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Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein–protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases. Synopsis: A potent small molecule TSLPR inhibitor was identified as a novel therapeutic option for atopic diseases. The small molecule BP79 effectively abrogates TSLP-triggered immune reactions at low micromolar concentrations in human skin and lungs. BP79 can be topically applied and, thus, provides significant advantages over the current TSLP antibodies. A human-based atopic disease drug discovery platform was developed with the potential to facilitate preclinical development of atopy-targeting drugs. A potent small molecule TSLPR inhibitor was identified as a novel therapeutic option for atopic diseases. [ABSTRACT FROM AUTHOR]

This study investigated photobiomodulation (PBM) effects in Sonic hedgehog (Shh) signaling as a potential approach to taste preservation and regeneration. Primary taste cell (TC) cultures were treated with Shh antagonist vismodegib and irradiated using a continuous wave type 630 nm light‐emitting diode (10 mW/cm2) array, with single or multiple doses of 30 J/cm2 to determine dose inducing significant upregulation effect. Shh, Ptch, Smo, and Gli1 were significantly upregulated at 120 J/cm2, used as the minimum dose in vivo. Vismodegib was administered via daily oral gavage for 21 days (30 mg/kg) to induce Shh inhibition in the tongue of rat animal models resulting in taste bud damage and taste dysfunction. PBM treatment using a 630 nm laser (3 W/cm2) at a radiant exposure of 120 J/cm2 (24 J/cm2 × 5) successfully upregulated the Shh protein expression, regenerated taste buds, and recovered taste function. [ABSTRACT FROM AUTHOR]

Vat polymerization allows for the accurate and fast fabrication of personalized implants and devices. While the technology advances rapidly and more materials become available, the fabrication of flexible yet tough resorbable materials for biomedical applications remains a challenge. Here, a formulation that can be 3D printed with high accuracy using vat polymerization, yielding materials that are tough, degradable, and non‐toxic is presented. This unique combination of properties is obtained by combining a long‐chain polycaprolactone macromonomer with a small molecule cross‐linker. A wide range of properties is achieved by tuning the ratio of these components. The use of benzyl alcohol as a non‐volatile, benign solvent enables fabrication on a low‐cost desktop 3D printer, with an exposure time of 8 s per 50‐micron layer. The 3D‐printed networks are tough and elastic with a tensile strength of 11 MPa at 116% elongation at break. Cells attach and proliferate on the networks with a viability of >91%. The networks are fully degradable to soluble products. This new 3D printable material opens up a range of opportunities in biomedical engineering and personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Past research on social support and dental visits in older people has been limited by cross‐sectional design, limited social support dimensions and non‐representative samples. Methods: Data came from men with natural teeth completing Waves 3 and 4 of the Concord Health and Ageing in Men Project in Sydney, Australia. The relationship between social support at Wave 3 (2011–2012) and at least one dental visit per year at Wave 4 (2014–2016) was examined by Poisson regression. Social support was measured by structural (marital status, living arrangements, family support and social interaction) and functional (social support satisfaction) domains. Results: About 673 men were analysed. Structural and functional social support were not associated with the pattern of usual dental visits 5 years later in univariable or multivariable analyses. The only consistent significant factor was income source, with older men who had other sources of income more likely to regularly visit the dentist than older men solely reliant on the pension for income (prevalence ratio: 1.31, 95% CI: 1.13–1.52). Conclusions: We found no differences in the pattern of usual dental visits between older men with different levels and types of social support. For older Australian men, income source seems to be the most important determinant of regular dental visits. © 2022 Australian Dental Association [ABSTRACT FROM AUTHOR]

Background: Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities. Methods: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi‐state model that attributed each hospitalisation to the current dialysis modality. Results: In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 (± 5.0) and for HD 1.4 (± 3.2) hospitalisations per patient‐year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02–1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1–1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient‐year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access‐related problems (33%). Conclusion: PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future. [ABSTRACT FROM AUTHOR]

Aim: The Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method: An online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 ('rarely') to 4 ('always'). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results: Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they 'most often' or 'always' adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from 'rarely' to 'always' in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions: Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation. [ABSTRACT FROM AUTHOR]

This article includes Author Insights, a video abstract available at https://vimeo.com/bjog/authorinsights16682 [ABSTRACT FROM AUTHOR]

Background: Premature development of cardiovascular disease in children living with HIV‐1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH. Methods: This was a cross‐sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation‐Canadian Child Cure Cohort (EPIC4) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein‐1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin‐6 (IL‐6)] and endothelial activation [angiopoietin‐2 (Ang2), soluble vascular endothelial growth factor‐1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme‐linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways. Results: Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL‐6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein‐1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir‐boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7–17, P = 0.0020). Conclusions: Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r. [ABSTRACT FROM AUTHOR]

Objective: To determine risk‐reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. Design: Multicentre, cohort, questionnaire study (IRSCTN:12310993). Setting: United Kingdom (UK). Population: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. Methods: Participants completed a 39‐item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. Main outcomes: RRESDO acceptability, menopausal sequelae, satisfaction/regret. Results: In all, 346 of 683 participants underwent risk‐reducing salpingo‐oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2–7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2–27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2–0.9, P = 0.025). Conclusion: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction. RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To describe the current testing practice, referral pathways and gynaecological services available to women with Lynch syndrome (LS) in the UK.Design: Cross-sectional nationwide survey of gynaecological oncologists and women with LS.Setting: United Kingdom.Methods: Gynaecological oncologists were contacted directly. Women with LS were identified from national and regional clinical databases and the patient support group, Lynch syndrome UK.Main Outcome Measures: Gynaecological oncologists were asked to report rates of LS testing and current practice regarding risk-reducing strategies and gynaecological surveillance for women with LS. Women with LS were asked to describe their experiences of gynaecological care.Results: In total, 41 gynaecological oncologists and 298 women with LS responded to the survey. Of the gynaecological oncologists surveyed, 37% were unfamiliar with any clinical guidelines for the management of LS. Only 29% of gynaecological oncologists supported universal testing of endometrial cancer for LS; one centre routinely performed such testing. In all, 83% said they perform risk-reducing gynaecological surgery and 43% were aware of a local gynaecological surveillance service for women with LS. Of women with LS, most had undergone a hysterectomy (n = 191/64.1%), most frequently to reduce their gynaecological cancer risk (n = 86/45%). A total of 10% were initially referred for LS testing by their gynaecologist and 55% of those eligible regularly attended gynaecological surveillance; however, 62% wanted more regular surveillance. Regional variation was evident across all standards of care.Conclusions: There is widespread variation in the services offered to women with LS in the UK. As a community, gynaecological oncologists should move towards a nationally agreed provision of services.Tweetable Abstract: A mismatch in care for mismatch repair. Survey finds significant variation in gynaecological care for #Lynchsyndrome in the UK. [ABSTRACT FROM AUTHOR]

The market of ready‐to‐eat minimally processed vegetables (RTE‐MPV) is increasing in Brazil and many other countries. During processing, these vegetables go through several steps that modify their natural structure while maintaining the same nutritional and sensory attributes as the fresh produce. One of the most important steps is washing‐disinfection, which aims to reduce the microbial load, prevent cross‐contamination and inactivate pathogenic microorganisms that may be present. Nonetheless, the presence of pathogens and occurrence of foodborne illnesses associated with consumption of RTE‐MPV concern consumers, governments and the food industry. This review brings an overview on the microbiological safety of RTE‐MPV, focusing on Brazilian findings. Most of the published data are on detection of Salmonella spp. and Listeria monocytogenes, indicating that their prevalence may range from 0.4% to 12.5% and from 0.6% to 3.1%, respectively. The presence of these pathogens in fresh produce is unacceptable and risky, mainly in RTE‐MPV, because consumers expect them to be clean and sanitized and consequently safe for consumption without any additional care. Therefore, proper control during the production of RTE‐MPV is mandatory to guarantee products with quality and safety to consumers. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) is a master regulator and is required for the effective coupling of angiogenesis and osteogenesis supporting both skeletal development and postnatal bone repair. A direct role for VEGF in intramembranous-derived osteoblast growth and differentiation is not clear. We investigated the expression of primary alveolar osteoblast VEGF receptors and the subsequent effects on mineralization and nodule formation in vitro following VEGFR inhibition.Methods: Primary human alveolar osteoblasts (HAOBs) were cultured in the presence of VEGF receptor inhibitors, exogenous VEGF or the bisphosphonate, zoledronic acid. VEGF, VEGFR1 and VEGFR2 mRNA expression and nodule formation following 21 days of culture. VEGFR1 protein expression was examined using immunofluorescence after 48 h.Results: The HAOBs expressed high levels of VEGF and VEGFR1 protein but VEGFR2 was not detected. The VEGFR1/2 inhibitors, ZM306416 and KRN633, lead to a dose-dependent decrease in mineralization. Treatment with zoledronic acid showed no difference in HAOB VEGF receptor expression.Conclusion: VEGF/VEGFR1 pathway appears to be important for intramembranous-derived osteoblast differentiation and maturation in vitro. [ABSTRACT FROM AUTHOR]

Background: Theileria orientalis infection causes a clinical syndrome in cattle characterised by weakness, reluctance to walk, anaemia, jaundice and death in peri‐parturient cows and young calves, referred to as bovine anaemia caused by Theileria orientalis group (BATOG). Abortions in pregnant cows are also reported. Pallor, pyrexia and elevated heart and respiratory rates are typical findings on physical examination. Case Report: A syndrome of abortions, lethargy, inappetence, jaundice and deaths in beef cattle on two separate properties and a separate cluster of three properties within 15 km west of the town of Denmark in Western Australia was associated with the presence of severe regenerative anaemia and the presence of Theileria orientalis Ikeda genotype in blood samples taken from affected cattle and their cohorts. A diagnosis of bovine anaemia caused by the T. orientalis group was based on consistent clinical, haematological, biochemical and PCR findings. Conventional PCR testing detected only the T. orientalis Ikeda type. On the two properties where it was investigated, quantitative PCR testing for parasite load was suggestive of recent infections. Sequencing of T. orientalis major piroplasm surface protein gene PCR products demonstrated that they were identical to those from similar bovine cases in New South Wales. Conclusion: The clinical history of affected cattle and the biochemical, haematological and PCR findings were consistent with bovine anaemia caused by the T. orientalis Ikeda genotype. This clinical syndrome had not been recognised in Western Australia before this series of cases. [ABSTRACT FROM AUTHOR]

Studying the flows of parent country nationals in multinational enterprises (MNEs) to subsidiary operations has a relatively long tradition. Studying flows of subsidiary employees to other subsidiaries, as third country nationals, and to the corporate headquarters, as inpatriates, however, has empirically much less pedigree. Drawing on a large-scale empirical study of MNEs in Ireland, this paper provides a benchmark of outward flows of international assignees from the Irish subsidiaries of foreign-owned MNEs to both corporate headquarters and other worldwide operations. Building on insights from the resource-based view and neo-institutional theory, we develop and test a theoretical model to explain outward staffing flows. The results show that almost half of all MNEs use some form of outward staffing flows from their Irish operations. Although the impact of specific variables in explaining inter-organization variation differs between the utilization of inpatriate and third country national assignments, overall we find that a number of headquarters, subsidiary, structural, and human resource systems factors emerge as strong predictors of outward staffing flows. © 2010 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status.Method: Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status.Results: Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour.Conclusions: Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour. [ABSTRACT FROM AUTHOR]

Objectives: To determine the compliance and clinical utility of weekly and daily electronic mood symptom monitoring in adolescents and young adults at risk for mood disorder. Methods: Fifty emerging adult offspring of bipolar parents were recruited from the Flourish Canadian high‐risk offspring cohort study along with 108 university student controls. Participants were assessed by KSADS/SADS‐L semi‐structured interviews and used a remote capture method to complete weekly and daily mood symptom ratings using validated scales for 90 consecutive days. Hazard models and generalized estimating equations were used to determine differences in summary scores and regularity of ratings. Results: Seventy‐eight and 77% of high‐risk offspring and 97% and 93% of controls completed the first 30 days of weekly and daily ratings, respectively. There were no differences in drop‐out rates between groups over 90 days (weekly P = 0.2149; daily P = 0.9792). There were no differences in mean summary scores or regularity of weekly anxiety, depressive or hypomanic symptom ratings between high‐risk offspring and control groups. However, high‐risk offspring compared to controls had daily ratings indicating lower positive affect, higher negative affect and lower self‐esteem (P = 0.0317). High‐risk offspring with remitted mood disorder compared to those without had more irregularity in weekly anxiety and depressive symptom ratings and daily ratings of lower positive affect, higher negative affect, and higher shame and self‐doubt (P = 0.0365). Conclusions: Findings support that high‐resolution electronic mood tracking may be a feasible and clinically useful approach in monitoring emerging psychopathology in young people at high‐risk offspring of mood disorder onset or recurrence. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that patient-initiated follow up reduces the fear of cancer recurrence (FCR) and healthcare use when compared with traditional hospital-based follow up.Design: Pragmatic, multicentre randomised trial.Setting: Four Danish departments of gynaecology between May 2013 and May 2016.Population: One hundred and fifty-six women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I low-intermediate risk endometrial carcinoma.Methods: Women allocated to the control group attended hospital-based follow up consisting of regular outpatient visits for 3 years after primary treatment. Women in the intervention group were instructed in patient-initiated follow up, which included careful instruction in alarm symptoms and options for self-referral rather than a schedule of examinations.Main Outcome Measures: The primary end point was FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) after 10 months of follow up. Secondary end points included cancer-related use of primary and secondary health care during the first 10 months after treatment.Results: In the primary analysis, FCR decreased significantly more in the control group from baseline to 10 months of follow up (difference -5.9, 95% CI -10.9 to -0.9). The majority of this improvement happened after only 3 months of follow up. Women receiving the intervention had fewer examinations at the department compared with the control group (0 versus 2 median visits, P < 0.01) and 58% of these examinations were scheduled because of vaginal bleeding.Conclusions: Hospital-based follow up alleviates FCR significantly more than patient-initiated follow up, though the estimated difference was small. Patient-initiated follow up is a feasible, potentially cost-reducing follow-up approach in a population of endometrial cancer survivors with low risk of recurrence. The decision to use patient-initiated follow up should balance these benefits and harms.Tweetable Abstract: Patient-initiated follow up reduces healthcare use but maintains fear of recurrence in endometrial cancer.Plain Language Summary: Why and how was the study carried out? Follow up of women with endometrial cancer is resource consuming and previous research suggests that it is not effective. Even though the women benefit from reassurance at follow up, routine examinations may also remind the women of the disease and induce fear of cancer recurrence. Furthermore, routine follow up may delay recurrence diagnosis, because the women do not report their symptoms until the next scheduled visit. In the research explained in this article, patient-initiated follow up was evaluated as an alternative to traditional follow up. The women were randomly assigned to one of two follow-up programmes: regular gynaecological examinations at the department of gynaecology or self-referral with careful instruction in alarm symptoms, that is, patient-initiated follow up. The level of fear of cancer recurrence in the two groups was obtained by questionnaires. Information on healthcare use was obtained by questionnaires and a chart review. What were the main findings? Regular examinations at the department of gynaecology reduced the fear of cancer recurrence significantly more than patient-initiated follow up, though the difference was small. Women who were instructed in alarm symptoms, under self-referral, were able to monitor their symptoms, and this approach significantly reduced the number of examinations at the department of gynaecology. What are the limitations of the work? Participants in the self-referral group knew that they were examined less than other women, and this may have induced fear of cancer recurrence. Similarly, the regular completion of questionnaires regarding fear of cancer recurrence may have reminded the women of the disease and diminished the difference between the two groups. What are the implications for patients Patient-initiated follow up reduced healthcare use but maintained fear of cancer recurrence in women who had survived early-stage endometrial cancer. Future analyses on quality of life and cost-effectiveness are needed to balance the benefits and harms of patient-initiated follow up. [ABSTRACT FROM AUTHOR]

Background: Dentomaxillofacial Radiology (DMFR) is comprised of the smallest cohort of specialists in Australia. A survey was undertaken to assess awareness of DMFR, radiology reporting and referring protocols as well as dental practitioners' satisfaction with their radiology reporting arrangements.Methods: An original online survey created using Checkbox† was sent to dental practitioners. The survey was promoted on Australian-based dental Facebook forums and emailed to targeted members via Australian professional dental associations.Results: A total of 399 responses were received, with over 80% of respondents aware of DMFR as a specialty. Approximately 40% of practitioners were self-reporting their imaging. There was correlation between increased satisfaction with external reporting and utilization of DMFR services and decreased satisfaction with medical radiology services. More than 90% of general dentists and greater than 85% of dental specialists prefer DMFR reports to medical radiology reports. Approximately 80% of practitioners believed that their satisfaction would change positively if they had access to a DMFR report.Conclusion: The research indicates a high degree of self-reporting or non-reporting by dental practitioners. There is low satisfaction with external reporting performed by Medical Radiologists primarily due to a lack of dental knowledge or detail and a preference for DMF Radiology reports. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to identify the participants' preference and perception of effectiveness with respect to nine commercially available tongue scrapers. As secondary aim, perception of discomfort and suspected sharpness were assessed. In addition, the first impression of the design of the various tongue scrapers was evaluated. Materials and methods This was an observational survey without blinding to the products. At first impression, participants were given nine tongue scrapers and were asked to immediately use all, and to point out which of the scrapers they preferred most. Subsequently, a 14-day familiarization period followed. At the follow-up appointment, all participants received a questionnaire which used a visual analogue scale ( VAS) to evaluate their perception of the various scrapers used. Questions regarding the perceived efficacy, discomfort and pain were posed. Data were analysed statistically by anova. T-tests were used for ' post hoc' analysis and Bonferroni corrections were used for multiple comparisons. Results In total, 50 participants completed the assessment. The primary parameter 'efficacy' showed scores that ranged from 4.09 to 6.43 ( P < 0.001) for the nine tongue scrapers. The secondary parameters 'sharpness' (range from 3.31 to 6.26) and 'discomfort' (range from 5.67 to 8.33) showed significant differences as well ( P < 0.001). A significant negative correlation ( R = −0.850; P = 0.004) between the perceived sharpness and discomfort was observed. Conclusion The perception of effectiveness varied among the various tongue-cleaning device designs. No single feature stood out as being specifically related to perception of effectiveness. Sharpness and comfort were negatively correlated. Comfort and effectiveness were positively correlated. The results from this study indicated that participants found TS6 and TS8 to be the most comfortable and the most effective. However, TS8 scored higher for inducing a higher gag reflex. [ABSTRACT FROM AUTHOR]

GPR40 mediates free fatty acid-induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK-8666, a partial GPR40 agonist, after once-daily multiple dosing in type 2 diabetes patients. This double-blind, multisite, parallel-group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14-day treatment. The results showed no serious adverse effects or treatment-related hypoglycemia. One patient (150-mg group) showed mild-to-moderate transaminitis at the end of dosing. Median MK-8666 Tmax was 2.0-2.5 h and mean apparent terminal half-life was 22-32 h. On Day 15, MK-8666 reduced fasting plasma glucose by 54.1 mg/dL (500 mg), 36.0 mg/dL (150 mg), and 30.8 mg/dL (50 mg) more than placebo, consistent with translational pharmacokinetic/pharmacodynamic model predictions. Maximal efficacy for longer-term assessment is projected at 500 mg based on exposure-response analysis. In conclusion, MK-8666 was generally well tolerated with robust glucose-lowering efficacy. [ABSTRACT FROM AUTHOR]

Objective To determine the prophylactic and therapeutic efficacy of Australian-registered insecticide formulations against Old World screwworm ( OWS) myiases for potential use in screwworm containment and eradication programs. Methods The longevity of protection provided by six insecticidal formulations (subcutaneous ivermectin, doramectin and abamectin, a topically applied aqueous formulation of spinosad, ivermectin controlled-release capsule and a dicyclanil spray-on formulation) was tested using implants of 1st-instar OWS larvae on Javanese thin-tail sheep. Therapeutic efficacy of four formulations (topical ivermectin, chlorfenvinphos/cypermethrin mixture, aerosol spinosad formulation and a formulation containing propetamphos and eucalyptus oil) was tested against 2- and 4-day-old OWS strikes. Results Both the ivermectin capsule and dicyclanil spray-on formulation gave 100% protection against screwworm implants for the full 12 weeks of the study. Ivermectin, doramectin and abamectin administered SC all gave 100% protection at 3 days post-treatment, but at 2 weeks the protection had become incomplete. Spinosad dipping did not give complete protection at any time. All four therapeutic treatments gave complete resolution of 2-day-old strikes and topical ivermectin, spinosad and chlorfenvinphos/cypermethrin, but not the propetamphos/eucalyptus oil formulation, gave complete resolution of all 4-day-old strikes. Conclusion Dicyclanil spray-on and ivermectin capsule formulations, both registered for use in sheep, but not for cattle or other livestock species, gave much longer protection against screwworm implants than the currently recommended SC ivermectin. Pre-emptive action to facilitate rapid deployment of these formulations in the event of a screwworm incursion is urgently needed. [ABSTRACT FROM AUTHOR]

Objectives: To test the hypothesis that the use of low-level laser therapy (LLLT) reduces elevated pain by controlling the release of neurochemicals during orthodontic tooth movement.Setting and Sample Population: Department of Orthodontics and Dentofacial Orthopedics, Okayama University. Sixty-five Sprague Dawley rats were subjected to tooth movement and LLLT.Materials and Methods: Adult Sprague Dawley rats were used in this study. Groups included day 0 controls, irradiation only controls and with or without irradiation sacrificed at 1, 3, 5, 7 and 14 days after tooth movement (n=5 each, total n=65). Tooth movement was achieved by insertion of an elastic module between molar teeth. Immunohistochemistry for CD-11b, GFAP and c-fos in the brain stem was performed. Stains were quantified by constructing a three-dimensional image using IMARIS, and counted using NEURON TRACER and WinROOF software. Two-way ANOVA followed by a Tukey's post hoc test (P<.05) was used for statistical comparison between groups.Results: C-fos expression was significantly increased at one and three days after tooth movement. LLLT significantly diminished this increase in c-fos expression only at one day after tooth movement CD-b11 and GFAP expression also significantly increased after tooth movement. No significant change was observed for CD-11b and GFAP expression in the central nervous system upon LLLT.Conclusion: Low-level laser therapy may reduce early neurochemical markers but have no effect on delayed pain neurochemical markers after tooth movement. [ABSTRACT FROM AUTHOR]

Research aimed at more fully emulating human biology in vitro has rapidly progressed in recent years with advancements in 3D tissue engineering and microphysiological systems. The initial target of such systems has been directed towards drug and chemical safety assessment, with the goal of improving sensitivity and predictive capabilities. Here we discuss recent developments of in vitro organ culture systems, and their future applications in modeling human disease. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptors (CARs) comprise a tumor-targeting moiety, often in the form of a single chain variable fragment derived from a monoclonal antibody, fused to one or more intracellular T-cell signaling sequences. Lymphodepletion chemotherapy followed by infusion of T cells that are genetically modified to express a CD19-specific CAR is a promising therapy for patients with refractory CD19+ B-cell malignancies, producing rates of complete remission that are remarkably high in acute lymphoblastic leukemia and encouraging in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Responses are often durable, although additional studies are needed to define the role of CAR-T cell immunotherapy in the context of other treatments. CAR-modified T-cell immunotherapy can be complicated by cytokine release syndrome and neurologic toxicity, which in most cases are manageable and reversible. Here we review recent clinical trial data and discuss issues for the field. [ABSTRACT FROM AUTHOR]

Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeakc) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeakc may add value beyond only assessing QTc. [ABSTRACT FROM AUTHOR]

Contents The aim of this study was to evaluate the influence that different protocols of urethral catheterization after pharmacological induction (Ur.Ca.P.I.) may have on the semen quality of the domestic cat. The study has been divided into two experiments: one in which different dosages of medetomidine administrated are evaluated and the second one in which the timing of the catheterization after pharmacological induction is tested. In the first experiment, 18 cats were sedated with the recommended dosage of medetomidine (130 μg/kg i.m.) while the other 18 were sedated with a lower dose of the same drug (50 μg/kg i.m.). In the second experiment, three groups were implemented, each containing 25 subjects. In group 1, the semen collection was performed immediately once the pharmacological effect of the drug was reached; in group 2, the semen collection was performed three times every 5 min after the pharmacological effect was reached; finally, in group 3, Ur.Ca.P.I. was performed 20 min after the pharmacological effect was reached. All the different protocols permitted sperm collection, nevertheless the first experiment showed a better quality in terms of volume, concentration, total number of spermatozoa (p < 0.01) and quality of the movement (motility p < 0.05 and forward progressive motility p < 0.01), using a high medetomidine dosage rather than 50 μg/kg i.m. In the second experiment, forward motility was statistically higher (p < 0.01) in the first group and total volume was higher (p < 0.01) in the second and third group, while other parameters were statistically not different. Results suggest that a single catheterization immediately after the onset of the pharmacological effect leads to a good-quality semen with the lowest possibility of damaging the urethra and that a sedation with 130 μg/kg of medetomidine leads to a better quality sperm collection than 50 μg/kg does. [ABSTRACT FROM AUTHOR]

Pancreatitis is a significant clinical problem and the lack of effective therapeutic options means that treatment is often palliative rather than curative. A deeper understanding of the pathogenesis of both acute and chronic pancreatitis is necessary to develop new therapies. Pathological changes in pancreatitis are dependent on innate immune cell recruitment to the site of initial tissue damage, and on the coordination of downstream inflammatory pathways. The chemokine receptor CXCR2 drives neutrophil recruitment during inflammation, and to investigate its role in pancreatic inflammation, we induced acute and chronic pancreatitis in wild-type and Cxcr2−/− mice. Strikingly, Cxcr2−/− mice were strongly protected from tissue damage in models of acute pancreatitis, and this could be recapitulated by neutrophil depletion or by the specific deletion of Cxcr2 from myeloid cells. The pancreata of Cxcr2−/− mice were also substantially protected from damage during chronic pancreatitis. Neutrophil depletion was less effective in this model, suggesting that CXCR2 on non-neutrophils contributes to the development of chronic pancreatitis. Importantly, pharmacological inhibition of CXCR2 in wild-type mice replicated the protection seen in C xcr2−/− mice in acute and chronic models of pancreatitis. Moreover, acute pancreatic inflammation was reversible by inhibition of CXCR2. Thus, CXCR2 is critically involved in the development of acute and chronic pancreatitis in mice, and its inhibition or loss protects against pancreatic damage. CXCR2 may therefore be a viable therapeutic target in the treatment of pancreatitis. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Vestibular nerve section is considered an effective modality in the treatment of refractory and incapacitating vertigo. Typically nerve section results are described on the basis of short-term follow-up. We have reviewed 41 cases of vestibular nerve section spanning an 18-year period. Although the majority of cases involved classic Meniere's disease, delayed endolymphatic hydrops, vestibular neuritis, and Meniere's syndrome secondary to head trauma were also included. Surgical approaches included translabyrinthine (20 cases), retrolabyrinthine (14 cases), retrosigmoid (six cases), and middle fossa (one case) procedures. Postoperative follow-up time averaged 102 months, with 46% of patients followed for a minimum of 9 years. Results are reported according to standards set forth by the American Academy of Otolaryngology--Head and Neck Surgery. Vertigo was cured or markedly improved in 88% of cases (90% in patients with Meniere's disease) at 18 to 24 months postoperatively. These vertigo results were sustained at the time of latest follow-up. Functional level was also preserved over time despite the development of bilateral symptoms in several cases. The rate of bilateral disease reached 22% of cases. Although vertigo results remained stable, long-term follow-up of successful hearing preservation cases demonstrated deterioration over time. Postoperative continuation of medical treatment is urged to optimize and sustain the vestibular neurectomy result. [ABSTRACT FROM AUTHOR]

Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org). [ABSTRACT FROM AUTHOR]

Objective To establish the prevalence of anthelmintic resistance in ovine gastrointestinal nematodes in southern Queensland. Design An observational parasitological study using the faecal egg count reduction test. Methods Sheep farms (n = 20) enrolled in this study met the twin criteria of using worm testing for drench decisions and having concerns about anthelmintic efficacy. On each farm, 105 sheep were randomly allocated to one of six treatment groups or an untreated control group. Faecal samples were collected on day 0 and days 10-14 for worm egg counts and larval differentiation. Single- and multi-combination anthelmintics, persistent and non-persistent, oral liquid or capsule, pour-on and injectable formulations were tested. Monepantel was not tested. Farmers also responded to a questionnaire on drenching practices. Results Haemonchus contortus was the predominant species. Efficacy <95% was recorded on 85% of farms for one or more anthelmintics and on 10% of farms for six anthelmintics. No resistance was identified on three farms. The 4-way combination product was efficacious (n = 4 farms). Napthalophos resistance was detected on one farm only. Resistance to levamisole (42% of farms), moxidectin injection (50% of farms) and the closantel/abamectin combination (67% of farms) was identified. Moxidectin oral was efficacious against Trichostrongylus colubriformis, which was predominant on only one farm. Of the farms tested, 55% ran meat breeds, 60% dosed more than the recommended dose rate and 70% always, mostly or when possible practised a 'drench and move' strategy. Conclusion This level of anthelmintic resistance in southern Queensland will severely compromise worm control and force increased use of monepantel. [ABSTRACT FROM AUTHOR]

Objective To determine the specificity and sensitivity of a commercial copro-antigen ELISA for the detection of Fasciola hepatica infection in cattle and sheep and to assess the suitability of the test for use in horses. Methods Testing was done on more than 100 negative faecal samples from each of sheep, cattle and horses and on at least 40 positive faecal samples from each species. Positive samples were selected based on a positive sedimentation test for liver fluke eggs. Faecal samples of animals from Western Australia, which is free of liver fluke infection, served as negative controls. Specificity and sensitivity were assessed for each species using the recommended kit cut-off and also custom cut-offs specific for each species based on the mean plus 3-fold standard deviation of the mean of the negative samples for each species. Results Using the cut-off recommended by the kit manufacturer, the specificity was 100% for all species and the sensitivity was 88%, 80% and 9% for sheep, cattle and horses, respectively. Using the lower custom cut-offs for each species improved the sensitivity to 100% for sheep, 87% for cattle and 28% for horses, while maintaining the specificity above 99% for all species. Conclusions The sensitivity of the commercial copro-antigen ELISA can be improved by using custom cut-off values for each species. With this modification, it is a suitable alternative screening test to the currently used sedimentation test for border control of sheep and cattle movement. The test is not suitable for use in horses. [ABSTRACT FROM AUTHOR]

Objectives To compare the sensitivity of inspections of cattle herds and adult fly trapping for detection of the Old World screw-worm fly ( OWS). Procedures The incidence of myiases on animals and the number of OWS trapped with Luci Trap®/ Bezzilure were measured concurrently on cattle farms on Sumba Island ( Indonesia) and in peninsular Malaysia (two separate periods for the latter). The numbers of animal inspections and traps required to achieve OWS detection at the prevalent fly densities were calculated. Results On Sumba Island, with low-density OWS populations, the sensitivity of herd inspections and of trapping for OWS detection was 0.30 and 0.85, respectively. For 95% confidence of detecting OWS, either 45 inspections of 74 animals or trapping with 5 sets of 4 Luci Traps for 14 days are required. In Malaysia, at higher OWS density, herd inspections of 600 animals (twice weekly, period 1) or 1600 animals (weekly, period 2) always detected myiases (sensitivity = 1), while trapping had sensitivities of 0.89 and 0.64 during periods 1 and 2, respectively. For OWS detection with 95% confidence, fewer than 600 and 1600 animals or 2 and 6 Luci Traps are required in periods 1 and 2, respectively. Conclusions Inspections of cattle herds and trapping with LuciTrap and Bezzilure can detect OWS populations. As a preliminary guide for OWS detection in Australia, the numbers of animals and traps derived from the Sumba Island trial should be used because the prevailing conditions better match those of northern Australia. [ABSTRACT FROM AUTHOR]

The INTERGROWTH-21(st) Project has in its mandate to develop prescriptive standards for fetal, neonatal and preterm post-neonatal growth. The project comprises three components: the Fetal Growth Longitudinal Study (FGLS), the Preterm Postnatal Follow-up Study (PPFS), and the Newborn Cross-Sectional Study (NCSS). We consider here the statistical aspects of the three components as they relate to the construction of these standards, in particular the sample size, and outline the principles that will guide the planned main analyses. [ABSTRACT FROM AUTHOR]

INTERGROWTH-21(st) is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care. [ABSTRACT FROM AUTHOR]