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Rugby union is a field sport that is played at amateur and professional levels by male and female players globally. One of the most prevalent injury risks associated with the sport involves tackle collisions with opposition players. This suggests that a targeted injury reduction strategy could focus on the tackle area in the game. In amateur rugby union, injuries to the head, face and shoulder are the most common injury sites in youth rugby playing populations. A suboptimal tackle technique may contribute to an increased injury risk in these populations. One proposed mitigation strategy to reduce tackle-related injuries in youth populations may be to increase tackle proficiency by coaching an effective tackle technique. The present study aimed to demonstrate a proof of concept for a tackle technique coaching platform using inertial measurement units (IMUs) and a bespoke mobile application developed for a mobile device (i.e., a mobile phone). The test battery provided a proof of concept for the primary objective of modelling the motion of a player in a tackle event. The prototype (bespoke mobile application) modelled the IMU in a 3D space and demonstrated the orientation during a tackle event. The participants simulated ten tackle events that were ten degrees above and ten degrees below the zero degree of approach, and these (unsafe tackles) were indicated by a red light on the mobile display unit. The parameters of ten degrees above and below the zero angle of approach were measured using an inclinometer mobile application. These tackle event simulations provided a real-time stream of data that displayed the angle of tackles on a mobile device. The novel coaching platform could therefore constitute part of an injury reduction strategy for amateur or novice coaches to instruct safer tackle practice in youth rugby playing populations.

Background Hospital-acquired disability (HAD) is common and often related to low physical activity while in the hospital. Objective To examine whether wearable hospital activity trackers can be used to predict HAD. Design A prospective observational study between January 2016 and March 2017. Setting An academic medical center. Participants Community-dwelling older adults, aged 60 years or older, enrolled within 24 hours of admission to general medicine (n = 46). Main measures Primary outcome was HAD, defined as having one or more new activity of daily living deficits, decline of four or greater on the Late-Life Function and Disability Instrument (calculated between baseline and discharge), or discharge to a skilled nursing facility. Hospital activity (mean active time, mean sedentary time, and mean step counts per day) was measured using ankle-mounted accelerometers. The association of the literature-based threshold of 900 steps/day with HAD was also evaluated. Results Mean age was 73.2 years (SD = 9.5 years), 48% were male, and 76% were white. Median length of stay was 4 days (interquartile range [IQR] = 2.0-6.0 days); 61% (n = 28) reported being able to walk without assistance of another person or walking aid at baseline. Median daily activity time and step counts were 1.1 h/d (IQR = 0.7-1.7 h/d) and 1455.7 steps/day (IQR = 908.5-2643 steps/day), respectively. Those with HAD (41%; n = 19) had lower activity time (0.8 vs 1.4 h/d; P = .04) and fewer step counts (1186 vs 1808 steps/day; P = .04), but no difference in sedentary time, compared to those without HAD. The 900 steps/day threshold had poor sensitivity (40%) and high specificity (85%) for detecting HAD. Conclusions Low hospital physical activity, as measured by wearable accelerometers, is associated with HAD. Clinicians can utilize wearable technology data to refer patients to physical/occupational therapy services or other mobility interventions, like walking programs. J Am Geriatr Soc 68:261-265, 2020.

Objective Venous thromboembolism (VTE) prophylaxis is an important consideration for hospitalized older adults, and the Padua Prediction Score (PPS) is a risk prediction tool used to prioritize patient selection. We developed an automated PPS (APPS) algorithm using electronic health record (EHR) data. This study examines the accuracy of APPS and its individual components versus manual data extraction. Methods This is a retrospective cohort study of hospitalized general internal medicine patients, aged 70 and over. Fourteen clinical variables were collected to determine their PPS; APPS used EHR data exports from health system databases, and a trained abstractor performed manual chart abstractions. We calculated sensitivity and specificity of the APPS, using manual PPS as the gold standard for classifying risk category (low vs. high). We also examined performance characteristics of the APPS for individual variables. Results PPS was calculated by both methods on 311 individuals. The mean PPS was 3.6 (standard deviation, 1.8) for manual abstraction and 2.8 (1.4) for APPS. In detecting patients at high risk for VTE, the sensitivity and specificity of the APPS algorithm were 46 and 94%, respectively. The sensitivity for APPS was poor (range: 6–34%) for detecting acute conditions (i.e., acute myocardial infarction), moderate (range: 52–74%) for chronic conditions (i.e., heart failure), and excellent (range: 94–98%) for conditions of obesity and restricted mobility. Specificity of the automated extraction method for each PPS variable was > 87%. Conclusion APPS as a stand-alone tool was suboptimal for classifying risk of VTE occurrence. The APPS accurately identified high risk patients (true positives), but lower scores were considered indeterminate.

Publisher's version (útgefin grein)., Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40–69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. © 2019 The Authors We demonstrate that after 3 yr of prostate-specific-antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening., We demonstrate that, after four annual PSA screening rounds, BRCA2 mutation carriers have a higher incidence of PrCa, are diagnosed at a younger age, and present with more clinically significant tumours than BRCA2 noncarriers. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Therefore, these data support the use of systematic PSA screening in male BRCA2 carriers. Author contributions : Rosalind A. Eeles had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design : Aaronson, Ardern-Jones, Bancroft, Bangma, Castro, Dearnaley, Eccles, Evans, Eyfjord, Falconer, Foster, Gronberg, Hamdy, Johannsson, Khoo, Kote-Jarai, Lilja, Lindeman, Lubinski, Mahle, Mikropoulos, Mitra, Moynihan, Page, Rennert, Suri. Acquisition of data: All authors. Analysis and interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis : Page, Bancroft, Brook, Assel, Vickers, Lilja. Obtaining funding : Eeles and all IMPACT collaborating sites obtained their own funding for running the study at their site. Administrative, technical, or material support: All authors. Supervision: Eeles. Other : None. Financial disclosures: Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker $1000. The remaining authors have no other conflict of interest to declare.000. The remaining authors have no other conflict of interest to declare. Funding/Support and role of the sponsor : This research is coordinated by the Institute of Cancer Research, London, UK, and is supported by grants from Cancer Research UK (grant references C5047/A21332, C5047/A13232, and C5047/A17528) and the Ronald and Rita McAulay Foundation. Judith Offman is supported by Cancer Research UK Programme Grant reference C8161/A16892. Mr. and Mrs. Jack Baker are acknowledged for supporting the study in NorthShore University HealthSystem, Evanston, IL, USA and Myriad Genetics Laboratory, Salt Lake City, UT, USA, for providing research BRCA testing rates for NorthShore University HealthSystem patients. We acknowledge funding from the National Institute for Health Research (NIHR) to the Biomedical Research Center at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, at Manchester University Foundation Trust (IS-BRC-1215-20007), the Oxford Biomedical Research Centre Program, and the Cambridge Clinical Research Centre, NIHR Cambridge Biomedical Research Centre. We acknowledge that in Australia, this project was cofunded by Cancer Council Tasmania and Cancer Australia (grant number 1006349 [2011–2013]), Prostate Cancer Foundation of Australia (grant number PCFA PRO4 [2008]), Cancer Councils of Victoria and South Australia (grant number 400048 [2006–2008]), the Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia and Prostate Cancer Foundation of Australia (2014–2016; grant number 1059423), and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10-0596). We acknowledge funding from the Basser Center for BRCA (to Susan Domchek). This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748), a SPORE grant in Prostate Cancer to Dr. H. Scher (P50-CA92629), the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation. This work was also supported in part by the NIHR Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (CAN 2017/559), the Swedish Research Council (VR-MH project no. 2016-02974), and General Hospital in Malmö Foundation for Combating Cancer. We acknowledge funding from the Slovenian Research Agency, Research programme P3-0352. We thank CERCA Program/Generalitat de Catalunya for their institutional support. Elena Castro acknowledges funding from Prostate Cancer Foundation. We acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad), “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI16/00563, JR18/00011 and CIBERONC), and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge funding support from Fundação para a Ciência e a Tecnologia to the IPO Porto study (project grant PTDC/DTP-PIC/1308/2014 to Manuel R. Teixeira and fellowship grant SFRH/BD/116557/2016 to Marta Cardoso).

ObjectiveRecent treatment developments for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV) have greatly improved prognoses. Current screening practices are mainly risk based and are suboptimal. Improved efforts are critically needed to identify persons with these viruses. The aims of this study were to assess the feasibility of an opt-out bloodborne virus (BBV) screening programme in an acute medical unit (AMU) and to describe the prevalence of HIV, HBV and HCV in this population.Design and settingThis was a cross-sectional observational study in the AMU of a tertiary referral hospital in Galway, a city in the west of Ireland.Participants1936 patients entered the study; 54% were male, mean age was 53.1 years (SD 19.6). During the study period, all patients attending the AMU aged ≧16 years who were having bloods drawn and who had the ability to verbally consent for an additional blood sample met the inclusion criteria for the study.ResultsOver 44 weeks, 1936/4793 (40.4%) patients consented to BBV panel testing. Diagnosed prevalence rates for HIV, HBV and HCV were 0.5/1000, 2/1000 and 1.5/1000, respectively. There was one HIV-positive result; the patient was already engaged in care. Four patients tested positive for HBV surface antigen; one new diagnosis, one previously lost to follow-up and two already engaged in care. Three patients had active HCV infection; two had been lost to follow-up and are now linked back into services.ConclusionBBV testing uptake of 40.4% is higher than previous studies in AMU settings that used opt-in strategies, but lower than expected, possibly due to not incorporating testing into routine practice. The diagnosed prevalence of HBV is notable as little data currently exist about its prevalence in Ireland. These data are valuable in order to inform further prevention strategies for these infections in low-prevalence settings.

Werner syndrome is a rare autosomal recessive disorder caused by mutations in the Werner syndrome WRN gene, on chromosome 8. Those affected manifest early the features of ageing. Cataract surgery is prone to post-operative complications in those with Werner syndrome. The development of cystoid macular oedema (CMO) is likely multifactorial. Patients with WS have diabetes mellitus type 2 which can contribute to macular oedema. There is a deposition of abnormal WRN proteins in the macula which also predisposes to macular oedema. The trauma of cataract surgery appears to be the main stimulus for the development of CMO. CMO may, as a result, be difficult to manage in Werner syndrome patients. Further study is needed to elucidate the precise role of retinal WRN protein expression in the development of CMO in those with Werner syndrome. A tailored and more successful approach to the treatment of CMO in such patients may result.

Background Medication nonadherence contributes to hospitalizations in recently discharged patients with heart failure (HF). We aimed to test the feasibility of telemonitoring medication adherence in patients with HF. Methods and Results We randomized 40 patients (1:1) hospitalized for HF to 30 days of loop diuretic adherence monitoring with telephonic support or to passive adherence monitoring alone. Eighty-three percent of eligible patients agreed to participate. The median age of patients was 64 years, 25% were female, and 45% were Hispanic. Overall, 67% of patients were nonadherent (percentage of days that the correct number of doses were taken

The epidermal growth factor receptor inhibitor gefitinib (Iressa) is currently being studied in patients with bladder cancer and it has significant anti-angiogenic activity. We investigated the relationship between the modulation of vascular endothelial growth factor (Santa Cruz Biotechnology, Santa Cruz, California) expression and the biological efficacy of gefitinib for bladder cancer.In vitro the 4 bladder cancer cell lines 253JB-V, UMUC-3, KU-7 and UMUC-13 were treated with gefitinib and vascular endothelial growth factor secretion was measured. The effects of gefitinib on vascular endothelial growth factor promoter, proliferation, cell cycle and downstream signals were evaluated. In vivo 253JB-V and UMUC-13 were injected into nude mice and tumors were treated with 2 mg gefitinib per day. Tumor kinetics were determined and the levels of phospho-epidermal growth factor receptor (Biosource), vascular endothelial growth factor, phospho-vascular endothelial growth factor (Cell Signaling Technology), angiogenesis and apoptosis were measured.Epidermal growth factor receptor (Neomarkers, Fremont, California) phosphorylation was blocked efficiently in all cell lines at concentrations of 0.5 microM or greater. Gefitinib (1 microM) induced an accumulation of cells in G0/G1 without apoptosis in 253J B-V cells, whereas it had no effect in other cell lines. Gefitinib inhibited vascular endothelial growth factor secretion in 253JB-V and UMUC-13 (concentration inhibiting a 50% response 0.5 and 0.1 microM, respectively) but not in UMUC-3 or KU-7. Gefitinib decreased vascular endothelial growth factor promoter activity in 253JB-V and UMUC-13 by 40% to 60%. In vivo the growth of 253JB-V tumors was significantly inhibited by gefitinib, whereas no effect was demonstrated in UMUC-13 tumors. Vascular endothelial growth factor expression and vascular endothelial growth factor receptor activation were significantly decreased in 253JB-V tumors and to a greater extent in resistant UMUC-13 tumors. Gefitinib inhibited angiogenesis and induced apoptosis in sensitive 253JB-V tumors only.Epidermal growth factor receptor blockade exerts an anti-angiogenic effect on bladder cancer cells, in part by modulating vascular endothelial growth factor expression. However, down-regulation of vascular endothelial growth factor expression is not sufficient to inhibit bladder cancer growth and it should not be used as a predictor of the therapeutic efficacy of gefitinib.

To appropriately manage uncontrolled hypertension, clinicians must decide whether blood pressure (BP) is above goal due to a need for additional medication or to medication nonadherence. Yet, clinicians are poor judges of adherence, and uncertainty about adherence may promote inertia with respect to medication modification.We aimed to determine the effect of sharing electronically-measured adherence data with clinicians on the management of uncontrolled hypertension.This was a cluster randomized trial.Twenty-four primary care providers (12 intervention, 12 usual care; cluster units) and 100 patients with uncontrolled hypertension (65 intervention, 35 usual care) were included in the study.At one visit per patient, clinicians in the intervention group received a report summarizing electronically measured adherence to the BP regimen and recommended clinical actions. Clinicians in the control group did not receive a report.The primary outcome was the proportion of visits with appropriate clinical management (i.e., treatment intensification among adherent patients and adherence counseling among nonadherent patients). Secondary outcomes included patient-rated quality of care and communication during the visit.The proportion of visits with appropriate clinical management was higher in the intervention group than the control group (45 out of 65; 69 %) versus (12 out of 35; 34 %; p = 0.001). A higher proportion of adherent patients in the intervention group had their regimen intensified (p = 0.01), and a higher proportion of nonadherent patients in the intervention group received adherence counseling (p = 0.005). Patients in the intervention group were more likely to give their clinician high ratings on quality of care (p = 0.05), and on measures of patient-centered (p = 0.001) and collaborative communication (p = 0.02).Providing clinicians with electronically-measured antihypertensive adherence reports reduces inertia in the management of uncontrolled hypertension.NCT01257347 ; http://clinicaltrials.gov/show/ NCT01257347.

Objective: Medication nonadherence is a major cause of uncontrolled hypertension, but clinicians are poor at judging adherence, and the gold standard for measuring adherence, electronic monitoring, is rarely available in clinical settings. Self-report questionnaires (SRQs), by contrast, are inexpensive, easy to administer, and hence, may be useful for ‘diagnosing’ nonadherence. In this study, we evaluated the validity of two commonly used medication adherence SRQs among patients with uncontrolled hypertension, using electronic pillbox measurement as the gold standard. Methods: A total of 149 patients with uncontrolled hypertension had adherence to their antihypertensive medication regimen monitored using a four-compartment electronic pillbox (MedSignals) between two primary care visits (median 50 days). Participants completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Visual Analog Scale (VAS) at the second visit. Likelihood ratios were calculated using less than 80% correct dosing adherence by electronic measurement as the gold standard. Results: SRQ scores indicating low adherence (MMAS-8

INTRODUCTION Malaria accounts for approximately 225 million infections and 781 000 deaths annually worldwide. Malaria should be considered in the Emergency Department as an important cause of illness in returning travellers. We were interested in evaluating the malarial caseload presenting to an urban inner city Emergency Department in terms of the nature and severity of clinical presentations. METHODS A retrospective study of all cases of malaria presenting to our Emergency Department from 1 January 2004 to the 31 December 2010 was conducted. Information about patient demographics, areas in which malaria was contracted, clinical course, treatment and complications was recorded from chart reviews. RESULTS Fifty-six cases of malaria were diagnosed in the period studied. The majority of patients had falciparum malaria (80%), were originally from West or Central Africa (75%), were mainly from Nigeria (48%), and were visiting friends and relatives in their country of origin. A total of 79% had not taken appropriate antimalarial chemoprophylaxis. A total of 7% were classified as severe malaria according to the WHO criteria. There was one death. CONCLUSION Malarial cases occurred predominantly in immigrants who were returning to endemic areas to visit friends and relatives in their country of origin. The majority of patients did not undergo antimalarial prophylaxis. Severe malaria is a medical emergency requiring urgent recognition and appropriate antimicrobial and critical care therapy. Improving public awareness and healthcare promotion regarding risks of travel-related malaria may help to improve compliance with prophylaxis and preventative measures, and thereby reduce the prevalence of malarial infection in this group.

Human bladder cancer cells resistant to anti-epidermal growth factor receptor therapy often co-express platelet-derived growth factor receptor-β. We determined whether there is functional crosstalk between epidermal growth factor receptor and platelet-derived growth factor receptor-β, and how this regulates biological functions in bladder cancer cases.We determined heterodimerization and co-localization of epidermal growth factor receptor and platelet-derived growth factor receptor-β by immunoprecipitation and confocal microscopy, respectively. We tested the antiproliferative effects of specific inhibitory monoclonal antibodies to each receptor by (3)H-thymidine uptake assay. We transfected the nonplatelet-derived growth factor receptor-β expressing bladder cancer cell line UMUC5 with the platelet-derived growth factor receptor-β gene. These cells were analyzed in vitro by (3)H-thymidine uptake and by Matrigel™ invasion assay, and in vivo for tumorigenicity, metastatic potential and orthotopic growth. In a treatment study nude mice were inoculated with orthotopic tumors and treated with the inhibitory antibodies alone and in combination.Immunoprecipitation revealed epidermal growth factor receptor/platelet-derived growth factor receptor-β heterodimers in all platelet-derived growth factor receptor-β expressing cell lines. Forced expression of platelet-derived growth factor receptor-β in epidermal growth factor receptor sensitive UMUC5 cells (50% inhibitory concentration less than 10 nM) significantly decreased responsiveness to epidermal growth factor receptor inhibition (50% inhibitory concentration greater than 100 nM) and increased invasive potential 3-fold as well as tumorigenicity. Increased invasiveness was associated with epidermal growth factor triggered platelet-derived growth factor receptor-β transactivation, increased mitogen activated protein kinase and glycogen synthase kinase-3β phosphorylation, and decreased E-cadherin. Inhibition of epidermal growth factor receptor and platelet-derived growth factor receptor-β receptors blocked cell invasion, decreased cell proliferation, reduced xenograft tumor growth and increased E-cadherin expression.In epidermal growth factor receptor expressing bladder cancer co-expression of platelet-derived growth factor receptor-β has implications for tumor biology. Thus, it should be further evaluated as a strategy involving dual receptor targeting.

Approach and avoidance are critical components of novelty seeking, which plays an important role in susceptibility to drug abuse and aspects of cognition. This experiment was designed to examine whether brief periods of handling or prior exposure to a novel environment affect various measures of novel object exploration in mice. Forty male C57BL/6J mice were handled by the experimenter or received minimal exposure to human contact. In addition to manipulating the degree of familiarity with the experimenter (handling), we also manipulated the degree of familiarity with the object. All mice were tested over a 3-day period. On day 1, all mice were tested in the open field for 60 min. On day 2, there were two, 30-min sessions. In the first 30-min session, there was no object present. In the second 30-min session, half of the mice were exposed to a novel object. On day 3, all mice were placed in the open field for 30 min followed by a 30-min period in which the object was placed in the center of the open field. Handled mice showed a trend toward more object exploration on day 2 compared to non-handled mice. Mice with prior exposure to the novel object showed more object exploration compared to object-naive mice on day 3. These results are consistent with the hypothesis that a certain degree of familiarity with the object or with the experimenter decreases avoidance and increases exploration of novel stimuli. In combination, these results show that the approach and avoidance dimensions of novelty seeking can be manipulated experimentally and may be used in subsequent studies to examine the effects of drugs of abuse.