Genetic variation of the prion protein gene (PRNP) in alpaca (Vicugna pacos)

Transmissible spongiform encephalopathies (TSE) are caused by accumulation of a misfolded form of the prion protein (PrP). The normal cellular isoform of PrP is produced by the prion gene (PRNP) and is highly expressed in the central nervous system. Currently, there is an absence of information regarding the genetic sequence of alpaca PRNP and the potential susceptibility of this species to TSE. The objective of this study was to sequence the open reading frame of the alpaca prion gene and analyze this sequence for variation within the alpaca population and for homology to TSE-susceptible species. We sequenced the open reading frame of the prion gene of 40 alpacas of Huacaya or Suri descent. Length polymorphisms were identified within the sampled population. A subset (15%) of animals contained an additional 24 base pairs within the putative octapeptide repeat region. This polymorphism was independent of breed and sex. The majority (52.5%) of animals were heterozygous, possessing both longer and shorter alleles. Comparison with proven TSE-susceptible species (sheep, cattle, deer) revealed the following amino acid sequence variations: I6M, A16V, M17T, G92del, Q95_G96insG, N111S, R167K, N/T177S, I206V, S225Y, Y228S, Q230G, and L237del. Sequence alignment showed high homology compared to camel (\u3e 95%), sheep (\u3e 88%), cattle (\u3e 87%) and deer (\u3e 88%) PRNP sequence. This study demonstrates intraspecies variability within the PRNP open reading frame in alpacas and overall high sequence homology to TSE-susceptible species, providing foundational data for further research on the potential susceptibility of alpacas to TSE

Le FORUM, Vol. 38 No. 4

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Le Forum, Vol. 41 No. 1

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Le FORUM, Vol. 37 No. 3

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The TA Framework: Designing Real-time Teaching Augmentation for K-12 Classrooms

Recently, the HCI community has seen increased interest in the design of teaching augmentation (TA): tools that extend and complement teachers' pedagogical abilities during ongoing classroom activities. Examples of TA systems are emerging across multiple disciplines, taking various forms: e.g., ambient displays, wearables, or learning analytics dashboards. However, these diverse examples have not been analyzed together to derive more fundamental insights into the design of teaching augmentation. Addressing this opportunity, we broadly synthesize existing cases to propose the TA framework. Our framework specifies a rich design space in five dimensions, to support the design and analysis of teaching augmentation. We contextualize the framework using existing designs cases, to surface underlying design trade-offs: for example, balancing actionability of presented information with teachers' needs for professional autonomy, or balancing unobtrusiveness with informativeness in the design of TA systems. Applying the TA framework, we identify opportunities for future research and design.Comment: to be published in Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems, 17 pages, 10 figure

Human adipose stem cells cell sheet constructs impact epidermal morphogenesis in full-thickness excisional wounds

Among the wide range of strategies to target skin repair/regeneration, tissue engineering (TE) with stem cells at the forefront, remains as the most promising route. Cell sheet (CS) engineering is herein proposed, taking advantage of particular cell-cell and cell-extracellular matrix (ECM) interactions and subsequent cellular milieu, to create 3D TE constructs to promote full-thickness skin wound regeneration. Human adipose derived stem cells (hASCs) CS were obtained within five days using both thermoresponsive and standard cell culture surfaces. hASCs-based constructs were then built by superimposing three CS and transplanted into full-thickness excisional mice skin wounds with delayed healing. Constructs obtained using thermoresponsive surfaces were more stable than the ones from standard cell culture surfaces due to the natural adhesive character of the respective CS. Both CS-generating strategies lead to prolonged hASCs engraftment, although no transdifferentiation phenomena were observed. Moreover, our findings suggest that the transplanted hASCs might be promoting neotissue vascularization and extensively influencing epidermal morphogenesis, mainly through paracrine actions with the resident cells. The thicker epidermis, with a higher degree of maturation characterized by the presence of rete ridges-like structures, as well as a significant number of hair follicles observed after transplantation of the constructs combining the CS obtained from the thermoresponsive surfaces, reinforced the assumptions of the influence of the transplanted hASCs and the importance of the higher stability of these constructs promoted by cohesive cell-cell and cell-ECM interactions. Overall, this study confirmed the potential of hASCs CS-based constructs to treat full-thickness excisional skin wounds and that their fabrication conditions impact different aspects of skin regeneration, such as neovascularisation, but mainly epidermal morphogenesis.We would like to thank Hospital da Prelada (Porto), in particular, to Dr. Paulo Costa for the lipoaspirates collection and for financial support by Skingineering (PTDC/SAU-OSM/099422/2008), Portuguese Foundation for Science and Technology (FCT) funded project. The research leading to these results has also received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. REGPOT-CT2012-316331-POLARIS

Photopatterned antibodies for selective cell attachment

We present a phototriggerable system that allows for the spatiotemporal controlled attachment of selected cell types to a biomaterial using immobilized antibodies that specifically target individual cell phenotypes.o-Nitrobenzyl caged biotin was used to functionalize chitosan membranes and mediate site-specific coupling of streptavidin and biotinylated antibodies after light activation. The ability of this system to capture and immobilize specific cells on a surface was tested using endothelial-specific biotinylated antibodies and nonspecific ones as controls. Homogeneous patterned monolayers of human umbilical vein endothelial cells were obtained on CD31-functionalized surfaces. This is a simple and generic approach that is applicable to other ligands, materials, and cell types and shows the flexibility of caged ligands to trigger and control the interaction between cells and biomaterials.We thank Martina Knecht (MPIP) for help with the synthesis of caged biotin and Dr. Ron Unger and Prof. C. J. Kirkpatrick (University Clinic Mainz, RepairLab) for providing HUVECs. C.A.C. acknowledges funding support from the Portuguese Foundation for Science and Technology (FCT) (fellowship SFRH/BD/61390/2009) and from the International Max-Planck Research School in Mainz. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. REGPOT-CT2012-316331-POLARIS

A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer.

Objective PF-04691502 and gedatolisib (PF-05212384) are potent, dual PI3K/mTOR inhibitors. This phase II study (B1271004) was conducted in patients with recurrent endometrial cancer following platinum-containing chemotherapy. The primary endpoint was to assess clinical benefit response (complete or partial response, or stable disease for ≥16weeks) following treatment with PF-04691502 or gedatolisib.Methods The main study consisted of four independent arms based on a Simon two-stage design. Patients were assigned to putative PI3K-basal (PF-04691502 or gedatolisib) or PI3K-activated (PF-04691502 or gedatolisib) arms based on stathmin-low or stathmin-high tumor expression, respectively. Japanese patients were also enrolled in a separate lead-in cohort.Results In stage 1 (main study), eighteen patients were randomized to PF-04691502 and 40 to gedatolisib. The two PF-04691502 arms were discontinued early due to unacceptable toxicity, including pneumonia and pneumonitis. The most common treatment-related adverse events associated with gedatolisib were nausea (53%), mucosal inflammation (50%), decreased appetite (40%), diarrhea (38%), fatigue (35%), and dysgeusia and vomiting (each 30%). Clinical benefit response rate was 53% (10/19) in the gedatolisib/stathmin-low arm and 26% (5/19) in the gedatolisib/stathmin-high arm. Safety profile and pharmacokinetic characteristics of both drugs in the Japanese lead-in cohort were comparable to the Western population.Conclusions Gedatolisib administered by weekly intravenous infusion demonstrated acceptable tolerability and moderate activity in patients with recurrent endometrial cancer. PF-04691502 daily oral dosing was not well tolerated. Clinical benefit response criteria for proceeding to stage 2 were only met in the gedatolisib/stathmin-low arm. Stathmin-high expression did not correlate with greater treatment efficacy. ClinicalTrials.gov registration ID: NCT01420081

Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).</p> <p>Methods</p> <p>Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.</p> <p>Results</p> <p>Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.</p> <p>Conclusion</p> <p>The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.</p

Healthcare professionals' intentions and behaviours: A systematic review of studies based on social cognitive theories

<p>Abstract</p> <p>Background</p> <p>There is an important gap between the implications of clinical research evidence and the routine clinical practice of healthcare professionals. Because individual decisions are often central to adoption of a clinical-related behaviour, more information about the cognitive mechanisms underlying behaviours is needed to improve behaviour change interventions targeting healthcare professionals. The aim of this study was to systematically review the published scientific literature about factors influencing health professionals' behaviours based on social cognitive theories. These theories refer to theories where individual cognitions/thoughts are viewed as processes intervening between observable stimuli and responses in real world situations.</p> <p>Methods</p> <p>We searched psycINFO, MEDLINE, EMBASE, CIHNAL, Index to theses, PROQUEST dissertations and theses and Current Contents for articles published in English only. We included studies that aimed to predict healthcare professionals' intentions and behaviours with a clear specification of relying on a social cognitive theory. Information on percent of explained variance (R²) was used to compute the overall frequency-weighted mean R²to evaluate the efficacy of prediction in several contexts and according to different methodological aspects. The cognitive factors most consistently associated with prediction of healthcare professionals' intention and behaviours were documented.</p> <p>Results</p> <p>Seventy eight studies met the inclusion criteria. Among these studies, 72 provided information on the determinants of intention and 16 prospective studies provided information on the determinants of behaviour. The theory most often used as reference was the Theory of Reasoned Action (TRA) or its extension the Theory of Planned Behaviour (TPB). An overall frequency-weighted mean R²of 0.31 was observed for the prediction of behaviour; 0.59 for the prediction of intention. A number of moderators influenced the efficacy of prediction; frequency-weighted mean R²varied from 0.001 to 0.58 for behaviour and 0.19 to 0.81 for intention.</p> <p>Conclusion</p> <p>Our results suggest that the TPB appears to be an appropriate theory to predict behaviour whereas other theories better capture the dynamic underlying intention. In addition, given the variations in efficacy of prediction, special care should be given to methodological issues, especially to better define the context of behaviour performance.</p