Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model.

Mutations in DNAJB6 are a well-established cause of limb girdle muscular dystrophy type D1 (LGMD D1). Patients with LGMD D1 develop progressive muscle weakness with histology showing fibre damage, autophagic vacuoles, and aggregates. Whilst there are many reports of LGMD D1 patients, the role of DNAJB6 in the muscle is still unclear. In this study, we developed a loss of function zebrafish model in order to investigate the role of Dnajb6. Using a double dnajb6a and dnajb6b mutant model, we show that loss of Dnajb6 leads to a late onset muscle weakness. Interestingly, we find that adult fish lacking Dnajb6 do not have autophagy or myofibril defects, however, they do show mitochondrial changes and damage. This study demonstrates that loss of Dnajb6 causes mitochondrial defects and suggests that this contributes to muscle weakness in LGMD D1. These findings expand our knowledge of the role of Dnajb6 in the muscle and provides a model to screen novel therapies for LGMD D1.

Spike ripples localize the epileptogenic zone best: an international intracranial study.

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Evaluation of Upper Extremity Reachable Workspace in Children With Brachial Plexus Birth Injury.

PURPOSE: Brachial plexus birth injury (BPBI) results in upper extremity (UE) movement limitations. Current assessments of UE function used to inform clinical decision-making only evaluate a limited set of static postures and/or movements and have been criticized for being insensitive to certain meaningful differences in function. Reachable workspace provides a numeric and visual assessment of global UE movement ability by quantifying the regions in space that patients can reach with their hands, and it can be collected using real-time feedback to elicit a best-effort acquisition of function. This study evaluated the ability of a real-time feedback reachable workspace tool to assess UE movement in BPBI. METHODS: Twenty-two children with BPBI participated. Reachable workspace data were collected with three-dimensional motion capture using real-time visual feedback to measure UE reaching ability in all regions surrounding the body. All outer, far-from-body points reached by the hand were recorded and analyzed by region. A two-way, within-subjects analysis of variance was used to assess interlimb differences in percentage workspace reached and median reach distance for each of the six regions. RESULTS: The affected limb had significantly less percentage workspace reached than the unaffected limb for all six regions (mean interlimb differences by region, 5.7%-38.6%). The affected limb had significantly less median reach distance than the unaffected limb for all six regions (mean interlimb differences by region, 3.1%-36.8%). CONCLUSIONS: The workspace approach was capable of detecting UE movement impairments of the BPBI-affected limb. The reported deficits in workspace on the affected limb correspond to common movement impairments in BPBI, such as limitations in shoulder elevation, external rotation, extension, and elbow extension. CLINICAL RELEVANCE: The real-time feedback reachable workspace tool is sufficiently robust for assessing UE movement impairments in children with BPBI.

Biophysical Principles and Computational Modeling of Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) has revolutionized the treatment of neurological disorders, yet the mechanisms of DBS are still under investigation. Computational models are important in silico tools for elucidating these underlying principles and potentially for personalizing DBS therapy to individual patients. The basic principles underlying neurostimulation computational models, however, are not well known in the clinical neuromodulation community. OBJECTIVE: In this study, we present a tutorial on the derivation of computational models of DBS and outline the biophysical contributions of electrodes, stimulation parameters, and tissue substrates to the effects of DBS. RESULTS: Given that many aspects of DBS are difficult to characterize experimentally, computational models have played an important role in understanding how material, size, shape, and contact segmentation influence device biocompatibility, energy efficiency, the spatial spread of the electric field, and the specificity of neural activation. Neural activation is dictated by stimulation parameters including frequency, current vs voltage control, amplitude, pulse width, polarity configurations, and waveform. These parameters also affect the potential for tissue damage, energy efficiency, the spatial spread of the electric field, and the specificity of neural activation. Activation of the neural substrate also is influenced by the encapsulation layer surrounding the electrode, the conductivity of the surrounding tissue, and the size and orientation of white matter fibers. These properties modulate the effects of the electric field and determine the ultimate therapeutic response. CONCLUSION: This article describes biophysical principles that are useful for understanding the mechanisms of neurostimulation.

Expression of the Z Variant of α1-Antitrypsin Suppresses Hepatic Cholesterol Biosynthesis in Transgenic Zebrafish.

Individuals homozygous for the Pi*Z allele of SERPINA1 (ZAAT) are susceptible to lung disease due to insufficient α1-antitrypsin secretion into the circulation and may develop liver disease due to compromised protein folding that leads to inclusion body formation in the endoplasmic reticulum (ER) of hepatocytes. Transgenic zebrafish expressing human ZAAT show no signs of hepatic accumulation despite displaying serum insufficiency, suggesting the defect in ZAAT secretion occurs independently of its tendency to form inclusion bodies. In this study, proteomic, transcriptomic, and biochemical analysis provided evidence of suppressed Srebp2-mediated cholesterol biosynthesis in the liver of ZAAT-expressing zebrafish. To investigate the basis for this perturbation, CRISPR/Cas9 gene editing was used to manipulate ER protein quality control factors. Mutation of erlec1 resulted in a further suppression in the cholesterol biosynthesis pathway, confirming a role for this ER lectin in targeting misfolded ZAAT for ER-associated degradation (ERAD). Mutation of the two ER mannosidase homologs enhanced ZAAT secretion without inducing hepatic accumulation. These insights into hepatic ZAAT processing suggest potential therapeutic targets to improve secretion and alleviate serum insufficiency in this form of the α1-antitrypsin disease.

A Competitive Hemagglutination Inhibition Assay for Dissecting Functional Antibody Activity against Influenza Virus.

Influenza remains one of the most contagious infectious diseases. Approximately, 25 to 50 million people suffer from influenza-like illness in the United States annually, leading to almost 1 million hospitalizations. Globally, the World Health Organization (WHO) estimates 250,000 to 500,000 mortalities associated with secondary respiratory complications due to influenza virus infection every year. Currently, seasonal vaccination represents the best countermeasure to prevent influenza virus spread and transmission in the general population. However, presently licensed influenza vaccines are about 60% effective on average, and their effectiveness varies from season to season and among age groups, as well as between different influenza subtypes within a single season. The hemagglutination inhibition (HAI) assay represents the gold standard method for measuring the functional antibody response elicited following standard-of-care vaccination, along with evaluating the efficacy of under-development influenza vaccines in both animal models and clinical trial settings. However, using the classical HAI approach, it is not possible to dissect the complexities of variable epitope recognition within a polyclonal antibody response. In this paper, we describe a straightforward competitive HAI-based method using a combination of influenza virus and recombinant hemagglutinin (HA) proteins to dissect the HAI functional activity of HA-specific antibody populations in a single assay format. IMPORTANCE The hemagglutination inhibition (HAI) assay is a well-established and reproducible method that quantifies functional antibody activity against influenza viruses and, in particular, the capability of an antibody formulation to inhibit the binding of hemagglutinin (HA) to sialic acid. However, the HAI assay does not provide full insights on the breadth and epitope recognition of the antibody formulation, especially in the context of polyclonal sera, where multiple antibody specificities contribute to the overall observed functional activity. In this report we introduce the use of Y98F point-mutated recombinant HA (HAΔSA) proteins, which lack sialic acid binding activity, in the context of the HAI assay as a means to absorb out certain HA-directed (i.e., strain-specific or cross-reactive) antibody populations. This modification to the classical HAI assay, referred to as the competitive HAI assay, represents a new tool to dissect the magnitude and breadth of polyclonal antibodies elicited through vaccination or natural infection.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

The Future of Laboratory Chemistry Learning and Teaching Must be Accessible.

This commentary is a call to make the future of chemistry laboratories accessible and inclusive. We draw from research and lived experience to put forward a list of recommendations for laboratory-based teaching. Our authorial team includes undergraduate and postgraduate chemistry students, graduate teaching assistants, teaching-focused and traditional research and teaching academics, and a Diversity Equality Inclusion (DEI/EDI) academic expert. We all have lived experiences of disability, chronic illness, neurodivergence, and other marginalizations related to race, religion, sexuality, or other characteristics. We believe that laboratory-based chemistry learning environments, teaching, assessment, and resources should be accessible to all students and staff.

Dendritic Micelles with Controlled Branching and Sensor Applications.

Although micelles derived from the solution self-assembly of amphiphilic molecules and polymers have been prepared with a wide variety of shapes, examples with well-defined branched structures have remained elusive. We describe a divergent, directed self-assembly approach to low dispersity dendritic micelles with a high degree of structural perfection and tailorable branch numbers and generations. We use block copolymer amphiphiles as precursors and a crystallization-driven seeded growth approach whereby the termini of fiber-like micelles function as branching sites. Different dendrimeric generations are accessible by adjusting the ratio of added unimers to pre-existing seed micelles where the branch positions are determined by the reduced coronal chain grafting density on the surface of the micelle crystalline core. We demonstrate the spatially defined decoration of the assemblies with emissive nanoparticles and utility of the resulting hybrids as fluorescent sensors for anions where the dendritic architecture enables ultrahigh sensitivity.

BAG3P215L/KO Mice as a Model of BAG3P209L Myofibrillar Myopathy.

BCL-2-associated athanogene 3 (BAG3) is a co-chaperone to heat shock proteins important in degrading misfolded proteins through chaperone-assisted selective autophagy. The recurrent dominant BAG3-P209L mutation results in a severe childhood-onset myofibrillar myopathy (MFM) associated with progressive muscle weakness, cardiomyopathy, and respiratory failure. Because a homozygous knock-in (KI) strain for the mP215L mutation homologous to the human P209L mutation did not have a gross phenotype, compound heterozygote knockout (KO) and KI mP215L mice were generated to establish whether further reduction in BAG3 expression would lead to a phenotype. The KI/KO mice have a significant decrease in voluntary movement compared with wild-type and KI/KI mice in the open field starting at 7 months. The KI/KI and KI/KO mice both have significantly smaller muscle fiber cross-sectional area. However, only the KI/KO mice have clear skeletal muscle histologic changes in MFM. As in patient muscle, there are increased levels of BAG3-interacting proteins, such as p62, heat shock protein B8, and αB-crystallin. The KI/KO mP215L strain is the first murine model of BAG3 myopathy that resembles the human skeletal muscle pathologic features. The results support the hypothesis that the pathologic development of MFM requires a significant decrease in BAG3 protein level and not only a gain of function caused by the dominant missense mutation.

Genetic compensation triggered by actin mutation prevents the muscle damage caused by loss of actin protein.

The lack of a mutant phenotype in homozygous mutant individuals' due to compensatory gene expression triggered upstream of protein function has been identified as genetic compensation. Whilst this intriguing process has been recognized in zebrafish, the presence of homozygous loss of function mutations in healthy human individuals suggests that compensation may not be restricted to this model. Loss of skeletal α-actin results in nemaline myopathy and we have previously shown that the pathological symptoms of the disease and reduction in muscle performance are recapitulated in a zebrafish antisense morpholino knockdown model. Here we reveal that a genetic actc1b mutant exhibits mild muscle defects and is unaffected by injection of the actc1b targeting morpholino. We further show that the milder phenotype results from a compensatory transcriptional upregulation of an actin paralogue providing a novel approach to be explored for the treatment of actin myopathy. Our findings provide further evidence that genetic compensation may influence the penetrance of disease-causing mutations.

Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death.

Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel NaV1.1. Brain NaV1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of NaV1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet syndrome mice without affecting the firing of excitatory neurons. Intracerebroventricular infusion of Hm1a rescues Dravet syndrome mice from seizures and premature death. This precision medicine approach, which specifically targets the molecular deficit in Dravet syndrome, presents an opportunity for treatment of this intractable epilepsy.

Solid-State Donor-Acceptor Coaxial Heterojunction Nanowires via Living Crystallization-Driven Self-Assembly.

The creation of organic heterojunctions from conjugated polymers on the nanoscale has attracted recent attention as a consequence of their considerable potential in optoelectronic devices. Herein, we report proof-of-concept results on a versatile synthetic strategy to access various linearly segmented nanowire heterojunctions with controlled dimensions using the seeded growth "living crystallization-driven self-assembly" method followed by a secondary crystallization step. Specifically, we describe the creation of coaxial and also segmented coaxial B-A-B and A-B-A nanowires with a solvophilic poly(ethylene glycol) (PEG) corona, an inner crystalline core that consists of poly(di-n-hexylfluorene) (PDHF), which functions as a donor, and an outer crystalline core of poly(3-(2'-ethylhexyl)thiophene) (P3EHT), which acts as an acceptor. The latter is present either along the entire nanowire or solely in the central or terminal segments. These assemblies were created by seeded growth of two types of π-conjugated polymeric building blocks, the triblock copolymer PDHF-b-P3EHT-b-PEG and the diblock copolymer PDHF-b-PEG, by using fiber-like seeds derived from either material. The nanowires with both solid-state donor and acceptor blocks exhibit Förster resonance energy transfer (FRET) from the PDHF inner core to the P3EHT outer core which was characterized by fluorescence spectroscopy and laser confocal scanning fluorescence microscopy (LCSM). The FRET in the solid-state coaxial heterojunctions with an inner PDHF core and an outer P3EHT core was enhanced relative to the directly analogous system in which the P3EHT block was solvated.

Biomass of the Cyanobacterium Lyngbya wollei Alters Copper Algaecide Exposure and Risks to a Non-target Organism.

Nuisance algal infestations are increasing globally in distribution and frequency. Copper-based algaecides are routinely applied to control these infestations, though there is an ever-present concern of risks to non-target species. This research evaluated risks associated with a commonly applied chelated copper algaecide (Captain® XTR; SePRO Corporation) to a sentinel non-target species (Daphnia magna) and further assessed alteration of the exposure and toxicity when a nuisance mat-forming cyanobacterium, Lyngbya wollei, was present in exposures. Aqueous copper concentrations in treatments with algae significantly decreased within 1 h after treatment and averaged 57.5% of nominal amended Cu through the experiment duration. The 48 h LC50 values were 371 µg Cu/L with no algae present in exposures and increased significantly to 531 µg Cu/L when L. wollei was simultaneously exposed. This research provides information on the short-term fate of copper and hazard assessment by incorporating targeted binding ligands, as present in operational treatments.

The role of ADHD associated genes in neurodevelopment.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood. It is primarily characterised by high levels of activity, inattention, and impulsivity, and has strong negative impacts on academic functioning. Children with ADHD show a reduction in volume, and hypoactivity, in a range of brain regions. The underlying mechanisms behind these phenotypes are unknown, however, variants in several genes with known roles in neurodevelopment are associated with ADHD. In this review we discuss how these ADHD associated genes contribute to neurodevelopment, and how variants in these genes could give rise to the neurological phenotypes seen in ADHD.

Linking life-history theory and metabolic theory explains the offspring size-temperature relationship.

Temperature often affects maternal investment in offspring. Across and within species, mothers in colder environments generally produce larger offspring than mothers in warmer environments, but the underlying drivers of this relationship remain unresolved. We formally evaluated the ubiquity of the temperature-offspring size relationship and found strong support for a negative relationship across a wide variety of ectotherms. We then tested an explanation for this relationship that formally links life-history and metabolic theories. We estimated the costs of development across temperatures using a series of laboratory experiments on model organisms, and a meta-analysis across 72 species of ectotherms spanning five phyla. We found that both metabolic and developmental rates increase with temperature, but developmental rate is more temperature sensitive than metabolic rate, such that the overall costs of development decrease with temperature. Hence, within a species' natural temperature range, development at relatively cooler temperatures requires mothers to produce larger, better provisioned offspring.

Uniform Biodegradable Fiber-Like Micelles and Block Comicelles via "Living" Crystallization-Driven Self-Assembly of Poly(l-lactide) Block Copolymers: The Importance of Reducing Unimer Self-Nucleation via Hydrogen Bond Disruption.

Fiber-like micelles based on biodegradable and biocompatible polymers exhibit considerable promise for applications in nanomedicine, but until recently no convenient methods were available to prepare samples with uniform and controllable dimensions and spatial control of functionality. "Living" crystallization-driven self-assembly (CDSA) is a seeded growth method of growing importance for the preparation of uniform 1D and 2D core-shell nanoparticles from a range of crystallizable polymeric amphiphiles. However, in the case of poly(l-lactide) (PLLA), arguably the most widely utilized biodegradable polymer as the crystallizable core-forming block, the controlled formation of uniform fiber-like structures over a substantial range of lengths by "living" CDSA has been a major challenge. Herein, we demonstrate that via simple modulation of the solvent conditions via the addition of trifluoroethanol (TFE), DMSO, DMF and acetone, uniform fiber-like nanoparticles from PLLA diblock copolymers with controlled lengths up to 1 µm can be prepared. The probable mechanism involves improved unimer solvation by a reduction of hydrogen bonding interactions among PLLA chains. We provide evidence that this minimizes undesirable unimer aggregation which otherwise favors self-nucleation that competes with epitaxial crystallization from seed termini. This approach has also allowed the formation of well-defined segmented block comicelles with PLLA cores via the sequential seeded-growth of PLLA block copolymers with different corona-forming blocks.

Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization.

This study establishes PYROXD1 variants as a cause of early-onset myopathy and uses biospecimens and cell lines, yeast, and zebrafish models to elucidate the fundamental role of PYROXD1 in skeletal muscle. Exome sequencing identified recessive variants in PYROXD1 in nine probands from five families. Affected individuals presented in infancy or childhood with slowly progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and normal to moderately elevated creatine kinase. Distinctive histopathology showed abundant internalized nuclei, myofibrillar disorganization, desmin-positive inclusions, and thickened Z-bands. PYROXD1 is a nuclear-cytoplasmic pyridine nucleotide-disulphide reductase (PNDR). PNDRs are flavoproteins (FAD-binding) and catalyze pyridine-nucleotide-dependent (NAD/NADH) reduction of thiol residues in other proteins. Complementation experiments in yeast lacking glutathione reductase glr1 show that human PYROXD1 has reductase activity that is strongly impaired by the disease-associated missense mutations. Immunolocalization studies in human muscle and zebrafish myofibers demonstrate that PYROXD1 localizes to the nucleus and to striated sarcomeric compartments. Zebrafish with ryroxD1 knock-down recapitulate features of PYROXD1 myopathy with sarcomeric disorganization, myofibrillar aggregates, and marked swimming defect. We characterize variants in the oxidoreductase PYROXD1 as a cause of early-onset myopathy with distinctive histopathology and introduce altered redox regulation as a primary cause of congenital muscle disease.

A transgenic zebrafish model of hepatocyte function in human Z α1-antitrypsin deficiency.

In human α1-antitrypsin deficiency, homozygous carriers of the Z (E324K) mutation in the gene SERPINA1 have insufficient circulating α1-antitrypsin and are predisposed to emphysema. Misfolding and accumulation of the mutant protein in hepatocytes also causes endoplasmic reticulum stress and underpins long-term liver damage. Here, we describe transgenic zebrafish (Danio rerio) expressing the wildtype or the Z mutant form of human α1-antitrypsin in hepatocytes. As observed in afflicted humans, and in rodent models, about 80% less α1-antitrypsin is evident in the circulation of zebrafish expressing the Z mutant. Although these zebrafish also show signs of liver stress, they do not accumulate α1-antitrypsin in hepatocytes. This new zebrafish model will provide useful insights into understanding and treatment of α1-antitrypsin deficiency.

Pharmacokinetic Study of Cefazolin in Short Daily Hemodialysis.

BACKGROUND: A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD. OBJECTIVE: The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin. METHODS: This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined. RESULTS: Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.