodegradable scaffold could significantly improve the treatment of cutaneous wounds with keratinocyte cell therapy. Several microcarrier-based systems for expanding keratinocytes already exist. A new method for expansion of human keratinocytes in a feeder-free, defined medium system on microcarriers has been developed. The cells retained their basal, proliferative phenotype after rapid expansion in a clinically relevant time-frame. The cell-laden microcarriers were further incorporated into collagen scaffolds fabricated by plastic compression. When cultured in vitro, cells continued to proliferate and migrate along the surface of the collagen scaffold. Using an in vitro wound bed model, cells were observed to form mostly single cell layers and in some areas multiple cell layers within 8 days, while retaining their basal, proliferative phenotype, indicating the suitability of this cell transplantation method to improve epithelial barrier restoration. This advanced cell expansion and delivery method for cutaneous cell therapy provides a flexible tool for use in clinical application. Copyright © 2017 John Wiley & Sons, Ltd.

Temperature dynamics of stormwater runoff in Australia and the USA.

Thermal pollution of surface waters by urban stormwater runoff is an often overlooked by-product of urbanization. Elevated stream temperatures due to an influx of stormwater runoff can be detrimental to stream biota, in particular for cold water systems. However, few studies have examined temperature trends throughout storm events to determine how these thermal inputs are temporally distributed. In this study, six diverse catchments in two continents are evaluated for thermal dynamics. Summary statistics from the data showed larger catchments have lower maximum runoff temperatures, minimum runoff temperatures, and temperature variability. This reinforces the understanding that subsurface drainage infrastructure in urban catchments acts to moderate runoff temperatures. The catchments were also evaluated for the presence of a thermal first flush using two methodologies. Results showed the lack of a first flush under traditional assessment methodologies across all six catchments, supporting the results from a limited number of studies in literature. However, the time to peak temperature was not always coincident with the time to peak flow, highlighting the variability of thermal load over time. When a new first flush methodology was applied, significant differences in temperature were noted with increasing runoff depth for five of the six sites. This study is the first to identify a runoff temperature first flush, and highlights the need to carefully consider the appropriate methodology for such analyses.

Safety and efficacy of abciximab in older adults undergoing percutaneous coronary intervention.

BACKGROUND: As a result of increased cost and bleeding concerns, older patients receive abciximab during percutaneous coronary intervention (PCI) less often than younger patients. OBJECTIVE: The aim of this was to evaluate the safety and efficacy of abciximab in older adults undergoing PCI. DESIGN: Retrospective, observational single centre cohort study. METHODS: The British Cardiovascular Intervention Society (BCIS) database was used to establish the impact of abciximab in people with advanced age (≥ 75 years) on in-hospital bleeding and ischaemic events and all-cause mortality in 5727 consecutive patients undergoing PCI between January 2008 and June 2014. RESULTS: Older patients represented 23% of the study population (n = 1298). Abciximab was used in 198 (15%) older patients and 970 (22%) younger patients (p < 0.001). Unadjusted bleeding and mortality rates were 1.2% and 5.6%, respectively, vs. 0.4% and 1.7% in younger patients (p = 0.001 and p < 0.001 respectively). On multivariate analysis older subjects were at higher risk of bleeding [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.26-6.04, p = 0.011] and had higher in-hospital mortality (OR 2.36, 95% CI 1.48-3.74, p < 0.001). The use of abciximab in older patients was not significantly associated with excess bleeding (adjusted OR 1.86, 95% CI 0.58-5.93, p = 0.3), ischaemic outcomes (adjusted OR, 95% CI, p = 0.12) or in-hospital mortality (adjusted OR, 95% CI, p = 0.11). Older patients having primary PCI had higher risk of bleeding irrespective of abciximab use (adjusted p = 0.042). CONCLUSION: Abciximab may not be associated with excess bleeding complications in older patients compared with younger individuals and may be safe to use in older people if indicated.

Simultaneous computerised activation of the primary percutaneous coronary intervention pathway reduces out-of-hours door-to-balloon time but not mortality.

BACKGROUND: In 2009 activation of out of hours (OOH) primary percutaneous coronary intervention (PPCI) in our institution changed from separate telephone calls to a simultaneous computerised alert. We assessed the impact of this protocol change on door-to-balloon (DTB) time, in hospital and 1 year mortality. METHODS: Retrospective survey of our Myocardial Ischaemia National Audit Project (MINAP) database. OOH patients were categorized--pre- (Group 1) and post- (Group 2) introduction of the computerised alert protocol. RESULTS: OOH PPCI was performed for 793 patients (mean age 61, 73.4% male)--295 in Group 1 and 498 in Group 2. Median DTB times were 92 min (interquartile range [IQR] 75-111) for Group 1 and 76 min (IQR 64-97) for Group 2 (p < 0.0001). Forty-eight percent achieved DTB in ≤ 90 min in Group 1 compared to 70% in Group 2 (p < 0.0001). Computerised alert was associated with a shorter DTB time on multivariate analysis (beta coefficient -0.09, p = 0.03 for linear regression and OR 2.8, 95% CI 1.6-5.0, p < 0.0001 for logistic regression). In hospital mortality was 4.1% in Group 1 and 5% in Group 2 (p = 0.60). All-cause mortality at 1 year was 6.1% in Group 1 and 9.9% in Group 2 (p = 0.09). CONCLUSIONS: Simultaneous computerised activation for OOH PPCI reduced DTB times, increased the number of patients achieving target DTB times but did not affect mortality.

3D culture model of fibroblast-mediated collagen creep to identify abnormal cell behaviour.

Native collagen gels are important biomimetic cell support scaffolds, and a plastic compression process can now be used to rapidly remove fluid to any required collagen density, producing strong 3D tissue-like models. This study aimed to measure the mechanical creep properties of such scaffolds and to quantify any enhanced creep occurring in the presence of cells (cell-mediated creep). The test rig developed applies constant creep tension during culture and measures real-time extension due to cell action. This was used to model extracellular matrix creep, implicated in the transversalis fascia (TF) in inguinal hernia. Experiments showed that at an applied tension equivalent to 15% break strength, cell-mediated creep over 24-h culture periods was identified at creep rates of 0.46 and 0.38%/h for normal TF and human dermal fibroblasts, respectively. However, hernia TF fibroblasts produced negligible cell-mediated creep levels under the same conditions. Raising the cell culture temperature from 4 to 37 °C was used to demonstrate live cell dependence of this creep. This represents the first in vitro demonstration of TF cell-mediated collagen creep and to our knowledge the first demonstration of a functional, hernia-related cell abnormality.

Conjugatable water-soluble Pt(II) and Pd(II) porphyrin complexes: novel nano- and molecular probes for optical oxygen tension measurement in tissue engineering.

Measurement of oxygen tension in compressed collagen sheets was performed using matrix-embedded optical oxygen sensors based on platinum(II) and palladium(II) porphyrins supported on polyacrylamide nanoparticles. Bespoke, fully water-soluble, mono-functionalised Pt(II) and Pd(II) porphyrin complexes designed for conjugation under mild conditions were obtained using microwave-assisted metallation. The new sensors display a linear response (1/τ vs. O2) to varying oxygen tension over a biologically relevant range (7.0 × 10(-4) to 2.7 × 10(-1) mM) in aqueous solutions; a behaviour that is maintained following conjugation to polyacrylamide nanoparticles, and following embedding of the nanosensors in compressed collagen sheets, paving the way to innovative approaches for real-time resolution of oxygen gradients throughout 3D matrices useful for tissue regeneration.

Pregnancies complicated by preeclampsia and non-preeclampsia-related nephrotic range proteinuria.

OBJECTIVE: To examine the impact of nephrotic range proteinuria during pregnancy on renal, maternal and fetal outcomes. METHODS: A retrospective study of pregnant women with proteinuria greater than 3 g/24 h. Outcome measures included: gestation and mode of delivery, maternal high dependency unit admission, birth weight, maternal blood pressure and proteinuria at time of last follow-up, renal biopsy. RESULTS: Two hundred and sixty four pregnancies in 262 women were reviewed. Postnatal data were available in 180; of these 104 (57%) had urinary protein quantified postnatally. Sixty three (60%) were pure preeclampsia and nine (9%) super-imposed preeclampsia. Biopsy-proven renal disease was newly diagnosed in nine (9%). Sixty three per cent required caesarean section and 34% required high dependency unit admission. There were no maternal deaths. Birth weight corrected for gestation was below the fifth centile in 33%. CONCLUSIONS: The incidence of underlying renal pathology in this cohort is significant and highlights the importance of careful follow-up.

Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients.

BACKGROUND: Toll-like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double-stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein-receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation. METHODS: The clinical characteristics of 611 liver recipients (HCV-infected: n = 153, non-HCV-infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes. RESULTS: TLR3 L412F is common, and it was significantly more prevalent among the HCV-infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13-2.65, P = 0.01). In an analysis that compared HCV-infected patients with wild-type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007-1.06, P = 0.02). CONCLUSION: TLR3 L412F is significantly common in HCV-infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

Chromosomally integrated human herpesvirus-6 in transplant recipients.

Human herpesvirus-6 (HHV-6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV-6 (CIHHV-6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV-6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV-6 from our recent study, together with 14 other published cases of CIHHV-6 were reviewed. Of the 21 cases, CIHHV-6B was reported most commonly among solid organ transplant recipients, while CIHHV-6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV-6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV-6 infection because of their very high HHV-6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft-versus-host disease that was mistaken for HHV-6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV-6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV-6 DNA load. Clinicians should be aware of this entity of CIHHV-6 so that antiviral therapy can be considered in the proper clinical context.

Effects of heparin and related drugs on neutrophil function.

We have previously demonstrated that heparin inhibits neutrophil activation, but the precise mechanism of action remains to be elucidated. The current aim was to further investigate the effects of heparin at inducing apoptosis of neutrophils and whether this was related to antagonism at IP(3) receptors. Furthermore, we investigated the ability of heparin and related molecules to inhibit acute neutrophil-induced injury to human bronchial epithelial cells (HBECs) in vitro. Neutrophils were isolated from human peripheral venous blood. Expression of annexin-V was determined in neutrophils following incubation with LMWH. The effects of LMWH and related molecules upon thapsigargin or m-3M3FBS (phospholipase C activator) induced neutrophil elastase (NE) release were also investigated. The cytotoxic effects of fMLP-activated neutrophils following co-incubation with HBECs were quantified through counting adherent cells before and after incubation. There was no detectable increase in annexin-V positive neutrophils following pre-incubation with LMWH at 30 min, 60 min or 16 h, but an increase was observed with Fas-activating antibody at 16 h. LMWH significantly inhibited NE release induced by either m-3M3FBS (73.4 ± 6.1%, 100 IU ml(-1), P < 0.01) or thapsigargin (62.4 ± 6.9%, 100 IU ml(-1), P < 0.01) in a sulphate-dependent manner. LMWH and related sulphated molecules all abrogated the cytotoxic effects of fMLP-activated neutrophils upon HBECs. In conclusion we were not able to demonstrate that heparin induces apoptosis and we did not find any evidence for heparin acting as an IP(3) receptor antagonist in neutrophils. Nonetheless, the potent inhibitory effects of heparin and related molecules upon neutrophil-induced injury to HBECs provide further evidence of the therapeutic potential of heparin and related molecules in the treatment of chronic inflammatory diseases.

Music preferences and personality among Japanese university students.

Little research has been conducted outside of the European-North American cultural area concerning the personality-based determinants of musical genre preferences The present research investigated the personality profiles and general music genre preferences of 268 Japanese college students. Six dimensions and 24 facets of personality, and 12 music genres, were assessed. Results indicated that, consistent with much previous research, openness (to experience) and particularly the facet of "aesthetic appreciation" were associated with a preference for "reflective" music (jazz, classical, opera, gospel, enka), while one extraversion facet (sociability) was associated with the preference for pop music. Other personality dimensions were less consistently associated with musical preferences, pointing to cultural differences and the need to assess both personality and music genres at more specific levels.

Engineering stable topography in dense bio-mimetic 3D collagen scaffolds.

Topographic features are well known to influence cell behaviour and can provide a powerful tool for engineering complex, functional tissues. This study aimed to investigate the mechanisms of formation of a stable micro-topography on plastic compressed (PC) collagen gels. The uni-directional fluid flow that accompanies PC of collagen gels creates a fluid leaving surface (FLS) and a non-fluid leaving surface (non-FLS). Here we tested the hypothesis that the resulting anisotropy in collagen density and stiffness between FLS and non-FLS would influence the fidelity and stability of micro-grooves patterned on these surfaces. A pattern template of parallel-aligned glass fibres was introduced to the FLS or non-FLS either at the start of the compression or halfway through, when a dense FLS had already formed. Results showed that both early and late patterning of the FLS generated grooves that had depth (25 ±7 µm and 19 ±8 µm, respectively) and width (55 ±11 µm and 50 ±12 µm, respectively) which matched the glass fibre diameter (50 µm). In contrast, early and late patterning of the non-FLS gave much wider (151 ±50 µm and 89 ±14 µm, respectively) and shallower (10 ±2.7 µm and 13 ±3.5 µm, respectively) grooves than expected. The depth to width ratio of the grooves generated on the FLS remained unaltered under static culture conditions over 2 weeks, indicating that grooves were stable under long term active cell-mediated matrix remodelling. These results indicate that the FLS, characterised by a higher matrix collagen density and stiffness than the non-FLS, provides the most favourable mechanical surface for precise engineering of a stable micro-topography in 3D collagen hydrogel scaffolds.

Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation.

Smokers (≥10 cigarettes per day, N=331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P=0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)=1.31, P<0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR=1.06, P=0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P=0.01) and in analyses predicting continuous abstinence (P's≤0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.