The influence of event similarity on the detailed recall of autobiographical memories.

Memories for life events are thought to be organised based on their relationships with one another, affecting the order in which events are recalled such that similar events tend to be recalled together. However, less is known about how detailed recall for a given event is affected by its associations to other events. Here, we used a cued autobiographical memory recall task where participants verbally recalled events corresponding to personal photographs. Importantly, we characterised the temporal, spatial, and semantic associations between each event to assess how similarity between adjacently cued events affected detailed recall. We found that participants provided more non-episodic details for cued events when the preceding event was both semantically similar and either temporally or spatially dissimilar. However, similarity along time, space, or semantics between adjacent events did not affect the episodic details recalled. We interpret this by considering organisation at the level of a life narrative, rather than individual events. When recalling a stream of personal events, we may feel obligated to justify seeming discrepancies between adjacent events that are semantically similar, yet simultaneously temporally or spatially dissimilar - to do so, we provide additional supplementary detail to help maintain global coherence across the events in our lives.

Caregivers with limited English proficiency: Satisfaction with primary pediatric healthcare.

With a growing 25.5 million people in the United States experiencing limited-English proficiency (LEP), there is a concern over these individuals' experiences in healthcare. Health outcomes of LEP status are well-documented for adults in hospitals; however, less is known about patient experience, pediatric populations, and primary care settings. This study investigated differences in caregiver satisfaction between families with and without LEP receiving healthcare for their child. A sample of 25,118 caregivers whose children from birth to 17 years had met with any healthcare providers in the past year was used. Analyses consisted of unpaired t-tests comparing mean satisfaction of LEP and English-proficient (EP) caregivers in the domains of how often primary healthcare providers spent enough time with the child, listened, provided specific information, demonstrated sensitivity to the family's values, and made the respondent feel like a partner. In all aspects of caregiver satisfaction, mean satisfaction scores were significantly lower for LEP caregivers than EP caregivers. The largest drops were seen in perceived time and sensitivity. These results highlight a need to ensure LEP families receive equitable and high-quality primary care services, ultimately building trust in the healthcare system and improving children's health and well-being.

A comprehensive investigation of the interactions of human serum albumin with polymeric and hybrid nanoparticles.

Nanoparticles (NPs) engineered as drug delivery systems continue to make breakthroughs as they offer numerous advantages over free therapeutics. However, the poor understanding of the interplay between the NPs and biomolecules, especially blood proteins, obstructs NP translation to clinics. Nano-bio interactions determine the NPs' in vivo fate, efficacy and immunotoxicity, potentially altering protein function. To fulfill the growing need to investigate nano-bio interactions, this study provides a systematic understanding of two key aspects: (i) protein corona (PC) formation and (ii) NP-induced modifications on protein's structure and stability. A methodology was developed by combining orthogonal techniques to analyze both quantitative and qualitative aspects of nano-bio interactions, using human serum albumin (HSA) as a model protein. Protein quantification via liquid chromatography-mass spectrometry, and capillary zone electrophoresis (CZE) clarified adsorbed protein quantity and stability. CZE further unveiled qualitative insights into HSA forms (native, glycated HSA and cysteinylated), while synchrotron radiation circular dichroism enabled analyzing HSA's secondary structure and thermal stability. Comparative investigations of NP cores (organic vs. hybrid), and shells (with or without polyethylene glycol (PEG)) revealed pivotal factors influencing nano-bio interactions. Polymeric NPs based on poly(lactic-co-glycolic acid) (PLGA) and hybrid NPs based on metal-organic frameworks (nanoMOFs) presented distinct HSA adsorption profiles. PLGA NPs had protein-repelling properties while inducing structural modifications on HSA. In contrast, HSA exhibited a high affinity for nanoMOFs forming a PC altering thereby the protein structure. A shielding effect was gained through PEGylation for both types of NPs, avoiding the PC formation as well as the alteration of unbound HSA structure.

Congenital tremor and myopathy secondary to novel MYBPC1 variant.

Congenital myopathy with tremor (MYOTREM) is a recently described disorder characterized by mild myopathy and a postural and intention tremor present since early infancy. MYOTREM is associated with pathogenic variants in MYBPC1 which encodes slow myosin-binding protein C, a sarcomere protein with regulatory and structural roles. Here, we describe a family with three generations of variably affected members exhibiting a novel variant in MYBPC1 (c.656 T > C, p.Leu219Pro). Among the unique features of affected family members is the persistence of tremor in sleep. We also present the first muscle magnetic resonance images for this disorder, and report muscle atrophy and fatty infiltration.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy.

BACKGROUND AND OBJECTIVES: Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE. METHODS: This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders. RESULTS: Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, p = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, p = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p > 0.1). DISCUSSION: Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes.

Nicotinic receptor activation augments muscarinic receptor-mediated eccrine sweating but not cutaneous vasodilatation in young males.

NEW FINDINGS: What is the central question of this study? Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors. Although each receptor can independently induce cutaneous vasodilatation and eccrine sweating, it remains to be elucidated whether the two receptors interact in order to mediate these responses. What is the main finding and its importance? We show that although nicotinic receptor activation does not modulate muscarinic cutaneous vasodilatation, it lowers the muscarinic receptor agonist threshold at which onset for eccrine sweating (augmentation of muscarinic eccrine sweating) occurs in young men in normothermic resting conditions. These results provide new insights into the physiological significance of nicotinic receptors in the regulation of cutaneous perfusion and eccrine sweating. Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors; each is known independently to induce cutaneous vasodilatation and eccrine sweating in humans. However, it is not known whether the two receptors interact in order to mediate cutaneous vasodilatation and eccrine sweating. In 10 young men (27 ± 6 years old), cutaneous vascular conductance and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with either lactated Ringer's solution (control) or three different concentrations of nicotine (0.1, 1 and 10 mm), a nicotinic receptor agonist. Co-administration of methacholine, a muscarinic receptor agonist, was performed at all skin sites in a dose-proportional fashion (0.0125, 0.25, 5, 100 and 2000 mm, each for 25 min). Administration of nicotine alone caused dose-dependent transient increases in cutaneous vascular conductance and sweat rate (all P ≤ 0.05), which thereafter returned to pre-nicotine levels, except that a portion of transient responses remained with continuous administration of 10 mm nicotine (both P ≤ 0.05). Cutaneous vascular conductance was increased by administration of ≥0.25 mm methacholine at the control site, and this response was likewise observed in the presence of co-administration of all doses of nicotine used (all P ≤ 0.05). Sweat rate at the control site was increased by administration of ≥0.25 mm methacholine, but the lowest dose of methacholine (0.0125 mm) was able to increase sweat rate in the presence of 10 mm nicotine (P ≤ 0.05). We conclude that nicotinic receptor activation lowers the muscarinic receptor agonist threshold for eccrine sweating (augmentation of muscarinic sweating) but does not affect muscarinic cutaneous vasodilatation in young men in normothermic resting conditions.

K+ channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of KCa, KATP, and KV channels?

Acetylcholine released from cholinergic nerves is involved in heat loss responses of cutaneous vasodilation and sweating. K(+) channels are thought to play a role in regulating cholinergic cutaneous vasodilation and sweating, though which K(+) channels are involved in their regulation remains unclear. We evaluated the hypotheses that 1) Ca(2+)-activated K(+) (KCa), ATP-sensitive K(+) (KATP), and voltage-gated K(+) (KV) channels all contribute to cholinergic cutaneous vasodilation; and 2) KV channels, but not KCa and KATP channels, contribute to cholinergic sweating. In 13 young adults (24 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with: 1) lactated Ringer (Control), 2) 50 mM tetraethylammonium (KCa channel blocker), 3) 5 mM glybenclamide (KATP channel blocker), and 4) 10 mM 4-aminopyridine (KV channel blocker). At all sites, cholinergic cutaneous vasodilation and sweating were induced by coadministration of methacholine (0.0125, 0.25, 5, 100, and 2,000 mM, each for 25 min). The methacholine-induced increase in CVC was lower with the KCa channel blocker relative to Control at 0.0125 (1 ± 1 vs. 9 ± 6%max) and 5 (2 ± 5 vs. 17 ± 14%max) mM methacholine, whereas it was lower in the presence of KATP (69 ± 7%max) and KV (57 ± 14%max) channel blocker compared with Control (79 ± 6%max) at 100 mM methacholine. Furthermore, methacholine-induced sweating was lower at the KV channel blocker site (0.42 ± 0.17 mg·min(-1)·cm(-2)) compared with Control (0.58 ± 0.15 mg·min(-1)·cm(-2)) at 2,000 mM methacholine. In conclusion, we show that KCa, KATP, and KV channels play a role in cholinergic cutaneous vasodilation, whereas only KV channels contribute to cholinergic sweating in normothermic resting humans.