Fistula development after anal abscess drainage-a multicentre retrospective cohort study.

PURPOSE: Anal abscesses are common and, despite correct treatment with surgical drainage, carry the risk of developing fistulas. Studies identifying risk factors for the development of anal fistulas are sparse. This study aimed to identify the risk factors for anal fistulas after anal abscess surgery. METHODS: This was a multicentre, retrospective cohort study of patients undergoing acute surgery for anal abscesses in the Capital Region of Denmark between 2018 and 2019. The patients were identified using ICD-10 codes for anal abscesses. Predefined clinicopathological factors and postoperative courses were extracted from patient records. RESULTS: A total of 475 patients were included. At a median follow-up time of 1108 days (IQR 946-1320 days) following surgery, 164 (33.7%) patients were diagnosed with an anal fistula. Risk factors for developing fistulas were low intersphincteric (OR 2.77, 95CI 1.50-5.06) and ischioanal (OR 2.48, 95CI 1.36-4.47) abscesses, Crohn's disease (OR 5.96, 95CI 2.33-17.2), a history of recurrent anal abscesses (OR 4.14, 95CI 2.47-7.01) or repeat surgery (OR 5.96, 95CI 2.33-17.2), E. coli-positive pus cultures (OR 4.06, 1.56-11.4) or preoperative C-reactive protein (CRP) of more than 100 mg/L (OR 3.21, 95CI 1.57-6.71). CONCLUSION: Several significant clinical risk factors were associated with fistula development following anal abscess surgery. These findings are clinically relevant and could influence the selection of patients for specialised follow-up, facilitate expedited diagnosis, and potentially prevent unnecessarily long treatment courses.

Socioeconomic differences in associations between living in a 20-min neighbourhood and diet, physical activity and self-rated health: Cross-sectional findings from ProjectPLAN.

The 20-min neighbourhood (20MN) concept aims to enable residents to meet daily needs using resources within a 20-min trip from home noting that there is no single definition of what services and amenities are required for daily needs nor what modes of transport constitute a 20 min trip. Whether 20MNs promote better health and whether associations differ by socio-economic status (SES) is unknown. Using cross-sectional data from adults randomly sampled in 2018-19 from Melbourne or Adelaide, Australia, we examined whether associations between neighbourhood type (20MN/non-20MN) and diet, physical activity or self-rated health vary according to individual- or area-level SES. We found no consistent patterns of interactions. The results do not consistently support the often assumed belief that 20MNs support more healthful behaviour and that these relationships vary by SES.

[Transanal endoscopic microsurgery for excision of a symptomatic tailgut cyst].

A tailgut cyst is a rare tumour originating from the embryonic remnant of the retrorectal space. The cyst is often asymptomatic, but it can cause abdominal or rectal pain and urogenital symptoms. When diagnosed, resection is the choice of treatment, and traditionally open surgery has been preferred. In this case report, we present a 30-year-old female patient with a painful tailgut cyst. She was found to be candidate for transanal endoscopic microsurgery, which was successfully performed.

Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer.

Endocrine therapies for prostate cancer inhibit the androgen receptor (AR) transcription factor. In most cases, AR activity resumes during therapy and drives progression to castration-resistant prostate cancer (CRPC). However, therapy can also promote lineage plasticity and select for AR-independent phenotypes that are uniformly lethal. Here, we demonstrate the stem cell transcription factor Krüppel-like factor 5 (KLF5) is low or absent in prostate cancers prior to endocrine therapy, but induced in a subset of CRPC, including CRPC displaying lineage plasticity. KLF5 and AR physically interact on chromatin and drive opposing transcriptional programs, with KLF5 promoting cellular migration, anchorage-independent growth, and basal epithelial cell phenotypes. We identify ERBB2 as a point of transcriptional convergence displaying activation by KLF5 and repression by AR. ERBB2 inhibitors preferentially block KLF5-driven oncogenic phenotypes. These findings implicate KLF5 as an oncogene that can be upregulated in CRPC to oppose AR activities and promote lineage plasticity.

Residential Area Sociodemographic and Breast Cancer Screening Venue Location Built Environmental Features Associated with Women's Use of Closest Venue in Greater Sydney, Australia.

Understanding environmental predictors of women's use of closest breast screening venue versus other site(s) may assist optimal venue placement. This study assessed relationships between residential-area sociodemographic measures, venue location features, and women's use of closest versus other venues. Data of 320,672 Greater Sydney screening attendees were spatially joined to residential state suburbs (SSCs) (n = 799). SSC-level sociodemographic measures included proportions of: women speaking English at home; university-educated; full-time employed; and dwellings with motor-vehicles. A geographic information system identified each woman's closest venue to home, and venue co-location with bus-stop, train-station, hospital, general practitioner, and shop(s). Multilevel logistic models estimated associations between environmental measures and closest venue attendance. Attendance at closest venue was 59.4%. Closest venue attendance was positively associated with SSC-level women speaking English but inversely associated with SSC-level women university-educated, full-time employed, and dwellings with motor-vehicles. Mobile venue co-location with general practitioner and shop was positively, but co-location with bus-stop and hospital was inversely associated with attendance. Attendance was positively associated with fixed venue co-location with train-station and hospital but inversely associated with venue co-location with bus-stop, general practitioner, and shop. Program planners should consider these features when optimising service locations to enhance utilisation. Some counterintuitive results necessitate additional investigation.

Ribosylation of the CD8αß heterodimer permits binding of the nonclassical major histocompatibility molecule, H2-Q10.

The CD8αß heterodimer plays a crucial role in the stabilization between major histocompatibility complex class I molecules (MHC-I) and the T cell receptor (TCR). The interaction between CD8 and MHC-I can be regulated by posttranslational modifications, which are proposed to play an important role in the development of CD8 T cells. One modification that has been proposed to control CD8 coreceptor function is ribosylation. Utilizing NAD+, the ecto-enzyme adenosine diphosphate (ADP) ribosyl transferase 2.2 (ART2.2) catalyzes the addition of ADP-ribosyl groups onto arginine residues of CD8α or ß chains and alters the interaction between the MHC and TCR complexes. To date, only interactions between modified CD8 and classical MHC-I (MHC-Ia), have been investigated and the interaction with non-classical MHC (MHC-Ib) has not been explored. Here, we show that ADP-ribosylation of CD8 facilitates the binding of the liver-restricted nonclassical MHC, H2-Q10, independent of the associated TCR or presented peptide, and propose that this highly regulated binding imposes an additional inhibitory leash on the activation of CD8-expressing cells in the presence of NAD+. These findings highlight additional important roles for nonclassical MHC-I in the regulation of immune responses.

Associations between breast cancer screening participation and residential area sociodemographic features, geographic accessibility, and features of screening venue location in Greater Sydney, Australia.

Breast cancer screening (BCS) participation rates are often suboptimal and vary geographically. Environmental features may influence BCS participation, but few studies have assessed this relationship. This study assessed the associations between BCS participation, residential area sociodemographic characteristics, distance to BCS venue, and venue location attributes. Data for 384,433 women residing in Greater Sydney, Australia, invited to BCS during 2011-2014 were spatially joined to their state suburb (SSC) (n = 800). SSC sociodemographic measures included women's median age, proportion women speaking English at home, full-time employed, and university educated; and proportion dwellings with motor-vehicles. Road network distance was calculated to each BCS venue. BCS venues were coded as co-located with bus-stop, train-station, hospital, general practitioner (GP), and shop. Hot spots were calculated to quantify spatial clustering of BCS participation. Multilevel logistic models were used to estimate the associations between environmental predictors and BCS participation, accounting for SSC-level clustering. BCS participation was 53.9% and spatially clustered. BCS was positively associated with SSC-level median age for women, proportions women speaking English and university educated, and dwellings with motor-vehicles. Distance to venue was inversely associated with BCS. Venue co-location with GP was positively associated and co-location with bus-stop, train-station, and shop, hospital were negatively associated with BCS. Residential sociodemographic features, geographic access, and venue location attributes are associated with BCS participation. These findings implicate the relevance of social and built environmental factors to programmatic aims to raise BCS participation. Additional research on venue location features is required to understand where best to site BCS venues.

Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.

INTRODUCTION: Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS: This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

AR gene rearrangement analysis in liquid biopsies reveals heterogeneity in lethal prostate cancer.

Castration-resistant prostate cancer (CRPC) is driven by AR gene aberrations that arise during androgen receptor (AR)-targeted therapy. AR amplification and mutations have been profiled in circulating tumor cells (CTCs), but whether AR gene rearrangements can be assessed in CTCs is unknown. In this study, we leveraged CRPC cell lines with defined AR gene rearrangements to develop and validate a CTC DNA analysis approach that utilized whole genome amplification and targeted DNA-sequencing of AR and other genes important in CRPC. We tested the utility of this approach by analyzing matched CTC DNA and plasma cell-free DNA (cfDNA) from a case series of ten CRPC patients. One of ten CTC samples and two of ten cfDNA samples were positive for AR gene rearrangements. All AR gene rearrangements were discordant between matched liquid biopsy samples. One patient harbored separate AR gene rearrangements in CTC DNA and cfDNA, but concordant AR amplification and AR T878A mutation. This patient also displayed concordant loss of TP53 and PTEN, but the loss of RB1 in cfDNA only. The overall frequency of discordant alterations in these genes between matched CTC DNA and cfDNA was high. This study establishes the technical feasibility of analyzing structural rearrangements, mutations, and copy number variants in AR and other CRPC genes using two different sources of DNA from a single blood sample. Paired CTC DNA and cfDNA analysis may have utility for capturing the heterogeneity of genetic alterations in CRPC patients.

Protein Phase Separation Arising from Intrinsic Disorder: First-Principles to Bespoke Applications.

The phase separation of biomolecules has become the focus of intense research in the past decade, with a growing body of research implicating this phenomenon in essentially all biological functions, including but not limited to homeostasis, stress responses, gene regulation, cell differentiation, and disease. Excellent reviews have been published previously on the underlying physical basis of liquid-liquid phase separation (LLPS) of biological molecules (Nat. Phys. 2015, 11, 899-904) and LLPS as it occurs natively in physiology and disease (Science 2017, 357, eaaf4382; Biochemistry 2018, 57, 2479-2487; Chem. Rev. 2014, 114, 6844-6879). Here, we review how the theoretical physical basis of LLPS has been used to better understand the behavior of biomolecules that undergo LLPS in natural systems and how this understanding has also led to the development of novel synthetic systems that exhibit biomolecular phase separation, and technologies that exploit these phenomena. In part 1 of this Review, we explore the theory behind the phase separation of biomolecules and synthetic macromolecules and introduce a few notable phase-separating biomolecules. In part 2, we cover experimental and computational methods used to study phase-separating proteins and how these techniques have uncovered the mechanisms underlying phase separation in physiology and disease. Finally, in part 3, we cover the development and applications of engineered phase-separating polypeptides, ranging from control of their self-assembly to create defined supramolecular architectures to reprogramming biological processes using engineered IDPs that exhibit LLPS.

3D Printed Acetabular Components for Complex Revision Arthroplasty.

Recent studies have shown high early failure rates with Cup Cage constructs in complex revision surgery for Paprosky 3B acetabular defects. As a result, the use of 3D printed custom-made acetabular components has become more common. In this case series, we present two cases that demonstrate the latest advancement in 3D printed implants for severe acetabular bone loss. The follow up was 3 and 7 years. Neither patient has undergone revision surgery of the acetabular component to date. One patient sustained a femoral peri-prosthetic fracture requiring plate fixation. This case study demonstrates that 3D printed implants have excellent intraoperative and immediate postoperative outcomes in revision surgery for severe acetabular bone defects.

Residential area and screening venue location features associated with spatial variation in breast cancer screening invitation response rates: an observational study in Greater Sydney, Australia.

OBJECTIVES: Participation in breast cancer screening (BCS) varies at the small-area level, which may reflect environmental influences. This study assessed small-area variation in BCS invitation response rates (IRRs) and associations between small-area BCS IRR, sociodemographic factors, BCS venue distance and venue location features in Greater Sydney, Australia. METHODS: BCS IRR data for 2011-2012 were compiled for 9528 Australian Bureau of Statistics Statistical Area Level 1 (SA1) units (n=227 474 women). A geographial information system was used to extract SA1-level sociodemographic features (proportions of women speaking English at home, full-time employed and university educated, and proportion of dwellings with motor vehicles), SA1-level distance to closest venue(s) (expressed as quartiles), and closest venue(s) colocated with bus stops, train station, hospital, general practitioner and shops. Associations between area-level features, BCS venue distance, venue location features and IRR were estimated using ordinary least square-type spatial lag models including area education as a covariate. RESULTS: BCS IRR varied across SA1s (mean=59.8%, range: 0%-100%), with notable spatial autocorrelation (Moran's I=0.803). BCS IRR was positively associated with greater SA1-level proportion of women speaking English at home (ß=2.283, 95% CI 2.024 to 2.543), women's education (in the model including speaking English at home ß=0.454, 95% CI 0.211 to 0.697), dwellings with motor vehicles (ß=1.836, 95% CI 1.594 to 2.078), greater distance to venue (eg, most distant quartile compared with closest: ß=6.249, 95% CI 5.489 to 7.008), and BCS venue colocated with shops (ß=0.762, 95% CI 0.273 to 1.251). Greater SA1-level women employment (ß=-0.613, 95% CI -0.898 to -0.328) and venue colocated with train station (ß=-1.889, 95% CI -2.376 to -1.402) or hospital (ß=-0.677, 95% CI -1.164 to -0.189) were inversely related to BCS IRR. CONCLUSIONS: Small-area variation in BCS IRR exists for Greater Sydney and is strongly related to sociodemographic factors that, together with BCS venue location features, could inform targeted attempts to improve IRR.

Phytotoxicity of Silver Nanoparticles on Tobacco Plants: Evaluation of Coating Effects on Photosynthetic Performance and Chloroplast Ultrastructure.

Silver nanoparticles (AgNPs) are the most exploited nanomaterial in agriculture and food production, and their release into the environment raises concern about their impact on plants. Since AgNPs are prone to biotransformation, various surface coatings are used to enhance their stability, which may modulate AgNP-imposed toxic effects. In this study, the impact of AgNPs stabilized with different coatings (citrate, polyvinylpyrrolidone (PVP), and cetyltrimethylammonium bromide (CTAB)) and AgNO3 on photosynthesis of tobacco plants as well as AgNP stability in exposure medium have been investigated. Obtained results revealed that AgNP-citrate induced the least effects on chlorophyll a fluorescence parameters and pigment content, which could be ascribed to their fast agglomeration in the exposure medium and consequently weak uptake. The impact of AgNP-PVP and AgNP-CTAB was more severe, inducing a deterioration of photosynthetic activity along with reduced pigment content and alterations in chloroplast ultrastructure, which could be correlated to their higher stability, elevated Ag accumulation, and surface charge. In conclusion, intrinsic properties of AgNP coatings affect their stability and bioavailability in the biological medium, thereby indirectly contributing changes in the photosynthetic apparatus. Moreover, AgNP treatments exhibited more severe inhibitory effects compared to AgNO3, which indicates that the impact on photosynthesis is dependent on the form of Ag.

Prevalence of overweight and obesity, and associations with socio-demographic factors in Kuwait.

BACKGROUND: Kuwait is amongst countries in the Gulf region with high income economy. According to the World Health Organisation (WHO), one in five adults in the Gulf region is obese. This study sought to evaluate the prevalence and magnitude of association between overweight, obesity, central obesity, and socio-demographic factors in Kuwait. METHODS: A population-based cross-sectional survey of diabetes and obesity in Kuwait - part of the Kuwait Diabetes Epidemiology Program - was conducted between 2011 and 2014, targeting adults aged 18-82 years using the WHO STEPwise approach to non-communicable disease surveillance. Body mass index (BMI) was calculated to classify overweight and obesity, and waist circumference (WC) used to express central obesity. Multivariable logistic regression was used to estimate relationships between socio-demographic factors, overweight (25.0-29.9 kg/m2), obesity (≥30.0 kg/m2) or central obesity (WC ≥ 80 cm women; WC ≥ 94 cm men). RESULTS: Records for gender (56% Men), age, BMI, governorate, and nationality existed for 4901 individuals. Mean age and BMI were 43 years and 30 kg/m2, respectively. Non-Kuwaiti nationals were more prevalent than Kuwaitis (76% vs 24%). Prevalence rates for overweight, obesity and central obesity were 40.6% (95%CI: 38.4-42.8%), 42.1% (95%CI: 40.0-44.3%) and 73.7% (95%CI: 71.7-75.6%), respectively. The youngest age group (18-29 years) had rates of 38.2% (95%CI: 29.2-47.7%), 27.2% (95%CI: 19.0-36.7%) and 49.9% (95%CI: 40.6-59.1%) for overweight, obesity and central obesity, respectively. In covariate-adjusted analyses, the odds of being overweight was 26% greater for men than for women. Conversely, women had a 54% (95%CI: 19-99%) and 7-fold (95%CI, 5-10-fold) greater odds of obesity/central obesity, respectively, than men. Greater educational attainment, physical activity, and non-Kuwaiti status were associated with lower odds of obesity/central obesity. History of smoking, elevated blood pressure, higher income, being married, greater age and female sex related to greater odds of obesity/central obesity. CONCLUSION: Overweight was greater in men, obesity greater in women. Overweight and obesity prevalence were high in young adults aged 18-29 years, a significant public health concern. Efforts to integrate mandatory physical education to the school curriculum and promoting the creation of recreation spaces/parks to promote physical activities, will play a vital role in the early prevention of overweight/obesity in Kuwait.

Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial.

BACKGROUND: Men who are overweight or obese frequently have low serum testosterone concentrations, which are associated with increased risk of type 2 diabetes. We aimed to determine whether testosterone treatment prevents progression to or reverses early type 2 diabetes, beyond the effects of a community-based lifestyle programme. METHODS: T4DM was a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial done at six Australian tertiary care centres. Men aged 50-74 years, with a waist circumference of 95 cm or higher, a serum testosterone concentration of 14·0 nmol/L or lower but without pathological hypogonadism, and impaired glucose tolerance (oral glucose tolerance test [OGTT] 2-h glucose 7·8-11·0 mmol/L) or newly diagnosed type 2 diabetes (provided OGTT 2-h glucose ≤15·0 mmol/L) were enrolled in a lifestyle programme and randomly assigned (1:1) to receive an intramuscular injection of testosterone undecanoate (1000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years. Randomisation was done centrally, including stratification by centre, age group, waist circumference, 2-h OGTT glucose, smoking, and first-degree family history of type 2 diabetes. The primary outcomes at 2 years were type 2 diabetes (2-h OGTT glucose ≥11·1 mmol/L) and mean change from baseline in 2-h OGTT glucose, assessed by intention to treat. For safety assessment, we did a masked monitoring of haematocrit and prostate-specific antigen, and analysed prespecified serious adverse events. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000287831. FINDINGS: Between Feb 5, 2013, and Feb 27, 2017, of 19 022 men who were pre-screened, 1007 (5%) were randomly assigned to the placebo (n=503) and testosterone (n=504) groups. At 2 years, 2-h glucose of 11·1 mmol/L or higher on OGTT was reported in 87 (21%) of 413 participants with available data in the placebo group and 55 (12%) of 443 participants in the testosterone group (relative risk 0·59, 95% CI 0·43 to 0·80; p=0·0007). The mean change from baseline 2-h glucose was -0·95 mmol/L (SD 2·78) in the placebo group and -1·70 mmol/L (SD 2·47) in the testosterone group (mean difference -0·75 mmol/L, -1·10 to -0·40; p<0·0001). The treatment effect was independent of baseline serum testosterone. A safety trigger for haematocrit greater than 54% occurred in six (1%) of 484 participants in the placebo group and 106 (22%) of 491 participants in the testosterone group, and a trigger for an increase of 0·75 µg/mL or more in prostate-specific antigen occurred in 87 (19%) of 468 participants in the placebo group and 109 (23%) of 480 participants in the testosterone group. Prespecified serious adverse events occurred in 37 (7·4%, 95% CI 5·4 to 10·0) of 503 patients in the placebo group and 55 (10·9%, 8·5 to 13·9) of 504 patients in the testosterone group. There were two deaths in each group. INTERPRETATION: Testosterone treatment for 2 years reduced the proportion of participants with type 2 diabetes beyond the effects of a lifestyle programme. Increases in haematocrit might be treatment limiting. Longer-term durability, safety, and cardiovascular effects of the intervention remain to be further investigated. FUNDING: Australian National Health and Medical Research Council, Bayer, Eli Lilly, University of Adelaide, and WW (formerly Weight Watchers).

Associations between area socioeconomic status, individual mental health, physical activity, diet and change in cardiometabolic risk amongst a cohort of Australian adults: A longitudinal path analysis.

Presumed pathways from environments to cardiometabolic risk largely implicate health behaviour although mental health may play a role. Few studies assess relationships between these factors. This study estimated associations between area socioeconomic status (SES), mental health, diet, physical activity, and 10-year change in glycosylated haemoglobin (HbA1c), comparing two proposed path structures: 1) mental health and behaviour functioning as parallel mediators between area SES and HbA1c; and 2) a sequential structure where mental health influences behaviour and consequently HbA1c. Three waves (10 years) of population-based biomedical cohort data were spatially linked to census data based on participant residential address. Area SES was expressed at baseline using an established index (SEIFA-IEO). Individual behavioural and mental health information (Wave 2) included diet (fruit and vegetable servings per day), physical activity (meets/does not meet recommendations), and the mental health component score of the 36-item Short Form Health Survey. HbA1c was measured at each wave. Latent variable growth models with a structural equation modelling approach estimated associations within both parallel and sequential path structures. Models were adjusted for age, sex, employment status, marital status, education, and smoking. The sequential path model best fit the data. HbA1c worsened over time. Greater area SES was statistically significantly associated with greater fruit intake, meeting physical activity recommendations, and had a protective effect against increasing HbA1c directly and indirectly through physical activity behaviour. Positive mental health was statistically significantly associated with greater fruit and vegetable intakes and was indirectly protective against increasing HbA1c through physical activity. Greater SES was protective against increasing HbA1c. This relationship was partially mediated by physical activity but not diet. A protective effect of mental health was exerted through physical activity. Public health interventions should ensure individuals residing in low SES areas, and those with poorer mental health are supported in meeting physical activity recommendations.

Coating-Dependent Effects of Silver Nanoparticles on Tobacco Seed Germination and Early Growth.

Silver nanoparticles (AgNPs) are used in a wide range of consumer products because of their excellent antimicrobial properties. AgNPs released into the environment are prone to transformations such as aggregation, oxidation, or dissolution so they are often stabilised by coatings that affect their physico-chemical properties and change their effect on living organisms. In this study we investigated the stability of polyvinylpyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB) coated AgNPs in an exposure medium, as well as their effect on tobacco germination and early growth. AgNP-CTAB was found to be more stable in the solid Murashige and Skoog (MS) medium compared to AgNP-PVP. The uptake and accumulation of silver in seedlings was equally efficient after exposure to both types of AgNPs. However, AgNP-PVP induced only mild toxicity on seedlings growth, while AgNP-CTAB caused severe negative effects on all parameters, even compared to AgNO3. Moreover, CTAB coating itself exerted negative effects on growth. Cysteine addition generally alleviated AgNP-PVP-induced negative effects, while it failed to improve germination and growth parameters after exposure to AgNP-CTAB. These results suggest that the toxic effects of AgNP-PVP are mainly a consequence of release of Ag+ ions, while phytotoxicity of AgNP-CTAB can rather be ascribed to surface coating itself.

Methods for accounting for neighbourhood self-selection in physical activity and dietary behaviour research: a systematic review.

BACKGROUND: Self-selection into residential neighbourhoods is a widely acknowledged, but under-studied problem in research investigating neighbourhood influences on physical activity and diet. Failure to handle neighbourhood self-selection can lead to biased estimates of the association between the neighbourhood environment and behaviour. This means that effects could be over- or under-estimated, both of which have implications for public health policies related to neighbourhood (re)design. Therefore, it is important that methods to deal with neighbourhood self-selection are identified and reviewed. The aim of this review was to assess how neighbourhood self-selection is conceived and accounted for in the literature. METHODS: Articles from a systematic search undertaken in 2017 were included if they examined associations between neighbourhood environment exposures and adult physical activity or dietary behaviour. Exposures could include any objective measurement of the built (e.g., supermarkets), natural (e.g., parks) or social (e.g., crime) environment. Articles had to explicitly state that a given method was used to account for neighbourhood self-selection. The systematic review was registered with the PROSPERO International Prospective Register of Systematic Reviews (number CRD42018083593) and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Of 31 eligible articles, almost all considered physical activity (30/31); few examined diet (2/31). Methods used to address neighbourhood self-selection varied. Most studies (23/31) accounted for items relating to participants' neighbourhood preferences or reasons for moving to the neighbourhood using multi-variable adjustment in regression models (20/23) or propensity scores (3/23). Of 11 longitudinal studies, three controlled for neighbourhood self-selection as an unmeasured confounder using fixed effects regression. CONCLUSIONS: Most studies accounted for neighbourhood self-selection by adjusting for measured attributes of neighbourhood preference. However, commonly the impact of adjustment could not be assessed. Future studies using adjustment should provide estimates of associations with and without adjustment for self-selection; consider temporality in the measurement of self-selection variables relative to the timing of the environmental exposure and outcome behaviours; and consider the theoretical plausibility of presumed pathways in cross-sectional research where causal direction is impossible to establish.

Development and evaluation of a patient decision aid for patients considering ongoing medical or surgical treatment options for ulcerative colitis using a mixed-methods approach: protocol for DISCUSS study.

INTRODUCTION: Approximately 20%-30% of patients with ulcerative colitis (UC) require surgery, the majority of these being elective due to chronic symptoms refractory to medical treatment. The decision for surgery is difficult and dependent on patient preferences. Current resources for patients considering surgery have been found not to meet minimum international standards. The overall aim of the 'DISCUSS' study is to develop and evaluate a new patient decision aid (PtDA) for patients considering surgery for UC created in line with international minimum standards. METHODS AND ANALYSIS: This is a prospective mixed-methods study of adults (18+ years) who are considering surgical intervention for UC across two regional centres in Yorkshire, UK. This study is in three stages. In stage 1 we will develop the PtDA and its content via systematic reviews and a patient questionnaire. In stage 2 we will assess the face validity of the PtDA using mixed-methods on key stakeholders using both semistructured interviews and questionnaires, following which the PtDA will be refined. In stage 3 we will assess the acceptability of using the PtDA in clinical practice. This will use a mixed-methods approach on clinicians and patients who are considering undergoing elective surgery. Questionnaires including the Preparation for Decision-Making Scale, a measure of anxiety and decisional conflict will be analysed at two timepoints using paired sample t-tests and CIs. Interviews with patients and clinicians will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Research ethics approval from North East-Tyne & Wear South Research Ethics Committee (Ref: 19/NE/0073) and Health Research Authority approval (Ref: 257044) have been granted. Results will be published in open access peer-reviewed journals, presented in conferences and distributed through the Crohn's and Colitis UK charity. External endorsement will be sought from the International Patient Decision Aid Standards Collaboration inventory of PtDAs. PROSPERO REGISTRATION NUMBER: CRD42018115513, CRD42019126186, CRD42019125193.

Ectoparasites of brown rats (Rattus norvegicus) in Grenada, West Indies.

BACKGROUND AND AIM: Arthropod ectoparasites (mites, lice, ticks, and fleas) on common house rats or brown rats (Rattus norvegicus) are known to transmit zoonotic pathogens and diminish rat health. To the best of our knowledge, there is no published information regarding the prevalence of ectoparasites on R. norvegicus in Grenada. This study aimed to determine the prevalence and types of ectoparasites present on brown rats from Grenada. MATERIALS AND METHODS: One hundred sixty-eight rats were collected live from the parishes of St. George and St. David, Grenada, from May to July 2017. Following euthanasia, external parasites were collected using fine combs, thumb forceps, and paper tape. Tape samples and free specimens were placed in containers with 70% ethanol. External parasites were evaluated using dissection microscopy. RESULTS: Over 2000 ectoparasites were collected from 149 of the 168 trapped rats (88.7%). Ectoparasites identified included mesostigmatid mites (found on 84.6% of infested rats), fur mites in the families Atopomelidae and Listrophoridae (67.1%), Polyplax spp. lice (6.7%), fleas (3.4%), an unidentified larval tick (0.7%), and a mite in the family Myobiidae (0.7%). Infestation rates were higher in St. David Parish (86/89; 96.6%) than in St. George Parish (63/79; 79.7%) (p=0.001). When comparing sex and age, males had a marginal increase in infestation rate (83/89; 93.3%) compared to females (66/79; 83.5%) (p=0.054), and adults had an infestation rate of 90.7% (97/107) compared to juvenile rats who had a 66.7% (14/21) infestation rate. CONCLUSION: Brown rats in Grenada are heavily infested with ectoparasites, including known vectors of pathogens. Future studies will examine the prevalence of zoonotic pathogens in these arthropods.