Safety Record Research Articles

Bilayer nonwovens using natural rubber, poly(lactic acid) and bactericidal nanoparticles for wound dressings

Wound healing poses a significant challenge in healthcare, impacting not only on patients' quality of life but also placing a substantial financial burden on healthcare systems. Bilayer nonwovens have emerged as a promising solution for wound dressings due to their porous morphology, providing a high surface area for cellular adhesion and growth, and their permeability, allowing proper oxygen and fluid exchange to promote wound healing. When bactericide materials are added to the formulation, they can decrease or prevent infection caused by microorganisms, further aiding the healing process. Solution blow spinning is an appealing technique for creating bilayer nonwovens as it can produce high yields at a low cost. Yet, even though natural rubber boasts a well-established safety record in biomaterials, it remains an underexplored candidate for generating micro-nanofibrous structures. In this study, solution blow spinning was employed to fabricate bilayer composite nonwovens for wound dressing materials. The material architecture consisted of a bottom layer composed of a blend of natural rubber, poly(lactic acid) (PLA), and polyethylene glycol in the respective proportion of 2:1:3 w/w and a top layer composed of PLA and ZnO nanoparticles added in concentrations of 1%, 2.5%, and 5% based on the PLA mass of this layer. The top layer was further functionalized with Ag nanoparticles through spraying. The obtained materials demonstrated satisfactory hydrophobicity for cellular adhesion in the bottom layer, ranging from 51.95° to 92.20° of water sessile drop contact angle, and tunable mechanical strength, which could be controlled by varying the content of ZnO nanoparticles. Additionally, the material showed antimicrobial properties due to the presence of added Ag nanoparticles, able to inhibit E. coli, S. enterica serovar Typhimurium, and S. aureus by direct contact. Besides, the nonwoven prevented the passage of microorganisms due to the pore size of the structure. Overall, the unique properties of the developed material, such as its low cost, ease of production, and remarkable wound-healing properties, make it a promising candidate for wound dressing applications.

A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern

As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and provide broader, more effective, and durable protection are urgently needed. Here, we have developed one such approach, a highly efficacious, intranasally delivered, trivalent measles-mumps-SARS-CoV-2 spike (S) protein (MMS) vaccine candidate that induces robust systemic and mucosal immunity with broad protection. This vaccine candidate is based on three components of the MMR vaccine, a measles virus Edmonston and the two mumps virus strains [Jeryl Lynn 1 (JL1) and JL2] that are known to provide safe, effective, and long-lasting protective immunity. The six proline-stabilized prefusion S protein (preS-6P) genes for ancestral SARS-CoV-2 WA1 and two important SARS-CoV-2 VoCs (Delta and Omicron BA.1) were each inserted into one of these three viruses which were then combined into a trivalent "MMS" candidate vaccine. Intranasal immunization of MMS in IFNAR1-/- mice induced a strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, mucosal IgA, and systemic and tissue-resident T cells. Immunization of golden Syrian hamsters with MMS vaccine induced similarly high levels of antibodies that efficiently neutralized SARS-CoV-2 VoCs and provided broad and complete protection against challenge with any of these VoCs. This MMS vaccine is an efficacious, broadly protective next-generation COVID-19 vaccine candidate, which is readily adaptable to new variants, built on a platform with a 50-y safety record that also protects against measles and mumps.

Safety outcomes of the first Rigi10™ malleable penile prostheses implanted worldwide.

Implantation of penile prosthesis is considered when conservative measures fail or are unacceptable to patients' wishing treatment for erectile dysfunction. In the United States (US), inflatable penile prostheses are more often used than malleable penile prostheses (MPP). Outside the US, the reverse is true because third-party reimbursement is not available, and MPP is considerably cheaper. Two American manufacturers make MPP; presently, a new manufacturer, Rigicon (Ronkonkoma NY), has recently begun to sell its MPP worldwide. Patient information forms submitted to the manufacturer between March 1, 2019, and December 8, 2022, were used to conduct an initial safety study for 605 first-time patients implanted with Rigicon10® by 46 physicians in 15 countries with a mean follow-up of 21.6 months. It has the same configuration of trimmable, paired silicone rods containing a twisted stainless-steel wire for bendability. However, it is available in six widths with hydrophilic coating compared to three widths offered by competitors. Revision or explantation was needed in 6 of 605 patients (0.99%) with half of those being removed for dissatisfaction (0.50%). Two (0.33%) suffered device infection and one (0.16%) required removal for erosion. Kaplan-Meier's statistical analysis showed three-year implant survival from revision = 99.2%. It demonstrated a comparable safety record with less than 1.00% of patients requiring reoperation.

Risk-ATTEND (Risk Anticipation Training to Enhance Novice Driving): Pilot Evaluation of a Risk Anticipation Training Program for Teen Drivers

Teen drivers have the highest crash risk when they start driving independently, and improving risk anticipation skills can help reduce this risk. Training can help teens acquire these skills faster and improve their overall safety record. The objective of this study was to evaluate an updated training program (based on RAPT and ACCEL) by introducing a more diverse set of training scenarios and leveraging deployment platforms that were better suited to modern devices. A pilot evaluation study was conducted with six teen drivers with less than six months of licensure to assess the updated training program (Risk-ATTEND). Risk-ATTEND was found to improve hazard anticipation-related gaze behaviors in teen drivers while also reducing workload. The research will aid in improving the training program’s usability, and web-based training will make the training program more accessible on modern devices.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Review of Established and Emerging Embolic Agents

Middle meningeal artery embolization is an increasingly common procedure involved in the treatment of chronic subdural hematoma (cSDH) that can be an adjuvant intervention or an alternative to traditional medical or surgical therapies. Our review aims to summarize the mechanism, properties, and available clinical data for current and investigative embolic agents used for the treatment of cSDH. Pubmed, Scopus, and clinicaltrials.gov were searched for relevant studies and ongoing trials that examine middle meningeal artery embolization for cSDH. Particle agents, liquid embolic agents, and coil embolization are the common classes of embolic materials used in clinical practice and in ongoing trials. These embolic agents are not only mechanical occlusive materials; they have unique properties that address the angiogenic and proinflammatory mechanisms that propagate and sustain cSDH. Particle agents, such as polyvinyl alcohol and Embosphere (tris‐acryl gelatin microspheres) have been the most commonly used embolic agents given the long‐term evidence base regarding efficacy and established safety record. Liquid embolic agents such as cyanoacrylate glues and copolymer agents such as Onyx, Squid, and PHIL are increasingly common in clinical settings due to improved visualization on imaging, durable embolization, and better control of distal embolization. Coil embolization is used in conjunction with other embolic agents or as monotherapy in the setting of dangerous middle meningeal artery anastomoses. There are several ongoing randomized clinical trials and prospective cohort studies that will clarify the safety, efficacy, and use cases of particle agents, liquid embolic agents, and coil embolization for the treatment of cSDH.

Fresh isolate adult telomerase positive stem cells: An addition to Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), and/or Mesenchymal Stem Cells (MSCs) for regenerative medicine

Currently, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) are the holy grail for regenerative medicine. Unfortunately, in clinical trials their efficacies have been less than ideal. While telomerase positive ESCs or iPSCs will form every cell type in the body, if implanted in their naïve state, they form teratomas. MSCs are a tripotent telomerase negative progenitor cell that will form fat, cartilage, and bone. MSCs’ efficacy for treating conditions other than fat, cartilage, and bone average 1-5%. We offer healing adult telomerase positive stem cells (aTPSCs) as an addition stem cell to regenerative medicine. The aTPSCs are few in number and reside in connective tissues throughout the body in a quiescent state. Upon stimulation, the aTPSCs divide symmetrically to large numbers due to the presence of the telomerase enzyme. Coupled with their ability to differentiate into any progenitor or differentiated cell in the body from their naïve state under the direction of locally released exosome cues, make them an ideal candidate for regenerative medicine. When tested in clinical studies, both autologous and allogeneic aTPSCs demonstrated a 100% safety record and a cumulative efficacy of 86.4% for reversing signs and symptoms in 20 chronic diseases or traumatic injuries. The results suggested that aTPSCs retain all the positive aspects of ESCs, iPSCs, and MSCs, while exhibiting none of their negative aspects. Therefore, I propose that aTPSCs be an added category of stem cells for use in regenerative medicine to increase efficacy of proposed treatments.

Increased In Vivo Exposure of N-(4-Hydroxyphenyl) Retinamide (4-HPR) to Achieve Plasma Concentrations Effective against Dengue Virus.

N-(4-hydroxyphenyl) retinamide (4-HPR, or fenretinide) has promising in vitro and in vivo antiviral activity against a range of flaviviruses and an established safety record, but there are challenges to its clinical use. This study evaluated the in vivo exposure profile of a 4-HPR dosage regime previously shown to be effective in a mouse model of severe dengue virus (DENV) infection, comparing it to an existing formulation for human clinical use for other indications and developed/characterised self-emulsifying lipid-based formulations of 4-HPR to enhance 4-HPR in vivo exposure. Pharmacokinetic (PK) analysis comprising single-dose oral and IV plasma concentration-time profiles was performed in mice; equilibrium solubility testing of 4-HPR in a range of lipids, surfactants and cosolvents was used to inform formulation approaches, with lead formulation candidates digested in vitro to analyse solubilisation/precipitation prior to in vivo testing. PK analysis suggested that effective plasma concentrations could be achieved with the clinical formulation, while novel lipid-based formulations achieved > 3-fold improvement. Additionally, 4-HPR exposure was found to be limited by both solubility and first-pass intestinal elimination but could be improved through inhibition of cytochrome P450 (CYP) metabolism. Simulated exposure profiles suggest that a b.i.d dosage regime is likely to maintain 4-HPR above the minimum effective plasma concentration for anti-DENV activity using the clinical formulation, with new formulations/CYP inhibition viable options to increase exposure in the future.

Intraperitoneal Paclitaxel Is a Safe and Effective Therapeutic Strategy for Treating Mucinous Appendiceal Adenocarcinoma.

The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.

Ivermectin as a novel malaria control tool: Getting ahead of the resistance curse

Reduction in malaria clinical cases is strongly dependent on the ability to prevent Anopheles infectious bites. Vector control strategies using long-lasting insecticidal nets and indoor residual spraying with insecticides have contributed to significantly reduce the incidence of malaria in many endemic countries, especially in the Sub-Saharan region. However, global progress in reducing malaria cases has plateaued since 2015 mostly due to the increased insecticide resistance and behavioral changes in Anopheles vectors. Additional control strategies are thus required to further reduce the burden of malaria and contain the spread of resistant and invasive Anopheles vectors. The use of endectocides such as ivermectin as an additional malaria control tool is now receiving increased attention, driven by its different mode of action compared to insecticides used so far and its excellent safety record for humans. In this opinion article, we discuss the advantages and disadvantages of using ivermectin for malaria control with a focus on the risk of selecting ivermectin resistance in malaria vectors. We also highlight the importance of understanding how ivermectin resistance could develop in mosquitoes and what its underlying mechanisms and associated molecular markers are, and propose a research agenda to manage this phenomenon.

Refueling the post COVID-19 brain: potential role of ketogenic medium chain triglyceride supplementation: an hypothesis.

COVID-19 infection causes cognitive changes in the acute phase, but also after apparent recovery. Over fifty post (long)-COVID symptoms are described, including cognitive dysfunction ("brain fog") precluding return to pre-COVID level of function, with rates twice as high in females. Additionally, the predominant demographic affected by these symptoms is younger and still in the workforce. Lack of ability to work, even for six months, has significant socio-economic consequences. This cognitive dysfunction is associated with impaired cerebral glucose metabolism, assessed using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), showing brain regions that are abnormal compared to age and sex matched controls. In other cognitive conditions such as Alzheimer's disease (AD), typical patterns of cerebral glucose hypometabolism, frontal hypometabolism and cerebellar hypermetabolism are common. Similar FDG-PET changes have also been observed in post-COVID-19, raising the possibility of a similar etiology. Ketone bodies (B-hydroxybutyrate, acetoacetate and acetone) are produced endogenously with very low carbohydrate intake or fasting. They improve brain energy metabolism in the face of cerebral glucose hypometabolism in other conditions [mild cognitive impairment (MCI) and AD]. Long-term low carbohydrate intake or prolonged fasting is not usually feasible. Medium chain triglyceride (MCT) is an exogenous route to nutritional ketosis. Research has supported their efficacy in managing intractable seizures, and cognitive impairment in MCI and AD. We hypothesize that cerebral glucose hypometabolism associated with post COVID-19 infection can be mitigated with MCT supplementation, with the prediction that cognitive function would also improve. Although there is some suggestion that post COVID-19 cognitive symptoms may diminish over time, in many individuals this may take more than six months. If MCT supplementation is able to speed the cognitive recovery, this will impact importantly on quality of life. MCT is readily available and, compared to pharmaceutical interventions, is cost-effective. Research shows general tolerability with dose titration. MCT is a component of enteral and parenteral nutrition supplements, including in pediatrics, so has a long record of safety in vulnerable populations. It is not associated with weight gain or adverse changes in lipid profiles. This hypothesis serves to encourage the development of clinical trials evaluating the impact of MCT supplementation on the duration and severity of post COVID-19 cognitive symptoms.

Implementation of neurological group-based telerehabilitation within existing healthcare during the COVID-19 pandemic: a mixed methods evaluation

BackgroundThere is a need to evaluate if and how telerehabilitation approaches might co-exist within healthcare in the long-term. Our aim was to implement and evaluate a multidisciplinary group-based telerehabilitation approach for people engaging in neurological rehabilitation.MethodsNeuroRehabilitation OnLine (NROL) was adapted and implemented within an existing healthcare system as a programme of repeating six-week blocks. A robust evaluation was undertaken simultaneously using a convergent parallel design underpinned by implementation frameworks. This included service data, and patient and staff interviews. Implementation success was conceptualised using the outcomes of appropriateness, acceptability and sustainability.ResultsEight NROL blocks delivered 265 sessions with 1347 patient contacts, and NROL continues as part of standard practice. The approach was appropriate for varied demographics and had positive patient opinions and outcomes for many. Staff perceived NROL provided a compatible means to increase therapy and help meet targets, despite needing to mitigate some challenges when fitting the approach within the existing system. NROL was considered acceptable due to good attendance (68%), low drop-out (12%), and a good safety record (one non-injury fall). It was accepted as a new way of working across rehabilitation disciplines as an ‘extra layer of therapy’. NROL had perceived advantages in terms of patient and staff resource (e.g. saving time, energy and travel). NROL provided staffing efficiencies (ratio 0.6) compared to one-to-one delivery. Technology difficulties and reluctance were surmountable with dedicated technology assistance. Leadership commitment was considered key to enable the efforts needed for implementation and sustained use.ConclusionPragmatic implementation of group-based telerehabilitation was possible as an adjunct to neurological rehabilitation within an existing healthcare system. The compelling advantages reported of having NROL as part of rehabilitation supports the continued use of this telerehabilitation approach. This project provides an exemplar of how evaluation can be run concurrently with implementation, applying a data driven rather than anecdotal approach to implementation.

Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants.

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, which are considered to be sufficient to protect against viral infection. Moreover, SARS-CoV-2 M2SR elicited cross-reactive serum and mucosal antibodies to the Omicron BA.4/BA.5 variant. The SARS-CoV-2 M2SR vaccine also maintained strong immune responses to influenza A with high titers of anti H3 serum IgG and hemagglutination inhibition (HAI) antibody titers corresponding to those seen from the control M2SR vector alone. With a proven safety record and robust immunological profile in humans that includes mucosal immunity, the M2SR influenza viral vector expressing key SARS-CoV-2 antigens could provide more efficient protection against influenza and SARS-CoV-2 variants.

Vertigoheel promotes rodent cognitive performance in multiple memory tests.

Cognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04's biological activity. In the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus. Administration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain. Our findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

E. coli Nissle 1917 ameliorates mitochondrial injury of granulosa cells in polycystic ovary syndrome through promoting gut immune factor IL-22 via gut microbiota and microbial metabolism.

Gut microbiota and its metabolites have regulatory effects on PCOS related ovarian dysfunction and insulin resistance. Escherichia coli Nissle 1917 (EcN) is a genetically controlled probiotic with an excellent human safety record for improving gut microbiome metabolic disorders and immune system disorders. Here we focused to explore the application and effect of probiotic EcN on the gut microbiota-metabolism-IL-22-mitochondrial damage axis in PCOS. PCOS mice were constructed with dehydroepiandrosterone (DHEA) and treated with EcN, FMT or IL-22 inhibitors. Clinically control and PCOS subjects were included for further analysis. Serum and follicular fluid supernatant levels of sex hormones, insulin, glucose, cholesterol, and inflammatory factors were detected by ELISA and biochemical reagents. The pathological changes of ovarian tissues were observed by HE staining. The JC-1 level and COX4 gene expression in granulosa cells was detected by ELISA and RT-qPCR. The expressions of progesterone receptor A (PR-A), LC3II/I, Beclin1, p62 and CytC were detected by western blot. The number of autophagosomes in granulosa cells was observed by electron microscopy. 16S rRNA and LC-MS/MS were used to analyze the changes of gut microbiota and metabolism. EcN promoted the recovery of sex hormone levels and ovarian tissue morphology, promoted the expression of IL-22, COX4 and PR-A in granulosa cells, and inhibited mitophagy in PCOS mice. EcN decreased the number of gut microbiota, and significantly increased the abundance of Adlercreutzia, Allobaculum, Escherichia-Shigella and Ileibacterium in PCOS mice. EcN improved metabolic disorders in PCOS mice by improving Amino sugar and nucleotide sugar metabolism pathways. IL-22 was positively associated with Ileibacterium, Adlercreutzia and Progesterone, negatively associated with RF39, Luteinizing hormone, Testosterone, N-Acetylglucosamin, L-Fucose and N-Acetylmannosamin. FMT reconfirmed that EcN ameliorated mitochondrial damage in granulosa cells of PCOS mice by gut microbiota, but this process was blocked by IL-22 inhibitor. Clinical trials have further demonstrated reduced IL-22 levels and mitochondrial damage in granulosa cells in PCOS patients. EcN improved IL-22 level and mitochondrial damage of granulosa cells in PCOS mice by promoting the recovery of sex hormone levels and ovarian tissue morphology, inhibiting the amount of gut microbiota, and promoting amino sugar and nucleotide sugar metabolism.

Regional variations in C1–C2 bone density on quantitated computed tomography and clinical implications

BackgroundOur elderly population is growing and the number of spine fractures in the elderly is also growing. The elderly population in general may be considered as poor surgical candidates experience a high rate of fractures at C1 and C2 compared with the general population. Nonoperative management of upper cervical fractures is not benign as there is a high nonunion rate for both C1 and C2 fractures in the elderly, and orthosis compliance is often suboptimal, or complicated by skin breakdown. The optimal technique for upper cervical stabilization in the elderly may be different than in younger populations as the bone quality is inferior in the elderly. The objective of this basic science study is to determine whether the bone mineral density (BMD) of C1 and C2 vary by region, and if this is a gender difference in this elderly age group. MethodsTwenty cadaveric spines from 45 to 83 years of age were used to obtain BMD using quantitated computed tomography (QCT). BMD was measured using a QCT. For C1, 8 regions were determined: anterior tubercle, bilateral anterior and medial lateral masses, bilateral posterior arches, and posterior tubercle. For C2, 7 regional BMDs were determined: top of odontoid, base of odontoid-body interface, mid body, bilateral lateral masses, anterior inferior body near the discs space, and the C2 spinous process. ResultsThe BMD was greatest at the C1 anterior tubercle (564.4±175.8 mg/cm3) and C1 posterior ring (420.8±110.2 mg/cm3), and least at the anterior and medial lateral masses (262.8±59.5 mg/cm3, 316.9±72.6 mg/cm3). At C2 QCT BMD was greatest at the top of the dens (400.6±107.9 mg/cm3) decreasing down through the odontoid-C2 body junction (267.8±103.5 mg/cm3) and least in the mid C2 body 249.1±68.8 mg/cm3). The posterior arch of C1 and the spinous process of C2 had higher BMD's 420.8±110.2 mg/cm3 and 284.1±93.0 mg/cm3, respectively. A high correlation was observed between the BMD at the interface of the dens-vertebral body with the vertebral body with a Pearson correlation coefficient of 0.86. The BMD of the top of dens was significantly higher (p<.05) than all the regions in C2. ConclusionsRegional and segmental BMD variations at C1 and C2 have clinical implications for surgical constructs in the elderly population. Given the higher BMDs of the C1 and C2 spinous process and posterior arches, consideration should be given to incorporate these areas using various C1–C2 wiring techniques. In the elderly, lateral masses particularly at C1 with lower BMD may result in potential screw loosening and nonunion in this age group. Old-school wiring techniques have a track record of efficacy and safety with less blood loss, reduced operative time, reduced X-ray exposure, and should be considered in the elderly as a primary stabilization technique or a belt-over suspenders approach based on regional variations in BMD in the elderly.

Smart Contact Lenses Keep an Eye on Health.

Contact lenses are ideal conduits for continuous health monitoring. They have a long safety record, and they sit on the eye, where they have access to a range of biological signals. Making the transition from vision correction to biological monitoring, however, requires advances in technological development so the lenses not only detect and report signals accurately, but retain the high level of comfort that users have come to expect.

Enhancement of immunogenicity and neutralizing responses against SARS-CoV-2 spike protein using the Fc fusion fragment.

Vaccination has played an important role in protecting against death and the severity of COVID-19. The recombinant protein vaccine platform has a long track record of safety and efficacy. Here, we fused the SARS-CoV-2 spike S1 subunit to the Fc region of IgG and investigated immunogenicity, reactivity to human vaccinated sera, and neutralizing activity as a candidate protein vaccine. We evaluated the immunogenicity of CHO-expressed S1-Fc fusion protein and tag-free S1 protein in rabbits via the production of S1-specific polyclonal antibodies. We subsequently compared the neutralizing activities of sera from immunized rabbits and human-vaccinated individuals using a surrogate Virus Neutralization Test (sVNT). The results indicate that S1-specific polyclonal antibodies were induced in all groups; however, antibody levels were higher in rabbits immunized with S1-Fc fusion protein than tag-free S1 protein. Moreover, the reactivity of human vaccinated sera against S1-Fc fusion protein was significantly higher than tag-free S1 protein. Lastly, the results of the virus-neutralizing activity revealed that vaccination with S1-Fc fusion protein induced the highest level of neutralizing antibody response against SARS-CoV-2. Our results demonstrate that the S1 protein accompanied by the Fc fragment significantly enhances the immunogenicity and neutralizing responses against SARS-CoV-2. It is hoped that this platform can be used for human vaccination.

Automatic for the People

Increasing disquiet about the seeming inevitability of deaths on US roads, which have by far the poorest safety record of the G7 nations, is leading to a change in attitudes towards automated enforcement on highways, which is still not legally allowed in most states. Jack Roper and Tom Stone find out more as they investigate a groundbreaking pilot in Connecticut

Review and assessment of the donor safety among plasma donors.

Review and assessment of the donor safety among plasma donors.

CD34 positive cells as endothelial progenitor cells in biology and medicine.

CD34 is a cell surface antigen expressed in numerous stem/progenitor cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which are known to be rich sources of EPCs. Therefore, regenerative therapy using CD34+ cells has attracted interest for application in patients with various vascular, ischemic, and inflammatory diseases. CD34+ cells have recently been reported to improve therapeutic angiogenesis in a variety of diseases. Mechanistically, CD34+ cells are involved in both direct incorporation into the expanding vasculature and paracrine activity through angiogenesis, anti-inflammatory, immunomodulatory, and anti-apoptosis/fibrosis roles, which support the developing microvasculature. Preclinical, pilot, and clinical trials have well documented a track record of safety, practicality, and validity of CD34+ cell therapy in various diseases. However, the clinical application of CD34+ cell therapy has triggered scientific debates and controversies in last decade. This review covers all preexisting scientific literature and prepares an overview of the comprehensive biology of CD34+ cells as well as the preclinical/clinical details of CD34+ cell therapy for regenerative medicine.