The Authors Respond.

No funding was received for the writing of this letter. Simpson reports consulting honoraria for participation in advisory boards for Bayer, CSL Behring, HEMA Biologics, Novo Nordisk, Octapharma and Takeda, and speakers bureau for Bayer and Novo Nordisk; Yan and Desai are employees of CSL Behring; Maro is an employee of Adivo Associates.

A Real-World Analysis of Commonly Prescribed FVIII Products Based on U.S. Medical Charts: Consumption and Bleeding Outcomes in Hemophilia A Patients.

Background: Patients with hemophilia A are commonly treated with replacement recombinant factor VIII (rFVIII) products, which can be standard-acting or long-acting. Long-acting products have modifications, offering the potential for reduced dosing frequency while maintaining therapeutic benefit. Extended dosing intervals reduce patient burden and can improve quality of life and adherence.

Comparing Factor Use and Bleed Rates in U.S. Hemophilia A Patients Receiving Prophylaxis with 3 Different Long-Acting Recombinant Factor VIII Products.

Background: Recombinant factor VIII (rFVIII) products have been developed with improved pharmacokinetics, offering some patients the potential to extend dosing intervals, thereby reducing their dosing frequency while minimizing the occurrence of bleeding events. No clinical trials have been conducted to compare the bleeding rates and use of these long-acting products.

Objectives: To (a) assess real-world use of prophylaxis regimens in patients using 1 of 3 different long-acting products-rVIII-SingleChain, rFVIIIFc, or PEG-rFVIII; and (b) compare bleeding rates, dosing frequency, and factor consumption in 3 cohorts of patients.

MADD-4/Punctin and Neurexin Organize C. elegans GABAergic Postsynapses through Neuroligin.

At synapses, the presynaptic release machinery is precisely juxtaposed to the postsynaptic neurotransmitter receptors. We studied the molecular mechanisms underlying this exquisite alignment at the C. elegans inhibitory synapses.

GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation.

AMPA receptors mediate most of the fast postsynaptic response at glutamatergic synapses. The abundance of AMPA receptors in neurons and at postsynaptic membranes is tightly regulated. It has been suggested that changes in synaptic AMPA receptor levels are an important regulatory event in synaptic plasticity and learning and memory.

Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.

The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals.

Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish.

In mammals, hypocretin/orexin (HCRT) neuropeptides are important sleep-wake regulators and HCRT deficiency causes narcolepsy. In addition to fragmented wakefulness, narcoleptic mammals also display sleep fragmentation, a less understood phenotype recapitulated in the zebrafish HCRT receptor mutant (hcrtr-/-). We therefore used zebrafish to study the potential mediators of HCRT-mediated sleep consolidation.

Characterization of two melanin-concentrating hormone genes in zebrafish reveals evolutionary and physiological links with the mammalian MCH system.

Melanin-concentrating hormone (MCH) regulates feeding and complex behaviors in mammals and pigmentation in fish. The relationship between fish and mammalian MCH systems is not well understood. Here, we identify and characterize two MCH genes in zebrafish, Pmch1 and Pmch2.

Deal breaker: semaphorin and specificity in the spinal stretch reflex circuit.

Stretch reflex circuits are a prime example of wiring specificity in the vertebrate spinal cord. Homonymous sensory afferents and motoneurons typically form monosynaptic connections, while neurons innervating antagonistic or unrelated muscles do not. Pecho-Vrieseling et al.

A beta-catenin-dependent Wnt pathway mediates anteroposterior axon guidance in C. elegans motor neurons.

Background: Wnts are secreted glycoproteins that regulate diverse aspects of development, including cell proliferation, cell fate specification and differentiation. More recently, Wnts have been shown to direct axon guidance in vertebrates, flies and worms. However, little is known about the intracellular signaling pathways downstream of Wnts in axon guidance.

Novel features of boundary cap cells revealed by the analysis of newly identified molecular markers.

Neural crest (NC) cells are a multipotent, highly migratory cell population that generates most of the components of the peripheral nervous system (PNS), including the glial Schwann cells (SC) and boundary cap (BC) cells. These latter cells are located at the interface between the central nervous system and PNS, at the exit/entry points of ventral motor/dorsal sensory axons and give rise to all SC in the nerve roots and to a subset of nociceptive neurons and satellite cells in the dorsal root ganglia. In the present study we have compared BC cells with two closely related cell types, NC and Schwann cell precursors (SCpr), by RNA profiling.

Neural crest boundary cap cells constitute a source of neuronal and glial cells of the PNS.

Boundary cap (BC) cells are neural crest derivatives that form clusters at the surface of the neural tube, at entry and exit points of peripheral nerve roots. Using various knock-in alleles of the mouse gene Egr2 (also known as Krox20), the expression of which, in trunk regions, is initially restricted to BC cells, we were able to trace BC cell progeny during development and analyze their fate. Trunk BC-derived cells migrated along peripheral axons and colonized spinal nerve roots and dorsal root ganglia (DRG).

Integrity of developing spinal motor columns is regulated by neural crest derivatives at motor exit points.

Spinal motor neurons must extend their axons into the periphery through motor exit points (MEPs), but their cell bodies remain within spinal motor columns. It is not known how this partitioning is established in development. We show here that motor neuron somata are confined to the CNS by interactions with a neural crest subpopulation, boundary cap (BC) cells that prefigure the sites of spinal MEPs.