Safe Countermeasures Research Articles

Nanomedicine approaches against SARS-CoV-2 and variants

The world is grappling with the ongoing crisis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a global pandemic that continues to have a detrimental impact on public health and economies worldwide. The virus's relentless mutation has led to more transmissible, immune-evasive strains, thereby escalating the incidence of reinfection. This underscores the urgent need for highly effective and safe countermeasures against SARS-CoV-2 and its evolving variants. In the current context, nanomedicine presents an innovative and promising alternative to mitigate the impacts of this pandemic wave. It does so by harnessing the structural and functional properties at a nanoscale in a straightforward and adaptable manner. This review emphasizes the most recent progress in the development of nanovaccines, nanodecoys, and nanodisinfectants to tackle SARS-CoV-2 and its variants. Notably, the insights gained and strategies implemented in managing the ongoing pandemic may also offer invaluable guidance for the development of potent nanomedicines to combat future pandemics.

Bioprinting of Cardiac Tissue in Space: Where Are We?

Bioprinting in space is the next frontier in tissue engineering. In the absence of gravity, novel opportunities arise, as well as new challenges. The cardiovascular system needs particular attention in tissue engineering, not only to develop safe countermeasures for astronauts in future deep and long-term space missions, but also to bring solutions to organ transplantation shortage. In this perspective, the challenges encountered when using bioprinting techniques in space and current gaps that need to be overcome are discussed. The recent developments that have been made in the bioprinting of heart tissues in space and an outlook on potential future bioprinting opportunities in space are described.

Recent Developments in Botulinum Neurotoxins Detection.

Botulinum neurotoxins (BoNTs) are produced as protein complexes by bacteria of the genus Clostridium that are Gram-positive, anaerobic and spore forming (Clostridium botulinum, C. butyricum, C. baratii and C. argentinense spp.). BoNTs show a high immunological and genetic diversity. Therefore, fast, precise, and more reliable detection methods are still required to monitor outbreaks and ensure surveillance of botulism. The botulinum toxin field also comprises therapeutic uses, basic research studies and biodefense issues. This review presents currently available detection methods, and new methods offering the potential of enhanced precision and reproducibility. While the immunological methods offer a range of benefits, such as rapid analysis time, reproducibility and high sensitivity, their implementation is subject to the availability of suitable tools and reagents, such as specific antibodies. Currently, the mass spectrometry approach is the most sensitive in vitro method for a rapid detection of active or inactive forms of BoNTs. However, these methods require inter-laboratory validation before they can be more widely implemented in reference laboratories. In addition, these surrogate in vitro models also require full validation before they can be used as replacement bioassays of potency. Cell-based assays using neuronal cells in culture recapitulate all functional steps of toxin activity, but are still at various stages of development; they are not yet sufficiently robust, due to high batch-to-batch cell variability. Cell-based assays have a strong potential to replace the mouse bioassay (MBA) in terms of BoNT potency determination in pharmaceutical formulations; they can also help to identify suitable inhibitors while reducing the number of animals used. However, the development of safe countermeasures still requires the use of in vivo studies to complement in vitro immunological or cell-based approaches.

Pulsed electromagnetic fields inhibit mandibular bone deterioration depending on the Wnt3a/β-catenin signaling activation in type 2 diabetic db/db mice

Type 2 diabetes mellitus (T2DM) patients have compromised mandibular bone architecture/quality, which markedly increase the risks of tooth loosening, tooth loss, and failure of dental implantation. However, it remains lacks effective and safe countermeasures against T2DM-related mandibular bone deterioration. Herein, we studied the effects of pulsed electromagnetic fields (PEMF) on mandibular bone microstructure/quality and relevant regulatory mechanisms in T2DM db/db mice. PEMF exposure (20 Gs, 15 Hz) for 12 weeks preserved trabecular bone architecture, increased cortical bone thickness, improved material properties and stimulated bone anabolism in mandibles of db/db mice. PEMF also upregulated the expression of canonical Wnt3a ligand (but not Wnt1 or Wnt5a) and its downstream β-catenin. PEMF improved the viability and differentiation of primary osteoblasts isolated from the db/db mouse mandible, and stimulated the specific activation of Wnt3a/β-catenin signaling. These positive effects of PEMF on mandibular osteoblasts of db/db mice were almost totally abolished after Wnt3a silencing in vitro, which were equivalent to the effects following blockade of canonical Wnt signaling using the broad-spectrum antagonist DKK1. Injection with Wnt3a siRNA abrogated the therapeutic effects of PEMF on mandibular bone quantity/quality and bone anabolism in db/db mice. Our study indicates that PEMF might become a non-invasive and safe treatment alternative resisting mandibular bone deterioration in T2DM patients, which is helpful for protecting teeth from loosening/loss and securing the dental implant stability.

Description and characterization of a novel live-attenuated tri-segmented Machupo virus in Guinea pigs

BackgroundMachupo virus (MACV) is a member of the Mammarenavirus genus, Arenaviridae family and is the etiologic agent of Bolivian hemorrhagic fever, which causes small outbreaks or sporadic cases. Several other arenaviruses in South America Junín virus (JUNV) in Argentina, Guanarito in Venezuela, Sabiá in Brazil and Chapare in Bolivia, also are responsible for human hemorrhagic fevers. Among these arenaviruses, JUNV caused thousands of human cases until 1991, when the live attenuated Candid #1 vaccine, was used. Other than Candid #1 vaccine, few other therapeutic or prophylactic treatments exist. Therefore, new strategies for production of safe countermeasures with broad spectrum activity are needed.FindingsWe tested a tri-segmented MACV, a potential vaccine candidate with several mutations, (r3MACV). In cell culture, r3MACV showed a 2-log reduction in infectious virus particle production and the MACV inhibition of INF-1β was removed from the construct and produced by infected cells. Furthermore, in an animal experiment, r3MACV was able to protect 50% of guinea pigs from a simultaneous lethal JUNV challenge. Protected animals didn’t display clinical symptoms nor were virus particles found in peripheral blood (day 14) or in organs (day 28 post-inoculation). The r3MACV provided a higher protection than the Candid #1 vaccine.ConclusionsThe r3MACV provides a potential countermeasure against two South America arenaviruses responsible of human hemorrhagic fever.

Prophylactic strategies to minimize the effect of whole body irradiation on hematopoietic, gastrointestinal and respiratory system leading to morbidity/mortality in animals

Increase in radionuclide application has gone far and wide in the last many decades; though its usage has benefited the society at large, however occasional unplanned exposure to radiation (terrorist/accidental) has also troubled human life. Exposure of humankind to nuclear disaster, accidental and natural background radiation exposure, has created the need to develop complete understanding of the subject and preparedness for having safe countermeasures. In whole-body radiation exposure scenario, all the three organs are responsible for leading the animal to its death; however, hematopoietic (HP) organ is the first to collapse followed by gastrointestinal (GI) and respiratory systems. Radiation-induced basic damage in these organs follows more or less similar pattern. Derangement starts with radiation-induced reactive oxygen species causing damage to DNA, lipids, and proteins and disturbing their regulatory pathways. However, damage in HP and GI is more rapid and severe due to the presence of highly radiosensitive multipotent stem cells essential to meet the need of high cell turnover rate in these organs. To overcome radiation-induced damage to these vital organs, serious efforts are continued globally to find safe remedial measure.

Predatory behavior of the backswimmer ( Anisops ogasawarensis) on larval medaka ( Oryzias latipes)

To establish ecologically and environmentally safe countermeasures to prevent the predation of aquatic insects on larval fish in aquaculture systems, the predatory behavior of a backswimmer ( Anisops ogasawarensis) on larval Medaka ( Oryzias latipes) was observed under laboratory conditions. Observations were conducted to describe the vertical distribution and predatory behaviors of A. ogasawarensis. Additionally, a predation experiment evaluated the effect of various light levels (0, 3, 30, 300, and 3000 lx) on predation. Both the vertical distribution of A. ogasawarensis and the occurrences of predatory behavior was the highest near the water surface. A. ogasawarensis showed ambush predatory behavior and initiated chases when the larval O. latipes were within 5 cm of the predator. In the experiment, the predation rate increased with an increase in light intensity from 0 to 300 lx and decreased at 3000 lx. The present study indicates that predation by A. ogasawarensis on larval O. latipes changes under conditions of visual obstruction for the larvae such as decreasing of light intensity in the fish pond. Encounters with predators during the seed production may be higher in shallower.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Vehicle accidents related to sleep: a review.

Falling asleep while driving accounts for a considerable proportion of vehicle accidents under monotonous driving conditions. Many of these accidents are related to work--for example, drivers of lorries, goods vehicles,...

Driver sleepiness.

Falling asleep at the wheel accounts for a sizeable number of vehicle accidents under monotonous driving conditions. The risk of driver death and serious injury is high. Circadian factors are profound and seem to be of equal (if not more) importance to the duration of the drive. Unfortunately, only the latter tends to be built into legislation. Young adults are the most likely to have these accidents, especially in the early morning, whereas older adults may be more vulnerable in the early afternoon. Drivers falling asleep are unlikely to recollect having done so, but they are aware of the precursory state of feeling sleepy, as normal sleep does not occur spontaneously without warning. Self-awareness of sleepiness is a better method for alerting the driver than in-car automatic devices. Car simulator studies show high inter-correlations between driving performance, EEG measures of drowsiness and self-assessments of sleepiness. Putative countermeasures to sleepiness during continued driving (for example cold air, playing car radio) have to be substantiated. The only safe countermeasure is to stop driving. At this point, a nap and/or coffee (caffeine) can be effective. Exercise is of little use. More driver education is needed about the dangers of driving whilst sleepy.