Dementia Care Research and Psychosocial Factors.

Background: HIV-associated neurocognitive disorders (HAND) are prevalent complications of ageing with treated HIV, disproportionally affecting sub-Saharan Africa. Causal HAND treatments are lacking worldwide; therefore, reversible factors are important to explore. Sleep duration and quality are frequently associated with risk of cognitive impairments.

A common stay-on-goal mechanism in anterior cingulate cortex for information and effort choices.

Humans and non-humans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision making.

Targeting the Leloir Pathway with Galactose-Based Antimetabolites in Glioblastoma.

Background: Glioblastoma (GBM) uses Glut3 and/or Glut14 and the Leloir pathway to catabolize D-Galactose (Gal). UDP-4-deoxy-4-fluorogalactose (UDP-4DFG) is a potent inhibitor of the two key enzymes, UDP-galactose-4-epimerase (GALE) and UDP-Glucose 6-dehydrogenase (UGDH), involved in Gal metabolism and in glycan synthesis. The Gal antimetabolite 4-deoxy-4-fluorogalactose (4DFG) is a good substrate for Glut3/Glut14 and acts as a potent glioma chemotherapeutic.

Risk of repeat self-harm among individuals presenting to healthcare services: development and validation of a clinical risk assessment model (OxSET).

Background: A self-harm episode is a major risk factor for repeat self-harm. Existing tools to assess and predict repeat self-harm have major methodological limitations, and few are externally validated.

Objective: To develop and validate a risk assessment model of repeat self-harm up to 6 months after an episode of non-fatal self-harm that resulted in an emergency visit to hospital or specialised care.

The Role of Hydrogen in ReRAM.

Previous research on transistor gate oxides reveals a clear link between hydrogen content and oxide breakdown. This has implications for redox-based resistive random access memory (ReRAM) devices, which exploit soft, reversible, dielectric breakdown, as hydrogen is often not considered in modeling or measured experimentally. Here quantitative measurements, corroborated across multiple techniques are reported, that reveal ReRAM devices, whether manufactured in a university setting or research foundry, contain concentrations of hydrogen at levels likely to impact resistance switching behavior.

Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial.

Background: Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients' care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study.

The Evolving Role of Chlorthalidone and Hydrochlorothiazide as First-Line Treatments for Hypertensive Patients.

Hypertension is attributable long-term to various negative health outcomes, including atherosclerotic cardiovascular disease and, more broadly, to cardiovascular events such as congestive heart disease, myocardial infarction, heart failure, and stroke. Effective hypertension treatment is essential to lower the risk of these outcomes. Treatment of hypertension includes both nonpharmacologic and, if necessary, pharmacologic interventions.

Advances in gene therapy for high-grade glioma: a review of the clinical evidence.

Introduction: High-grade glioma (HGG) is one of the most deadly and difficult cancers to treat. Despite intense research efforts, there has not been a significant breakthrough in treatment outcomes since the early 2000's. Anti-glioma gene therapy has demonstrated promise in preclinical studies and is under investigation in numerous clinical trials.

Dopamine Release in the Nucleus Accumbens Core Encodes the General Excitatory Components of Learning.

Dopamine release in the nucleus accumbens core (NAcC) is generally considered to be a proxy for phasic firing of the ventral tegmental area dopamine (VTA) neurons. Thus, dopamine release in NAcC is hypothesized to reflect a unitary role in reward prediction error signaling. However, recent studies reveal more diverse roles of dopamine neurons, which support an emerging idea that dopamine regulates learning differently in distinct circuits.

Cognitive representations of intracranial self-stimulation of midbrain dopamine neurons depend on stimulation frequency.

Dopamine neurons in the ventral tegmental area support intracranial self-stimulation (ICSS), yet the cognitive representations underlying this phenomenon remain unclear. Here, 20-Hz stimulation of dopamine neurons, which approximates a physiologically relevant prediction error, was not sufficient to support ICSS beyond a continuously reinforced schedule and did not endow cues with a general or specific value. However, 50-Hz stimulation of dopamine neurons was sufficient to drive robust ICSS and was represented as a specific reward to motivate behavior.

Electric-field-assisted proton coupling enhanced oxygen evolution reaction.

The discovery of Mn-Ca complex in photosystem II stimulates research of manganese-based catalysts for oxygen evolution reaction (OER). However, conventional chemical strategies face challenges in regulating the four electron-proton processes of OER. Herein, we investigate alpha-manganese dioxide (α-MnO) with typical Mn-O-Mn-HO motifs as a model for adjusting proton coupling.

HEIDI: an experiment-management platform enabling high-throughput fragment and compound screening.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.

Patient and Medical Unit Staff Experiences of Proactive and Integrated Consultation-Liaison Psychiatry in The HOME Study: A Qualitative Investigation.

Background: Consultation-liaison (C-L) psychiatry services aim to help general hospital staff provide better care for their patients. Recently, many inpatient C-L psychiatry services have adopted proactive and integrated approaches to achieve this aim. Despite these developments, there have been no interview-based studies of patients' and staff members' experiences of the new approaches.

Dopamine projections to the basolateral amygdala drive the encoding of identity-specific reward memories.

To make adaptive decisions, we build an internal model of the associative relationships in an environment and use it to make predictions and inferences about specific available outcomes. Detailed, identity-specific cue-reward memories are a core feature of such cognitive maps. Here we used fiber photometry, cell-type and pathway-specific optogenetic manipulation, Pavlovian cue-reward conditioning and decision-making tests in male and female rats, to reveal that ventral tegmental area dopamine (VTA) projections to the basolateral amygdala (BLA) drive the encoding of identity-specific cue-reward memories.

Fragment-based screening targeting an open form of the SARS-CoV-2 main protease binding pocket.

To identify starting points for therapeutics targeting SARS-CoV-2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X-ray crystallographic fragment screen against its main protease. Fragment-based screening was carried out using crystals with a pronounced open conformation of the substrate-binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal-packing interfaces (two hits).

Context learning: Dividing up the camp.

A new study reveals that ventral hippocampus integrates information about where we can get rewards into a decision to seek out those rewards. This helps maximise the number of rewards received, while reducing the effort we expend to procure them.

Proactive and integrated consultation-liaison psychiatry for older medical inpatients: A mixed methods description of training, care provided and clinician experience in the HOME study.

Objectives: To describe the practical experience of delivering a proactive and integrated consultation-liaison (C-L) psychiatry service model (PICLP). PICLP is designed for older medical inpatients and is explicitly biopsychosocial and discharge-focused. In this paper we report: (a) observations on the training of 15 clinicians (seven senior C-L psychiatrists and eight assisting clinicians) to deliver PICLP; (b) the care they provided to 1359 patients; (c) their experiences of working in this new way.

Safety, Efficacy, and Ease of Insertion of Gnana Laryngeal Airway (GLA-4): A Prospective Clinical Study Utilizing the Unique Laryngeal Mask Airway With a Suction Tubing.

Introduction: Utilizing laryngeal mask airways to maintain patients' airways is advantageous because it enables the anesthesiologist to keep the patient spontaneously inhaling and is less traumatic to the airway than intubation. Newer designs such as the Gnana laryngeal mask airway design permit real-time suctioning while the mask is on a patient.

Methods: This is a prospective observational study of the efficacy of Gnana laryngeal airway 4 (GLA-4) in 50 patients undergoing colonoscopy.

Spinning magnetic field patterns that cause oncolysis by oxidative stress in glioma cells.

Raising reactive oxygen species (ROS) levels in cancer cells to cause macromolecular damage and cell death is a promising anticancer treatment strategy. Observations that electromagnetic fields (EMF) elevate intracellular ROS and cause cancer cell death, have led us to develop a new portable wearable EMF device that generates spinning oscillating magnetic fields (sOMF) to selectively kill cancer cells while sparing normal cells in vitro and to shrink GBM tumors in vivo through a novel mechanism. Here, we characterized the precise configurations and timings of sOMF stimulation that produce cytotoxicity due to a critical rise in superoxide in two types of human glioma cells.

Fast fragment and compound screening pipeline at the Swiss Light Source.

Crystallography-based fragment screening is a highly effective technique employed in structure-based drug discovery to expand the range of lead development opportunities. It allows screening and sorting of weakly binding, low molecular mass fragments, which can be developed into larger high-affinity lead compounds. Technical improvements at synchrotron beamlines, design of innovative libraries mapping chemical space efficiently, effective soaking methods and enhanced data analysis have enabled the implementation of high-throughput fragment screening pipelines at multiple synchrotron facilities.