Assessing motivational interviewing integrity in the Toddler Oral Health Intervention study.

Objectives: The Toddler Oral Health Intervention (TOHI) was launched in 2017 to promote oral health prevention at well-baby clinics, with a focus on parents with children aged 6-48 months. This study aims to evaluate the integrity of motivational interviewing (MI) as one of the core intervention pillars in the TOHI study.

Methods: The TOHI study was conducted at nine well-baby clinics in the central and southern regions of the Netherlands, with 11 trained oral health coaches (OHCs) delivering a tailored individual counselling programme.

Efficacy of local infiltration analgesia on recovery after total hip arthroplasty using direct anterior approach under spinal anaesthesia: a randomized, double-blind, placebo-controlled trial.

The utilization of local infiltration analgesia (LIA) is a common practice in total hip arthroplasty (THA) procedures to mitigate postoperative pain and diminish the necessity for opioids. However, contemporary literature reports conflicting results. Our working hypothesis was that LIA renders better postoperative VAS-scores and reduces the need for oral analgetics.

Trunk training following stroke.

Background: Previous systematic reviews and randomised controlled trials have investigated the effect of post-stroke trunk training. Findings suggest that trunk training improves trunk function and activity or the execution of a task or action by an individual. But it is unclear what effect trunk training has on daily life activities, quality of life, and other outcomes.

Antibody:CD47 ratio regulates macrophage phagocytosis through competitive receptor phosphorylation.

Cancer immunotherapies often modulate macrophage effector function by introducing either targeting antibodies that activate Fcγ receptors (FcγRs) or blocking antibodies that disrupt inhibitory SIRPα-CD47 engagement. However, how these competing signals are integrated is poorly understood, raising questions about how to effectively titrate immune responses. Here, we find that macrophage phagocytic decisions are regulated by the ratio of activating ligand to inhibitory ligand over a broad range of absolute molecular densities.

Technology-supported sitting balance therapy versus usual care in the chronic stage after stroke: a pilot randomized controlled trial.

Background: Technology development for sitting balance therapy and trunk rehabilitation is scarce. Hence, intensive one-to-one therapist-patient training is still required. We have developed a novel rehabilitation prototype, specifically aimed at providing sitting balance therapy.

Individualized mechanical ventilation in a shared ventilator setting: limits, safety and technical details.

The COVID-19 pandemic has resulted in an increased need for ventilators. The potential to ventilate more than one patient with a single ventilator, a so-called split ventilator setup, provides an emergency solution. Our hypothesis is that ventilation can be individualized by adding a flow restrictor to limit tidal volumes, add PEEP, titrate FiO and monitor ventilation.

Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): autopsy reveals a ferroptosis signature.

Aims: Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID-19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID-19 lethal cardiogenic shock.

Functional characterization of the selective pan-allele anti-SIRPα antibody ADU-1805 that blocks the SIRPα-CD47 innate immune checkpoint.

Background: Accumulating preclinical data indicate that targeting the SIRPα/CD47 axis alone or in combination with existing targeted therapies or immune checkpoint inhibitors enhances tumor rejection. Although several CD47-targeting agents are currently in phase I clinical trials and demonstrate activity in combination therapy, high and frequent dosing was required and safety signals (acute anemia, thrombocytopenia) were recorded frequently as adverse events. Based on the restricted expression pattern of SIRPα we hypothesized that antibodies targeting SIRPα might avoid some of the concerns noted for CD47-targeting agents.

Single-cell activity tracking reveals that orbitofrontal neurons acquire and maintain a long-term memory to guide behavioral adaptation.

Learning to predict rewards based on environmental cues is essential for survival. The orbitofrontal cortex (OFC) contributes to such learning by conveying reward-related information to brain areas such as the ventral tegmental area (VTA). Despite this, how cue-reward memory representations form in individual OFC neurons and are modified based on new information is unknown.

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding.

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown.

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time Task in Rats.

Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats.

The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1.

Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells.

MASTL promotes cyclin B1 destruction by enforcing Cdc20-independent binding of cyclin B1 to the APC/C.

When cells enter mitosis, the anaphase-promoting complex/cyclosome (APC/C) is activated by phosphorylation and binding of Cdc20. The RXXL destruction box (D-box) of cyclin B1 only binds Cdc20 after release of the spindle checkpoint in metaphase, initiating cyclin B1 ubiquitination upon chromosome bi-orientation. However, we found that cyclin B1, through Cdk1 and Cks, is targeted to the phosphorylated APC/C(Cdc20) at the start of prometaphase, when the spindle checkpoint is still active.

Inefficient degradation of cyclin B1 re-activates the spindle checkpoint right after sister chromatid disjunction.

Sister chromatid separation creates a sudden loss of tension on kinetochores, which could, in principle, re-activate the spindle checkpoint in anaphase. This so-called "anaphase problem" is probably avoided by timely inactivation of cyclin B1-Cdk1, which may prevent the spindle tension sensing Aurora B kinase from destabilizing kinetochore-microtubule interactions as they lose tension in anaphase. However, exactly how spindle checkpoint re-activation is prevented remains unclear.

LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial.

Objective: Tight blood glucose control (TGC) in critically ill patients is difficult and labor intensive, resulting in poor efficacy of glycemic control and increased hypoglycemia rate. The LOGIC-Insulin computerized algorithm has been developed to assist nurses in titrating insulin to maintain blood glucose levels at 80-110 mg/dL (normoglycemia) and to avoid severe hypoglycemia (<40 mg/dL). The objective was to validate clinically LOGIC-Insulin relative to TGC by experienced nurses.

MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.

Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the human orthologue of Gwl called microtubule-associated serine/threonine kinase-like (MASTL).

Interaction of FOXO with beta-catenin inhibits beta-catenin/T cell factor activity.

Wingless (Wnt) signaling regulates many aspects of development and tissue homeostasis, and aberrant Wnt signaling can lead to cancer. Upon a Wnt signal beta-catenin degradation is halted and consequently the level of beta-catenin in the cytoplasm increases. This allows entry of beta-catenin into the nucleus where it can regulate gene transcription by direct binding to members of the lymphoid enhancer factor/T cell factor (TCF) family of transcription factors.