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Selective attention is an important cognitive phenomenon that allows organisms to flexibly engage with certain environmental cues or activities while ignoring others, permitting optimal behaviour. It has been proposed that selective attention can be present in many different animal species and, more recently, in plants. The phenomenon of attention in plants would be reflected in its electrophysiological activity, possibly being observable through electrophytographic (EPG) techniques. Former EPG time series obtained from the parasitic plant Cuscuta racemosa in a putative state of attention towards two different potential hosts, the suitable bean (Phaseolus vulgaris) and the unsuitable wheat (Triticum aestivum), were revisited. Here, we investigated the potential existence of different band frequencies (including low, delta, theta, mu, alpha, beta, and gamma waves) using a protocol adapted from neuroscientific research. Average band power (ABP) was used to analyse the energy distribution of each band frequency in the EPG signals, and time dispersion analysis of features (TDAF) was used to explore the variations in the energy of each band. Our findings indicated that most band waves were centred in the lower frequencies. We also observed that C. racemosa invested more energy in these low-frequency waves when suitable hosts were present. However, we also noted peaks of energy investment in all the band frequencies, which may be linked to extremely low oscillatory electrical signals in the entire tissue. Overall, the presence of suitable hosts induced a higher energy power, which supports the hypothesis of attention in plants. We further discuss and compare our results with generic neural systems.

Despite several advances in medicine, ischaemic heart disease remains a major cause of morbidity and mortality. The unravelling of molecular mechanisms underlying disease pathophysiology has revealed targets for pharmacological interventions. However, transfer of these pharmcological possibilities to clinical use has been disappointing. Considering the complexity of ischaemic disease at the cellular and molecular levels, an equally multifaceted treatment approach may be envisioned. The pharmacological principle of ‘one target, one key’ may fall short in such contexts, and optimal treatment may involve one or many agents directed against complementary targets. Here, we introduce a ‘multi‐target approach to cardioprotection’ and propose heat shock protein 90 (HSP90) as a target of interest. We report on a member of a distinct class of HSP90 inhibitor possessing pleiotropic activity, which we found to exhibit potent infarct‐sparing effects.

The sessile lifestyle of plants exposes them to many challenges that must be overcome to ensure their survival. Despite their apparent lack of movement and behaviour, plants are very active organisms that constantly respond to external cues and internal signals, making fine tunings at the metabolic, cellular and tissue levels. To accomplish this, plants largely rely on their relationship between phenotypic plasticity and cognitive abilities, which requires an information (or signalling) system. This information system is composed of many different signals, and among them are the electrical ones. Besides, in plants, there are many electrical activities that are not necessarily considered electrical signals. However, the sum of all electrical activity of a plant, considering all levels of organization, engenders the electrical dimension of their life. This dimension of life that encompasses all the living beings has recently been named “electrome”, in analogy with the other ‘omics’ from system biology approach. In the present review, we will explore this concept to describe the plant electrical activities. Furthermore, some basic aspects that are underlying the plant electrome will be presented, including the principles of biophysics that sustain the electrical activity of the cells. Moreover, some examples of electrical activities and signals that are vital to the plants will be exposed. Then, our most relevant and recent breakthroughs about plant electrome dynamics under different environmental conditions will be presented. Finally, some considerations about the possible involvement of the electrome plasticity and cognition features associated with the adaptive behaviour of plants will be discussed.

This is an overview of radiological imaging of the hand highlighting the various imaging modalities used in the work-up and diagnosis of a range of orthopaedic and rheumatological disorders. The biomechanics and anatomy of the human hand is extremely complex, and a good understanding is required to diagnose pathology. In this article we explain the anatomy and highlight pathology of the hand from a radiological perspective with respect to plain film, CT, ultrasound and MR imaging. Trauma of the hand is extremely common and radiology plays an important role in the diagnosis of treatable injuries including fractures, dislocations and ligament tears. Plain radiography and CT are excellent at evaluating bony injury (e.g. Rolondo or Bennett's fracture) whereas ultrasound and MR are better at evaluating soft tissue injury (e.g. Stener lesion). The hands are a common location for degenerate and inflammatory arthropathies which all have hallmark radiological features. Radiology also plays an important role in the diagnosis and work-up of bone lesions in the hand including enchondromas, osteoid osteomas and chondrosarcomas.

Clinical introductionA healthy 8-year-old boy presented to the ED with acute left shoulder pain. He had been playing football and his left arm was pulled by an opposition team member. He fell to the ground and landed on his left shoulder causing pain. On examination after analgesia, active and passive movement of the shoulder joint was possible in all directions but range of motion was limited by pain. There was no visible swelling or bruising throughout the shoulder girdle. A radiograph of the shoulder was obtained (figure 1).Figure 1Plain radiograph of the left shoulder.QuestionWhat radiographic finding is seen for this patient?Glenohumeral lipohaemarthrosis.Acromioclavicular joint disruption.Intra-articular gas.Intra-articular loose body.

A penile fracture is defined as a tear of the tunica albuginea, surrounding the corpus cavernosa. It occurs when the erect penis is subjected to an abnormal ‘bending’ force, inducing an acute increase in intracavernosal pressures, exceeding the tensile strength of the tunica albuginea, which is

Recent studies on plant-environment and plant-human relationships reveal the need to reassess thescales of perception, sensitiveness and cognition of living systems. The complexity of plant's emergingbehaviors in interaction with the environment is supported by the signature of the electrome and theplant sensorium, a strong argument to establish the singularity of the living and weights its consequencesin evolutionary, ecological or socioeconomic terms. This paper highlights the cognitive value of access tothe experience of plants and its fundamentally mesological or ecoplastic nature, that is to say in directconnection with a singular milieu. This dynamic coupling makes it possible to explain the co-construction ofan intelligible and sensible world without the use of a brain, principle that reframes the concept of intelligentbehavior while revealing both the frontiers in cognition and the strong transdisciplinary challenges of anacute awareness of the man's fragility as of the planetary ecosystem at the era of the Antropocene.

Aneuploidy, defined as the loss and gain of whole and part chromosomes, is a near-ubiquitous feature of cancer genomes, is prognostic, and likely an important determinant of cancer cell biology. In colorectal cancer (CRC), aneuploidy is found in virtually all tumours, including precursor adenomas. However, the temporal evolutionary dynamics that select for aneuploidy remain broadly uncharacterised. Here we perform genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that cross-sectionally represent the distinct stages of tumour evolution, and longitudinally track individual tumours through metastasis and treatment. Precancer lesions (adenomas) exhibited low levels of aneuploidy but high intra-tumour heterogeneity, whereas cancers had high aneuploidy but low heterogeneity, indicating that progression is through a genetic bottleneck that suppresses diversity. Individual CRC glands from the same tumour have similar karyotypes, despite prior evidence of ongoing instability at the cell level. Pseudo-stable aneuploid genomes were observed in metastatic lesions sampled from liver and other organs, after chemo- or targeted therapies, and late recurrences detected many years after the diagnosis of a primary tumour. Modelling indicates that these data are consistent with the action of stabilising selection that ‘traps’ cancer cell genomes on a fitness peak defined by the specific pattern of aneuploidy. These data show that the initial progression of CRC requires the traversal of a rugged fitness landscape and subsequent genomic evolution, including metastatic dissemination and therapeutic resistance, is constrained by stabilising selection.

Plasticity is a fundamental property of the matter, among which the self-folding or the adaptability reflect some laws inherent to the mechanical behaviour of materials, space-time geometry, biochemical processes or morphogenesis at the interface between developmental biology and physics. Contrarily to elasticity, it does not, however, limits itself to it, dressing a high predictive value of the dynamic behaviour of complex systems, what makes it a founding, and not only an emergent or purely systemic property of the matter and the evolution of living systems. Matter-form complexes from which folds are expressions are then defined as aggregates of bound couples directly acting at the anchor of irreducible dimensions or expressions by including the subject in the plasticity of the world.

Background: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined. Methods: Adcy9 -inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9 Gt/Gt and CETPtg Adcy9 WT ), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated. Results: Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P Adcy9 Gt/Gt mice compared to WT animals ( P Adcy9 Gt/Gt mice (versus WT, P Adcy9 Gt/Gt ( P Adcy9 Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P Adcy9 Gt/Gt compared to WT mice ( P P P =0.0572). Adcy9 inactivation–induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9 Gt/Gt mice ( P >0.05 versus CETPtg Adcy9 WT ). Conclusions: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

Nephrolithiasis contributes significantly to the worldwide healthcare burden. Patient-reported outcome measures (PROMs) are widely recognized as important outcome measures for patient-centered care. We sought to summarize what is currently known about PROMs in urinary stone disease and to characterize use of PROMs in randomized controlled trials (RCTs) for nephrolithiasis.Health-related quality of life (HRQOL) in patients with nephrolithiasis is reviewed. A search of both MEDLINE and EMBASE databases for RCTs in nephrolithiasis was performed to assess utilization of PROMs in these trials. All searches were for articles published between 1990 and 2014. Two independent reviewers reviewed all abstracts to determine inclusion for full-text review, with disagreements reviewed by a separate arbitrator.Validated methods for collecting PROMs include symptom diaries, pain scales, and validated HRQOL instruments. HRQOL is impacted in patients with nephrolithiasis and may be related to gender, proximity of a recent colic episode, or treatment modality. One validated instrument has been created in the nephrolithiasis population, while a treatment-specific questionnaire on ureteral stents has also been developed. PROMs are variably reported in RCTs for nephrolithiasis. Few trials utilize validated HRQOL instruments and none utilizes a disease-specific instrument.HRQOL is diminished in patients with urolithiasis, especially in times near to an acute stone event. Only one validated HRQOL instrument exists specific to nephrolithiasis. No validated instrument exists to assess the outcomes from different management options for renal and ureteral stones. Development of condition-specific PROMs instruments should aim to account for the heterogeneous and episodic nature of the disease and its treatment. Effective reporting of PROMs is lacking in the RCTs for nephrolithiasis. Future RCTs for urolithiasis standardize reporting of PROMs.

Aneuploidy, defined as the loss and gain of whole and part chromosomes, is a near-ubiquitous feature of cancer genomes, and has clinical relevance as a prognostic marker and potential therapeutic target. We have previously shown that in colorectal cancer (CRC), aneusomies largely occur upon the transition from benign adenoma to invasive carcinoma (Cross et al., 2018), however the temporal evolutionary dynamics that select for aneuploidy throughout CRC progression remain broadly uncharacterised. We performed multi-region genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that cross-sectionally represent the distinct stages of CRC progression, and longitudinally tracked 22 individual CRC tumours through metastasis and treatment. Genetic diversity measures revealed that although adenomas exhibited low levels of aneuploidy (8.5% genome altered), they harboured high intra-tumour heterogeneity (ITH), whereas cancers had significantly higher aneuploidy (27.2% genome altered) but proportionally lower ITH (p=0.0017), indicating that progression to malignancy is through a genetic bottleneck that suppresses diversity. We generated genome-wide copy number profiles from individual CRC glands, and showed that glands from the same tumour had similar karyotypes, yet displayed ongoing instability at the single cell level. Remarkably, we found that aneuploid genomes were broadly stable in metastatic lesions, even after chemo- or targeted therapies, and in recurrences detected many years after the primary diagnosis. Computational modelling of the dynamics of aneusomy accrual during CRC progression to metastasis was consistent with stabilising selection acting to ‘trap’ cancer cell genomes on a fitness peak defined by the optimal patterns of aneuploidy. These data show that although a genetic bottleneck underlies the initial progression from adenoma to CRC, further evolution of CRC is constrained largely by stabilising selection, even through metastatic dissemination and therapeutic resistance. References Cross, W., Kovac, M., Mustonen, V., Temko, D., Davis, H., Baker, A.-M., … Tomlinson, I. P. M. (2018). The evolutionary landscape of colorectal tumorigenesis. Nature Ecology & Evolution, 2(10), 1661–1672. https://doi.org/10.1038/s41559-018-0642-z Citation Format: Salpie Nowinski, William Cross, Maximilian Mossner, George Cresswell, Abhirup Banerjee, Marc Williams, Laura Gay, Ann-Marie Baker, Binxgin Lu, Christopher Kimberley, Hayley Davis, Nik Matthews, Miangela M. Lacle, Ian P.M. Tomlinson, Marnix Jansen, Alan Watson, Chris Barnes, Nicholas A. Wright, John Bridgewater, Manuel Rodriguez-Justo, Hemant Kocher, Simon J. Leedham, Andrea Sottoriva, Trevor A. Graham. Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PR06.

Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib on cardiovascular events, atherosclerosis imaging and body weight variation. The underlying mechanisms responsible for the interactions between ADCY9 and CETP have not yet been determined. Adcy9 -inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETP Gt and CETP WT ), were submitted to an atherogenic protocol (injection of an AAV8 expressing a PCSK9 gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, cell adhesion, vasorelaxation, telemetry and adipose tissue MRI were evaluated. Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P Adcy9 Gt/Gt mice compared to WT animals ( P Adcy9 inactivation did not change counts of blood monocytes and their subsets. Splenocytes showed reduced adhesion to native aortic endothelium from Adcy9 Gt/Gt mice ( P Adcy9 Gt/Gt mice (versus WT, P Adcy9 Gt/Gt versus WT ( P Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet, and this was associated with an increase in whole body adipose tissue volume ( P Adcy9 Gt/Gt compared to WT mice ( P P =0.0572) and prolonged cardiac RR interval ( P Adcy9 inactivation-induced effects on atherosclerosis, endothelium-dependent vasodilation, weight gain and feed efficiency were lost in CETP Gt mice ( P >0.05 vs CETP WT ). Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, improved endothelial function and autonomic tone.