Cardiac events in newly diagnosed acute myeloid leukaemia during treatment with venetoclax + hypomethylating agents.

Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non-ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A-mutated cases less likely (p < 0.01) to be affected. Treatment-emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination.

Characterising underwater noise and changes in harbour porpoise behaviour during the decommissioning of an oil and gas platform.

Many man-made marine structures (MMS) will have to be decommissioned in the coming decades. While studies on the impacts of construction of MMS on marine mammals exist, no research has been done on the effects of their decommissioning. The complete removal of an oil and gas platform in Scotland in 2021 provided an opportunity to investigate the response of harbour porpoises to decommissioning. Arrays of broadband noise recorders and echolocation detectors were used to describe noise characteristics produced by decommissioning activities and assess porpoise behaviour. During decommissioning, sound pressure spectral density levels in the frequency range 100 Hz to 48 kHz were 30-40 dB higher than baseline, with vessel presence being the main source of noise. The study detected small-scale (< 2 km) and short-term porpoise displacement during decommissioning, with porpoise occurrence increasing immediately after this. These findings can inform the consenting process for future decommissioning projects.

Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients.

Venetoclax + hypomethylating agent (Ven-HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND-AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND-AML was to identify molecular predictors of treatment response to Ven-HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, "favorable" predictors of CR/CRi were NPM1 (86% vs. 56%), IDH2 (80% vs. 58%), and DDX41 (100% vs. 58%) and "unfavorable" TP53 (40% vs. 67%), FLT3-ITD (36% vs. 63%), and RUNX1 (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy-related qualification. CR/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow-up of 8.5 months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR/CRi (HR 3.4, 95% CI 2.5-4.8), adverse karyotype (1.6, 1.1-2.6), TP53 mutation (1.6, 1.0-2.4), and absence of IDH2 mutation (2.2, 1.0-4.7); these risk factors were subsequently applied to construct an HR-weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low (n = 130; median survival 28.9 months), intermediate (n = 105; median 9.6 months), and high (n = 66; median 3.1 months; p < .001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3-tiered, CR/CRi-based, and genetics-enhanced survival model for AML patients receiving upfront therapy with Ven-HMA.

Variation in foraging activity influences area-restricted search behaviour by bottlenose dolphins.

Area-restricted search (ARS) behaviour is commonly used to characterize spatio-temporal variation in foraging activity of predators, but evidence of the drivers underlying this behaviour in marine systems is sparse. Advances in underwater sound recording techniques and automated processing of acoustic data now provide opportunities to investigate these questions where species use different vocalizations when encountering prey. Here, we used passive acoustics to investigate drivers of ARS behaviour in a population of dolphins and determined if residency in key foraging areas increased following encounters with prey. Analyses were based on two independent proxies of foraging: echolocation buzzes (widely used as foraging proxies) and bray calls (vocalizations linked to salmon predation attempts). Echolocation buzzes were extracted from echolocation data loggers and bray calls from broadband recordings by a convolutional neural network. We found a strong positive relationship between the duration of encounters and the frequency of both foraging proxies, supporting the theory that bottlenose dolphins engage in ARS behaviour in response to higher prey encounter rates. This study provides empirical evidence for one driver of ARS behaviour and demonstrates the potential for applying passive acoustic monitoring in combination with deep learning-based techniques to investigate the behaviour of vocal animals.

Are there roles for heterogeneous ribosomes during sleep in the rodent brain?

The regulation of mRNA translation plays an essential role in neurons, contributing to important brain functions, such as brain plasticity and memory formation. Translation is conducted by ribosomes, which at their core consist of ribosomal proteins (RPs) and ribosomal RNAs. While translation can be regulated at diverse levels through global or mRNA-specific means, recent evidence suggests that ribosomes with distinct configurations are involved in the translation of different subsets of mRNAs. However, whether and how such proclaimed ribosome heterogeneity could be connected to neuronal functions remains largely unresolved. Here, we postulate that the existence of heterologous ribosomes within neurons, especially at discrete synapses, subserve brain plasticity. This hypothesis is supported by recent studies in rodents showing that heterogeneous RP expression occurs in dendrites, the compartment of neurons where synapses are made. We further propose that sleep, which is fundamental for brain plasticity and memory formation, has a particular role in the formation of heterologous ribosomes, specialised in the translation of mRNAs specific for synaptic plasticity. This aspect of our hypothesis is supported by recent studies showing increased translation and changes in RP expression during sleep after learning. Thus, certain RPs are regulated by sleep, and could support different sleep functions, in particular brain plasticity. Future experiments investigating cell-specific heterogeneity in RPs across the sleep-wake cycle and in response to different behaviour would help address this question.

Prey encounters and spatial memory influence use of foraging patches in a marine central place forager.

Given the patchiness and long-term predictability of marine resources, memory of high-quality foraging grounds is expected to provide fitness advantages for central place foragers. However, it remains challenging to characterize how marine predators integrate memory with recent prey encounters to adjust fine-scale movement and use of foraging patches. Here, we used two months of movement data from harbour seals (Phoca vitulina) to quantify the repeatability in foraging patches as a proxy for memory. We then integrated these data into analyses of fine-scale movement and underwater behaviour to test how both spatial memory and prey encounter rates influenced the seals' area-restricted search (ARS) behaviour. Specifically, we used one month's GPS data from 29 individuals to build spatial memory maps of searched areas and archived accelerometery data from a subset of five individuals to detect prey catch attempts, a proxy for prey encounters. Individuals were highly consistent in the areas they visited over two consecutive months. Hidden Markov models showed that both spatial memory and prey encounters increased the probability of seals initiating ARS. These results provide evidence that predators use memory to adjust their fine-scale movement, and this ability should be accounted for in movement models.

Extreme Exposure to Filtered Far-UVC: A Case Study†.

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1500 mJ cm-2 ; whereas, skin yellowing that appeared immediately and resolved within 24 h occurred with a 6000 mJ cm-2 exposure. No erythema was observed at any time point with exposures up to 18 000 mJ cm-2 . These results combined with Monte Carlo Radiative Transfer computer modeling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.

Revealing hydrogen peroxide as an external stressor in macrophyte-dominated coastal ecosystems.

Benthic primary producers in coastal ecosystems provide important habitat for marine organisms through the provision of complex 3D habitat. Primary producers produce organic matter, while simultaneously producing reactive oxygen species, including hydrogen peroxide (H2O2), a driver of oxidative stress. Through their high biomass, productivity and effect on local hydrodynamics, benthic primary producers can potentially increase H2O2 concentrations surrounding the biogenic structures they form. The aim of this study was to identify the potential role of H2O2 produced by benthic primary producers as an external stressor in coastal ecosystems. This was achieved by measuring H2O2 concentrations within sea lettuce blooms (Ulva sp.), giant kelp forests (Macrocystis pyrifera), and seagrass meadows (Zostera muelleri); quantifying H2O2 production rates of these species; and testing heterotrophic bacterial response to relevant H2O2 concentrations. Ulva sp. produced five times more H2O2 than other species. At in situ concentrations, H2O2 inhibited bacterial production and carbon flow through the microbial loop by 75%. This study reveals H2O2 as an additional stressor in bloom-forming Ulva sp. with higher H2O2 production compared to the ecosystem engineers M. pyrifera and Z. muelleri. H2O2 production by benthic primary producers can affect carbon flow through the microbial loop, with the potential to propagate a stress signal up the food web.

Harbour porpoise responses to pile-driving diminish over time.

Estimating impacts of offshore windfarm construction on marine mammals requires data on displacement in relation to different noise levels and sources. Using echolocation detectors and noise recorders, we investigated harbour porpoise behavioural responses to piling noise during the 10-month foundation installation of a North Sea windfarm. Current UK guidance assumes total displacement within 26 km of pile driving. By contrast, we recorded a 50% probability of response within 7.4 km (95% CI = 5.7-9.4) at the first location piled, decreasing to 1.3 km (95% CI = 0.2-2.8) by the final location; representing 28% (95% CI = 21-35) and 18% (95% CI = 13-23) displacement of individuals within 26 km. Distance proved as good a predictor of responses as audiogram-weighted received levels, presenting a more practicable variable for environmental assessments. Critically, acoustic deterrent device (ADD) use and vessel activity increased response levels. Policy and management to minimize impacts of renewables on cetaceans have concentrated on pile-driving noise. Our results highlight the need to consider trade-offs between efforts to reduce far-field behavioural disturbance and near-field injury through ADD use.

Key changes in gene expression identified for different stages of C4 evolution in Alloteropsis semialata.

C4 photosynthesis is a complex trait that boosts productivity in tropical conditions. Compared with C3 species, the C4 state seems to require numerous novelties, but species comparisons can be confounded by long divergence times. Here, we exploit the photosynthetic diversity that exists within a single species, the grass Alloteropsis semialata, to detect changes in gene expression associated with different photosynthetic phenotypes. Phylogenetically informed comparative transcriptomics show that intermediates with a weak C4 cycle are separated from the C3 phenotype by increases in the expression of 58 genes (0.22% of genes expressed in the leaves), including those encoding just three core C4 enzymes: aspartate aminotransferase, phosphoenolpyruvate carboxykinase, and phosphoenolpyruvate carboxylase. The subsequent transition to full C4 physiology was accompanied by increases in another 15 genes (0.06%), including only the core C4 enzyme pyruvate orthophosphate dikinase. These changes probably created a rudimentary C4 physiology, and isolated populations subsequently improved this emerging C4 physiology, resulting in a patchwork of expression for some C4 accessory genes. Our work shows how C4 assembly in A. semialata happened in incremental steps, each requiring few alterations over the previous step. These create short bridges across adaptive landscapes that probably facilitated the recurrent origins of C4 photosynthesis through a gradual process of evolution.

Fine scale spatial variability in the influence of environmental cycles on the occurrence of dolphins at coastal sites.

Environmental cycles often influence the presence of animals, creating patterns at different temporal scales, which may mean that their effects overlap and/or interact. Interactions between diel and seasonal cycles have been reported to influence fish behaviour but little is known about such interactions in marine top predators. Here, we studied the combined effect of seasonal, tidal and diel cycles on the occurrence of bottlenose dolphins (Tursiops truncatus) within a Marine Protected Area in Scotland. Our analyses were based on echolocation detections from passive acoustic devices (CPODs) deployed at three coastal sites between 2010 and 2016. We described patterns of dolphins' occurrence using circular statistics and then used generalised additive mixed models to explore the relative importance of each cycle and any interactions between them. We found site-specific cyclical patterns of presence that remained constant across years. There was a highly significant interaction between seasonal and diel cycles at two sites around deep channels, where occurrence was diurnal in summer but became nocturnal in autumn. The study demonstrates the highly plastic behaviour of bottlenose dolphins and shows a previously unreported behaviour that has management implications for this and other marine protected areas.

Effect of Zuccagnia punctata Cav. (Fabaceae) extract on pro-inflammatory enzymes and on planktonic cells and biofilm from Staphylococcus aureus. Toxicity studies.

Zuccagnia punctata Cav. (Fabaceae), a native plant from Argentina has been used traditionally as medicinal species. The aim of the study was to validate the antibiotic and anti-inflammatory potential of Z. punctata organic extract (ZpE) and the major compounds; 2',4'-dihydroxy-3'-methoxychalcone (DHMC), 2',4'-dihydroxychalcone (DHC), 7-hydroxyflavanone (7-HF) and 3,7-dihydroxyflavone (DHF); using an in vitro model. The antibiotic activity was determined using a broth microdilution method and the minimum inhibitory concentration (MIC) was determined. The extract and the isolation compounds affect the normal growth of all assayed Staphylococcus aureus strains. The MIC values for ZpE and isolated compounds were between 125 and 500 µg/mL and between 25 and 400 µg/mL, respectively, against all assayed strains. The inhibitory effect of extract and isolated compounds on biofilm formation and on pro-inflammatory enzymes (sPLA2, COX-2, LOX) was analyzed. The compound DHC was the most active on sPLA2 while DHF and DHMC showed the highest activity on LOX. Both the extract and pure compounds except DHMC were active against COX-2. It can be concluded that the phytocomplex and the pure compounds possessed antibiotic and anti-inflammatory activities under the conditions tested, and could be a good alternative therapy for infective and inflammatory processes.

[A communication intervention in autism spectrum disorder by means of the programme 'More than Words'. A case study]. / Intervencion en comunicacion en el trastorno del espectro autista mediante el programa 'More than Words'. Estudio de caso.

INTRODUCTION: The 'More than Words' programme aims to enable parents to take advantage of day-to-day situations as communication learning settings, through the use of instruction in responsive-type interaction strategies. AIM: To describe the effects of this programme on the communication skills of a child with autism spectrum disorder and on the language the parents use to address him. PATIENTS AND METHODS: A three-phase design (pre-intervention, intervention and post-intervention) was employed, in which the responsive interactions of the parents and the child's communicative acts were measured. RESULTS: The intervention can modify the parents' communicative style, especially when the family receives guidance from a speech therapist. Nevertheless, the responsive nature of the parents' communication tends to diminish when the intervention finishes. Conversely, the child's communicative acts increase, with a medium-sized effect of the treatment. CONCLUSIONS: The 'More than Words' programme can be a good starting point for parents to become familiar with strategies that foster communication with their children who have autism spectrum disorder.

TITLE: Intervencion en comunicacion en el trastorno del espectro autista mediante el programa 'More than Words'. Estudio de caso.Introduccion. El programa 'More than Words' pretende capacitar a los padres para aprovechar las situaciones cotidianas como entornos de aprendizaje de la comunicacion, a traves de la instruccion en estrategias de interaccion de tipo responsivo. Objetivo. Describir los efectos de este programa en las habilidades de comunicacion de un niño con trastorno del espectro autista y en el lenguaje que sus padres le dirigen. Pacientes y metodos. Se siguio un diseño de tres fases (preintervencion, intervencion y postintervencion), en el que se midieron las intervenciones responsivas de los padres y los actos comunicativos del niño. Resultados. La intervencion puede modificar el estilo comunicativo de los padres, particularmente cuando la familia recibe las orientaciones de la logopeda. Sin embargo, el caracter responsivo de la comunicacion de los padres tiende a disminuir cuando finaliza la intervencion. Por su parte, los actos comunicativos del niño se incrementan, con un tamaño medio del efecto del tratamiento. Conclusiones. El programa 'More than Words' puede ser un buen punto de partida para que los padres conozcan estrategias que promuevan la comunicacion con sus hijos con trastorno del espectro autista.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

Divided visual attention: A comparison of patients with multiple sclerosis and controls, assessed with an optokinetic nystagmus suppression task.

Multiple sclerosis (MS) frequently causes impairment of cognitive function. We compared patients with MS with controls on divided visual attention tasks. The MS patients' and controls' stare optokinetic nystagmus (OKN) was recorded in response to a 24°/s full field stimulus. Suppression of the OKN response, judged by the gain, was measured during tasks dividing visual attention between the fixation target and a second stimulus, central or peripheral, static or dynamic. All participants completed the Audio Recorded Cognitive Screen. MS patients had lower gain on the baseline stare OKN. OKN suppression in divided attention tasks was the same in MS patients as in controls but in both groups was better maintained in static than in dynamic tasks. In only dynamic tasks, older age was associated with less effective OKN suppression. MS patients had lower scores on a timed attention task and on memory. There was no significant correlation between attention or memory and eye movement parameters. Attention, a complex multifaceted construct, has different neural combinations for each task. Despite impairments on some measures of attention, MS patients completed the divided visual attention tasks normally.

Flour from Prosopis alba cotyledons: A natural source of nutrient and bioactive phytochemicals.

The Prosopis alba seed is a waste material in the process to produce pod flour. To suggest a potential use of these seeds it is necessary to determine the nutritional, phytochemical and functional quality of cotyledon flour from Prosopis alba. This flour showed high level of proteins (62%), low content of total carbohydrate and fat. Free polyphenol (1150±20mg GAE/100g flour) and carotenoids (10.55±0.05mg ß-CE/100g flour) compounds were the dominant compounds. The main identified constituents in the polyphenolic extracts were C- glycosyl flavones, including schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin. The extract enriched in polyphenolic compounds exhibited ABTS(+) reducing capacity and scavenging activity of H2O2; and was able to inhibit phospholipase, lipoxygenase and cyclooxygenase, three pro-inflammatory enzymes. According to our results, the P. alba cotyledon flour could be considered as a new alternative in the formulation of functional foods or food supplements.

Validating the use of intrinsic markers in body feathers to identify inter-individual differences in non-breeding areas of northern fulmars.

Many wildlife studies use chemical analyses to explore spatio-temporal variation in diet, migratory patterns and contaminant exposure. Intrinsic markers are particularly valuable for studying non-breeding marine predators, when direct methods of investigation are rarely feasible. However, any inferences regarding foraging ecology are dependent upon the time scale over which tissues such as feathers are formed. In this study, we validate the use of body feathers for studying non-breeding foraging patterns in a pelagic seabird, the northern fulmar. Analysis of carcasses of successfully breeding adult fulmars indicated that body feathers moulted between September and March, whereas analyses of carcasses and activity patterns suggested that wing feather and tail feather moult occurred during more restricted periods (September to October and September to January, respectively). By randomly sampling relevant body feathers, average values for individual birds were shown to be consistent. We also integrated chemical analyses of body feather with geolocation tracking data to demonstrate that analyses of δ13C and δ15N values successfully assigned 88 % of birds to one of two broad wintering regions used by breeding adult fulmars from a Scottish study colony. These data provide strong support for the use of body feathers as a tool for exploring non-breeding foraging patterns and diet in wide-ranging, pelagic seabirds.