Anatomical factors causing oedema of the lower limb during pregnancy

Background: The objective of this study was to investigate the morphology of the common iliac artery and vein (CIA&V) comparing right and left sides in females versus males. Pregnant women favour lying on one side at rest and during sleep. The reason for this may be due to the morphology and orientation between the CIA&V. Virtually all women during their pregnancy suffer from lower limb swelling. This study provides an anatomical explanation forthe propensity to lie consistently on one side, for lower limb swelling, and offers prevention measures.Materials and methods: A literature search was conducted on anatomical texts, atlases, journals, and websites regarding the morphology and orientation of the right and left CIA&V, lower limb oedema, and sleeping positions during pregnancy. Measurements from 15 dissected cadavers were conductedon the right and left CIA&V.Results: The literature search revealed very limited studies on the morphology and orientation of the right and left CIA&V with no studies relating this orientation to lower limb oedema or sleeping positions during pregnancy. Cadaver dissection revealed a relatively direct anterior to posterior orientation left CIA&Vand an oblique lateral to medial right CIA&V.Conclusions: This study suggests an explanation of why women lie on their left side when resting and sleeping during the third trimester due to the clinically relevant anatomy between the CIA&V

NGS-Based Diagnosis of Treatable Neurogenetic Disorders in Adults: Opportunities and Challenges.

The identification of neurological disorders by next-generation sequencing (NGS)-based gene panels has helped clinicians understand the underlying physiopathology, resulting in personalized treatment for some rare diseases. While the phenotype of distinct neurogenetic disorders is generally well-known in childhood, in adulthood, the phenotype can be unspecific and make the standard diagnostic approach more complex. Here we present three unrelated adults with various neurological manifestations who were successfully diagnosed using NGS, allowing for the initiation of potentially life-changing treatments. A 63-year-old woman with progressive cognitive decline, pyramidal signs, and bilateral cataract was treated by chenodeoxycholic acid following the diagnosis of cerebrotendinous xanthomatosis due to a homozygous variant in CYP27A1. A 32-year-old man with adult-onset spastic paraplegia, in whom a variant in ABCD1 confirmed an X-linked adrenoleukodystrophy, was treated with corticoids for adrenal insufficiency. The third patient, a 28-year-old woman with early-onset developmental delay, epilepsy, and movement disorders was treated with a ketogenic diet following the identification of a variant in SLC2A1, confirming a glucose transporter type 1 deficiency syndrome. This case study illustrates the challenges in the timely diagnosis of medically actionable neurogenetic conditions, but also the considerable potential for improving patient health through modern sequencing technologies

Multicolour correlative imaging using phosphor probes

Correlative light and electron microscopy exploits the advantages of optical methods, such as multicolour probes and their use in hydrated live biological samples, to locate functional units, which are then correlated with structural details that can be revealed by the superior resolution of electron microscopes. One difficulty is locating the area imaged by the electron beam in the much larger optical field of view. Multifunctional probes that can be imaged in both modalities and thus register the two images are required. Phosphor materials give cathodoluminescence (CL) optical emissions under electron excitation. Lanthanum phosphate containing thulium or terbium or europium emits narrow bands in the blue, green and red regions of the CL spectrum; they may be synthesised with very uniform-sized crystals in the 10- to 50-nm range. Such crystals can be imaged by CL in the electron microscope, at resolutions limited by the particle size, and with colour discrimination to identify different probes. These materials also give emissions in the optical microscope, by multiphoton excitation. They have been deposited on the surface of glioblastoma cells and imaged by CL. Gadolinium oxysulphide doped with terbium emits green photons by either ultraviolet or electron excitation. Sixty-nanometre crystals of this phosphor have been imaged in the atmospheric scanning electron microscope (JEOL ClairScope). This probe and microscope combination allow correlative imaging in hydrated samples. Phosphor probes should prove to be very useful in correlative light and electron microscopy, as fiducial markers to assist in image registration, and in high/super resolution imaging studies

The use of visual methods to explore how children construct and assign meaning to the ''self'' within two urban communities in the Western Cape, South Africa

This study aimed to explore how children construct and assign meaning to the ''self'' within two urban communities of Cape Town in South Africa. Using a child participation methodological framework data were collected using Photovoice and community maps with 54 participants between the ages of 9 and 12. Feelings of safety, social connectedness, and children's spaces were found to be central to the ways in which the participants constructed and assigned meaning to the ''self.'' The study provides implications for intervention programmes aimed at improving children's well-being to be inclusive of activities aimed at improving children's self-concept, including the construction of safe spaces for children to play, learn, and form meaningful relationships

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

Profilin 1 is required for peripheral nervous system myelination

Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actinbinding protein involved in microfilament polymerization. Pfn1 is inhibited upon phosphorylation by ROCK, a downstream effector of the integrin linked kinase pathway. Thus, a dramatic reduction of radial lamellipodia formation is observed in SCs lacking integrinlinked kinase or treated with the Rho/ROCK activator lysophosphatidic acid. Knocking down Pfn1 expression by lentiviralmediated shRNA delivery impairs SC lamellipodia formation in vitro, suggesting a direct role for this protein in PNS myelination. Indeed,SC-specific gene ablation of Pfn1 in mice led to profound radial sorting and myelination defects, confirming a central role for this protein in PNS development. Our data identify Pfn1 as a key effector of the integrin linked kinase/Rho/ROCK pathway. This pathway, acting in parallel with integrin β1/LCK/Rac1 and their effectors critically regulates SC lamellipodia formation, radial sorting and myelination during peripheral nervous system maturation

Electrophysiological Properties of Embryonic Stem Cell-Derived Neurons

In vitro generation of functional neurons from embryonic stem (ES) cells and induced pluripotent stem cells offers exciting opportunities for dissecting gene function, disease modelling, and therapeutic drug screening. To realize the potential of stem cells in these biomedical applications, a complete understanding of the cell models of interest is required. While rapid advances have been made in developing the technologies for directed induction of defined neuronal subtypes, most published works focus on the molecular characterization of the derived neural cultures. To characterize the functional properties of these neural cultures, we utilized an ES cell model that gave rise to neurons expressing the green fluorescent protein (GFP) and conducted targeted whole-cell electrophysiological recordings from ES cell-derived neurons. Current-clamp recordings revealed that most neurons could fire single overshooting action potentials; in some cases multiple action potentials could be evoked by depolarization, or occurred spontaneously. Voltage-clamp recordings revealed that neurons exhibited neuronal-like currents, including an outward current typical of a delayed rectifier potassium conductance and a fast-activating, fast-inactivating inward current, typical of a sodium conductance. Taken together, these results indicate that ES cell-derived GFP+ neurons in culture display functional neuronal properties even at early stages of differentiation

International consensus statement on allergy and rhinology: Allergic rhinitis – 2023

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment

Children’s discursive constructions of the ‘self’

The ways in which children construct and assign meaning to the ‘self’ could have an impact on their social and emotional well-being, including their coping skills, relationship formation, and behaviour. Furthermore, a child’s understanding of the ‘self’ could influence the way in which they make meaning out of their experiences and internalize these experiences as a means of understanding one’s abilities and self-worth. Conditions of poverty and oppression could negatively impact the development of the self-concept and a child’s overall well-being. Such conditions exist in South Africa, where the aftermath of apartheid’s system of structural racism continues in the form of social inequity, poverty, and violence. This study utilized a child participation framework to explore children’s discursive constructions of and meanings assigned to the ‘self’ within two urban communities of the Western Cape, South Africa. Eight focus group discussions were conducted amongst fifty-four children between the ages of nine to twelve. Thematic and discourse analysis were used to analyse the findings. The themes of childhood, social connectedness, and children’s spaces were identified as key influences on a child’s self-concept. Four underlying discourses emerged within the themes as central to the participant’s self-constructions. These included; (1) ‘forfeited childhood,’ (2) ‘vulnerability and helplessness,’ (3) ‘preserving the integrity of the self,’ and (4) opportunitiwes for escape.