Developing Photoactive Coumarin-Caged -Hydroxysulfonamides for Generation of Nitroxyl (HNO).

Photoactive -hydroxysulfonamides photocaged with the (6-bromo-7-hydroxycoumarin-4-yl)methyl chromophore have been successfully synthesized, and the mechanisms of photodecomposition investigated for two of the compounds. Upon irradiation up to 97% of a diagnostic marker for (H)NO release, sulfinate was observed for the trifluoromethanesulfonamide system. In the absence of a species that reacts rapidly with (H)NO, (H)NO instead reacts with the carbocation intermediate to ultimately generate ()-BHC-oxime and ()-BHC-oxime.

Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial.

Background And Aims: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure?

Methods: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100 µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death.

Results: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .

How can I find what I want? Can children, chimpanzees and capuchin monkeys form abstract representations to guide their behavior in a sampling task?

concepts are a powerful tool for making wide-ranging predictions in new situations based on little experience. Whereas looking-time studies suggest an early emergence of this ability in human infancy, other paradigms like the relational match to sample task often fail to detect abstract concepts until late preschool years. Similarly, non-human animals show difficulties and often succeed only after long training regimes.

The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction.

Background: In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial.

Method And Results: IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men).

Evaluation and treatment approaches for neurological post-acute sequelae of COVID-19: A consensus statement and scoping review from the global COVID-19 neuro research coalition.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

Objectives: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM).

Do they know or just do it? Investigating implicit and explicit sequence learning by capuchin monkeys, human adults and children.

In humans, it is now established that sequential regularities can be learned implicitly (i.e. without acquiring conscious knowledge) or explicitly (with acquisition of conscious knowledge).

Clinical and Diagnostic Findings of Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy in the COVID-19 Era.

Background: Growing evidence suggests an association between the infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and eye disorders. The aim of this review was to analyze the clinical presentation and diagnostic features of acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM) associated with COVID-19 infection. The features are then compared with previous reports regarding these retinal disorders, to recognize possible specific characteristics and to assess the role of multimodal ophthalmic imaging.

Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics.

Background And Aims: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide.

Methods And Results: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h).

The shifting shelf task: a new, non-verbal measure for attentional set shifting.

Attentional set shifting is a core ingredient of cognition, allowing for fast adaptation to changes in the environment. How this skill compares between humans and other primates is not well known. We examined performance of 3- to 5-year-old children and chimpanzees on a new attentional set shifting task.

Evidence for abstract representations in children but not capuchin monkeys.

The use of abstract higher-level knowledge (also called overhypotheses) allows humans to learn quickly from sparse data and make predictions in new situations. Previous research has suggested that humans may be the only species capable of abstract knowledge formation, but this remains controversial. There is also mixed evidence for when this ability emerges over human development.

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial.

Background: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure.

Methods: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK.

Do capuchin monkeys () use exploration to form intuitions about physical properties?

Humans' flexible innovation relies on our capacity to accurately predict objects' behaviour. These predictions may originate from a "physics-engine" in the brain which simulates our environment. To explore the evolutionary origins of intuitive physics, we investigate whether capuchin monkeys' object exploration supports learning.

Exploring the development of attentional set shifting in young children with a novel Intradimensional/Extradimensional shift task.

Attentional set shifting is a core part of cognition, allowing quick and flexible adaption to new demands. The study of its development during early childhood has been hampered by a shortage of measures not requiring language. This article argues for a revival of the Intradimensional/Extradimensional (ID/ED) shift task by presenting a new nonverbal version of the task (Shifting Tray task).

The structure of executive functions in preschool children and chimpanzees.

Executive functions (EF) are a core aspect of cognition. Research with adult humans has produced evidence for unity and diversity in the structure of EF. Studies with preschoolers favour a 1-factor model, in which variation in EF tasks is best explained by a single underlying trait on which all EF tasks load.

Inhibitory control and cue relevance modulate chimpanzees' (Pan troglodytes) performance in a spatial foraging task.

Inhibition tasks usually require subjects to exert control to act correctly when a competing action plan is prepotent. In comparative psychology, one concern about the existing inhibition tasks is that the relative contribution of inhibitory control to performance (as compared to learning or object knowledge) is rarely explicitly investigated. We addressed this problem by presenting chimpanzees with a spatial foraging task in which they could acquire food more efficiently by learning which objects were baited.

Exploring the Potential of 2-(2-Nitrophenyl)ethyl-Caged -Hydroxysulfonamides for the Photoactivated Release of Nitroxyl (HNO).

The emergence of nitroxyl (HNO) as a biological signaling molecule is attracting increasing attention. HNO-based prodrugs show considerable potential in treating congestive heart failure, with HNO reacting rapidly with metal centers and protein-bound and free thiols. A new class of 2-(2-nitrophenyl)ethyl (2-NPE)-photocaged -hydroxysulfonamides has been developed, and the mechanisms of photodecomposition have been investigated.

Thinking inside the box: Mental manipulation of working memory contents in 3- to 7-year-old children.

We developed a non-verbal task assessing updating and manipulation of working memory contents. 80 3- to 7-year-olds (47 girls; predominantly European White) were tested with a 4 × 4 grid containing 8 boxes (in the 4 centre cells and 4 outer corners). A sticker was hidden and children searched for it after a delay phase.

What happened? Do preschool children and capuchin monkeys spontaneously use visual traces to locate a reward?

The ability to infer unseen causes from evidence is argued to emerge early in development and to be uniquely human. We explored whether preschoolers and capuchin monkeys could locate a reward based on the physical traces left following a hidden event. Preschoolers and capuchin monkeys were presented with two cups covered with foil.

Mechanistic Insights into Rapid Generation of Nitroxyl from a Photocaged -Hydroxysulfonamide Incorporating the (6-Hydroxynaphthalen-2-yl)methyl Chromophore.

HNO is a highly reactive molecule that shows promise in treating heart failure. Molecules that rapidly release HNO with precise spatial and temporal control are needed to investigate the biology of this signaling molecule. (Hydroxynaphthalen-2-yl)methyl-photocaged -hydroxysulfonamides are a new class of photoactive HNO generators.

The primary prevention implantable cardioverter-defibrillator (ICD) during the COVID-19 pandemic.

During the recent 'first wave' of the COVID-19 pandemic, the National Health Service (NHS) has triaged planned services to create surge capacity. The primary prevention implantable cardioverter-defibrillator (ICD) was in a grey area of triage guidance, but it was suggested as a procedure that could be reasonably stopped. Recent reports have highlighted deaths of patients awaiting ICDs who may have been deferred during the pandemic.

Understanding Human Cognitive Uniqueness.

Humanity has regarded itself as intellectually superior to other species for millennia, yet human cognitive uniqueness remains poorly understood. Here, we evaluate candidate traits plausibly underlying our distinctive cognition (including mental time travel, tool use, problem solving, social cognition, and communication) as well as domain generality, and we consider how human cognitive uniqueness may have evolved. We conclude that there are no traits present in humans and absent in other animals that in isolation explain our species' superior cognitive performance; rather, there are many cognitive domains in which humans possess unusually potent capabilities compared to those found in other species.

Inferring Unseen Causes: Developmental and Evolutionary Origins.

Human adults can infer unseen causes because they represent the events around them in terms of their underlying causal mechanisms. It has been argued that young preschoolers can also make causal inferences from an early age, but whether or not non-human apes can go beyond associative learning when exploiting causality is controversial. However, much of the developmental research to date has focused on fully-perceivable causal relations or highlighted the existence of a causal relationship verbally and these were found to scaffold young children's abilities.

Lessons of the month: Nitrous oxide-induced functional vitamin B deficiency causing subacute combined degeneration of the spinal cord.

We discuss the case of a 22-year-old man who presented with paraesthesia, reduced sensation and weakness in his limbs. Examination was in keeping with a myeloneuropathy. Initial investigations including vitamin B were unremarkable but magnetic resonance imaging of the spinal cord showed subacute combined degeneration.