Selecting informative patients for phase 2 progressive trials in MS: Design considerations for phase 2 clinical trials in progressive MS.

While relapsing-remitting multiple sclerosis (MS) has many therapeutic options, progressive forms of MS remain largely untreatable. Phase 2 clinical trials are our main tool to advance new treatments for progressive MS. Given the complexities of progressive MS, it will likely require many phase 2 trials to improve its treatment. To conduct informative and efficient phase 2 trials, it is important that such trials are designed in a way that they can identify a successful treatment as quickly and with as few participants as possible. In this topical review, we discuss cohort selection, outcome selection, cohort enrichment, and dosing selection as strategies to optimize the efficiency of phase 2 clinical trials in progressive MS.

A reporter Oropouche virus expressing ZsGreen from the M segment enables pathogenesis studies in mice.

Oropouche fever caused by Oropouche virus (OROV) is a significant zoonosis in Central and South America. Despite its public health significance, we lack high-throughput diagnostics, therapeutics, and a comprehensive knowledge of OROV biology. Reporter viruses are valuable tools to rapidly study virus dynamics and develop neutralization and antiviral screening assays. OROV is a tri-segmented bunyavirus, which makes generating a reporter virus challenging, as introducing foreign elements into the viral genome typically affects fitness. We previously demonstrated that the non-structural gene NSm on the OROV medium (M) segment is non-essential for replication in vitro. Taking advantage of this, we have now generated a recombinant OROV expressing fluorescent protein ZsGreen in place of NSm. This reporter OROV is both stable and pathogenic in IFNAR-/- mice and provides a powerful tool for OROV pathogenesis studies and assay development.IMPORTANCEEmerging and reemerging infectious agents such as zoonotic bunyaviruses are of global health concern. Oropouche virus (OROV) causes recurring outbreaks of acute febrile illness in the Central and South American human populations. Biting midges are the primary transmission vectors, whereas sloths and non-human primates are their reservoir hosts. As global temperatures increase, we will likely see an expansion in arthropod-borne pathogens such as OROV. Therefore, developing reagents to study pathogen biology to aid in identifying druggable targets is essential. Here, we demonstrate the feasibility and use of a fluorescent OROV reporter in mice to study viral dynamics and pathogenesis. We show that this reporter OROV maintains characteristics such as growth and pathogenicity similar to the wild-type virus. Using this reporter virus, we can now develop methods to assist OROV studies and establish various high-throughput assays.

Failure of Pavlik Harness Treatment in Infants Under 6 Months Old with Dislocated Hips: Short- and Intermediate-Term Results of Subsequent Treatment Modalities.

Objective: This study aimed to determine the short- and medium-term outcomes of hip dislocation in infants who failed Pavlik harness therapy and were subsequently treated with brace, closed reduction (CR) or open reduction (OR) before 6 months of age. Methods: Fifty infants (66 hip dislocations) who failed Pavlik harness therapy between 2000 and 2018 and were treated with a rigid abduction brace or undergoing a CR or OR/cast were evaluated. All demographic data obtained from the medical system, developments and complications during the follow-up and treatment process were recorded and evaluated. Results: Fifty infants (66 hips) with dislocated hips failed Pavlik harness therapy. Of these, 9 infants (12 hips) underwent rigid abduction splint therapy: 9 hips were successful, 2 hips had CR and 1 had OR. Thirty-eight infants (51 hips) had index CR, of which 3 (3 hips) failed and had OR. Radiographs of 49 hips (44 patients) were normal at the final evaluation. Pavlik harness therapy starting after 3 weeks (P = 0.028) and unilateral dislocations (P = 0.028) increased the risk of needing operating room. There was an association between OR and avascular necrosis (P = 0.025), but not between OR and other complications-dysplasia and re-dislocation/subluxation (P = 0.257 and P = 0.508, respectively). Conclusion: Closed treatment of hip dislocation is possible in most babies who fail Pavlik treatment. Babies who are started on Pavlik therapy after 3 weeks of age may be at increased risk of needing an operating room. Level of Evidence: IV.

Assessing the Effect of Twisting and Twisting Fatigue on ZnO:Al Thin Film Performance on PEN and PET Substrates.

This study examines the electromechanical characteristics of aluminium-doped zinc oxide (AZO) films. The films were produced using the RF magnetron sputtering process with a consistent thickness of 150 nm on various polymer substrates. The study focuses on assessing the electro-mechanical failure processes of coated segments using flexible substrates, namely polyethylene naphthalate (PEN) and polyethylene terephthalate (PET), with a specific emphasis on typical cracking and delamination occurrences. This examination involves conducting twisting deformation together with using standardised electrical resistance measurements and optical microscope monitoring instruments. It was found that the crack initiation angle is mostly dependent on the mechanical mismatch between the coating and substrate. Higher critical twisting angle values are observed for the AZO/PEN film during twisting testing. Relative to the perpendicular plane of the untwisted sample, it was found that cracks initiated at a twist angle equal to 42° ± 2.1° and 38° ± 1.7° for AZO/PEN and AZO/PET, respectively, and propagated along the sample length. SEM images indicate that the twisting motion results in deformation in the thin film material, leading to the presence of both types of stress in the film structure. These discoveries emphasise the significance of studying the mechanical properties of thin films under different stress conditions, as it can impact their performance and reliability in real-world applications. The electromechanical stability of AZO was found to be similar on both substrates during fatigue testing. Studying the electromechanical properties of various material combinations is important for selecting polymer substrates and predicting the durability of flexible electronic devices made from polyester.

"Clicking" trimeric peptides onto hybrid T8POSS nanocages and identifying synthesis limitations.

Macromolecule branching upon polyhedral oligomeric silsesquioxanes (POSS) via "click" chemistry has previously been reported for promoting natural biological responses in vitro, particularly when regarding their demonstrated biocompatibility and structural robustness as potential macromolecule anchoring points. However, "clicking" of large molecules around POSS structures uncovers two main challenges: (1) a synthetic challenge encompassing multi-covalent attachment of macromolecules to a single nanoscale-central position, and (2) purification and separation of fully adorned nanocages from those that are incomplete due to their similar physical characteristics. Here we present peptide decoration to a T8POSS nanocage through the attachment of azido-modified trimers. Triglycine- and trialanine-methyl esters "clicked" to 97% and 92% completion, respectively, resulting in 84% and 68% yields of the fully-adorned octamers. The "clicks" halt within 27-h of the reaction time, and efforts to further increase the octamer yield were of negligible benefit. Exploration of reaction conditions reveals multiple factors preventing full octa-arm modification to all available POSS nanocages, and offers insights into macromolecule attachment between both peptides and small inorganic-organic structures, all of which require consideration for future work of this nature.

Delineation of the complete reaction cycle of a natural Diels-Alderase.

The Diels-Alder reaction is one of the most effective methods for the synthesis of substituted cyclohexenes. The development of protein catalysts for this reaction remains a major priority, affording new sustainable routes to high value target molecules. Whilst a small number of natural enzymes have been shown capable of catalysing [4 + 2] cycloadditions, there is a need for significant mechanistic understanding of how these prospective Diels-Alderases promote catalysis to underpin their development as biocatalysts for use in synthesis. Here we present a molecular description of the complete reaction cycle of the bona fide natural Diels-Alderase AbyU, which catalyses formation of the spirotetronate skeleton of the antibiotic abyssomicin C. This description is derived from X-ray crystallographic studies of AbyU in complex with a non-transformable synthetic substrate analogue, together with transient kinetic analyses of the AbyU catalysed reaction and computational reaction simulations. These studies reveal the mechanistic intricacies of this enzyme system and establish a foundation for the informed reengineering of AbyU and related biocatalysts.

Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study.

INTRODUCTION: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are orally administered fumarate disease-modifying therapies (DMTs) for multiple sclerosis (MS). The safety, tolerability, and exploratory efficacy of DRF were evaluated in the phase 3 EVOLVE-MS-1 study. No Evidence of Disease Activity (NEDA-3) is a composite efficacy endpoint used in clinical trials for MS defined as no relapse, no 24-week confirmed disability progression (CDP), no new/newly enlarging T2 lesions, and no new gadolinium-enhancing lesions. As NEDA outcomes in studies may be confounded by initial disease activity, the objective of this analysis was to evaluate NEDA-3 in EVOLVE-MS-1 for newly enrolled patients and patients who were re-baselined after approximately 7 weeks. METHODS: Patients entered EVOLVE-MS-1 as either newly enrolled or having completed the 5-week phase 3 EVOLVE-MS-2 study of DRF and DMF. Magnetic Resonance Imaging (MRI) was performed at baseline before each study (approx. 7 weeks apart) and at weeks 48 and 96 in EVOLVE-MS-1. Therefore, patients entering from EVOLVE-MS-2 were re-baselined after approximately 7 weeks. NEDA-3 outcomes on DRF are reported for prior DRF, prior DMF, and de novo patient groups. RESULTS: Of 1057 patients in EVOLVE-MS-1, 239 (22.6%) had rolled over from receiving DRF in EVOLVE-MS-2 ("prior DRF"), 225 (21.3%) had rolled over from receiving DMF in EVOLVE-MS-2 ("prior DMF"), and 593 (56.1%) were newly enrolled ("de novo"). At week 48, Kaplan-Meier estimates of NEDA-3 were 72.3% (prior DRF), 72.1% (prior DMF), and 62.1% (de novo); at week 96, estimates were 50.2% (prior DRF), 48.2% (prior DMF), and 36.5% (de novo). CONCLUSIONS: In EVOLVE-MS-1, after re-baselining at approximately 7 weeks, approximately half of DRF-treated patients achieved NEDA-3 at week 96, compared with 36.5% of patients who were not re-baselined. Re-baselining may be useful for assessing efficacy of DMTs by mitigating the influence of disease activity prior to the onset of efficacy. CLINICAL TRIAL REGISTRATIONS: NCT03093324 (EVOLVE-MS-2); NCT02634307 (EVOLVE-MS-1).

Type-2 diabetes mellitus enhances Klebsiella pneumoniae pathogenesis.

Klebsiella pneumoniae is an opportunistic pathogen and an important cause of pneumonia, bacteremia, and urinary tract infection. K. pneumoniae infections are historically associated with diabetes mellitus. There is a fundamental gap in our understanding of how diabetes mellitus, specifically type 2 diabetes, influences K. pneumoniae pathogenesis. K. pneumoniae pathogenesis is a multifactorial process that often begins with gut colonization, followed by an escape from the gut to peripheral sites, leading to host damage and infection. We hypothesized that type 2 diabetes enhances K. pneumoniae pathogenesis. To test this, we used well-established mouse models of K. pneumoniae colonization and lung infection in conjunction with a mouse model of spontaneous type 2 diabetes mellitus (T2DM). We show that T2DM enhances susceptibility to both K. pneumoniae colonization and infection. The enhancement of gut colonization is dependent on T2DM-induced modulation of the gut microbiota community structure. In contrast, lung infection is exacerbated by the increased availability of amino acids in the lung, which is associated with higher levels of vascular endothelial growth factor. These data lay the foundation for mechanistic interrogation of the relationship between K. pneumoniae pathogenesis and type 2 diabetes mellitus, and explicitly establish T2DM as a risk factor for K. pneumoniae disease.

New insights into morphological adaptation in common mole-rats (Cryptomys hottentotus hottentotus) along an aridity gradient.

Morphological adaptation is the change in the form of an organism that benefits the individual in its current habitat. Mole-rats (family Bathyergidae), despite being subterranean, are impacted by both local and broad-scale environmental conditions that occur above ground. Common mole-rats (Cryptomys hottentotus hottentotus) present an ideal mammalian model system for the study of morphological variation in response to ecology, as this species is found along an aridity gradient and thus can be sampled from geographically non-overlapping populations of the same species along an environmental longitudinal cline. Using the mass of five internal organs, ten skeletal measurements and 3D morphometric analyses of skulls, we assessed the morphology of wild non-breeding individuals from five common mole-rat populations in South Africa. We found that the body mass and mean relative mass of the spleen and kidneys in arid populations was larger, and individuals from arid regions possessed shorter legs and larger inter-shoulder widths compared to individuals from mesic regions. Additionally, arid populations demonstrated greater skull depth, and shape change of features such as angular processes of the lower jaw than mesic individuals, indicating that these distinct geographic populations show differences corresponding to the aridity gradient, potentially in response to environmental factors such as the variation in food sources found between different habitats, in addition to different soil compositions found in the different regions. Arid populations potentially require a stronger jaw and neck musculature associated with mastication to chew xeric-adapted plants and to dig through hard soil types, whereas mesic populations excavate through soft, looser soil and may make use of their front limbs to aid the movement of soils when digging. Aridity influences the morphology of this species and could indicate the impact of environmental changes on speciation and mammalian skull morphology.

Combining total synthesis and genetic engineering to probe dihydropyran formation in ambruticin biosynthesis.

The ambruticins are a family of potent antifungal polyketide derived natural products isolated from the myxobacterium Sorangium cellulosum. Their unusual structures include a trisubstituted cyclopropyl group and two oxygen heterocycles, a tetrahydropyran (THP) and dihydropyran (DHP). Herein we report a flexible modular approach for the total synthesis of ambruticins which is used to prepare ambruticins F and S as well as in the first total synthesis of 20,21-dihydroambruticin F. The flexible strategy unites 3 fragments via Julia-Kocienski olefinations and provides important standards for investigation of dihydropyran formation in ambruticin biosynthesis. Cultures of wild-type S. cellulosum So ce10 produce mainly ambruticin S and the VS series of metabolites. An efficient electroporation method enabled gene knockout experiments which revealed that the ΔambP-S mutant of S. cellulosum accumulated the bisTHP polyketide 20,21-dihydroambruticin F. In contrast, the ΔambN-S mutant gave ambruticin F with the 20,21-alkene as the major metabolite confirming that AmbP and AmbO (a Rieske enzyme and flavin-dependent monooxygenase respectively) are implicated in 20,21-alkene formation. The results of feeding studies to a Sorangium strain containing only ambP and ambO are in accord with formation of the 20,21-alkene occurring prior to generation of the C3 to C7 dihydroxylated tetrahydropyran in ambruticin biosynthesis.

Engineering Nitrogen-Doped Carbon Quantum Dots: Tailoring Optical and Chemical Properties through Selection of Nitrogen Precursors.

The process of N-doping is frequently employed to enhance the properties of carbon quantum dots. However, the precise requirements for nitrogen precursors in producing high-quality N-doped carbon quantum dots (NCQDs) remain undefined. This research systematically examines the influence of various nitrogen dopants on the morphology, optical features, and band structure of NCQDs. The dots are synthesized using an efficient, eco- friendly, and rapid continuous hydrothermal flow technique. This method offers unparalleled control over synthesis and doping, while also eliminating convention-related issues. Citric acid is used as the carbon source, and urea, trizma base, beta-alanine, L-arginine, and EDTA are used as nitrogen sources. Notably, urea and trizma produced NCQDs with excitation-independent fluorescence, high quantum yields (up to 40%), and uniform dots with narrow particle size distributions. Density functional theory (DFT) and time-dependent DFT modelling established that defects and substituents within the graphitic structure have a more significant impact on the NCQDs' electronic structure than nitrogen-containing functional groups. Importantly, for the first time, this work demonstrates that the conventional approach of modelling single-layer structures is insufficient, but two layers suffice for replicating experimental data. This study, therefore, provides essential guidance on the selection of nitrogen precursors for NCQD customization for diverse applications.

Relapse recovery in relapsing-remitting multiple sclerosis: An analysis of the CombiRx dataset.

BACKGROUND: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery. OBJECTIVE: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS). METHODS: Using data from CombiRx, a large RRMS trial (clinicaltrials.gov identifier NCT00211887), we measured the time to recovery from the first on-trial relapse. We used Kaplan-Meier survival analyses and Cox regression models to investigate the association of patient factors with the time to unconfirmed and confirmed relapse recovery. RESULTS: CombiRx included 1008 participants. We investigated 240 relapses. Median time to relapse recovery was 111 days. Most recovery events took place within 1 year of relapse onset: 202 of 240 (84%) individuals recovered during follow-up, 161 of 202 (80%) by 180 days, and 189 of 202 (94%) by 365 days. Relapse severity was the only factor associated with relapse recovery. CONCLUSION: Recovery from relapses takes place up to approximately 1 year after the event. Relapse severity, but no other patient factors, was associated with the speed of relapse recovery. Our findings inform clinical practice and trial design in RRMS.

Describing the state of a research network: A mixed methods approach to network evaluation.

Diabetes Action Canada Strategy for Patient-Oriented Research (SPOR) Network in Chronic Disease was formed in 2016 and is funded primarily through the Canadian Institutes of Health Research (CIHR). We propose a novel mixed-methods approach to a network evaluation integrating the State of Network Evaluation framework and the Canadian Academy of Health Sciences (CAHS) preferred framework and indicators. We measure key network themes of connectivity, health and results, and impact and return on investment associated with health research networks. Our methods consist of a longitudinal cross-sectional network survey of members and social network analysis to examine Network Connectivity and assess the frequency of interactions, the topics discussed during them, and how networking effectively facilitates interactions and collaboration among members. Network Health will be evaluated through semistructured interviews, a membership survey inquiring about satisfaction and experience with the Network, and a review of documentary sources related to funding and infrastructure to evaluate Network Sustainability. Finally, we will examine Network Results and Impact using the CAHS preferred framework and indicators to measure returns on investment in health research across the five domains of the CAHS framework, which include: advancing knowledge, capacity building, informing decision making, health impact, and economic and social impact. Indicators will be assessed with various methods, including bibliometric analyses, review of relevant documentary sources (annual reports), member activities informing health and research policy, and Patient Partner involvement. The Network Evaluation will provide members and stakeholders with information for planning, improvements, and funding future Network endeavors.

Remission of severe myasthenia gravis after autologous stem cell transplantation.

OBJECTIVE: Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. METHODS: As part of a pilot study of HDIT/HCT for patients with treatment-resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G-CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. RESULTS: The patient had been diagnosed with AChR antibody-positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom-free. After HDIT/HCT, AChR-binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. INTERPRETATION: HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell-mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.

Surface texture heterogeneity in maculated bird eggshells.

Many of the world's 10 000 bird species lay coloured or patterned eggs. The large diversity of eggshell patterning among birds, achieved through pigment, has been attributed to a few selective agents such as crypsis, thermoregulation, egg recognition, mate signalling, egg strength and protecting the embryo from UV. Pigmentation may influence the texture of eggshells, which in turn may be important for dealing with water and microbes. We measured surface roughness (Sa, nm), surface skewness (Ssk) and surface kurtosis (Sku), which describe different aspects of surface texture, across 204 bird species with maculated (patterned) eggs and 166 species with immaculate (non-patterned) eggs. Using phylogenetically controlled analyses, we tested whether maculated eggshells have different surface topography between the foreground colour and background colour, and between the background colour of maculated eggshells and the surface of immaculate eggshells. Secondly, we determined to what extent variation in eggshell pigmentation of the foreground and background colour is determined by phylogenetic relatedness, and whether certain life-history traits are important predictors of eggshell surface structure. We show that the surface of maculated eggs consists of a rougher foreground pigment compared to the background pigment across 71% of the 204 bird species (54 families) investigated. Species that lay immaculate eggs showed no difference in surface roughness, kurtosis or skewness compared to background pigment of maculated eggs. The difference in eggshell surface roughness between foreground and background pigmentation was greater among species that occupied dense habitats, such as forests with closed canopies, compared to those that nest in open and semi-open habitats (e.g. cities, deserts, grasslands, open shrubland and seashores). Among maculated eggs, foreground texture was correlated with habitat, parental care, diet, nest location, avian group and nest type, while background texture was correlated with clutch size, annual temperature, development mode and annual precipitation. Surface roughness among immaculate eggs was greatest for herbivores, and species that have larger clutch sizes. Together, this suggests that multiple life-history traits have influenced the evolution of eggshell surface textures in modern birds.

Threshold definitions for significant change on the timed 25-foot walk and nine-hole peg test in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: The timed 25-foot walk (T25FW) and nine-hole peg test (NHPT) exhibit random variability in the short term. A threshold of ≥20% change from baseline has been used to indicate true disability change, but other threshold definitions may be better suited to exclude false and include true change events. The aim of this study was to use patient-level original trial data to investigate the short-term variation in T25FW and NHPT, and to compare its extent with disability change at 12-month follow-up in people with primary progressive multiple sclerosis (PPMS). METHODS: We used original patient-level data from PROMISE, a large PPMS trial. In this trial, three separate T25FW and NHPT measurements were performed 1 week apart during screening. We used these repeated measures to describe the extent of short-term variation. We used binary logistic regression models to investigate the association between screening characteristics and unacceptable short-term variation. RESULTS: The traditional 20% threshold excluded a reasonable number of false change events, while also yielding a large number of change events at follow-up. Increasing index values on the T25FW and NHPT were associated with higher short-term variation. CONCLUSIONS: The traditional ≥20% change threshold for the T25FW and NHPT represents a reasonable compromise between reducing the number of false change events and achieving the largest number of change events in people with PPMS. Our analyses inform the design of clinical trials in PPMS.

Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis.

BACKGROUND: Focal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity. METHODS: We used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs. We determined the proportion of participants developing new T2 lesions, contrast-enhancing lesions (CELs) and relapses over 2 years of follow-up as a function of age, and investigated the association of age with time to first relapse using time-to-event analyses. RESULTS: At baseline, there were no differences between age groups in T2 lesion volume and number of relapses in the year before inclusion. In SENTINEL, older participants had a significantly lower number of CELs. During both trials, the number of new CELs and the proportion of participants developing new CELs were significantly lower in older age groups. The number of new T2 lesions and the proportion of participants with any radiological disease activity during follow-up were also lower in older age groups, especially in the control arms. CONCLUSIONS: Older age is associated with a lower prevalence and degree of focal inflammatory disease activity in treated and untreated RRMS. Our findings inform the design of RCTs, and suggest that patient age should be taken into consideration when deciding on immunomodulatory treatment in RRMS.

Eggshell composition and surface properties of avian brood-parasitic species compared with non-parasitic species.

The eggs of avian obligate brood-parasitic species have multiple adaptations to deceive hosts and optimize development in host nests. While the structure and composition of the eggshell in all birds is essential for embryo growth and protection from external threats, parasitic eggs may face specific challenges such as high microbial loads, rapid laying and ejection by the host parents. We set out to assess whether eggshells of avian brood-parasitic species have either (i) specialized structural properties, to meet the demands of a brood-parasitic strategy or (ii) similar structural properties to eggs of their hosts, due to the similar nest environment. We measured the surface topography (roughness), wettability (how well surfaces repel water) and calcium content of eggshells of a phylogenetically and geographically diverse range of brood-parasitic species (representing four of the seven independent lineages of avian brood-parasitic species), their hosts and close relatives of the parasites. These components of the eggshell structure have been demonstrated previously to influence such factors as the risk of microbial infection and overall shell strength. Within a phylogenetically controlled framework, we found no overall significant differences in eggshell roughness, wettability and calcium content between (i) parasitic and non-parasitic species, or (ii) parasitic species and their hosts. Both the wettability and calcium content of the eggs from brood-parasitic species were not more similar to those of their hosts' eggs than expected by chance. By contrast, the mean surface roughness of the eggs of brood-parasitic species was more similar to that of their hosts' eggs than expected by chance, suggesting brood-parasitic species may have evolved to lay eggs that match the host nest environment for this trait. The lack of significant overall differences between parasitic and non-parasitic species, including hosts, in the traits we measured, suggests that phylogenetic signal, as well as general adaptations to the nest environment and for embryo development, outweigh any influence of a parasitic lifestyle on these eggshell properties.