Selective activation of BK channels in small-headed dendritic spines suppresses excitatory postsynaptic potentials

Dendritic spines are the main receptacles of excitatory information in the brain. Their particular morphology, with a small head connected to the dendrite by a slender neck, has inspired theoretical and experimental work to understand how these structural features affect the processing, storage and integration of synaptic inputs in pyramidal neurons (PNs).The activation of glutamate receptors in spines triggers a large voltage change as well as calcium signals at the spine head. Thus, voltage-gated and calcium-activated potassium channels located in the spine head likely play a key role in synaptic transmission. Here we study the presence and function of large conductance calcium-activated potassium (BK) channels in spines from layer 5 PNs. We find that BK channels are localized to dendrites and spines regardless of their size, but their activity can only be detected in spines with small head volumes (≤ 0.09 µm3), which reduces the amplitude of two-photon (2P) uncaging (u) excitatory postsynaptic potentials (EPSPs) recorded at the soma. In addition, we find that calcium signals in spines with small head volumes are significantly larger than those observed in spines with larger head volumes. In accordance with our experimental data, numerical simulations predict that synaptic inputs impinging onto spines with small head volumes generate voltage responses and calcium signals within the spine head itself that are significantly larger than those observed in spines with bigger head volumes, which are sufficient to activate spine BK channels. These results show that BK channels are selectively activated in small-headed spines, suggesting a new level of dendritic spine-mediated regulation of synaptic processing, integration, and plasticity in cortical PNs.

Congenital Zika Infection and the Risk of Neurodevelopmental, Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review

It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.

Small head movements increase and colour noise in data from five video-based P–CR eye trackers

We empirically investigate the role of small, almost imperceptible balance and breathing movements of the head on the level and colour of noise in data from five commercial video-based P-CR eye trackers. By comparing noise from recordings with completely static artificial eyes to noise from recordings where the artificial eyes are worn by humans, we show that very small head movements increase levels and colouring of the noise in data recorded from all five eye trackers in this study. This increase of noise levels is seen not only in the gaze signal, but also in the P and CR signals of the eye trackers that provide these camera image features. The P and CR signals of the SMI eye trackers correlate strongly during small head movements, but less so or not at all when the head is completely still, indicating that head movements are registered by the P and CR images in the eye camera. By recording with artificial eyes, we can also show that the pupil size artefact has no major role in increasing and colouring noise. Our findings add to and replicate the observation by Niehorster et al., (2021) that lowpass filters in video-based P–CR eye trackers colour the data. Irrespective of source, filters or head movements, coloured noise can be confused for oculomotor drift. We also find that usage of the default head restriction in the EyeLink 1000+, the EyeLink II and the HiSpeed240 result in noisier data compared to less head restriction. Researchers investigating data quality in eye trackers should consider not using the Gen 2 artificial eye from SR Research / EyeLink. Data recorded with this artificial eye are much noisier than data recorded with other artificial eyes, on average 2.2–14.5 times worse for the five eye trackers.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials

ABSTRACTBackgroundMeta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design.ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes.MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I2 and Tau2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials and types of comparisons.ResultsSQ-LNS provision decreased stunting (length-for-age z-score < −2) by 12% (relative reduction), wasting (weight-for-length (WLZ) z-score < −2) by 14%, low mid-upper arm circumference (MUAC < 125 mm or MUACZ < −2) by 18%, acute malnutrition (WLZ < −2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z-score < −2) by 13%, and small head size (head-circumference z-score < −2) by 9%. Effects of SQ-LNS on growth outcomes generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. Effects of SQ-LNS on stunting, wasting, low MUAC and small head size were greater among girls than among boys; effects on stunting, underweight and low MUAC were greater among later-born (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses.ConclusionsThe positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Small-head metal on metal total hip arthroplasty is associated with a high rate of complication and reoperation at mid-term follow-up

Background: Adverse reactions to metal debris are significant complications after metal-on-metal total hip arthroplasty. Recently, late appearances of adverse reactions to metal debris and subsequent need for reoperations have been reported with small-diameter head metal-on-metal devices. We retrospectively investigated mid-term clinical outcomes of small-head metal-on-metal total hip arthroplasty. Methods: We reviewed 159 hips in 139 patients who had a small-head metal-on-metal total hip arthroplasty (M2a Taper; Biomet, Warsaw, IN) with a minimum 5-year follow-up and documented postoperative complications. Results: Focal osteolysis in either the femur or acetabulum was observed in 12 hips (7.5%, 44 months after surgery on average), with pseudotumor observed in 8 hips (5%, 120 months after surgery on average). Four hips (2.5%) had dislocations (84 months after surgery on average) and six hips (3.8%, 122 months after surgery on average) underwent reoperation. Conclusion: Small-head metal-on-metal total hip arthroplasty is associated with a high degree of complications at mid-term follow-up period. Considering this, we discourage the use of metal-on-metal total hip arthroplasty regardless of head size.