Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long-Term MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement

Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are challenging to detect in vivo. In this study, a CPC construct is designed with gadolinium-oxide nanoparticles incorporated to act as an MRI/CT multimodal contrast agent. The gadolinium(III) oxide nanoparticles are synthesized via the polyol method and surface functionalized with a bisphosphonate (BP) derivative to give a construct (gadolinium-based contrast agents (GBCAs)-BP) with strong affinity toward calcium phosphate. The CPC-GBCAs-BP functional material is longitudinally monitored after in vivo implantation in a condyle defect rat model. The synthetic method developed produces nanoparticles that are stable in aqueous solution (hydrodynamic diameter 70 nm) with significant T1and T2relaxivity demonstrated in both clinical 3 T and preclinical 11.7 T MRI systems. The combination of GBCAs-BP nanoparticles with CPC gives an injectable material with handling properties that are suitable for clinical applications. The BP functionalization prolongs the residence of the contrast agent within the CPC to allow long-term follow-up imaging studies. The useful contrast agent properties combined with biological compatibility indicate further investigation of the novel bone substitute hybrid material toward clinical application

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Predatory midges of the tribes Palpomyiini and Sphaeromiini (Diptera: Ceratopogonidae) from the Middle East, with keys and descriptions of new species

The Middle East biting midges of the tribes Palpomyiini (20 species in three genera) and Sphaeromiini s. lat. (six species in five genera) are reviewed. Three new species are described and illustrated: Bezzia libanensis Alwin & Szadziewski sp. nov., B. sharjahi Alwin & Szadziewski sp. nov. and Palpomyia freidbergi Alwin & Szadziewski sp. nov. Bezzia aegyptia Kieffer, 1925 is recognized as a new junior synonym of B. albicornis (Meigen, 1818) (syn. nov.) and B. omanensis Boorman & van Harten, 2002, is recognized as a junior synonym of B. (Sivabezzia) pachypyga Remm, 1974 (syn. nov.). Keys to the genera and species of the tribes Palpomyiini and Sphaeromiini of the Middle East are also provided

Predatory midges of the tribes Palpmyiini and Sphaeromiini (Diptera: Ceratopogonidae) from the Middle East, with keys and descriptions of new species

The Middle East biting midges of the tribes Palpomyiini (20 species in three genera) and Sphaeromiini s. lat. (six species in five genera) are reviewed. Three new species are described and illustrated: Bezzia libanensis Alwin & Szadziewski sp. nov., B. sharjahi Alwin & Szadziewski sp. nov. and Palpomyia freidbergi Alwin & Szadziewski sp. nov. Bezzia aegyptia Kieffer, 1925 is recognized as a new junior synonym of B. albicornis (Meigen, 1818) (syn. nov.) and B. omanensis Boorman & van Harten, 2002, is recognized as a junior synonym of B. (Sivabezzia) pachypyga Remm, 1974 (syn. nov.). Keys to the genera and species of the tribes Palpomyiini and Sphaeromiini of the Middle East are also provided

Clinical evidence for use of a non-invasive biosensor for tear glucose as an alternative to painful finger-prick for diabetes management utilizing biopolymer coating

Diabetes is a metabolic condition that is exponentially increasing worldwide. Current monitoring methods for diabetes are invasive, painful, and expensive. Herein, we present the first multipatient clinical trial that demonstrates clearly that tear fluid may be a valuable marker for systemic glucose measurements. The NovioSense Glucose Sensor, worn under the lower eye lid (inferior conjunctival fornix), is reported to continuously measure glucose levels in the basal tear fluid with good correlation to blood glucose values, showing clear clinical feasibility in both animals and humans. Furthermore, the polysaccharide coated device previously reported by our laboratory when worn, does not induce pain or irritation. In a phase II clinical trial, six patients with type 1 Diabetes Mellitus were enrolled and the capability of the device to measure glucose in the tear fluid was evaluated. The NovioSense Glucose Sensor gives a stable signal and the results correlate well to blood glucose values obtained from finger-prick measurements determined by consensus error grid analysis

Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

International audienceThe commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T2 MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial

Background: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT). Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. Findings: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. Interpretation: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. Funding: UK Vaccine Taskforce and National Institute for Health Research