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https://www.readbyqxmd.com/read/28798678/striatal-neuropeptides-enhance-selection-and-rejection-of-sequential-actions
#1
David Buxton, Enrico Bracci, Paul G Overton, Kevin Gurney
The striatum is the primary input nucleus for the basal ganglia, and receives glutamatergic afferents from the cortex. Under the hypothesis that basal ganglia perform action selection, these cortical afferents encode potential "action requests." Previous studies have suggested the striatum may utilize a mutually inhibitory network of medium spiny neurons (MSNs) to filter these requests so that only those of high salience are selected. However, the mechanisms enabling the striatum to perform clean, rapid switching between distinct actions that form part of a learned action sequence are still poorly understood...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28741687/a-distinct-plasma-lipid-signature-associated-with-poor-prognosis-in-castration-resistant-prostate-cancer
#2
H-M Lin, K L Mahon, J M Weir, P A Mundra, C Spielman, K Briscoe, H Gurney, G Mallesara, G Marx, M R Stockler, PRIMe Consortium, R G Parton, A J Hoy, R J Daly, P J Meikle, L G Horvath
Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients...
July 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28691093/wnt-antagonists-exhibit-unique-combinatorial-antitumor-activity-with-taxanes-by-potentiating-mitotic-cell-death
#3
Marcus M Fischer, Belinda Cancilla, V Pete Yeung, Fiore Cattaruzza, Cecile Chartier, Christopher L Murriel, Jennifer Cain, Raymond Tam, Chieh-Yang Cheng, James W Evans, Gilbert O'Young, Xiaomei Song, John Lewicki, Ann M Kapoun, Austin Gurney, Wan-Ching Yen, Timothy Hoey
The WNT pathway mediates intercellular signaling that regulates cell fate in both normal development and cancer. It is widely appreciated that the WNT pathway is frequently dysregulated in human cancers through a variety of genetic and epigenetic mechanisms. Targets in the WNT pathway are being extensively pursued for the development of new anticancer therapies, and we have advanced two WNT antagonists for clinical development: vantictumab (anti-FZD) and ipafricept (FZD8-Fc). We examined the antitumor efficacy of these WNT antagonists in combination with various chemotherapies in a large set of patient-derived xenograft models...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28687178/a-randomized-pilot-evaluation-of-individual-level-abortion-stigma-resulting-from-pennsylvania-mandated-abortion-counseling
#4
Sarita Sonalkar, Elizabeth P Gurney, Arden Mcallister, Courtney A Schreiber
OBJECTIVE: To investigate the effect of mandated abortion counseling requirements intended to dissuade women from having abortions on patients' individual-level abortion stigma. METHODS: We randomized women presenting for abortion to complete a demographic survey and the validated Individual Level Abortion Stigma (ILAS) scale either before (unexposed) or after (exposed) hearing the mandatory Pennsylvania Abortion Control Act counseling via a standardized video. A sample size of 46 (23 per group) allowed us to detect a one standard deviation difference in mean ILAS score between the groups...
July 4, 2017: Contraception
https://www.readbyqxmd.com/read/28667354/dose-individualization-of-sunitinib-in-metastatic-renal-cell-cancer-toxicity-adjusted-dose-or-therapeutic-drug-monitoring
#5
Dhanusha Sabanathan, Alison Zhang, Peter Fox, Sally Coulter, Val Gebski, Bavanthi Balakrishnar, Mathew Chan, Christopher Liddle, Howard Gurney
PURPOSE: Dose individualization of sunitinib has been proposed using therapeutic drug monitoring (TDM) or toxicity-adjusted dose (TAD). We prospectively studied aspects of TDM and TAD to inform future trials, namely (1) intrapatient variability (CV) of sunitinib and (2) feasibility of a TAD protocol. METHODS: Sunitinib dose was adjusted to ensure grade 1 or 2 toxicity on 10-20 days of each 42-day cycle. Total trough levels (TTL) C min of sunitinib and its active metabolite were measured every 6 weeks...
August 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28654092/risk-factors-for-cryptorchidism
#6
REVIEW
Jason K Gurney, Katherine A McGlynn, James Stanley, Tony Merriman, Virginia Signal, Caroline Shaw, Richard Edwards, Lorenzo Richiardi, John Hutson, Diana Sarfati
Undescended testis - known as cryptorchidism - is one of the most common congenital abnormalities observed in boys, and is one of the few known risk factors for testicular cancer. The key factors that contribute to the occurrence of cryptorchidism remain elusive. Testicular descent is thought to occur during two hormonally-controlled phases in fetal development - between 8-15 weeks (the first phase of decent) and 25-35 weeks gestation (the second phase of descent); the failure of a testis to descend permanently is probably caused by disruptions to one or both of these phases, but the causes and mechanisms of such disruptions are still unclear...
June 27, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28649702/dose-considerations-for-anti-cancer-drugs-in-metastatic-prostate-cancer
#7
REVIEW
Megan Crumbaker, Howard Gurney
Despite a growing number of treatment options, metastatic castrate resistant prostate cancer remains almost universally fatal. Dose individualization ensures patients receive the maximal benefit from each line of treatment potentially leading to improved outcomes, a reduction in quality of life impairment and minimization of premature cessation for avoidable toxicity. Herein, we review drug-specific issues that may be associated with unexpected or unrecognized variations in drug systemic exposure despite the use of protocol doses...
June 26, 2017: Prostate
https://www.readbyqxmd.com/read/28629565/a-tri-exponential-model-for-intravoxel-incoherent-motion-analysis-of-the-human-kidney-in-silico-and-during-pharmacological-renal-perfusion-modulation
#8
René van der Bel, Oliver J Gurney-Champion, Martijn Froeling, Erik S G Stroes, Aart J Nederveen, C T Paul Krediet
In the kidneys, there is both blood flow through the capillaries and flow of pre-urine through the tubuli and collecting ducts. We hypothesized that diffusion-weighted (DW) MRI measures both blood and pre-urine flow when using a tri-exponential intravoxel incoherent motion (IVIM) model. Our aim was to systematically investigate and optimize tri-exponential IVIM-analysis for the kidney and test its sensitivity to renal perfusion changes in humans. The tri-exponential fit probes the diffusion coefficient (D), the intermediate (D*i) and fast (D*f) pseudo-diffusion coefficients, and their signal fractions, fD, fi and ff...
June 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28616080/pedobarography-as-a-clinical-tool-in-the-management-of-diabetic-feet-in-new-zealand-a-feasibility-study
#9
Jason K Gurney, Uwe G Kersting, Dieter Rosenbaum, Ajith Dissanayake, Steve York, Roger Grech, Anthony Ng, Bobbie Milne, James Stanley, Diana Sarfati
BACKGROUND: The peripheral complications of diabetes mellitus remain a significant risk to lower-limb morbidity. In New Zealand, risk of diabetes, comorbidity and lower-limb amputation are highly-differential between demographic groups, particularly ethnicity. There is growing and convincing evidence that the use of pedobarography - or plantar pressure measurement - can usefully inform diabetic foot care, particularly with respect to the prevention of re-ulceration among high-risk patients...
2017: Journal of Foot and Ankle Research
https://www.readbyqxmd.com/read/28610221/first-record-of-spongillaflies-neuroptera-sisyridae-from-colombia
#10
Adrian Ardila-Camacho, Caleb C Martins
The family Sisyridae (spongillaflies) is a small group of neuropterans distributed in all Biogeographic realms (Cover & Resh 2008). As in Nevrorthidae, Sisyridae is distinguished among other Neuroptera families by their strictly aquatic larvae (Wichard et al. 2002). The phylogenetic relationships of Sisyridae have been controversial i.e. the family was recovered at different positions within the Neuropterida phylogeny as a basal group among members of Neuroptera or whitin the suborder Hemerobiiformia with a very variable placement (Randolf et al...
June 9, 2017: Zootaxa
https://www.readbyqxmd.com/read/28591075/comparison-of-the-vacuum-mattress-versus-the-spine-board-alone-for-immobilization-of-the-cervical-spine-injured-patient-a-biomechanical-cadaveric-study
#11
Mark L Prasarn, Per Kristian Hyldmo, Laura A Zdziarski, Evan Loewy, Dewayne Dubose, MaryBeth Horodyski, Glenn R Rechtine
STUDY DESIGN: Biomechanical cadaveric study. SUMMARY OF BACKGROUND DATA: Trauma patients in the United States are immobilized on a rigid spine board, whereas in many other places vacuum mattresses are used with the proposed advantages of improved comfort and better immobilization of the spine. OBJECTIVE: We sought to determine the amount of motion generated in an unstable cervical spine fracture with use of the vacuum mattress versus the spine board alone...
June 6, 2017: Spine
https://www.readbyqxmd.com/read/28549248/metastatic-chromophobe-renal-cell-carcinoma-treated-with-targeted-therapies-a-renal-cross-channel-group%C3%A2-study
#12
Emeline Colomba, Gwénaël Le Teuff, Tim Eisen, Grant D Stewart, Kate Fife, James Larkin, Andrea Biondo, Lisa Pickering, Anandagopal Srinivasan, Helen Boyle, Lisa Derosa, Cora N Sternberg, Federica Recine, Christy Ralph, Carolina Saldana, Philippe Barthélémy, Jean Christophe Bernhard, Howard Gurney, Gregory Verhoest, Elodie Vauleon, Pierre Bigot, Julien Berger, Christian Pfister, Gwenaelle Gravis, Jean-Michel Rodier, Stéphane Culine, Armelle Caty, Frederic Rolland, Franck Priou, Bernard Escudier, Laurence Albiges
BACKGROUND: Treatment of non-clear cell renal cell carcinoma (RCC) remains controversial despite several recent prospective studies of targeted therapies (TT). Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC. METHODS: We performed a retrospective data analysis within the Renal Cross Channel Group to determine metastatic chromophobe RCC (mChRCC) outcomes in the TT era...
May 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28544085/e-tc-development-and-pilot-testing-of-a-web-based-intervention-to-reduce-anxiety-and-depression-in-survivors-of-testicular-cancer
#13
L E Heiniger, A B Smith, I Olver, P Grimison, B Klein, A Wootten, J-A M Abbott, M A Price, M McJannett, B Tran, M R Stockler, H Gurney, P N Butow
e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme...
May 22, 2017: European Journal of Cancer Care
https://www.readbyqxmd.com/read/28542295/therapeutic-benefits-of-phosphodiesterase-4b-inhibition-after-traumatic-brain-injury
#14
Nicole M Wilson, Mark E Gurney, W Dalton Dietrich, Coleen M Atkins
Traumatic brain injury (TBI) initiates a deleterious inflammatory response that exacerbates pathology and worsens outcome. This inflammatory response is partially mediated by a reduction in cAMP and a concomitant upregulation of cAMP-hydrolyzing phosphodiesterases (PDEs) acutely after TBI. The PDE4B subfamily, specifically PDE4B2, has been found to regulate cAMP in inflammatory cells, such as neutrophils, macrophages and microglia. To determine if PDE4B regulates inflammation and subsequent pathology after TBI, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury (2 ± 0...
2017: PloS One
https://www.readbyqxmd.com/read/28514618/aerobic-or-resistance-exercise-or-both-in-dieting-obese-older-adults
#15
RANDOMIZED CONTROLLED TRIAL
Dennis T Villareal, Lina Aguirre, A Burke Gurney, Debra L Waters, David R Sinacore, Elizabeth Colombo, Reina Armamento-Villareal, Clifford Qualls
BACKGROUND: Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia. METHODS: In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs - aerobic training, resistance training, or combined aerobic and resistance training - or to a control group (no weight-management or exercise program)...
May 18, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28513321/active-travel-to-and-from-school-among-school-age-children-during-1997-2011-and-associated-factors-in-china
#16
Yong Yang, Xue Hong, James G Gurney, Youfa Wang
BACKGROUND: Active travel to school (ATS) is positively associated with various health indicators. The rapid social, economic and environmental changes in China provide a unique setting to study changes and predictors of ATS over time. METHODS: Using logistic regression modeling, we analyzed data from the China Health and Nutrition Survey during 1997-2011 (N=9487, ages 6-17 years) to estimate the change over time in ATS and to identify associated factors. RESULTS: The prevalence of reported ATS among children dropped from 95...
May 17, 2017: Journal of Physical Activity & Health
https://www.readbyqxmd.com/read/28488360/cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-safety-and-quality-of-life-data-from-the-australian-early-access-program
#17
Phillip Parente, Siobhan Ng, Francis Parnis, Alex Guminski, Howard Gurney
AIM: Cabazitaxel is a next generation taxane that has been shown to improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed during or after docetaxel-based therapy. A worldwide early access program (EAP) study was established to provide access to cabazitaxel ahead of commercial availability and to evaluate its safety and tolerability. The Australian EAP included patient-reported outcomes to evaluate the impact of cabazitaxel on quality of life (QoL)...
May 10, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28475622/target-distractor-synchrony-affects-performance-in-a-novel-motor-task-for-studying-action-selection
#18
Sebastian James, Olivia A Bell, Muhammed A M Nazli, Rachel E Pearce, Jonathan Spencer, Katie Tyrrell, Phillip J Paine, Timothy J Heaton, Sean Anderson, Mauro Da Lio, Kevin Gurney
The study of action selection in humans can present challenges of task design since our actions are usually defined by many degrees of freedom and therefore occupy a large action-space. While saccadic eye-movement offers a more constrained paradigm for investigating action selection, the study of reach-and-grasp in upper limbs has often been defined by more complex scenarios, not easily interpretable in terms of such selection. Here we present a novel motor behaviour task which addresses this by limiting the action space to a single degree of freedom in which subjects have to track (using a stylus) a vertical coloured target line displayed on a tablet computer, whilst ignoring a similarly oriented distractor line in a different colour...
2017: PloS One
https://www.readbyqxmd.com/read/28429452/real-world-experience-of-the-feasibility-and-tolerability-of-the-2-1-dosing-schedule-with-sunitinib-in-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-in-australia
#19
Megan Crumbaker, Alexander Guminski, Howard Gurney, Dhanusha Sabanathan, Shirley Wong, Nick Pavlakis
AIM: Sunitinib is a first-line treatment option for metastatic renal cell carcinoma (mRCC) funded by the Australian Pharmaceutical Benefits Scheme. Toxicities are common with the standard schedule leading to alternative dosing schedules to be suggested. We reviewed Australian treatment practices to evaluate the safety and outcomes of patients on a 2 weeks on, 1 week off treatment schedule (2/1). METHODS: We performed a retrospective review of 63 patients with mRCC treated with first-line sunitinib on a 2/1 schedule at four Australian centers...
April 21, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28426558/combat-surgical-workload-in-operation-iraqi-freedom-and-operation-enduring-freedom-the-definitive-analysis
#20
Caryn A Turner, Zsolt T Stockinger, Jennifer M Gurney
BACKGROUND: Relatively few publications exist on surgical workload in the deployed military setting. This study analyzes US military combat surgical workload in Iraq and Afghanistan to gain a more thorough understanding of surgical training gaps and personnel requirements. METHODS: A retrospective analysis of the Department of Defense Trauma Registry was performed for all Role 2 (R2) and Role 3 (R3) military treatment facilities from January 2001 to May 2016. International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes were grouped into 18 categories based on functional surgical skill sets...
July 2017: Journal of Trauma and Acute Care Surgery
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