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We herein describe the development of a novel dual-modality optical/radio-imaging agent for general and site-specific labeling of biovectors through a 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. The CBT-based multifunctional single-attachment-point (MSAP) agent enables a single-step synthesis of various dual-modality probes characterized by rapid conjugation, high labeling yields, metabolically stable products and applicability to orthogonal two-step labeling of sensitive biomolecules. In addition, the two-step radiolabeling protocol and click reaction were optimized by using CBT scavengers to improve the reaction rate and molar activity of the imaging probes. Our methodology allows for a simple and efficient synthetic route to produce a variety of dual-modality imaging agents for preoperative surgical planning and intraoperative surgical guidance.

Plants as sessile organisms use calcium ions (Ca2+) as secondary messengers to respond to biotic and abiotic stimuli. In order to interpret Ca2+ signatures, plants process many Ca2+ sensor proteins, including the large family of Calmodulin-like proteins (CMLs). The functions of most CMLs in plants remains unclear. CML13 is a biochemically-unique CML whose role in cells is unstudied but recent data from the Snedden Lab suggests it interacts with several cytoskeletal proteins and a class of transcriptional activators. To gain insight into CML13 function, I investigated the gene promoter activity of CML13 in transgenic Arabidopsis at different developmental stages and tissues using CML13-promoter--glucuronidase (GUS) reporter assays. I also explored the phenotype of a cml13 loss-of-function transgenic line. In seeds of cml13 plants, the germination rate was lower than wild-type (WT) plants in response to 1 µM ABA at 24 h and 48 h suggesting CML13 may function in ABA pathways regulating germination. Other than this sensitivity to ABA, cml13 plants did not show any observable phenotypic differences from WT throughout development under my growth conditions. In GUS assays of CML13pro::GUS plants, CML13 promoter activity was detected throughout Arabidopsis development in a variety of tissues. The broad distribution of CML13 may indicate involvement of CML13 in a fundamental or “housekeeping” cell process. The spatial promoter activity at points of lateral-root emergence, and points of probable vascular connection of lateral and parental roots, suggests CML13 may also function in developmental pathways under auxin control but this remains speculative. Collectively, my research suggests a broad expression pattern of CML13 in Arabidopsis and suggests future work should explore a role for CML13 in germination and root patterning.

Combining peginterferon-alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 μg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti-HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti-HBs antibodies.

Phenology, or the timing of life cycle events, is a key trait of organisms that has significance for how communities are assembled and ecosystems function. Although variation in phenology in plants has received increased attention over the past decade as a result of changing climate, we are only beginning to understand the role of genetic variation in these phenological traits on ecological interactions and ecosystem-level processes. The influence of tree species on riparian environments presents an interesting system for understanding the effects of phenology in terrestrial species on aquatic ecosystems. Here, we used a dominant riparian tree (Populus trichocarpa: Salicaceae) and tested intraspecific genetic variation in the phenological timing of leaf drop, which influenced leaf-litter inputs into our experimental aquatic ecosystems. Our empirical results found that genotypic differences in P. trichocarpa explained much of the variation both in leaf-litter decomposition and aquatic invertebrate species richness within our experimental ponds. Moreover, our results showed that variation in the timing of leaf-litter inputs outweighed the effects of variation in leaf-litter quality among P. trichocarpa genotypes on aquatic invertebrate species richness. Taken together, our results suggest that genetic variation in the timing of litter inputs from dominant plant species is likely to be a strong underlying mechanism driving litter decomposition and invertebrate communities in aquatic ecosystems. This emphasises that studies disregarding phenology may significantly underestimate an important and variable component in communities and ecosystems. Fil: Rodriguez Cabal, Mariano Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. University of British Columbia; Canadá Fil: Barrios Garcia Moar, Maria Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of British Columbia; Canadá. Administración de Parques Nacionales. Parque Nacional "Nahuel Huapi"; Argentina Fil: Rudman, Seth M.. University of British Columbia; Canadá Fil: McKown, Athena D.. University of British Columbia; Canadá Fil: Sato, Takuya. Kobe University; Japón Fil: Crutsinger, Gregory M.. University of British Columbia; Canadá

Even though the WHO Essential Medicines List has been published and updated for the last 40 years, diagnostics only got their due recognition in the last two years. WHO published the first Essential Diagnostics List (EDL) in 2018 and subsequently updated in 2019...

Abstract European countries have been the key destination for many Syrians since the beginning of the civil war in 2011. In this new context, refugees have faced various challenges, including negative public attitudes and pressure of assimilation that might negatively influence psychophysical adaptation. This indicates the necessity of exploring the factors associated with the adaptation of refugees in their new society. Using a multidimensional individual difference acculturation (MIDA) model as a theoretical framework, the present study investigated the psychophysical adaptation of Syrian refugees (N = 265, Mage = 33.03 years) in Germany. The MIDA model is a theoretical model on immigrants’ adaptation that takes into account the role of psychosocial resources (e.g., psychological strength), co-national connectedness (e.g., ingroup support), hassles, and acculturation orientations in predicting adaptation of immigrants. Using structural equation modelling, specific hypotheses drawn from the MIDA model were tested. It was found that Syrian refugees with high psychological strength and cultural competence reported high levels of adjustment as indicated by low levels of distress. On the other hand, refugees with high levels of perceived hassles reported low levels of adjustment as indicated by high level of distress. The results highlight the importance of psychological strength, cultural competence, and hassles in refugees’ adaption. The study’s findings have the potential to inform host country policymakers regarding the positive integration of refugees into German society, and specific recommendations have been made.

Summary Cancer is a substantial health burden for Inuit populations, an Indigenous peoples who primarily inhabit the circumpolar regions of Alaska, Canada, Greenland, and Russia. Access to radiotherapy is lacking or absent in many of these regions, despite it being an essential component of cancer treatment. This Review presents an overview of factors influencing radiotherapy delivery in each of the four circumpolar Inuit regions, which include population and geography, health-systems infrastructure, and cancer epidemiology. This Review also provides insight into the complex patient pathways needed to access radiotherapy, and on radiotherapy use. The unique challenges in delivering radiotherapy to circumpolar Inuit populations are discussed, which, notably, include geographical and cultural barriers. Recommendations include models of care that have successfully addressed these barriers, and highlight the need for increased collaboration between circumpolar referral centres in Alaska, Canada, Greenland, and Russia to ultimately allow for better delivery of cancer treatment.

Overexpression of legumain is closely associated with tumor proliferation, invasion, and metastasis. Because of its intrinsic properties, such as high sensitivity and resolution, positron emission tomography (PET) has become an effective imaging technique for early diagnosis, treatment response prediction, and monitoring. Herein, two legumain-targeting radiofluorinated smart probes (18F-2 and 18F-3) as well as a control probe (18F-1) were specifically designed for PET imaging of legumain activity in tumors. 18F-1, 18F-2, and 18F-3 were obtained with high radiochemical yield (RCY > 60%) and radiochemical purity (RCP > 99%) using a convenient "one-step" 18F-labeling method. The probes 18F-2 and 18F-3 exhibited high response to legumain activity and reductive environment and revealed comparable uptake in HCT116 cells (4.22% ± 0.14% and 4.64% ± 0.32% for 18F-2 and 18F-3, respectively; 8.46% ± 0.33% and 9.05% ± 0.24% for co-treatment of 18F-2 + 2 and 18F-3 + 3 at 1 h), while the control probe 18F-1 showed no response. PET imaging of tumor-bearing mice showed that the co-injection strategy (18F-2 + 2 and 18F-3 + 3) resulted in higher tumor uptake (3.57% ± 0.37% and 3.72% ± 0.19% ID/g at 10 min, respectively) than the single injection strategy (2.59% ± 0.19% and 2.60% ± 0.46% ID/g for 18F-2 and 18F-3, respectively). In addition, introduction of the trimeric histidine-glutamate (HEHEHE) tag to 18F-3 reduced the liver uptake by almost two-fold without any noticeable effect on the tumor uptake. All the results indicate that 18F-3 holds great potential applications in clinics for sensitive and specific PET imaging of legumain activity in tumors.

Abstract Background The purpose of this prospective study was to understand the relation between gait outcomes and patient satisfaction one year after total knee arthroplasty (TKA). Methods Seventy-nine patients were evaluated before and one year after TKA using clinical gait analysis. Specific gait outcomes were analyzed: gait speed, stance phase, range of motion (ROM) knee flexion and maximal knee flexion. The parameters of interest selected for the statistical analysis were: gait speed and maximal knee flexion during gait. The Western Ontario and MacMaster Osteoarthritis Index (WOMAC) and patient satisfaction were also assessed. The satisfaction was evaluated using a questionnaire and was splited in five categories: very unsatisfied, unsatisfied, neutral, satisfied or very satisfied. To assess associations between patient satisfaction and maximal knee flexion during gait and gait speed, an unadjusted ordinal logistic regression analysis was used. The analysis was then adjusted for covariates: age and Body Mass Index (BMI) before surgery and WOMAC pain one year after surgery. Results All gait outcomes after TKA had significantly improved. The ordinal logistic regression analysis found significant associations between patient satisfaction and maximal knee flexion after TKA (unadjusted and adjusted) but not for gait speed. Conclusion These findings show that all patients improved their gait outcomes one year after TKA but only a higher maximal knee flexion during gait may influence the level of patient satisfaction.