Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function.

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. Previous work has demonstrated that xenobiotic pulmonary exposure to nanoparticles during gestation leads to maternal vascular impairments, as well as cardiovascular dysfunction within the fetus. Few studies have assessed the toxicological consequences of maternal nanoplastic (NP) exposure; therefore, the objective of this study was to assess maternal and fetal health after a single maternal pulmonary exposure to polystyrene NP in late gestation. We hypothesized that this acute exposure would impair maternal and fetal cardiovascular function. Pregnant rats were exposed to nanopolystyrene on gestational day 19 via intratracheal instillation. 24 h later, maternal and fetal health outcomes were evaluated. Cardiovascular function was assessed in dams using vascular myography ex vivo and in fetuses in vivo function was measured via ultrasound. Both fetal and placental weight were reduced after maternal exposure to nanopolystyrene. Increased heart weight and vascular dysfunction in the aorta were evident in exposed dams. Maternal exposure led to vascular dysfunction in the radial artery of the uterus, a resistance vessel that controls blood flow to the fetoplacental compartment. Function of the fetal heart, fetal aorta, and umbilical artery after gestational exposure was dysregulated. Taken together, these data suggest that exposure to NPs negatively impacts maternal and fetal health, highlighting the concern of MNPs exposure on pregnancy and fetal development.

Nanoparticles at the maternal-fetal interface.

The increasing production of intentional and unintentional nanoparticles (NPs) has led to their accumulation in the environment as air and ground pollution. The heterogeneity of these particles primarily relies on the NP physicochemical properties (i.e., chemical composition, size, shape, surface chemistry, etc.). Pregnancy represents a vulnerable life stage for both the woman and the developing fetus. The ubiquitous nature of these NPs creates a concern for developmental fetal exposures. At the maternal-fetal interface lies the placenta, a temporary endocrine organ that facilitates nutrient and waste exchange as well as communication between maternal and fetal tissues. Recent evidence in human and animal models identifies that gestational exposure to NPs results in placental translocation leading to local effects and endocrine disruption. Currently, the mechanisms underlying placental translocation and cellular uptake of NPs in the placenta are poorly understood. The purpose of this review is to assess the current understanding of the physiochemical factors influencing NP translocation, cellular uptake, and endocrine disruption at the maternal-fetal interface within the available literature.

Whole-genome sequencing to investigate transmission of SARS-CoV-2 in the acute healthcare setting: a systematic review.

BACKGROUND: Whole-genome sequencing (WGS) has been used widely to elucidate transmission of SARS-CoV-2 in acute healthcare settings, and to guide infection, prevention, and control (IPC) responses. AIM: To systematically appraise available literature, published between January 1st, 2020 and June 30th, 2022, describing the implementation of WGS in acute healthcare settings to characterize nosocomial SARS-CoV-2 transmission. METHODS: Searches of the PubMed, Embase, Ovid MEDLINE, EBSCO MEDLINE, and Cochrane Library databases identified studies in English reporting the use of WGS to investigate SARS-CoV-2 transmission in acute healthcare environments. Publications involved data collected up to December 31st, 2021, and findings were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. FINDINGS: In all, 3088 non-duplicate records were retrieved; 97 met inclusion criteria, involving 62 outbreak analyses and 35 genomic surveillance studies. No publications from low-income countries were identified. In 87/97 (90%), WGS supported hypotheses for nosocomial transmission, while in 46 out of 97 (47%) suspected transmission events were excluded. An IPC intervention was attributed to the use of WGS in 18 out of 97 (18%); however, only three (3%) studies reported turnaround times ≤7 days facilitating near real-time IPC action, and none reported an impact on the incidence of nosocomial COVID-19 attributable to WGS. CONCLUSION: WGS can elucidate transmission of SARS-CoV-2 in acute healthcare settings to enhance epidemiological investigations. However, evidence was not identified to support sequencing as an intervention to reduce the incidence of SARS-CoV-2 in hospital or to alter the trajectory of active outbreaks.

Repeated transmission of SARS-CoV-2 in an overcrowded Irish emergency department elucidated by whole-genome sequencing.

AIM: To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS). METHODS: SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0-1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences. RESULTS: In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED 'COVID Zone'. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simultaneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED. CONCLUSION: Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.

Maternal, placental, and fetal distribution of titanium after repeated titanium dioxide nanoparticle inhalation through pregnancy.

Epidemiological studies have associated ambient engineered nanomaterials or ultrafine particulate matter (PM0.1), collectively referred to as nanoparticles (NPs), with adverse pregnancy outcomes including miscarriage, preterm labor, and fetal growth restriction. Evidence from non-pregnant models demonstrate that NPs can cross the lung air-blood barrier and circulate systemically. Therefore, inhalation of NPs during pregnancy leading to fetoplacental exposure has garnered attention. The purpose of this study was to evaluate the distribution of inhaled titanium dioxide nanoparticles (nano-TiO2) from the maternal lung to maternal and fetal systemic tissues. Pregnant Sprague Dawley rats were administered whole-body exposure to filtered air or of nano-TiO2 aerosols (9.96 ± 0.06 mg/m3) between gestational day (GD) 4 and 19. On GD 20 maternal, placental, and fetal tissues were harvested then digested for ICP-MS analysis to measure concentrations of titanium (Ti). TEM was used to visualize particle internalization by the placental syncytium. The results demonstrate the extrapulmonary distribution of Ti to various maternal organs during pregnancy. Our study found Ti accumulation in the decidua/junctional and labyrinth zones of placentas embedded in all sections of uterine horns. Further, NPs deposited in the placenta, identified by TEM, were found intracellularly within nuclear, endoplasmic reticulum, and vesicle organelles. This study identified the systemic distribution and placental accumulation of Ti after nano-TiO2 aerosol inhalation in a pregnancy model. These findings arouse concerns for poor air quality for pregnant women and possible contributions to adverse pregnancy outcomes.

Micro- and nanoplastic transfer, accumulation, and toxicity in humans.

Plastics impact our daily lives. Unfortunately, it is the disuse and disposal of these items that may affect us the greatest. Plastic micro- and nanosized particles, likely from bulk degradation, have been identified in air pollution and water sources. Recently, plastic particles have also been identified in consumable products. The purpose of this review is to identify the likely routes of human exposure, the toxicological outcomes and concerns currently reported, and to provide some considerations for future assessments.

Australian Community and Health Professionals Perceptions of Equine-Assisted Psychotherapy.

Mental health conditions are increasingly prevalent in the Australian population, and despite the large evidence-based support for contemporary treatments, there are barriers which inhibit their efficacy. Thus, there is a perceived need for therapists to consider other therapeutic options which have potential to enhance treatment outcomes. There is increasing acceptance for complementary and alternative medicines (CAM) among general practitioners and clients/general community. Specifically, more than 70% of Australians utilize CAM. Equine-assisted psychotherapy (EAP) is an underutilized, culturally sensitive, complementary therapy, which has the potential to mitigate barriers of conventional therapy. The present study aimed to determine the level of knowledge about and general acceptance of EAP as a treatment for general psychopathology symptomology within community members and health professionals. The current sample included 144 community members and 55 health professionals, all with Australian citizenship. Data analysis comprised the independent t-test and two hierarchical multiple regressions. Results indicated that community members are significantly more accepting of EAP as a treatment compared to health professionals. Of the predictors tested, higher social support and openness within community members were significant predictors of accepting perceptions, and rural location was the only significant predictor for health professional's accepting perceptions of EAP. This is one of the first studies to investigate perceptions of EAP outside the EAP field and through comparison between community members and health professionals. The current study identifies the need for future research to further investigate perceptions of EAP among Australian health professionals.

Considering intrauterine location in a model of fetal growth restriction after maternal titanium dioxide nanoparticle inhalation.

Fetal growth restriction (FGR) is a condition with several underlying etiologies including gestational disease (e.g., preeclampsia, gestational diabetes) and xenobiotic exposure (e.g., environmental contaminants, pharmaceuticals, recreational drugs). Rodent models allow study of FGR pathogenesis. However, given the multiparous rodent pregnancy, fetal growth variability within uterine horns may arise. To ascertain whether intrauterine position is a determinant of fetal growth, we redesigned fetal weight analysis to include litter size and maternal weight. Our FGR model is produced by exposing pregnant Sprague Dawley rats to aerosolized titanium dioxide nanoparticles at 9.44 ± 0.26 mg/m3 on gestational day (GD) 4, GD 12 or GD 17 or 9.53 ± 1.01 mg/m3 between GD 4-GD 19. In this study fetal weight data was reorganized by intrauterine location [i.e., right/left uterine horn and ovarian/middle/vaginal position] and normalized by maternal weight and number of feti per uterine horn. A significant difference in fetal weight in the middle location in controls (0.061g ± 0.001 vs. 0.055g ± 0.002), GD 4 (0.033g ± 0.003 vs. 0.049g ± 0.004), and GD 17 (0.047g ± 0.002 vs. 0.038g ± 0.002) exposed animals was identified. Additionally, GD 4 exposure produced significantly smaller feti in the right uterine horn at the ovarian end (0.052g ± 0.003 vs. 0.029g ± 0.003) and middle of the right uterine horn (0.060g ± 0.001 vs. 0.033g ± 0.003). GD 17 exposure produced significantly smaller feti in the left uterine horn middle location (0.055g ± 0.002 vs. 0.033 ± 0.002). Placental weights were unaffected, and placental efficiency was reduced in the right uterine horn middle location after GD 17 exposure (5.74g ± 0.16 vs. 5.09g ± 0.14). These findings identified: 1) differences in fetal weight of controls between the right and left horns in the middle position, and 2) differential effects of single whole-body pulmonary exposure to titanium dioxide nanoparticles on fetal weight by position and window of maternal exposure. In conclusion, these results indicate that consideration for intrauterine position, maternal weight, and number of feti per horn provides a more sensitive assessment of FGR from rodent reproductive and developmental studies.

Large effects of brief meditation intervention on EEG spectra in meditation novices.

This study investigated the impact of a brief meditation workshop on a sample of 223 novice meditators. Participants attended a three-day workshop comprising daily guided seated meditation sessions using music without vocals that focused on various emotional states and intentions (open focus). Based on the theory of integrative consciousness, it was hypothesized that altered states of consciousness would be experienced by participants during the meditation intervention as assessed using electroencephalogram (EEG). Brainwave power bands patterns were measured throughout the meditation training workshop, producing a total of 5616 EEG scans. Changes in conscious states were analysed using pre-meditation and post-meditation session measures of delta through to gamma oscillations. Results suggested the meditation intervention had large varying effects on EEG spectra (up to 50 % increase and 24 % decrease), and the speed of change from pre-meditation to post-meditation state of the EEG co-spectra was significant (with 0.76 probability of entering end-meditation state within the first minute). There was a main 5 % decrease in delta power (95 % HDI = [-0.07, -0.03]); a global increase in theta power of 29 % (95 % HDI = [0.27, 0.33]); a global increase of 16 % (95 % HDI = [0.13, 0.19]) in alpha power; a main effect of condition, with global beta power increasing by 17 % (95 % HDI = [0.15, 0.19]); and an 11 % increase (95 % HDI = [0.08, 0.14]) in gamma power from pre-meditation to end-meditation. Findings provided preliminary support for brief meditation in altering states of consciousness in novice meditators. Future clinical examination of meditation was recommended as an intervention for mental health conditions particularly associated with hippocampal impairments.

Toxicological considerations of nano-sized plastics.

Undoubtedly, plastics have changed human existence. These pervasive products are used in nearly every field to include technological, biomedical, and domestic applications. Post-consumer plastic waste disposal leading to plastic pollution in landfills, waterways, and oceans represents a worldwide environmental challenge. Accumulation and continued material fragmentation from micro- to nanoplastics has identified concerns pertaining to environmental and human exposures and toxicity. While many studies have focused on particle fate and identification, the toxicological considerations must focus on the biological relevance of particle deposition within a particular organism, compartment, organ, and tissue. Further, concerns exist regarding the physical and chemical properties of the plastic particles during their production and/or degradation. In this mini-review we will discuss (1) particle characterization and assessment, (2) environmental concerns, and (3) human toxicity.

Evaluating the use of whole genome sequencing for the investigation of a large mumps outbreak in Ontario, Canada.

In 2017 Ontario experienced the largest mumps outbreak in the province in 8 years, at a time when multiple outbreaks were occurring across North America. Of 259 reported cases, 143 occurred in Toronto, primarily among young adults. Routine genotyping of the small hydrophobic gene indicated that the outbreak was due to mumps virus genotype G. We performed a retrospective study of whole genome sequencing of 26 mumps virus isolates from early in the outbreak, using a tiling amplicon method. Results indicated that two of the cases were genetically divergent, with the remaining 24 cases belonging to two major clades and one minor clade. Phylogeographic analysis confirmed circulation of virus from each clade between Toronto and other regions in Ontario. Comparison with other genotype G strains from North America suggested that the presence of co-circulating major clades may have been due to separate importation events from outbreaks in the United States. A transmission network analysis performed with the software program TransPhylo was compared with previously collected epidemiological data. The transmission tree correlated with known epidemiological links between nine patients and identified new potential clusters with no known epidemiological links.

Identification and quantification of gold engineered nanomaterials and impaired fluid transfer across the rat placenta via ex vivo perfusion.

Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 µL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.

Effect of Gestational Age on Maternofetal Vascular Function Following Single Maternal Engineered Nanoparticle Exposure.

Normal pregnancy outcome is accomplished, in part, by rapid and expansive physiological adaptations to the systemic circulation, the extent of which is specific to gestational day (GD) and anatomical location. Pregnancy-related hemodynamic changes in uterine placental blood flow stimulate compensatory vascular signaling and remodeling that begins early and continues throughout gestation. Exposure of the maternal environment to engineered nanomaterials (ENM) during pregnancy has been shown to impact health of the dam, fetus, and adult offspring; however, the consequences of specific temporal (gestational age) and spatial (vascular location) considerations are largely undetermined. We exposed pregnant Sprague-Dawley rats to nano-TiO2 aerosols at three critical periods of fetal development (GD 4, 12, and 17) to identify vascular perturbations associated with ENM exposure at these developmental milestones. Vascular reactivity of the maternal thoracic aorta, the uterine artery, the umbilical vein, and the fetal thoracic aorta were evaluated using wire myography on GD 20. While impairments were noted at each level of the maternofetal vascular tree and at each exposure day, our results indicate the greatest effects may be identified within the fetal vasculature (umbilical vein and fetal aorta), wherein effects of a single maternal inhalational exposure to nano-TiO2 on GD 4 modified responses to cholinergic, NO, and α-adrenergic signaling.

Estrous cycle-dependent modulation of in vivo microvascular dysfunction after nanomaterial inhalation.

Preconceptive health encompasses male and female reproductive capability. In females, this takes into account each of the stages of the estrous cycle. Microvascular reactivity varies throughout the estrous cycle in response to hormonal changes and in preparation for pregnancy. Microvascular alterations in response to engineered nanomaterial (ENM) exposure have been described within 24-h of inhalation; however, the impact upon the uterine vasculature at differing estrous stages and at late-stage pregnancy is unclear. Female Sprague Dawley (SD) rats (virgin and late stage pregnancy [GD 19]) were exposed to nano-TiO aerosols (173.2 ±â€¯6.4 nm, 10.2 ±â€¯0.46 mg/m3, 5 h) 24-h prior to experimentation leading to a single calculated deposition of 42.2 ±â€¯1.9 µg nano- TiO2 (exposed) or 0 µg (control). Animals were anesthetized, estrous status verified, and prepared for in situ assessment of leukocyte trafficking and vascular function by means of intravital microscopy, Uterine basal arteriolar reactivity was stimulated using iontophoretically applied chemicals: acetylcholine (ACh, 0.025 M; 20, 40, 100, 200 nA), sodium nitroprusside (SNP, 0.05 M; 20, 40, 100 nA), phenylephrine (PE, 0.05 M; 20, 40, 100 nA). Finally, adenosine (ADO, 10-4 M) was superfused over the tissue to identify maximum diameter. In situ vessel reactivity after exposure was significantly blunted based on estrous stage, but not at late-stage pregnancy. Local uterine venular leukocyte trafficking and systemic inflammatory markers were also significantly affected during preparatory (proestrus), fertile (estrus), and infertile (diestrus) periods after ENM inhalation. Overall, these deficits in reactivity and increased inflammatory activity may impair female fertility after ENM exposure.

Engineered nanomaterial applications in perinatal therapeutics.

Engineered nanomaterials (ENM) are widely used in commercial, domestic, and more recently biomedical applications. While the majority of exposures to ENM are unintentional, biomedical platforms are being evaluated for use in individualized and/or tissue-targeted therapies. Treatments are often avoided during prenatal periods to reduce adverse effects on the developing fetus. The placenta is central to maternal-fetal medicine. Perturbation of placental functions can limit transfer of necessary nutrients, alter production of hormones needed during pregnancy, or allow undesired passage of xenobiotics to the developing fetus. The development of therapeutics to target specific maternal, placental, or fetal tissues would be especially important to reduce or circumvent toxicities. Therefore, this review will discuss the potential use of ENM in perinatal medicine, the applicable physiochemical properties of ENM in therapeutic use, and current methodologies of ENM testing in perinatal medicine, and identify maternal, fetal, and offspring concerns associated with ENM exposure during gestation. As potential nanoparticle-based therapies continue to develop, so does the need for thorough consideration and evaluation for use in perinatal medicine.

Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome.

BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. Pregnant dams were exposed to nano-titanium dioxide (nano-TiO2) aerosols (10 ± 0.5 mg/m3) for 7-8 days (calculated, cumulative lung deposition = 217 ± 1 µg) and on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. RESULTS: The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO2 exposed progeny. The most notable alterations in major biologic systems included immune adaptation and organismal growth. Changes in normal physiology were linked with other tissues, including liver and kidneys. CONCLUSIONS: These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome.

Staphylococcus aureus interaction with Pseudomonas aeruginosa biofilm enhances tobramycin resistance.

Antimicrobial resistance is a significant threat to the treatment of infectious disease. Multiple mechanisms of resistance to different classes of antibiotics have been identified and well-studied. However, these mechanisms are studied with bacteria in isolation, whereas often, infections have a polymicrobial basis. Using a biofilm slide chamber model, we visualized the formation and development of clinical Pseudomonas aeruginosa biofilms in the presence of secreted Staphylococcus aureus exoproducts, two bacteria that commonly co-infect pediatric patients with cystic fibrosis. We showed that, over time, certain isolates of P. aeruginosa can form different biofilm architecture in the presence of S. aureus exoproducts. We further determined that this interaction was dependent on Psl produced by P. aeruginosa and staphylococcal protein A from S. aureus. Importantly, we identified a mechanism of antibiotic resistance to tobramycin that is dependent on the polymicrobial interactions between these two bacteria. This interaction occurred in isolates of P. aeruginosa recovered from children with cystic fibrosis who failed to clear P. aeruginosa following inhaled tobramycin treatment.

Advantages of melodic over rhythmic movement sonification in bimanual motor skill learning.

An important question for skill acquisition is whether and how augmented feedback can be designed to improve the learning of complex skills. Auditory information triggered by learners' actions, movement sonification, can enhance learning of a complex bimanual coordination skill, specifically polyrhythmic bimanual shape tracing. However, it is not clear whether the coordination of polyrhythmic sequenced movements is enhanced by auditory-specified timing information alone or whether more complex sound mappings, such as melodic sonification, are necessary. Furthermore, while short-term retention of bimanual coordination performance has been shown with movement sonification training, longer term retention has yet to be demonstrated. In the present experiment, participants learned to trace a diamond shape with one hand while simultaneously tracing a triangle with the other to produce a sequenced 4:3 polyrhythmic timing pattern. Two groups of participants received real-time auditory feedback during training: melodic sonification (individual movements triggered a separate note of a melody) and rhythmic sonification (each movement triggered a percussive sound), while a third control group received no augmented feedback. Task acquisition and performance in immediate retention were superior in the melodic sonification group as compared to the rhythmic sonification and control group. In a 24-h retention phase, a decline in performance in the melodic sonification group was reversed by brief playback of the target pattern melody. These results show that melodic sonification of movement can provide advantages over augmented feedback which only provides timing information by better structuring the sequencing of timed actions, and also allow recovery of complex target patterns of movement after training. These findings have important implications for understanding the role of augmented perceptual information in skill learning, as well as its application to real-world training or rehabilitation scenarios.

Antibiotic resistance patterns of Escherichia coli urinary isolates and comparison with antibiotic consumption data over 10 years, 2005-2014.

INTRODUCTION: Escherichia coli is a common cause of urinary tract infections (UTI). Reviews of antibiotic resistance of this organism can inform choice of empiric treatment of UTI and other infections and strategies for combating antimicrobial resistance. We reviewed laboratory and hospital pharmacy records to assess trends in non-susceptibility rates and the effect of antimicrobial stewardship interventions. METHODS: A retrospective observational study of isolates of E. coli from MSU samples at a Dublin teaching hospital from inpatients and community, obtained from January 2005 to December 2014. Susceptibility to a panel of antibiotics was determined using the disc diffusion method, as well as extended-spectrum beta-lactamase (ESBL) production status. Trends in resistance were plotted graphically and analysed in a descriptive manner. RESULTS: Except for nitrofurantoin and gentamicin, non-susceptibility increased for all antimicrobials tested. Co-amoxiclav non-susceptibility reached 48% in hospital and 32.6% in the community by 2014. Piperacillin-tazobactam non-susceptibility increased from 6.8 to 23.8% in hospital and from <1 to 12.5% in community, with similar increases for ESBL producing isolates. Ciprofloxacin non-susceptibility peaked at 25.5% in hospital in 2012 and 11.44% in the community in 2014. CONCLUSION: Escherichia coli isolates from community MSU samples have high rates of non-susceptibility to trimethoprim and co-amoxiclav. Nitrofurantoin remains the best empiric therapy for cystitis. Increasing non-susceptibility to co-amoxiclav and piperacillin-tazobactam in hospital isolates is concerning. Ciprofloxacin non-susceptibility is increasing faster in the community than in hospital. A sharp reduction in hospital fluoroquinolone consumption did not result in a significant reduction in ciprofloxacin non-susceptibility of hospital E. coli isolates.

Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2 together with epidermal keratinocytes and skin irritation.

OBJECTIVES: The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. METHODS: Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. RESULTS: Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies. CONCLUSIONS: Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol did not. As a result, we show that ethanol-based sanitizers are better tolerated by skin, particularly in high-use settings, than other alcohols and should be the active ingredient of choice.