External Responsiveness of the SuperOpTM Device to Assess Recovery After Exercise : A Pilot Study

Post-exercise recovery is a complex process involving a return of performance and a physiological or perceptual feeling close to pre-exercise status. The hypothesis of this study is that the device investigated here is effective in evaluating the recovery state of professional cyclists in order to plan effective training. Ten professional male cyclists belonging to the same team were enrolled in this study. Participants performed a 7-day exercise program [D1, D4, and D7: low-intensity training; D2 and D5: passive recovery; D3: maximum oxygen consumption (VO2Max) test (for maximum mechanical power assessment only); and D6: constant load test]. During the week of monitoring, each morning before getting up, the device assessed each participant's so-called Organic Readiness {OR [arbitrary unit (a.u.)]}, based on blood pressure (BP), heart rate (HR), features of past exercise session, and following self-perceived condition. Based on its readings and algorithm, the device graphically displayed four different colors/values, indicating general exercise recommendations: green/3 = \u201cyou can train hard,\u201d yellow/2 = \u201cyou can train averagely,\u201d orange/1 = \u201cyou can train lightly,\u201d or red/0 = \u201cyou should recover passively.\u201d During the week of research, morning OR values and Bonferroni post-hoc comparisons showed significant differences between days and, namely, values (1) D2 (after low intensity training) was higher than D4 (after VO2Max test; P = 0.033 and d = 1.296) and (2) D3 and D6 (after passive recovery) were higher than D4 (after VO2Max test; P = 0.006 and d = 2.519) and D5 (after low intensity training; P = 0.033 and d = 1.341). The receiver operating characteristic analysis area under curve (AUC) recorded a result of 0.727 and could differentiate between D3 and D4 with a sensitivity and a specificity of 80%. Preliminarily, the device investigated is a sufficiently effective and sensitive/specific device to assess the recovery state of athletes in order to plan effective training

Genotyping of invasive Ponto-Caspian gobies in Croatia

The biology and ecology of non-native freshwater Ponto-Caspian (P-C) gobies: monkey goby, Neogobius fluviatilis (Pallas, 1814), round goby, Neogobius melanostomus (Pallas, 1814) and bighead goby, Ponticola kessleri (Günther, 1861) have been studied in Croatia, but the genetic structure of populations in the Sava River catchment remains unknown. Only a single mitochondrial DNA cytochrome b haplotype, consistent with native Black Sea populations, has been detected within Croatian populations. Based on emerging molecular evidence, the invasive potential (e.g. upstream migration and environmental plasticity) of individual non-native gobies within the Sava River catchment, may be influenced by genetic structuring

Patient-Derived Xenografts and Organoids Recapitulate Castration-Resistant Prostate Cancer with Sustained Androgen Receptor Signaling

Castration-resistant prostate cancer (CRPC) remains an incurable and lethal malignancy. The development of new CRPC treatment strategies is strongly impeded by the scarcity of representative, scalable and transferable preclinical models of advanced, androgen receptor (AR)-driven CRPC. Here, we present contemporary patient-derived xenografts (PDXs) and matching PDX-derived organoids (PDXOs) from CRPC patients who had undergone multiple lines of treatment. These models were comprehensively profiled at the morphologic, genomic ( n = 8) and transcriptomic levels ( n = 81). All are high-grade adenocarcinomas that exhibit copy number alterations and transcriptomic features representative of CRPC patient cohorts. We identified losses of PTEN and RB1, MYC amplifications, as well as genomic alterations in TP53 and in members of clinically actionable pathways such as AR, PI3K and DNA repair pathways. Importantly, the clinically observed continued reliance of CRPC tumors on AR signaling is preserved across the entire set of models, with AR amplification identified in four PDXs. We demonstrate that PDXs and PDXOs faithfully reflect donor tumors and mimic matching patient drug responses. In particular, our models predicted patient responses to subsequent treatments and captured sensitivities to previously received therapies. Collectively, these PDX-PDXO pairs constitute a reliable new resource for in-depth studies of treatment-induced, AR-driven resistance mechanisms. Moreover, PDXOs can be leveraged for large-scale tumor-specific drug response profiling critical for accelerating therapeutic advances in CRPC. </p

Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment

We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on 18F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had 11C-PBR28 PET to measure microglial activation and 43 had 18F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were associated with increased overall binding for both 11C-PBR28 and 18F-MK-6240 (p’s < 0.01). While there was no interaction between amyloid and cognitive status in their association with 11C-PBR28 binding (p = 0.6722), there was an interaction in their association with 18F-MK-6240 binding (p = 0.0115). Binding of both radioligands was greater in amyloid-positive controls than in amyloid-negative controls; however, this difference was seen in neocortical regions for 11C-PBR28 and only in medial temporal cortex for 18F-MK-6240. We conclude that, in the absence of cognitive symptoms, amyloid deposition has a greater association with microglial activation than with tau pathology

Spatial Registration Evaluation of [18F]-MK6240 PET

Image registration is an important preprocessing step in neuroimaging which allows for the matching of anatomical and functional information between modalities and subjects. This can be challenging if there are gross differences in image geometry or in signal intensity, such as in the case of some molecular PET radioligands, where control subjects display relative lack of signal relative to noise within intracranial regions, and may have off target binding that may be confused as other regions, and may vary depending on subject. The use of intermediary images or volumes have been shown to aide registration in such cases. To account for this phenomena within our own longitudinal aging cohort, we generated a population specific MRI and PET template from a broad distribution of 30 amyloid negative subjects. We then registered the PET image of each of these subjects, as well as a holdout set of thirty 'template-naive' subjects to their corresponding MRI images using the template image as an intermediate using three different sets of registration parameters and procedures. To evaluate the performance of both conventional registration and our method, we compared these to the registration of the attenuation CT (acquired at time of PET acquisition) to MRI as the reference. We then used our template to directly derive SUVR values without the use of MRI. We found that conventional registration was comparable to an existing CT based standard, and there was no significant difference in errors collectively amongst all methods tested. In addition, there were no significant differences between existing and MR-less tau PET quantification methods. We conclude that a template-based method is a feasible alternative to, or salvage for, direct registration and MR-less quantification; and, may be preferred in cases where there is doubt about the similarity between two image modalities

Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response

Oxidative stress and its end-products, such as 4-hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/KEAP1 signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of ARE-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy